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Sample records for aspirin exacerbated respiratory

  1. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    OpenAIRE

    Shrestha Palikhe, Nami; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Nam, Young Hee; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the resp...

  2. Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory disease

    National Research Council Canada - National Science Library

    Song, Young-Sin; Yang, Eun-Mi; Kim, Seung-Hyun; Jin, Hyun Jung; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome associated with chronic inflammation in the airways coincident with chronic rhinitis, sinusitis, recurrent polyposis and asthma...

  3. Aspirin exacerbated respiratory disease: Current topics and trends.

    Science.gov (United States)

    Rodríguez-Jiménez, José Carlos; Moreno-Paz, Fernanda Judith; Terán, Luis Manuel; Guaní-Guerra, Eduardo

    2018-02-01

    Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets. In this review, we summarize the most important clinical aspects of the disease, including the current topics about diagnosis and treatment, like provocation challenges and aspirin desensitization. We also discuss recent findings in the pathogenesis of the disease, as well as future trends in diagnosis and treatment, including monoclonal antibodies and a low salicylate diet as a treatment option. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Adappa, Nithin D; Ranasinghe, Viran J; Trope, Michal; Brooks, Steven G; Glicksman, Jordan T; Parasher, Arjun K; Palmer, James N; Bosso, John V

    2018-01-01

    In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin-exacerbated respiratory disease (AERD). A retrospective chart review was conducted for patients with aspirin challenge-proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality-of-life measures using the 22-item Sino-Nasal Outcomes Test (SNOT-22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post-desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed-effects model was used for data analysis. Thirty-four patients met the inclusion criteria for this study. Thirty-two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow-up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT-22 scores. Our results demonstrate that total SNOT-22 scores remained statistically unchanged from immediate post-desensitization throughout the 30-month follow-up period. Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long-term management of sinus disease in patients with AERD. © 2017 ARS-AAOA, LLC.

  5. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    Directory of Open Access Journals (Sweden)

    Nami Shrestha Palikhe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

  6. Exonic variants associated with development of aspirin exacerbated respiratory diseases.

    Directory of Open Access Journals (Sweden)

    Seung-Woo Shin

    Full Text Available Aspirin-exacerbated respiratory disease (AERD is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study was to identify AERD-associated exonic SNPs and examine the diagnostic potential of a combination of these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects with aspirin-tolerant asthma (ATA, and 398 normal controls were subjected to an Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1 were generated from combinations of the top 10 SNPs, selected by the p-values in association with AERD. The area under the curve (AUC of the receiver operating characteristic (ROC curves was calculated for each model. SNP Function Portal and PolyPhen-2 were used to validate the functional significance of candidate SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p = 3.40×10-8 in its association with AERD risk. From the top 10 SNPs, a combination model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237, exm396794, and exm791954 showed the best AUC of 0.75 (asymptotic p-value of 7.94×10-21, with 34% sensitivity and 93% specificity to discriminate AERD from ATA. Amino acid changes due to exm83523 in CHIA were predicted to be "probably damaging" to the structure and function of the protein, with a high score of '1'. A combination model of seven SNPs may provide a useful, non-invasive genetic marker combination for predicting AERD.

  7. State of the Art: Medical treatment of aspirin exacerbated respiratory disease (AERD).

    Science.gov (United States)

    Ta, Von; Simon, Ronald

    2015-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized as adult onset asthma, nasal polyps, chronic rhinosinusitis, and hypersensitivity to a cyclooxygenase-1 (COX-1) inhibitor, viz aspirin or nonsteroidal antiinflammatory drugs (NSAIDs). The method for diagnosing AERD is with aspirin challenge, and treatment includes aspirin desensitization followed by continued daily aspirin. Although oral challenge has been the mainstay in the United States, lysyl-aspirin has been validated as a diagnostic tool for aspirin-sensitive asthma and will be discussed further in this article. The challenges with aspirin therapy surrounding endoscopy and perioperative aspirin therapy will be discussed. Additionally, daily aspirin therapy is not for everyone. Aspirin is relatively contraindicated in those with a history of gastrointestinal bleed and an absolute contraindication in pregnancy. Aspirin desensitization and subsequent treatment has been shown to be highly effective for AERD.

  8. The role of aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD).

    Science.gov (United States)

    Spies, Jonas Willian; Valera, Fabiana Cardoso Pereira; Cordeiro, Daniel Loiola; de Mendonça, Taís Nociti; Leite, Marcelo Gonçalves Junqueira; Tamashiro, Edwin; Arruda, Luiza Karla; Anselmo-Lima, Wilma Terezinha

    2016-01-01

    Aspirin-exacerbated respiratory disease (AERD) consists of a classic tetrad: moderate/severe asthma, chronic rhinosinusitis, nasal polyps, and intolerance to aspirin or other nonsteroidal anti-inflammatory drugs. Clinical control with drugs, surgery, and desensitization are treatment options. To evaluate the efficacy and tolerability of aspirin desensitization in patients with AERD. Periodic symptom assessment and endoscopy in patients with AERD undergoing surgery who were desensitized. Seventeen patients were desensitized. Eight patients completed the desensitization and were followed for a minimum of a one-year period (mean 3.1 years). These patients showed improvement in all symptoms. Moreover, surgical reassessment was not indicated in any of these patients and there was a decrease in costs with medication and procedures. Eight patients did not complete desensitization, mainly due to procedure intolerance and uncontrolled asthma, whereas another patient was lost to follow-up. Aspirin desensitization, when tolerated, was effective in patients with AERD and with poor clinical/surgical response. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  9. Update on Recent Advances in the Management of Aspirin Exacerbated Respiratory Disease

    OpenAIRE

    Palikhe, Nami Shrestha; Kim, Joo-Hee; Park, Hae-Sim

    2009-01-01

    Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; howev...

  10. Safety and outcomes of aspirin desensitization for aspirin-exacerbated respiratory disease: A single-center study.

    Science.gov (United States)

    Waldram, Jeremy; Walters, Kristen; Simon, Ronald; Woessner, Katherine; Waalen, Jill; White, Andrew

    2018-01-01

    Aspirin desensitization is an effective treatment option for aspirin-exacerbated respiratory disease. Aspirin desensitization protocol modifications have improved the safety and efficiency of this procedure, yet some providers remain reluctant to perform it. The primary objective of this study was to evaluate the safety and outcomes of outpatient aspirin desensitization procedures. A secondary objective was to assess clinical characteristics that might predict reaction severity during aspirin desensitization. Two hundred seventy-five patients underwent aspirin desensitization at Scripps Clinic between January 2009 and August 2015. Baseline patient characteristics and reaction results were analyzed in the 167 patients who reacted during desensitization. All of the 167 reactors, including 23 who were classified as severe reactors, were successfully desensitized in the outpatient setting. The average desensitization duration among reactors was 1.67 days, and the average duration for gastrointestinal reactors was 2.29 days. The mean baseline Sino-Nasal Outcome Test score was higher in severe reactors compared with nonsevere reactors (P = .05). Overall, patients receiving omalizumab had a similar reaction profile to those not receiving omalizumab. Most patients undergoing aspirin desensitization will have symptoms. It remains difficult to predict the severity of these symptoms. However, desensitization can be done safely and efficiently in an appropriately equipped outpatient setting. This treatment option should be made available to all patients with aspirin-exacerbated respiratory disease. The Sino-Nasal Outcome Test score might be able to predict more severe reactions and merits further study. Eight of the 9 patients receiving omalizumab reacted during desensitization, suggesting that it does not block reactions during aspirin desensitization. Published by Elsevier Inc.

  11. Effect of aspirin desensitization on T-cell cytokines and plasma lipoxins in aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Aksu, Kurtuluş; Kurt, Emel; Alatas, Özkan; Gülbas, Zafer

    2014-01-01

    The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is thought to be based on, mainly, overproduction of eicosanoid lipid mediators and on defective anti-inflammatory regulators. Aspirin desensitization treatment, the mainstay of controlling asthma and rhinitis in AERD patients, however, is the least understood aspect of the disease. The study was designed to determine the effect of aspirin desensitization on T-lymphocyte cytokine expression and on plasma lipoxin levels in AERD. Spirometry, skin-prick test and asthma control test were documented and intracellular cytokine expression in T lymphocytes and plasma lipoxin levels were measured in 23 AERD patients, 17 aspirin-tolerant asthmatic (ATA) patients, and 16 healthy controls. In the AERD group nasal symptom and smell scores were assessed. Of the 23 AERD patients 15 accepted to undergo aspirin desensitization protocol and 14 of them were desensitized successfully. In the desensitized AERD group, cytokine and lipoxin measurements were repeated after 1-month aspirin treatment. CD4(+) IL-10 levels were higher in AERD patients than in healthy controls and CD4(+) interferon (IFN) gamma levels were higher in AERD and ATA patients than in controls. Plasma lipoxin-A4 and 15-epi-lipoxin-A4 levels were similar among the three study groups. In the AERD group, subjects underwent aspirin desensitization followed by a 1-month aspirin treatment. Clinical parameters improved and CD4(+) IFN-gamma levels decreased significantly. No significant change in lipoxin levels was recorded. CD4(+) IFN-gamma and CD4(+) IL-10 levels in AERD patients after 1-month aspirin desensitization treatment were similar to the healthy controls. The study confirms aspirin desensitization is effective clinically in AERD patients and suggests that IFN gamma and IL-10 expression in CD4(+) T lymphocytes may be related to the mechanism of action.

  12. Prostaglandin D₂: a dominant mediator of aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Cahill, Katherine N; Bensko, Jillian C; Boyce, Joshua A; Laidlaw, Tanya M

    2015-01-01

    Aspirin desensitization followed by high-dose aspirin therapy is routinely performed for patients with aspirin-exacerbated respiratory disease (AERD). Little is known about the contributions of mediators other than cysteinyl leukotrienes to aspirin reactions and to the therapeutic benefit of high-dose aspirin therapy. We investigated differences in urinary eicosanoid metabolite levels and blood eosinophil counts in patients with AERD who tolerate and those who fail aspirin desensitization and also in patients with AERD who were successfully treated with high-dose aspirin therapy. Twenty-nine patients with AERD were stratified into those who tolerated aspirin desensitization (group I) and those who did not (group II). Urine was analyzed for eicosanoid metabolites at baseline, during aspirin reactions, and during high-dose aspirin therapy. Blood was analyzed for cell differentials at baseline and during aspirin therapy. Basal prostaglandin D2 metabolite (PGD-M; 13.6 ± 2.7 vs 7.0 ± 0.8 pmol/mg creatinine [Cr], P < .05) and thromboxane metabolite (TX-M; 1.4 ± 0.3 vs 0.9 ± 0.1 pmol/mg Cr, P < .01) levels were higher in group II than in group I. During aspirin reactions, PGD-M levels remained unchanged, whereas TX-M levels (0.7 ± 0.1 pmol/mg Cr, P = .07) tended to decrease in group I. In contrast, PGD-M levels increased dramatically in group II (61.3 ± 19.9 pmol/mg Cr, P < .05), whereas TX-M levels did not change. The decrease in FEV1 inversely correlated with basal urinary levels of both leukotriene E4 and PGD-M. Blood eosinophil and basophil levels increased and urinary PGD-M levels (2.2 ± 0.8 pmol/mg Cr, P < .001) decreased on 2 months of high-dose aspirin therapy in group I. Failure to tolerate aspirin desensitization in a subset of patients with AERD is associated with prostaglandin D2 overproduction. The increase in blood eosinophil and basophil counts during high-dose aspirin therapy might reflect the functional consequences of decreased prostaglandin D2

  13. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Aspirin-exacerbated respiratory disease: Prevalence, diagnosis, treatment, and considerations for the future

    Science.gov (United States)

    Stoner, Ashley N.; Borish, Larry

    2016-01-01

    Aspirin-exacerbated respiratory disease (AERD) is a late onset condition characterized by the Samter triad (aspirin sensitivity [as well as sensitivity to any nonselective cyclooxygenase inhibitor], nasal polyps, asthma) and additional features, including eosinophilic chronic rhinosinusitis, hypereosinophilia, anosmia, frequent absence of atopy, and, intolerance to ingestion of red wine and other alcoholic beverages. The diagnosis is rare, and, because of this, it is also often missed by physicians. However, it is highly overexpressed in patients with severe asthma (and severe chronic rhinosinusitis with nasal polyps), which makes its recognition essential. For this review, we considered mechanisms involved in the pathogenesis of this disease and discussed the clinical symptoms of AERD. We also discussed the role of aspirin desensitization in the treatment of AERD. Also, we considered medications (e.g, leukotriene modifiers) and surgical interventions that have a role in the treatment of AERD. PMID:28124651

  15. Management of patients with nonaspirin-exacerbated respiratory disease aspirin hypersensitivity reactions.

    Science.gov (United States)

    Saff, Rebecca R; Banerji, Aleena

    2015-01-01

    Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of all adverse drug reactions, with hypersensitivity reported in ∼1% of the population. NSAID hypersensitivity can be categorized into five types by the underlying disease, symptoms of reaction, and timing of reaction. These include rhinitis and asthma induced by NSAIDs (also known as aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with chronic urticaria who develop an exacerbation of their urticaria, sometimes with angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that inhibit cyclooxygenase (COX)-1. In urticaria or angioedema induced by multiple NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90 minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single NSAID-induced reactions are immediate and specific to a single NSAID and are thought to occur because of an IgE-mediated reaction against a specific epitope of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an NSAID. These are T-cell mediated and not amenable to desensitization or rechallenge. Classifying the type of NSAID hypersensitivity is important because many patients with a prior history of urticaria or angioedema induced by multiple NSAIDs will often tolerate aspirin test dose. This would allow the use of an aspirin for primary or secondary prevention in patients with coronary artery disease despite a presumed history of NSAID hypersensitivity.

  16. Aspirin-Exacerbated Asthma

    OpenAIRE

    Varghese, Mathew; Lockey, Richard F

    2008-01-01

    This review focuses on aspirin-exacerbated asthma (AEA). The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1). Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2). The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipoo...

  17. An update on the management of aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Lee, Ji-Ho; Jung, Chang-Gyu; Park, Hae-Sim

    2018-02-01

    Clinical features of aspirin-exacerbated respiratory disease (AERD) consist of moderate to severe asthma associated with chronic rhinosinusitis (CRS), which are derived from overproduction of cysteinyl leukotrienes along with chronic type 2 mediated inflammation in the upper and lower airway mucosa. Area covered: This review provides recent up-to-date information regarding phenotypes of AERD and encompasses comprehensive diagnostic methods and treatment options. To confirm the diagnosis of AERD, provocation testing via nasal, inhalation or the oral route of aspirin remains the gold standard; in vitro diagnostic methods are still not available. Essential management is to avoid cross-reacting cyclooxygenase 1 (COX-1) inhibitors along with use of highly selective COX-2 inhibitors and to maintain pharmacologic treatment depending on the severity of asthma and chronic rhinosinusitis. Recent biologics, including anti-IgE and anti-IL5 antibodies, are required in severe AERD patients with CRS. Aspirin desensitization can be recommended when indicated. Expert commentary: AERD is a heterogeneous disease in terms of severity and associated allergic disease. When performing diagnosis and treatment for AERD, such disease characteristics need to be kept in mind.

  18. Association Analysis of Polymorphisms with Aspirin-Exacerbated Respiratory Disease in a Korean Population

    Directory of Open Access Journals (Sweden)

    Jin Sol Lee

    2014-06-01

    Full Text Available The tyrosine-protein kinase Tec (TEC is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second (FEV1 by aspirin provocation, two variations (rs7664091 and rs12500534 and one haplotype (TEC_BL2_ht4 showed nominal associations with FEV1 decline (p = 0.03-0.04. However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.

  19. Association analysis of ILVBL gene polymorphisms with aspirin-exacerbated respiratory disease in asthma.

    Science.gov (United States)

    Chang, Hun Soo; Park, Jong Sook; Lee, Ho Sung; Lyu, Jiwon; Son, Ji-Hye; Choi, Inseon S; Shin, Hyoung Doo; Park, Choon-Sik

    2017-12-16

    We previously reported that the ILVBL gene on chromosome 19p13.1 was associated with the risk for aspirin-exacerbated respiratory disease (AERD) and the percent decline of forced expired volume in one second (FEV1) after an oral aspirin challenge test. In this study, we confirmed the association between polymorphisms and haplotypes of the ILVBL gene and the risk for AERD and its phenotype. We recruited 141 AERD and 995 aspirin-tolerant asthmatic (ATA) subjects. All study subjects underwent an oral aspirin challenge (OAC). Nine single nucleotide polymorphisms (SNPs) with minor allele frequencies above 0.05, which were present in the region from 2 kb upstream to 0.5 kb downstream of ILVBL in Asian populations, were selected and genotyped. In an allelic association analysis, seven of nine SNPs were significantly associated with the risk for AERD after correction for multiple comparisons. In a codominant model, the five SNPs making up block2 (rs2240299, rs7507755, rs1468198, rs2074261, and rs13301) showed significant associations with the risk for AERD (corrected P = 0.001-0.004, OR = 0.59-0.64). Rs1468198 was also significantly associated with the percent decline in FEV1 in OAC tests after correction for multiple comparisons in the codominant model (corrected P = 0.033), but the other four SNPs in hapblock2 were not. To the best of our knowledge, this is the first report of an association between SNPs on ILVBL and AERD. SNPs on ILVBL could be promising genetic markers of this condition.

  20. Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease pathogenesis.

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    White, Andrew A; Doherty, Taylor A

    2018-01-01

    Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic nasal polyps, asthma, and airway reactions upon cyclooxygenase (COX) 1 inhibition. AERD is present in up to 7% of adult patients with asthma and the underlying pathogenesis remains largely elusive but prostaglandin D2, cysteinyl leukotrienes, mast cells, and type 2 cytokines are thought to contribute. A wealth of studies have recently implicated group 2 innate lymphoid cells (ILC2), a novel lineage-negative lymphocyte population that produces type 2 cytokines, in human allergic disease pathogenesis. Importantly, our recent work identified that ILC2s are recruited to the nasal mucosa of patients on AERD after COX-1 inhibitor administration. Here, we review the potential impact of ILC2s in the development and propagation of type 2 inflammation in AERD.

  1. Prostaglandin E2 resistance in granulocytes from patients with aspirin-exacerbated respiratory disease.

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    Laidlaw, Tanya M; Cutler, Anya J; Kidder, Molly S; Liu, Tao; Cardet, Juan Carlos; Chhay, Heng; Feng, Chunli; Boyce, Joshua A

    2014-06-01

    Aspirin-exacerbated respiratory disease (AERD) is an inflammatory condition of the respiratory tract and is characterized by overproduction of leukotrienes (LT) and large numbers of circulating granulocyte-platelet complexes. LT production can be suppressed by prostaglandin E(2) (PGE(2)) and the cyclic AMP-dependent protein kinase A (PKA). To determine if PGE(2)-dependent control of LT production by granulocytes is dysregulated in AERD. Granulocytes from well-characterized patients with and without AERD were activated ex vivo and subjected to a range of functional and biochemical analyses. Granulocytes from subjects with AERD generated more LTB4 and cysteinyl LTs than did granulocytes from controls with aspirin-tolerant asthma and controls without asthma. When compared with controls, granulocytes from subjects with AERD had comparable levels of EP(2) protein expression and PGE(2)-mediated cAMP accumulation, yet were resistant to PGE(2)-mediated suppression of LT generation. Percentages of platelet-adherent neutrophils correlated positively with LTB4 generation and inversely with responsiveness to PGE(2)-mediated suppression of LTB(4). The PKA inhibitor H89 potentiated LTB4 generation by control granulocytes but was inactive in granulocytes from individuals with AERD and had no effect on platelet P-selectin induction. Both tonic PKA activity and levels of PKA catalytic gamma subunit protein were significantly lower in granulocytes from individuals with AERD relative to those from controls. Impaired granulocyte PKA function in AERD may lead to dysregulated control of 5-lipoxygenase activity by PGE(2), whereas adherent platelets lead to increased production of LTs, which contributes to the features of persistent respiratory tract inflammation and LT overproduction. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. Certain subphenotypes of aspirin-exacerbated respiratory disease distinguished by latent class analysis.

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    Bochenek, Grazyna; Kuschill-Dziurda, Joanna; Szafraniec, Krystyna; Plutecka, Hanna; Szczeklik, Andrzej; Nizankowska-Mogilnicka, Ewa

    2014-01-01

    Aspirin-exacerbated respiratory disease (AERD) is recognized as a distinct asthma phenotype. It usually has a severe course accompanied by chronic hyperplastic eosinophilic sinusitis with nasal polyps, blood eosinophilia, and increased concentrations of urinary leukotriene E4 (LTE4). More insightful analysis of individual patients shows this group to be nonhomogeneous. We sought to identify any likely subphenotypes in a cohort of patients with AERD through the application of latent class analysis (LCA). Clinical data from 201 patients with AERD (134 women) were collected from questionnaires. Standard spirometry, atopy traits, blood eosinophilia, and urinary LTE4 concentrations were evaluated. LCA was applied to identify possible AERD subphenotypes. Four classes (subphenotypes) within the AERD phenotype were identified as follows: class 1, asthma with a moderate course, intensive upper airway symptoms, and blood eosinophilia (18.9% of patients); class 2, asthma with a mild course, relatively well controlled, and with low health care use (34.8% of patients); class 3, asthma with a severe course, poorly controlled, and with severe exacerbations and airway obstruction (41.3% of patients); and class 4, poorly controlled asthma with frequent and severe exacerbations in female subjects (5.0% of patients). Atopic status did not affect class membership. Patients with particularly intensive upper airway symptoms had the highest levels of blood eosinophilia and the highest concentrations of urinary LTE4. LCA revealed unique AERD subphenotypes, thus corroborating the heterogeneity of this population. Such discrimination might facilitate more individualized treatment in difficult-to-treat patients. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. A plane screw fixation is a nidus for Paecilomyces sinusitis in a patient with aspirin exacerbated respiratory disease

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    Anthony M. Szema

    2017-01-01

    Full Text Available Titanium plane screw fixation of the frontal sinus is an approach used by otolaryngologists to obliterate this space in an attempt to reduce sinus infections. In this case, however, the titanium used became a nidus of infection which cultured the fungus Paecilomyces. The patient also had a hypersensitivity reaction to mold with positive skin tests and IgE, as well as eosinophilic esophagitis. Treatment entailed anti-fungals, anti-IgE, and fungal immunotherapy to multiple fungal antigens prevalent to the geographic region. The patient also had aspirin exacerbated respiratory disease which responded to aspirin desensitization. Her symptoms resolved after 3 months.

  4. Factors associated with asthma control in patients with aspirin-exacerbated respiratory disease.

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    Bochenek, Grazyna; Szafraniec, Krystyna; Kuschill-Dziurda, Joanna; Nizankowska-Mogilnicka, Ewa

    2015-05-01

    Effective control of asthma is the primary goal of its treatment. Despite an improved understanding of asthma pathogenesis and accessibility of novel therapies, the rate of uncontrolled asthma remains high. To find potential factors associated with asthma control in patients with aspirin-exacerbated respiratory disease (AERD). Clinical data were collected from a specifically structured questionnaire. Demographics, a history of upper airway symptoms, asthma course, exacerbations expressed as emergency department (ED) visits/hospitalizations, and asthma treatment were considered. Spirometry, skin prick tests, total IgE concentration, and blood eosinophil count were evaluated. Asthma control was assessed through the Asthma Control Test (ACT). Out of 201 AERD patients, 41 (20.4%), 69 (34.3%), and 91 (45.3%) had controlled, partially controlled, and uncontrolled asthma, respectively. A multivariate ordered logistic regression analysis revealed that hospitalizations for asthma in the previous 12 months (OR 2.88; 95%CI, 1.11-7.46), ED visits for asthma throughout its duration (OR 1.05; 95%CI, 1.004-1.10), and total IgE concentration (OR 1.28; 95%CI, 1.02-1.60) were positively associated with poor asthma control, whereas FEV1 values (OR 0.98; 95%CI, 0.96-0.99) and medical care at a referential specialty clinic (OR 0.50; 95%CI, 0.27-0.95) were positively associated with good asthma control. The prevalence of uncontrolled asthma in AERD patients is high and similar to that observed in different asthmatic populations. Owing both to the specificity and complexity of the disease, AERD patients should stay under regular care of well experienced referential medical centers to ensure that this asthma phenotype is dealt with effectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Aspirin-Exacerbated Asthma

    Directory of Open Access Journals (Sweden)

    Varghese Mathew

    2008-06-01

    Full Text Available This review focuses on aspirin-exacerbated asthma (AEA. The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1. Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2. The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO. Leukotriene C4 (LTC4 synthase is the enzyme responsible for the production of leukotriene C4, the chief cysteinyl leukotriene responsible for AEA. There have been familial occurences of AEA. An allele of the LTC4 synthase gene in AEA is known as allele C. Allele C has a higher frequency in AEA. Clinical presentation includes a history of asthma after ingestion of aspirin, nasal congestion, watery rhinorrhea and nasal polyposis. Treatment includes leukotriene receptor antagonists, leukotriene inhibitors, aspirin desinsitaztion and surgery. AEA is the most well-defined phenotype of asthma. Although AEA affects adults and children with physician-diagnosed asthma, in some cases there is no history of asthma and AEA often goes unrecognized and underdiagnosed.

  6. NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity.

    Science.gov (United States)

    Morales, D R; Guthrie, B; Lipworth, B J; Jackson, C; Donnan, P T; Santiago, V H

    2015-07-01

    The prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID-exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified. A systematic review was performed by identifying studies diagnosing NERD using blinded, placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random-effects meta-analysis. The prevalence of NERD in adults with asthma was 9.0% (95% CI 6-12%) using OPCTs and 9.9% (95% CI 9.4-10.5%) using self-reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9-97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25-3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15-2.16) and RR 1.59 (95% CI 1.21-2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29-2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12-1.67)) compared to people with NSAID-tolerant asthma. Respiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self-reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow-up. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The IL1B-511 Polymorphism (rs16944 AA Genotype Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

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    Ramcés Falfán-Valencia

    2012-01-01

    Full Text Available Aspirin exacerbated respiratory disease (AERD is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1 inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO route, inducing increased synthesis of leukotrienes (LT. The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073 and IL1B-511 (rs16944 polymorphisms in AERD, aspirin-tolerant asthma (ATA, and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944. Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, =0.018, OR 2.98, and 95% CI 1.17–7.82. This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1 is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  8. Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: Meta-analysis of controlled clinical trials.

    Science.gov (United States)

    Morales, Daniel R; Lipworth, Brian J; Guthrie, Bruce; Jackson, Cathy; Donnan, Peter T; Santiago, Virginia H

    2014-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) cause bronchospasm in susceptible patients with asthma, often termed aspirin-exacerbated respiratory disease (AERD), with the risk being greatest after acute exposure. Selective NSAIDs that preferentially inhibit COX-2 might be safer. We sought to systematically evaluate changes in symptoms and pulmonary function after acute selective NSAID or COX-2 inhibitor exposure in patients with the AERD phenotype. A systematic review of databases was performed to identify all blinded, placebo-controlled clinical trials evaluating acute selective NSAID or COX-2 inhibitor exposure in patients with AERD. Effect estimates for changes in respiratory function and symptoms were pooled by using fixed-effects meta-analysis, with heterogeneity investigated. No significant difference in respiratory symptoms (risk difference, -0.01; 95% CI, -0.03 to 0.01; P = .57), decrease in FEV1 of 20% or greater (RD, 0.00; 95% CI, -0.02 to 0.02; P = .77), or nasal symptoms (RD, -0.01; 95% CI, -0.04 to 0.02; P = .42) occurred with COX-2 inhibitors (eg, celecoxib). Selective NSAID exposure caused respiratory symptoms in approximately 1 in 13 patients with AERD (RD, 0.08; 95% CI, 0.02 to 0.14; P = .01). No significant differences were found according to leukotriene antagonist exposure or whether NSAIDs were randomly allocated. According to clinical trial evidence in patients with stable mild-to-moderate asthma with AERD, acute exposure to COX-2 inhibitors is safe, and selective NSAIDs exhibit a small risk. Thus COX-2 inhibitors could be used in patients with AERD or in patients with general asthma unwilling to risk nonselective NSAID exposure when oral challenge tests are unavailable. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  9. Low E-prostanoid 2 receptor levels and deficient induction of the IL-1β/IL-1 type I receptor/COX-2 pathway: Vicious circle in patients with aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Machado-Carvalho, Liliana; Martín, Margarita; Torres, Rosa; Gabasa, Marta; Alobid, Isam; Mullol, Joaquim; Pujols, Laura; Roca-Ferrer, Jordi; Picado, Cesar

    2016-01-01

    We hypothesized that the 2 reported alterations in aspirin-exacerbated respiratory disease (AERD), reduced expression/production of COX-2/prostaglandin (PG) E2 and diminished expression of E-prostanoid (EP) 2 receptor, are closely linked. We sought to determine the mechanisms involved in the altered regulation of the COX pathway in patients with AERD. Fibroblasts were obtained from nasal mucosa; samples of control subjects (NM-C, n = 8) and from nasal polyps from patients with aspirin-exacerbated respiratory disease (NP-AERD, n = 8). Expression of the autocrine loop components regulating PGE2 production and signaling, namely IL-1 type I receptor (IL-1RI), COX-2, microsomal prostaglandin E synthase 1 (mPGES-1), and EP receptors, was assessed at baseline and after stimulation with IL-1β, PGE2, and specific EP receptor agonists. Compared with NM-C fibroblasts, basal expression levels of IL-1RI and EP2 receptor were lower in NP-AERD fibroblasts. IL-1β-induced IL-1RI, COX-2, and mPGES-1 expression levels were also lower in these cells. Levels of IL-1RI positively correlated with COX-2 and mPGES-1 expression in both NM-C and NP-AERD fibroblasts. Incubation with either exogenous PGE2 or selective EP2 agonist significantly increased expression of IL-1RI in NM-C fibroblasts and had hardly any effect on NP-AERD fibroblasts. Alterations in IL-1RI, COX-2, and mPGES-1 expression that were found in NP-AERD fibroblasts were corrected when EP2 receptor expression was normalized by transfection of NP-AERD fibroblasts. Altered expression of EP2 in patients with AERD contributes to deficient induction of IL-1RI, reducing the capacity of IL-1β to increase COX-2 and mPGES-1 expression, which results in low PGE2 production. This impairment in the generation of PGE2 subsequently reduces its ability to induce IL-1RI. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Risk of asthma exacerbation associated with nonsteroidal anti-inflammatory drugs in childhood asthma

    OpenAIRE

    Lo, Pei-Chia; Tsai, Yueh-Ting; Lin,Shun-Ku; Lai, Jung-Nien

    2016-01-01

    Abstract Patients allergic to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) who develop respiratory reactions such as bronchospasm or asthma exacerbation have aspirin-induced asthma or NSAIDs-exacerbated respiratory disease. However, large-scale studies have not been conducted to investigate the risk of aspirin/NSAIDs exposure in children with asthma. Therefore, this study evaluated the relationship between aspirin/NSAIDs and the risk of asthma exacerbation in children with asthma....

  11. Aspirin-Exacerbated Respiratory Disease: Evaluation and Management

    Science.gov (United States)

    2011-01-01

    ly helpful in patients who have suboptimal control with current- ly available pharmacotherapy or if they require multiple opera- tions due to re... pregnancy , unstable asthma, gastric ulcers or bleeding disorders. We screen out patients with the above conditions and require that all patients

  12. Clinical and Pulmonary Function Markers of Respiratory Exacerbation Risk in Subjects With Quadriplegic Cerebral Palsy.

    Science.gov (United States)

    Vianello, Andrea; Carraro, Elena; Pipitone, Emanuela; Marchese-Ragona, Rosario; Arcaro, Giovanna; Ferraro, Marco; Paladini, Luciana; Martinuzzi, Andrea

    2015-10-01

    Although respiratory exacerbations are common in patients with quadriplegic cerebral palsy (CP), little is known about the factors that are related to increased exacerbation risk. This study aimed to identify the clinical and pulmonary function variables signaling risk of exacerbation in this type of patient. Thirty-one children and young adults with quadriplegic CP underwent a comprehensive history, physical examination, and pulmonary function test, including arterial blood gas analysis, airway resistance using the interrupter technique, and home overnight SpO2 monitoring. Subjects were divided into 2 groups depending on the number of respiratory exacerbations reported during the year before study entry: frequent exacerbators (ie, ≥ 2 exacerbations) and infrequent exacerbators (ie, < 2 exacerbations). The frequent exacerbators were more likely to require hospitalization due to respiratory disorders compared with the infrequent exacerbators (13/14 vs 9/17, P = .02). Respiratory exacerbation was found to be associated with diagnosis of gastroesophageal reflux (adjusted odds ratio of 23.95 for subjects with confirmed diagnosis, P = .02) and higher PaCO2 levels (adjusted odds ratio of 12.60 for every 5-mm Hg increase in PaCO2 , P = .05). Subjects with PaCO2 ≥ 35 mm Hg showed an exacerbation odds ratio of 15.2 (95% CI 1.5-152.5, P = .01). Gastroesophageal reflux and increased PaCO2 can be considered simple, clinically useful markers of increased exacerbation risk in young subjects with quadriplegic CP. Copyright © 2015 by Daedalus Enterprises.

  13. Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies.

    Science.gov (United States)

    Quao, Zola Chihombori; Tong, Mancy; Bryce, Elena; Guller, Seth; Chamley, Lawrence W; Abrahams, Vikki M

    2018-01-01

    Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin (LMWH) or aspirin (ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells (HEECs), and the influence of LMWH and ASA. HEECs were exposed to aPL or control IgG, with or without low-dose LMWH and ASA, alone or in combination. Chemokine and angiogenic factor secretion were measured by ELISA. A tube formation assay was used to measure angiogenesis. aPL increased HEEC secretion of pro-angiogenic VEGF and PlGF; increased anti-angiogenic sFlt-1; inhibited basal secretion of the chemokines MCP-1, G-CSF, and GRO-α; and impaired angiogenesis. LMWH and ASA, alone and in combination, exacerbated the aPL-induced changes in the HEEC angiogenic factor and chemokine profile. There was no reversal of the aPL inhibition of HEEC angiogenesis by either single or combination therapy. By aPL inhibiting HEEC chemokine secretion and promoting sFlt-1 release, the uterine endothelium may contribute to impaired placentation and vascular transformation. LMWH and ASA may further contribute to endothelium dysfunction in women with obstetric APS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. A novel respiratory symptom scoring system for CF pulmonary exacerbations.

    Science.gov (United States)

    Jarad, N A; Sequeiros, I M

    2012-02-01

    There is currently no simple scoring system to evaluate change in symptoms during a pulmonary exacerbation (PEx) in adult cystic fibrosis (CF) patients. We evaluated 265 episodes in 58 adult CF patients. A simple symptom score was administered at the start and the end of each PEx. The score evaluated four symptoms: cough, sputum, breathlessness and fatigue. Each symptom was scored from one (mild symptoms) to four (severe symptoms). The total symptom score was the summation of all the four symptoms. The total symptom score was compared with CF Respiratory Questionnaire (CFRQ) and with spirometry. There was significant internal correlation between scores for each pair of symptoms. The total symptom score correlated with the functional activity score and the respiratory score domains and with the summary score for CFRQ. The total symptom score correlated with spirometry values. Symptom score improved after 2-week treatment with intravenous (IV) antibiotics in 88.3%, remained unchanged in 7.3% and worsened in 4.4% of all episodes. Changes in symptom score after IV treatment correlated with changes of all main spirometry measurements. This new symptom score is simple and sensitive to change over a short period. It correlates with established quality-of-life questionnaires and with spirometry. The changes of symptom score over a short period correlate with changes in spirometry. This score can be used as an added tool to assess the outcome of CF PExs.

  15. Changes of Respiratory Mechanics in COPD Patients from Stable State to Acute Exacerbations with Respiratory Failure.

    Science.gov (United States)

    Ceriana, Piero; Vitacca, Michele; Carlucci, Annalisa; Paneroni, Mara; Pisani, Lara; Nava, Stefano

    2017-04-01

    Symptoms, clinical course, functional and biological data during an exacerbation of chronic obstructive pulmonary disease (EXCOPD) have been investigated, but data on physiological changes of respiratory mechanics during a severe exacerbation with respiratory acidosis requiring noninvasive mechanical ventilation (NIMV) are scant. The aim of this study was to evaluate changes of respiratory mechanics in COPD patients comparing data observed during EXCOPD with those observed during stable state in the recovery phase. In 18 COPD patients having severe EXCOPD requiring NIMV for global respiratory failure, we measured respiratory mechanics during both EXCOPD (T0) and once the patients achieved a stable state (T1). The diaphragm and inspiratory muscles effort was significantly increased under relapse, as well as the pressure-time product of the diaphragm and the inspiratory muscle (PTPdi and PTPes). The resistive loads to breathe (i.e., PEEPi,dyn, compliance and inspiratory resistances) were also markedly increased, while the maximal pressures generated by the diaphragm and the inspiratory muscles, together with forced expired volumes were decreased. All these indices statistically improved but with a great intrasubject variability in stable condition. Moreover, tension-time index (TTdi) significantly improved from the EXCOPD state to the condition of clinical stability (0.156 ± 0.04 at T0 vs. 0.082 ± 0.02 at T1 p respiratory pump is impaired, and although the patients exhibit a rapid shallow breathing pattern, this does not necessarily correlate with a TTdi ≥ 0.15. These changes are reverted once they recover from the EXCOPD, despite a large variability between patients.

  16. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

    Science.gov (United States)

    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  17. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Kwak, Hyun Jung; Park, Dong Won; Kim, Jee Eun; Park, Min Kyung; Koo, Gun Woo; Park, Tai Sun; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Kim, Sang-Heon

    2016-10-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

  19. NEW OPPORTUNITIES OF PROPHYLAXIS OF BRONCHIAL ASTHMA EXACERBATIONS IN CHILDREN WITH ACUTE RESPIRATORY INFECTION

    Directory of Open Access Journals (Sweden)

    V.N. Chernyshov

    2010-01-01

    Full Text Available The data on pidotimod (Imunorix effectiveness in prophylaxis of bronchial asthma exacerbations in children are analyzed. Authors’ trial included 55 children 5–10 years old with exacerbations of a disease caused by acute respiratory infections. Authors studied influence of pidotimod on antioxidant system of blood serum. The effectiveness of the drug for the prophylaxis of respiratory infections in children with bronchial asthma was shown, and this effect favored to the decrease of rate of exacerbations.Key words: children, bronchial asthma, prophylaxis, pidotimod.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:54-57

  20. Prophylactic intranasal alpha 2 interferon and viral exacerbations of chronic respiratory disease.

    OpenAIRE

    Wiselka, M. J.; Nicholson, K G; Kent, J.; Cookson, J B; Tyrrell, D. A.

    1991-01-01

    BACKGROUND As respiratory virus infections often lead to exacerbations of chronic bronchitis and asthma an effective antiviral drug may be helpful in such patients. Alpha 2 interferon has been shown to give protection against rhinovirus infections in field studies. METHODS Patients with chronic respiratory disease exposed to close contacts with symptoms of upper respiratory tract infection were randomly allocated to receive nasal sprays of recombinant alpha 2 interferon (3 x 10(6) IU) or plac...

  1. Asthma exacerbations: Understanding role of viral respiratory tract infections and possible treatment strategies

    Directory of Open Access Journals (Sweden)

    Kavita Sekhri

    2015-01-01

    Full Text Available Asthma is common, affecting around 500 billion people worldwide. It is a complex disease influenced by both genetic and environmental factors. Upper respiratory tract infections with viruses commonly precipitate severe and sustained asthma exacerbations (AEs. Exacerbations are responsible for the enormous amount of emotional and economic stress apart from imposing risk of hospitalization and even death. Hence, agents targeting these infections can contribute toward decreasing asthma morbidity and associated financial burden. Over the past years novel, pharmacological therapies are evolved for the treatment of asthma, but their exact role in exacerbations is still unclear. This article reviews the role of respiratory viral infections in AEs and discusses role of new therapeutic approaches to overcome it. Medline, Medscape, EMBASE, Cochrane database, Scopus and clinicaltrials.gov were searched using terms such as "asthma," "AE" and "viral respiratory infections." Journal articles published from 2000 to 2013 describing AEs were screened.

  2. [Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

    Science.gov (United States)

    Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

    2017-04-12

    Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95% CI 1.51-16.48, P =0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

  3. Respiratory infections cause the release of extracellular vesicles: implications in exacerbation of asthma/COPD.

    Directory of Open Access Journals (Sweden)

    Suffwan Eltom

    Full Text Available Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs in vitro and in bodily fluids. ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations. Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation. Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs. When exposed to ATP the EVs release IL-1β/IL-18 via a P2X7/caspase-dependent mechanism. Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia.This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area.

  4. Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2013-02-01

    Full Text Available Abstract Background Bronchiectasis unrelated to cystic fibrosis (CF is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed to receive: 1 azithromycin (5 mg/kg daily with placebo amoxycillin-clavulanate or 2 amoxycillin-clavulanate (22.5 mg/kg twice daily with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and

  5. Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    Miguel Angel Fernandez-Granero

    2015-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients’ quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD. The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a a respiratory sensor embedded in a self-tailored housing for ageing users; (b a telehealth framework; (c CARS and (d machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA and a support vector machine (SVM classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems.

  6. ASPIRIN VERSUS INDOMETHACIN TREATMENT OF PATENT DUCTUS-ARTERIOSUS IN PRETERM INFANTS WITH RESPIRATORY-DISTRESS SYNDROME

    NARCIS (Netherlands)

    VANOVERMEIRE, B; BRUS, F; VANACKER, KJ; VANDERAUWERA, JC; SCHASFOORT, M; ELZENGA, NJ; OKKEN, A

    1995-01-01

    Indomethacin (Indo) is commonly used for treatment of patent ductus arteriosus (PDA) but has renal failure as a main side effect. Aspirin (ASA) is an alternative, but there are no controlled trials on its efficacy. We randomly assigned 75 premature infants suffering from respiratory distress

  7. Impact of exacerbations on respiratory system impedance measured by a forced oscillation technique in COPD: a prospective observational study.

    Science.gov (United States)

    Kamada, Takahiro; Kaneko, Masahiro; Tomioka, Hiromi

    2017-01-01

    Forced oscillation technique (FOT) has been reported to be useful in the evaluation and management of obstructive lung disease, including COPD. To date, no data are available concerning long-term changes in respiratory system impedance measured by FOT. Additionally, although exacerbations have been reported to be associated with excessive lung function decline in COPD, the impact of exacerbations on the results of FOT has not been demonstrated. The aim of this study was to investigate the longitudinal changes in respiratory system impedance and the influence of exacerbations thereon. Between March 2011 and March 2012, outpatients who attended Kobe City Medical Center West Hospital with a diagnosis of COPD were assessed for eligibility. Baseline patient characteristics (age, sex, body mass index, smoking history, current smoking status, COPD stage), lung function (post-bronchodilator forced expiratory volume in 1 second [FEV 1 ]), blood tests (neutrophils and eosinophils), FOT, and COPD assessment test results were collected at enrollment. Lung function and FOT were examined every 6 months until March 2016. Annual changes in FEV 1 and FOT parameters were obtained from the slope of the linear regression curve. The patients were divided into 2 groups based on exacerbation history. Fifty-one of 58 patients with COPD were enrolled in this study. The median follow-up period was 57 (52-59) months. Twenty-five (49%) patients experienced exacerbations. A significant annual decline in FEV 1 and respiratory system impedance were shown. Additionally, annual changes in FEV 1 , respiratory system resistance at 5 Hz, respiratory system reactance at 5 Hz, and resonant frequency were greater in patients with exacerbations than in those without exacerbations. Exacerbations of COPD lead not only to a decline in lung function but also to an increase in respiratory system impedance.

  8. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction.

    Science.gov (United States)

    Rose, Jason J; Voora, Deepak; Cyr, Derek D; Lucas, Joseph E; Zaas, Aimee K; Woods, Christopher W; Newby, L Kristin; Kraus, William E; Ginsburg, Geoffrey S

    2015-01-01

    Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the

  9. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Jason J Rose

    Full Text Available Influenza infection is associated with myocardial infarction (MI, suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1 a validated blood gene expression signature of respiratory viral infection (viral GES was associated with MI and 2 respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES of platelet function in response to aspirin that is associated with MI.A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV (n=20, Human Rhinovirus (HRV (n=20, Influenza A virus subtype H1N1 (H1N1 (n=24, Influenza A Virus subtype H3N2 (H3N2 (n=17. We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status.In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32 had MI versus 12.2% (69/567 among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04. In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04.A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the

  10. Sodium Cromoglycate Prevents Exacerbation of IgE-Mediated Food-Allergic Reaction Induced by Aspirin in a Rat Model of Egg Allergy.

    Science.gov (United States)

    Yokooji, Tomoharu; Matsuo, Hiroaki

    2015-01-01

    Aspirin (ASP)-facilitated absorption of ingested allergens is considered an exacerbating factor in the development of food allergy. Sodium cromoglycate (SCG) is used for the treatment of atopic dermatitis with food allergy, but the efficacy of SCG in ASP-exacerbated food-allergy reactions is unclear. In this study, we evaluated the effect of SCG on ASP-exacerbated food-allergic reactions, as well as allergen absorption, in egg-allergic model rats. Plasma concentrations of ovalbumin (OVA) and fluorescein isothiocyanate-labeled dextran (FD-40), a marker for nonspecific-absorption pathways, were measured after oral administration of mixtures of OVA and FD-40 in OVA-unsensitized and OVA-sensitized rats. IgE-mediated allergic reactions were evaluated by measuring changes in rectal temperature and Evans blue dye (EBD) extravasation in the intestine and liver after oral challenge with OVA. The effects of ASP and SCG on such absorption and allergic reactions were also evaluated kinetically. In OVA-sensitized rats, plasma concentrations of OVA and FD-40 were significantly higher than those in unsensitized rats after oral administration. ASP increased the intestinal absorption of OVA and FD-40 via the paracellular pathway, and a lower rectal temperature and higher EBD extravasation were detected in the intestine and liver of OVA-sensitized rats. SCG ameliorated these ASP-facilitated absorptions and allergic reactions in a dose-dependent manner. In particular, high-dose SCG (195.2 μmol/kg) completely inhibited these absorptions and reactions. SCG can prevent ASP-exacerbated allergic reactions in patients with food allergy resulting from inhibition of increases in allergen absorption. © 2015 S. Karger AG, Basel.

  11. Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations.

    Science.gov (United States)

    Kloepfer, Kirsten M; Lee, Wai Ming; Pappas, Tressa E; Kang, Theresa J; Vrtis, Rose F; Evans, Michael D; Gangnon, Ronald E; Bochkov, Yury A; Jackson, Daniel J; Lemanske, Robert F; Gern, James E

    2014-05-01

    Detection of either viral or bacterial pathogens is associated with wheezing in children; however, the influence of both bacteria and viruses on illness symptoms has not been described. We evaluated bacterial detection during the peak rhinovirus season in children with and without asthma to determine whether an association exists between bacterial infection and the severity of rhinovirus-induced illnesses. Three hundred eight children (166 with asthma and 142 without asthma) aged 4 to 12 years provided 5 consecutive weekly nasal samples during September and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were performed on all nasal samples. Detection rates were 53%, 17%, and 11% for H influenzae, S pneumoniae, and M catarrhalis, respectively, with detection of rhinovirus increasing the risk of detecting bacteria within the same sample (odds ratio [OR], 2.0; 95% CI, 1.4-2.7; P rhinovirus, S pneumoniae was associated with increased cold symptoms (mean, 2.7 [95% CI, 2.0-3.5] vs 1.8 [95% CI, 1.5-2.2]; P = .006) and moderate asthma exacerbations (18% [95% CI, 12% to 27%] vs 9.2% [95% CI, 6.7% to 12%]; P = .006). In the presence of rhinovirus, S pneumoniae was associated with increased moderate asthma exacerbations (22% [95% CI, 16% to 29%] vs 15% [95% CI, 11% to 20%]; P = .01). Furthermore, M catarrhalis detected alongside rhinovirus increased the likelihood of experiencing cold symptoms, asthma symptoms, or both compared with isolated detection of rhinovirus (OR, 2.0 [95% CI, 1.0-4.1]; P = .04). Regardless of rhinovirus status, H influenzae was not associated with respiratory symptoms. Rhinovirus infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M catarrhalis and S pneumoniae contribute to the severity of respiratory tract illnesses, including asthma exacerbations

  12. Experiences of patients undergoing pulmonary rehabilitation during an exacerbation of chronic respiratory disease.

    Science.gov (United States)

    Vincent, Emma E; Chaplin, Emma J; Williams, Johanna Ea; Harvey-Dunstan, Theresa; Greening, Neil J; Steiner, Michael C; Morgan, Mike D; Singh, Sally J

    2017-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized in the later stages by acute exacerbations that often require hospitalization. Pulmonary rehabilitation is recommended for patients with COPD to aid symptom control, improve quality of life and increase physical activity. We have previously reported a large intervention trial commenced during a hospital admission. The aim of this sub-study was to evaluate the patients' experiences of discharge following the hospitalization for an acute exacerbation of COPD. During a programme of early rehabilitation (ER) patient perceptions, experiences and healthcare use were collated during the month that followed their discharge. ER (started during their admission) was comprised of exercise training techniques that were modified to suit the environment of acute illness, together with an education and self-management programme. Each patient was then supported on the programme by telephone contact, following their discharge home, at 48 hours, 2 weeks and 4 weeks. We collected information in relation to the walking and exercise progression; we monitored patient recall of healthcare use, compliance/understanding of medical therapy, as well as their wider perceptions that may have influenced the recovery process. Healthcare use was captured using GP records and data analysis. Of the 100 patients, 47 males, (mean (standard deviation)) 71 (9.3) years, FEV1 1.14 L (0.6), BMI 26.6 (6.9), pack smoked years 45.8 (29.6), ethnicity White British 97%, were discharged home following an acute exacerbation of their respiratory symptoms, to an ER programme. At 48 hours following discharge, a minority (20%) of patients stated their symptoms were 'feeling better'; 15% highlighted that they found the prescribed 'exercise difficult'; 44% of patients felt at the end of the month that prescribed exercise programme had a 'positive effect' on their recovery from their exacerbation; 38% of patients felt their family had a positive effect on

  13. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose : a pilot study

    NARCIS (Netherlands)

    van Geffen, Wouter H.; Bruins, Marcel; Kerstjens, Huib A. M.

    2016-01-01

    Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose

  14. Respiratory infectious phenotypes in acute exacerbation of COPD: an aid to length of stay and COPD Assessment Test

    Directory of Open Access Journals (Sweden)

    Dai MY

    2015-10-01

    Full Text Available Meng-Yuan Dai,1 Jin-Ping Qiao,2 Yuan-Hong Xu,2 Guang-He Fei1 1Pulmonary Department, 2Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China Purpose: To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS and the COPD Assessment Test (CAT Scale in acute exacerbation of COPD (AECOPD. Patients and methods: We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups. The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture. LOS and CAT as well as demographic information were recorded. Results: Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both. Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus. Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae. The longest LOS and the highest CAT score were detected in coinfection group. CAT score was positively correlated with LOS. Conclusion: Respiratory infection is a common causative agent of exacerbations in COPD. Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS. CAT score may be a predictor of longer LOS in AECOPD. Keywords: COPD, acute exacerbation, respiratory infectious, phenotypes, LOS, CAT

  15. Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for readmission and mortality – a systematic review

    Science.gov (United States)

    Puhan, Milo A; Scharplatz, Madlaina; Troosters, Thierry; Steurer, Johann

    2005-01-01

    Background Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems. Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity. To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses. Methods Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings. We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation. Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality. We pooled the results using fixed effects models where statistically significant heterogeneity (p ≤ 0.1) was absent. Results We identified six trials including 230 patients. Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12–0.54]) and mortality (0.45 [0.22–0.91]). Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13–1.61) for the fatigue domain, 1.36 (0.94–1.77) for emotional function and 1.88 (1.67–2.09) for mastery. Weighted mean differences for the St. Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials, rehabilitation improved exercise capacity (64–215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48–115). Conclusion Evidence from six trials suggests that

  16. Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for readmission and mortality -- a systematic review.

    Science.gov (United States)

    Puhan, Milo A; Scharplatz, Madlaina; Troosters, Thierry; Steurer, Johann

    2005-06-08

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems. Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity. To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses. Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings. We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation. Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality. We pooled the results using fixed effects models where statistically significant heterogeneity (p Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and mortality (0.45 [0.22-0.91]). Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain, 1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery. Weighted mean differences for the St. Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials, rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115). Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation. Larger trials, however, are needed to further

  17. Exacerbation of pathology by oxidative stress in respiratory and locomotor muscles with Duchenne muscular dystrophy.

    Science.gov (United States)

    Lawler, John M

    2011-05-01

    Duchenne muscular dystrophy (DMD) is the most devastating type of muscular dystrophy, leading to progressive weakness of respiratory (e.g. diaphragm) and locomotor muscles (e.g. gastrocnemius). DMD is caused by X-linked defects in the gene that encodes for dystrophin, a key scaffolding protein of the dystroglycan complex (DCG) within the sarcolemmal cytoskeleton. As a result of a compromised dystroglycan complex, mechanical integrity is impaired and important signalling proteins (e.g. nNOS, caveolin-3) and pathways are disrupted. Disruption of the dystroglycan complex leads to high susceptibility to injury with repeated, eccentric contractions as well as inflammation, resulting in significant damage and necrosis. Chronic damage and repair cycling leads to fibrosis and weakness. While the link between inflammation with damage and weakness in the DMD diaphragm is unresolved, elevated oxidative stress may contribute to damage, weakness and possibly fibrosis. While utilization of non-specific antioxidant interventions has yielded inconsistent results, recent data suggest that NAD(P)H oxidase could play a pivotal role in elevating oxidative stress via integrated changes in caveolin-3 and stretch-activated channels (SACs). Oxidative stress may act as an amplifier, exacerbating disruption of the dystroglycan complex, upregulation of the inflammatory transcription factor NF-B, and thus functional impairment of force-generating capacity.

  18. Eosinophilic and non-eosinophilic COPD patients with chronic respiratory failure: neutrophil-to-lymphocyte ratio as an exacerbation marker

    OpenAIRE

    Acartürk Tunçay E; Karakurt Z; Aksoy E; Saltürk C; Gungor S; Cıftaslan N; Irmak I; Yavuz D; Ocakli B; Adıgüzel N

    2017-01-01

    Eylem Acartürk Tunçay, Zuhal Karakurt, Emine Aksoy, Cuneyt Saltürk, Sinem Gungor, Nezihe Ciftaslan, Ä°lim Irmak, Dilek Yavuz, Birsen Ocakli, Nalan Adıgüzel Respiratory Intensive Care Unit, Sureyyapaşa Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, Istanbul, Turkey Aim: Increased dyspnea, sputum volume, and purulence are subjective symptoms in COPD patients. To diagnose COPD exacerbations with chroni...

  19. Low-intensity noninvasive ventilation: Lower pressure, more exacerbations of chronic respiratory failure

    Directory of Open Access Journals (Sweden)

    Toru Kadowaki

    2016-01-01

    Conclusions: Attention should be paid to CRF patients who are initially administered LI-NPPV; they should be carefully observed because they can develop more exacerbations of CRF than patients undergoing C-NPPV. If possible, higher initial PS should be administered to prevent CRF exacerbations.

  20. Eosinophilic and non-eosinophilic COPD patients with chronic respiratory failure: neutrophil-to-lymphocyte ratio as an exacerbation marker

    Directory of Open Access Journals (Sweden)

    Acartürk Tunçay E

    2017-11-01

    Full Text Available Eylem Acartürk Tunçay, Zuhal Karakurt, Emine Aksoy, Cuneyt Saltürk, Sinem Gungor, Nezihe Ciftaslan, İlim Irmak, Dilek Yavuz, Birsen Ocakli, Nalan Adıgüzel Respiratory Intensive Care Unit, Sureyyapaşa Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, Istanbul, Turkey Aim: Increased dyspnea, sputum volume, and purulence are subjective symptoms in COPD patients. To diagnose COPD exacerbations with chronic respiratory failure (CRF and to assess the requirement for antibiotic treatment, physicians require more objective criteria. We aimed to investigate whether neutrophil-to-lymphocyte ratio (NLR can be used as an infectious exacerbation marker in COPD patients with CRF.Patients and methods: This retrospective cross-sectional study was performed in the intensive care outpatient clinic of a tertiary training hospital between 2014 and 2015. Patients admitted with CRF due to COPD and who had complete blood count (CBC results were enrolled. CBC results and C-reactive protein (CRP levels were obtained from the hospital online database. The “modified exacerbation model (MEM” was defined as follows: exacerbation A, leukocytes ≥12,000/mm3, CRP >10 mg/dL; exacerbation B, leukocytes ≥10,000/mm3, CRP >10 mg/dL; exacerbation C, leukocytes ≥10,000/mm3, CRP >8 mg/dL; exacerbation D, leukocytes ≥10,000/mm3, CRP >5 mg/dL. The cutoff value of NLR was defined for each model. Patients were split into two groups based on the NLR cutoff value according to the “NLR exacerbation model” and further subgrouped according to peripheral eosinophil percentage (eosinophils ≥2% and <2% and compared with the MEM.Results: A total of 1,066 COPD patients (430 females, 40.3%, with a mean age of 66±13 years, were included. A NLR cutoff value of 3.54 (NLR ≥3.54, n=366, 34% showed the highest sensitivity and specificity for model A (78%, 69%, model B (63%, 71%, model C (61%, 72%, and model D (58%, 72

  1. What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

    Science.gov (United States)

    Kim, Deog Kyeom; Lee, Jungsil; Park, Ju Hee; Yoo, Kwang Ha

    2018-01-24

    Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is

  2. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

    OpenAIRE

    Chang SC; Shi JD; Fu CP; Wu X; Li SQ

    2016-01-01

    Suchi Chang,1 Jindong Shi,2 Cuiping Fu,1 Xu Wu,1 Shanqun Li1 1Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Respiratory Medicine, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China Background: COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Inten...

  3. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.

    Science.gov (United States)

    van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

    2016-06-16

    Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in 'smelling' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.

  4. Detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: Exacerbation versus stable condition.

    Science.gov (United States)

    Kokturk, Nurdan; Bozdayi, Gulendam; Yilmaz, Senay; Doğan, Bora; Gulbahar, Ozlem; Rota, Seyyal; Tatlicioglu, Turkan

    2015-08-01

    Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.

  5. Evaluation of the association between atypical bacteria infections and respiratory tract diseases with emphasis on bronchial asthma exacerbations in children.

    Science.gov (United States)

    Szczepanik, Agnieszka; Kozioł-Montewka, Maria; Tuszkiewicz-Misztal, Ewa; Niedzielska, Grazyna; Górnicka, Grazyna; Niedźwiadek, Justyna; Niedzielski, Artur

    2004-01-01

    Mycoplasma pneumoniae and Chlamydia pneumonie are important etiological agents responsible for human respiratory tract diseases. Recently, these atypical microorganisms received much attention regarding their role in bronchial asthma pathogenesis, which is one of the most frequent chronic diseases in children. The aim of the study was to investigate the association between infections caused by these pathogens and respiratory tract diseases in children. Levels of M. pneumoniae and C. pneumoniae-specific antibodies were determined in serum samples obtained from 30 patients suffering from bronchial asthma exacerbations, 10 patients with pneumonia, 28 patients with chronic otitis media with effusion (COME) and 22 sinusitis patients. Specific anti-M. pneumoniae antibodies were detected more frequently in the patients enrolled in the study than in control subjects. The highest percentage of the serum samples, which demonstrated the presence of M. pneumoniae-specific antibodies was demonstrated in patients with asthma (60%) and it was twofold higher than in control subjects. Serologic profile of 26.6% patients with asthma, 50% of patients with pneumonia, 39.2% of patients with COME, 45.4% of patients with sinusitis and 10% of control subjects was consistent with a possible acute infection caused by M. pneumoniae. The presence of specific anti-C. pneumoniae antibodies was demonstrated in a smaller percentage of patients--in 13.3% of children with asthma, 10% of children with pneumonia and in 7.1% of patients with COME; the level of specific antiobodies was suggestive of acute chlamydial infection only in COME patients. Analysis of serologic markers for atypical bacteria infections indicates a possible association between infections caused by M. pneumoniae and bronchial asthma exacerbations and other respiratory tract disorders including pneumonia, sinusitis and COME.

  6. Analgesic and Decongestant Efficacy of the Combination of Aspirin with Pseudoephedrine in Patients With Symptoms of Upper Respiratory Tract Infection

    Science.gov (United States)

    Eccles, Ronald; Voelker, Michael

    2014-01-01

    The study investigated the efficacy and safety of a combination therapy of 1,000 mg aspirin (ASA) and 60 mg pseudoephedrine (PSE) on the symptoms of pain (combined score for headache and sore throat) and nasal congestion in 833 patients with acute upper respiratory tract viral infection (URTI), over 4 hours after a single dose in the clinic and over 3 days with multiple doses at home. The study demonstrated that over 4 hours in the clinic the combination ASA plus PSE was superior to PSE or placebo for relief of pain symptoms measured subjectively with pain scores, and was superior to ASA or placebo for relief of nasal congestion as measured objectively with rhinomanometry and subjectively with congestion scores. After 3 days of treatment, ASA plus PSE was superior to PSE but not to placebo or ASA for global pain assessments, and ASA plus PSE was superior to ASA and placebo but not to PSE for congestion assessments. No unexpected adverse events occurred and no serious adverse events were attributed to study medicines. This study demonstrates that a combination therapy of ASA plus PSE provides safe and effective relief of both common cold pain related symptoms and nasal congestion. PMID:26097788

  7. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial.

    Science.gov (United States)

    Greening, Neil J; Williams, Johanna E A; Hussain, Syed F; Harvey-Dunstan, Theresa C; Bankart, M John; Chaplin, Emma J; Vincent, Emma E; Chimera, Rudo; Morgan, Mike D; Singh, Sally J; Steiner, Michael C

    2014-07-08

    To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status. Prospective, randomised controlled trial. An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom. 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193). The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome. Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package. Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year. Early rehabilitation during hospital admission for chronic respiratory disease

  8. TNF-α and Macrophages Are Critical for Respiratory Syncytial Virus-Induced Exacerbations in a Mouse Model of Allergic Airways Disease.

    Science.gov (United States)

    Nguyen, Thi Hiep; Maltby, Steven; Simpson, Jodie L; Eyers, Fiona; Baines, Katherine J; Gibson, Peter G; Foster, Paul S; Yang, Ming

    2016-05-01

    Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV. Dexamethasone treatment completely inhibited all features of allergic disease, including AHR and eosinophil infiltration, in uninfected OVA-sensitized/challenged mice. Conversely, dexamethasone treatment following RSV-induced exacerbation only partially suppressed AHR and failed to dampen macrophage and neutrophil infiltration or inflammatory cytokine production (TNF-α, MCP-1, and KC). This mimics clinical observations in patients with exacerbations, which is associated with increased neutrophils and often poorly responds to corticosteroid therapy. Interestingly, we also observed increased TNF-α levels in sputum samples from patients with neutrophilic asthma. Although RSV-induced exacerbation was resistant to steroid treatment, inhibition of TNF-α and MCP-1 function or depletion of macrophages suppressed features of disease, including AHR and macrophage and neutrophil infiltration. Our findings highlight critical roles for macrophages and inflammatory cytokines (including TNF-α and MCP-1) in viral-induced exacerbation of asthma and suggest examination of these pathways as novel therapeutic approaches for disease management. Copyright © 2016 by The American Association of Immunologists, Inc.

  9. Aspirin overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002542.htm Aspirin overdose To use the sharing features on this page, please enable JavaScript. An overdose of aspirin means you have too much aspirin in your ...

  10. Aspirin Desensitization

    Science.gov (United States)

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

  11. Community-acquired pneumonia and survival of critically ill acute exacerbation of COPD patients in respiratory intensive care units

    Directory of Open Access Journals (Sweden)

    Lu ZW

    2016-08-01

    Full Text Available Zhiwei Lu,* Yusheng Cheng,* Xiongwen Tu, Liang Chen, Hu Chen, Jian Yang, Jinyan Wang, Liqin Zhang Department of Respiratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to appraise the effect of community-acquired pneumonia (CAP on inhospital mortality in critically ill acute exacerbation of COPD (AECOPD patients admitted to a respiratory intensive care unit.Patients and methods: A retrospective observational study was performed. Consecutive critically ill AECOPD patients receiving treatment in a respiratory intensive care unit were reviewed from September 1, 2012, to August 31, 2015. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed by Mann–Whitney U-test. Kaplan–Meier analysis was used to assess the association of CAP with survival of critically ill AECOPD patients for univariate analysis. Cox’s proportional hazards regression model was performed to identify risk factors for multivariate analysis.Results: A total of 80 consecutive eligible individuals were reviewed. These included 38 patients with CAP and 42 patients without CAP. Patients with CAP had a higher inhospital rate of mortality than patients without CAP (42% vs 33.3%, P<0.05. Kaplan–Meier survival analysis showed that patients with CAP had a worse survival rate than patients without CAP (P<0.05. Clinical characteristics, including Acute Physiology and Chronic Health Evaluation II (APACHE II score, C-reactive protein, and CAP, were found to be closely associated with survival of AECOPD individuals. Further multivariate Cox regression analysis confirmed that CAP and APACHE II were independent risk factors for inhospital mortality in critically ill AECOPD patients (CAP: hazard ratio, 5.29; 95% CI, 1.50–18.47, P<0.01 and APACHE II: hazard ratio, 1.20; 95% CI, 1.06–1.37, P<0.01.Conclusion: CAP may be

  12. MACULAR DEGENERATION AND ASPIRIN USE.

    Science.gov (United States)

    Small, Kent W; Garabetian, Christine A; Shaya, Fadi S

    2017-09-01

    To review current literature of the benefits that aspirin provides for patients' cardiovascular health compared with the risk of AMD worsening. We performed a review and critically analyzed six cardiovascular and four ophthalmological trials regarding risks and benefits of aspirin use. The prospective randomized cardiovascular trials had a cumulative 167,580 while the 3 smaller ophthalmological data sets had a cumulative 12,015 subjects. The reviewed meta-analysis literature demonstrated a statistically significant 32% reduction in the risk of nonfatal stroke with regular aspirin users. The study also documented that aspirin users decreased the risk of fatal vascular deaths by 15%. Of the three ophthalmological studies highlighting the adverse affects of aspirin association with AMD, all suggested an exacerbation of AMD without statistical significance and broad confidence bands. Overall, the number, size, and quality of the cardiovascular studies recommending aspirin use are far superior to the fewer, smaller and conflicting studies suggesting a possible adverse effect of aspirin use in relation to AMD. The benefits of aspirin usage include preserving the duration and quality of life by decreasing stroke and heart attack risk. These benefits seem to far outweigh the theoretical risks of possibly exacerbating wet AMD, which can be reasonably controlled with anti-VEGF therapy.

  13. Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

    Science.gov (United States)

    Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

    2015-09-01

    Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. [The impact of viruses in lower respiratory tract infections of the adult. Part II: acute bronchitis, acute exacerbated COPD, pneumonia, and influenza].

    Science.gov (United States)

    Ott, S R; Rohde, G; Lepper, P M; Hauptmeier, B; Bals, R; Pletz, M W R; Schumann, C; Steininger, C; Kleines, M; Geerdes-Fenge, H

    2010-01-01

    In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options. Georg Thieme Verlag KG Stuttgart New York.

  15. Aspirin revealed

    Science.gov (United States)

    Lacey, D.; Hu, X. K.; Loboda, A. V.; Mosey, N. J.; Lipson, R. H.

    2007-03-01

    Experiments are described where the experimental conditions have been optimized to detect aspirin by MALDI mass spectrometry. Although protonated aspirin was not observed by MALDI, sodium and potassium aspirin adducts could be found. Significantly better signals could be obtained by using Rb and Cs salts as cationization sources. Quantum calculations were carried out to determine the structure and energetics of the Li, K, Rb, and Cs alkali--aspirin adducts.

  16. Efficacy of a respiratory rehabilitation exercise training package in hospitalized elderly patients with acute exacerbation of COPD: a randomized control trial.

    Science.gov (United States)

    Liao, Lin-Yu; Chen, Kuei-Min; Chung, Wei-Sheng; Chien, Jung-Yien

    2015-01-01

    NCT02329873. Acute exacerbation (AE) of COPD is characterized by a sudden worsening of COPD symptoms. Previous studies have explored the effectiveness of respiratory rehabilitation for patients with COPD; however, no training program specific to acute exacerbation in elderly patients or unstable periods during hospitalization has been developed. To evaluate the effects of a respiratory rehabilitation exercise training package on dyspnea, cough, exercise tolerance, and sputum expectoration among hospitalized elderly patients with AECOPD. A randomized control trial was conducted. Pretest and posttest evaluations of 61 elderly inpatients with AECOPD (experimental group n=30; control group n=31) were performed. The experimental group received respiratory rehabilitation exercise training twice a day, 10-30 minutes per session for 4 days. The clinical parameters (dyspnea, cough, exercise tolerance, and sputum expectoration) were assessed at the baseline and at the end of the fourth day. All participants (median age =70 years, male =60.70%, and peak expiratory flow 140 L) completed the study. In the patients of the experimental group, dyspnea and cough decreased and exercise tolerance and sputum expectoration increased significantly compared with those of the patients in the control group (all Prespiratory rehabilitation exercise training package reduced symptoms and enhanced the effectiveness of the care of elderly inpatients with AECOPD.

  17. Type 2 Cysteinyl Leukotriene Receptors Drive IL-33-Dependent Type 2 Immunopathology and Aspirin Sensitivity.

    Science.gov (United States)

    Liu, Tao; Barrett, Nora A; Kanaoka, Yoshihide; Yoshimoto, Eri; Garofalo, Denise; Cirka, Haley; Feng, Chunli; Boyce, Joshua A

    2018-02-01

    Cysteinyl leukotrienes (cysLTs) facilitate mucosal type 2 immunopathology by incompletely understood mechanisms. Aspirin-exacerbated respiratory disease, a severe asthma subtype, is characterized by exaggerated eosinophilic respiratory inflammation and reactions to aspirin, each involving the marked overproduction of cysLTs. Here we demonstrate that the type 2 cysLT receptor (CysLT2R), which is not targeted by available drugs, is required in two different models to amplify eosinophilic airway inflammation via induced expression of IL-33 by lung epithelial cells. Endogenously generated cysLTs induced eosinophilia and expanded group 2 innate lymphoid cells (ILC2s) in aspirin-exacerbated respiratory disease-like Ptges-/- mice. These responses were mitigated by deletions of either Cysltr2 or leukotriene C4 synthase (Ltc4s). Administrations of either LTC4 (the parent cysLT) or the selective CysLT2R agonist N-methyl LTC4 to allergen sensitized wild-type mice markedly boosted ILC2 expansion and IL-5/IL-13 generation in a CysLT2R-dependent manner. Expansion of ILC2s and IL-5/IL-13 generation reflected CysLT2R-dependent production of IL-33 by alveolar type 2 cells, which engaged in a bilateral feed-forward loop with ILC2s. Deletion of Cysltr1 blunted LTC4-induced ILC2 expansion and eosinophilia but did not alter IL-33 induction. Pharmacological blockade of CysLT2R prior to inhalation challenge of Ptges-/- mice with aspirin blocked IL-33-dependent mast cell activation, mediator release, and changes in lung function. Thus, CysLT2R signaling, IL-33-dependent ILC2 expansion, and IL-33-driven mast cell activation are necessary for induction of type 2 immunopathology and aspirin sensitivity. CysLT2R-targeted drugs may interrupt these processes. Copyright © 2018 by The American Association of Immunologists, Inc.

  18. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure.

    Science.gov (United States)

    Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

    2016-01-01

    COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. We evaluated pressure-regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation - volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2-4 hours and 48 hours. Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2-4 hours were lower and higher, respectively, in the test group than those in the control group (P0.05). Vital signs during 2-4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2-4 hours and 48 hours was significantly lower than that in the control group (P0.05). Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining a low peak inspiratory pressure. PRVC can reduce pulmonary barotrauma risk, making it a safer protective ventilation mode than synchronized intermittent mandatory ventilation - volume control.

  19. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

    Directory of Open Access Journals (Sweden)

    Chang SC

    2016-05-01

    Full Text Available Suchi Chang,1 Jindong Shi,2 Cuiping Fu,1 Xu Wu,1 Shanqun Li1 1Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Respiratory Medicine, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China Background: COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. Objective: We evaluated pressure-regulated volume control (PRVC ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Patients and methods: Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation – volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2–4 hours and 48 hours. Results: Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2, and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2 levels. The pH and PaCO2 levels at 2–4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both; after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05. Vital signs during 2–4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05. The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2–4 hours and 48

  20. Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

    Science.gov (United States)

    Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S., IV; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

    2011-01-01

    Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders…

  1. Promoting long-term benefits of pulmonary rehabilitation: the role of reducing the impact of respiratory exacerbations.

    Science.gov (United States)

    Fahy, Bonnie F

    2014-06-01

    The importance of exercise for pulmonary patients is unquestioned. Decreased functional status has been attributed to increased hospitalizations, leading to further decreases in functionality, decreased quality of life and increased mortality. Despite known benefits of pulmonary rehabilitation, recruitment and retention of program participants can be a challenge. Alternatives to traditional pulmonary rehabilitation are reviewed with an emphasis on physical activity, exacerbation awareness and a reduction in hospital admissions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Efficacy of a respiratory rehabilitation exercise training package in hospitalized elderly patients with acute exacerbation of COPD: a randomized control trial

    Directory of Open Access Journals (Sweden)

    Liao LY

    2015-08-01

    Full Text Available Lin-Yu Liao,1,2 Kuei-Min Chen,2 Wei-Sheng Chung,3 Jung-Yien Chien4 1Department of Nursing, Chest Hospital, Ministry of Health and Welfare, Rende District, Tainan, 2College of Nursing, Kaohsiung Medical University, Sanmin District, Kaohsiung, 3Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, 4Department of Medicine, Chest Hospital, Ministry of Health and Welfare, Rende District, Tainan, Taiwan Clinical trials identifier: NCT02329873 Background: Acute exacerbation (AE of COPD is characterized by a sudden worsening of COPD symptoms. Previous studies have explored the effectiveness of respiratory rehabilitation for patients with COPD; however, no training program specific to acute exacerbation in elderly patients or unstable periods during hospitalization has been developed.Objective: To evaluate the effects of a respiratory rehabilitation exercise training package on dyspnea, cough, exercise tolerance, and sputum expectoration among hospitalized elderly patients with AECOPD.Methods: A randomized control trial was conducted. Pretest and posttest evaluations of 61 elderly inpatients with AECOPD (experimental group n=30; control group n=31 were performed. The experimental group received respiratory rehabilitation exercise training twice a day, 10–30 minutes per session for 4 days. The clinical parameters (dyspnea, cough, exercise tolerance, and sputum expectoration were assessed at the baseline and at the end of the fourth day.Results: All participants (median age =70 years, male =60.70%, and peak expiratory flow 140 L completed the study. In the patients of the experimental group, dyspnea and cough decreased and exercise tolerance and sputum expectoration increased significantly compared with those of the patients in the control group (all P<0.05. Within-group comparisons revealed that the dyspnea, cough, and exercise tolerance significantly improved in the experimental group by the end of the fourth

  3. [A multicenter study of respiratory multiple index in predicting weaning from mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease].

    Science.gov (United States)

    Li, Zhi-bo; Gao, Xin-jing; Wang, Dong-hao; Zhang, Bo; Zhang, Zhen-ping; Hu, Zhong-min; Xu, Lei; Qin, Ying-zhi

    2013-06-01

    To study the result of respiratory multiple index(compliance, respiratory rate, oxygenation, pressure, CROP) in predicting weaning from mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A prospective study was conducted. Two hundred and fifteen patients weaning from mechanical ventilation with AECOPD in intensive care unit (ICU) of five tertiary hospitals from September 2010 to October 2012 were enrolled. All of the AECOPD patients were troubled with respiratory failure and received non-invasive mechanical ventilation for more than 24 hours. They were conscious and cooperative at the time of extubation, and passed the spontaneous breathing trial (SBT) for 30 minutes. Before weaning, the maximal inspiratory pressure (PImax), the peak airway pressure (Ppeak), the total positive end expiratory pressure (PEEPtot), tidal volume (VT) and respiratory frequency (f) were recorded; the arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂) were detected; the effective compliance of the respiratory system (Crs) and alveolar oxygen pressure(PAO₂) were calculated. The above indexes were substituted into the formula: CROP= Crs × 1/f × PaO₂/PAO₂× PImax to get the value of CROP. Successful weaning from mechanical ventilation was defined if there was no indication for intubation within 72 hours. The receiver operating characteristic curve (ROC curve) was drawn to analyze the predict value of CROP on result of weaning from mechanical ventilation in patients with AECOPD. In 215 patients, 182 patients successfully weaned from mechanical ventilation, and 33 failed. There were no significant differences in gender, age and the acute physiology and chronic health evaluation II (APACHEII) score between the successfully weaned patients and the failed. Before weaning from mechanical ventilation, PaCO₂ in failed group was significantly higher than that in successful group (60

  4. Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells.

    Science.gov (United States)

    Kim, Ki-Hye; Lee, Young-Tae; Hwang, Hye Suk; Kwon, Young-Man; Jung, Yu-Jin; Lee, Youri; Lee, Jong Seok; Lee, Yu-Na; Park, Soojin; Kang, Sang-Moo

    2015-01-01

    Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FI-RSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A) induced severe vaccine-enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease.

  5. Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells.

    Directory of Open Access Journals (Sweden)

    Ki-Hye Kim

    Full Text Available Respiratory syncytial virus (RSV is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FI-RSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A induced severe vaccine-enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease.

  6. Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells.

    Science.gov (United States)

    Le Goffic, Ronan; Bouguyon, Edwige; Chevalier, Christophe; Vidic, Jasmina; Da Costa, Bruno; Leymarie, Olivier; Bourdieu, Christiane; Decamps, Laure; Dhorne-Pollet, Sophie; Delmas, Bernard

    2010-10-15

    The PB1-F2 protein of the influenza A virus (IAV) contributes to viral pathogenesis by a mechanism that is not well understood. PB1-F2 was shown to modulate apoptosis and to be targeted by the CD8(+) T cell response. In this study, we examined the downstream effects of PB1-F2 protein during IAV infection by measuring expression of the cellular genes in response to infection with wild-type WSN/33 and PB1-F2 knockout viruses in human lung epithelial cells. Wild-type virus infection resulted in a significant induction of genes involved in innate immunity. Knocking out the PB1-F2 gene strongly decreased the magnitude of expression of cellular genes implicated in antiviral response and MHC class I Ag presentation, suggesting that PB1-F2 exacerbates innate immune response. Biological network analysis revealed the IFN pathway as a link between PB1-F2 and deregulated genes. Using quantitative RT-PCR and IFN-β gene reporter assay, we determined that PB1-F2 mediates an upregulation of IFN-β expression that is dependent on NF-κB but not on AP-1 and IFN regulatory factor-3 transcription factors. Recombinant viruses knocked out for the PB1-F2 and/or the nonstructural viral protein 1 (the viral antagonist of the IFN response) genes provide further evidence that PB1-F2 increases IFN-β expression and that nonstructural viral protein 1 strongly antagonizes the effect of PB1-F2 on the innate response. Finally, we compared the effect of PB1-F2 variants taken from several IAV strains on IFN-β expression and found that PB1-F2-mediated IFN-β induction is significantly influenced by its amino acid sequence, demonstrating its importance in the host cell response triggered by IAV infection.

  7. Incidence of aspirin hypersensitivity in patients with chronic rhinosinusitis and diagnostic value of urinary leukotriene E4.

    Science.gov (United States)

    Celejewska-Wójcik, Natalia; Mastalerz, Lucyna; Wójcik, Krzysztof; Nieckarz, Rafał; Januszek, Rafał; Hartwich, Patryk; Szaleniec, Joanna; Hydzik-Sobocińska, Karolina; Oleś, Krzysztof; Cybulska, Agnieszka; Stręk, Paweł; Sanak, Marek

    2012-01-01

    Chronic rhinosinusitis (CRS) with nasal polyposis (NP) may be associated with hypersensitivity to nonsteroidal anti-inflammatory drugs, representing a syndrome of aspirin-exacerbated respiratory disease (AERD). The aim of the study was to validate a simple measurement of urinary leukotriene E4 (uLTE4) excretion for the diagnosis of AERD in patients with CRS and indication for surgery. Subjects requiring functional endoscopic sinus surgery (FESS) were recruited from the Department of Otolaryngology (n = 24). Before surgery, a standard oral placebo-controlled aspirin challenge was performed to diagnose aspirin hypersensitivity. Urine samples were collected on the placebo day and both before and within 2 to 4 hours after aspirin challenge for uLTE4 measurement. All patients with CRS had sinusitis confirmed by computed tomography. Previous ear, nose, and throat surgery was performed in 70% of the patients, NP was present in 86%, and asthma was diagnosed in 62.5%. AERD was diagnosed in 8 subjects (7 women and 1 man). Five of those patients had bronchoconstriction. At baseline, median uLTE4 was 7.5-times higher in AERD subjects than in the remaining patients. It increased almost 6-fold following the challenge, while remained unchanged in patients without aspirin hypersensitivity. Pretest uLTE4 had a sensitivity of 87.5% and specificity of 93.75% to diagnose aspirin hypersensitivity in patients with CRS. After the challenge, the values improved to 100% sensitivity and 93% specificity. Among CRS subjects requiring FESS, as many as 33.3% may have AERD and respond to a small provocative dose of aspirin with bronchoconstriction and/or mucosal and skin edema. A simple and inexpensive measurement of uLTE4 can help diagnose AERD in patients with CRS with sensitivity of 87.5%, but its specificity is limited and depends on the arbitrary threshold of uLTE4.

  8. Respiratory

    Science.gov (United States)

    The words "respiratory" and "respiration" refer to the lungs and breathing. ... Boron WF. Organization of the respiratory system. In: Boron WF, Boulpaep EL, eds. Medical Physiology . 3rd ed. Philadelphia, PA: Elsevier; 2017:chap 26.

  9. Aspirin and Omeprazole

    Science.gov (United States)

    The combination of aspirin and omeprazole is used to reduce the risk of stroke or heart attack in patients who have had or ... risk of developing a stomach ulcer when taking aspirin. Aspirin is in a class of medications called ...

  10. Aspirin Resistance

    OpenAIRE

    Khaled Mansour; Ali T. Taher; Khaled M. Musallam; Samir Alam

    2009-01-01

    The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management...

  11. Effect of aspirin in "aspirin sensitive" patients.

    OpenAIRE

    Asad, S I; Kemeny, D M; Youlten, L J; Frankland, A W; Lessof, M H

    1984-01-01

    Eighteen patients with a history of urticaria or asthma, or both, induced by aspirin were studied before and after provocation of symptoms with aspirin. The plasma prostaglandin F2 alpha concentration, which was characteristically raised before challenge, fell significantly at the time of adverse reactions. Repeated administration of aspirin up to a dose of 650 mg daily induced tolerance in most of the patients, and several developed bronchodilator responses to aspirin. Although median total ...

  12. Aspirin Resistance

    Directory of Open Access Journals (Sweden)

    Khaled Mansour

    2009-01-01

    Full Text Available The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management strategies are currently limited to dosing alteration and introduction of other anitplatelet agents. However, these measures have not met the expected efficacy or safety.

  13. Efficacy of a respiratory rehabilitation exercise training package in hospitalized elderly patients with acute exacerbation of COPD: a randomized control trial

    National Research Council Canada - National Science Library

    Liao, Lin-Yu; Chen, Kuei-Min; Chung, Wei-Sheng; Chien, Jung-Yien

    2015-01-01

    .... To evaluate the effects of a respiratory rehabilitation exercise training package on dyspnea, cough, exercise tolerance, and sputum expectoration among hospitalized elderly patients with AECOPD...

  14. Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity.

    Science.gov (United States)

    Knowles, Sandra R; Drucker, Aaron M; Weber, Elizabeth A; Shear, Neil H

    2007-07-01

    To evaluate and provide management strategies for patients with aspirin or nonselective nonsteroidal antiinflammatory drug (NSAID) sensitivity. Literature retrieval was accessed through MEDLINE (1966-March 2007) using the terms acetaminophen, aspirin, antiinflammatory agents nonsteroidal, urticaria, angioedema, asthma, leukotriene antagonists, desensitization, and tacrolimus. Article references retrieved were hand-searched for other relevant articles. All studies published in English were evaluated. Studies, review articles, and commentaries on aspirin-induced asthma and aspirin- or NSAID-induced urticaria/angioedema were included in the review. Aspirin sensitivity is most often manifested as respiratory reactions (eg, bronchospasm, profuse rhinorrhea, conjunctival injection) or urticaria/angioedema. The primary mechanism is believed to be inhibition of the cyclooxygenase 1 (COX-1) enzyme; as such, patients with aspirin sensitivity often display cross-reactions to nonselective NSAIDs that inhibit the COX-1 enzyme. Management strategies include avoidance of aspirin and cross-reacting nonselective NSAIDs. However, desensitization to aspirin is a viable option for patients with aspirin-induced respiratory reactions, especially for those who require aspirin for thromboembolic prophylaxis. Aspirin desensitization is maintained indefinitely with a daily aspirin dose. There is limited evidence of the use of leukotriene modifiers in preventing aspirin-induced asthma. COX-2 selective NSAIDs, especially in patients with aspirin-induced asthma, have not been found to cross-react. However, approximately 4% of patients with a history of aspirin-induced skin reactions may experience a cutaneous reaction following a challenge to a COX-2 selective NSAID. Since acetaminophen is a weak inhibitor of the COX-1 enzyme, patients with aspirin-induced asthma should not take more than 1000 mg of acetaminophen in a single dose. Management of patients with aspirin/NSAID sensitivity includes

  15. Aspirin, Butalbital, and Caffeine

    Science.gov (United States)

    The combination of aspirin, butalbital, and caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 ... explain any part you do not understand. Take aspirin, butalbital, and caffeine exactly as directed. Do not ...

  16. Aspirin in Neurology

    OpenAIRE

    Yolanda Aburto-Murrieta; Dulce Bonifacio-Delgadillo; Juan Marquez

    2011-01-01

    Aspirin is widely used for the prevention of recurrent stroke in patients with transient ischaemic attack (TIA) of arterial origin, because it is effective and inexpensive. Clopidogrel and the combination of aspirin and extended-release dipyridamole are more effective than aspirin, but are also much more expensive. No other antithrombotic regimens provide significant advantages over aspirin, although cilostazol and the novel platelet protease-activated receptor-1 antagonist, SCH 530348, are c...

  17. Experiments with Aspirin.

    Science.gov (United States)

    Borer, Londa L.; Barry, Edward

    2000-01-01

    Presents a series of experiments that can be used to demonstrate how aspirin can be synthesized and characterized, how the hydrolysis of aspirin can be used as an introduction to kinetics, and how coordination chemistry (chelation) can be introduced by preparing and characterizing the copper complexes of aspirin and salicylic acid. (Contains over…

  18. An observational study of PM10 and hospital admissions for acute exacerbations of chronic respiratory disease in Tasmania, Australia 1992-2002.

    Science.gov (United States)

    Mészáros, D; Markos, J; FitzGerald, D G; Walters, E H; Wood-Baker, R

    2015-01-01

    Particulate matter with a diameter below 10 µ (PM10) has been a major concern in the Tamar Valley, Launceston, where wood heaters are extensively used. We examined the relationship between PM10 levels, meteorological variables, respiratory medications and hospital admissions for respiratory disease over the decade 1992-2002. PM10 levels were provided by the Department of Primary Industry Water, Parks and Environment, and meteorological variables from the Bureau of Meteorology. We obtained hospital discharge codes for the Launceston General Hospital. Poisson regression was used for statistical analyses. Mean daily PM10 levels declined from 50.7 to 16.5 μg/m(3). Hospitalisations for asthma decreased from 29 to 21 per month, whereas chronic obstructive pulmonary disease (COPD) increased and bronchitis/bronchiolitis remained unchanged. We found a 10 μg/m(3) increase in PM10 to be associated with a 4% increase in admissions for acute bronchitis/bronchiolitis (p0.05), but no association with asthma or COPD was found. All respiratory diseases showed seasonal patterns of hospitalisation. This is the first long-term study in Australia to demonstrate an association between PM10 levels and respiratory diseases. Reducing exposure to PM10 may decrease hospital admissions for respiratory diseases. Better preventive measures, including sustained public health initiatives to combat air pollution, are required to reduce respiratory morbidity.

  19. Temporary CD8(+) T-cell depletion in pigs does not exacerbate infection with porcine reproductive and respiratory syndrome virus (PRRSV)

    DEFF Research Database (Denmark)

    Lohse, Louise; Nielsen, Jens; Eriksen, Lis

    2004-01-01

    Several studies have demonstrated a consistent increase in the CD8(+) T-cell subset of pigs following infection with porcine reproductive and respiratory virus (PRRSV). Consequently, it has been suggested that CD8(+) T-cells may play an important role in protection against this infection. In order...

  20. Paradoxical Effect of Aspirin

    Directory of Open Access Journals (Sweden)

    Christian Doutremepuich

    2012-01-01

    Full Text Available Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 −/−, and COX 2 −/− mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena.

  1. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration.

    Science.gov (United States)

    Plant, P K; Owen, J L; Elliott, M W

    2000-07-01

    Non-invasive ventilation (NIV) reduces mortality and intubation rates in patients with chronic obstructive pulmonary disease (COPD) admitted to hospital with respiratory acidosis. This study aimed to determine the prevalence of respiratory acidosis in patients admitted with COPD, to draw inferences about oxygen therapy, and to determine the need for NIV services for acute COPD in typical UK hospitals. This one year prospective prevalence study identified patients with COPD aged 45-79 years inclusive who were admitted to Leeds General Infirmary, St James's University, and Killingbeck Hospitals, Leeds between 1 March 1997 and 28 February 1998. The prevalence of respiratory acidosis and the relationship with oxygenation are described. Other outcomes included intensive care use and in hospital mortality. From this data population prevalence estimates were determined for respiratory acidosis, from which the need for NIV in a typical district general hospital was modelled. 983 patients were admitted, 11 of whom required immediate intubation. 20% of the remaining 972 had a respiratory acidosis. Acidosis was associated with subsequent admission to the intensive care unit (ICU): pHarterial oxygen tension (PaO(2)) in the 47% of patients who were hypercapnic, with a PaO(2) of >10 kPa being associated with acidosis in most hypercapnic patients. 80% remained acidotic after initial treatment, giving an age/sex specific prevalence for England and Wales of 75 (95% CI 61 to 90)/100 000/year for men aged 45-79 years and 57 (95% CI 46 to 69)/100 000/year for women. Modelling the need for NIV for all COPD patients indicates that a typical UK hospital will admit 90 patients per year with acidosis of which 72 will require NIV. In patients with acute COPD the PaO(2) should be maintained at 7.3-10 kPa (SaO(2) 85-92%) to avoid the dangers of hypoxia and acidosis. If all COPD patients with a respiratory acidosis (pH<7.35) after initial treatment are offered NIV, a typical UK hospital will

  2. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Ingebrigtsen, Truls Sylvan; Marott, Jacob Louis

    2013-01-01

    Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients.......Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients....

  3. Aspirin for Primary Prevention.

    Science.gov (United States)

    Richman, Ilana B; Owens, Douglas K

    2017-07-01

    Aspirin reduces the risk of nonfatal myocardial infarction and stroke, and the risk of colorectal cancer. Aspirin increases the risk of gastrointestinal and intracranial bleeding. The best available evidence supports initiating aspirin in select populations. In 2016, the US Preventive Services Task Force recommended initiating aspirin for the primary prevention of both cardiovascular disease and colorectal cancer among adults ages 50 to 59 who are at increased risk for cardiovascular disease. Adults 60 to 69 who are at increased cardiovascular disease risk may also benefit. There remains considerable uncertainty about whether younger and older patients may benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  5. Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles.

    Science.gov (United States)

    Lee, Youri; Lee, Young-Tae; Ko, Eun-Ju; Kim, Ki-Hye; Hwang, Hye Suk; Park, Soojin; Kwon, Young-Man; Kang, Sang Moo

    2017-08-30

    Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost vaccination of F VLP induced effective protection, prevented infiltration of eosinophils, and vaccine- enhanced disease after challenge. This study provides insight into developing an effective and safe RSV vaccine candidate.

  6. Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells.

    Science.gov (United States)

    Dando, Samantha J; Ipe, Deepak S; Batzloff, Michael; Sullivan, Matthew J; Crossman, David K; Crowley, Michael; Strong, Emily; Kyan, Stephanie; Leclercq, Sophie Y; Ekberg, Jenny A K; St John, James; Beacham, Ifor R; Ulett, Glen C

    2016-07-01

    Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an often severe infection that regularly involves respiratory disease following inhalation exposure. Intranasal (i.n.) inoculation of mice represents an experimental approach used to study the contributions of bacterial capsular polysaccharide I (CPS I) to virulence during acute disease. We used aerosol delivery of B. pseudomallei to establish respiratory infection in mice and studied CPS I in the context of innate immune responses. CPS I improved B. pseudomallei survival in vivo and triggered multiple cytokine responses, neutrophil infiltration, and acute inflammatory histopathology in the spleen, liver, nasal-associated lymphoid tissue, and olfactory mucosa (OM). To further explore the role of the OM response to B. pseudomallei infection, we infected human olfactory ensheathing cells (OECs) in vitro and measured bacterial invasion and the cytokine responses induced following infection. Human OECs killed >90% of the B. pseudomallei in a CPS I-independent manner and exhibited an antibacterial cytokine response comprising granulocyte colony-stimulating factor, tumor necrosis factor alpha, and several regulatory cytokines. In-depth genome-wide transcriptomic profiling of the OEC response by RNA-Seq revealed a network of signaling pathways activated in OECs following infection involving a novel group of 378 genes that encode biological pathways controlling cellular movement, inflammation, immunological disease, and molecular transport. This represents the first antimicrobial program to be described in human OECs and establishes the extensive transcriptional defense network accessible in these cells. Collectively, these findings show a role for CPS I in B. pseudomallei survival in vivo following inhalation infection and the antibacterial signaling network that exists in human OM and OECs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Aspirin and heart disease

    Science.gov (United States)

    ... attack . Your provider may recommend to take daily aspirin if: You do not have a history of heart disease or stroke, but you are at high risk for a heart attack or stroke. You have been diagnosed ... already. Aspirin helps get more blood flowing to your legs. ...

  8. Rhinovirus-Induced Exacerbations of Asthma and COPD

    Science.gov (United States)

    Hershenson, Marc B.

    2013-01-01

    Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted. PMID:24278777

  9. Asthma Exacerbation in Children: A Practical Review

    Directory of Open Access Journals (Sweden)

    Lin-Shien Fu

    2014-04-01

    Full Text Available Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important.

  10. Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.

    Science.gov (United States)

    Gold, Diane R; Litonjua, Augusto A; Carey, Vincent J; Manson, JoAnn E; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

    2016-03-01

    Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)--to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Intranasal immunization of pigs with porcine reproductive and respiratory syndrome virus-like particles plus 2', 3'-cGAMP VacciGrade™ adjuvant exacerbates viremia after virus challenge.

    Science.gov (United States)

    Van Noort, Alexandria; Nelsen, April; Pillatzki, Angela E; Diel, Diego G; Li, Feng; Nelson, Eric; Wang, Xiuqing

    2017-04-12

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure in pregnant sows and acute respiratory disease in young pigs. It is a leading infectious agent of swine respiratory complex, which has significant negative economic impact on the swine industry. Commercial markets currently offer both live attenuated and killed vaccines; however, increasing controversy exists about their efficacy providing complete protection. Virus-like particles (VLPs) possess many desirable features of a potent vaccine candidate and have been proven to be highly immunogenic and protective against virus infections. Here we explored the efficacy of PRRSV VLPs together with the use of a novel 2', 3'-cGAMP VacciGrade™ adjuvant. Animals were immunized twice intranasally with phosphate buffered saline (PBS), PRRSV VLPs, or PRRSV VLPs plus 2', 3'-cGAMP VacciGrade™ at 2 weeks apart. Animals were challenged with PRRSV-23983 at 2 weeks post the second immunization. PRRSV specific antibody response and cytokines were measured. Viremia, clinical signs, and histological lesions were evaluated. PRRSV N protein specific antibody was detected in all animals at day 10 after challenge, but no significant difference was observed among the vaccinated and control groups. Surprisingly, a significantly higher viremia was observed in the VLPs and VLPs plus the adjuvant groups compared to the control group. The increased viremia is correlated with a higher interferon-α induction in the serum of the VLPs and the VLPs plus the adjuvant groups. Intranasal immunizations of pigs with PRRSV VLPs and VLPs plus the 2', 3'-cGAMP VacciGrade™ adjuvant exacerbates viremia. A higher level of interferon-α production, but not interferon-γ and IL-10, is correlated with enhanced virus replication. Overall, PRRSV VLPs and PRRSV VLPs plus the adjuvant fail to provide protection against PRRSV challenge. Different dose of VLPs and alternative route of vaccination such as intramuscular

  12. Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.

    Science.gov (United States)

    Keene, Jason D; Jacobson, Sean; Kechris, Katerina; Kinney, Gregory L; Foreman, Marilyn G; Doerschuk, Claire M; Make, Barry J; Curtis, Jeffrey L; Rennard, Stephen I; Barr, R Graham; Bleecker, Eugene R; Kanner, Richard E; Kleerup, Eric C; Hansel, Nadia N; Woodruff, Prescott G; Han, MeiLan K; Paine, Robert; Martinez, Fernando J; Bowler, Russell P; O'Neal, Wanda K

    2017-02-15

    Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux. To determine the value of adding blood biomarkers to clinical variables to predict exacerbations. Subjects from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) (n = 1,544) and COPDGene (Genetic Epidemiology of COPD) (n = 602) cohorts had 90 plasma or serum candidate proteins measured on study entry using Myriad-RBM multiplex panels. We defined total exacerbations as subject-reported worsening in respiratory health requiring therapy with corticosteroids and/or antibiotics, and severe exacerbations as those leading to hospitalizations or emergency room visits. We assessed retrospective exacerbations during the 12 months before enrollment and then documented prospective exacerbations in each cohort. Exacerbations were modeled for biomarker associations with negative binomial regression including clinical covariates (age, sex, percent predicted FEV1, self-reported gastroesophageal reflux, St. George's Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis. Between the two cohorts, 3,471 total exacerbations (1,044 severe) were reported. We identified biomarkers within each cohort that were significantly associated with a history of exacerbation and with a future exacerbation, but there was minimal replication between the cohorts. Although established clinical features were predictive of exacerbations, of the blood biomarkers only decorin and α2-macroglobulin increased predictive value for future severe exacerbations. Blood biomarkers were significantly associated with the occurrence of exacerbations but were not robust between cohorts and added little to the

  13. Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products

    Science.gov (United States)

    updated 3/10/08 Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products © National Reye's Syndrome Foundation Inc. 2008 Epidemiologic research has shown an association between the development of Reye's ...

  14. Aspirin: yesterday, today, and tomorrow

    Directory of Open Access Journals (Sweden)

    Marina Nikołajewna Dołżenko

    2014-06-01

    Full Text Available Clinical utility of aspirin (acetylsalicylic acid, ASA is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, highlighting the especially important role of aspirin in women at the age of >65 years, and its utility in all women, irrespectively of age, and those who are at high risk of cardiovascular disease, including atherosclerosis-related cardiovascular disease. Moreover, the mechanisms of aspirin resistance, characterized by inability of aspirin to prevent thromboembolic complications or inadequate platelet inhibition showed in laboratory results, were mentioned. Prevalence of resistance in aspirin-treated patients is estimated to be between 1 and 68%. Stress was also put on the aspirin safety, associated with prophylaxis of peptic ulcer disease, which can be achieved i.e. by the use of the enteric-coated aspirin. This form of aspirin is associated with lower risk of gastrointestinal mucosae damage and bleeding from the gastrointestinal tract. At the end of the article, the importance of the adherence to therapeutic guidelines of aspirin use, including assessment of variation in aspirin bioavailability associated with improper dosing and altered absorption in the gastrointestinal tract, was stressed.

  15. Low dose aspirin and pregnancy: how important is aspirin resistance?

    OpenAIRE

    Navaratnam, K; Alfirevic, A; Alfirevic, Z

    2016-01-01

    Antiplatelet agents are pivotal for prevention of coronary artery disease and cerebrovascular disease worldwide. Individual patient data meta?analysis indicates that low?dose aspirin causes a 10% risk reduction in pre?eclampsia for women at high individual risk. However, in the last 15 years it has emerged that a significant proportion of aspirin?treated individuals exhibit suboptimal platelet response, determined biochemically and clinically, termed ?aspirin non?responsiveness?, ?aspirin res...

  16. The Christmas Season as a Risk Factor for Chronic Obstructive Pulmonary Disease Exacerbations

    Directory of Open Access Journals (Sweden)

    Neil W Johnston

    2010-01-01

    Full Text Available BACKGROUND: Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections.

  17. Aspirin: yesterday, today, and tomorrow

    OpenAIRE

    Marina Nikołajewna Dołżenko

    2014-01-01

    Clinical utility of aspirin (acetylsalicylic acid, ASA) is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, hi...

  18. Aspirin and Cancer.

    Science.gov (United States)

    Patrignani, Paola; Patrono, Carlo

    2016-08-30

    The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Virus-induced exacerbations in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Daisuke eKurai

    2013-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses.COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage.In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.

  20. Twisted aspirin crystals.

    Science.gov (United States)

    Cui, Xiaoyan; Rohl, Andrew L; Shtukenberg, Alexander; Kahr, Bart

    2013-03-06

    Banded spherulites of aspirin have been crystallized from the melt in the presence of salicylic acid either generated from aspirin decomposition or added deliberately (2.6-35.9 mol %). Scanning electron microscopy, X-ray diffraction analysis, and optical polarimetry show that the spherulites are composed of helicoidal crystallites twisted along the growth directions. Mueller matrix imaging reveals radial oscillations in not only linear birefringence, but also circular birefringence, whose origin is explained through slight (∼1.3°) but systematic splaying of individual lamellae in the film. Strain associated with the replacement of aspirin molecules by salicylic acid molecules in the crystal structure is computed to be large enough to work as the driving force for the twisting of crystallites.

  1. Aspirin desensitization for cardiovascular disease.

    Science.gov (United States)

    Woessner, Katharine M

    2015-08-01

    The use of aspirin in coronary artery disease and address the unmet need of aspirin therapy in patients with history of hypersensitivity reactions to aspirin (acetylsalicylic acid; ASA) or other nonsteroidal inflammatory drugs (NSAIDs). Aspirin hypersensitivity is reported in 1.5% of patients with cardiovascular disease. However, many of those labeled as allergic to aspirin had experienced side-effects and could be safely treated with aspirin. Those with true hypersensitivity reactions were often not placed on appropriate antiplatelet therapy. A number of protocols of varying complexity exist in the literature for aspirin desensitization. The focus of this review is to identify the types of aspirin reactions that can occur and provide a rational approach to oral aspirin challenge and desensitization. In summary, with rare exceptions, patients with a history of 'aspirin/NSAID allergy' who need ASA for cardiovascular issues will be able to safely take aspirin either after a graded challenge or desensitization providing a central role of the allergist in the management of these patients.

  2. Reye Syndrome and Aspirin

    OpenAIRE

    J Gordon Millichap

    1987-01-01

    Twenty-six cases of Reye syndrome occurring between 1973 and 1982 have been reviewed in relation to aspirin ingestion at the Children’s Hospital, Camperdown, Australia (formerly the Royal Alexandra Hospital for Children in Sydney), where Reye first described his syndrome of encephalopathy and fatty degeneration of the viscera in 1963.

  3. Early use of noninvasive techniques for clearing respiratory secretions during noninvasive positive-pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease and hypercapnic encephalopathy: A prospective cohort study.

    Science.gov (United States)

    Wang, Jinrong; Cui, Zhaobo; Liu, Shuhong; Gao, Xiuling; Gao, Pan; Shi, Yi; Guo, Shufen; Li, Peipei

    2017-03-01

    Noninvasive positive-pressure ventilation (NPPV) might be superior to conventional mechanical ventilation (CMV) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Inefficient clearance of respiratory secretions provokes NPPV failure in patients with hypercapnic encephalopathy (HE). This study compared CMV and NPPV combined with a noninvasive strategy for clearing secretions in HE and AECOPD patients.The present study is a prospective cohort study of AECOPD and HE patients enrolled between October 2013 and August 2015 in a critical care unit of a major university teaching hospital in China.A total of 74 patients received NPPV and 90 patients received CMV. Inclusion criteria included the following: physician-diagnosed AECOPD, spontaneous airway clearance of excessive secretions, arterial blood gas analysis requiring intensive care, moderate-to-severe dyspnea, and a Kelly-Matthay scale score of 3 to 5. Exclusion criteria included the following: preexisting psychiatric/neurological disorders unrelated to HE, upper gastrointestinal bleeding, upper airway obstruction, acute coronary syndromes, preadmission tracheostomy or endotracheal intubation, and urgent endotracheal intubation for cardiovascular, psychomotor agitation, or severe hemodynamic conditions.Intensive care unit participants were managed by NPPV. Participants received standard treatment consisting of controlled oxygen therapy during NPPV-free periods; antibiotics, intravenous doxofylline, corticosteroids (e.g., salbutamol and ambroxol), and subcutaneous low-molecular-weight heparin; and therapy for comorbidities if necessary. Nasogastric tubes were inserted only in participants who developed gastric distension. No pharmacological sedation was administered.The primary and secondary outcome measures included comparative complication rates, durations of ventilation and hospitalization, number of invasive devices/patient, and in-hospital and 1-year mortality rates

  4. Prevention of COPD exacerbations

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Lange, Peter

    2015-01-01

    Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is eviden...

  5. Acute exacerbations of fibrotic interstitial lung disease.

    Science.gov (United States)

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy. © 2010 Blackwell Publishing Limited.

  6. The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada

    Directory of Open Access Journals (Sweden)

    Tam Dang-Tan

    2017-01-01

    Full Text Available Background. Chronic obstructive pulmonary disease (COPD prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe. Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations. Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p<0.01 for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p<0.001. Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.

  7. Viruses and bacteria in acute asthma exacerbations - A GA2LEN-DARE* systematic review

    NARCIS (Netherlands)

    Papadopoulos, N. G.; Christodoulou, I.; Rohde, G.; Agache, I.; Almqvist, C.; Bruno, A.; Bonini, S.; Bont, L.; Bossios, A.; Bousquet, J.; Braido, F.; Brusselle, G.; Canonica, G. W.; Carlsen, K. H.; Chanez, P.; Fokkens, W. J.; Garcia-Garcia, M.; Gjomarkaj, M.; Haahtela, T.; Holgate, S. T.; Johnston, S. L.; Konstantinou, G.; Kowalski, M.; Lewandowska-Polak, A.; Lodrup-Carlsen, K.; Makela, M.; Malkusova, I.; Mullol, J.; Nieto, A.; Eller, E.; Ozdemir, C.; Panzner, P.; Popov, T.; Psarras, S.; Roumpedaki, E.; Rukhadze, M.; Stipic-Markovic, A.; Bom, A. Todo; Toskala, E.; van Cauwenberge, P.; van Drunen, C.; Watelet, J. B.; Xatzipsalti, M.; Xepapadaki, P.; Zuberbier, T.

    P>A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced

  8. [Asthmatic exacerbations: specific features in children].

    Science.gov (United States)

    Carsin, A; Pham-Thi, N

    2011-12-01

    Asthma concerns more than 10% of 10-year-old children. Despite the similarities between adult and childhood asthma, the pediatric population presents some specific characteristics, notably in relation to exacerbations. Asthma in the newborn infant is a specific entity, the definition of which has recently been officially recognized. In exacerbations, the most important trigger factors are respiratory virus infections, the strain having prognostic importance. The indoor and outdoor environments are risk factors, particularly high levels of atmospheric pollution. Nutrients seem to play a prognostic role through vitamin D or food allergy. Measurement of exhaled nitric oxide and examination of induced sputum may help in diagnosis and adjustment of treatment but these tools are not yet effective as predictive factors in asthma exacerbations. Prevention, early management and continued education of children and their families remain the best methods to improve asthma control. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. Aspirin, 110 years later.

    Science.gov (United States)

    Patrono, C; Rocca, B

    2009-07-01

    Although conceived at the end of the 19th century as a synthetic analgesic agent with improved gastric tolerability vs. naturally occurring salicylates, acetylsalicylic acid (marketed as aspirin in 1899) turned out to be an ideal antiplatelet agent about 90 years later, following the understanding of its mechanism of action, the development of a mechanism-based biomarker for dose-finding studies, and the initiation of a series of appropriately sized, randomized clinical trials to test its efficacy and safety at low doses given once daily. At the turn of its 110th anniversary, aspirin continues to attract heated debates on a number of issues including (i) the optimal dose to maximize efficacy and minimize toxicity; (ii) the possibility that some patients may be 'resistant' to its antiplatelet effects; and (iii) the balance of benefits and risks in primary vs. secondary prevention.

  10. Infective Exacerbation of Pasteurella multocida

    Directory of Open Access Journals (Sweden)

    Mayumi Hamada

    2016-01-01

    Full Text Available An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD. She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin.

  11. Transrectal ultrasound-guided biopsy of the prostate: aspirin increases the incidence of minor bleeding complications

    Energy Technology Data Exchange (ETDEWEB)

    Halliwell, O.T. [Department of Radiology, Southampton General Hospital, Southampton (United Kingdom)], E-mail: hallo99@doctors.org.uk; Yadegafar, G. [Public Health Sciences and Medical Statistics Division, School of Medicine, Southampton General Hospital, Southampton University, Southampton (United Kingdom); Lane, C.; Dewbury, K.C. [Department of Radiology, Southampton General Hospital, Southampton (United Kingdom)

    2008-05-15

    Aim: To assess whether patients taking aspirin were more likely to experience bleeding complications after transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and methods: Three hundred and eighty-seven patients taking aspirin who underwent prostate biopsy over a 3.5 year period and 731 patients not taking aspirin over a 2 year period returned a questionnaire assessing the incidence and severity of bleeding complications. Results: Patients taking aspirin had a significantly higher cumulative incidence of haematuria and rectal bleeding, but not of haemospermia. They also had a longer mean duration of bleeding, but no increase in bleeding severity. Severe bleeding was very uncommon in both groups and no patients required intervention for bleeding complications. Conclusion: Aspirin exacerbates minor bleeding complications in patients undergoing TRUS guided biopsy of the prostate, but in this large group of aspirin-taking patients no dangerous bleeding complications were encountered. It may be that the risks associated with aspirin cessation outweigh the risks of haemorrhagic complications.

  12. Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation.

    Science.gov (United States)

    Matsuo, Hiroaki; Yokooji, Tomoharu; Morita, Hironobu; Ooi, Mina; Urata, Kana; Ishii, Kaori; Takahagi, Shunsuke; Yanase, Yuhki; Hiragun, Takaaki; Mihara, Shoji; Hide, Michihiro

    2013-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release. The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated. Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls. Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  13. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events

    NARCIS (Netherlands)

    Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

    2017-01-01

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review

  14. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease

    NARCIS (Netherlands)

    Squizzato, Alessandro; Keller, Tymen; Romualdi, Erica; Middeldorp, Saskia

    2011-01-01

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease. To quantify the benefit and harm of adding clopidogrel

  15. Greener Methods for Aspirin Synthesis

    OpenAIRE

    Barilone, Jessica

    2013-01-01

    In this semester long study, I used microwave irradiation to synthesize aspirin. I compared this method to a traditional method that utilizes a strong acid. I compared the percent yield and the purity of the methods to pure aspirin

  16. Desensitization to acetyl-salicylic acid as a treatment for non-steroid anti-inflammatory drugs (NSAIDs-exacerbated respiratory disease = Desensibilización al ácido acetil-salicílico como tratamiento para la enfermedad respiratoria exacerbada por antiinflamatorios no esteroides

    Directory of Open Access Journals (Sweden)

    Cardona Villa, Ricardo

    2014-07-01

    Full Text Available Desensitization to acetyl-salicylic acid as a treatment for non-steroid anti-inflammatory drugs (NSAIDs-exacerbated respiratory disease The coexistence of hypersensitivity to acetylsalicylic acid (ASA and other NSAIDs with disease of the upper or the lower airways (rhinosinusitis/sinonasal polyposis, or asthma is defined as NSAIDs-exacerbated respiratory disease. Treatment options include the avoidance of all analgesics that inhibit COX-1 or ASA desensitization, continuing its daily consumption. The latter treatment has shown to improve quality of life, reduce the formation of sinonasal polyps, the episodes of sinus infection, the frequency of hospitalizations and surgeries for resection of polyps and the need for systemic steroid treatment. Multiple desensitization schedules have been used, trying to reduce the risk associated with the procedure and the adverse effects of chronic use of ASA. In this paper we present a review of the different methods of desensitization and two illustrative clinical cases to help understand the factors that influence the choice of treatment for these patients.

  17. Comparative bioequivalence assessment of aspirin tablets marketed ...

    African Journals Online (AJOL)

    Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

  18. Taking Aspirin to Protect Your Heart

    Science.gov (United States)

    Toolkit No. 23 Taking Aspirin to Protect Your Heart What can taking aspirin do for me? If you are at high risk for or if you have heart disease, taking a low dose aspirin every day may help. Aspirin can also help ...

  19. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested Udgivelsesdato: 2008/5/5...

  20. Immune Responses in Rhinovirus-Induced Asthma Exacerbations.

    Science.gov (United States)

    Steinke, John W; Borish, Larry

    2016-11-01

    Acute asthma exacerbations are responsible for urgent care visits and hospitalizations; they interfere with school and work productivity, thereby driving much of the morbidity and mortality associated with asthma. Approximately 80 to 85 % of asthma exacerbations in children, adolescents, and less frequently adults are associated with viral upper respiratory tract viral infections, and rhinovirus (RV) accounts for ∼60-70 % of these virus-associated exacerbations. Evidence suggests that it is not the virus itself but the nature of the immune response to RV that drives this untoward response. In particular, evidence supports the concept that RV acts to exacerbate an ongoing allergic inflammatory response to environmental allergens present at the time of the infection. The interaction of the ongoing IgE- and T cell-mediated response to allergen superimposed on the innate and adaptive immune responses to the virus and how this leads to triggering of an asthma exacerbation is discussed.

  1. Aspirin-Induced Acute Liver Injury

    OpenAIRE

    Laster, Janese; Satoskar, Rohit

    2014-01-01

    Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent.

  2. Platelets, aspirin, and cardiovascular disease.

    Science.gov (United States)

    Elwood, P C; Hughes, C; O'Brien, J R

    1998-10-01

    Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and an overview of the first six trials was presented to the inaugural meeting of the Society for Clinical Trials in Philadelphia in 1980. There have been two further major overviews and the most recent, based on 145 trials, established that low-dose aspirin reduces vascular events by around one third. It has been estimated that, used appropriately, aspirin could prevent 100,000 premature deaths each year worldwide, at a cost of about 250 Pounds ($400) per life saved, and about 80 Pounds ($130) per cardiovascular event prevented. The evidence indicates that it is seriously underused at present. The aspirin story continues and trials are in progress to test other possible uses of aspirin, in vascular dementia, colorectal cancer, and cataract.

  3. Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin

    NARCIS (Netherlands)

    Jaspers Focks, J.; Tielemans, M.M.; Rossum, L.G.M. van; Eikendal, T.; Brouwer, M.A.; Jansen, J.B.M.J.; Laheij, R.J.F.; Verheugt, F.W.A.; Oijen, M.G.H. van

    2014-01-01

    BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy

  4. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria.

    Science.gov (United States)

    Cavkaytar, Ozlem; Arik Yilmaz, Ebru; Buyuktiryaki, Betul; Sekerel, Bulent E; Sackesen, Cansin; Soyer, Ozge U

    2015-02-01

    Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. For children with chronic urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Platelets, aspirin, and cardiovascular disease.

    OpenAIRE

    Elwood, P. C.; Hughes, C.; O'Brien, J. R.

    1998-01-01

    Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and a...

  6. Lipoxin and Aspirin-Triggered Lipoxins

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2010-01-01

    Full Text Available Lipoxins and their 15 epimers, aspirin triggered lipoxins (ATL, are eicosanoids derived from sequential lipoxygenase (LO metabolism of arachidonic acid. The main routes of lipoxin biosynthesis involve cooperation between 15- and 5-LO, and between 12- and 5-LO. ATL are generated by interactions between 5-LO and aspirin-acetylated cyclooxygenase-2. Cellular models recapitulating these interactions involve leukocytes, platelets, vascular endothelium, and epithelium. To circumvent rapid lipoxin and ATL metabolism and inactivation, stable analogs, bearing potent and long-lasting biological activity, have been synthesized. Some of these analogs displayed therapeutic potential by showing strong anti-inflammatory activity in a number of animal models of disease, including reperfusion injury; arthritis; gastrointestinal, renal, respiratory, and vascular inflammatory disorders; eye damage; periodontitis; and selected infectious diseases. Counter-regulatory signaling by lipoxin A4 and 15-epi-lipoxin A4 is triggered by the activation of a seven-transmembrane domain receptor, termed FPR2/ALX, which is highly expressed in myeloid cells and has been recognized as a main anti-inflammatory receptor.

  7. Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

    Science.gov (United States)

    Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

    2014-01-01

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

  8. Daily Aspirin Therapy: Understand the Benefits and Risks

    Science.gov (United States)

    Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

  9. Dark chocolate exacerbates acne.

    Science.gov (United States)

    Vongraviopap, Saivaree; Asawanonda, Pravit

    2016-05-01

    The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin. © 2015 The International Society of Dermatology.

  10. Colds as predictors of the onset and severity of COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Johnston NW

    2017-03-01

    Full Text Available Neil W Johnston,1 Marita Olsson,2 Staffan Edsbäcker,3 Maria Gerhardsson de Verdier,4 Per Gustafson,5 Christopher McCrae,3 Peter V Coyle,6 R Andrew McIvor11Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada; 2Early Clinical Development Biometrics, 3Respiratory, Inflammation & Autoimmunity Unit, Innovative Medicines & Early Development, 4Medical Evidence and Observational Research Centre, 5Respiratory, Inflammation & Autoimmunity Translational Medicine Unit, Early Clinical Development, Innovative Medicines & Early Development, AstraZeneca Research and Development, Gothenburg, Molndal, Sweden; 6Regional Virology Laboratory, Belfast HS C Trust, Belfast, UKRationale: Common colds are associated with acute respiratory symptom exacerbations in COPD patients.Objective: To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds.Methods: Global initiative for chronic Obstructive Lung Disease stage I–IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009. Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway. A composite daily symptom score was derived for each subject from diarized symptom data. The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models.Results: Daily diary transmission compliance of >97% enabled detection of all possible exacerbations. Among 262 exacerbations meeting Anthonisen criteria, 218 (83% had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%. Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P<0.001 greater with colds present. Compared to cold

  11. Diagnosis and management of acute exacerbations of chronic ...

    African Journals Online (AJOL)

    for at least 2 consecutive days.2,3. However, the severity of exacerbations can be extremely heterogeneous, ranging from a mild increase in symptoms to more serious manifestations and severe respiratory failure. The magnitude of the problem is substantial for the patient, as well as economically. In the USA alone, in 2000, ...

  12. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen in ac...

  13. Detection of rhinovirus-associated asthma exacerbations using ...

    African Journals Online (AJOL)

    Background: Acute exacerbations of asthma are the leading cause of emergency department visits in pediatric patients. The development of sensitive diagnostic polymerase chain reaction (PCR) based techniques permitted demonstration of an already clinically suspected association between common viral respiratory ...

  14. Aspirin and aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Gross, Bradley A; Rosalind Lai, Pui Man; Frerichs, Kai U; Du, Rose

    2014-12-01

    Recent evidence has suggested a potential beneficial effect of aspirin on the risk of aneurysm rupture. This benefit must be weighed against its potential adverse effects as an antiplatelet agent in the setting of acute aneurysmal subarachnoid hemorrhage (SAH). A total of 747 consecutive patients with cerebral aneurysms were reviewed, comparing demographics, aneurysm features, presenting clinical and radiographic grades, vasospasm, and outcome at 1 year between patients with aneurysmal SAH taking aspirin on presentation and those who were not. The rate of hemorrhagic presentation was significantly greater in patients not taking aspirin (40% vs. 28%; P = 0.016). Among 274 patients presenting with aneurysmal SAH, there was no significant difference in presenting clinical (Hunt and Hess) and radiographic (Fisher) grade between patients taking aspirin and those who were not. There was also no significant difference in the rate of subsequent angiographic and delayed cerebral ischemia. Multivariate analysis of outcome at 1 year found only increasing age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.12), Hunt and Hess grade (OR 3.01, 95% CI 1.81-5.03), and associated hypertension (OR 3.30, 95% CI 1.39-7.81) to be statistically significant risk factors for poor outcome (death or dependence), whereas aspirin use was not associated with poor outcome (OR 1.19, 95% CI 0.35-4.09; P = 0.78). In the present study, patients taking aspirin had a lower rate of hemorrhagic presentation. In addition, taking aspirin did not adversely impact presenting clinical grade or radiographic grade, vasospasm, and outcome in the setting of aneurysmal SAH. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Non invasive proportional assist ventilation in management of severe asthma exacerbation

    Directory of Open Access Journals (Sweden)

    Khaled Hussein

    2012-07-01

    Conclusion: NIV can relieve respiratory distress and improve gas exchange in the majority of patients with severe asthma exacerbation who are candidate for intubation after failure of conventional medical therapy.

  16. Novel Proresolving Aspirin-Triggered DHA Pathway

    National Research Council Canada - National Science Library

    Serhan, Charles N; Fredman, Gabrielle; Yang, Rong; Karamnov, Sergey; Belayev, Ludmila S; Bazan, Nicolas G; Zhu, Min; Winkler, Jeremy W; Petasis, Nicos A

    2011-01-01

    .... We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1...

  17. Aspirin to Zoloft: Ways Medicines Work

    Science.gov (United States)

    ... View All Articles | Inside Life Science Home Page Aspirin to Zoloft: Ways Medicines Work By Emily Carlson ... biology of how cancer cells grow. Antihistamines, Antidepressants, Aspirin Adrenergic receptor with carazolol, a beta-blocker. View ...

  18. Aspirin during Pregnancy: Is It Safe?

    Science.gov (United States)

    Healthy Lifestyle Pregnancy week by week Is it safe to take aspirin during pregnancy? Answers from Yvonne Butler Tobah, M. ... 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/expert-answers/aspirin-during-pregnancy/ ...

  19. Aspirin resistant patients with recent ischemic stroke.

    Science.gov (United States)

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin). Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. Aspirin: past, present and future.

    Science.gov (United States)

    Elwood, P C

    2001-01-01

    Many folk remedies used since pre-historic times have depended upon salicylates for their effect. One hundred years ago aspirin was formulated from salicylic and acetic acids. It was the first drug to be synthesised and its formulation is regarded as the foundation of the modern pharmaceutical industry. The benefit of low-dose aspirin as a prophylactic after a thrombotic event was first reported 25 years ago. Its use after coronary or cerebral thrombosis is virtually mandatory, unless there are signs of intolerance. A 'loading dose' of soluble aspirin should be given on first contact with a patient who may be suffering from myocardial infarction. Patients considered to be at increased risk of a vascular event should also be advised to carry their own aspirin and, if they experience sudden severe chest pain, to chew and swallow a 300 mg tablet or a soluble preparation immediately. The current phase of the aspirin story is, however, not over, and its possible value in a variety of conditions, including dementia and certain cancers, seems likely to ensure that it will long continue to play a remarkable part in clinical practice.

  1. The role of aspirin in women's health

    NARCIS (Netherlands)

    Verheugt, F.W.A.; Bolte, A.C.

    2011-01-01

    BACKGROUND: The aim of this review is to discuss the role of aspirin for various conditions in women. METHODS: A nonsystematic review of articles published on PubMed((R)) that examines the role of aspirin in women. RESULTS: Aspirin is associated with a significant reduction of stroke risk in women,

  2. COPD exacerbation: Lost in translation

    Directory of Open Access Journals (Sweden)

    Bouros Demosthenes

    2009-01-01

    Full Text Available Abstract The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events. The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease. This definition is pragmatic and compromises the different approaches for exacerbation. However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication" in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiologal process which characterizes exacerbations. It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition. In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism that can masquerade as exacerbations but they should not be considered as causes of them. The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition. Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung fuction. These fundamental aspects should be accounted in diagnosis/definition of exacerbations. This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events. The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations. However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward

  3. Fine particulate pollution and asthma exacerbations.

    Science.gov (United States)

    Bouazza, Naïm; Foissac, Frantz; Urien, Saik; Guedj, Romain; Carbajal, Ricardo; Tréluyer, Jean-Marc; Chappuy, Hélène

    2017-12-19

    As the results from epidemiological studies about the impact of outdoor air pollution on asthma in children are heterogeneous, our objective was to investigate the association between asthma exacerbation in children and exposure to air pollutants. A database of 1 264 585 paediatric visits during the 2010-2015 period to the emergency rooms from 20 emergency departments (EDs) of 'Assistance Publique Hôpitaux de Paris (APHP)', the largest hospital group in Europe, was used. A total of 47 107 visits were classified as asthma exacerbations. Concentration of air pollutants (nitrogen dioxide, ozone, fine particulate matter (PM) with an aerodynamic diameter smaller than 10  µm (PM10) and 2.5 µm (PM2.5)), as well as meteorological data, evolution of respiratory syncytial virus infection and pollen exposition, were collected on an hourly or daily basis for the same period using institutional databases. To assess the association between air pollution and asthma, mixed-effects quasi-Poisson regression modelling was performed. The only compound independently associated with ED visits for asthma was PM2.5 (Peffect, was estimated at 13.5 µg/m3. We found an association between daily asthma exacerbation in paediatric visits to the ED and fine particulate air pollutants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Aspirin: Pharmacology and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Enma V. Paez Espinosa

    2012-01-01

    Full Text Available Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management of thrombosis-based disorders includes the use of heparin, oral anticoagulants, and the preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended to be used as an antiplatelet agent; rather, after being repurposed, it has become one of the most widely prescribed antithrombotic drugs. To this end, there have been several milestones in the development of antiplatelet agents in the last few decades, such as adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, and GPIIb/IIIa inhibitors. However, given some of the limitations of these therapies, aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come.

  5. Technetium-aspirin molecule complexes

    Energy Technology Data Exchange (ETDEWEB)

    El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M. (Assiut Univ. (Egypt))

    1993-01-01

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author).

  6. Exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-01-01

    that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care...... to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome....

  7. TRUE RESISTANCE AND PSEUDORESISTANCE TO ASPIRIN

    Directory of Open Access Journals (Sweden)

    A. I. Martynov

    2013-01-01

    Full Text Available Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of aspirin resistance has emerged, and estimates of its incidence have varied remarkably. Researchers from university of Pennsylvania (Philadelphia, the USA, led by Dr. Tilo Grosser, aimed to determine the specific phenotype of true pharmacological resistance to aspirin — such as might be explained by genetic causes. However the study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.

  8. Compound list: aspirin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available aspirin ASA 00014 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/aspirin....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/aspirin....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/aspirin....Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/aspirin.Rat.in_vivo.Liver.Repeat.zip ...

  9. Acute kidney injury in stable COPD and at exacerbation

    Directory of Open Access Journals (Sweden)

    Barakat MF

    2015-09-01

    Full Text Available MF Barakat,1 HI McDonald,1 TJ Collier,1 L Smeeth,1 D Nitsch,1 JK Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: While acute kidney injury (AKI alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.Methods: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107 and identified confounding factors.Results: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03 increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.Conclusion: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome. Keywords: acute renal failure, mortality, emphysema, chronic bronchitis, prognosis

  10. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I

    2014-01-01

    BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10......,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before...... the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum...

  11. Exacerbations of asthma - A descriptive study of 425 severe exacerbations

    NARCIS (Netherlands)

    Tattersfield, AE; Postma, DS; Barnes, PJ; Svensson, K; Bauer, CA; O'Byrne, PM; Lofdahl, CG; Pauwels, RA; Ullman, A

    The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue p-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high

  12. Ambient pollution and respiratory outcomes among

    African Journals Online (AJOL)

    economic position from effects of ambient air pollutant concentrations, with regard to both short-term exacerbations and prevalence of specific respiratory diagnoses and symptoms. All primary schools in the selected communities were assessed ...

  13. Rapid Aspirin Challenge in Patients with Aspirin Allergy and Acute Coronary Syndromes.

    Science.gov (United States)

    Cook, Kevin A; White, Andrew A

    2016-02-01

    Aspirin allergy in a patient with acute coronary syndrome represents one of the more urgent challenges an allergist may face. Adverse reactions to aspirin are reported in 1.5% of patients with coronary artery disease. A history of adverse reaction to aspirin often leads to unnecessary withholding of this medication or use of alternative antiplatelet therapy which may be inferior or more costly. Aspirin therapy has been shown to reduce morbidity and mortality in patients with coronary artery disease. Rapid aspirin challenge/desensitization in the aspirin allergic patient has been consistently shown to be both safe and successful in patients with acute coronary syndromes.

  14. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

  15. Viruses and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE* systematic review

    DEFF Research Database (Denmark)

    Papadopoulos, N G; Christodoulou, I; Rohde, G

    2011-01-01

    and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02505.x. ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections...... and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most...... prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively...

  16. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

    Science.gov (United States)

    Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

    2017-12-14

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I 2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall

  17. The causes and consequences of seasonal variation in COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Donaldson GC

    2014-10-01

    Full Text Available Gavin C Donaldson, Jadwiga A Wedzicha Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK Abstract: The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease. The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality. The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number. The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure. The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions. Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels. The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. Keywords: exacerbations of COPD, seasonality, winter mortality, winter morbidity

  18. Antibiotics usefulness and choice in BPCO acute exacerbation

    Directory of Open Access Journals (Sweden)

    Bruno Tartaglino

    2005-10-01

    Full Text Available Although the debate on the role of bacterial infections and antibiotic treatment in AE-COPD remains open, there is evidence that the persistence of bacteria after acute exacerbation (residual bacterial colony influences the frequency and severity of subsequent acute exacerbation and that antibiotic treatment that induces faster and more complete eradication produces better clinical outcomes. New aspects must now be considered, given that COPD is a chronic illness subject to acute exacerbations of varying frequencies and that acute exacerbations correspond to functional respiratory deterioration. One of the parameters that is currently acquiring clinical relevance is the interval free of infection (IFI, the period that elapses between one acute exacerbation and the next, caused by bacterial infection. Another guiding concept in the choice of antibiotic treatment is that not all patients benefit in the same way; those requiring more aggressive treatment are most likely to be those with FEV1 < 50%, frequent exacerbations (> 3/year treated with antibiotics, relevant co-morbidity, under chronic steroid treatment, etc., for these patients it is recommended to administer antibiotics active on the three most common pathogens (in particular H. influenzae, considering the resistance acquired in recent years, and on Pseudomomias aeruginosa.

  19. The role of aspirin in cancer prevention.

    Science.gov (United States)

    Thun, Michael J; Jacobs, Eric J; Patrono, Carlo

    2012-04-03

    Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding. Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily). This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin. It also considers how even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.

  20. Aspirin resistance following pediatric cardiac surgery.

    Science.gov (United States)

    Cholette, Jill M; Mamikonian, Lara; Alfieris, George M; Blumberg, Neil; Lerner, Norma B

    2010-09-01

    Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (paspirin-treated subjects who experienced thrombosis had higher POD#5 uTxB2. This finding did not reach statistical significance (p=0.07). Elevated pre-operative C-reactive protein (CRP) was independently associated with thrombosis (paspirin. Aspirin inhibited ex-vivo platelet function with a low incidence of resistance. Elevated POD#5 uTxB2 and pre-operative CRP were correlated with thrombosis in aspirin treated subjects. Further studies are needed to determine whether children with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  1. [Pathogenesis and prevention tactics of aspirin resistance].

    Science.gov (United States)

    Zhang, Ren-gang; Zhang, Jun-ping

    2007-05-01

    Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug. Despite its wide uses for more than 100 years, knowledge about mechanism of action and therapeutic issues of aspirin are still under discussion. The use of aspirin has been changed from an analgesic, anti-pyretic and anti-inflammatory agent to an anti-thrombotic agent, especially in secondary prevention of cardiovascular events. Aspirin has reduced the risk of cardiovascular events by 25%. However, the phenomenon of "aspirin resistance" has been described that in 5%-60% of patients aspirin may not achieve adequate efficacy of suppressing platelet activity. The convinced causes of this phenomenon are still unknown. It is probably due to drugs interaction, inadequate dosage and so on. By far the existing studies of aspirin are insufficient to explain all phenomena of aspirin resistance. And the results are not always uniform about the same research. Therefore, the characteristics in different population with aspirin resistance may account for the complexity. It is unrealistic to elucidate all aspirin resistance by only one pathway. More studies are required to investigate the mechanisms in different population respectively. According to the theory of traditional Chinese medicine and the trait of cardiovascular disease, which often relapses and has a long history, aspirin resistance should be considered as collaterals disease. It can be treated with aspirin and traditional Chinese drugs which have the power to strengthen body resistance, reduce phlegm, remove blood stasis and toxic materials from meridians. The problem of aspirin resistance might be solved by this way, because the traditional Chinese medicine has the superiority of selecting appropriate therapeutic methods based on syndrome differentiation for different population and regulating the whole body's function. Subsequently, cardiovascular disease might be effectively prevented.

  2. The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations.

    Science.gov (United States)

    Johnston, Neil W; McIvor, Andrew; Lambert, Kim; Greene, Justina M; Hussack, Pat; Gerhardsson de Verdier, Maria; Higenbottam, Tim; Lewis, Jonathan; Newbold, Paul; Herath, Athula; Jenkins, Martin

    2010-01-01

    Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections. To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season. Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing. Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections. The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas - in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence.

  3. Effectiveness and safety of seasonal influenza vaccination in children with underlying respiratory diseases and allergy.

    Science.gov (United States)

    Kang, Jin-Han

    2014-04-01

    Influenza causes acute respiratory infections and various complications. Children in the high-risk group have higher complication and hospitalization rates than high-risk elderly individuals. Influenza prevention in children is important, as they can be a source infection spread in their communities. Influenza vaccination is strongly recommended for high-risk children with chronic underlying circulatory and respiratory disease, immature infants, and children receiving long-term immunosuppressant treatment or aspirin. However, vaccination rates in these children are low because of concerns regarding the exacerbation of underlying diseases and vaccine efficacy. To address these concerns, many clinical studies on children with underlying respiratory diseases have been conducted since the 1970s. Most of these reported no differences in immunogenicity or adverse reactions between healthy children and those with underlying respiratory diseases and no adverse effects of the influenza vaccine on the disease course. Further to these studies, the inactivated split-virus influenza vaccine is recommended for children with underlying respiratory disease, in many countries. However, the live-attenuated influenza vaccine (LAIV) is not recommended for children younger than 5 years with asthma or recurrent wheezing. Influenza vaccination is contraindicated in patients with severe allergies to egg, chicken, or feathers, because egg-cultivated influenza vaccines may contain ovalbumin. There has been no recent report of serious adverse events after influenza vaccination in children with egg allergy. However, many experts recommend the trivalent influenza vaccine for patients with severe egg allergy, with close observation for 30 minutes after vaccination. LAIV is still not recommended for patients with asthma or egg allergy.

  4. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... En español Talk with Your Doctor about Taking Aspirin to Prevent Disease Browse Sections The Basics Overview ... and Risks What are the benefits of taking aspirin regularly? Low-dose aspirin can reduce your risk ...

  5. Aspirin to Prevent a First Heart Attack or Stroke

    Science.gov (United States)

    ... NHLBI on Twitter. Aspirin to Prevent a First Heart Attack or Stroke Also known as aspirin primary prevention. ... if I’m taking aspirin to prevent another heart attack or stroke? The information discussed in Who may ...

  6. Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

    OpenAIRE

    Undas, Anetta; Brummel-Ziedins, Kathleen E.; Mann, Kenneth G.

    2007-01-01

    Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A2 production. Aspirin can reduce thromb...

  7. How Successful is Non-Invasive Ventilation Treatment that is Initiated in the Emergency Department in Cases of COPD Exacerbations with Acute Hypercapnic Respiratory Failure? Can We Predict Treatment Failure?

    Directory of Open Access Journals (Sweden)

    Meltem Çoban Ağca

    2017-04-01

    Full Text Available Objective: We aimed to investigate the success rate of non-invasive ventilation (NIV in wards and the predictors of failure in cases of chronic obstructive pulmonary disease (COPD-related acute hypercapnic respiratory failure (AHRF. Methods: The was a retrospective study conducted in a tertiary teaching hospital between May 2011 and 2013. Patients who were admitted to the emergency department (ED because of COPD with AHRF were evaluated; 544 patients who initially received NIV in ED and were transferred to wards were included. Patient characteristics, baseline and follow-up pH values, and partial arterial carbon dioxide (PaCO2 values were recorded. Baseline pH values were categorized as severe (pH<7.26, moderate (pH≥7.26–7.30, and mild (pH≥7.30 acidosis. According to the in-hospital outcome, patients were classified in 2 groups: Group 1: home discharge, Group 2: death or intensive care unit transfer. Results: Treatment resulted in success in 477 (88% patients. Albumin levels were significantly low and the mean Charlson index (CI score was significantly high in Group 2. Admission pH and PaCO2 values did not affect the treatment outcome. Patients in Group 2 had higher PaCO2 and lower pH values as well as a lower level of decrease in PaCO2 values within 2 hours of treatment in ED. Similarly, higher PaCO2 and lower pH values at the end of the first day in wards were indicative of NIV failure (p<0.05. Conclusion: The success rate of NIV in wards in cases of AHRF is high. Patients with low albumin levels and higher CI scores have worse response to treatment. pH or PaCO2 values after a few hours of treatment and not the baseline pH or PaCO2 values are better predictors than the baseline pH and PaCO2 values.

  8. Effects of Aspirin on Rheological Properties of Erythrocytes In Vitro

    OpenAIRE

    Elblbesy, Mohamed A.; Hereba, Abdel Rahman M.; Shawki, Mamdouh M.

    2012-01-01

    Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. Most studies on the mechanism of action of aspirin have concentrated on the effect of aspirin on platelets. In the present study we have tried to prove that there is another biophysical mechanism of aspirin, and that is through the effect of aspirin on erythrocytes. In this study ten blood samples were incubated with aspirin at different concentrations. The ...

  9. Genetic Markers for Differentiating Aspirin-Hypersensitivity

    OpenAIRE

    Kim, Seung-Hyun; Park, Hae-Sim

    2006-01-01

    Aspirin-induced asthma (AIA) and aspirin-induced urticaria/angioedema (AIU) are two major aspirin-related allergies. We summarize recent findings related to their molecular genetic mechanisms in order to identify genetic susceptibility markers for differentiating AIU and AIA. The overproduction of cysteinyl leukotriene has been suggested as a mechanism in both AIU and AIA. Increased expression of CYSLTR1 with CYLSTR1 and CYSLTR2 polymorphisms are new findings in AIA, while the ALOX5 promoter ...

  10. [From the willow to aspirin].

    Science.gov (United States)

    Lafont, Olivier

    2007-07-01

    At the beginning was the willow bark, which was considered as a medicine by Hippocrates, Dioscorides and Plinus. During the XVIIIth century, the Reverend Edward Stone re-discovered the willow for the cure of agues. In 1829, the french pharmacist Pierre Joseph Leroux isolated salicin. Raffaelle Piria was the first to synthesize salicylic acid from salicin (salicoside). Hermann Kolbe prepared salicylic acid from sodium phenate and carbon dioxide. And then acetylsalicylic acid was first prepared by Charles Gerhardt in 1853, but he did not succeed in identifying its structure. Felix Hoffmann, Arthur Eichengrun and Heinrich Dresen from Bayer Laboratories were at the origin of the use of Aspirin as a medicine. In 1971, John Vane showed that aspirin-like drugs inhibited prostaglandine synthesis.

  11. Respiratory acidosis

    Science.gov (United States)

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...

  12. Limited influence of aspirin intake on mast cell activation in patients with food-dependent exercise-induced anaphylaxis: comparison using skin prick and histamine release tests.

    Science.gov (United States)

    Fukunaga, Atsushi; Shimizu, Hideki; Tanaka, Mami; Kikuzawa, Ayuko; Tsujimoto, Mariko; Sekimukai, Akiko; Yamashita, Junji; Horikawa, Tatsuya; Nishigori, Chikako

    2012-09-01

    Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe systemic syndrome induced by physical exercise after ingesting causative food. Aspirin is a well-known trigger for anaphylaxis in patients with FDEIA. Possible mechanisms by which symptoms are aggravated by aspirin include enhanced antigen absorption and mast cell activation. The aim of this study was to determine whether aspirin intake has an influence on mast cell/basophil activation in patients with FDEIA. Provocation tests revealed that adding aspirin to the causative food challenge in 7 of 9 (77.8%) patients with FDEIA provoked symptoms. In most cases, pretreatment with aspirin did not enhance skin tests (71.4%) or histamine release tests (88.9%) with food allergen challenges. The study confirms that histamine release and skin prick tests can be adjunctive tools for diagnosing FDEIA. In addition, our results suggest that exacerbation of FDEIA symptoms by aspirin is not mediated by direct effects of aspirin on mast cell/basophil activation.

  13. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): A multicentre randomised double-blind placebo-controlled trial

    NARCIS (Netherlands)

    G.G. Brusselle (Guy); C. VanderStichele (Christine); P. Jordens (Paul); R. Deman (René); H. Slabbynck (Hans); V. Ringoet (Veerle); G. Verleden (Geert); I.K. Demedts (Ingel); K.M.C. Verhamme (Katia); A. Delporte (Anja); B. Demeyere (Bénédicte); T. Claeys (Tine); J. Boelens (Jerina); E. Padalko (Elizaveta); J. Verschakelen (Johny); G. van Maele (Georges); E. Deschepper (Ellen); G.F. Joos (Guy)

    2013-01-01

    markdownabstract__Background:__ Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases

  14. A Case-Control Study of the Role of Cold Symptoms and other Historical Triggering Factors in Asthma Exacerbations

    Directory of Open Access Journals (Sweden)

    Susan M Tarlo

    2000-01-01

    Full Text Available BACKGROUND: Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study.

  15. Is non-therapeutic aspirin use in children a problem in South Africa?

    Science.gov (United States)

    Donald, Kirsten; Hall, Susan; Seaton, Cylene; Tanyanyiwa, Donald

    2011-11-01

    Aspirin should not be used in children except for specific therapeutic reasons. We report on a severely ill infant who had ingested aspirin contained in a traditional medicine and review 21 other patients with pre-admission non-therapeutic salicylate exposure. We reviewed laboratory, clinical and poisons unit records to determine how many children were admitted to our hospital over an 18-month period with evidence of salicylate ingestion not prescribed for therapeutic reasons. We determined the source of the salicylate, elapsed time between ingestion and laboratory assay, morbidity and mortality and final diagnosis. Twenty-one children meeting our criteria, including 9 under 6 months of age, were admitted during this period. The most prevalent source of salicylate was over-the-counter (OTC) aspirin, but some had reportedly only been given traditional medicines. Nineteen were seriously ill, 4 died and 3 had severe brain injury. Two, initially diagnosed with Reye's syndrome, probably had inherited metabolic disorders. Only 2 patients had salicylate levels that at the time of measurement are normally considered toxic; however, the literature suggests that lower levels may exacerbate illness severity in young children. We found inappropriate use of OTC aspirin in children that requires explanation. There may be policy implications for the content and presentation of patient information; the incorporation of pharmaceuticals in traditional medicines merits further study. Salicylate toxicity should be considered in children with unexplained metabolic acidosis out of keeping with the severity of their acute illness.

  16. Home Non Invasive Ventilation (NIV) treatment for COPD patients with a history of NIV-treated exacerbation

    DEFF Research Database (Denmark)

    Ankjærgaard, Kasper Linde; Tønnesen, Philip; Laursen, Lars Christian

    2016-01-01

    BACKGROUND: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory...... or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases. DISCUSSION: Though previous studies of long...

  17. Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin.

    Science.gov (United States)

    Cîrstea, M; Suhaciu, G; Cîrje, M; Ciontescu, L

    1976-10-01

    Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.

  18. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer

    DEFF Research Database (Denmark)

    Verdoodt, F.; Kjaer, S. K.; Friis, S.

    2017-01-01

    Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...

  19. Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

    Directory of Open Access Journals (Sweden)

    Søgaard M

    2016-03-01

    Full Text Available Mette Søgaard,1 Morten Madsen,1 Anders Løkke,2 Ole Hilberg,2 Henrik Toft Sørensen,1 Reimar W Thomsen1 1Department of Clinical Epidemiology, 2Department of Respiratory Medicine, Aarhus University Hospital, Aarhus C, Denmark Background: Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD exacerbation and influence their outcomes.Methods: We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012.Results: We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%. Pneumonia was frequent in first-time exacerbations (36.1%, but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days, intensive care unit admission (7.7% vs 12.5%, and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24. Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18, and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13. In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations.Conclusions: Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care

  20. Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study

    OpenAIRE

    Mohan, Sindu; Ho, Terence; Kjarsgaard, Melanie; Radford, Katherine; Borhan, A. S. M.; Thabane, Lehana; Nair, Parameswaran

    2017-01-01

    Background Infective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum. Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation. Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD. The purpose of our study was to determine if hemosiderin in sputum ...

  1. Post-traumatic stress symptoms and exacerbations in COPD patients.

    Science.gov (United States)

    Teixeira, Paulo Josè Zimermann; Porto, Lucia; Kristensen, Christian Haag; Santos, Alvaro Huber; Menna-Barreto, Sergio Saldanha; Do Prado-Lima, Pedro AntÙnio Schmidt

    2015-02-01

    Post-Traumatic Stress Disorder (PTSD) is a common psychological consequence of exposure to traumatic stressful life events. During COPD exacerbations dyspnea can be considered a near-death experience that may induce post-traumatic stress symptoms. The aim of this study was to evaluate the relationship between COPD exacerbations and PTSD- related symptoms. Thirty-three in-patients with COPD exacerbations were screened for the following: PTSS (Screen for Posttraumatic Stress Symptoms), anxiety (Beck Anxiety Inventory) and depression (Beck Depression Inventory). Patients had a median age of 72 years and 72.7% were female. Mean FEV1 and FVC were 0.8 ± 0.3 (37.7 ± 14.9% of predicted) and 1.7 ± 0.6 (60 ± 18.8% of predicted), respectively with a mean exacerbation of 2.9 episodes over the past year. Post-traumatic stress symptoms related to PTSD were found in 11 (33.3%) patients (SPTSS mean score 4.13 ± 2.54); moderate to severe depression in 16 (48.5%) (BDI mean score 21.2 ± 12.1) and moderate to severe anxiety in 23 (69.7%) (BAI mean score 23.5 ± 12.4). In a linear regression model, exacerbations significantly predicted post-traumatic stress symptoms scores: SPTSS scores increased 0.9 points with each exacerbation (p = 0.001). Significant correlations were detected between PTSD-related symptoms and anxiety (rs = 0.57; p = 0.001) and PTSD symptoms and depression (rs = 0.62; p = 0.0001). In a multivariable analysis model, two or more exacerbation episodes led to a near twofold increase in the prevalence ratio of post-traumatic stress symptoms related to PTSD(PR1.71; p = 0.015) specially those requiring hospitalization (PR 1.13; p = 0.030) CONCLUSION: PTSD symptoms increase as the patient's exacerbations increase. Two or more exacerbation episodes lead to a near twofold increase in the prevalence ratio of post-traumatic symptomatology. Overall, these findings suggest that psychological domains should be addressed along with respiratory function and exacerbations in

  2. EFFECT OF ACETYLSALICYCLIC ACID (ASPIRIN ) AND ...

    African Journals Online (AJOL)

    LIVINGSTON

    Aspirin as such, irreversibly blocks the enzyme cyclo-oxygenase (prostaglandin synthase) which catalyzes the conversion of. Archidonic acid to endoperoxide compounds. In addition to reducing the synthesis of eicosanoid mediators, ASA also interferes with the chemical mediators of the kalikrein system. As a result, aspirin ...

  3. Pharmacogenetics of the antiplatelet effect of aspirin.

    Science.gov (United States)

    Würtz, Morten; Kristensen, Steen Dalby; Hvas, Anne-Mette; Grove, Erik Lerkevang

    2012-01-01

    The concept of "pharmacogenetics" addresses genetically determined variation in how individuals respond to drugs. Accordingly, specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although with considerable interindividual variation. According to meta-analyses, a reduced antiplatelet effect of aspirin confers an increased risk of cardiovascular events. The platelet response to aspirin is assessed by in vitro evaluation of thromboxane-dependent platelet function. A reduced antiplatelet effect of aspirin can be explained by several mechanisms, which are largely determined by clinical, pharmacodynamic, biological and genetic factors. During the past decade, numerous studies have identified genetic polymorphisms significantly associated with cardiovascular events and modulating the antiplatelet effect of aspirin. However, results have been contradictory allowing only few firm conclusions to be drawn. Polymorphisms in genes encoding glycoproteins (IIb/IIIa, Ia/IIa, VI and Ibα), cyclooxygenases (1 and 2), adenosine diphosphate receptors (P2Y1 and P2Y12) and proteins of importance for haemostasis (thromboxane A2 receptor, coagulation factor XIII, etc.) have been investigated. In particular, a polymorphism in the gene encoding glycoprotein IIb/IIIa has been associated with a reduced antiplatelet effect of aspirin. The additive value of an individual's genetic makeup in predicting the antiplatelet effect of aspirin and the risk of cardiovascular events remains controversial. The present review outlines the pharmacology of aspirin and provides an overview of specific genetic variations considered to influence the antiplatelet effect of aspirin.

  4. Effect of aspirin on nasal resistance to airflow.

    OpenAIRE

    Jones, A S; Lancer, J M; Moir, A A; Stevens, J C

    1985-01-01

    The effect of aspirin on nasal resistance to airflow was investigated by rhinomanometry in 25 healthy subjects before and after ingestion of aspirin or vitamin C in a double blind crossover trial. Aspirin caused a significant increase in nasal resistance compared with vitamin C. The effect of aspirin may be due to its inhibition of the synthesis of prostaglandins.

  5. Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

    Directory of Open Access Journals (Sweden)

    Caroline Knaut

    2017-01-01

    Full Text Available Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT. Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p=0.004 and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p=0.008 and pulse oximetry (SpO2 decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p<0.001. Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p=0.092, and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe.

  6. Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

    Science.gov (United States)

    Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

    2013-11-01

    Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

  7. Acute asthma exacerbations: an overview

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2014-07-01

    Full Text Available Asthma is a chronic inflammatory disease of the airways. All patient with asthma are at risk of having exacerbations characterized by worsening symptoms, airflow obstruction, and an increased requirement for rescue bronchodilators. Asthma exacerbations can be classified as mild, moderate, severe, or life threatening. The goals of treatment are correction of severe hypoxemia, rapid reversal of airflow obstruction, and reduction of the risk of relapse.http://dx.doi.org/10.7175/rhc.v5i3.932

  8. Diagnostic Utility of Urinary LTE4 in Asthma, Allergic Rhinitis, Chronic Rhinosinusitis, Nasal Polyps, and Aspirin Sensitivity.

    Science.gov (United States)

    Divekar, Rohit; Hagan, John; Rank, Matthew; Park, Miguel; Volcheck, Gerald; O'Brien, Erin; Meeusen, Jeffrey; Kita, Hirohito; Butterfield, Joseph

    2016-01-01

    Urinary leukotriene E4 (LTE4) is a well-validated marker of the cysteinyl leukotriene pathway, and LTE4 elevation has been described in conditions such as asthma, aspirin sensitivity, and chronic rhinosinusitis (CRS). There have been a number of reports investigating the role of spot urine LTE4 to predict aspirin sensitivity; however, variability in urinary LTE4 may affect the accuracy of this approach. Here, we explored the utility of 24-hour urinary LTE4 in 5 clinical diagnoses of allergic rhinitis, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), CRS without nasal polyps, and aspirin sensitivity. This was a retrospective review of patients who had 24-hour quantification of urinary LTE4 by a clinically validated liquid chromatography tandem mass spectrometry method and their assigned diagnoses after assessment and clinical care. Twenty-four-hour urinary LTE4 elevations were seen in those with asthma and those with CRSwNP but influenced by underlying aspirin sensitivity. Elevation in LTE4 was significant in those with CRSwNP after adjusting for aspirin sensitivity. Allergic rhinitis was not associated with elevated LTE4 excretion. Receiver operator characteristic analysis of 24-hour urinary LTE4 showed that a cutoff value of 166 pg/mg Cr suggested the presence of history of aspirin sensitivity with 89% specificity, whereas a cutoff value of 241 pg/mg Cr discriminated "challenge-confirmed" aspirin-sensitive subjects with 92% specificity. Elevated 24-hour excretion of urinary LTE4 is a reliable and simple test to identify aspirin sensitivity in patients with respiratory diagnoses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study

    Directory of Open Access Journals (Sweden)

    Mallia Patrick

    2006-09-01

    Full Text Available Abstract Background Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists. Methods We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II. Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage. Results All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events. Conclusion Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.

  10. Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

    2017-02-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease

  11. Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

    Science.gov (United States)

    Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2018-01-01

    Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p < 0.05). The grade of severity correlated with the depth of inflammation (r s = 0.492, p < 0.001). Maximal dose aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

  12. Exacerbation of asthma secondary to fentanyl transdermal patch.

    Science.gov (United States)

    Parmar, Malvinder S

    2009-01-01

    Asthma is a common chronic inflammatory disorder of the airways associated with hyperresponsiveness, reversible airflow limitation and respiratory symptoms.1 All patients with asthma are at risk for exacerbations that may range from mild to life threatening. Different triggers cause asthma exacerbation by inducing airway inflammation and/or provoking bronchospasm. Allergen-induced bronchospasm results from IgE-dependent release of mediators including histamine, prostaglandins and leukotrienes.2 Opiates are commonly used to treat chronic pain.3 Although hypersensitivity to opiates or accumulation of opiates can cause respiratory depression, opiates are also used in the management of cough and dyspnoea associated with advanced COPD and heart failure.4(,)5 Here, a report is presented on a patient who developed persistent exacerbation of underlying stable asthma after initiating fentanyl transdermal therapy for chronic low back pain. He underwent extensive investigations and a detailed reassessment of history, especially medication history, led to the possible causative factor; once recognised, removal of the offending agent (fenatnyl) resulted in complete improvement in his symptoms within 72 h.

  13. The Aspirin Foundation Scientific Conference: the history, the present state and the future of aspirin prophylaxis

    OpenAIRE

    Smith, Tom; Elwood, Peter; Keating, Conrad; Rothwell, Peter; Detering, Elmar; Freedman, Andrew; Langley, Ruth; Logan, Richard; Phillips, Ceri; DeCensi, Andrea

    2014-01-01

    The 2013 Aspirin Foundation Conference covered a range of topics from clinical and medical history, epidemiology, health economics, and the current uses of aspirin in general practice and in the treatment and prevention of cancer. The use of aspirin as primary prevention in people at risk of atherosclerotic events is now well known, but its use as a preventative agent in some cancer types is still under discussion, and data on colorectal and lung cancer were presented at this meeting. The pot...

  14. Respiratory alkalosis

    Science.gov (United States)

    Alkalosis - respiratory ... leads to shortness of breath can also cause respiratory alkalosis (such as pulmonary embolism and asthma). ... Treatment is aimed at the condition that causes respiratory alkalosis. Breathing into a paper bag -- or using ...

  15. Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study.

    Science.gov (United States)

    Mohan, Sindu; Ho, Terence; Kjarsgaard, Melanie; Radford, Katherine; Borhan, A S M; Thabane, Lehana; Nair, Parameswaran

    2017-04-12

    Infective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum. Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation. Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD. The purpose of our study was to determine if hemosiderin in sputum macrophages is related to infective exacerbations of COPD. We undertook a retrospective observational study of 54 consecutive patients who presented with an exacerbation of COPD and had sputum examined including assessment for hemosiderin in alveolar macrophages. The relation between infective exacerbations in the previous two years and the percent of hemosiderin-positive macrophages was analyzed with linear regression. To account for the non-parametric distribution of infective exacerbations, negative binomial regression modelling was used to account for other covariates. The percent of hemosiderin positive alveolar macrophages (hemosiderin index), analyzed parametrically and non-parametrically, demonstrated a significant correlation with increasing numbers of infective exacerbations in the previous two years. In a multivariate regression analysis, hemosiderin index was an independent predictor of infective exacerbations. COPD patients with raised hemosiderin index (≥20%) had higher levels of sputum IL-6 compared to patients with lower levels (hemosiderin index in sputum alveolar macrophages measured at the time of AECOPD may be related to the frequency of infective exacerbations of COPD.

  16. Exacerbations in Chronic Obstructive Pulmonary Disease: Identification and Prediction Using a Digital Health System.

    Science.gov (United States)

    Shah, Syed Ahmar; Velardo, Carmelo; Farmer, Andrew; Tarassenko, Lionel

    2017-03-07

    Chronic obstructive pulmonary disease (COPD) is a progressive, chronic respiratory disease with a significant socioeconomic burden. Exacerbations, the sudden and sustained worsening of symptoms, can lead to hospitalization and reduce quality of life. Major limitations of previous telemonitoring interventions for COPD include low compliance, lack of consensus on what constitutes an exacerbation, limited numbers of patients, and short monitoring periods. We developed a telemonitoring system based on a digital health platform that was used to collect data from the 1-year EDGE (Self Management and Support Programme) COPD clinical trial aiming at daily monitoring in a heterogeneous group of patients with moderate to severe COPD. The objectives of the study were as follows: first, to develop a systematic and reproducible approach to exacerbation identification and to track the progression of patient condition during remote monitoring; and second, to develop a robust algorithm able to predict COPD exacerbation, based on vital signs acquired from a pulse oximeter. We used data from 110 patients, with a combined monitoring period of more than 35,000 days. We propose a finite-state machine-based approach for modeling COPD exacerbation to gain a deeper insight into COPD patient condition during home monitoring to take account of the time course of symptoms. A robust algorithm based on short-period trend analysis and logistic regression using vital signs derived from a pulse oximeter is also developed to predict exacerbations. On the basis of 27,260 sessions recorded during the clinical trial (average usage of 5.3 times per week for 12 months), there were 361 exacerbation events. There was considerable variation in the length of exacerbation events, with a mean length of 8.8 days. The mean value of oxygen saturation was lower, and both the pulse rate and respiratory rate were higher before an impending exacerbation episode, compared with stable periods. On the basis of the

  17. Aspirin

    Science.gov (United States)

    ... Circulation My alerts Sign In Join Sign out Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Doodle Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  18. Aspirin

    Science.gov (United States)

    ... not make sense fear or nervousness dizziness double vision uncontrollable shaking of a part of the body confusion abnormally excited mood hallucination (seeing things or hearing voices that are not ...

  19. Mechanisms of aggregation inhibition by aspirin and nitrate-aspirin prodrugs in human platelets.

    Science.gov (United States)

    Harmon, Shona; Inkielewicz-Stepniak, Iwona; Jones, Michael; Ledwidge, Mark; Santos-Martinez, Maria Jose; Medina, Carlos; Radomski, Marek W; Gilmer, John F

    2012-01-01

    Aspirin is the mainstay of anti-platelet therapy in the secondary prevention of cardiovascular disease. However, problems with aspirin safety and resistance demand clinical strategies based on multiple pharmacological approaches. Prodrugs of aspirin may offer beneficial effects in terms of gastro-intestinal safety and multiple pharmacological approaches. However, the pharmacological profile of aspirin prodrugs in human platelets has not been completed yet. We aimed to compare the effects of aspirin and prodrugs of aspirin (1-5) on human platelet aggregation stimulated by ADP and collagen and associated receptor expression (GPIIb/IIIa and P-selectin) in platelet-rich plasma (PRP) and washed platelets (WP). As aspirin is released from prodrugs following esterase hydrolysis we studied the expression and activity of butyrylcholineterase (BuChE) and carboxyesterase (CE) in plasma and platelets. The mechanism of prodrug-induced platelet aggregation inhibition was explored by studying the effects of plasma and purified human BuChE on aggregation. Finally, the relative contribution of nitric oxide (NO) bioactivity to nitrate-containing prodrugs of aspirin-induced inhibition of aggregation was determined using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,) a selective inhibitor of the soluble guanylyl cyclase. ST0702, 2, a nicotinic acid-aspirin codrug was equipotent with aspirin with respect to inhibition of collagen-induced platelet aggregation. Compound 4, a NO releasing aspirin was the most potent inhibitor of ADP-induced platelet aggregation, an effect partially reversed by ODQ. The platelet inhibitory effects of aspirin prodrugs were time-dependent as the maximal inhibitory effects against collagen-induced aggregation were achieved by aspirin at 2 min, 1 at 5 min and ST0702 at 15 min. The aspirin prodrugs were significantly less potent in WP than in PRP and the reverse was true of aspirin. In the presence of complete BuChE inhibition in PRP, there was almost

  20. [Aspirin: Indications and use during pregnancy].

    Science.gov (United States)

    Belhomme, N; Doudnikoff, C; Polard, E; Henriot, B; Isly, H; Jego, P

    2017-12-01

    Aspirin (acetylsalicylic acid) has been used ever since the Antiquity for its painkilling and anti-inflammatory effects. Its antiplatelet properties have then extended its indications to the field of coronaropathy and vascular cerebral disease, and finally to vascular placental disease. Aspirin has been widely prescribed since the 1980's to prevent pre-eclampsia, intra-uterine growth retardation and fetal death of vascular origin. It has also been proposed to prevent unexplained recurrent miscarriages. Its use during pregnancy is considered as safe, provided the daily doses do not exceed 100mg. Aspirin has been proven efficient to prevent pre-eclampsia and fetal growth restriction in high-risk patients. The benefits of prescribing aspirin have been demonstrated neither for vascular placental disease prevention in low risk patients, nor in cases of unexplained recurrent miscarriages. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  1. The use of cellular and molecular biomarkers to manage COPD exacerbations.

    Science.gov (United States)

    Ho, Terence; Dasgupta, Angira; Hargreave, Frederick E; Nair, Parameswaran

    2017-05-01

    Chronic obstructive pulmonary disease (COPD) exacerbations are a common cause of respiratory morbidity and mortality, and have various etiologies. Multiple cellular and molecular biomarkers have been associated with exacerbations. Quantitative sputum cell counts are able to identify the presence and type of bronchitis, which is an important contributor to exacerbations. Their utility to monitor bronchitis and to help treat exacerbations has been evaluated, yet they are not used in routine clinical practice. Areas covered: This review will provide a brief summary of biomarkers utilized in COPD, with a focus on the application of cellular markers for the management of exacerbations. A case study will demonstrate the application of these methods. With quantitative sputum cell counts, the presence of eosinophilic bronchitis predicts corticosteroid-responsiveness, while neutrophilic bronchitis identifies infection and suggests the need for antibiotics. Gastroesophageal reflux-related aspiration and heart failure can also be identified by examining sputum. Expert commentary: Quantitative sputum cytometry is an essential tool in the management of exacerbations of COPD, particularly those prone to frequent exacerbations. Treatment based on sputum cell counts is superior to current guideline-based recommendations to prevent future exacerbations and hospitalizations in observational and single-centre controlled trials. Large multicentre clinical trials are necessary to confirm this.

  2. Inhibitory Effect of Aspirin on Cholangiocarcinoma Cells

    Science.gov (United States)

    Boueroy, Parichart; Aukkanimart, Ratchadawan; Boonmars, Thidarut; Sriraj, Pranee; Ratanasuwan, Panaratana; Juasook, Amornrat; Wonkchalee, Nadchanan; Vaeteewoottacharn, Kulthida; Wongkham, Sopit

    2017-11-26

    Aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of cancer due to their anti-proliferative and apoptotic effects, which are the important mechanisms for their anti-tumor activity. Here, the effect of aspirin on human cholangiocarcinoma cells (KKU-214) and the underlying mechanisms of its action were explored. Cell proliferation was measured by sulforhodamine B (SRB) assay, while cell cycle distribution and apoptosis were determined by flow cytometry. Western blotting was used to explore protein expression underlying molecular mechanisms of anti-cancer treatment of aspirin. Aspirin reduced cell proliferation in a dose- and time-dependent manner, and altered the cell cycle phase distribution of KKU-214 cells by increasing the proportion of cells in the G0/G1 phase and reducing the proportion in the S and G2/M phases. Consistent with its effect on the cell cycle, aspirin also reduced the expression of cyclin D1 and cyclin‑dependent kinase 4 (Cdk-4), which are important for G0/G1 cell cycle progression. Treatment with aspirin led to increased induction of apoptosis in a dose-dependent manner. Further analysis of the mechanism underlying the effect of this drug showed that aspirin induced the expression of the tumor-suppressor protein p53 while inhibiting the anti-apoptotic protein B‑cell lymphoma-2 (Bcl-2). Correspondingly, the activation of caspase-9 and -3 was also increased. These findings suggest that aspirin causes cell cycle arrest and apoptosis, both of which could contribute to its anti-proliferative effect. Creative Commons Attribution License

  3. Toward a Consensus Definition for COPD Exacerbations

    National Research Council Canada - National Science Library

    Roberto Rodriguez-Roisin

    2000-01-01

    .... Exacerbations are associated with a significant increase in mortality, hospitalization, and health-care utilization, but there is currently no widely accepted definition of what constitutes an exacerbation of COPD...

  4. Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations

    OpenAIRE

    Vilaró, Jordi; Ramirez-Sarmiento, Alba; Martínez-Llorens, Juana Ma; Mendoza, Teresa; Alvarez, Miguel; Sánchez-Cayado, Natalia; Vega, Ángeles; Gimeno, Elena; Coronell, Carlos; Gea, Joaquim; Roca, Josep; Orozco-Levi, Mauricio

    2010-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. METHODS: A multicentre study was carried out in 121 COPD patients ...

  5. Frequency of self-reported COPD exacerbation and airflow obstruction in five Latin American cities: the Proyecto Latinoamericano de Investigacion en Obstruccion Pulmonar (PLATINO) study.

    Science.gov (United States)

    Montes de Oca, Maria; Tálamo, Carlos; Halbert, Ronald J; Perez-Padilla, Rogelio; Lopez, Maria Victorina; Muiño, Adriana; Jardim, José Roberto B; Valdivia, Gonzalo; Pertuzé, Julio; Moreno, Dolores; Menezes, Ana Maria B

    2009-07-01

    Recurrent exacerbations are common in COPD patients. Limited information exists regarding exacerbation frequency in COPD patients from epidemiologic studies. We examined the frequency of self-reported exacerbations and the factors influencing exacerbation frequency among COPD patients in a population-based study conducted in Latin America. We used a post-bronchodilator FEV(1)/FVC ratio of < 0.70 to define COPD. Exacerbation was self-reported and defined by symptoms (deterioration of breathing symptoms that affected usual daily activities or caused missed work). Spirometry was performed in 5,314 subjects. There were 759 subjects with airflow limitation; of these, 18.2% reported ever having had an exacerbation, 7.9% reported having an exacerbation, and 6.2% reported having an exacerbation requiring at least a doctor visit within the past year. The proportion of individuals with an exacerbation significantly increased by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, from 4.2% in stage 1 to 28.9% in stages 3 and 4. The self-reported exacerbation rate was 0.58 exacerbations per year. The rate of exacerbations requiring at least a doctor visit and length of stay in hospital due to exacerbations also increased as COPD severity progressed. The factors associated with having an exacerbation in the past year were dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and disease severity of GOLD stages 3 and 4. The proportion of individuals with airflow limitation and self-reported exacerbation increases as the disease severity progresses. Dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and more severe obstruction were significantly associated with having an exacerbation in the past year.

  6. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    Science.gov (United States)

    Mastalerz, L.; Sanak, M.; Kumik, J.; Gawlewicz-Mroczka, A.; Celejewska-Wójcik, N.; Ćmiel, A.; Szczeklik, A.

    2012-01-01

    Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity. PMID:22291720

  7. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    Directory of Open Access Journals (Sweden)

    L. Mastalerz

    2012-01-01

    Full Text Available Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS and high-performance liquid chromatography/mass spectrometry (HPLC-MS2 or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs. At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE which were higher in aspirin-induced asthma (AIA than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity.

  8. High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction.

    Science.gov (United States)

    Adamek, Anna; Hu, Kai; Bayer, Barbara; Wagner, Helga; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan

    2007-07-01

    Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.

  9. Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study

    Science.gov (United States)

    Lee, Meng; Wu, Yi-Ling; Saver, Jeffrey L; Lee, Hsuei-Chen; Lee, Jiann-Der; Chang, Ku-Chou; Wu, Chih-Ying; Lee, Tsong-Hai; Wang, Hui-Hsuan; Rao, Neal M; Ovbiagele, Bruce

    2014-01-01

    Objective There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Design Retrospective. Setting We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Participants Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010. Primary and secondary outcome measures The primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Results Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, paspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation. PMID:25468508

  10. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

    Science.gov (United States)

    Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A

    2006-05-20

    Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

  11. Exacerbation of asthma and airway infection: is the virus the villain?

    Directory of Open Access Journals (Sweden)

    Lusmaia D.C. Costa

    2014-11-01

    Conclusions: Respiratory viruses are present in the majority of asthmatic children during episodes of exacerbation. The involved physiopathological mechanisms are yet to be fully established, and the synergism between allergic inflammation and viral infection appears to determine uncontrolled disease. The role of other triggering and protective agents is yet to be clearly determined.

  12. Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

    Science.gov (United States)

    Jouneau, S; Dres, M; Guerder, A; Bele, N; Bellocq, A; Bernady, A; Berne, G; Bourdin, A; Brinchault, G; Burgel, P R; Carlier, N; Chabot, F; Chavaillon, J M; Cittee, J; Claessens, Y E; Delclaux, B; Deslée, G; Ferré, A; Gacouin, A; Girault, C; Ghasarossian, C; Gouilly, P; Gut-Gobert, C; Gonzalez-Bermejo, J; Jebrak, G; Le Guillou, F; Léveiller, G; Lorenzo, A; Mal, H; Molinari, N; Morel, H; Morel, V; Noel, F; Pégliasco, H; Perotin, J M; Piquet, J; Pontier, S; Rabbat, A; Revest, M; Reychler, G; Stelianides, S; Surpas, P; Tattevin, P; Roche, N

    2017-04-01

    Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  13. Exacerbations and healthcare resource utilization among COPD patients in a Swedish registry-based nation-wide study.

    Science.gov (United States)

    Johansson, Gunnar; Mushnikov, Vasili; Bäckström, Tobias; Engström, Andreas; Khalid, Javaria Mona; Wall, Jennifer; Hoti, Fabian

    2018-01-25

    Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality. We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities. Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death. Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits. Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index. In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations. COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.

  14. Relation of aspirin failure to clinical outcome and to platelet response to aspirin in patients with acute myocardial infarction.

    Science.gov (United States)

    Beigel, Roy; Hod, Hanoch; Fefer, Paul; Asher, Elad; Novikov, Ilia; Shenkman, Boris; Savion, Naphtaly; Varon, David; Matetzky, Shlomi

    2011-02-01

    Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p aspirin-failure group (14.3% vs 2.5% p aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Enhancement of matrix metalloproteinase 2 and 9 inhibitory action of minocycline by aspirin: an approach to attenuate outcome of acute myocardial infarction in diabetes.

    Science.gov (United States)

    Bhatt, Lokesh K; Veeranjaneyulu, Addepalli

    2014-04-01

    Diabetes is a risk factor for exacerbated outcome after acute myocardial infarction (AMI) and doubles the risk of mortality after MI. Increased levels of MMP-2 and MMP-9 in diabetes cause vascular remodelling, which leads to cardiovascular complications of diabetes. We hypothesized that inhibition of MMP-2 and MMP-9 can reduce worsening of myocardial ischemia in diabetic patients. Further, we hypothesized that minocycline induced MMP-2 and MMP-9 inhibition will be potentiated by aspirin and the combination of both drugs will prevent worsening of MI in diabetic patients. In the present study, efficacy of combination of minocycline and aspirin to attenuate exacerbation of myocardial ischemia/reperfusion (I/R) injury in diabetic rats was evaluated. Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Three weeks after diabetes induction, rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 3 weeks. At the end of week 6, I/R injury was induced by ligating the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. Percentage infarct volume, arrhythmias, mortality, collagen level and MMP-2 and MMP-9 level were significantly increased in vehicle-treated diabetic group when compared with normoglycemic rats. Treatment with a combination of minocycline and aspirin decreased percentage infarct volume, arrhythmias, mortality and collagen level when compared with vehicle-treated diabetic controls and showed reduced levels of MMP-2 and MMP-9. Results of the present study suggest that the combination of minocycline and aspirin prevent worsening of AMI in diabetic rats. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  16. Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations

    Directory of Open Access Journals (Sweden)

    Kai-Michael Beeh

    2009-02-01

    Full Text Available Kai-Michael Beeh1, Bettina Hederer2, Thomas Glaab2, Achim Müller2, Maureen Rutten-van Moelken3, et al1insaf–Respiratory Research Institute, Wiesbaden, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Institute for Medical Technology Assessment, Erasmus Medical Centre, Rotterdam, The Netherlands, et alAbstract: Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol have demonstrated beneficial effects on exacerbations in placebo-controlled trials. However, there have been no direct comparisons of these drugs with exacerbations as the primary outcome and consequently COPD treatment guidelines do not indicate a preference for either bronchodilator. Therefore, an international, randomized, double-blind, double-dummy, parallelgroup clinical trial has been designed to investigate the comparative efficacy of 2 long-acting bronchodilators tiotropium 18 μg daily and salmeterol 50 μg bid on exacerbations. The trial will include at least 6800 randomized patients with diagnosis of COPD, 10 pack-year history of smoking, post-bronchodilator FEV1 ≤ 70% predicted, and a history of exacerbations in the previous year. The primary endpoint is time to first COPD exacerbation. Secondary endpoints include number of exacerbations and time to premature discontinuation of trial medication. The trial has been designed to address several of the challenges in studying exacerbations in a controlled trial by a symptom and event-based definition of exacerbations, frequent follow-up contacts, selection of time to first event as the primary endpoint and using exposure adjusted analysis when examining number of events. Other challenges in designing exacerbation trials such as differential discontinuation and follow-up of discontinued patients are discussed.Keywords: chronic obstructive pulmonary disease, exacerbation, salmeterol, study methodology, tiotropium

  17. Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations.

    Science.gov (United States)

    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Lin, Zhi-Min; Jiang, Mei; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

    2015-08-01

    Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of -2.2%, -0.8%, and -1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and -0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and

  18. Relationship between periodontitis-related antibody and frequent exacerbations in chronic obstructive pulmonary disease.

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    Tamaki Takahashi

    Full Text Available BACKGROUND: To identify patients with chronic obstructive pulmonary disease (COPD who are susceptible to frequent exacerbations is important. Although periodontitis aggravated by poor oral hygiene might increase the risk of lower respiratory tract infection, the relationship between periodontitis and COPD exacerbations remains unknown. This prospective cohort study investigates the relationship between periodontitis-related antibody and exacerbation frequency over a one-year period. METHODS: We assessed an IgG antibody titer against Porphyromonas gingivalis, which is a major pathogen of periodontitis, and then prospectively followed up 93 individuals over one year to detect exacerbations. RESULTS: The numbers of exacerbations and the rate of individuals with frequent exacerbations (at least two per year were significantly lower in patients with higher IgG titer than those with normal IgG titer (0.8 vs. 1.2 per year, p= 0.045 and 14.3 vs. 38.6%, p= 0.009, respectively. Multivariate logistic regression analysis showed that being normal-IgG titer for periodontitis-related antibody significantly increased the risk of frequent exacerbations (relative risk, 5.27, 95% confidence interval, 1.30-25.7; p = 0.019 after adjusting for other possible confounders, such as a history of exacerbations in the past year, disease severity, COPD medication and smoking status. CONCLUSIONS: Normal-IgG titer for periodontitis-related antibody can be an independent predictor of frequent exacerbations. Measuring periodontitis-related antibody titers might be useful to identify patients with susceptibility to frequent exacerbations so that an aggressive prevention strategy can be designed.

  19. Effects of Immunoglobulin Replacement on Asthma Exacerbation in Adult Asthmatics with IgG Subclass Deficiency.

    Science.gov (United States)

    Kim, Joo Hee; Ye, Young Min; Ban, Ga Young; Shin, Yoo Seob; Lee, Hyun Young; Nam, Young Hee; Lee, Soo Keol; Cho, You Sook; Jang, Seung Hun; Jung, Ki Suck; Park, Hae Sim

    2017-11-01

    Recurrent respiratory tract infection is a common manifestation of primary immunodeficiency disease, and respiratory viruses or bacteria are important triggers of asthma exacerbations. Asthma often coexists with humoral immunodeficiency in adults, and some asthmatics with immunoglobulin (Ig) G subclass deficiency (IgGSCD) suffer from recurrent exacerbations. Although some studies suggest a benefit from Ig replacement, others have failed to support its use. This study aimed to assess the effect of Ig replacement on asthma exacerbation caused by respiratory infection as well as the asthma control status of adult asthmatics with IgGSCD. This is a multi-center, open-label study of adult asthmatics with IgGSCD. All patients received monthly intravenous immunoglobulin (IVIG) for 6 months and were evaluated regarding asthma exacerbation related to infection, asthma control status, quality of life, and lung function before and after IVIG infusion. A total of 30 patients were enrolled, and 24 completed the study. Most of the patients had a moderate degree of asthma severity with partly (52%) or uncontrolled (41%) status at baseline. IVIG significantly reduced the proportion of patients with asthma exacerbations, lowered the number of respiratory infections, and improved asthma control status, compared to the baseline values (P<0.001). The mean asthma-specific quality of life and asthma control test scores were improved significantly (P=0.009 and P=0.053, respectively); however, there were no significant changes in lung function. IVIG reduced the frequency of asthma exacerbations and improved asthma control status in adult asthmatics with IgGSCD, suggesting that IVIG could be an effective treatment option in this population.

  20. Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

    Directory of Open Access Journals (Sweden)

    Hayasaka M

    2013-02-01

    Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

  1. Aspirin and Reye's syndrome — do parents know?

    OpenAIRE

    Hall, R. W.

    1987-01-01

    Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (P

  2. Aspirin and Reye's syndrome — do parents know?

    Science.gov (United States)

    Hall, R.W.

    1987-01-01

    Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (PReye's syndrome as the reason. PMID:3505289

  3. Acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Marco Confalonieri

    2017-04-01

    Full Text Available Since its first description, the acute respiratory distress syndrome (ARDS has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care.

  4. The mechanism of action of aspirin.

    Science.gov (United States)

    Vane, J R; Botting, R M

    2003-06-15

    The therapy of rheumatism began thousands of years ago with the use of decoctions or extracts of herbs or plants such as willow bark or leaves, most of which turned out to contain salicylates. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of salicylic acid in 1897. This drug was named "Aspirin" and became the most widely used medicine of all time. In 1971, Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in PG synthesis, the aspirin-like drugs also prevented the production of physiologically important PGs which protect the stomach mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required. This conclusion provided a unifying explanation for the therapeutic actions and shared side effects of the aspirin-like drugs. Twenty years later, with the discovery of a second COX gene, it became clear that there are two isoforms of the COX enzyme. The constitutive isoform, COX-1, supports the beneficial homeostatic functions, whereas the inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis.

  5. Molecular targets of aspirin and cancer prevention

    Science.gov (United States)

    Alfonso, L; Ai, G; Spitale, R C; Bhat, G J

    2014-01-01

    Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug. PMID:24874482

  6. Aspirin-induced gastrointestinal damage is associated with an inhibition of epithelial cell autophagy.

    Science.gov (United States)

    Hernández, Carlos; Barrachina, Maria Dolores; Vallecillo-Hernández, Jorge; Álvarez, Ángeles; Ortiz-Masiá, Dolores; Cosín-Roger, Jesús; Esplugues, Juan Vicente; Calatayud, Sara

    2016-07-01

    Aspirin (ASA) causes gastrotoxicity by hampering the epithelial defense against luminal contents through cyclooxygenase inhibition. Since cell survival in tough conditions may depend on rescue mechanisms like autophagy, we analyzed whether epithelial cells rely on this process to defend themselves from aspirin's damaging action. Rats received a single dose of ASA (150 mg/kg, p.o.) with or without pretreatment with the autophagy inhibitor 3-methyladenine, and gastric injury and epithelial autophagy were evaluated 3 h later. The effects of ASA on cell viability and autophagy were also evaluated in gastric epithelial AGS cells. Basal autophagy in the gastric mucosa was inhibited by ASA as demonstrated by increased levels of p62 and ubiquitinated proteins and total LC3 and a reduced LC3-II/LC3-I ratio. Similarly, ASA increased p62 and decreased LC3-II accumulation and the number of EmGFP/LC3B puncta in AGS cells. ASA activated the PI3K/Akt-GSK3-mTOR pathway, which phosphorylates ULK1 to prevent autophagy initiation, changes that were inhibited by the PI3K-inhibitor wortmannin. Autophagy inhibition seems to enhance the vulnerability of gastric epithelial cells as a combination of ASA with 3-methyladenine exacerbated rat gastric damage and AGS cell apoptosis. Our data highlight the importance of autophagy in the gastric mucosa as a protective mechanism when the epithelium is injured. In the stomach, aspirin induces mucosal damage and reduces autophagy, thus, eliminating a protective mechanism that epithelial cells could use to escape death. We hypothesize that the combination of aspirin with drugs that activate autophagy could protect against gastric damage.

  7. Pneumococcal vaccination and chronic respiratory diseases

    Directory of Open Access Journals (Sweden)

    Froes F

    2017-12-01

    Full Text Available Filipe Froes,1 Nicolas Roche,2 Francesco Blasi3,4 1Chest Department, Hospital Pulido Valente, North Lisbon Hospital Center, Lisbon, Portugal; 2Department of Respiratory and Intensive Care Medicine, Cochin Hospital, Paris Descartes University, Paris, France; 3Department of Pathophysiology and Transplantation, University of Milan, 4Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS ca Granda Ospedale Maggiore Policlinico, Milan, Italy Abstract: Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases

  8. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  9. A critical appraisal of the phenomenon of aspirin resistance

    DEFF Research Database (Denmark)

    Svenstrup Poulsen, Tina; Risom Kristensen, Søren; Atar, Dan

    2005-01-01

    Aspirin is the mainstay antiplatelet treatment in patients with high risk of cardiovascular atherothrombotic events, and its beneficial effect is documented in several clinical trials. Nevertheless, the effectiveness of aspirin has been questioned by the emergence of the concept of 'aspirin...

  10. PIXE analysis of trace metals in aspirin-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rinsvelt, H.A.; Sater, R.; Hurd, R.W.; Andres, J.M.

    1985-01-01

    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  11. PIXE analysis of trace metals in aspirin-treated rats

    Science.gov (United States)

    Van Rinsvelt, H. A.; Sater, R.; Hurd, R. W.; Andres, J. M.

    1985-05-01

    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  12. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...

  13. Influence of Pseudomonas aeruginosa on exacerbation in patients with bronchiectasis

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    Kiran Chawla

    2015-01-01

    Full Text Available Background: A majority of the studies done on the western population have shown that Pseudomonas aeruginosa causes many severe infections in patients with bronchiectasis as compared to other pathogens. There is scarcity of similar data from the Asian population. Materials and Methods: A prospective study was undertaken to identify the various pathogens isolated from the respiratory samples of 117 patients with bronchiectasis from south India and to compare the clinicomicrobiological profile of infections caused by P. aeruginosa and other respiratory pathogens. Results: The respiratory pathogens were isolated from 63 (53.8% patients. P. aeruginosa was the most common isolate (46.0% followed by Klebsiella pneumoniae (14.3% and other pathogenic bacteria. Patients included in the P. aeruginosa group had a higher number of exacerbations (p: 0.008, greater number of hospital admissions (p: 0.007, a prolonged hospital stay (p: 0.03, and poor lung function, compared to the patients infected with the non-Pseudomonas group. Conclusion: It is necessary to investigate the etiology of respiratory tract infections among bronchiectasis patients followed by the prompt management of cases diagnosed with P. aeruginosa infections, so as to lower the morbidity and have a better prognosis.

  14. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    OpenAIRE

    Chang Anne B; Grimwood Keith; Robertson Colin F; Wilson Andrew C; van Asperen Peter P; O’Grady Kerry-Ann F; Sloots Theo P; Torzillo Paul J; Bailey Emily J; McCallum Gabrielle B; Masters Ian B; Byrnes Catherine A; Chatfield Mark D; Buntain Helen M; Mackay Ian M

    2012-01-01

    Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amox...

  15. Mechanisms of aspirin-sensitive asthma

    Directory of Open Access Journals (Sweden)

    Sun Ying

    2004-01-01

    Full Text Available It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs, may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte–macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C4 synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT1, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E2 (PGE2 serves as a ‘brake’ to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of

  16. Aspirin and colorectal cancer: the promise of precision chemoprevention.

    Science.gov (United States)

    Drew, David A; Cao, Yin; Chan, Andrew T

    2016-03-01

    Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action.

  17. Asthma exacerbation prediction: recent insights.

    Science.gov (United States)

    Fleming, Louise

    2018-04-01

    Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them.

  18. The role of aspirin-triggered lipoxins in the mechanism of action of aspirin.

    Science.gov (United States)

    Gilroy, Derek W

    2005-01-01

    Few drugs have treated so many diseases, provided us with so much understanding of their pathogenesis, and tested our scientific creativity over the last 100 years as much as aspirin. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase (COX 2)-derived prostanoids, fatty acid metabolites that modulate host defense and regulate the cardiovascular system. However, the inhibition of COX 2 enzyme activity and prostaglandin synthesis has never fully explained aspirin's repertoire of anti-inflammatory effects, leaving many questions pertaining to its true mechanism of action unanswered. Here, data from a series of comparatively recent experiments exploring aspirin's unique ability to acetylate the active site of inducible COX 2 and generate a family of lipid mediators called the epi-Lipoxins will be discussed in light of their ability to exert profound modulatory effects on the innate and adaptive immune systems.

  19. Preventing and managing exacerbations in COPD – critical appraisal of the role of tiotropium

    Directory of Open Access Journals (Sweden)

    Donald P Tashkin

    2010-02-01

    Full Text Available Donald P TashkinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA,Los Angeles, CA, USAAbstract: The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (≥6 months’ duration tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13 and/or a longacting beta-agonist (LABA; n = 4, tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an

  20. Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.

    Science.gov (United States)

    Sperlich, Johannes M; Grimbacher, Bodo; Workman, Sarita; Haque, Tanzina; Seneviratne, Suranjith L; Burns, Siobhan O; Reiser, Veronika; Vach, Werner; Hurst, John R; Lowe, David M

    Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated. To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations. We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID. There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%. Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  1. Oral aspirin for treating venous leg ulcers.

    Science.gov (United States)

    de Oliveira Carvalho, Paulo Eduardo; Magolbo, Natiara G; De Aquino, Rebeca F; Weller, Carolina D

    2016-02-18

    Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwide; prevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. In May 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for

  2. A General Chemistry Laboratory Theme: Spectroscopic Analysis of Aspirin

    Science.gov (United States)

    Byrd, Houston; O'Donnell, Stephen E.

    2003-02-01

    In this paper, we describe the introduction of spectroscopy into the general chemistry laboratory using a series of experiments based on a common substance, aspirin. In the first lab the students synthesize and recrystallize aspirin and take melting points of their product, an aspirin standard, and salicylic acid. The students perform the remaining experiments on a rotating basis where the following four labs run simultaneously: structural characterization of the synthesized aspirin by IR and NMR; analysis of synthesized aspirin and commercial products by UV vis spectroscopy; analysis of synthesized aspirin and commercial products by HPLC; and analysis of calcium in commercial buffered aspirin tablets by AAS. In each of the analysis experiments, students collect, graph, and analyze their data using a spreadsheet. We have found that this series of labs has been very beneficial to our students. From the course evaluations, students indicate that they are beginning to understand how chemistry is applied outside of the classroom.

  3. Rivaroxaban with or without aspirin in stable cardiovascular disease

    DEFF Research Database (Denmark)

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie

    2017-01-01

    BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive...... rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after...... a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P

  4. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2012-08-01

    Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

  5. Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

    Science.gov (United States)

    Lee, Meng; Wu, Yi-Ling; Saver, Jeffrey L; Lee, Hsuei-Chen; Lee, Jiann-Der; Chang, Ku-Chou; Wu, Chih-Ying; Lee, Tsong-Hai; Wang, Hui-Hsuan; Rao, Neal M; Ovbiagele, Bruce

    2014-12-02

    There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Retrospective. We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis. Patients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010. The primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, paspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Reverse effect of aspirin: is the prothrombotic effect after aspirin discontinuation mediated by cyclooxygenase 2 inhibition?

    Science.gov (United States)

    Doutremepuich, Christian; Aguejouf, Omar; Eizayaga, Francisco X; Desplat, Vanessa

    2007-01-01

    While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients. We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways. We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398. We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient's blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway. Copyright 2008 S. Karger AG, Basel.

  7. Genetic associations with viral respiratory illnesses and asthma control in children

    DEFF Research Database (Denmark)

    Loisel, D A; Du, G; Ahluwalia, T S

    2016-01-01

    BACKGROUND: Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. OBJECTIVE: We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses...... and the risk of virus-induced exacerbations during the peak fall season. METHODS: The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication...... differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma....

  8. Impact of overlap syndrome on severity of acute exacerbation of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Gothi, Dipti; Gupta, Shiv Sagar; Kumar, Nishith; Sood, Kartik

    2015-01-01

    The severity of exacerbation in chronic obstructive pulmonary disease (COPD) due to the overlap of obstructive sleep apnea syndrome (OSAS) is not known. To find out the 1) severity of acute exacerbation of COPD (AECOPD) in patients with overlap syndrome compared to only COPD, 2) prevalence of overlap syndrome in AECOPD, and 3) clinical characteristics of COPD compared to overlap syndrome. Fifty-one patients admitted with AECOPD were classified into; Mild exacerbation: Normal arterial blood gases (ABG) treated with antibiotics, Moderate: Normal ABG treated with parenteral corticosteroids, Severe: Type 1 respiratory failure, Very severe: Type 2 respiratory failure with normal pH and Life-threatening: Type 2 respiratory failure with pH overlap syndrome. The majority of only COPD cases (26/38) had mild and moderate exacerbations whereas majority of overlap patients (9/13) had severe, very severe and life-threatening exacerbations (statistically significant, P = 0.021). Of 51 patients, 13 had OSAS i.e. the prevalence of overlap in AECOPD was 25.5%. The mean BMI in only COPD and overlap syndrome was 20.70 ± 8.03 kg/m(2) and 31.82 ± 5.80 kg/m(2) (P syndrome was recorded in 2/36 (5.3%) patients in only COPD and 6/13 (46.2%) patients in overlap (P Overlap syndromes are more likely have respiratory failure compared to only COPD during AECOPD. AECOPD have a high prevalence of OSAS. Overlap syndrome have significantly higher likelihood of obesity and metabolic syndrome compared to only COPD.

  9. Inappropriate combination of warfarin and aspirin.

    Science.gov (United States)

    Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2016-03-01

    A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (paspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (paspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

  10. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    Science.gov (United States)

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  11. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

    Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

  12. Van der Waals Interactions in Aspirin

    Science.gov (United States)

    Reilly, Anthony; Tkatchenko, Alexandre

    2015-03-01

    The ability of molecules to yield multiple solid forms, or polymorphs, has significance for diverse applications ranging from drug design and food chemistry to nonlinear optics and hydrogen storage. In particular, aspirin has been used and studied for over a century, but has only recently been shown to have an additional polymorphic form, known as form II. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant form II. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body van der Waals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of form II as making it metastable.

  13. Aspirin treatment reduces platelet resistance to deformation.

    Science.gov (United States)

    Burris, S M; Smith, C M; Rao, G H; White, J G

    1987-01-01

    The present investigation has evaluated the influence of aspirin, its constituents, and other nonsteroidal anti-inflammatory agents on the resistance of human platelets to aspiration into micropipettes. Aspirin increased the length of platelet extensions into the micropipette over the entire negative tension range of 0.04 to 0.40 dynes/cm after exposure to the drug in vitro or after ingestion of the agent. Other cyclooxygenase inhibitors, ibuprofen and indomethacin, did not increase platelet deformability. The influence of aspirin was mimicked to some degree by high concentrations of salicylic acid, but acetylation of platelets with acetic anhydride had little influence on platelet deformability. Incubation of platelets with both salicylic acid and acetic anhydride had no more effect than salicylic acid alone. Benzoic acid, chemically similar to salicylic acid, had a minimal effect. The studies demonstrate that aspirin makes platelets more deformable, while components of the drug or other nonsteroidal antiinflammatory agents and cyclooxygenase inhibitors do not have the same influence on resistance to deformation.

  14. Aspirin in pregnancy : clinical and biochemical studies

    NARCIS (Netherlands)

    H.A. Bremer (Henk)

    1994-01-01

    textabstractAspirin, acetylsalicylic acid, is the most frequently consumed drug in pregnancy,47 mostly taken without a prescription because of headache or a minor ailment. 226,277 Numerous preparations containing acetylsalicylic acid are freely available over the counter under a variety of

  15. Lung ultrasound B-lines in exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Sriram, Krishna B; Singh, Maninder

    2017-03-01

    We report on preliminary observations on performing lung ultrasound (LUS) in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD). We found that LUS had high specificity and moderate sensitivity in identifying patients with elevated B-type natriuretic peptide. Thus, we hypothesise that LUS may have utility in screening COPD patients with an exacerbation to identify the sub-group with elevated natriuretic peptides and are at risk of increased cardiovascular mortality. The use of LUS in patients with acute and chronic respiratory disorders is increasing and its role in COPD patients is an interesting subject for future research. © 2017 Royal Australasian College of Physicians.

  16. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Zielen, Stefen; Garcia-Garcia, María Luz

    2005-01-01

    The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel......-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms...

  17. Lipopeptide-adjuvanted respiratory syncytial virus virosomes : A safe and immunogenic non-replicating vaccine formulation

    NARCIS (Netherlands)

    Stegmann, Toon; Kamphuis, Tobias; Meijerhof, Tjarko; Goud, Ellen; de Haan, Aalzen; Wilschut, Jan

    2010-01-01

    Respiratory syncytial virus (RSV) causes severe respiratory disease in children and the elderly. There is no registered RSV vaccine. Early experimental non-replicating vaccines have been found to exacerbate RSV symptoms upon infection causing enhanced respiratory disease. Here we show that

  18. Platelet hyperfunction is decreased by additional aspirin loading in patients presenting with myocardial infarction on daily aspirin therapy.

    Science.gov (United States)

    Fuchs, Ingrid; Spiel, Alexander O; Frossard, Martin; Derhaschnig, Ulla; Riedmüller, Eva; Jilma, Bernd

    2010-06-01

    Currently 162-325 mg aspirin is recommended for the treatment of acute coronary syndrome. We tested the effect of an additional loading dose of 250 mg aspirin at the onset of acute coronary syndrome in patients who were already on chronic therapy with 100 mg aspirin. This was a prospective trial in patients presenting with symptoms suggestive of acute coronary syndrome that included a randomized, double-blind, placebo-controlled trial subgroup. An emergency department in a tertiary care center. Consecutive patients with symptoms suggestive of acute coronary syndrome were enrolled, including a cohort already on chronic aspirin therapy. Patients received an intravenous infusion of 250 mg aspirin. Platelet function was measured with a platelet function analyzer in 234 patients before and after aspirin infusion. Aspirin infusion prolonged collagen epinephrine closure times in almost all patients. Aspirin infusion further lowered thromboxane B(2) levels in patients with acute coronary syndrome who were on chronic aspirin therapy before admission. Concomitantly, collagen epinephrine closure times increased by 22% from 223 secs (95% confidence interval, 192-255 secs) before to 273 secs (95% confidence interval, 252-294 secs) after aspirin infusion (p myocardial infarction on daily aspirin therapy (53%) displayed platelet hyperfunction (collagen epinephrine closure times aspirin infusion further decreased platelet function in these patients with ST-elevation myocardial infarction (30% prolongation of collagen epinephrine closure times; p myocardial infarction still displayed platelet hyperfunction (p = .02). Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.

  19. Asthmatic exacerbations and environmental pollen concentration in La Comarca Lagunera (Mexico).

    Science.gov (United States)

    Ordaz, V A; Castaneda, C B; Campos, C L; Rodríguez, V M; Saenz, J G; Ríos, P C

    1998-01-01

    In order to determine the correlation between the concentration of environmental pollen and the frequency of asthmatic exacerbations in La Comarca Lagunera (México), a study in a cohort of a 104 diagnosed patients suffering allergic asthma was carried out monitoring monthly from July '93 to July '95 in order to register the existence of asthmatic exacerbations. Environmental samples were taken weekly during the same period of time through a PST high volume collector (Andersen Samplers Inc). The above mentioned samples were processed under acetolysis technics and the pollen grain count under light microscopy. Linear correlation measures were made between the rates of asthmatic exacerbations and the concentration of pollen grain in m3 of air by means of a statistical computer program SAS. There was a 1469 persons/month follow up ('X 15.5) and the correlation between the rates of asthmatic exacerbations and the concentration of environmental pollen was relevant (r = 0.63, r2 = 0.39, p < 0.01). The correlation increased (r = 0.70, r2 = 0.49 and p < 0.01) when the asthmatic exacerbations associated to infectious disease in the upper respiratory system were restricted. The conclusion reached is that the concentration of environment pollen has influence in the development of asthmatic exacerbations in patients with allergic asthma.

  20. Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Geiger-Brown, Jeanne; Lindberg, Sarah; Krachman, Samuel; McEvoy, Charlene E; Criner, Gerard J; Connett, John E; Albert, Richard K; Scharf, Steven M

    2015-01-01

    Many patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients. This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire. Outcomes included time to first exacerbation and exacerbation rate. Sleep quality was "poor" (Pittsburgh Sleep Quality Index >5) in 53% of participants but was not related to age or severity of airflow obstruction. Quality of life scores were worse in "poor" sleepers than in "good" sleepers. Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the "poor" sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days) and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor sleepers, but no differences were observed after adjusting for medications and comorbid conditions associated with poor sleep. Poor sleepers had greater exacerbation rates than did good sleepers. This appeared to be due largely to them having more, or more severe, concomitant medical conditions and taking more medications.

  1. Sensitization to indoor allergens and frequency of asthma exacerbations in children

    Directory of Open Access Journals (Sweden)

    Irene Irene

    2011-08-01

    Full Text Available Background The rapid increase in asthma incidence has implicated the importance of environmental influences over genetic influences. Sensitization to perennial indoor allergens has been associated with increased asthma symptoms. Objective To examine the correlation between sensitization to indoor allergens and frequency of asthma exacerbations in children. Methods A cross-sectional study was carried out on asthmatic children aged 6 to 12 years in the Department of Child Health, Udayana University Medical School /Sanglah Hospital, Denpasar. Degree of sensitization was assessed by mean wheal diameter (positive defined as 3 mm greater than negative control for seven common indoor allergens. Frequency of asthma exacerbation for three consecutive months prior to data collection was retrospectively reviewed. Results Positive skin test results for one or more allergens were found in 84 of 89 (94% asthmatic children. Higher frequency of asthma exacerbations weakly correlated with the number of allergens with positive sensitization (r=0.284; P=0.007. Mean wheal diameter of each allergen did not correlate to the frequency of asthma exacerbations. In addition, the frequency of asthma exacerbations was independent for parental and sibling atopic history, preceding respiratory infections, use of asthma controllers and passive environmental tobacco smoke exposure. Conclusions Sensitization to common indoor allergens correlates weakly with frequency of asthma exacerbations.

  2. Blood Coagulation and Asthma Exacerbation in Children.

    Science.gov (United States)

    Manuyakorn, Wiparat; Mairiang, Dara; Sirachainan, Nongnuch; Kadegasem, Praguywan; Kamchaisatian, Wasu; Benjaponpitak, Suwat; Chuansumrit, Ampaiwan

    2016-01-01

    Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children. Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state. A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p coagulation in asthma exacerbation. © 2016 S. Karger AG, Basel.

  3. [Treatment and prevention of COPD exacerbation].

    Science.gov (United States)

    Yamaya, Mutsuo; Yasuda, Hiroyasu; Yoshida, Motoki; Nishimura, Hidekazu; Nakayama, Katsutoshi

    2007-04-01

    Airway inflammation, mucosal edema, epithelial hyperpermeability, mucus secretion and airway smooth muscle contraction induced by airway bacterial, virus infection and exposure to air pollution may be associated with COPD exacerbation. Severity of COPD exacerbation is estimated by blood gas analysis, serum CRP values and the chest radiograph. Patients with COPD exacerbations are recommended to be treated with additional inhalations of beta-2 agonists and anti -cholinergic agents, systemic administered glucocorticosteroids, oxygen inhalation, and, in cases with purulent sputum, antibiotics. Glucocorticosteroids, beta-2 agonists and anti-cholinergic agents reduce the frequency of COPD exacerbation. We reported the inhibitory effects of glucocorticosteroids on rhinovirus infection, the major cause of common colds, and the inhibitory effects of L-carbocisteine and erythromycin on COPD exacerbations and rhinovirus infection.

  4. Optimizing antibiotic selection in treating COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  5. Dietary Salt Exacerbates Experimental Colitis.

    Science.gov (United States)

    Tubbs, Alan L; Liu, Bo; Rogers, Troy D; Sartor, R Balfour; Miao, Edward A

    2017-08-01

    The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature of processed foods, has not been considered as a possible environmental factor that might drive IBD. We set out to bridge this gap. We examined murine models of colitis on either a high salt diet (HSD) or a low salt diet. We demonstrate that an HSD exacerbates inflammatory pathology in the IL-10-deficient murine model of colitis relative to mice fed a low salt diet. This was correlated with enhanced expression of numerous proinflammatory cytokines. Surprisingly, sodium accumulated in the colons of mice on an HSD, suggesting a direct effect of salt within the colon. Similar to the IL-10-deficient model, an HSD also enhanced cytokine expression during infection by Salmonella typhimurium This occurred in the first 3 d of infection, suggesting that an HSD potentiates an innate immune response. Indeed, in cultured dendritic cells we found that high salt media potentiates cytokine expression downstream of TLR4 activation via p38 MAPK and SGK1. A third common colitis model, administration of dextran sodium sulfate, was hopelessly confounded by the high sodium content of the dextran sodium sulfate. Our results raise the possibility that high dietary salt is an environmental factor that drives increased inflammation in IBD. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. A Review on the Relationship between Aspirin and Bone Health

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2017-01-01

    Full Text Available Aspirin is a cyclooxygenase inhibitor commonly used in primary prevention of cardiovascular diseases and cancers. Its users are elderly population susceptible to osteoporosis. It also inhibits the synthesis of prostaglandin E2 essential in bone remodeling. This prompts the question whether it can influence bone health among users. This review aimed to summarize the current literature on the use of aspirin on bone health. A literature search on experimental and clinical evidence on the effects of aspirin on bone health was performed using major scientific databases. In vitro studies showed that aspirin could enhance the survival of bone marrow mesenchymal stem cells, the progenitors of osteoblasts, and stimulate the differentiation of preosteoblasts. Aspirin also inhibited the nuclear factor kappa-B (NFκB pathway and decreased the expression of receptor activator of NFκB ligand, thus suppressing the formation of osteoclast. Aspirin could prevent bone loss in animal models of osteoporosis. Despite a positive effect on bone mineral density, the limited human epidemiological studies revealed that aspirin could not reduce fracture risk. A study even suggested that the use of aspirin increased fracture risk. As a conclusion, aspirin may increase bone mineral density but its effect on fracture prevention is inconclusive. More data are needed to determine the effects of aspirin and bone health in human.

  7. Duration of increased bleeding tendency after cessation of aspirin therapy.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

  8. The role of aspirin in childhood tuberculous meningitis.

    Science.gov (United States)

    Schoeman, Johan F; Janse van Rensburg, Anita; Laubscher, Jacoba A; Springer, Priscilla

    2011-08-01

    Arterial stroke is the main cause of poor outcome in childhood tuberculous meningitis. Aspirin has an antithrombotic action at low dose and anti-ischemic and anti-inflammatory properties, which are dose-related. The aim of the study was to explore the possible benefits of aspirin in children with tuberculous meningitis. A total of 146 consecutive children with a diagnosis of probable tuberculous meningitis were studied. Patients were randomized into 3 groups: (1) placebo group, (2) low-dose aspirin group, and (3) high-dose aspirin group. Twenty-nine additional patients who received aspirin before admission were excluded from the randomized study, but continued on low-dose aspirin. Aspirin, irrespective of dose, did not show any significant benefit regarding morbidity (hemiparesis and developmental outcome) and mortality. Aspirin was well tolerated, but 1 death was probably related to aspirin. The fact that the outcome of the high-dose aspirin group compared favorably with the other treatment groups despite younger age and more severe neurological involvement at baseline needs further investigation.

  9. Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Fukuchi Y

    2016-04-01

    Full Text Available Yoshinosuke Fukuchi,1 Koichiro Tatsumi,2 Hiromasa Inoue,3 Yukinori Sakata,4 Kai Shibata,4 Hideaki Miyagishi,4 Yasuhiro Marukawa,4 Masakazu Ichinose5 1Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, 2Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, 3Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 4Eisai Co., Ltd., Tokyo, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background/aim: Lysozyme (mucopeptide N-acetyl-muramyl hydrolase is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. Methods: In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness leading to a change in medication. The primary endpoint was exacerbation rate. Results: A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression. However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6. Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that

  10. Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index.

    Science.gov (United States)

    Hoch, Heather E; Calatroni, Agustin; West, Joseph B; Liu, Andrew H; Gergen, Peter J; Gruchalla, Rebecca S; Khurana Hershey, Gurjit K; Kercsmar, Carolyn M; Kim, Haejin; Lamm, Carin I; Makhija, Melanie M; Mitchell, Herman E; Teach, Stephen J; Wildfire, Jeremy J; Busse, William W; Szefler, Stanley J

    2017-10-01

    A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. A higher saEPI was associated with an exacerbation in both the GBT alone (P asthma exacerbation in both groups. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  11. Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation

    Science.gov (United States)

    Sorkness, Ron L.; Lee, Wai-Ming; Evans, Michael D.; Wolff, Michele J.; Mathur, Sameer K.; Crisafi, Gina M.; Gaworski, Katie L.; Pappas, Tressa E.; Vrtis, Rose F.; Kelly, Elizabeth A.; Gern, James E.; Jarjour, Nizar N.

    2011-01-01

    Rationale: Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds. Objectives: To evaluate viral strain and load in a prospective asthma cohort during a natural cold. Methods: Adults were enrolled at the first sign of a cold, with daily monitoring of symptoms, medication use, and peak expiratory flow rate until resolution. Serial nasal lavage and induced sputum samples were assessed for viral copy number and inflammatory cell counts. Measurements and Main Results: A total of 52 persons with asthma and 14 control subjects without atopy or asthma were studied for over 10 weeks per subject on average; 25 participants developed an asthma exacerbation. Detection of HRVs in the preceding 5 days was the most common attributable exposure related to exacerbation. Compared with other infections, those by a minor group A HRV were 4.4-fold more likely to cause exacerbation (P = 0.038). Overall, sputum neutrophils and the burden of rhinovirus in the lower airway were similar in control subjects without atopy and the asthma group. However, among HRV-infected participants with asthma, exacerbations were associated with greater sputum neutrophil counts (P = 0.005). Conclusions: HRV infection is a frequent cause of exacerbations in adults with asthma and a cold, and there may be group-specific differences in severity of these events. The absence of large differences in viral burden among groups suggests differential lower airway sensitization to the effects of neutrophilic inflammation in the patients having exacerbations. PMID:21816938

  12. Lower airway rhinovirus burden and the seasonal risk of asthma exacerbation.

    Science.gov (United States)

    Denlinger, Loren C; Sorkness, Ron L; Lee, Wai-Ming; Evans, Michael D; Wolff, Michele J; Mathur, Sameer K; Crisafi, Gina M; Gaworski, Katie L; Pappas, Tressa E; Vrtis, Rose F; Kelly, Elizabeth A; Gern, James E; Jarjour, Nizar N

    2011-11-01

    Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds. To evaluate viral strain and load in a prospective asthma cohort during a natural cold. Adults were enrolled at the first sign of a cold, with daily monitoring of symptoms, medication use, and peak expiratory flow rate until resolution. Serial nasal lavage and induced sputum samples were assessed for viral copy number and inflammatory cell counts. A total of 52 persons with asthma and 14 control subjects without atopy or asthma were studied for over 10 weeks per subject on average; 25 participants developed an asthma exacerbation. Detection of HRVs in the preceding 5 days was the most common attributable exposure related to exacerbation. Compared with other infections, those by a minor group A HRV were 4.4- fold more likely to cause exacerbation (P = 0.038). Overall, sputum neutrophils and the burden of rhinovirus in the lower airway were similar in control subjects without atopy and the asthma group. However, among HRV-infected participants with asthma, exacerbations were associated with greater sputum neutrophil counts (P = 0.005). HRV infection is a frequent cause of exacerbations in adults with asthma and a cold, and there may be group-specific differences in severity of these events. The absence of large differences in viral burden among groups suggests differential lower airway sensitization to the effects of neutrophilic inflammation in the patients having exacerbations.

  13. Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis

    Science.gov (United States)

    2014-01-01

    Background Gastro esophageal reflux (GER) is common in cystic fibrosis (CF) and may contribute to lung disease. Approximately 50% of patients with cystic fibrosis are being treated with proton pump inhibitors (PPIs). Methods In a randomized controlled study in adults, we compared treatment with esomeprazole 40 mg twice daily versus placebo in patients with CF and frequent respiratory exacerbations over a thirty-six week treatment period to determine effect on time to first exacerbation and other health related outcomes. Results 17 patients without symptoms of GER were randomized and 15 completed the study. 13 subjects underwent 24 hour ambulatory pH probe monitoring; 62% had pH probe evidence of GER. Forty one percent of subjects had a pulmonary exacerbation during the study. There was no significant difference in time to first pulmonary exacerbation (log rank test p = 0.3169). Five of nine subjects in the esomeprazole group compared with 2 of eight subjects in the placebo group experienced exacerbations (esomeprazole vs. placebo: odds ratio = 3.455, 95% CI = (0.337, 54.294), Fisher’s exact test: p = 0.334). There was no change in Forced Expiratory Volume in one second, Gastroesophageal Symptom Assessment Score or CF Quality of Life score between the two treatment groups. Conclusions There was a trend to earlier exacerbation and more frequent exacerbations in subjects randomized to esomeprazole compared with placebo. The effect of proton pump inhibitors on pulmonary exacerbations in CF warrants further investigation. Clinical trials registration Clinicaltrials.gov, NCT01983774 PMID:24528942

  14. An alkyne-aspirin chemical reporter for the detection of aspirin-dependent protein modification in living cells.

    Science.gov (United States)

    Bateman, Leslie A; Zaro, Balyn W; Miller, Stephanie M; Pratt, Matthew R

    2013-10-02

    Aspirin (acetylsalicylic acid) is widely used for the acute treatment of inflammation and the management of cardiovascular disease. More recently, it has also been shown to reduce the risk of a variety of cancers. The anti-inflammatory properties of aspirin in pain-relief, cardio-protection, and chemoprevention are well-known to result from the covalent inhibition of cyclooxygenase enzymes through nonenzymatic acetylation of key serine residues. However, any additional molecular mechanisms that may contribute to the beneficial effects of aspirin remain poorly defined. Interestingly, studies over the past 50 years using radiolabeled aspirin demonstrated that other proteins are acetylated by aspirin and enrichment with antiacetyl-lysine antibodies identified 33 potential targets of aspirin-dependent acetylation. Herein we describe the development of an alkyne-modified aspirin analogue (AspAlk) as a chemical reporters of aspirin-dependent acetylation in living cells. When combined with the Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition, this chemical reporter allowed for the robust in-gel fluorescent detection of acetylation and the subsequent enrichment and identification of 120 proteins, 112 of which have not been previously reported to be acetylated by aspirin in cellular or in vivo contexts. Finally, AspAlk was shown to modify the core histone proteins, implicating aspirin as a potential chemical-regulator of transcription.

  15. Prevention of exacerbations of COPD with pharmacotherapy.

    Science.gov (United States)

    Miravitlles, M

    2010-06-01

    Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD) patients. Individuals with COPD have a mean of 1-3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations. Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results. Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.

  16. Prevention of exacerbations of COPD with pharmacotherapy

    Directory of Open Access Journals (Sweden)

    M. Miravitlles

    2010-06-01

    Full Text Available Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations. Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results. Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.

  17. Aspirin overutilization for the primary prevention of cardiovascular disease

    Directory of Open Access Journals (Sweden)

    VanWormer JJ

    2014-12-01

    Full Text Available Jeffrey J VanWormer,1 Aaron W Miller,2 Shereif H Rezkalla3 1Center for Clinical Epidemiology and Population Health, 2Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA; 3Department of Cardiology, Marshfield Clinic, Marshfield, WI, USA Background: Aspirin is commonly used for the primary prevention of cardiovascular disease (CVD in the US. Previous research has observed significant levels of inappropriate aspirin use for primary CVD prevention in some European populations, but the degree to which aspirin is overutilized in the US remains unknown. This study examined the association between regular aspirin use and demographic/clinical factors in a population-based sample of adults without a clinical indication for aspirin for primary prevention.Methods: A cross-sectional analysis was performed using 2010–2012 data from individuals aged 30–79 years in the Marshfield Epidemiologic Study Area (WI, USA. Regular aspirin users included those who took aspirin at least every other day.Results: There were 16,922 individuals who were not clinically indicated for aspirin therapy for primary CVD prevention. Of these, 19% were regular aspirin users. In the final adjusted model, participants who were older, male, lived in northern Wisconsin, had more frequent medical visits, and had greater body mass index had significantly higher odds of regular aspirin use (P<0.001 for all. Race/ethnicity, health insurance, smoking, blood pressure, and lipid levels had negligible influence on aspirin use. A sensitivity analysis found a significant interaction between age and number of medical visits, indicating progressively more aspirin use in older age groups who visited their provider frequently.Conclusion: There was evidence of aspirin overutilization in this US population without CVD. Older age and more frequent provider visits were the strongest predictors of inappropriate aspirin use. Obesity was the only significant

  18. Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin.

    Science.gov (United States)

    Duzenli, Mehmet Akif; Ozdemir, Kurtulus; Aygul, Nazif; Soylu, Ahmet; Tokac, Mehmet

    2008-08-15

    The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to

  19. The role of aspirin in the prevention of cardiovascular disease.

    Science.gov (United States)

    Ittaman, Sunitha V; VanWormer, Jeffrey J; Rezkalla, Shereif H

    2014-12-01

    Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. © 2013 Marshfield Clinic.

  20. The Role of Aspirin in the Prevention of Cardiovascular Disease

    Science.gov (United States)

    Ittaman, Sunitha V.; VanWormer, Jeffrey J.; Rezkalla, Shereif H.

    2014-01-01

    Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. PMID:24573704

  1. Prevention of exacerbations of COPD with pharmacotherapy

    OpenAIRE

    M. Miravitlles

    2010-01-01

    Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD) patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- an...

  2. Respiratory mechanics

    CERN Document Server

    Wilson, Theodore A

    2016-01-01

    This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...

  3. Aspirin resistance: Prevalence and clinical outcome in Egypt

    OpenAIRE

    Ahmed Salah; Mohammed El-Desuky; Amal Rizk; Amr El-Hadidy

    2015-01-01

    Introduction: The antiplatelet drug aspirin is considered as a cornerstone in medical treatment of patients with CV or cerebrovascular diseases. Despite its use, a significant number of patients had recurrent adverse ischemic events. Inter-individual variability of platelet aggregation in response to aspirin may be an explanation for some of these events. Multiple trials have linked aspirin resistance to these adverse events. Objectives: The aim of this study was to estimate the prevalence...

  4. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  5. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

    Science.gov (United States)

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie; Dagenais, Gilles R; Hart, Robert G; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M; Anand, Sonia S; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S; Branch, Kelley R H; Probstfield, Jeffrey; Bhatt, Deepak L; Zhu, Jun; Liang, Yan; Maggioni, Aldo P; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K; Fox, Keith A A; Parkhomenko, Alexander N; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L; Lanas, Fernando; Commerford, Patrick J; Torp-Pedersen, Christian; Guzik, Tomek J; Verhamme, Peter B; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M; Lewis, Basil S; Felix, Camilo; Yusoff, Khalid; Steg, P Gabriel; Metsarinne, Kaj P; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim

    2017-10-05

    We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; Paspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; Paspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

  6. Improving the Gastrointestinal Tolerability of Aspirin in Older People

    OpenAIRE

    Newton, Julia L.

    2006-01-01

    Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to...

  7. Aspirin and Other COX-1 inhibitors.

    Science.gov (United States)

    Patrono, Carlo; Rocca, Bianca

    2012-01-01

    Currently available antiplatelet drugs interfere with the process of platelet activation and aggregation by selectively blocking key enzymes involved in the synthesis of platelet agonists, or membrane receptors mediating activation signals. Pharmacological interference with critical molecular pathways of platelet activation and aggregation may reduce the risk of atherothrombotic complications through mechanisms that are also responsible for an increased risk of bleeding. Acetylsalicylic acid (aspirin) represents a prototypic antiplatelet agent. The aim of this chapter is to integrate our current understanding of the molecular mechanism of action of aspirin with the results of clinical trials and epidemiological studies assessing its efficacy and safety. Moreover, the antiplatelet properties of reversible inhibitors of the same drug target will also be reviewed.

  8. A score to predict short-term risk of COPD exacerbations (SCOPEX

    Directory of Open Access Journals (Sweden)

    Make BJ

    2015-01-01

    Full Text Available Barry J Make,1 Göran Eriksson,2 Peter M Calverley,3 Christine R Jenkins,4 Dirkje S Postma,5 Stefan Peterson,6 Ollie Östlund,7 Antonio Anzueto8 1Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado Denver School of Medicine, Denver, CO, USA; 2Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 3Pulmonary and Rehabilitation Research Group, University Hospital Aintree, Liverpool, UK; 4George Institute for Global Health, The University of Sydney and Concord Clinical School, Woolcock Institute of Medical Research, Sydney, NSW, Australia; 5Department of Pulmonology, University of Groningen and GRIAC Research Institute, University Medical Center Groningen, Groningen, The Netherlands; 6StatMind AB, Lund, Sweden; 7Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; 8Department of Pulmonary/Critical Care, University of Texas Health Sciences Center and South Texas Veterans Healthcare System, San Antonio, TX, USA Background: There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Methods: Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0–100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC curves and the corresponding C-index were used to investigate the discriminatory

  9. Association between incidence of acute exacerbation and medication therapy in patients with COPD.

    Science.gov (United States)

    Suh, Dong-Churl; Lau, Helen; La, Hyen-Oh; Choi, In-Sun; Geba, Gregory P

    2010-02-01

    As exacerbations of chronic obstructive pulmonary disease (COPD) significantly worsen patients' health status and increase disease-related mortality, greater control of exacerbations has important implications for improving patients' health and survival. The incremental benefits of pharmacologic therapies in preventing COPD exacerbations remain unclear. The objective of this observational study was to examine the risk of COPD-related exacerbations between groups of patients receiving inhaled corticosteroids (ICS), anticholinergics (AC), long-acting beta(2)-agonists (LABA), or fixed-dose combinations of ICS and LABA. A 12-month retrospective cohort analysis of 2923 patients, who were at least 40 years old with the first time COPD in 12 months (i.e., no COPD for 12 months prior to this time) between 2000 and 2004, was conducted using the MarketScan research databases. Patients with at least two prescriptions for ICS, AC, LABA, or ICS + LABA during the observation period were followed from the index prescription date for the duration of the study. COPD-related exacerbations were defined as clinical events in which a primary diagnosis for a respiratory condition had resulted in hospitalization, an emergency room visit, or an outpatient visit followed by a prescription fill of oral corticosteroids or antibiotics within 14 days of the visit. Exacerbation rates were evaluated using a Cox proportional hazard model with adjustment for age, gender, comorbidities, hospitalizations, emergency room visits, and the number of outpatient visits. Compared with ICS alone, COPD exacerbation rates were 35% (CI:22-42%) lower with ICS + LABA, 32% (CI:13-43%) lower with LABA, and 28% (CI:15-36%) lower with AC. The hazard ratio of the first observed COPD exacerbation was 13-18% lower with the use of bronchodilators, with or without ICS, than with ICS alone. In addition, patients receiving ICS alone experienced more exacerbations during the 12-month period following initiation of therapy

  10. Fine particulate matter in acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Lei eNi

    2015-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress, immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden.

  11. Aspirin: a history, a love story.

    Science.gov (United States)

    Wick, Jeannette Y

    2012-05-01

    Most pharmacists know that aspirin's origins lie with willow bark, but they may be unaware of its role in the development of the pharmaceutical industry. Evolving from salacin (the active ingredient in many plant remedies) to salicylic acid (an analgesic in its own right) to the more effective, less toxic acetylsalicylic acid, this pain reliever cornered the nonsteroidal anti-inflammatory market for more than 70 years. It helped the dye industry branch into pharmaceuticals, and is now used in multiple indications.

  12. Aspirin for primary prevention of cardiovascular disease in diabetes mellitus

    Science.gov (United States)

    Pignone, Michael; Williams, Craig D.

    2011-01-01

    Aspirin is effective for the prevention of cardiovascular events in patients with a history of vascular disease, as so-called secondary prevention. In general populations with no history of previous myocardial infarction or stroke, aspirin also seems useful for primary prevention of cardiovascular events, although the absolute benefits are smaller than those seen in patients with previous cardiovascular disease. Patients with diabetes mellitus are at an increased risk of cardiovascular events, but new trials have raised questions about the benefit of aspirin for primary prevention in patients with this disorder. This Review comprehensively examines the basic pharmacology of aspirin and provides an overview of the randomized, controlled trials of aspirin therapy that have included patients with diabetes mellitus. On the basis of currently available evidence from primary prevention trials, aspirin is estimated to reduce the relative risk of myocardial infarction and stroke by about 10% in patients with diabetes mellitus; however, aspirin also increases the risk of gastrointestinal bleeding. As such, low-dose aspirin therapy (75–162 mg) is reasonable for patients with diabetes mellitus and a 10-year risk of cardiovascular events >10%. Results from upcoming large trials will help clarify the effects of aspirin with greater precision, including whether the benefits differ between men and women. PMID:20856266

  13. Aspirin and metformin exhibit antitumor activity in murine breast cancer.

    Science.gov (United States)

    Zhao, Maoyuan; Wang, Yuyi; Du, Chi; Liu, Yanyang; Zhang, Nan; Luo, Feng

    2018-03-01

    Studies have shown that aspirin and metformin play important roles in chemoprevention and repression of breast cancers, even though the exact mechanism remains unclear. Aspirin is capable of stimulating apoptosis through prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-β). In the present study, we report a new link between aspirin, metformin, TGF-β1 and murine breast cancer inhibition. Specifically, we showed that aspirin and metformin enhanced 4T1 cell apoptosis by inducing secretion of TGF-β1, whereas estradiol weakened the effect.

  14. NO-aspirin: mechanism of action and gastrointestinal safety.

    Science.gov (United States)

    Fiorucci, S; Del Soldato, P

    2003-05-01

    Nitric oxide-releasing aspirins are new chemical entities obtained by adding a nitric oxide-releasing moiety to aspirin. NCX-4016 is the prototype of this family of molecules. NCX-4016 consists of the parent molecule (aspirin) linked to a 'spacer' via an ester linkage, which is in turn connected to a nitric oxide-releasing moiety. Both aspirin and nitric oxide moieties of NCX-4016 contribute to its effectiveness, the latter occurring via both cyclic guanosyl monophosphate-dependent and -independent mechanisms. In vitro studies have shown that NCX-4016 inhibits platelet aggregation induced by aspirin-sensitive (arachidonic acid) and aspirin-insensitive (thrombin) agonist. In contrast to aspirin, NCX-4016 exerts a multilevel regulation of inflammatory target, including caspase-1 and NF-kappaB. This broad spectrum of activities translates to an increased potency of this drug in modulating cardiovascular inflammation. Human studies have shown, that while nitric oxide-aspirin maintains its anti-thrombotic activity, it spares the gastrointestinal tract. Indeed, a 7-day course of NCX-4016 results in 90% reduction of gastric damage caused by equimolar doses of aspirin. Further studies are ongoing to define whether this superior anti-inflammatory and anti-thrombotic profile translates in clinical benefits in patients with cardiovascular diseases.

  15. Protocatechualdehyde synergizes with aspirin at the platelet cyclooxygenase-1 level.

    Science.gov (United States)

    Sun, Shiqing; Hao, Haiping; Gong, Ping; Tang, Zhiyuan; Li, Feiyan; Chen, Xiaohu; Shi, Haibo; Wang, Guangji

    2011-11-01

    Polyphenol-aspirin interactions were recently identified; however, the interaction mode and underlying mechanisms remained elusive. Here, we quantitatively assessed the potential interactions among two important polyphenolic compounds, caffeic acid (CA) and protocatechualdehyde (Pro), and aspirin in the AA-induced platelet aggregation model by applying the isobologram and universal response surface approach (URSA) methods. A molecular docking approach and an originally developed platelet-associated aspirin clearance approach (PAACA) were then applied to explore the potential interaction mechanisms. Although Pro and CA themselves exhibited weak inhibitory effect on arachidonic acid (AA)-induced platelet aggregation and the production of thromboxane B₂ (TXB₂), both Pro and CA potentiated aspirin action in a synergistic manner. The most prominent synergism was found between Pro and aspirin. Pro formed a stable complex into the cyclooxygenase-1 (COX-1) channel by in silico docking and significantly promoted the platelet-associated aspirin clearance, suggesting that the Pro interaction with COX-1 was favorable to the binding of aspirin with COX-1. Taken together, our findings suggest that the capacity of Pro and potentially other structurally similar polyphenolic compounds on promoting the binding of aspirin on platelet COX-1 might be the main mechanism of their synergism with aspirin. © Georg Thieme Verlag KG Stuttgart · New York.

  16. ESPRIT: is aspirin plus dipyridamole superior to aspirin alone in TIA or minor stroke patients?

    Science.gov (United States)

    Rouhl, R P W; Lodder, J

    2008-11-01

    Transient ischemic attack (TIA) or a (minor) ischemic stroke increases the risk of a recurrent stroke or death. Antiplatelet therapy with aspirin or clopidogrel is, in the absence of a potential cardiac embolic source, common practice to lower this risk. Until recently, adjuvant dipyridamole or low intensity oral anticoagulation were not generally prescribed in secondary prevention. In this article, we will summarize and discuss the published results of the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT). In this trial, treatments with anticoagulants, aspirin alone and the combination of aspirin plus dipyridamole were compared, in a multicenter, three-armed, randomized, open-label study in patients with TIA or minor stroke.

  17. CLINICAL AND BACTERIOLOGICAL EFFICACY AND TOLERABILITY OF FCE-22891 IN PATIENTS WITH EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

    NARCIS (Netherlands)

    BOERSMA, WG; PUISTER, SMT; VANALTENA, R; DEVRIESHOSPERS, HG; MOLINARI, M; KOETER, GH

    A beta-lactamase-stable antibiotic, the oral penem FCE 22891 (ritipenem acoxil), was investigated for use in exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen of the 15 COPD patients had a proven lower respiratory tract infection. Symptom scores and forced expiratory volumes in

  18. Respiratory protection.

    Science.gov (United States)

    Cohen, Howard J; Birkner, Jeffrey S

    2012-12-01

    Respiratory protection is used as a method of protecting individuals from inhaling harmful airborne contaminants and in some cases to supply them with breathable air in oxygen-deficient environments. This article focuses on the use and types of personal respiratory protection (respirators) worn by individuals at workplaces where airborne hazardous contaminants may exist. Respirators are increasingly also being used in nonindustrial settings such as health care facilities, as concerns regarding infectious epidemics and terrorist threats grow. Pulmonologists and other clinicians should understand fundamental issues regarding respiratory protection against airborne contaminants and the use of respirators. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Vitamin D deficiency and adult asthma exacerbations.

    Science.gov (United States)

    Salas, Natalie Mariam; Luo, Li; Harkins, Michelle S

    2014-11-01

    There is growing evidence indicating a connection between vitamin D deficiency and the severity of asthma exacerbations. This study seeks to assess the relationship between vitamin D deficiency and the number and severity of asthma exacerbation in adults. A retrospective analysis was conducted in 92 patients being treated for asthma at the University of New Mexico Adult Asthma Clinic. Serum 25-hydroxyvitamin D3 levels were analyzed in adults with mild to severe persistent asthma. Using multi-variant modeling, the relationship was examined between serum vitamin D levels and the odds of asthma exacerbations ranging in severity from moderate to severe over the span of five years. This study demonstrates that vitamin D sufficiency was significantly associated with a decreased total number of asthma exacerbations (incidence rate ratio [IRR]: 0.61, 95% confidence interval [CI]: 0.44-0.84, p = 0.002), decreased total severe asthma exacerbations (IRR: 0.41, 95% CI: 0.24-0.72, p = 0.002) and decreased emergency room visits (IRR: 0.42, 95% CI: 0.20-0.88, p = 0.023). Vitamin D deficiency may be linked to the risk of severe asthma exacerbations in adults.

  20. [Rapid aspirin desensitization in patients with a history of aspirin hypersensitivity requiring coronary angioplasty. Report of four cases].

    Science.gov (United States)

    Veas P, Nicolás; Martínez, Gonzalo; Jalil M, Jorge; Martínez S, Alejandro; Castro G, Pablo

    2013-02-01

    Aspirin use is necessary after a coronary angioplasty. It should not be used in patients with a history of hypersensitivity. However, rapid desensitization protocols have been reported to allow its use in such patients. One of these protocols consists in the administration of progressive doses of aspirin, from 1 to 100 mg in a period of 5.5 hours, in a controlled environment. We report four male patients aged 45,49, 59 and 73 years with a history of aspirin hypersensitivity, who were subjected to a coronary angioplasty. In all, the rapid aspirin desensitization protocol was successfully applied, allowing the use of the drug after the intervention without problems.

  1. Aspirin content determination with control systems by image processing technology. Gazo shori gijutsu wo katsuyoshita jozai aspirin kensa sochi

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, K. (Lion Corp., Tokyo (Japan))

    1990-08-05

    An inspection apparatus for aspirin tablets utilizing image processing technology was developed. One side of a tablet consists of aspirin layer and another side consists of alkiline layer. The alkaline layer is opaque at all but the aspirin layer is translucent. Image of overall configuration of the tablet is taken in CCD camera by illumination from all surrounding sides. The area is measured by using these images. Then, when switching off the surrounding illumination and illuminating the aspirin side, only aspirin side layer shines. The area is determined by taking the image in CCD. Aspirin content is calculated by the ratio of overall images to aspirin image and the predetermined tablet weight. Tablets of different aspirin content were prepared, and the content determined by this method and the chemically determined contents were compared. High correlation was found between both contents, indicating the validity of the image processing method. When the aspirin content is out of 330 {plus minus} 10mg, the controlling mechanism works, by which unmanned operation will be possible. 8 figs.

  2. Acute exacerbation of idiopathic pulmonary fibrosis after inhalation of a water repellent

    Directory of Open Access Journals (Sweden)

    David Bennett

    2015-08-01

    Full Text Available The natural course of idiopathic pulmonary fibrosis (IPF is unpredictable at the time of diagnosis. Some patients may experience episodes of acute respiratory worsening that have been termed acute exacerbations. A 58-year-old male was admitted to our Emergency Department due to progressive and intense dyspnea and dry cough after accidental inhalation of waterproof’s vapor containing siloxanes. Chest high resolution computed tomography (HRCT scan showed diffuse and bilateral ground glass attenuation, basal predominant reticular abnormalities and subpleural honeycombing. The patient didn’t know that he suffered from IPF and siloxanes’ inhalation triggered an acute exacerbation of his disease. Clinical course after the inhalation was aggressive and, despite steroids and cyclophosphamide therapy, the patient died 3 months after due to a respiratory failure. Inhalation of water repellents has been associated with an acute onset of respiratory symptoms and acute lung injury; usually, however, the prognosis is commonly good with a complete recovery. Our case is an example of an extremely negative reaction probably because of pre-existing and misdiagnosed IPF. Currently, no literature concerning water repellent inhalation as a trigger of acute exacerbation of IPF is available.

  3. Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available We have previously reported that acetylsalicylic acid (aspirin, ASA induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO, prior to ASA treatment, cytotoxicity of the drug is augmented. On the other hand, when GSH-depleted cells were treated with N-acetyl cysteine (NAC, cytotoxicity/apoptosis caused by ASA was attenuated with a significant recovery in oxidative stress, GSH homeostasis, DNA fragmentation and some of the mitochondrial functions. NAC treatment, however, had no significant effects on the drug-induced inhibition of mitochondrial aconitase activity and ATP synthesis in GSH-depleted cells. Our results have confirmed that aspirin increases apoptosis by increased reactive oxygen species production, loss of mitochondrial membrane potential and inhibition of mitochondrial respiratory functions. These effects were further amplified when GSH-depleted cells were treated with ASA. We have also shown that some of the effects of aspirin might be associated with reduced GSH homeostasis, as treatment of cells with NAC attenuated the effects of BSO and aspirin. Our results strongly suggest that GSH dependent redox homeostasis in HepG2 cells is critical in preserving mitochondrial functions and preventing oxidative stress associated complications caused by aspirin treatment.

  4. Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells.

    Science.gov (United States)

    Raza, Haider; John, Annie

    2012-01-01

    We have previously reported that acetylsalicylic acid (aspirin, ASA) induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH)-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO), prior to ASA treatment, cytotoxicity of the drug is augmented. On the other hand, when GSH-depleted cells were treated with N-acetyl cysteine (NAC), cytotoxicity/apoptosis caused by ASA was attenuated with a significant recovery in oxidative stress, GSH homeostasis, DNA fragmentation and some of the mitochondrial functions. NAC treatment, however, had no significant effects on the drug-induced inhibition of mitochondrial aconitase activity and ATP synthesis in GSH-depleted cells. Our results have confirmed that aspirin increases apoptosis by increased reactive oxygen species production, loss of mitochondrial membrane potential and inhibition of mitochondrial respiratory functions. These effects were further amplified when GSH-depleted cells were treated with ASA. We have also shown that some of the effects of aspirin might be associated with reduced GSH homeostasis, as treatment of cells with NAC attenuated the effects of BSO and aspirin. Our results strongly suggest that GSH dependent redox homeostasis in HepG2 cells is critical in preserving mitochondrial functions and preventing oxidative stress associated complications caused by aspirin treatment.

  5. Use of aspirin, non-steroidal anti-inflammatory drugs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis: a cohort study.

    Science.gov (United States)

    Wu, Shaowei; Han, Jiali; Qureshi, Abrar A

    2015-02-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, non-aspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women, the Nurses' Health Study II (1991-2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95,540 participants during the follow-up. During 1,321,280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios of 3.60 [95% confidence interval (CI): 2.02-6.41] and 2.10 (95% CI: 1.11-3.96) for PsA, respectively. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs for long-term periods.

  6. Respiratory Therapists

    Science.gov (United States)

    ... saturated with workers, and other areas (more often, rural areas) will be in need of respiratory therapists’ ... workers in the occupation, including what tools and equipment they use and how closely they are supervised. ...

  7. Aspirin decreases vascular endothelial growth factor release during myocardial ischemia.

    Science.gov (United States)

    Gerrah, Rabin; Fogel, Mina; Gilon, Dan

    2004-03-01

    Vascular Endothelial Growth Factor (VEGF) is an important angiogenesis factor involved in pathophysiology of cardiovascular diseases. Controlling this factor's level in the serum might have significant prognostic outcomes. Twenty-four patients undergoing coronary artery bypass grafting were prospectively categorized into two groups according to aspirin administration before surgery. Vascular Endothelial Growth Factor levels were compared and correlated and adjusted with platelets count between two groups in the serum, before and after the surgery. Serum creatine kinase (CK) levels were determined before and after the operation in parallel to other clinical data. Vascular Endothelial Growth Factor levels were significantly lower in patients of the aspirin group compared to those of the non-aspirin group; 94+/-61 vs. 241+/-118 pg/ml, p=0.0003, respectively, this-despite an absence of difference in the platelet count between the groups. These titers decreased postoperatively in both groups, 94+/-61 to 10+/-9 pg/ml, p=0.001 in aspirin group and from 241+/-118 to 84+/-54 pg/ml, p=0.001 in control group. Serum creatine kinase levels were higher in the non-aspirin group, 214+/-83 u/l compared to 70+/-32 u/l in the aspirin group. Creatine kinase levels increased significantly postoperatively in both groups; however, the aspirin group had a significantly lower creatine kinase levels compared to non-aspirin group, 107+/-51 vs. 401+/-127 u/l, respectively, p=<0.0001. A significant correlation was seen between VEGF levels and platelets count in both groups, r=0.5. Aspirin treated patients have lower Vascular Endothelial Growth Factor titer levels in the perioperative course. This difference between the aspirin and the non-aspirin group is not accounted for by the platelets count.

  8. Aspirin use and endometrial cancer risk and survival.

    Science.gov (United States)

    Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

    2018-01-01

    The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Aspirin dose and ticagrelor benefit in PLATO: fact or fiction?

    Science.gov (United States)

    Serebruany, Victor L

    2010-01-01

    To summarize the available evidence regarding whether or not a higher aspirin maintenance dose inversely affects the ticagrelor benefit observed in the US cohort of the PLATO trial. In the recent PLATO trial, the daily aspirin dosages in the USA were split between 81 and 325 mg while the vast majority of dosing outside of the USA was 75 or 100 mg. The FDA conducted exhaustive analyses of the aspirin dosage in a framework of primary clinical efficacy. Considering the post hoc, not prespecified nature of such analyses as well as multiple confounding problems with biologic plausibility, sensitivity to reclassification of small numbers of cases regarding loading versus maintenance aspirin dosing, and the distribution of events in high-dose aspirin observed outside of the USA, the FDA documents clearly suggest that aspirin dosing does not explain the disparate outcome results. In addition, the Advisory Committee members found no evidence to establish a reasonable link, and they uniformly rejected the hypothesis that aspirin dose affects the heterogeneity of outcomes in PLATO. Additional evidence driven from the FDA review on aspirin dose and PLATO outcomes is reassessed. The wide distribution of outcomes differing from country to country, and inconsistency in European data despite identical aspirin doses, preclude the acceptance of the hypothesis that aspirin affects PLATO outcomes in general or adversely impacts the benefit of ticagrelor in the US cohort in particular. Differences in primary site monitoring by the study sponsor in most countries versus a third-party CRO in the USA represent an alternative explanation and deserve further attention. There is no solid evidence that aspirin dose affects outcomes after ticagrelor. Reevaluation of the overall endpoint differences, especially focusing on mortality, driven from sponsor-monitored sites versus outcomes observed by independent CROs is neccessary. The practice of self-monitoring in pivotal indication

  10. Respiratory viruses and torque teno virus in adults with acute respiratory infections.

    Science.gov (United States)

    Prasetyo, Afiono Agung; Desyardi, Martinus Nuherwan; Tanamas, Jimmy; Suradi; Reviono; Harsini; Kageyama, Seiji; Chikumi, Hiroki; Shimizu, Eiji

    2015-01-01

    To define the molecular epidemiology of respiratory viral infections in adult patients. Nasal and throat swabs were collected from all adult patients with influenza-like illness (ILI), acute respiratory infection (ARI), or severe ARI (SARI) admitted to a tertiary hospital in Surakarta, Indonesia, between March 2010 and April 2011 and analyzed for 19 respiratory viruses and for torque teno virus (TTV) and human gyrovirus (HGyV). Respiratory viruses were detected in 61.3% of the subjects, most of whom had ARI (90.8%, OR = 11.39), were hospitalized (96.9%, OR = 22.31), had asthma exacerbation (90.9%, OR = 8.67), and/or had pneumonia (80%, OR = 4.0). Human rhinovirus (HRV) A43 predominated. Influenza A H3N2, human metapneumovirus (HMPV) subtypes A1 and A2, the influenza B virus, human adenovirus B, and human coronavirus OC43 were also detected. All respiratory viruses were detected in the transition month between the rainy and dry seasons. No mixed respiratory virus infection was found. Coinfections of the influenza A H3N2 virus with TTV, HMPV with TTV, HRV with TTV, and human parainfluenza virus-3 with TTV were found in 4.7, 2.8, 19.8, and 0.9% of the samples, respectively. This study highlights the need to perform routine detection of respiratory viruses in adults hospitalized with ARI, asthma exacerbation, and/or pneumonia. © 2015 S. Karger AG, Basel

  11. Home Non Invasive Ventilation (NIV) treatment for COPD patients with a history of NIV-treated exacerbation

    DEFF Research Database (Denmark)

    Ankjærgaard, Kasper Linde; Tønnesen, Philip; Laursen, Lars Christian

    2016-01-01

    BACKGROUND: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory...... ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death...

  12. Asthma Exacerbations and Unconventional Natural Gas Development in the Marcellus Shale

    Science.gov (United States)

    Rasmussen, Sara G.; Ogburn, Elizabeth L.; McCormack, Meredith; Casey, Joan A.; Bandeen-Roche, Karen; Mercer, Dione G.; Schwartz, Brian S.

    2017-01-01

    Importance Asthma is common and can be exacerbated by air pollution and stress. Unconventional natural gas development (UNGD) has community and environmental impacts. In Pennsylvania, development began in 2005 and by 2012, 6,253 wells were drilled. There are no prior studies of UNGD and objective respiratory outcomes. Objective To evaluate associations between UNGD and asthma exacerbations. Design A nested case-control study comparing asthma patients with exacerbations to asthma patients without exacerbations from 2005–12. Setting The Geisinger Clinic, which provides primary care services to over 400,000 patients in Pennsylvania. Participants Asthma patients aged 5–90 years (n = 35,508) were identified in electronic health records; those with exacerbations were frequency-matched on age, sex, and year of event to those without. Exposure(s) On the day before each patient’s index date (cases: date of event or medication order; controls: contact date), we estimated UNGD activity metrics for four phases (pad preparation, drilling, stimulation [“fracking”], and production) using distance from the patient’s home to the well, well characteristics, and the dates and durations of phases. Main Outcome(s) and Measure(s) We identified mild, moderate, and severe asthma exacerbations (new oral corticosteroid medication order, emergency department encounter, and hospitalization, respectively). Results We identified 20,749 mild, 1,870 moderate, and 4,782 severe asthma exacerbations, and frequency-matched these to 18,693, 9,350, and 14,104 control index dates, respectively. In three-level adjusted models, there was an association between the highest group of the activity metric for each UNGD phase compared to the lowest group for 11 out of 12 UNGD-outcome pairs (odds ratios [95% CI] ranged from 1.5 [1.2–1.7] for the association of the pad metric with severe exacerbations to 4.4 [3.8–5.2] for the association of the production metric with mild exacerbations). Six of

  13. The thrombolytic effect of aspirin in animal model.

    Science.gov (United States)

    Karmohapatra, Soumendra K; Kahn, Nighat N; Sinha, Asru K

    2007-10-01

    The aspirin induced platelet aggregation has been reported to be mediated through the inhibition of platelet prostaglandin synthesis. This compound has also been recently reported to stimulate nitric oxide synthesis in platelets. Since nitric oxide has been reported to produce fibrinogen/fibrinolytic effect, investigation was carried out to determine fibrinolytic effect of in vivo exposure of platelets to aspirin in normal volunteers on the fibrinolysis of the clotted platelet-rich plasma in vitro. The thrombolytic effect of aspirin in situ was also carried out by injecting aspirin solution in the mice with ADP induced formed thrombi in the coronary artery. It was found that the clotted platelet-rich plasma prepared from the volunteers (n = 10, F = 5, M = 5) who ingested 150 mg aspirin, began to undergo spontaneous and progressive fibrinolysis for 200 min at 37 degrees C with the generation of fibrin degradation products in the lysate. No such fibrinolysis could be seen in control experiments. When platelet thrombi were produced in the coronary artery of mice by injecting ADP, and these animals subsequently received intravenous injection of aspirin (4 muM final), they not only survived (P < 0.0001, n = 10) the thrombogenic assault but the lysis of the platelet thrombi was also noted in the post mortem examination. The thrombolytic effect of aspirin was found to be comparable to that of streptokinase in these animals. Aspirin, through the stimulation of NO synthesis, may produce thrombolysis in vivo.

  14. Aspirin and lipid mediators in the cardiovascular system.

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Synthesis of peptide derivatives of aspirin and their antibiogram ...

    African Journals Online (AJOL)

    Peptide derivatives of Aspirin (1 to 8) were synthesized by using Ac2O/AcOH reaction with Salicyclic acid. Aspirin was coupled with amino acid amide and dipeptide amide and tripeptide amide using its p-nitro phenyl (NP) ester. The ester (Aspirin–ONP) was prepared using p-nitro phenol and DCC in EtOAc and was ...

  16. Aspirin Risks in Perspective: A Comparison against Marathon Running

    Science.gov (United States)

    Morgan, Gareth

    2014-01-01

    Aspirin has public health potential to reduce the risk of ischaemic vascular events and sporadic cancer. One objection to the wider use of aspirin for primary prevention, however, is the undesirable effects of the medicine, which include increasing risk of bleeding and haemorrhagic stroke. Marathons also carry risks of serious events such as…

  17. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

    NARCIS (Netherlands)

    Eikelboom, John W.; Connolly, Stuart J.; Bosch, Jackie; Dagenais, Gilles R.; Hart, Robert G.; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M.; Anand, Sonia S.; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S.; Branch, Kelley R. H.; Probstfield, Jeffrey; Bhatt, Deepak L.; Zhu, Jun; Liang, Yan; Maggioni, Aldo P.; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K.; Fox, Keith A. A.; Parkhomenko, Alexander N.; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L.; Lanas, Fernando; Commerford, Patrick J.; Torp-Pedersen, Christian; Guzik, Tomek J.; Verhamme, Peter B.; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M.; Lewis, Basil S.; Felix, Camilo; Yusoff, Khalid; Steg, P. Gabriel; Metsarinne, Kaj P.; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim; Aboyans, V.; Ha, J.; Keltai, K.; Lamy, A.; Liu, L.; Moayyedi, P.; Sharma, M.; Stoerk, S.; Varigos, J.; Bhagirath, V.; Bogaty, P.; Botto, F.; Catanese, L.; Donato Magno, J.; Fabbri, G.; Gabizon, I.; Gosselin, G.; Halon, D.; Heldmann, M.; Lamelas, P.; Lauw, M.; Leong, Y.; Liang, D.; Lutay, Y.; Maly, M.; Mikulik, R.; Nayar, S.; Ng, K.; Perera, K.; Pirvu, O.; Ronner, E.; Sato, S.; Smyth, A.; Sokolova, E.; Wiendl, M.; Winkelmann, B.; Yang, X.; Yufereva, Y.; Cairns, J.; Sleight, P.; deMets, D.; Momomura, S. I.; Prins, M. [=Martin H.; Ramsay, T.; Goto, S.; Rouleau, J. L.; Schumi, J.; Thabane, L.; Casanova, A.; Bangdiwala, S.; Deng, E.; Dyal, L.; Khatun, R.; Marsden, T.; Pogue, J.; Tang, C.; Wong, G.; Yuan, F.; Aman, S.; Ariz, A.; Ashton, H.; Belanger, J.; Belanger, M.; Brettell, K.; Chandra, J.; Choppick, C.; Cisternino, D.; Cuncins-Hearn, A.; Di Marino, M.; Diao, L.; Dwomoh, S.; Dykstra, A.; Galatsis, E.; Gasic, T.; Gutierrez, J.; Hamilton, L.; Irwin, L.; Lapensee, C.; Li, A.; Lu, X.; MacRae, L.; Malik, S.; Malvestiti, A.; Mastrangelo, J.; Maystrenko, A.; O'Donnell, L.; Reeh, K.; Szymkow, P.; Thomas, S.; Thrasher, D.; Tyrwhitt, J.; White, L.; Bastone, R.; Berkowitz, S.; Dias, A.; Ho, K.; Keller, L.; Lanius, V.; Lister, K.; Merten, C.; Muehlhofer, E.; Schmidt, K.; Tasto, C.; Tsihlias, E.; Woroniecka-Osio, A.; Orlandini, A.; Niemann, G.; Pascual, A.; Toscanelli, S.; Cabezón, M.; Debaveye, B.; Meeusen, K.; Luys, C.; Broos, K.; Vandenberghe, K.; Luyten, A.; Oliveira, G. B. F.; Vila Nova, D. C.; Konishi, M. Y. N.; Lonn, A.; Turbide, G.; Cayer, M.; Rovito, C.; Standen, D.; Li, J.; Lopez Pico, M.; Dusek, R.; Buzalka, V.; Larsen, J.; Paucar, M. J.; Saarinen, M.; Simon, T.; Bezault, M.; Le Lay, M.; Epstein, L.; Fajardo-Moser, M.; Röser, C.; Putz-Todd, G.; Scheidemantel, F.; Poehler, D.; Renner, J.; Hargitai, A.; Doherty, A. O.; Duffy, N.; Roarty, C.; Nolan, A.; Power, A.; Yuval, R.; Ben Ari, M.; Greenblatt, S.; Marmor, Y.; Lucci, D.; Ceseri, M.; Baldini, E.; Cipressa, L.; Miccoli, M.; Goto, M.; Yamasowa, H.; Kajiwara, M.; Takase, D.; Ikeguchi, K.; Matsumoto, M.; Ishii, M.; Asai, J.; Nozaki, D.; Akatsuka, T.; Yoshida, T.; Shahadan, S.; Md Nasir, N.; Schut, Astrid; Vinck, Leonie; van Leeuwen, Marjelle; Sanchez, J.; Aquino, M. R.; Mararac, T.; Benedyk, K.; Iordache, A.; Ciobanu, A.; Rimbas, R.; Dragoi Galrinho, R.; Magda, S.; Mihaila, S.; Mincu, R.; Suran, B.; Cotoban, A.; Matei, L.; Kursakov, A.; Rusnak, P.; Zakharova, A.; Demidova, E.; Commerford, A.; Lee, S.; Ju, I.; Gunolf, M.; Lorimer, A.; Parkhomenko, L.; Johnson, J.; Anderson, J.; Norby-Slycord., C.; Sala, J.; Sicer, M.; Rasmussen, M.; Luciani, C.; Cartasegna, L.; Beltrano, C.; Medek, G.; Vico, M.; Lanchiotti, P.; Martella, C.; Hominal, M.; Castoldi, M.; Casali, W.; Raimondi, S.; Hasbani, E.; Prado, A.; Paterlini, G.; Waisman, F.; Leonard, M.; Caccavo, A.; Alarcon, V.; Zaidman, C.; Guerlloy, F.; Vogel, D.; Imposti, H.; Dominguez, A.; Hrabar, A.; Fernandez, A.; Schygiel, P.; Sokn, F.; Cuneo, C.; Gutierrez Carrillo, N.; Martinez, G.; Luquez, H.; Costantino, M.; Ruiz, M.; Beccetti, N.; Mackinnon, I.; Cluigt, N.; Ahuad Guerrero, R.; Fanuele, M.; Campisi, V.; Costabel, J.; Romanelli, M.; Bartolacci, I.; Echeverria, M.; Pedrotti, M.; Montaña, O.; Camino, A.; Crespo, C.; Barbieri, M.; Lopez Santi, R.; Tonin, H.; Heffes, R.; Gomez Vilamajo, O.; Vanesio, F.; Allegrini, E.; Garcia Duran, R.; Garcia, C.; Garcia Duran, L.; Schiavi, L.; Mana, M.; Bordonava, A.; Rodriguez, M.; Gutierrez, M.; Garrido, M.; Rodriguez, C.; Ingaramo, A.; Costamagna, O.; Almagro, S.; Gerbaudo, C.; Pelagagge, M.; Bustamante Labarta, M.; Novaretto, L.; Maldini, A.; Lopez, L.; Albisu Di Gennero, J.; Ibanez Saggia, L.; Garcia Vilkas, A.; Alvarez, M.; Stoermann, W.; Vita, N.; Vottero, E.; Macin, S.; Cocco, M.; Onocko, M.; Dran, R.; Gimenez, C.; Cardona, M.; Guzman, L.; Guzman, P.; Martinez, D.; Sarjanovich, R.; Huerta, C.; Scaro, G.; Cuadrado, J.; Rodriguez, G.; Nani, S.; Guardiani, F.; Litvak Bruno, M.; Ceconi, G.; Chacon, C.; Casado, M.; Fernandez Moutin, M.; Maffei, L.; Sassone, S.; Yantorno, M.; Grinfeld, D.; Vensentini, N.; Rolandi, F.; Fallabrino, L.; Majul, C.; Paez, O.; Visser, M.; Luciardi, H.; Mansilla, V.; Gonzalez Colaso, P.; Ferre Pacora, F.; Jure, H.; Parody, M.; Espeche, E.; Whelan, A.; Boyle, A.; Collins, N.; Roberts-Thomson, P.; Rogers, J.; Caroll, P.; Colquhoun, D.; Williams, L.; Shaw, J.; Blombery, P.; Amerena, J.; Lee, C.; Hii, C.; Royse, A.; Royse, C.; Singh, B.; Selvanayagam, J.; Jansen, S.; Thompson, P.; Lo, W.; Hammett, C.; Poulter, R.; Graves, S.; Narasimhan, S.; van den Heuvel, P.; Wollaert, B.; Sinnaeve, P.; Fourneau, I.; Meuris, B.; Vanassche, T.; Ector, B.; Janssens, L.; Debonnaire, P.; Vandekerckhove, Y.; van de Borne, P.; Wautrecht, J.; Motte, S.; Leroy, J.; Schroë, H.; Vrolix, M.; Ferdinande, B.; Vranckx, P.; Benit, E.; Elegeert, I.; Lerut, P.; Wallaert, P.; Hoffer, E.; Borgoens, P.; Dujardin, K.; Brasil, C. K. O. I.; del Monaco, M. I.; Uint, L.; Pavanello, R.; Precoma, D. B.; Vianna, H. S.; Abrantes, J.; Morelli, J.; Manenti, E.; Jaeger, C.; Reis, G.; Giorgeto, F. E.; França, C. C. B.; Quadros, T. F. S.; Saraiva, J.; Costa, M.; de Camargo, O.; Marson Lopes, M.; Silva, J.; Maia, L. N.; Nakazone, M. A.; Mouco, O. M. C. C.; Lemos, M. A. B. T.; Hernandes, M. E.; Pântano, G. S.; de Castro, J. C. M.; Rossi, P. R. F.; Guedes, A. A. M.; Dos Santos, L. B.; dos Santos, F. R.; Vidotti, M. H.; Zimmermann, S. L.; Rech, R.; Nunes, C.; Abib, E.; Oliveira, K. L. C.; Leaes, P. E.; Botelho, R. V.; Navarro, A. L. C.; Silva, R. A.; Arantes, F. B. B.; Dutra, O.; Vaz, R.; Souza, W. K. S. B.; Souza, A. S. B.; Queiroz, W. C. B.; Braile, M.; Ferreira, V.; Izukawa, N. M.; Prakasan, A. K.; Nicolau, J. C.; Dalçóquio, T. F.; Tanajura, L. F. L.; Serrano, C. V.; Hueb, W. A.; Minelli, C.; Borsetti Neto, F. A.; Nasi, L. A.; Martins, S. C. O.; Oliveira, L. F. A.; Silva, M. A. V.; Ferreira, J. O.; de Carvalho Cantarelli, M. J.; Tytus, R.; Pasyk, E.; Pandey, A. S.; Rowe, A.; Cha, J.; Vizel, S.; Babapulle, M.; Semelhago, L.; Saunders, K.; Haligowski, D.; Berlingieri, J.; Nisker, W.; Kiaii, B.; Romsa, J.; Chu, M.; Nagpal, D.; Guo, R.; Mckenzie, N.; Quantz, M.; Bhargava, R.; Bhargava, M.; Mehta, P.; Hill, L.; Heslop, W.; Fell, D.; Hess, A.; Zadra, R.; Zeman, P.; Srivamadevan, M.; Lam, A.; Tai, S.; Al-Qoofi, F.; Spence, F.; Anderson, T.; Kieser, T.; Kidd, W.; Fedak, P.; Smith, E.; Har, B.; Brown, C.; Forgie, R.; Hassan, A.; Pelletier, M.; Searles, G.; Marr, D.; Bessoudo, R.; Douglas, G.; Legare, J.; Petrella, R.; Pavlosky, W.; Ricci, J.; Galiwango, P.; Janmohamed, A.; Kassam, S.; Mukherjee, A.; Vijayaraghavan, R.; Burstein, J.; D'Mello, N.; Glanz, A.; Noiseux, N.; Stevens, L. M.; Basile, F.; Prieto, I.; Normandin, L.; Helou, J.; Do, Q. B.; Bainey, K.; Tymchak, W.; Welsh, R.; Merali, F.; Pandith, V.; Heffernan, M.; Orfi, J.; Mcconachie, D.; Jedrzkiewicz, S.; Della Siega, A.; Robinson, S.; Nadra, I.; Poirier, P.; Dagenais, F.; Voisine, P.; Mohammadi, S.; Doyle, D.; Baillot, R.; Charbonneau, E.; Dumont, E.; Kalavrouziotis, D.; Perron, J.; Jacques, F.; Laflamme, M.; Brulotte, S.; Crete, M.; Degrâce, M.; Delage, F.; Grondin, F.; Lemieux, A.; Michaud, N.; Saulnier, D.; Ross, M. K.; Nguyen, M.; Harvey, R.; Daneault, B.; Hartleib, M.; Guzman, R.; Nguyen, T.; Singal, R.; Bourgeois, R.; Landry, D.; Kamel, S.; Rupka, D.; Kuritzky, R.; Khaykin, Y.; Phaneuf, D. C.; Desjardins, V.; Coll, X.; Huynh, T.; Pilon, C.; Mansour, S.; Lemire, F.; Kokis, A.; Potvin, J.; Campeau, J.; Audet, M.; Boulianne, M.; Dupuis, R.; Lauzon, C.; Pruneau, G.; Senay, B.; Pichette, F.; Cieza, T.; Breton, R.; Belisle, P.; Barabas, M.; Diaz, A.; Costa, R.; Absi, F.; Garand, M.; Rheault, A.; Lemay, C.; Gisbert, A.; Raymond, A.; Barrero, M.; Gagne, C. E.; Rheault, P.; Pepin-Dubois, Y.; Johnston, J.; Mundi, A.; Cohen, G.; Shukle, P.; Baskett, R.; Hirsch, G.; Ali, I.; Stewart, K.; Fenton, J.; Pudupakkam, S.; Willoughby, R.; Czarnecki, W.; Roy, A.; Montigny, M.; Descarries, L.; Mayrand, H.; Comtois, H.; Essiambre, R.; Ringuette, G.; Boutros, G.; Gendreau, R.; Pham, L.; Nguyen, V.; Nguyen-Thanh, H. K.; Ben-Yedder, N.; Nawaz, S.; Fremes, S.; Moussa, F.; Shukla, D.; Labonte., R.; Jano, G.; Bobadilla, B.; Saavedra, J.; Bahamondes, J.; Cobos, J.; Grunberg, E.; Corbalan, R.; Verdejo, H.; Medina, M.; Vega, M.; Nahuelpan, L.; Castañia, F.; Raffo, C.; Vargas, A.; Reyes, T.; Vargas, D.; Perez, L.; Arriagada, G.; Potthoff, S.; Godoy, J.; Stockins, B.; Larenas, G.; Quiñinao, F.; Sepulveda, P.; Trucco, V.; Pincetti, C.; Saavedra, S.; Silva, P.; Vejar, M.; Rodríguez, T.; Rodriguez, J.; Tian, H.; Zhang, J.; Meng, Y.; Wu, X.; Wu, Q.; Wang, Q.; Mu, Y.; Yang, J.; Wang, F.; Zhang, W.; Ke, Y.; Jiang, H.; Yin, P.; Jia, K.; Chen, C.; Wang, Z.; Qi, B.; Yu, L.; Feng, G.; Li, L.; Jiang, L.; Wu, S.; Yu, H.; Wu, Z.; Ding, R.; Liu, S.; Xu, H.; Cao, H.; Bai, X.; Zheng, Y.; Liu, Z.; Sun, H.; Yang, P.; Li, B.; Feng, Z.; Yang, Y.; Xu, Z.; Wu, W.; Meng, Q.; Ge, J.; Dai, Y.; Yang, H.; Chen, X.; Tian, X.; Shi, Y.; Hu, T.; Zhang, R.; Zhao, Q.; Quan, W.; Zhu, Y.; Zheng, Z.; Zhang, S.; Zhao, Y.; Zhao, C.; Wang, R.; Tao, L.; Hu, D.; Wang, Y.; Fan, F.; Huang, W.; Xia, X.; Fu, G.; Jiang, D.; Wang, M.; Li, C.; Xu, K.; Dong, Y.; Chen, Y.; Wu, D.; Wang, C.; Sun, X.; Lu, S.; Zhou, X.; Kong, Y.; Zhang, B.; Sotomayor, A.; Suarez, M.; Ripoll, D.; Herrera, O.; Accini Mendoza, J.; Saad Cure, C.; Reyes, M.; Vidal, T.; Donado Beltran, P.; Hernandez Jaimes, E.; Castillo, H.; Rocha, C.; Forero, L.; Zarate Bernal, D.; Vanstrrahle Gonzalez, L.; Urina Triana, M.; Quintero, A.; Ramirez, N.; Balaguera Mendoza, J.; Aroca Martinez, G.; Cotes, C.; Mercado, A.; Lastra Percy, X.; Perez Mayorga, M.; Rodriguez, N.; Molina de Salazar, D.; Perez Agudelo, J.; Lopez Villegas, L.; Agudelo Ramos, L.; Melo Polo, M.; Esparza Albornoz, A.; Forero Gomez, J.; Sanchez Vallejo, G.; Aristizabal, J.; Gallego, A.; Contreras, C.; Yepez, J.; Angel Escobar, J.; Manzur J, F.; Cohen, L.; Boneu, D.; Garcia Lozada, H.; Barrios, L.; Celemin, C.; Diego, M.; Garcia Ortiz, L.; Montoya, C.; Ramirez, E.; Arcos Palma, E.; Ceron, J.; Acosta, G.; Gomez Mesa, J.; Velasquez, J.; Barreto, D.; Trujillo Dada, F.; Trujillo Accini, F.; Cano, R.; Corredor de La Cruz, K.; Maria, V.; Palmera, J.; Vesga, B.; Hernandez, H.; Moreno Silgado, G.; Aruachan Vesga, S.; Burgos Martinez, E.; Quintero Villareal, G.; Solano Ayazo, F.; Porto Valiente, J.; Zidkova, E.; Krupicka, P.; Bultas, J.; Mandysova, E.; Lubanda, J.; Horak, J.; Belohlavek, J.; Kovarnik, T.; Gorican, K.; Rucka, D.; Smid, O.; Dostalova, G.; Skalicka, H.; Karetova, D.; Pavlinak, V.; Kuchynkova, S.; Marek, J.; Rob, D.; Ravlykova, K.; Prochazka, P.; Siranec, M.; Urbanec, T.; Vareka, T.; Nesvadbova, P.; Kaletova, M.; Indrakova, J.; Kryza, R.; Heczko, M.; Hanak, P.; Jancar, R.; Kocurkova, L.; Marcinek, G.; Cermak, O.; Drasnar, T.; Richter, M.; Kaspar, J.; Spinar, J.; Parenica, J.; Parenicova, I.; Schildberger, J.; Toman, O.; Ludka, O.; Poloczek, M.; Musil, V.; Miklik, R.; Labrova, R.; Lokaj, P.; Felsoci, M.; Bocek, O.; Kanovsky, J.; Zatocil, T.; Jerabek, P.; Matuska, J.; Jankovic, M.; Jankovicova, H.; Tesak, M.; Sulc, D.; Svacinova, H.; Radvan, M.; Bednar, J.; Motovska, Z.; Petr, R.; Fischerova, M.; Branny, M.; Vodzinska, A.; Cerny, J.; Indrak, J.; Sknouril, L.; Maly, J.; Vacek, T.; Prazak, O.; Broulikova, K.; Hajsl, M.; Jarkovsky, P.; Kamenik, L.; Kotik, I.; Krcova, E.; Sedlon, P.; Skvaril, J.; Cernohous, M.; Kohoutek, J.; Levcik, M.; Holek, M.; Hajdusek, P.; Foltynova Caisova, L.; Novak, V.; Kladivkova, M.; Slaby, J.; Houra, M.; Vojtisek, P.; Novotny, V.; Lazarak, T.; Pliva, M.; Pirk, J.; Barciakova, L.; Jandova, R.; Adamkova, V.; Galovcova, M.; Peterkova, L.; Turek, D.; Prochazka, J.; Belohoubek, J.; Spinarova, L.; Panovsky, R.; Novotny, P.; Krejci, J.; Hude, P.; Ozabalova, E.; Godava, J.; Honek, T.; Kincl, V.; Benesova, M.; Buckova, J.; Canadyova, J.; Mokracek, A.; Homza, M.; Stverka, P.; Florian, J.; Lukac, B.; Polasek, R.; Kucera, P.; Seiner, J.; Karasek, J.; Coufal, Z.; Stastny, J.; Cernicek, V.; Skalnikova, V.; Jiresova, E.; Brat, R.; Sieja, J.; Gloger, J.; Berger, P.; Prochazkova, I.; Samlik, J.; Brtko, M.; Tuna, M.; Polansky, P.; Omran, N.; Myjavec, A.; Hrdinova, M.; Jansky, P.; Kratochvilova, R.; Burkert, J.; Koubek, F.; Fiala, R.; Paulasova Schwabova, J.; Lindner, J.; Hlubocky, J.; Spacek, M.; Marcian, P.; Hanak, V.; Pozdisek, Z.; Lonsky, V.; Santavy, P.; Troubil, M.; Straka, Z.; Budera, P.; Fojt, R.; Talavera, D.; Tretina, M.; Nemec, P.; Orban, M.; Bedanova, H.; Wiggers, H.; Tougaard, R.; Larsen, A.; Nielsen, H.; Mattsson, N.; Gunnar, G.; Bruun, N.; Folke, F.; Soendergaard, K.; Koeber, L.; Frydland, M.; Fuchs, A.; Bang, L.; Houlind, K.; Olsen, M.; Soerensen, V.; Overgaard Andersen, U.; Dixen, U.; Refsgaard, J.; Moeller, D.; Zeuthen, E.; Lund, J.; Soegaard, P.; Jensen, S.; Duarte, Y.; Duarte, W.; Cáceres, S.; Pow Chon Long, F.; Peñaherrera, C.; Anzules, N.; Sánchez, M.; Zuleta, I.; López, J.; Villota, M.; Sánchez, H.; Perugachi, C.; Gómez, S.; Morejón, P.; Mármol, R.; Guamán, S.; Trujillo, F.; Escobar, M.; Carrera, F.; Ponce, F.; Terán, P.; Carrasco, S.; Tuomilehto, J.; Humaloja, K.; Lindberg, L.; Tuomilehto, H.; Tuominen, M.-L.; Kantola, I.; Juliard, J.; Feldman, L.; Ducrocq, G.; Boulogne, C.; Petitalot, V.; Leclercq, F.; Roubille, F.; Agullo, A.; Ferrari, E.; Chiche, O.; Moceri, P.; Boccara, F.; Charbonnier, M.; Azeddine, B.; Ederhy, S.; Soulat Dufour, L.; Cohen, A.; Etienney, A.; Messas, E.; Calvalido, A.; Galloula, A.; Zarka, S.; Courtois, M.-C.; Mismetti, P.; Accassat, S.; Buchmuller, A.; Moulin, N.; Bertoletti, L.; Seffert, B.; Sevestre, M.; Samy Modeliar Remond, S.; Dupas, S.; Mardyla, J.; Le Gloan, S.; Cayla, G.; Cornillet, L.; Schmutz, L.; Motreff, P.; Souteyrand, G.; Amonchot, A.; Barber-Charmoux, N.; Combaret, N.; Malcles, G.; Brenner, S.; Christa, M.; Duengen, H.; Krackhardt, F.; Bobenko, A.; Hashemi, D.; Stellbrink, C.; Stellbrink, E.; Köster, C.; Guerocak, O.; Bourhaial, H.; Oumbe Tiam, S.; Kemala, E.; Froemke, J.; Kadel, C.; Moellinger, H.; Friedrich, K.; Rafoud, K.; Braun-Dullaeus, R.; Herold, J.; Ganzer, M.; Jeserich, M.; Kimmel, S.; Haggenmiller, S.; Schoengart, H.; Voehringer, H.; Opitz, C.; Appel, K.; Appel, S.; Utech, A.; Finger, C.; Duersch, M.; Dorsel, T.; Wistorf, N.; Grude, M.; Nikol, S.; Ueberschaer, D.; Kast, P.; Darius, H.; Sommer, S.; Girke, F.; Oeztuerk, C.; Ranft, J.; Mikalo, A.; Schellong, S.; Voigts, B.; Mueller, C.; Jungmair, W.; Davierwala, P.; Misfeld, M.; Bomke, K.; Akhavuz, O.; Haensig, M.; Vorpahl, M.; Blem, A.; Langer, G.; Nover, I.; Koehler, T.; Bajnok, L.; Marton, Z.; Laszlo, Z.; Noori, E.; Veress, G.; Fogarassy, G.; Aradi, D.; Kelemen, B.; Vertes, A.; Davidovits, Z.; Zsary, A.; Kis, E.; Hepp, T.; Koranyi, L.; Peterfai, E.; Bezzegh, K.; Bakai, J.; Agardi, I.; Boda, Z.; Razso, K.; Poor, F.; Varallyay, Z.; Jarai, Z.; Sallai, L.; Dudas, M.; Barton, J.; Mahmood, K.; Makki, H.; McAdam, B.; Salim, T.; Murphy, A.; Crean, P.; Liddy, A. M.; Mahon, N.; Khan, I.; Hassan, S.; Curtin, R.; McFadden, E.; MacNeill, B.; Kyvelou, S.; Canavan, M.; Veerasingam, D.; Dinneen, S.; Halabi, M.; Rosenfeld, I.; Levinas, T.; Goldberg, A.; Khateeb, A.; Zimlichman, R.; Ben-Aharon, J.; Beniashvili, A.; Betsalel, A.; Zeltser, D.; Rogowski, O.; Mardi, T.; Rozenbaum, Z.; Turgeman, Y.; Or, T.; Rabkin, Y.; Klainman, E.; Halabi, S.; Halon, D. A.; Katz, A.; Plaev, T.; Drogenikov, T.; Atar, S.; Kilimnik, M.; Wishniak, A.; Merei, M.; Zvi, Y.; Nikolsky, E.; Zukermann, R.; Petcherski, S.; Bosi, S.; Gaitani, S.; Naldi, M.; Barbieri, A.; Faggiano, P.; Guidetti, F.; Adamo, M.; D’Aloia, A.; Magatelli, M.; Robba, D.; Mos, L.; Vriz, O.; Sinagra, G.; Maras, P.; Doimo, S.; Cosmi, F.; D'Orazio, S.; Oltrona Visconti, L.; Leonardi, S.; Vullo, E.; Sbaffi, A.; Azzara, G.; Mauri, S.; Gianni, U.; de Matteis, C.; Campidonico, U.; Di Pasquale, G.; Di Niro, M.; Riva, L.; Filippini, E.; Di Biase, M.; Ieva, R.; Martone, A.; Mandorla, S.; Regni, O.; Capponi, E. A.; Martinelli, S.; Bernardinangeli, M.; Proietti, G.; Piccinni, G. C.; Gualtieri, M. R.; Gulizia, M. M.; Francese, G. M.; Portale, A.; Galvani, M.; Ottani, F.; Capatano, O. G.; Conficoni, E.; Longhi, S.; Bachetti, C.; Venturi, F.; Capati, E.; Morocutti, G.; Bisceglia, T.; Fresco, C.; Baldin, M. G.; Gamba, C.; Olivieri, C.; Perna, G. P.; Battistoni, I.; Marini, M.; Cirrincione, V.; Ingrilli, F.; Kanno, T.; Ishii, Y.; Kohmura, C.; Igawa, T.; Izawa, K.; Daida, H.; Miyauchi, K.; Shimada, K.; Ohmura, H.; Ito, S.; Okazaki, S.; Konishi, H.; Miyazaki, T.; Hiki, M.; Kurata, T.; Suzuki, H.; Morimoto, R.; Yokoyama, M.; Yamamoto, T.; Okai, I.; Isoda, K.; Fujimoto, S.; Dohi, T.; Shimada, A.; Ozaki, Y.; Watanabe, E.; Kawai, H.; Naruse, H.; Takada, K.; Okuda, K.; Okumura, M.; Ishikawa, M.; Ohtsuki, M.; Ohta, M.; Sarai, M.; Koshikawa, M.; Kawai, M.; Miyagi, M.; Motoyama, S.; Matsui, S.; Ichikawa, T.; Kato, Y.; Nagahara, Y.; Muramatsu, T.; Hashimoto, Y.; Hoshino, N.; Harada, M.; Yamada, A.; Yoshiki, Y.; Motoike, Y.; Nomura, Y.; Miyajima, K.; Takatsu, H.; Nishimura, H.; Nagasaka, R.; Kawada, Y.; Miyamoto, N.; Seki, K.; Inoue, A.; Higashiue, S.; Kojima, S.; Kuroyanagi, S.; Furuya, O.; Komooka, M.; Yamamoto, S.; Wakabayashi, N.; Domae, H.; Ata, T.; Hashidomi, H.; Kawahara, R.; Hosokawa, S.; Hiasa, Y.; Otani, R.; Kishi, K.; Takahashi, T.; Yuba, K.; Miyajima, H.; Tobetto, Y.; Yoneda, K.; Ogura, R.; Kobayashi, H.; Takamura, T.; Enkou, K.; Ochi, Y.; Yamada, D.; Kuramochi, T.; Misumi, K.; Iiduka, D.; Hirose, M.; Tone, K.; Taniguchi, Y.; Ebihara, T.; Makino, M.; Yokota, M.; Nitta, M.; Udo, A.; Shimizu, S.; Fujii, K.; Iwakura, K.; Okamura, A.; Inoue, K.; Nagai, H.; Hirao, Y.; Tanaka, K.; Tanaka, N.; Yamasaki, T.; Oka, T.; Iwamoto, M.; Tanaka, T.; Nakamaru, R.; Okada, M.; Takayasu, K.; Sumiyoshi, A.; Inoue, H.; Kitagaki, R.; Ninomiya, Y.; Mizutomi, K.; Koizumi, I.; Funada, A.; Tagawa, S.; Kamide, S.; Saku, K.; Ideishi, M.; Ogawa, M.; Uehara, Y.; Iwata, A.; Nishikawa, H.; Ike, A.; Sugihara, M.; Imaizumi, S.; Fujimi, K.; Kawamura, A.; Sako, H.; Morito, N.; Morii, J.; Fukuda, Y.; Yahiro, E.; Matsunaga, A.; Matsumoto, N.; Noda, K.; Shiga, Y.; Nagata, Y.; Kimura, K.; Ebina, T.; Hibi, K.; Iwahashi, N.; Maejima, N.; Konishi, M.; Matsushita, K.; Minamimoto, Y.; Kawashima, C.; Nakahashi, H.; Kimura, Y.; Takahashi, H.; Matsuzawa, Y.; Kirigaya, J.; Sato, R.; Kikuchi, S.; Ogino, Y.; Kirigaya, H.; Kashiwase, K.; Hirata, A.; Takeda, Y.; Amiya, R.; Higuchi, Y.; Sakaguchi, T.; Nakano, T.; Matsusaki, N.; Suzuki, S.; Hayashi, T.; Nakatani, S.; Koide, M.; Kobayashi, T.; Hamanaka, Y.; Makino, N.; Sotomi, Y.; Abe, M.; Fujieda, H.; Hashimoto, K.; Teratani, Y.; Abe, Y.; Yokoyama, Y.; Higashino, H.; Okuda, H.; Yamazato, M.; Noda, T.; Arai, M.; Ono, K.; Hirose, T.; Iwama, M.; Warita, S.; Goto, Y.; Abe, S.; Kojima, T.; Yoshizane, T.; Tanihata, S.; Fujii, T.; Yagasaki, H.; Miwa, H.; Ishiguro, M.; Kato, T.; Watanabe, R.; Horio, S.; Mita, T.; Hirayama, A.; Watanabe, I.; Hiro, T.; Nakai, T.; Takayama, T.; Yoda, S.; Yajima, Y.; Okubo, K.; Okumura, Y.; Kato, M.; Fukamachi, D.; Aizawa, Y.; Sonoda, K.; Iida, K.; Sasaki, N.; Iso, K.; Takahashi, K.; Kougo, T.; Haruta, H.; Kurokawa, S.; Mano, H.; Nagashima, K.; Onaka, H.; Doi, H.; Hirano, N.; Okamoto, F.; Mori, K.; Ri, G.; Zushi, R.; Otsuka, K.; Inoko, M.; Haruna, T.; Nakane, E.; Miyamoto, S.; Izumi, T.; Honjo, S.; Ikeda, H.; Wada, Y.; Funasako, M.; Hayashi, H.; Hamasaki, A.; Sasaki, K.; Seko, Y.; Nakasone, K.; Hanyu, M.; Iwasaki, Y.; Iwasaki, K.; Ayano, S.; Hirokami, M.; Omoto, Y.; Sasaki, H.; Sato, H.; Yuda, S.; Okubo, M.; Matsuo, H.; Tsuchiya, K.; Kawase, Y.; Miyake, T.; Kondo, H.; Hattori, A.; Kikuchi, J.; Okamoto, S.; Hirata, T.; Kawamura, I.; Ota, H.; Omori, H.; Tanigaki, T.; Kamiya, H.; Sobue, Y.; Komoda, T.; Akatsuka, Y.; Yamamoto, M.; Isegawa, K.; Takanezawa, M.; Kataoka, C.; Imamaki, M.; Shibata, Y.; Yasuda, K.; Shimano, M.; Ozaki, R.; Morishita, Y.; Okabe, K.; Kondo, K.; Miura, A.; Manita, M.; Tabata, K.; Asahi, T.; Mashidori, T.; Higa, N.; Nakata, M.; Himi, T.; Matsudo, Y.; Sekine, T.; Hou, K.; Tonoike, N.; Hama, Y.; Tanaka, S.; Ge, B.; Takahara, M.; Ishimura, M.; Shikada, T.; Ueno, H.; Amemiya, H.; Hisamatsu, Y.; Sada, K.; Sato, T.; Harada, K.; Nakamura, T.; Ako, J.; Tojo, T.; Shimohama, T.; Kishihara, J.; Ishii, S.; Fukaya, H.; Meguro, K.; Nishino, Y.; Inoue, M.; Matsui, Y.; Omura, Y.; Kawakami, H.; Matsuoka, H.; Oshita, A.; Seike, F.; Kondo, N.; Miyoshi, T.; Yamada, Y.; Uchiya, T.; Kikuchi, Y.; Koretsune, Y.; Abe, H.; Shinouchi, K.; Nishida, H.; Yasumura, K.; Date, M.; Ueda, Y.; Iida, Y.; Idemoto, A.; Toriyama, C.; Yokoi, K.; Mishima, T.; Yamada, T.; Fukunami, M.; Morita, T.; Furukawa, Y.; Kawasaki, M.; Kikuchi, A.; Tamaki, S.; Seo, M.; Shirakawa, Y.; Ikeda, I.; Fukuhara, E.; Kawai, T.; Kayama, K.; Kawahira, M.; Tanabe, K.; Nakamura, J.; Shimomura, H.; Kudo, T.; Morisaki, S.; Ogura, Y.; Chazono, N.; Onoue, Y.; Matsumuro, Y.; Shirakawa, T.; Nishi, M.; Kinoshita, N.; Nakamura, R.; Miyai, N.; Ohta, K.; Sawanishi, T.; Takahashi, A.; Hada, T.; Nakajima, S.; Taniguchi, N.; Mizuguchi, Y.; Takahashi, Y.; Hashimoto, S.; Machida, M.; Hirabayashi, K.; Morimoto, S.; Higashino, Y.; Otsuji, S.; Takiuchi, S.; Yabuki, M.; Hasegawa, K.; Shishikura, D.; Ibuki, M.; Ishibuchi, K.; Nagayama, S.; Ishii, R.; Tamaru, H.; Yamamoto, W.; Utsu, N.; Miyakoshi, K.; Nakashima, D.; Tsukuda, K.; Ueda, K.; Nakano, A.; Fukuda, T.; Ikeda, S.; Tsuchiya, H.; Toshima, S.; Tateno, R.; Ishikubo, T.; Suguta, M.; Nakamura, S.; Funatsu, A.; Mizobuchi, M.; Tanaka, M.; Nagai, T.; Hirano, S.; Hashimoto, T.; Doi, T.; Shirasaka, A.; Takeda, S.; Sasaki, Y.; Ohya, H.; Hosokawa, A.; Nishina, N.; Koki, B.; Ando, K.; Hiramori, S.; Soga, Y.; Tomoi, Y.; Tohoku, S.; Shirai, S.; Hyodo, M.; Isotani, A.; Domei, T.; Kuramitsu, S.; Morinaga, T.; Hayashi, M.; Hiromasa, T.; Nagae, A.; Yamaji, Y.; Nakao, K.; Sakamoto, T.; Taguchi, E.; Tsurugi, T.; Tanaka, Y.; Suzuyama, H.; Koyama, J.; Nagano, M.; Okamatsu, H.; Kodama, K.; Nakamura, M.; Horibata, Y.; Sone, M.; Tsunemori, M.; Bando, M.; Nakayama, T.; Tanigaito, Y.; Nomoto, M.; Sawamura, T.; Unoki, T.; Lim, C. W.; Zainal Rashid, R.; Najme Khir, R.; Ibrahim, K. S.; Wan Azman, W. A.; Sridhar, G. S.; Watson, T.; Abu Kassim, Z.; Mahmood Zuhdi, A. S.; Abdul Hafidz, M. I.; Abu Hassan, M. R.; Wan Rahimi Shah, W. F.; Karthikesan, D.; Mohd Suan, M. A.; Md Ali, S. M.; Kasim, S.; Mohd Arshad, M. K.; Ismail, J. R.; Ibrahim, Z. O.; Chua, N. Y. L.; Abdul Rahim, A. A.; Rusani, B. I.; Yap, L. B.; Zamrin, D. M.; Amir, M. A.; Ismail, N. I.; Mohammad Razi, A. A.; Prins, F.; Bendermacher, P.; Burg, M.; Lok, D.; van der Sluis, A.; Martens, F.; Badings, E.; Milhous, J.; van Rossum, P.; Viergever, E.; van Hessen, M.; Willems, F.; Tjon Joe Gin, R.; Swart, H.; Oomen, A.; Kromhout, S.; Lauwerijssen, I.; Daalmans, M.; Breedveld, R.; de Vries, K.; Feenema Aardema, M.; Hofma, S.; van der Borgh, R.; van Nes, E.; Göbel, E.; Oei, F.; Dorman, H.; Bos, R.; Zoet-Nugteren, S.; Emans, M.; Kragten, H.; Lenderink, T.; Feld, R.; Herrman, J.; van Bergen, P.; Gosselink, M.; Elvan, A.; Hoekstra, E.; The, S.; de Vries, R.; Zegers, E.; Oude Ophuis, T.; Remmen, J.; Bech, J.; Kooistra, J.; den Hartog, F.; Oosterhof, T.; Bartels, G.; Posma, J.; Nierop, P.; Liem, A.; van der Zwaan, C.; Asselman, M.; van Eck, J.; Gevers, R.; van Gorselen, E.; van Hal, J.; Terpstra, W.; Groenemeijer, B.; Jerzewski, A.; Hoogslag, P.; Geertman, J.; de Groot, M.; Dijkstra, B.; Loyola, A.; Sulit, D.; Mercado, M. J.; Rey, N.; Evangelista, L.; Abola, M.; Padua, L.; Morales, D.; Palomares, E.; Abat, M.; Santos, R.; Rogelio, G.; Chua, P.; Baello, R.; del Pilar, J.; Alianza, M.; Alcaraz, J.; Alcaraz, L.; Ebo, G.; Guido-Saliot, I.; Tirador, L.; Estoce, E.; Ygpuara, M.; Cruz, J.; Anonuevo, J.; Pitargue, A.; Janion, M.; Drewniak, Z.; Guzik, B.; Nowak, M.; Nosal, M.; Niewiara, Ł; Gajos, G.; Bury, K.; Czubek, U.; Misztal, M.; Grzybczak, R.; Zalewski, J.; Kruszelnicka-Kwiatkowska, O.; Żabówka, M.; Rynkiewicz, A.; Grzybowski, A.; Szałkowski, P.; Broncel, M.; Gorzelak, P.; Możdżan, M.; Olszewska Banaszczyk, M.; Szuba, A.; Tabin, M.; Chachaj, A.; Czarnecka, D.; Terlecki, M.; Klocek, M.; Maga, P.; Coman, I.; Tarlea, M.; Ghionea, M.; Gavrila, C.; Dimulescu, D.; Popescu, A.; Stoicescu, C.; Vintila, V.; Florescu, M.; Baghilovici Cretu, D.; Suran, M.; Mihalcea, D.; Lungeanu Juravle, L.; Cinteza, M.; Calin, I.; Bicescu, G.; Vasile Toma, N.; Udroiu, C.; Gherghinescu, C.; Darabont, R.; Patrascu, N.; Constantinescu, C.; Popescu, I.; Sinescu, C.; Andrei, C.; Axente, L.; Arsenescu, C.; Statescu, C.; Ardeleanu, I.; Anghel, L.; Benedek, I.; Benedek, T.; Kinga, P.; Banga, D. K.; Bobescu, E.; Doka, B.; Dobreanu, D.; Sirbu, V.; Rudzik, R.; Kantor, K.; Sus, I.; Gaita, D.; Maximov, D.; Brie, D.; Mosteoru, S.; Olariu, I.; Iancu, A.; Marc, M.; Hagiu, R.; Manole, V.; Molnar, A.; Dregoesc, I.; Iliesiu, A.; Armean, P.; Parvu, I.; Deleanu, A.; Lighezan, D.; Buzas, R.; Petrescu, L.; Nicola, R.; Dan, R.; Crisan, S.; Trasca, L.; Teodorescu, I.; Zara, O.; Tiron, T.; Tesloianu, D.; Spiridon, M.; Vintila, M.; Baluta, M.; Chioncel, O.; Stoica, E.; Kulcsar, I.; Antohi, L.; Strazhesko, I.; Tkacheva, O.; Sharashkina, N.; Pykhtina, V.; Vasyuk, Y.; Shkolnik, E.; Khadzegova, A.; Sadulaeva, I.; Ivanova, S.; Nesterova, E.; Nesvetov, V.; Shupenina, E.; Shcherbak, M.; Sizova, Z.; Beloborodova, A.; Pozdnyakov, Y.; Tarasov, A.; Shvedov, I.; Zabashta, S.; Ryzhikova, I.; Barbarash, O.; Pecherina, T.; Vatutin, M.; Inozemceva, A.; Kazachek, Y.; Mineeva, E.; Kupriyanova, T.; Voevoda, M.; Gafarov, V.; Gromova, E.; Panov, D.; Voevoda, E.; Kovalkova, N.; Ragino, Y.; Poponina, T.; Poponina, Y.; Garganeeva, N.; Repin, A.; Vershinina, E.; Borodina, E.; Kalashnikova, T.; Safyanova, O.; Osipova, I.; Antropova, O.; Pyrikova, N.; Polyakova, I.; Efremushkina, A.; Guryanova, N.; Kiseleva, E.; Lomteva, E.; Shtyrova, T.; Novikova, N.; Parfenov, D.; Volovchenko, A.; Averkov, O.; Pavlikova, E.; Vaulina, L.; Pletnikova, I.; Mishchenko, L.; Saranin, S.; Tsupko, I.; Kuznetsova, N.; Zateyshchikov, D.; Dankovtseva, E.; Vlazneva, Y.; Tolokonnikova, N.; Zhurina, M.; Zubova, E.; Aseycheva, O.; Sigalovich, E.; Vertkin, A.; Rodiukova, I.; Komissarov, S.; Sokolova, R.; Ausheva, A.; Salbieva, A.; Yusubova, A.; Isakova, S.; Hranai, M.; Obona, P.; Cisar, P.; Semetko, J.; Vanova, P.; Ferencikova, Z.; Vykoukalova, T.; Gaspar, L.; Caprnda, M.; Bendzala, M.; Pella, D.; Fedacko, J.; Hatalova, K.; Drozdakova, E.; Peter, O.; Ntsekhe, M.; de Andrade, M.; Seedat, S.; Gani, M.; van Zyl, L.; Naude, M.; Cronje, T.; van Zyl, F.; Engelbrecht, J.; Jansen, J.; Roos, J.; Makotoko, E.; Pretorius, C.; Mirna, S.; Nell, H.; Pretorius, M.; Basson, M.; Njovane, X.; Mohamed, Z.; Pillay, T.; Dawood, S.; Horak, A.; Lloyd, E.; Hitzeroth, J.; Mabin, T.; Abelson, M.; Klug, E.; Gebka, M.; Hellig, F.; Alison, M.; Bae, J.; Kim, C.; Kim, D.; Joo, S.; Park, C.; Kim, Y.; Jarnert, C.; Rydén, L.; Mooe, T.; Binsell-Gerdin, E.; Dellborg, M.; Torstensson, I.; Albertsson, P.; Hiller, M.; Perers, E.; Johansson, L.; Jansson, J. H.; Al-Khalili, F.; Almroth, H.; Andersson, T.; Eriksson Östman, M.; Pantev, E.; Utter, F.; Tengmark, B. O.; Olsson, Å; Liu, B.; Rasmanis, G.; Wahlgren, C. M.; Thott, O.; Moccetti, T.; Rossi, M. G.; Crljenica, C.; Dovgan, N.; Skarzhevskyi, O.; Kozhukhov, S.; Tseluyko, V.; Mishchuk, N.; Kuznetsov, I.; Semenikhin, S.; Matviichuk, N.; Matuzok, O.; Yakovleva, L.; Volkov, V.; Zaprovalna, O.; Serik, S.; Riabukha, V.; Koval, O.; Kaplan, P.; Ivanov, A.; Romanenko, S.; Skoromna, A.; Kononenko, L.; Saprychova, L.; Lazareva, S.; Prokhorov, O.; Vdovychenko, V.; Bychkov, M.; Demydova, A.; Kapustynska, O.; Bazylevych, A.; Dutka, R.; Vlasyuk, Z.; Shabat, M.; Rudenko, L.; Beregova, O.; Fedtchouk, L.; Gusak, I.; Vizir, V.; Sadomov, A.; Shkolovoy, V.; Nasonenko, O.; Demidenko, O.; Karpenko, O.; Ponomarenko, K.; Oryshych, G.; Nevolina, I.; Mitskevych, L.; Bezuglova, S.; Kizim, S.; Todoriuk, L.; Brodi, N.; Karpenko, L.; Malynovsky, Y.; Fedotov, S.; Malynovska, O.; Goydenko, O.; Miroshnykov, S.; Rabota, I.; Koval, V.; Ohirko, O.; Khaba, U.; Storozhuk, B.; Danylchuk, I.; Danylchuk, A.; Gutsuliak, R.; Cotton, J.; Luckraz, H.; Wrigley, B.; Venkataraman, A.; Maher, A.; Moriarty, A.; McEneaney, D.; Connolly, D.; Davis, R.; Banerjee, P.; Davey, P.; Elmahi, E.; Senior, R.; Ahmed, A.; Birdi, I.; Gedela, S.; Singh, A.; Calvert, J.; Butler, M.; Donnelly, P.; Jasinka, A.; Orr, C.; Trevelyan, J.; Routledge, H.; Carter, J.; Oxenham, H.; Peace, A.; McNeill, A.; Austin, D.; Jackson, M.; Kukreja, N.; Kotwinski, P.; Hilton, T.; Bilizarian, S.; Srivastava, S.; Walsh, R.; Fields, R.; Portnay, E.; Gogia, H.; Deits, R.; Salacata, A.; Hunter, J.; Bacharach, J.; Shammas, N.; Suresh, D.; Gurbel, P.; Banerjee, S.; Grena, P.; Bedwell, N.; Sloan, S.; Lupovitch, S.; Soni, A.; Gibson, K.; Pepper, D.; Sangrigoli, R.; Mehta, R.; Patel, J.; I-Hsuan Tsai, P.; Gillespie, E.; Harrison, A.; Dempsey, S.; Phillips, R.; Hamroff, G.; Hametz, C.; Black, R.; Lader, E.; Kostis, J.; Bittner, V.; Mcguinn, W.; Cheng, R.; Pal, J.; Malhotra, V.; Michaelson, S.; Vacante, M.; Mccormick, M.; Arimie, R.; Dukkipati, R.; Camp, A.; Dagher, G.; Kosh y, N.; Culp, J.; Thew, S.; Ferraro, A.; Costello, F.; Heiman, M.; Chilton, R.; Moran, M.; Adler, F.; Balingit, P.; Comerota, A.; Seiwert, A.; French, W.; Vardi, G.; Singh, T.; Serota, H.; Qayyum, U.; Das, S.; Harrison, R.; Vora, A.; Bakeen, F.; Omer, S.; Chandra, L.; Casaccia, G.; Tinto, J.; Sighel, C.; Giozzi, E.; Morell, Y.; Bianchini, M.; Yossen, M.; Hoyos, M.; Venturini, C.; Merkusa, C.; Carrique, A.; Carrique, P.; Fracaro, V.; Torres, M.; Crunger, P.; Espinosa, M.; Passarello, A.; Zaidman, M.; Ledesma, M.; Troncoso, C.; Aviles, A.; Rodera Vigil, S.; Vogel, M.; Takla, M.; Funosas, C.; Ferreiro, M.; Bruno, T.; Buzzetti, C.; Lozano, J.; Alvarez Dámelio, A.; Bocanera, M.; Vicente, D.; Cenci, A.; Deluca, C.; Santana, R.; Ahuad Calvelo, A.; Alvarez D'Amelio, A.; Ahuad Calvelo, J.; Herrero, S.; Robertson, M.; Tapia, D.; Escalante, M.; Cañas, M.; Cendali, G.; Esposito, L.; Muñiz, M.; Montaña, J.; Di Vruno, M.; Strevezza, M.; Lopez Santi, M.; Massei, N.; Garate, V.; Perlo, D.; Campora, F.; Jakubowski, I.; Gonzalez Moisello, M.; Actis, M.; Schiavi, S.; Aguirre, M.; Ceirano, C.; Zillo, M.; Yunis, M.; Berdini, A.; Gerbaudo, R.; Berdini, J.; Palma, F.; Pinero, S.; Virulio, S.; Vitale, A.; Sosa Flores, G.; Ibanez Saggia, C.; Ibanez Saggia, D.; Roses, A.; Martinelli, C.; Vargas, L.; Galarza Salazan, M.; Dran, P.; Tinnirello, V.; Pelayes, S.; Bordoni, P.; Navarro, A.; Barilati, P.; Serra, R.; Nigro, A.; Cleiman, S.; Bianchi, M.; Vallejo, M.; Ingratta, M.; Tonelli, L.; Levantini, M.; Bonifacio, M.; Hansen, V.; Chaieb, A.; Majul, S.; Medina, F.; Gallinotti, P.; Madariaga, T.; Andrea, G.; Blumberg, C.; Volpe, M.; Gandur, H.; Benincasa, V.; Barreto, M.; Jure, D.; Tulloch, G.; Greenwell, D.; Forrest, N.; Nyman, E.; Mcintosh, C.; O'May, V.; Grabek, T.; Conway, B.; O’Donoghue, M.; Brady, L.; Duroux, M.; Ratcliffe, M.; Shone, S.; Connelly, A.; Ferreira-Jardim, A.; Vandernet, R.; Downes, R.; Davids, F.; Teal, L.; Knight, S.; Soraghan, D.; Spence, C.; Smith, K.; Tivendale, L.; Williams, Z.; O'Connor, M.; Walker, I.; Ferguson, L.; Holiday, J.; Griffin, R.; Palethorpe, L.; Hindom, L.; Lilwall, L.; Wadham, S.; Narasimhan, K.; van Extergem, P.; Joris, I.; Oreglia, M.; Jacobs, C.; Leus, W.; Robesyn, V.; Vanheule, K.; van den Bossche, K.; Albertijn, S.; Vissers, C.; Badts, G.; Vangenechten, K.; Derycker, K.; Dejaegher, K.; de Grande, T.; de Clippel, M.; Gayet, F.; Jorion, M.; Jourdan, A.; Tartaglia, K.; Zwinnen, W.; Roijakkers, I.; van Genechten, G.; Schoonis, A.; Bollen, J.; Janssen, A.; de Coninck, M.; Ruell, S.; Grimonprez, A.; Bouckaert, N.; van Eeckhoutte, H.; Malmendier, D.; Massoz, M.; Jacquet, S.; Vanhalst, E.; Casier, T.; Barroso, S. L.; Tamashiro, N.; Correa, C. P.; Sehnem, E. A. B.; Precoma, C. B.; Pinheiro, L.; Ruschel, K. B.; dos Reis, A. L.; Santos, M. S.; de Oliveira, L. O. S. P.; de Carvalho, L. M. G.; dos Santos, M. E. S.; Reis, L. L. F.; da Cunha, G. T.; França, F. F.; Bessa, S. K.; Vicente, C.; Ormundo, C.; Trama, L.; Pires, N. F.; Esteves, D.; Sila, O. L.; Góes, N. C.; Amorin, R. C.; Faria, M. O.; Bucalon, E. C.; Marin, L. P.; Herek, L.; Araujo, V. L.; Silva, A. F.; Lima, F.; Gomes, C. G.; Pagnan, L. G.; Novelli, C. M.; Carvalho, J. K. C.; Teodoro, A. R.; Zimmermann, E. M. B.; Beiersdorf, J. R.; Machado, B. G.; Pedroso, F. B. V.; de Vargas, T.; Peres, C. S.; dos Santos, T. F.; de Souza, S. F.; Luiz, R. O.; Ferreira, P.; Souza, D. F.; Cunha, S. M. C.; de Resende, I. M.; Furtado, C. C. F.; Soprane, A. A.; Brum, A. B.; Zorzo, J. A. T.; dos Santos, J. C.; Queiroz, L. B.; Barros, F. E.; Vianna, C. O.; Zanateli, A.; Vieira, A. P. Z.; Melo, G.; Zambonin, G. E. C.; Paiva, P.; Viana, R. M. M.; Yagihara, M. M.; Takiuti, M. M.; Miyamoto, P. B.; da Silva, M. F.; Borin, L. A.; Chiazzini, S. M. L.; Fleck, N.; Batista, R. F.; Cardoso, D. T.; MCamasmie, P.; Assompção, R. P.; Marques, L. L.; Leung, S.; Lewis, C.; Tytus, A.; Clarus, S.; Juranics, S.; Pandey, M.; Frenette, L.; Magi, A.; Nowacki, B.; Otis, J.; Fox, B.; Corke, R.; Miller, B.; Rizzo, A.; Trombetta, L.; Power, P.; Richert, L.; Haligowski, R.; Macrae, C.; Kooistra, L.; Urso, C.; Fox, S.; Felbel, S.; Stafford, C.; Stata, C.; Barnabe, B.; Mehta, K.; Faul, J.; Gohel, J.; Bhakta, S.; Harwood, A.; McPherson, C.; Marucci, J.; Manasterski, L.; Veenhuyzen, J.; Ramadan, D.; Madden, B.; Jetha, A.; Pajevic, M.; Dube, C.; Rolfe, B.; O’Blenis, G.; Roy, L.; Dihel, C.; Butler, J.; Simmavong, K.; Bartol, C.; Bozek, B.; Hart, B.; Shier, M.; Coughlin, M.; Lamantia, C.; Lamantia, D.; Vilag, C.; Fecteau, J.; Dionne, J.; Péloquin, G.; Hogg, N.; Welsh, S.; Weerasingam, S.; Lantz, M.; Lounsbury, N.; Martin, E.; Mitchell, L.; Morgen, G.; Nelson, S.; Pelzer, E.; Sorensen, S.; Leblanc, A.; Bourlaud, A. S.; Prémont, A.; Léger, P.; Larivière, M. M.; Tremblay, H.; Bergeron, A.; Dumont, J.; Keilani, S.; Landry, P.; Deneufbourg, I.; Breton, C.; Bilodeau, N.; Côté, M.; Dumont, F.; Dufort, L.; Marcoux, D.; David, M.; Otis, R.; Parks, J.; Cepidoza, C.; Janz, W.; Weighell, W.; Yaworski, S.; Boyd, K.; Lambert, J.; Shea-Landry, G.; Reid, K.; Thiessen, S.; Nemtean, D.; Futers, S.; Drouin, K.; Masson, C.; Arseneault, M. C.; Lachance, N.; Bergeron, C.; Boudreault, C.; Perkins, L.; Barnett, A.; Fortin, J.; Duclos, R.; Vallières, C.; Bouchard-Pilote, C.; Ouimet, F.; Roberge, B.; Couture, M. L.; Deshaies, D.; Bastien, A.; Chartrand, M. J.; Gagné, N. L.; Desbiens, K.; Alarie, P.; Cassan, J.; Ducharme, Y.; Roy D Tapps, I.; Bolduc, H.; Laliberté, J.; Hickey, L.; Spero, M.; Bernstein, M.; Clement, J.; Pawluch, A.; Ricci-Bonzey, M.; Richer, J.; Vaillancourt, J.; Ward, B.; Mostafai Rad, P.; Oleski, L.; Karkhanis, R.; Hartleib, V.; Poirier, R.; Hidalgo, J.; Hernandez, C.; Obreque, C.; Quilapi, D.; Villa, F.; Iturriaga, C.; Ferrada, M.; Navarrete, S.; Becerra, E.; Vargas, C.; Roque, C.; Alarcon, J.; Diaz, D.; Sepulveda, M.; Villan, C.; Garcia, N.; Lara, C.; Lezana, B.; Basso, N.; Torres, G.; Pasmino, C.; Gonzalez, S.; Medina, D.; Rodriguez, T.; Guo, T.; Chen, S.; Han, W.; Shi, D.; Zhang, Q.; Li, W.; Cui, L.; Huang, Z.; Gong, X.; Liu, D.; Tan, S.; Caicedo, L.; Rodriguez, A.; Mejia, I.; Escalante Ruiz, J.; Camera Ochoa, C.; Conrrado Ortega, Y.; Accini Diaz, A.; Rodriguez, B.; Lopez-Lopez, J.; Di Stefano, K.; Florez, L.; Manco, T.; Rodriguez, D.; Urina, A.; de La Hoz, L.; Almendrales, L.; Bello, O.; Urrea Valencia, H.; Correa Rivera, P.; Perdomo, I.; Alzate, J.; Rivera, E.; Jimenez, N. N.; DMoreno, N.; Guzman, A.; Betancourt, S.; Mendoza Marin, H.; Leyva, M.; Ortiz, M.; Marin, E.; Angie Lorena, A.; Alvarez, Y.; Cervantes Hurtado, A.; Accini Mendoza, A.; Trujillo Accini, M.; Eguis, B.; del Portillo, C.; Ortega, M.; Delgado, P.; Arciniegas, J.; Rodriguez, L.; Melo Sanchez, S.; Chavera, I.; Pastrana Mendoza, M.; Negrette Quintero, A.; Zidek, M.; Hajkova, D.; Rozskowska, P.; Opavska, I.; Souckova, E.; Matuskova, E.; Kratochvilova, T.; Pavelec, P.; Zelenkova, V.; Dolezalova, Z.; Márquez, M.; Moreira, D.; Zuleta, M.; Santana, G.; Coello, A.; Andrade, G.; Salazar, J.; Rivadeneira, J.; Vaerma, J.; Lappalainen, S.; Silvennoinen, S.; Haaraoja, A.; Valimaki, S.; Roine, E.; Abergel, H.; Msakni, W.; Fuentes, A.; Briday, G.; David, A.; Soltani, S.; Decorps, A.; Chettouh, M.; Douillet, M.; Zamiti-Smondel, A.; Cuccu, L.; Salhi, N.; Helene, M.; Martin, S.; Merah, A.; Daher, P.; Laurie, S.; Roussel, L.; Leperchois, C.; Delelo, E.; Thalamy, A.; Chazot, E.; Tahirovic, E.; Watson, S.; Brettschneider, B.; Maas, M.; Euler, K.; Rahn, G.; Beissner, S.; Anuschek, V.; Tu, E.; Buerger, M.; Schemann, J.; Klinger, C.; Kurzidim, T.; Sahbani, S.; Laszig, S.; Beilfuss, M.; Foerster, A.; Eichinger, G.; Rupprecht, M.; Kuehnert, J.; Wendler-Huelse, I.; Buelow-Johansen, B.; Baierlein, A.; Iselt, M.; Sievert, B.; Frommhold, R.; Wolf, T.; Hahn, M.; Schoen, B.; Acimic, C.; Ludwig, M.; Funkat, A.; Wagner, I.; Schink, M.; Calvo-Sanchez, D.; Felfoldine Feil, J.; Patakine Sumegi, T.; Miko-Pauer, R.; Courcy, M.; Kelly, C.; Farrell, D.; Kirrane, C.; Hall, M.; Gilroy, E.; Kelsey, M.; Andrew, G.; Joyce, M.; Conway, S.; Duane, L.; Omer, T.; Zuker, S.; Platner, N.; Saranga, H.; Kaufman, E.; Livshitz, L.; Genin, I.; Klainman, M.; Uziel Iunger, K.; Abitbul, A.; Fishman, B.; Greenshtein, I.; Tubul, O.; Lasri, E.; Zvi, R.; Yablonski, A.; Helmer Levin, L.; Lunetto, M. L.; Savoldi, D.; Fiorini, M.; Ramani, F.; Mariottoni, B.; Rizzotti, D.; Di Matteo, C.; Musio, S.; Pieroni Minciaroli, S.; Serani, S.; Aloisi, A.; Attanasio, C.; Tricoli, M.; Giordano, V.; Andrioli, V.; Biundo, V.; Tullio, L.; Schiff, D.; Trovarelli, P.; Chiodi, R.; Sampaolesi, S.; Cina, M. T.; Abatello, M.; de Tora, M.; Pietrucci, F.; Pezzetta, S.; Chiminelli, E.; Dall’Asta, A.; Bennati, M.; Elia, A.; Bizzoco, M.; Iaquaniello, A.; Spigarelli, R.; Cremonesi, C.; Gagliardi, M.; Torricelli, L.; Ijichi, N.; Shiraiwa, K.; Murakami, M.; Takeshita, K.; Sato, M.; Shiratori, A.; Kinjo, K.; Tomita, K.; Mizuno, M.; Kurihara, F.; Tachibana, M.; Nitta, Y.; Unno, K.; Hiramatsu, H.; Sano, A.; Nanatsumura, M.; Tanikawa, I.; Uesugi, K.; Banno, S.; Miyata, T.; Kujuji, A.; Kawai, K.; Maegawa, A.; Koseki, T.; Watanabe, Y.; Aoki, S.; Maesawa, M.; Suzuki, A.; Itose, Y.; Konishi, K.; Fujieda, K.; Nakade, S.; Minami, M.; Yoneda, J.; Akiyama, R.; Sakai, S.; Nakatani, K.; Yamazaki, A.; Funama, M.; Kaneko, E.; Morii, S.; Onishi, M.; Sone, A.; Sagawa, N.; Iwai, F.; Kawahara, A.; Hasimoto, C.; Ueki, M.; Kamiji, M.; Ando, M.; Yokoo, M.; Okada, Y.; Yamada, H.; Matsushige, N.; Nagato, A.; Matsumoto, R.; Nishikawa, M.; Oka, I.; Kitou, S.; Tachiuchi, M.; Nakagawa, M.; Yoneda, S.; Iwasa, K.; Matsuda, J.; Oda, A.; Tokudome, S.; Kaneyuki, Y.; Higaki, M.; Yoneda, H.; Kajita, C.; Suwa, K.; Sato, E.; Nagata, T.; Kubo, Y.; Umesu, A.; Ohashi, K.; Takeuchi, M.; Tanaka, I.; Nobehara, T.; Yamano, R.; Yumiba, A.; Hamada, M.; Nishihata, T.; Ohashi, Y.; Morita, M.; Endo, M.; Matsugi, M.; Tateishi, H.; Nakamori, R.; Yamashita, Y.; Okabe, M.; Matsuo, M.; Ono, T.; Shigeyama, Y.; Ichiyanagi, M.; Sugimori, K.; Ohmura, C.; Igarashi, M.; Aotsuka, S.; Komoda, N.; Watanabe, M.; Enomoto, Y.; Suzuki, Y.; Kawaguchi, A.; Kasahara, A.; Koide, A.; Sakatani, T.; Kurihara, T.; Yokota, S.; Futagi, R.; Amemiya, Y.; Ono, E.; Maeda, A.; Kadono, K.; Ishiguchi, Y.; Kikuchi, R.; Kuramatsu, M.; Nakamura, E.; Chiba, S.; Higa, A.; Kitahashi, M.; Tanaka, H.; Ito, T.; Oba, M.; Tsubouchi, M.; Toshima, M.; Morishita, M.; Miyano, A.; Kondo, M.; Watanabe, K.; Shibata, R.; Tosaki, Y.; Ito, Y.; Saoda, M.; Yamasaki, E.; Kadosaki, S.; Motooka, S.; Akiyoshi, H.; Morio, S.; Nemoto, H.; Yoshizawa, S.; Okabe, N.; Semba, K.; Yoshida, A.; Lee, Y.; Yoshida, M.; Iwashita, Y.; Takeda, A.; Maezato, M.; Kawahira, K.; Yoshikawa, M.; Okamoto, N.; Nishimura, M.; Matsuura, K.; Fukunaga, M.; Fukai, K.; Osakabe, Y.; Yamamura, K.; Koike, M.; Shibuya, S.; Shiramata, M.; Ono, Y.; Tsujimoto, Y.; Tadokoro, T.; Morishita, N.; Matsuo, Y.; Yumoto, I.; Sakazaki, S.; Atarashi, A.; Nabata, Y.; Okuda, N.; Fujita, A.; Matsuo, A.; Ishizawa, Y.; Shibata, H.; Ootsuka, M.; Taimatsu, R.; Takeuchi, A.; Sumi, Y.; Yamamoto, F.; Araki, Y.; Tanaka, A.; Kuroda, S.; Sakata, R.; Okada, N.; Sawada, Y.; Miyata, M.; Asayama, H.; Koga, N.; Miki, T.; Yamaguchi, N.; Hashimoto, A.; Fukuike, C.; Kubo, A.; Yamasaki, M.; Mori, Y.; Nakayama, S.; Kobayashi, Y.; Takenaka, S.; Mashima, M.; Katsuta, H.; Matsumura, T.; Yanagida, S.; Watanabe, N.; Kodama, S.; Kusano, M.; Yamamoto, N.; Kamada, R.; Suzuki, K.; Itami, K.; Hasebe, Y.; Fujita, N.; Kubota, S.; Usuki, A.; Okamoto, M.; Uno, S.; Chikuma, A.; Kishikawa, H.; Yano K Nakano, C.; Otaguro, M.; Kayashima, Y.; Shinoda, M.; Jaafar, S. M.; Baharuddin, S.; Gembor, J.; Ahmad, H.; Syed Mansor, S. M.; Abdullah, W. M.; Shafie, Z.; Muhamad Yunus, S.; Alwi, S. M.; Hussin, N.; Basri, N. A.; Ling Ling, L.; Naem, N. S.; Rutten, R.; Rademaker, H.; van Buijsen, M.; Scholten, M.; Stuij, S.; van Zeijst, M.; van Houwelingen, K.; Engelen, W.; Kramer, H.; Maassen, E.; Verhoeven, P.; Awater, J.; Terwisscha van Scheltinga, C.; Meijlis, P.; Blom, L.; Bos, M.; van der Wal, M.; van Laerhoven, G.; Jacobs, T.; Tan-Urgert, B.; van de Gaag, J.; den Boer, P.; Verlek, E.; Lardinois, R.; Coenjaerds, C.; Hendrick, R.; Schoep, J.; Froma, E.; van Nes, C.; Beuving, D.; Krikken, J.; Drent, I.; Geerlings, F.; Buvelot, S.; Wissenburg, A.; Dijkshoorn, A.; van Setten van der Meer, L.; Singerling, M.; van Wijk, D.; Bor, A.; Aukema-Wouda, Z.; Hendriks-van Woerden, M.; Kort, I.; Danse, I.; van der Knaap, M.; de Jong, C.; Temminck, M.; Schaefer, T.; van der Ven, N.; Drost, I.; Mulder, R.; de Vos, A.; de Hoop, M.; Post, G.; Wielandt, D.; Edorot, N.; de Castro, K.; Flotildes, M.; Mulingtapang, T.; Vasquez, S.; Facundo, S.; Peralta, M.; Jose, M.; Bandiez, J.; Sulit, P.; Joaquin, F.; Arbis, M. G.; Silva, C.; Delgado, D.; de Leon, R.; Maglasang, P.; Sian, A.; Alagban, C.; Alcorano, J.; Marcelo, M. J.; Dela Pena, C.; Hyra, I.; Malkiewicz, B.; Mosakowska, K.; Cana, I.; Dobrin, I.; Lautaru, A.; Manescu, G.; Samoila, N.; Lacatus, M.; Apostoie, A.; Prunoiu, M.; Tilinca, M.; Budeanu, A.; Nedelcu, C.; Dumitrache, N.; Boeru, L.; Zhuravleva, E.; Gundova, M.; Hoffmannova, J.; Svitkova, M.; Pekarova, T.; Ujacka, K.; Zsoriova, T.; Kubincova, K.; Jankovicova, Z.; Talliard, C.; Tyumbu, N.; Mngoma, N.; Kannemeyer, M.; Mostert, J.; Page, A.; Krahenbuhl, C.; Tredoux, C.; Hendricks, L.; Oliver, S.; Le Grange, M.; Naidoo, V.; Bae, Y.; Kim, H.; Lee, J.; Yu, N.; An, S.; Kim, E.; Yang, K.; Woo, J.; Kim, S.; Rasck, J.; Smetana, S.; Ajax, K.; Bylander, L.; Lindberg, A.; Dellborg, H.; Hultsberg-Olsson, G.; Harsmar, K.; Knutsson, A.; Håkansson, L.; Kåveryd-Holmström, M.; Lundmark, L. M.; Norrfors, B.; Löf, P.; Skoglund, K.; Torgersruud, M.; Johansson, K.; Mattsson, A.; Quist, M.; Haglund, P.; Lundell, L.; Gunvasdotter, S.; Rangman, B.; Liu, R.; Shi, J.; Förstedt, G.; Nylund, L.; Welin-Berger, B.; Nilsson, O.; Garcia-Värlid, A.; Forlenza, R.; Kaminska, K.; Nagorna, T.; Cottam, V.; Harper, R.; Gilchrist, M.; Musanhu, R.; Mackin, A.; Turner, A.; Willetts, S.; Cadd, A.; Evans, J.; Young, G.; Sevillano, A.; Brodie, K.; Eccles, A.; Kelly, S.; Doughty, A.; Gray, J.; Gibson, M.; Finlayson, M.; Domingo, D.; Brazee, L.; Renaud, K.; Doman, A.; Meyer, R.; Beatty, J.; Morgan, T.; Rodas, E.; Campbell, D.; Mcquarrie, M.; Battistelli, E.; Eisenbraun, P.; Farley, R.; Park, H.; Dwyer, J.; Adams, K.; Schneider, W.; Barbour, C.; Whyne, E.; Budzinski, S.; Craig, M.; Gilley Elmore, J.; Scott, D.; Bellini, S.; Pepper, M.; Gunderson, K.; Stipek, I.; Schwarz, L.; Watkins, K.; Moore, V.; Palao, A.; Keane-Richmond, P.; Franklin, L.; Ward, L.; Kostedt, G.; Bailey, S.; Hollenweger, L.; Solomon, A.; Johnson, D.; Gloer, K.; Meyer, M.; Boleyn, M.; Nieters, D.; Humphrey, K.; Bohn, A.; Mueller, G.; Mckenzie, H.; Edwards, T.; Velky, J.; Cole, C.; Diederick, M.; Burg, S.; Coulson, T.; Karunaratne, K.; Gunasekera, R.; Cook, S.; Fisher, S.; Garrison, K.; Passey, L.; Kuykendall, K.; Luck, K.; Ramia, L.; Joan, H.; Reynoso, F.; Farley, M.; Shuman, S.; Santana-Fernandes, E.; Ventimiglia, A.; Steele, V.; Gers, L.; Brown, P.; Wilson, J.; Freebersyser, J.; Reno, M.; Buettner, N.; McGovern, M.; Hubbard, T.; Elmore, H.; Payne, D.; Mccann, M.; Decker, S.; Sharp, A.; Forgey, E.; Broussard, E.; Juett, U.; Siddiqui, A.

    2017-01-01

    We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg

  18. The role of aspirin in women’s health

    Directory of Open Access Journals (Sweden)

    Verheugt FWA

    2011-06-01

    Full Text Available Freek WA Verheugt1, Antoinette C Bolte21Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG, Amsterdam, The Netherlands; 2VU University Medical Center, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Amsterdam, The NetherlandsBackground: The aim of this review is to discuss the role of aspirin for various conditions in women.Methods: A nonsystematic review of articles published on PubMed® that examines the role of aspirin in women.Results: Aspirin is associated with a significant reduction of stroke risk in women, which may be linked to age. However, despite this evidence, underutilization of aspirin in eligible women is reported. In women of reproductive age, it may also have a role to play in reducing early-onset preeclampsia and intrauterine growth restriction, and in the prevention of recurrent miscarriage in women with antiphospholipid antibodies; it may also reduce cardiovascular risk in associated systemic conditions such as lupus. Aspirin may reduce colorectal cancer risk in women, but its role in breast cancer warrants further data from controlled trials.Conclusions: The risk–benefit threshold for aspirin use in women has been established for several conditions. Reasons why women are less likely to be prescribed aspirin have not been established, but the overall underuse of aspirin in women needs to be addressed.Keywords: CVD, cancer, menopause, preeclampsia

  19. Synthesis, characterization and antibacterial activity of aspirin and ...

    African Journals Online (AJOL)

    Dr J. T. Ekanem

    Novel complexes of Co (11), Ni (11) and Fe (111) with aspirin and paracetamol have synthesized and characterized using infrared, electronic and Hnmr spectral, melting point and conductivity measurements. The two ligands have been found to act as bidentate chelating agents. Aspirin complexes coordinate through the ...

  20. Aspirin plus Heparin or Aspirin Alone in Women with Recurrent Miscarriage

    NARCIS (Netherlands)

    Kaandorp, Stef P.; Goddijn, Mariette; van der Post, Joris A. M.; Hutten, Barbara A.; Verhoeve, Harold R.; Hamulyak, Karly; Mol, Ben Willem; Folkeringa, Nienke; Nahuis, Marleen; Papatsonis, Dimitri N. M.; Buller, Harry R.; van der Veen, Fulco; Middeldorp, Saskia

    2010-01-01

    BACKGROUND Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS In this randomized

  1. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

    NARCIS (Netherlands)

    Kaandorp, Stef P.; Goddijn, Mariëtte; van der Post, Joris A. M.; Hutten, Barbara A.; Verhoeve, Harold R.; Hamulyák, Karly; Mol, Ben Willem; Folkeringa, Nienke; Nahuis, Marleen; Papatsonis, Dimitri N. M.; Büller, Harry R.; van der Veen, Fulco; Middeldorp, Saskia

    2010-01-01

    Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. In this randomized trial, we enrolled 364

  2. High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations -NDASH- a prospective cohort study

    DEFF Research Database (Denmark)

    Bjerregaard, Asger; Laing, Ingrid A; Backer, Vibeke

    2017-01-01

    BACKGROUND: The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus...... the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils > 1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI 1.6-35.2, p=0.010), as did having FeNO > 25 ppb (HR 3.4 95% CI 1.1-10.4, p=0.033). This article...... is protected by copyright. All rights reserved....

  3. Acute bacterial exacerbations in bronchitis and asthma.

    Science.gov (United States)

    Chodosh, S

    1987-04-27

    Symptomatic exacerbations are frequent problems in the management of chronic bronchitis and bronchial asthma. Identification of a bacterial etiology as the cause of specific exacerbations should be based on changes in clinical symptoms and documentation of significant bronchial bacterial flora and a neutrophilic inflammatory response. Most acute bacterial exacerbations in patients with bronchitis or asthma are caused by Hemophilus influenzae, Streptococcus pneumoniae, or Branhamella catarrhalis. Treatment with ampicillins, synthetic tetracyclines, or trimethoprim/sulfamethoxazole is successful in 80 to 90 percent of bacterial exacerbations. Emergence of resistant Hemophilus species and pneumococci motivates development of new orally administered antimicrobial drugs. Appropriate treatment depends on the prompt recognition that bacterial infection is present. Once instituted, antimicrobial therapy should be continued for a minimum of 10 to 14 days, which should increase the duration of the infection-free period until the next bacterial exacerbation. Adequate response should be evaluated by the return of symptoms to pre-infectious levels and by decreased sputum bacterial flora and neutrophilic inflammation.

  4. Aspirin as a Chemopreventive Agent for Cancer: a New Hope?

    Directory of Open Access Journals (Sweden)

    Isnatin Miladiyah

    2016-01-01

    Full Text Available Introduction: inflammation has been shown to play a major role in the pathogenesis of cancer. Inflammatory process activates the immune system through pro-inflammatory mediators and subsequent triggers transformation into malignant cells. Some tumors or cancers has been associated with chronic infections, such as hepatitis B and C viruses (hepatocellular carcinoma, human papilloma virus (cervical cancer, Helicobacter pylori (gastric cancer and lymphoma, and prostatitis (prostate cancer. A considerable study have investigated the benefits of aspirin for the prevention and treatment of cancer or tumors. Objectives: This paper aims to describe the relationship between inflammation and cancer incidence, so that use of aspirin as an anti-inflammatory agent is a rational choice in the treatment and prevention of cancer. Conclusion: Aspirin potential for chemoprevention of various types of cancer. Considering the high risk of side effects of aspirin, aspirin is not intended as a routine therapy to prevent the occurrence of cancer.

  5. Monitoring aspirin therapy with the Platelet Function Analyzer-100

    DEFF Research Database (Denmark)

    Mortensen, Jette; Poulsen, Tina Svenstrup; Grove, Erik Lerkevang

    2008-01-01

    . The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin....... MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before...... aspirin treatment in healthy subjects. Serum-thromboxane B(2) (S-TxB(2)) was measured to assess compliance. RESULTS: In healthy volunteers not receiving aspirin, duplicate measurements resulted in coefficients of variation (CV) of 7.9 % for the PFA-100 and 5.2 % for OPA. During aspirin treatment, CVs were...

  6. Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Mackey, W.C.; Connolly, R.J.; Callow, A.D.; Keough, E.M.; Ramberg-Laskaris, K.; McCullough, J.L.; O' Donnell, T.F. Jr.; Melaragno, A.; Valeri, C.R.; Weiblen, B.

    1984-07-01

    The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency.

  7. Is aspirin a cause of Reye's syndrome? A case against.

    Science.gov (United States)

    Orlowski, James P; Hanhan, Usama A; Fiallos, Mariano R

    2002-01-01

    Reye's syndrome was a rare disease which appeared suddenly in the early 1950s and disappeared just as suddenly in the late 1980s. An association between Reye's syndrome and the ingestion of aspirin (acetylsalicylic acid) was claimed, although no proof of causation was ever established. The presence of salicylates in the blood or urine of Reye's syndrome patients has not been demonstrated, and no animal model of Reye's syndrome has been developed where aspirin causes the disease. It is clear from epidemiological data that the incidence of Reye's syndrome was decreasing well before warning labels were placed on aspirin products. Reye's syndrome disappeared from countries where aspirin was not used in children as well as from countries which continued to use aspirin in children. Reye's syndrome was probably either a viral mutation which spontaneously disappeared, or a conglomeration of metabolic disorders that had not been recognized or described at that time.

  8. Willow species and aspirin: different mechanism of actions.

    Science.gov (United States)

    Vlachojannis, J; Magora, F; Chrubasik, S

    2011-07-01

    Many believe that willow is the natural source of aspirin. However, willow species contain only a low quantity of the prodrug salicin which is metabolized during absorption into various salicylate derivatives. If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia. Salicylic acid concentrations following an analgesic dose of aspirin are an order of magnitude higher. Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-inflammatory effect. The multi-component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    Science.gov (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

    Science.gov (United States)

    Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

    2011-01-01

    Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

  11. Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

    Science.gov (United States)

    Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.

  12. Aspirin: History and Applications; Cross-Curricular Instructional Strategies, Ideas, and Applications for Teaching about Aspirin in the Science Classroom

    Science.gov (United States)

    Hademenos, George

    2005-01-01

    Of the thousands of drugs and medicines available for the prevention, treatment, and control of human disease and discomfort, the most widely used is aspirin. The primary reason for aspirin's popularity is its capabilities as a pain reliever, fever reducer, and anti-inflammatory agent. This article explores the historical development of aspirin…

  13. Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems.

    Science.gov (United States)

    Tang, Yu; Singh, Jagdish

    2008-06-05

    The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (pdegradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.

  14. Acute exacerbation of asthma: a case report

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2011-09-01

    Full Text Available Asthma is a chronic inflammatory disease of the airways with a worldwide prevalence ranging from 1% to 18%. We report the case of a 43-year-old man with acute asthma exacerbation admitted to Emergency Department. All patients with asthma are at risk of having exacerbations characterised by worsening symptoms, airflow obstruction, and an increased requirement for rescue bronchodilators. Patients should be evaluated and triaged quickly to assess the presence of exacerbations and the need for urgent intervention. The goals of treatment may be summarised as maintenance of adequate oxygen saturation with supplemental oxygen, relief of airway obstruction with repetitive administration of rapid-acting inhaled bronchodilators, and treatment of airway inflammation with systemic corticosteroids.

  15. Comparative effect of clopidogrel and aspirin versus aspirin alone on laboratory parameters: a retrospective, observational, cohort study

    Science.gov (United States)

    2013-01-01

    Background Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Combination therapy of clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in patients in routine clinical practice. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters using a clinical database. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between November 2004 and April 2011, to identify cohorts of new users (n = 159) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and new users (n = 834) of aspirin alone (100 mg/day). We used a multivariable regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between settings, and compare the mean changes in serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and hematological parameters, including hemoglobin level, hematocrit, and white blood cell (WBC), red blood cell and platelet counts up to two months after the start of study drug administration. Results After adjustment, the reduction of WBC count in clopidogrel plus aspirin users was significantly greater than that in aspirin alone users. All other tests showed no statistically significant difference in the mean change from baseline to during the exposure period between clopidogrel plus aspirin users and aspirin alone users. The combination of clopidogrel and aspirin increased the risk of gastrointestinal bleeding compared with aspirin alone, with a relative risk ranging from 2.06 (95% CI, 1.02 to 4.13; p = 0.043) for the multivariate model and 2.61 (95% CI, 1.18 to 5.80; p = 0.0184) for propensity adjustment. Conclusion Our findings suggested that

  16. Respiratory Mechanics

    OpenAIRE

    Martin R. Miller

    2016-01-01

    Respiratory Mechanics by Theodore Wilson is a slim paperback volume (64 pages) describing three aspects of the way the lungs work: 1) pressure?volume relationships with regard to the lungs, 2) chest wall and muscles with regard to how the respiratory pump works, and 3) gas flow and transport. Relevant details about the author are missing, which I think is a loss. He is Emeritus Professor of Aerospace Engineering and Mechanics and this background and his expertise was a perfect fit for the inv...

  17. Climate change and respiratory health.

    Science.gov (United States)

    Gerardi, Daniel A; Kellerman, Roy A

    2014-10-01

    To discuss the nature of climate change and both its immediate and long-term effects on human respiratory health. This review is based on information from a presentation of the American College of Chest Physicians course on Occupational and Environmental Lung Disease held in Toronto, Canada, June 2013. It is supplemented by a PubMed search for climate change, global warming, respiratory tract diseases, and respiratory health. It is also supplemented by a search of Web sites including the Environmental Protection Agency, National Oceanic and Atmospheric Administration, World Meteorological Association, National Snow and Ice Data Center, Carbon Dioxide Information Analysis Center, Inter-Governmental Panel on Climate Change, and the World Health Organization. Health effects of climate change include an increase in the prevalence of certain respiratory diseases, exacerbations of chronic lung disease, premature mortality, allergic responses, and declines in lung function. Climate change, mediated by greenhouse gases, causes adverse health effects to the most vulnerable patient populations-the elderly, children, and those in distressed socioeconomic strata.

  18. Rhinovirus-associated pulmonary exacerbations show a lack of FEV1 improvement in children with cystic fibrosis.

    Science.gov (United States)

    Cousin, Mathias; Molinari, Nicolas; Foulongne, Vincent; Caimmi, Davide; Vachier, Isabelle; Abely, Michel; Chiron, Raphael

    2016-03-01

    Respiratory viral infections lead to bronchial inflammation in patients with cystic fibrosis, especially during pulmonary exacerbations. The aim of this study was to determine the impact of viral-associated pulmonary exacerbations in children with cystic fibrosis and failure to improve forced expiratory volume in 1 s (FEV1 ) after an appropriate treatment. We lead a pilot study from January 2009 until March 2013. Children with a diagnosis of cystic fibrosis were longitudinally evaluated three times: at baseline (Visit 1), at the diagnosis of pulmonary exacerbation (Visit 2), and after exacerbation treatment (Visit 3). Nasal and bronchial samples were analyzed at each visit with multiplex viral respiratory PCR panel (qualitative detection of 16 viruses). Pulmonary function tests were recorded at each visit, in order to highlight a possible failure to improve them after treatment. Lack of improvement was defined by an increase in FEV1 less than 5% between Visit 2 and Visit 3. Eighteen children were analyzed in the study. 10 patients failed to improve by more than 5% their FEV1 between Visit 2 and Visit 3. Rhinovirus infection at Visit 2 or Visit 3 was the only risk factor significantly associated with such a failure (OR, 12; 95% CI, 1·3-111·3), P = 0·03. Rhinovirus infection seems to play a role in the FEV1 recovery after pulmonary exacerbation treatment in children with cystic fibrosis. Such an association needs to be confirmed by a large-scale study because this finding may have important implications for pulmonary exacerbation management. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  19. [Aspirin hypersensitivity: characteristics and diagnostic approach].

    Science.gov (United States)

    Baudrand, H; Zaouche, S; Dubost, R; Carsin, A; Chatte, G; Freymond, N; Piperno, D; Dubreuil, C; Froehlich, P; Pacheco, Y; Devouassoux, G

    2015-03-01

    In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. To compare asthmatics with and without AH. The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  20. Beclin 1 acetylation impairs the anticancer effect of aspirin in colorectal cancer cells

    OpenAIRE

    Sun, Ting; Ming, Liang; Yan, Yunmeng; Zhang, Yan; Xue, Haikuo

    2017-01-01

    Regular use of aspirin can reduce cancer incidence, recurrence, metastasis and cancer-related mortality. Aspirin suppresses proliferation and induces apoptosis and autophagy in colorectal cancer cells, but the precise mechanism is not clear. In this study, we demonstrated that aspirin induced autophagosome formation in colorectal cancer cells, but autophagic degradation was blocked through aspirin-mediated Beclin 1 acetylation. Blocked autophagic degradation weakened aspirin-induced cell deat...

  1. Respiratory Support

    African Journals Online (AJOL)

    can be caused by inappropriate mechanical ventilation. This soft-cover review of the current practice of appropriate respiratory support is not controversia(it describes in an easily readable and concise fashio-n the development, physiological implications, mechanical and technological basis, safety aspects and careful ...

  2. Mechanistic insights into a classic wonder drug--aspirin.

    Science.gov (United States)

    Lei, Jinping; Zhou, Yanzi; Xie, Daiqian; Zhang, Yingkai

    2015-01-14

    Aspirin, one of the oldest and most common anti-inflammatory agents, has recently been shown to reduce cancer risks. The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidated. In this work, we have filled this gap by employing a state-of-the-art computational approach, Born-Oppenheimer molecular dynamics simulations with ab initio quantum mechanical/molecular mechanical potential and umbrella sampling. Our studies have characterized a substrate-assisted inhibition mechanism for aspirin acetylating COX: it proceeds in two successive stages with a metastable tetrahedral intermediate, in which the carboxyl group of aspirin serves as the general base. The computational results confirmed that aspirin would be 10-100 times more potent against COX-1 than against COX-2, and revealed that this inhibition specificity between the two COX isoforms can be attributed mainly to the difference in kinetics rate of the covalent inhibition reaction, not the aspirin-binding step. The structural origin of this differential inhibition of the COX enzymes by aspirin has also been elucidated.

  3. Mode of action of aspirin as a chemopreventive agent.

    Science.gov (United States)

    Dovizio, Melania; Bruno, Annalisa; Tacconelli, Stefania; Patrignani, Paola

    2013-01-01

    Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses.

  4. The complexity of managing COPD exacerbations: a grounded theory study of European general practice.

    Science.gov (United States)

    Risør, Mette Bech; Spigt, Mark; Iversen, R; Godycki-Cwirko, M; Francis, N; Altiner, A; Andreeva, E; Kung, K; Melbye, H

    2013-12-05

    To understand the concerns and challenges faced by general practitioners (GPs) and respiratory physicians about primary care management of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). 21 focus group discussions (FGDs) were performed in seven countries with a Grounded Theory approach. Each country performed three rounds of FGDs. Primary and secondary care in Norway, Germany, Wales, Poland, Russia, The Netherlands, China (Hong Kong). 142 GPs and respiratory physicians were chosen to include urban and rural GPs as well as hospital-based and out patient-clinic respiratory physicians. Management of acute COPD exacerbations is dealt with within a scope of concerns. These concerns range from 'dealing with comorbidity' through 'having difficult patients' to 'confronting a hopeless disease'. The first concern displays medical uncertainty regarding diagnosis, medication and hospitalisation. These clinical processes become blurred by comorbidity and the social context of the patient. The second concern shows how patients receive the label 'difficult' exactly because they need complex attention, but even more because they are time consuming, do not take responsibility and are non-compliant. The third concern relates to the emotional reactions by the physicians when confronted with 'a hopeless disease' due to the fact that most of the patients do not improve and the treatment slows down the process at best. GPs and respiratory physicians balance these concerns with medical knowledge and practical, situational knowledge, trying to encompass the complexity of a medical condition. Knowing the patient is essential when dealing with comorbidities as well as with difficult relations in the consultations on exacerbations. This study suggests that it is crucial to improve the collaboration between primary and secondary care, in terms of, for example, shared consultations and defined work tasks, which may enhance shared knowledge of patients

  5. The complexity of managing COPD exacerbations: a grounded theory study of European general practice

    Science.gov (United States)

    Risør, Mette Bech; Spigt, Mark; Iversen, R; Godycki-Cwirko, M; Francis, N; Altiner, A; Andreeva, E; Kung, K; Melbye, H

    2013-01-01

    Objectives To understand the concerns and challenges faced by general practitioners (GPs) and respiratory physicians about primary care management of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Design 21 focus group discussions (FGDs) were performed in seven countries with a Grounded Theory approach. Each country performed three rounds of FGDs. Setting Primary and secondary care in Norway, Germany, Wales, Poland, Russia, The Netherlands, China (Hong Kong). Participants 142 GPs and respiratory physicians were chosen to include urban and rural GPs as well as hospital-based and out patient-clinic respiratory physicians. Results Management of acute COPD exacerbations is dealt with within a scope of concerns. These concerns range from ‘dealing with comorbidity’ through ‘having difficult patients’ to ‘confronting a hopeless disease’. The first concern displays medical uncertainty regarding diagnosis, medication and hospitalisation. These clinical processes become blurred by comorbidity and the social context of the patient. The second concern shows how patients receive the label ‘difficult’ exactly because they need complex attention, but even more because they are time consuming, do not take responsibility and are non-compliant. The third concern relates to the emotional reactions by the physicians when confronted with ‘a hopeless disease’ due to the fact that most of the patients do not improve and the treatment slows down the process at best. GPs and respiratory physicians balance these concerns with medical knowledge and practical, situational knowledge, trying to encompass the complexity of a medical condition. Conclusions Knowing the patient is essential when dealing with comorbidities as well as with difficult relations in the consultations on exacerbations. This study suggests that it is crucial to improve the collaboration between primary and secondary care, in terms of, for example, shared consultations

  6. Acute exacerbation of airspace enlargement with fibrosis

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kakugawa

    2014-01-01

    Full Text Available In 2008, Kawabata et al. described a lesion which they termed “airspace enlargement with fibrosis” that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6 for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation.

  7. The effects of real-time telemedicine consultations between hospital based nursing and severe COPD patients discharged after exacerbation admission

    DEFF Research Database (Denmark)

    Hounsgaard, Lise; Sorknæs, Anne Dichmann; Madsen, H.

    2014-01-01

    We investigated the effect of daily real-time teleconsultations for one week between hospital-based nurses specialised in respiratory diseases and patients with severe COPD discharged after acute exacerbation. Patients admitted with acute exacerbation of chronic obstructive pulmonary disease...... or mean number of readmission days with AECOPD calculated at 4, 8, 12 and 26 weeks. Thus the addition of one week of teleconsultations between hospital-based nurses and patients with severe COPD discharged after hospitalisation did not significantly reduce readmissions or affect mortality....

  8. Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  9. A novel microbiota stratification system predicts future exacerbations in bronchiectasis.

    Science.gov (United States)

    Rogers, Geraint B; Zain, Nur Masirah M; Bruce, Kenneth D; Burr, Lucy D; Chen, Alice C; Rivett, Damian W; McGuckin, Michael A; Serisier, David J

    2014-05-01

    Although airway microbiota composition correlates with clinical measures in non-cystic fibrosis bronchiectasis, these data are unlikely to provide useful prognostic information at the individual patient level. A system enabling microbiota data to be applied clinically would represent a substantial translational advance. This study aims to determine whether stratification of patients according to the predominant microbiota taxon can provide improved clinical insight compared with standard diagnostics. The presence of bacterial respiratory pathogens was assessed in induced sputum from 107 adult patients by culture, quantitative PCR, and, in 96 samples, by ribosomal gene pyrosequencing. Prospective analysis was performed on samples from 42 of these patients. Microbiological data were correlated with concurrent clinical measures and subsequent outcomes. Microbiota analysis defined three groups: Pseudomonas aeruginosa dominated (n = 26), Haemophilus influenzae dominated (n = 34), and other taxa dominated (n = 36). Patients with P. aeruginosa- and H. influenzae-dominated communities had significantly worse lung function, higher serum levels of C-reactive protein (CRP), and higher sputum levels of IL-8 and IL-1β. Predominance of P. aeruginosa, followed by Veillonella species, was the best predictor of future exacerbation frequency, with H. influenzae-dominated communities having significantly fewer episodes. Detection of P. aeruginosa was associated with poor lung function and exacerbation frequency, irrespective of analytical strategy. Quantitative PCR revealed significant correlations between H. influenzae levels and sputum IL-8, IL-1β, and serum CRP. Genus richness was negatively correlated with 24-hour sputum weight, age, serum CRP, sputum IL-1β, and IL-8. Stratification of patients with non-cystic fibrosis bronchiectasis on the basis of predominant bacterial taxa is more clinically informative than either conventional culture or quantitative PCR-based analysis

  10. Aspirin and clonidine in non-cardiac surgery

    DEFF Research Database (Denmark)

    Garg, Amit; Kurz, Andrea; Sessler, Daniel I

    2014-01-01

    INTRODUCTION: Perioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce...... and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome. ETHICS AND DISSEMINATION: The authors were competitively awarded a grant...

  11. Living with Respiratory Failure

    Science.gov (United States)

    ... Research Home / Respiratory Failure Respiratory Failure What Is Respiratory (RES-pih-rah-tor- ... injure your lungs. Normal Lungs and Conditions Causing Respiratory Failure Figure A shows the location of the ...

  12. What Causes Respiratory Failure?

    Science.gov (United States)

    ... Research Home / Respiratory Failure Respiratory Failure What Is Respiratory (RES-pih-rah-tor- ... injure your lungs. Normal Lungs and Conditions Causing Respiratory Failure Figure A shows the location of the ...

  13. Comparative effects of aspirin and enteric-coated aspirin on loss of chromium 51-labeled erythrocytes from the gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, D.C.; Schwartz, R.S.; Kutny, K.; Vallejo, G.; Horton, E.S.; Cotter, J.M.

    1984-01-01

    Sodium chromate Cr 51 was used to label red blood cells of 19 healthy male volunteers, whose stools were collected for four days before and four days during oral administration of either uncoated (N . 9) or enteric-coated (N . 10) aspirin. Each subject received 2.925 gm/day of aspirin, in three equal doses separated by eight-hour intervals, for a total of seven days. During drug use, stools were collected on days 4 through 7. Fecal blood content, estimated by measuring radioactivity in the stools, was significantly higher (P less than 0.001) during use of either type of aspirin than at baseline, but losses measured during use of the coated aspirin (mean, 1.54 ml/day) were significantly lower (P less than 0.001) than those measured during use of the uncoated aspirin (mean, 4.33 ml/day). The two types of aspirin produced equivalent serum concentrations of salicylates. We conclude that enteric-coated aspirin reduces gastrointestinal blood loss.

  14. Prevalence and risk of viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease: a meta-analysis.

    Science.gov (United States)

    Wu, Xiaodong; Chen, Du; Gu, Xiaoling; Su, Xin; Song, Yong; Shi, Yi

    2014-07-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) lead to substantial morbidity and mortality. Viral infections could be an important cause of acute exacerbations of COPD (AECOPD) and only a few studies report the prevalence of respiratory viruses on this disease. We aimed to update the review on the prevalence of respiratory viral infection in patients with AECOPD with a meta-analysis. We reviewed the prevalence of respiratory viruses on this disease by searching PubMed systematically to identify primary studies published from Jan 1990 to March 2012. Studies met with seven criteria were extracted for meta-analysis. A total of 17 studies were eligible for the meta-analysis. Weighted overall prevalence of respiratory viruses in patients with AECOPD was 39.3% (95% CI 36.9-41.6) with a high degree of a heterogeneity (I (2) > 75%). In contrast, the rate in stable COPD patients from four studies was 13.6% (95% CI 9.0-18.2) without any apparent heterogeneity. Pooled risk ratio for respiratory viral infection was 4.1 (95% CI 2.0-8.5) for AECOPD as compared with stable COPD. Rhinovirus was the most common virus and with a weighted prevalence of 14.8% (95% CI 13.3-16.5). Respiratory viruses probably are important etiological agents in patients with AECOPD as compared with the stable COPD patients. This result would help to provide better strategies for management of AECOPD and health-care planning.

  15. Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation.

    Science.gov (United States)

    Toussaint, Marie; Jackson, David J; Swieboda, Dawid; Guedán, Anabel; Tsourouktsoglou, Theodora-Dorita; Ching, Yee Man; Radermecker, Coraline; Makrinioti, Heidi; Aniscenko, Julia; Edwards, Michael R; Solari, Roberto; Farnir, Frédéric; Papayannopoulos, Venizelos; Bureau, Fabrice; Marichal, Thomas; Johnston, Sebastian L

    2017-06-01

    Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or by degrading NETs with DNase protects mice from type-2 immunopathology. Furthermore, the injection of mouse genomic DNA alone is sufficient to recapitulate many features of rhinovirus-induced type-2 immune responses and asthma pathology. Thus, NETosis and its associated extracellular dsDNA contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations.

  16. 25-hydroxyvitamin D deficiency, exacerbation frequency and human rhinovirus exacerbations in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Quint Jennifer K

    2012-06-01

    Full Text Available Abstract Background 25-hydroxyvitamin D deficiency is associated with COPD and increased susceptibility to infection in the general population. Methods We investigated whether COPD patients deficient in 25-hydroxyvitamin D were more likely to be frequent exacerbators, had reduced outdoor activity and were more susceptible to human rhinovirus (HRV exacerbations than those with insufficient and normal levels. We also investigated whether the frequency of FokI, BsmI and TaqIα 25-hydroxyvitamin D receptor (VDR polymorphisms differed between frequent and infrequent exacerbators. Results There was no difference in 25-hydroxyvitamin D levels between frequent and infrequent exacerbators in the summer; medians 44.1nmol/L (29.1 – 68.0 and 39.4nmol/L (22.3 – 59.2 or winter; medians 24.9nmol/L (14.3 – 43.1 and 27.1nmol/L (19.9 – 37.6. Patients who spent less time outdoors in the 14 days prior to sampling had lower 25-hydroxyvitamin D levels (p = 0.02. Day length was independently associated with 25-hydroxyvitamin D levels (p = 0.02. There was no difference in 25-hydroxyvitamin D levels between baseline and exacerbation; medians 36.2nmol/L (IQR 22.4-59.4 and 33.3nmol/L (23.0-49.7; p = 0.43. HRV positive exacerbations were not associated with lower 25-hydroxyvitamin D levels at exacerbation than exacerbations that did not test positive for HRV; medians 30.0nmol/L (20.4 – 57.8 and 30.6nmol/L (19.4 – 48.7. There was no relationship between exacerbation frequency and any VDR polymorphisms (all p > 0.05. Conclusions Low 25-hydroxyvitamin D levels in COPD are not associated with frequent exacerbations and do not increase susceptibility to HRV exacerbations. Independent of day length, patients who spend less time outdoors have lower 25-hydroxyvitamin D concentration.

  17. Flexible semiparametric joint modeling: an application to estimate individual lung function decline and risk of pulmonary exacerbations in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Dan Li

    2017-11-01

    Full Text Available Abstract Background Epidemiologic surveillance of lung function is key to clinical care of individuals with cystic fibrosis, but lung function decline is nonlinear and often impacted by acute respiratory events known as pulmonary exacerbations. Statistical models are needed to simultaneously estimate lung function decline while providing risk estimates for the onset of pulmonary exacerbations, in order to identify relevant predictors of declining lung function and understand how these associations could be used to predict the onset of pulmonary exacerbations. Methods Using longitudinal lung function (FEV1 measurements and time-to-event data on pulmonary exacerbations from individuals in the United States Cystic Fibrosis Registry, we implemented a flexible semiparametric joint model consisting of a mixed-effects submodel with regression splines to fit repeated FEV1 measurements and a time-to-event submodel for possibly censored data on pulmonary exacerbations. We contrasted this approach with methods currently used in epidemiological studies and highlight clinical implications. Results The semiparametric joint model had the best fit of all models examined based on deviance information criterion. Higher starting FEV1 implied more rapid lung function decline in both separate and joint models; however, individualized risk estimates for pulmonary exacerbation differed depending upon model type. Based on shared parameter estimates from the joint model, which accounts for the nonlinear FEV1 trajectory, patients with more positive rates of change were less likely to experience a pulmonary exacerbation (HR per one standard deviation increase in FEV1 rate of change = 0.566, 95% CI 0.516–0.619, and having higher absolute FEV1 also corresponded to lower risk of having a pulmonary exacerbation (HR per one standard deviation increase in FEV1 = 0.856, 95% CI 0.781–0.937. At the population level, both submodels indicated significant effects of birth

  18. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  19. The Role of Platelet and its Interaction with Aspirin

    Directory of Open Access Journals (Sweden)

    Luisa Fernanda Zúñiga Cerón

    2016-04-01

    Conclusion. It is recognized the role of platelet in different physiopathological processes and thus its interaction with aspirin, preventing its aggregation and thrombus formation in the spleen and other organs, this way contributing to the prevention of future cardiovascular events.

  20. Perioperative aspirin and clonidine and risk of acute kidney injury

    DEFF Research Database (Denmark)

    Garg, Amit X; Kurz, Andrea; Sessler, Daniel I

    2014-01-01

    IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain...... and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905...... patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days...

  1. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Mickley, Hans; Korsholm, Lars

    2007-01-01

    INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had...... platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week...... period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  2. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

    DEFF Research Database (Denmark)

    Weitz, Jeffrey I; Lensing, Anthonie W A; Prins, Martin H

    2017-01-01

    BACKGROUND: Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. METHODS: In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous...... thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months...... in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio...

  3. Can an Aspirin a Day Keep a Pregnancy Complication Away?

    Science.gov (United States)

    ... html Can an Aspirin a Day Keep a Pregnancy Complication Away? Odds of preeclampsia dropped 62 percent for ... suggests. "Preeclampsia is one of the most serious complications of pregnancy, with a high risk of death for the ...

  4. Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations

    Directory of Open Access Journals (Sweden)

    Gundu H. R. Rao

    2012-01-01

    Full Text Available Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor “at-risk” individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies.

  5. Aspirin resistance: Prevalence and clinical outcome in Egypt

    Directory of Open Access Journals (Sweden)

    Ahmed Salah

    2015-04-01

    Results: Prevalence of aspirin resistance was 48% in our study group. Aspirin resistance was significantly higher in patients with family history of CAD (p = 0.044, smoking (p = 0.011, history of MI (p = 0.024, history of percutaneous coronary intervention (PCI (p = 0.001, and concomitant NSAIDs intake (p = 0.047. Moreover, aspirin resistance was more common among patients with multi-vessel CAD (p = 0.024. Aspirin-resistant patients had a significantly higher rate of UA (p = 0.001 and all major adverse cardiac events (MACE (p < 0.001.

  6. [Study of aspirin and its interaction with DNA by Raman and UV spectroscopies].

    Science.gov (United States)

    Kang, Qian-qian; Zhou, Guang-ming

    2012-03-01

    Normal Raman spectroscopy and surface-enhanced Raman spectroscopy of aspirin and aspirin tablet were reported, and the vibrational and enhanced peaks were assigned; the interaction of aspirin with DNA was investigated by SERS and UV. The results showed that NRS and SERS of aspirin and aspirin tablet were consistent basically, which indicated that excipient hardly affected the detection of aspirin; in SERS, aspirin was absorbed perpendicularly on silver colloid through the carboxyl group and the benzene ring; The interaction was mainly caused by the inserting-action mode between aspirin and DNA, and the benzene ring and C=O of aspirin were inserted between the base pair of the double helix structure of DNA, which provided important information and useful reference for understanding deeply the mechanism of action of this kind of drug.

  7. Novel Resveratrol-Based Aspirin Prodrugs: Synthesis, Metabolism, and Anticancer Activity.

    Science.gov (United States)

    Zhu, Yingdong; Fu, Junsheng; Shurlknight, Kelly L; Soroka, Dominique N; Hu, Yuhui; Chen, Xiaoxin; Sang, Shengmin

    2015-08-27

    Regular aspirin use has been convincingly shown to reduce the risk of colorectal cancer. However, long-term use of aspirin leads to gastrotoxicity. Herein, we designed and synthesized a novel class of resveratrol-based aspirin prodrugs to simultaneously release aspirin and resveratrol to attenuate the side effects caused by aspirin. Prodrug RAH exerted enhanced anticancer activities which are better than a physical mixture of aspirin and resveratrol as well as each individually. Metabolism of RAH in mice showed that the majority of RAH is decomposed to release resveratrol and aspirin or salicylic acid either in the intestine or after absorption. Mechanistic studies demonstrate RAH inhibits cell cycle arrest through downregulation of cyclins and induces apoptosis by activation of caspase-3 in cancer cells. These findings highlighted the improved anticancer properties of resveratrol-based aspirin prodrugs. RAH may represent novel and safe alternatives of aspirin for the purpose of daily use in the future.

  8. Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen

    2015-01-01

    (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P history of respiratory infections (6.8 vs 1.4%, P disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did......BACKGROUND AND OBJECTIVE: We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). METHODS: Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD...... and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We...

  9. Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD

    Directory of Open Access Journals (Sweden)

    Wilson R

    2015-06-01

    Full Text Available Robert Wilson,1 Antonio Anzueto,2 Marc Miravitlles,3 Pierre Arvis,4 Daniel Haverstock,5 Mila Trajanovic,6 Sanjay Sethi7 1Host Defence Unit, Royal Brompton Hospital, London, UK; 2University of Texas Health Science Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 3Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Bayer HealthCare Pharmaceuticals, Loos, France; 5Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA; 6Bayer HealthCare Pharmaceuticals, Toronto, ON, Canada; 7University at Buffalo, Buffalo, NY, USA Background: Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old outpatients with acute Anthonisen type 1 exacerbations.Trial registration: NCT00656747.Methods: Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease trial (MAESTRAL database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT and 8 weeks posttherapy.Results: The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8

  10. Antiplatelet effects of aspirin in chronic kidney disease patients.

    Science.gov (United States)

    Polzin, A; Dannenberg, L; Sansone, R; Levkau, B; Kelm, M; Hohlfeld, T; Zeus, T

    2016-02-01

    ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale. The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events. Chronic kidney disease (CKD) is suggested to affect the pharmacodynamic response to antiplatelet medication. High on-treatment platelet reactivity (HTPR) to clopidogrel has been reported to partially account for the enhanced risk of death and cardiovascular events in CKD patients. Objective To investigate the antiplatelet effects of aspirin in patients with CKD. We conducted a cross-sectional study in 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. HTPR to aspirin was more frequent in patients with impaired renal function (47% vs. 22%; odds ratio, 3.16; 95% confidence interval [CI], 1.34-7.41; P = 0.008). The pharmacodynamic response to aspirin was impaired in patients with moderate/severe CKD (92; interquartile range [IQR], 282 ng mL(-1) ) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL(-1) ; difference in medians, 57; CI, 5-110 ng mL(-1) ; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = -0.303; R(2) = 0.092; P = 0.001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis revealed that the correlation was independent of age (R = -0.314; R(2) = 0.082; P = 0.002) and gender (R = -0.305; R(2) = 0.077; P = 0.006). Renal function is correlated with pharmacodynamic response to

  11. Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin

    Science.gov (United States)

    Grosser, Tilo; Fries, Susanne; Lawson, John A.; Kapoor, Shiv C.; Grant, Gregory R.; FitzGerald, Garret A.

    2013-01-01

    Background Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of “aspirin resistance” has emerged and estimates of its incidence have varied remarkably. We aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes. Methods and Results Healthy volunteers (n=400) were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin's molecular target, cyclooxygenase-1. Individuals who appeared “aspirin resistant” on one occasion underwent repeat testing and if still “resistant” were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each. Variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo. Conclusions Pharmacological resistance to aspirin is rare; this study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT00948987. PMID:23212718

  12. 'Aspirin resistance' or treatment non-compliance: Which is to blame for cardiovascular complications?

    Directory of Open Access Journals (Sweden)

    Shantsila Eduard

    2008-08-01

    Full Text Available Abstract Aspirin is one of the 'cornerstone' drugs in our current management of cardiovascular disorders. However, despite the prescription of aspirin recurrent vascular events still occur in 10–20% of patients. These, data together with the observations of diminished antiaggregatory response to aspirin in some subjects have provided the basis of the current debate on the existence of so-called "aspirin resistance". Unfortunately, many of the tests employed to define 'aspirin resistance' lack sufficient sensitivity, specificity, and reproducibility. The prevalence of 'aspirin resistance' as defined by each test varies widely, and furthermore, the value of a single point estimate measure of aspirin resistance is questionable. The rate of 'aspirin resistance' is law if patients observed to ingest aspirin, with large proportion of patients to be pseudo-'aspirin resistant', due to non-compliance. What are the implications for clinical practice? Possible non-adherence to aspirin prescription should also be carefully considered before changing to higher aspirin doses, other antiplatelet drugs (e.g. clopidogrel or even combination antiplatelet drug therapy. Given the multifactorial nature of atherothrombotic disease, it is not surprising that only about 25% of all cardiovascular complications can usually be prevented by any single medication. We would advocate against routine testing of platelet sensitivity to aspirin (as an attempt to look for 'aspirin resistance' but rather, to highlight the importance of clinicians and public attention to the problem of treatment non-compliance.

  13. Aspirin for primary prevention of cardiovascular disease in diabetes mellitus

    OpenAIRE

    Pignone, Michael; Williams, Craig D.

    2010-01-01

    Aspirin is effective for the prevention of cardiovascular events in patients with a history of vascular disease, as so-called secondary prevention. In general populations with no history of previous myocardial infarction or stroke, aspirin also seems useful for primary prevention of cardiovascular events, although the absolute benefits are smaller than those seen in patients with previous cardiovascular disease. Patients with diabetes mellitus are at an increased risk of cardiovascular events...

  14. An Efficient Microscale Procedure for the Synthesis of Aspirin

    Science.gov (United States)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

    The synthesis of aspirin is a part of many undergraduate organic synthesis labs and is frequently used in qualitative organic analysis laboratory for the identification of salicylic acid. We have found that aspirin can be synthesized on microscale by a simple and efficient procedure that eliminates the heating step employed in literature procedures and gives a pure, ferric-negative product (no purple color with alcoholic ferric chloride solution).

  15. A Review on the Relationship between Aspirin and Bone Health

    OpenAIRE

    Chin, Kok-Yong

    2017-01-01

    Aspirin is a cyclooxygenase inhibitor commonly used in primary prevention of cardiovascular diseases and cancers. Its users are elderly population susceptible to osteoporosis. It also inhibits the synthesis of prostaglandin E2 essential in bone remodeling. This prompts the question whether it can influence bone health among users. This review aimed to summarize the current literature on the use of aspirin on bone health. A literature search on experimental and clinical evidence on the effects...

  16. Aspirin Use and Mortality in Two Contemporary US Cohorts.

    Science.gov (United States)

    Huang, Wen-Yi; Daugherty, Sarah E; Shiels, Meredith S; Purdue, Mark P; Freedman, Neal D; Abnet, Christian C; Hollenbeck, Albert R; Hayes, Richard B; Silverman, Debra T; Berndt, Sonja I

    2018-01-01

    Daily aspirin use has been recommended for secondary prevention of cardiovascular disease, but its use for primary prevention remains controversial. We followed 440,277 men and women from the NIH-AARP Diet and Health Study (ages 50-71) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (ages 55-74) for mortality for 13 years on average. Frequency of aspirin use was ascertained through self-report, and cause of death by death certificates. We calculated multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis. We found a consistent U-shaped relationship between aspirin use and mortality in both studies, with differential risk patterns for cardiovascular mortality by disease history. Among individuals with a history of cardiovascular disease, daily aspirin use was associated with reduced cardiovascular mortality [HR = 0.78 (95% CI, 0.74, 0.82)]. However, among those without a previous history, we observed no protection for daily aspirin users [HR = 1.06 (1.02, 1.11)], and elevated risk of cardiovascular mortality for those taking aspirin twice daily or more [HR = 1.29 (1.19, 1.39)]. Elevated risk persisted even among participants who lived beyond 5 years of follow-up and used aspirin without other nonsteroidal antiinflammatory drugs [HR = 1.31 (1.17, 1.47)]. Results from these 2 large population-based US cohorts confirm the utility of daily aspirin use for secondary prevention of cardiovascular mortality; however, our data suggest that caution should be exercised in more frequent use, particularly among individuals without a history of cardiovascular disease.

  17. Effect of Aspirin on Fractalkine in Rats with Pulmonary Embolism ...

    African Journals Online (AJOL)

    Results: The serum levels of FKN, IL-8, TNF-α and IL-1β were significantly decreased by treatment with aspirin compared with the PE group (p < 0.05). Furthermore, mRNA expressions of lung FKN, TNF- α and IL-1β in PE group were markedly decreased by treatment with aspirin compared with that in PE group. PE-induced ...

  18. Mechanistic Insights into a Classic Wonder Drug?Aspirin

    OpenAIRE

    Lei, Jinping; Zhou, Yanzi; Xie, Daiqian; Zhang, Yingkai

    2014-01-01

    Aspirin, one of the oldest and most common anti-inflammatory agents, has recently been shown to reduce cancer risks. The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidated. In this work, we have filled this gap by employing a state-of-the-art computational approach, Born?Oppenheimer molecular dynami...

  19. Pneumonic vs nonpneumonic acute exacerbations of COPD.

    Science.gov (United States)

    Lieberman, David; Lieberman, Devora; Gelfer, Yevgenia; Varshavsky, Raiesa; Dvoskin, Bella; Leinonen, Maija; Friedman, Maureen G

    2002-10-01

    To describe and compare the background, clinical manifestations, disease course, and infectious etiologies of pneumonic acute exacerbations (PNAE) vs nonpneumonic acute exacerbations (NPAE) of COPD. A prospective, observational study. A tertiary university medical center in southern Israel. Twenty-three hospitalizations for PNAE and 217 hospitalizations for NPAE were included in the study. Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. Only a significant change in antibody titers or levels was considered diagnostic. No significant differences were found between the two groups for any of the parameters related to COPD or comorbidity. The clinical type of the exacerbation was not significantly different between the groups. Compared to NPAE, patients with PNAE had lower PO(2) values at hospital admission (p = 0.004) but higher rates of abrupt onset (p = 0.005), ICU admissions (p = 0.006), invasive mechanical ventilation (p = 0.01), mortality (p = 0.007), and longer hospital stay (p = 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (p = 0.001). Mixed infection was found in 13 patients with PNAE (59%) and in 59 patients with NPAE (39%; not significant [NS]). Viral etiology was identified in 18 patients with PNAE (78%) compared with 99 patients with NPAE (46%; p = 0.003). Pneumococcal etiology was found in 10 patients with PNAE (43%) and in 38 patients with NPAE (18%; p = 0.006). An atypical etiology was identified in 8 patients with PNAE (35%) and 64 patients with NPAE (30%; NS). Community-acquired pneumonia is common among patients hospitalized for an acute exacerbation of COPD and is generally manifested by more severe clinical and laboratory parameters. In PNAE, compared to NPAE, viral and pneumococcal etiologies are more common, but the rate of atypical pathogens is similar. The therapeutic significance of these findings

  20. Interaction of aspirin and vitamin C with bovine serum albumin.

    Science.gov (United States)

    Nafisi, Shohreh; Bagheri Sadeghi, Golshan; PanahYab, Ataollah

    2011-12-02

    Vitamin C (L-ascorbic acid) has a major biological role as a natural antioxidant. Aspirin belongs to the nonsteroidal anti-inflammatory drugs and functions as an antioxidant via its ability to scavenge-OH radicals. Bovine serum albumin (BSA) is the major soluble protein constituent of the circulatory system and has many physiological functions including transport of a variety of compounds. In this report, the competitive binding of vitamin C and aspirin to bovine serum albumin has been studied using constant protein concentration and various drug concentrations at pH 7.2. FTIR and UV-Vis spectroscopic methods were used to analyze vitamin C and aspirin binding modes, the binding constants and the effects of drug complexation on BSA stability and conformation. Spectroscopic evidence showed that vitamin C and aspirin bind BSA via hydrophilic interactions (polypeptide and amine polar groups) with overall binding constants of K(vitamin C-BSA)=1.57×10(4)M(-1) and K(aspirin-BSA)=1.15×10(4)M(-1); assuming that there is one drug molecule per protein. The BSA secondary structure was altered with major decrease of α-helix from 64% (free protein) to 57% (BSA-vitamin C) and 54% (BSA-aspirin) and β-sheet from 15% (free protein) to 6-7% upon drug complexation, inducing a partial protein destabilization. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Aspirin resistance as cardiovascular risk after kidney transplantation

    Science.gov (United States)

    Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

    2014-05-01

    International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  2. European guidelines on perioperative venous thromboembolism prophylaxis: Aspirin.

    Science.gov (United States)

    Jenny, Jean-Yves; Pabinger, Ingrid; Samama, Charles Marc

    2018-02-01

    : There is a good rationale for the use of aspirin in venous thromboembolism prophylaxis in some orthopaedic procedures, as already proposed by the 9th American College of Chest Physicians' guidelines (Grade 1C). We recommend using aspirin, considering that it may be less effective than or as effective as low molecular weight heparin for prevention of deep vein thrombosis and pulmonary embolism after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1C). Aspirin may be less effective than or as effective as low molecular weight heparins for prevention of deep vein thrombosis and pulmonary embolism after other orthopaedic procedures (Grade 2C). Aspirin may be associated with a low rate of bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1B). Aspirin may be associated with less bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery than other pharmacological agents (Grade 1B). No data are available for other orthopaedic procedures. We do not recommend aspirin as thromboprophylaxis in general surgery (Grade 1C). However, this type of prophylaxis could be interesting especially in low-income countries (Grade 2C) and adequate large-scale trials with proper study designs should be carried out (Grade 1C).

  3. TRIAL OF ASPIRIN AND CALCIUM ON PREVENTION OF PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    ALI AKBA TAHERIAN

    2002-06-01

    Full Text Available ntroduction. Preelampsia is a common and serious complication of pregnancy that affects both mother and newborn. This study designed to determine whether low-dose aspirin or calcium supplements taken throughout pregnancy reduce the incidence of preeclampsia. Methods. The present study was a randomized controlled clinical trial. 990 healthy nulliparous women, who were pregnant for 13 to 20 weeks were chosen to receive daily treatment with low dose of aspirin 75 mg (330 patients, aspirin group, calcium D 500 mg (330 Patients, calcium group and no medication (330 patients, control group for remainder of theirs pregnancies. Data included demographic, obstetric, prenatal care, hospital records and final diagnosis were collected. Statistical analysis was performed using Chi-Squre, ANOVA and Duncan test at significance level of 0.05. Results. Preeclampsia occurred in 15 of 330 women in the aspirin group (4.6%, 13 of 330 women in the calcium group (4% and in 33 of 330 women in control group (10.1%. There were significant differences between aspirin and control groups (4.6% vs. 10.1% P < 0.05 also between calcium and control group (4% vs. 10.1% P < 0.05. Discussion. These results suggest that low dose of aspirin or calcium D during pregnancy in healthy nulliparous women is effective to reduce the prevalence of preeclampsia.

  4. Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent

    Directory of Open Access Journals (Sweden)

    Paola Patrignani

    2012-12-01

    Full Text Available Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg, the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX-1 in platelets (in the pre-systemic circulation while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (approximately 20 min; nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites.

  5. [Prevention of COPD exacerbation: a fundamental challenge].

    Science.gov (United States)

    Roche, N; Aguilaniu, B; Burgel, P-R; Durand-Zaleski, I; Dusser, D; Escamilla, R; Perez, T; Raherison, C; Similowski, T

    2012-06-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a cause of suffering for patients and a burden for healthcare systems and society. Their prevention represents individual and collective challenge. The present article is based on the work of a group of experts who met on 5th and 6th May 2011 and seeks to highlight the importance of AECOPD. In the absence of easily quantifiable criteria, the definition of AECOPD varies in the literature, making identification difficult and affecting interpretation of study results. Exacerbations increase mortality and risk of cardiovascular disease. They also increase the risk of developing further exacerbations, accelerate the decline in lung function and contribute to reduction in muscle mass. By limiting physical activity and affecting mental state (anxiety, depression), AECOPD are disabling and impair quality of life. They increase work absenteeism and are responsible for about 60% of the global cost of COPD. Earlier identification with simple criteria, possibly associated to patient phenotyping, could be helpful in preventing hospitalization. Given their immediate and delayed impact, AECOPD should not be trivialized or neglected. Their prevention is a fundamental issue. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  6. Respiratory system determinants of peripheral fatigue and endurance performance.

    Science.gov (United States)

    Dempsey, Jerome A; Amann, Markus; Romer, Lee M; Miller, Jordan D

    2008-03-01

    We briefly summarize recent evidence pertaining to how mechanisms primarily under the control of the respiratory system-namely, arterial oxyhemoglobin desaturation, respiratory muscle work and fatigue, and cyclical fluctuations in intrathoracic pressure-may contribute to exercise limitation. Respiratory influences on cardiac output and on sympathetic vasoconstrictor activity and blood flow distribution are shown to be important determinants of performance. We also address how a compromised O2 transport exacerbates the rate of development of peripheral muscle fatigue and, in turn, precipitates central fatigue and exercise limitation.

  7. Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

    Directory of Open Access Journals (Sweden)

    Sora Yasr

    2017-02-01

    Full Text Available An important problem in management of the case with myasthenia gravis (MG is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

  8. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.

    OpenAIRE

    Hawthorne, A B; Mahida, Y R; Cole, A T; Hawkey, C J

    1991-01-01

    1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin...

  9. Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Geiger-Brown J

    2015-02-01

    Full Text Available Jeanne Geiger-Brown,1 Sarah Lindberg,2 Samuel Krachman,3 Charlene E McEvoy,4 Gerard J Criner,3 John E Connett,2 Richard K Albert,5 Steven M Scharf6 1Center for Health Outcomes Research, University of Maryland School of Nursing, Baltimore, MD, 2University of Minnesota School of Public Health, Division of Biostatistics, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Health Partners Institute of Education and Research, St Paul, MN, 5The Medicine Service, Denver Health and Department of Medicine, the University of Colorado Denver Health Sciences Center, Denver, CO, 6Department of Medicine, Pulmonary and Critical Care Division, University of Maryland School of Medicine, Baltimore, MD, USA Background: Many patients with chronic obstructive pulmonary disease (COPD suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients. Methods: This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire. Outcomes included time to first exacerbation and exacerbation rate. Results: Sleep quality was “poor” (Pittsburgh Sleep Quality Index >5 in 53% of participants but was not related to age or severity of airflow obstruction. Quality of life scores were worse in “poor” sleepers than in “good” sleepers. Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the “poor” sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days and exacerbation rate (1

  10. Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

    Science.gov (United States)

    García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

    2017-08-01

    Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

  11. Evaluation of aspirin use in patients with diabetes receiving care in community health.

    Science.gov (United States)

    Fosmire Rundgren, Elaine W; Anderson, Sarah L; Marrs, Joel C

    2015-02-01

    The American Diabetes Association (ADA) recommends low-dose aspirin therapy as a primary prevention strategy in patients with type 1 or type 2 diabetes mellitus (DM) at increased cardiovascular risk. However, not all patients who are indicated are taking aspirin therapy, and it is not routinely documented in the electronic health record (EHR). To determine frequencies of appropriate aspirin use and documentation in the EHR in adult patients with DM. Adult patients with DM were randomized and contacted for participation in a telephonic survey between January and October 2013. Patients who consented were administered a standardized oral telephone survey regarding aspirin use. Patient demographics, current medications, allergies, past medical history, and pertinent laboratory values were collected. Patients were then stratified by the ADA-defined indication for aspirin. The primary outcomes were rates of appropriate aspirin use and documentation of aspirin therapy in the EHR. Investigators contacted 276 patients for inclusion. Of the 81 patients surveyed, 74% were indicated for aspirin therapy. Nearly all (92.3%) patients reporting aspirin use were indicated for aspirin therapy compared with only 57.1% of patients who did not report aspirin but were indicated (P = 0.0003). Alternatively, 96.7% of patients with aspirin use documented in their EHR were indicated for aspirin therapy compared with only 60.8% of patients who did not have aspirin use documented in the EHR but had an indication (P = 0.0002). Approximately 20% of the patients indicated for and reporting aspirin use did not have aspirin documented in their EHR. Aspirin use in patients with DM who are indicated for therapy is significantly underutilized and underdocumented. © The Author(s) 2014.

  12. Home intravenous antibiotic treatment for acute pulmonary exacerbations in cystic fibrosis ? Is it good for the patient?

    OpenAIRE

    Sequeiros Iara; Jarad Nabil

    2009-01-01

    There is a worldwide drive for the home management of chronic respiratory diseases. With the widespread use of home intravenous (IV) treatment for cystic fibrosis (CF) pulmonary exacerbations (PExs), evidence pointing to an inferior outcome of care for home-treated patients in comparison to hospital-treated patients is a cause of concern. Currently, patients who self-administer IV antibiotics at home are provided with equipment and instructions on the use of antibiotics. Policies vary; but in...

  13. Medically treated exacerbations in COPD by GOLD 1-4

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S.; Marott, Jacob L.; Lange, Peter

    2015-01-01

    -up. Construct validity of this definition of medically treated exacerbations was assessed by studying baseline determinants as well as by studying the association between GOLD 1 through 4 grades and time to first exacerbation during follow-up. RESULTS: Among individuals with COPD, 964 individuals (7.1%) had...... definition of exacerbations was robust and without major biases. CONCLUSIONS: Compared to individuals with GOLD 1, the risk of exacerbations was 17-fold for GOLD 4, 5-fold for GOLD 3, and 2-fold for GOLD 2. Medically treated exacerbations defined by register linkage seem a valid, robust, and low...

  14. Potentiation of LPS-Induced Apoptotic Cell Death in Human Hepatoma HepG2 Cells by Aspirin via ROS and Mitochondrial Dysfunction: Protection by N-Acetyl Cysteine.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available Cytotoxicity and inflammation-associated toxic responses have been observed to be induced by bacterial lipopolysaccharides (LPS in vitro and in vivo respectively. Use of nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin, has been reported to be beneficial in inflammation-associated diseases like cancer, diabetes and cardiovascular disorders. Their precise molecular mechanisms, however, are not clearly understood. Our previous studies on aspirin treated HepG2 cells strongly suggest cell cycle arrest and induction of apoptosis associated with mitochondrial dysfunction. In the present study, we have further demonstrated that HepG2 cells treated with LPS alone or in combination with aspirin induces subcellular toxic responses which are accompanied by increase in reactive oxygen species (ROS production, oxidative stress, mitochondrial respiratory dysfunction and apoptosis. The LPS/Aspirin induced toxicity was attenuated by pre-treatment of cells with N-acetyl cysteine (NAC. Alterations in oxidative stress and glutathione-dependent redox-homeostasis were more pronounced in mitochondria compared to extra- mitochondrial cellular compartments. Pre-treatment of HepG2 cells with NAC exhibited a selective protection in redox homeostasis and mitochondrial dysfunction. Our results suggest that the altered redox metabolism, oxidative stress and mitochondrial function in HepG2 cells play a critical role in LPS/aspirin-induced cytotoxicity. These results may help in better understanding the pharmacological, toxicological and therapeutic properties of NSAIDs in cancer cells exposed to bacterial endotoxins.

  15. Clopidogrel and Aspirin versus Aspirin Alone for Stroke Prevention: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Shuai Tan

    Full Text Available Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.Randomized controlled trials were searched in PubMed (1966-May, 2015, EMBASE (1947-May, 2015, the Cochrane Central Register of Controlled Trials (CENTRAL (1948-May, 2015, WHO International Clinical Trial (ICTRP (2004-May, 2015, China Biology Medicine disc (CBM disc (1978-May, 2015 and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR was pooled with 95% confidence interval (CI for dichotomous data. The heterogeneity was considered significant if the χ2 test was significant (P value 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59-0.82, P <0.05; RR = 0.84, 95% CI: 0.72-0.98, P = 0.03, respectively. With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03-2.23, P = 0.04; RR = 1.54, 95% CI: 1.32-1.79, P<0.05, respectively.Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.

  16. Stability of the frequent COPD exacerbator in the general population

    DEFF Research Database (Denmark)

    Reilev, Mette; Lykkegaard, Jesper; Halling, Anders

    2017-01-01

    Exacerbation frequency is central in treatment strategies for chronic obstructive pulmonary disease. However, whether chronic obstructive pulmonary disease patients from the general population with frequent exacerbations continue to have frequent exacerbations over an extended period of time...... is currently unknown. In this study, we aimed to investigate the stability of the frequent exacerbator in a population-based setting. To this end, we conducted a nationwide register-based descriptive study with a 10-year follow-up period of chronic obstructive pulmonary disease patients with at least one...... medically treated exacerbation in 2003. Each subsequent year, we divided the population into frequent, infrequent and non-exacerbators and quantified the flow between categories. Further, we estimated the percentage of frequent exacerbators at baseline who stayed in this category each year during a 5-year...

  17. Stability studies of aspirin-magaldrate double layer tablets.

    Science.gov (United States)

    al-Gohary, O M; al-Kassas, R S

    2000-04-01

    Accelerated stability testing was performed on aspirin-magaldrate double layer tablets as well as aspirin-maalox marketed double layer tablets (Ascriptin) in order to evaluate the effect of the presence of the alkaline moieties of the antacid (magaldrate and maalox) on the chemical stability of aspirin. The results were compared simultaneously with that obtained from the marketed Aspro plain tablets. The results revealed that the presence of the alkaline moieties in the tested tablets has increased the rate of aspirin decomposition and reduced its shelf-life. This effect was more pronounced for aspirin tablets containing magaldrate antacid. Determination of shelf-lives at 25 degrees C for the prepared and the marketed tablets was carried out using Arrhenius plots and the results showed that they were 35, 34.5 and 13.5 months for Aspro, Ascriptin and aspirin-magaldrate double layer tablets, respectively. The effect of storage for 50 days and at different temperatures, on the crushing strength and the disintegration time of the prepared and the marked tablets showed a slight decrease in the disintegration time and the crushing strength of the tablets as the storage temperature increased. Aspro tablets did not produce the same results. The in vitro release data of the prepared aspirin-magaldrate double layer tablets and the marketed Ascriptin tablets stored for 50 days and at different storage temperatures as well as Aspro tablets stored at 70 degrees C were best fitted to the first-order kinetics model. The release data of Aspro tablets stored at 50 and 60 degrees C for 50 days were best fitted to Higuchi's model.

  18. Low prevalence and assay discordance of "aspirin resistance" in children.

    Science.gov (United States)

    Yee, D L; Dinu, B R; Sun, C W; Edwards, R M; Justino, H; Teruya, J; Bray, P F; Bomgaars, L

    2008-07-01

    Although "aspirin resistance" (AR-inadequate platelet inhibition as suggested by in vitro testing of aspirin-treated patients) has been widely studied in adults and linked to increased risk of adverse outcomes, its prevalence and clinical significance are largely unknown in children. To determine AR prevalence in children and its relationship to assay methodology, we undertook a cross-sectional study of 44 children (1-17 years, 24 male) on aspirin for various indications and considered three published definitions of AR in adults: platelet aggregation >/=70% to 10 microM adenosine diphosphate and >/=20% to 0.5 mg/ml arachidonic acid (AA), normal PFA-100(R) closure time and elevated urinary 11-dehydro thromboxane B(2) (11dhTxB(2)) concentration. Six subjects exhibited AR according to at least one of the criteria (5 by PFA-100(R), 1 by aggregometry and 11dhTxB(2) criteria); nearly all subjects had low levels of 11dhTxB(2) compared with controls. Subjects studied prior to therapy showed pronounced changes in AR parameters after aspirin dosing (e.g., mean aggregation to AA decreased from 82% to 6%, P aspirin effect. Subjects with AR did not differ from aspirin responsive subjects in terms of age, race, platelet count, or aspirin dose, indication or therapy duration. There was minimal correlation between assays. In this initial prevalence study of a clinically diverse group of pediatric patients, frequencies of AR were assay-dependent; however, the prevalence of true AR is likely low in children (2.3%; 95% CI 0.1-10.7%), in agreement with adult studies. To better define the clinical relevance of AR in children, multicenter, prospective cohort studies are imperative. (c) 2008 Wiley-Liss, Inc.

  19. Perioperative modifications of respiratory function.

    LENUS (Irish Health Repository)

    Duggan, Michelle

    2012-01-31

    Postoperative pulmonary complications contribute considerably to morbidity and mortality, especially after major thoracic or abdominal surgery. Clinically relevant pulmonary complications include the exacerbation of underlying chronic lung disease, bronchospasm, atelectasis, pneumonia and respiratory failure with prolonged mechanical ventilation. Risk factors for postoperative pulmonary complications include patient-related risk factors (e.g., chronic obstructive pulmonary disease (COPD), tobacco smoking and increasing age) as well as procedure-related risk factors (e.g., site of surgery, duration of surgery and general vs. regional anaesthesia). Careful history taking and a thorough physical examination may be the most sensitive ways to identify at-risk patients. Pulmonary function tests are not suitable as a general screen to assess risk of postoperative pulmonary complications. Strategies to reduce the risk of postoperative pulmonary complications include smoking cessation, inspiratory muscle training, optimising nutritional status and intra-operative strategies. Postoperative care should include lung expansion manoeuvres and adequate pain control.

  20. Reduced rhinovirus-specific antibodies are associated with acute exacerbations of chronic obstructive pulmonary disease requiring hospitalisation

    Science.gov (United States)

    2012-01-01

    Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are often linked to respiratory infections. However, it is unknown if COPD patients who experience frequent exacerbations have impaired humoral immunity. The aim of this study was to determine if antibodies specific for common respiratory pathogens are associated with AECOPD. Methods Plasma was obtained from COPD patients when clinically stable. AECOPD requiring hospitalisation were recorded. IgG1 antibodies to H. Influenzae outer membrane protein 6 (P6), pneumococcal surface protein C (PspC) and the VP1 viral capsid protein of rhinovirus were measured. Results COPD patients who had an AECOPD (n = 32) had significantly lower anti-VP1 IgG1 antibody levels when stable compared to COPD patients who did not have an AECOPD (n = 28, p = 0.024). Furthermore, the number of hospitalisations was inversely proportional to anti-VP1 antibody levels (r = −0.331, p = 0.011). In contrast, antibodies specific for P6 and PspC were present at similar concentrations between groups. Plasma IL-21, a cytokine important for B-cell development and antibody synthesis, was also lower in COPD patients who had an AECOPD, than in stable COPD patients (p = 0.046). Conclusion Deficient humoral immunity specific for rhinoviruses is associated with AECOPD requiring hospitalisation, and may partly explain why some COPD patients have an increased exacerbation risk following respiratory viral infections. PMID:22849333

  1. RESPIRATORY GYMNASTICS AS A REHABILITATION MEANS FOR THE PRESCHOOL CHILDREN WITH THE RESPIRATORY PATHOLOGY

    Directory of Open Access Journals (Sweden)

    T.A. Shemyakina

    2007-01-01

    Full Text Available The researchers analyzed the efficacy of the new medical technology aimed at rehabilitation of the preschool children with the respiratory pathology. 177 children aged between 2 and 7 with recurrent respiratory diseases, bronchial asthma or chronic pathology of the end organs have been examined for 9 months. It was uncovered that among children (n = 90, who performed the sets of the therapeutic physical training and respiratory gymnastics according to the methods developed by the authors, the recurrence of the acute respiratory diseases and exacerbations of bronchial asthma was lower by 1,83 and 1,86 timers respectively. Besides, among children of this group the researchers noted the significant improvement of the physical qualities, spirometric indices and cytological picture of the substance removed from the nasal cavity if compared with the children from the screening group (n = 87, who performed the sets of the conventional gymnastics at the physical training lessons. Thus, the researchers proved the high efficacy of the proposed technology for the rehabilitation of the children, suffering from the chronic respiratory pathology.Key words: acute respiratory diseases, asthma, therapeutic physical training, respiratory gymnastics, children.

  2. Impact of an integrated disease management program in reducing exacerbations in patients with severe asthma and COPD.

    Science.gov (United States)

    Jain, Vipul V; Allison, Richard; Beck, Sandra J; Jain, Ratnali; Mills, Paul K; McCurley, James W; Van Gundy, Karl P; Peterson, Michael W

    2014-12-01

    Conflicting data exists on the effectiveness of integrated programs in reducing recurrent exacerbations and hospitalizations in patients with Asthma and chronic obstructive lung disease (COPD). We developed a Pulmonologist-led Chronic Lung Disease Program (CLDP) for patients with severe asthma and COPD and analyzed its impact on healthcare utilization and predictors of its effectiveness. CLDP elements included clinical evaluation, onsite pulmonary function testing, health education, and self-management action plan along with close scheduled and on-demand follow-up. Patients with ≥2 asthma or COPD exacerbations requiring emergency room visit or hospitalization within the prior year were enrolled, and followed for respiratory related ER visits (RER) and hospitalizations (RHA) over the year (357 ± 43 days) after CLDP interventions. A total of 106 patients were enrolled, and 104 patients were subject to analyses. During the year of follow-up after CLDP enrollment, there was a significant decrease in mean RER (0.56 ± 1.48 versus 2.62 ± 2.81, p logistic regression analysis revealed lack of spirometry utilization as an independent risk factor for severe exacerbations. A Pulmonologist-led disease management program integrating key elements of care is cost effective and significantly decreases severe exacerbations. Integrated programs should be encouraged for care of frequent exacerbators of asthma and COPD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Aspirin for Reducing Your Risk of Heart Attack and Stroke: Know the Facts

    Science.gov (United States)

    ... the-Counter Medicines Safe Daily Use of Aspirin Aspirin for Reducing Your Risk of Heart Attack and ... State & Local Officials Consumers Health Professionals Science & Research Industry Scroll back to top Popular Content Home Latest ...

  4. Aspirin, but not clopidogrel, reduces collateral conductance in a rabbit model of femoral artery occlusion

    NARCIS (Netherlands)

    Hoefer, Imo E.; Grundmann, Sebastian; Schirmer, Stephan; van Royen, Niels; Meder, Benjamin; Bode, Christoph; Piek, Jan J.; Buschmann, Ivo R.

    2005-01-01

    OBJECTIVES The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). BACKGROUND Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet

  5. Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery

    DEFF Research Database (Denmark)

    Graham, Michelle M; Sessler, Daniel I; Parlow, Joel L

    2017-01-01

    Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a mul...

  6. Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed-Pharmacogenomics

    Science.gov (United States)

    Yerges-Armstrong, Laura M.; Ellero-Simatos, Sandrine; Georgiades, Anastasia; Zhu, Hongjie; Lewis, Joshua; Horenstein, Richard B.; Beitelshees, Amber L.; Dane, Adrie; Reijmers, Theo; Hankemeier, Thomas; Fiehn, Oliver; Shuldiner, Alan R.; Kaddurah-Daouk, Rima

    2014-01-01

    Though aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study. Many metabolites, including known aspirin catabolites, changed upon exposure to aspirin and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Further, purines were associated with aspirin response and poor responders had higher post-aspirin adenosine and inosine than good responders (N=76;paspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response - an important step toward personalized treatment approaches for cardiovascular disease. PMID:23839601

  7. Predicting high risk of exacerbations in bronchiectasis: the E-FACED score

    Directory of Open Access Journals (Sweden)

    Martinez-Garcia MA

    2017-01-01

    countries (Brazil, Argentina, and Chile. The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED. The results obtained after the application of FACED and E-FACED were compared in both the cohorts.Results: A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points, meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year that was statistically better than that of the FACED score (0.72 and 0.78, P<0.05, respectively. The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED.Conclusion: E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score’s simplicity and prognostic capacity for death. Keywords: FACED score, E-FACED score, mortality, bronchiectasis, exacerbations

  8. Lungs and Respiratory System

    Science.gov (United States)

    ... Transplant Vision Facts and Myths Lungs and Respiratory System KidsHealth > For Parents > Lungs and Respiratory System Print ... have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't happen ...

  9. Neonatal respiratory distress syndrome

    Science.gov (United States)

    Hyaline membrane disease (HMD); Infant respiratory distress syndrome; Respiratory distress syndrome in infants; RDS - infants ... after that. Some infants with severe respiratory distress syndrome will die. This most often occurs between days ...

  10. Impact of aspirin on the transcriptome of Streptococcus pneumoniae D39

    OpenAIRE

    Afzal, Muhammad; Shafeeq, Sulman

    2017-01-01

    Aspirin or acetylsalicylic acid (ASA) is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5?mM aspirin in chemically-defined medium (CDM) using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Ort...

  11. The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs.

    Science.gov (United States)

    Thomason, J; Archer, T; Wills, R; Press, S; Mackin, A

    2016-07-01

    Cyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets. Our hypothesis was that the concurrent administration of low-dose aspirin and cyclosporine would inhibit cyclosporine-associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis. Seven healthy dogs. A randomized, crossover study utilized turbidimetric aggregometry and a platelet function analyzer to evaluate platelet function during the administration of low-dose aspirin (1 mg/kg PO q24h), high-dose aspirin (10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12h), and combined low-dose aspirin and cyclosporine. The urine 11-dehydro-thromboxane-B2 (11-dTXB2 )-to-creatinine ratio also was determined. On days 3 and 7 of administration, there was no difference in the aggregometry amplitude or the platelet function analyzer closure time between the low-dose aspirin group and the combined low-dose aspirin and cyclosporine group. On day 7, there was a significant difference in amplitude and closure time between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. High-dose aspirin consistently inhibited platelet function. On both days, there was a significant difference in the urinary 11-dTXB2 -to-creatinine ratio between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. There was no difference in the urinary 11-dTXB2 -to-creatinine ratio among the low-dose aspirin, high-dose aspirin, and combined low-dose aspirin and cyclosporine groups. Low-dose aspirin inhibits cyclosporine-induced thromboxane synthesis, and concurrent use of these medications does not alter the antiplatelet effects of aspirin. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  12. Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery.

    Science.gov (United States)

    Emani, Sirisha; Zurakowski, David; Mulone, Michelle; DiNardo, James A; Trenor, Cameron C; Emani, Sitaram M

    2017-11-01

    Thrombosis is associated with increased morbidity and mortality in pediatric patients undergoing cardiac surgery. Although aspirin commonly is used for thromboprophylaxis, the utility of laboratory-based tests that assess aspirin efficacy have not been evaluated. We sought to determine the relationship between platelet aggregation testing and aspirin dose adjustment on thrombosis rates in this population. Pediatric patients undergoing cardiac surgery who received aspirin and underwent platelet testing were studied retrospectively. Patients were excluded if they were treated with multiple agents or experienced thrombosis before the initiation of aspirin. Thrombosis events within 30 days after initiation of aspirin were recorded. Associations between aspirin responsiveness and thrombosis rate and aspirin dose adjustment and thrombosis rate were assessed with the use of multivariable logistic regression analysis. Suboptimal platelet response to aspirin was detected in 64 of 430 patients (15%) and thrombosis was detected in 11 patients (2.6%). Lack of aspirin responsiveness on initial testing was a significant risk factor for thrombosis (P aspirin dose. Dose escalation based on aspirin testing was performed in 40 of 64 patients, and significantly lower rate of thrombosis was observed in patients who underwent dose escalation compared with those without dose escalation (0/40 vs 9/24, P aspirin dose after initial unresponsiveness (P aspirin dosing may lead to subtherapeutic platelet inhibition in some children. Aspirin unresponsiveness is associated with increased risk of thrombosis after specific pediatric cardiac surgical procedures. Aspirin dose increase in unresponsive patients is associated with reduced risk of thrombosis. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  13. The efficacy of extrafine beclomethasone dipropionate–formoterol fumarate in COPD patients who are not "frequent exacerbators": a post hoc analysis of the FORWARD study

    Directory of Open Access Journals (Sweden)

    Singh D

    2017-11-01

    Full Text Available Dave Singh,1 Stefano Vezzoli,2 Stefano Petruzzelli,2 Alberto Papi3 1Medicines Evaluation Unit, University of Manchester, Manchester, UK; 2Chiesi Farmaceutici SpA, Parma, 3Section of Respiratory Diseases, University of Ferrara, Ferrara, Italy Abstract: The GOLD 2017 strategy document recommends that the pharmacological management of COPD patients be based on the risk of future exacerbations and the severity of symptoms. A threshold of two moderate exacerbations or one hospitalization is used to define high-risk patients. The FORWARD study was a randomized, double-blind, parallel-group trial that compared 48 weeks’ treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP-FF versus FF in severe COPD patients with a history of one or more exacerbations in the previous year. The new GOLD 2017 recommendations mean that many patients in the FORWARD study are now reclassified as GOLD B. We conducted a post hoc analysis of the FORWARD study, in order to investigate the effects of extrafine BDP/FF in patients with one exacerbation in the previous year, focusing on those categorized as group B using the GOLD 2017 definition. The analysis showed a 35% reduction in exacerbation rate with an inhaled corticosteroid (ICS + long-acting β-agonist (LABA versus LABA. We propose that ICS-LABA treatment is a therapeutic option for COPD patients with one exacerbation in the previous year. Keywords: COPD, GOLD B, GOLD 2017, exacerbations, corticosteroid

  14. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

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    Kunal Kanani

    2015-08-01

    Full Text Available Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA is rapidly converted into its main active metabolite, salicylic acid (SA. Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

  15. Aspirin Prevents Colorectal Cancer by Normalizing EGFR Expression.

    Science.gov (United States)

    Li, Haitao; Zhu, Feng; Boardman, Lisa A; Wang, Lei; Oi, Naomi; Liu, Kangdong; Li, Xiang; Fu, Yang; Limburg, Paul J; Bode, Ann M; Dong, Zigang

    2015-05-01

    Aspirin intake reduces the risk of colorectal cancer (CRC), but the molecular underpinnings remain elusive. Epidermal growth factor receptor (EGFR), which is overexpressed in about 80% of CRC cases, is implicated in the etiology of CRC. Here, we investigated whether aspirin can prevent CRC by normalizing EGFR expression. Immunohistochemistry staining was performed on paraffin-embedded tissue sections from normal colon mucosa, adenomatous polyps from FAP patients who were classified as regular aspirin users or nonusers. The interplay between cyclooxygenase-2 (COX-2) and EGFR was studied in primary intestinal epithelial cells isolated from Apc(Min) mice, immortalized normal human colon epithelial cells (HCEC) as well as murine embryonic fibroblasts (MEFs). Immunohistochemistry staining results established that EGFR overexpression is an early event in colorectal tumorigenesis, which can be greatly attenuated by regular use of aspirin. Importantly, EGFR and COX-2 were co-overexpressed and co-localized with each other in FAP patients. Further mechanistic studies revealed that COX-2 overexpression triggers the activation of the c-Jun-dependent transcription factor, activator protein-1 (AP-1), which binds to the Egfr promoter. Binding facilitates the cellular accumulation of EGFR and lowers the threshold required for pre-neoplastic cells to undergo transformation. Aspirin might exert its chemopreventive activity against CRC, at least partially, by normalizing EGFR expression in gastrointestinal precancerous lesions.

  16. Aspirin: promise and resistance in the new millennium.

    Science.gov (United States)

    Patrono, Carlo; Rocca, Bianca

    2008-03-01

    Although conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy. Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among high-risk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin "resistance"; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk. The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug.

  17. UVRAG Deficiency Exacerbates Doxorubicin-Induced Cardiotoxicity

    Science.gov (United States)

    An, Lin; Hu, Xiao-wen; Zhang, Shasha; Hu, Xiaowen; Song, Zongpei; Naz, Amber; Zi, Zhenguo; Wu, Jian; Li, Can; Zou, Yunzeng; He, Lin; Zhu, Hongxin

    2017-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity. Mouse models of acute or chronic DOX-induced cardiotoxicity were established. UVRAG deficiency exacerbated DOX-induced mortality and cardiotoxicity manifested by increased cytoplasmic vacuolization, enhanced collagen accumulation, elevated serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, higher ROS levels, aggravated apoptosis and more depressed cardiac function. Autophagic flux was impaired in DOX-induced cardiotoxicity. UVRAG deficiency aggravated impaired autophagic flux in DOX-induced cardiotoxicity. Intermittent fasting restored autophagy and ameliorated pathological alterations of DOX-induced cardiotoxicity. Collectively, our data suggest that UVRAG deficiency exacerbates DOX-induced cardiotoxicity, at least in part, through aggravation of DOX-induced impaired autophagic flux. Intermittent fasting, which restores blunted autophagic flux and ameliorates pathology in the mouse models of DOX-induced cardiotoxicity, may be used as a potential preventive or therapeutic approach for DOX cardiotoxicity. PMID:28225086

  18. Use and Safety of Non-Steroidal Inflammatory Drugs and Aspirin

    NARCIS (Netherlands)

    V.E. Valkhoff (Vera)

    2012-01-01

    textabstractThe use of acetylsalicylic acid, better known as aspirin, dates back to the Egyptians in 1534 BC. Aspirin-like compounds are naturally derived from willow tree bark and myr-tle. At the end of the 19th century aspirin was patented by Bayer as the world’s first syn-thetic drug. The

  19. Aspirin resistance in children with heart disease at risk for thromboembolism: prevalence and possible mechanisms.

    Science.gov (United States)

    Heistein, Lisa C; Scott, William A; Zellers, Thomas M; Fixler, David E; Ramaciotti, Claudio; Journeycake, Janna M; Lemler, Matthew S

    2008-03-01

    Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

  20. Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells.

    Science.gov (United States)

    Sonnemann, Jürgen; Hüls, Isabel; Sigler, Michael; Palani, Chithra D; Hong, Le Thi Thu; Völker, Uwe; Kroemer, Heyo K; Beck, James F

    2008-07-01

    Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1- and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy.

  1. Seasonal Risk Factors for Asthma Exacerbations among Inner City Children

    Science.gov (United States)

    Teach, Stephen J.; Gergen, Peter J.; Szefler, Stanley J.; Mitchell, Herman E.; Calatroni, Agustin; Wildfire, Jeremy; Bloomberg, Gordon; Kercsmar, Carolyn; Liu, Andrew H.; Makhija, Melanie; Matsui, Elizabeth; Morgan, Wayne; O'Connor, George; Busse, William W.

    2015-01-01

    Background Exacerbations of asthma remain common even in children and adolescents despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective Define host risk factors for asthma exacerbations unique to their season of occurrence. Methods This is a retrospective analysis of patients aged 6-20 years who comprised the control groups of the Asthma Control Evaluation trial and the Inner City Anti-IgE Therapy for Asthma trial. Univariate and multivariate models were constructed to determine if patient demographic and historical factors, allergic sensitization, fractional exhaled nitric oxide, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results The analysis included 400 patients (54.5% male; 59.0% African American; median age 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis, impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis, exacerbation in the previous season was the strongest predictor in fall and winter while a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions Among a large cohort of inner city children with asthma, patient risk factors for exacerbations vary by season. Thus, individual patient information may be beneficial in strategies to prevent these seasonal events. Clinical Implications Inner city children remain at risk for asthma exacerbations despite appropriate therapy. Because their risk factors vary by season, strategies to prevent them may need to differ as

  2. Impact of ventilator associated pneumonia on outcome in patients with chronic obstructive pulmonary disease exacerbation

    Directory of Open Access Journals (Sweden)

    Vijay Hadda

    2014-01-01

    Full Text Available Background and Objective: There are sparse data regarding the impact of ventilator-associated pneumonia (VAP on outcome among patients with chronic obstructive pulmonary disease (COPD exacerbation. Materials and Methods: This retrospective study included patients with COPD exacerbation requiring endotracheal intubation for more than 48 h admitted in a single respiratory unit from January 2008 to December 2009. Records of these patients were checked for the occurrence of VAP. Results: One hundred and fifty-three patients required endotracheal intubation for COPD exacerbation during this period. The mean age of this cohort was 61.46 ± 11.3 years. The median duration of COPD was 6 years (range: 1-40. A total of 35 (22.8% patients developed VAP (early: 9 and late: 26. The risk of mortality was comparable between two groups, that is, patients with and without VAP [odd′s ratio (OR−1.125; 95% confidence interval (CI, 0.622-2.035]. The duration of mechanical ventilation and hospital stay (median ± standard error, 95% CI was 32 ± 10 (95% CI, 13-51 versus 10 ± 2 (95% CI, 6-14 days; P ≤ 0.001 and 53 ± 26 (95% CI, 3-103 versus 18 ± 7 (95% CI, 5-31 days; P = 0.031, respectively was higher among patients with VAP. Conclusions: Our study has shown that VAP leads to increased duration of mechanical ventilation and hospital stay; however, the mortality is not affected.

  3. Indoor tobacco legislation is associated with fewer emergency department visits for asthma exacerbation in children.

    Science.gov (United States)

    Ciaccio, Christina E; Gurley-Calvez, Tami; Shireman, Theresa I

    2016-12-01

    During the past 3 decades, numerous cities and states have adopted laws that ban smoking in public indoor spaces. The rationale for these policies has been to protect nonsmokers from the adverse health effects of secondhand smoke. To determine whether the implementation of indoor smoking legislation is associated with a decrease in emergency department visits for asthma in children. This retrospective analysis used a natural experiment to estimate the impact of clean indoor air legislation on the rate of emergency department admissions for asthma exacerbation in children. Data were obtained from the Pediatric Health Information System. A Poisson regression was used for analyses and controlled for age, sex, race, payer source, seasonality, and secular trends. Asthma emergency department visits were captured from 20 hospitals in 14 different states plus the District of Columbia from July 2000 to January 2014 (n = 335,588). Indoor smoking legislation, pooled across all cities, was associated with a decreased rate of severe asthma exacerbation (adjusted rate ratio 0.83, 95% confidence interval 0.82-0.85, P legislation is associated with a decrease in emergency department visits for asthma exacerbation. Such legislation should be considered in localities that remain without this legislation to protect the respiratory health of their children. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Benefits and complications of noninvasive mechanical ventilation for acute exacerbation of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Rocha, Eduardo; Carneiro, Elida Mara

    2008-06-01

    Chronic obstructive pulmonary disease (COPD) is defined as a syndrome characterized by usually progressive chronic airflow limitation which is associated to a bronchial hyperresponsiveness and is partially reversible. Noninvasive mechanical ventilation is an alternative treatment for patients with COPD exacerbations. The objective of the literature reviews was to verify noninvasive mechanical ventilation benefits and complications in acute exacerbations of chronic obstructive pulmonary disease in patients. This national and international's scientific literature review was developed according to criteria established for documentary research in the MedLine, LILACS, SciElo, PubMed and Cochrane, databases using the key words: chronic obstructive pulmonary disease and noninvasive mechanical ventilation. Inclusion criteria were articles published from 1995 to 2007; in English, Spanish and Portuguese; studies in the human model and with no gender restriction. Noninvasive mechanical ventilation can reduce partial pressure of carbon dioxide, improve gas exchange, alleviate symptoms as dyspnea caused by fatigue of the respiratory muscles, reduce duration of hospitalization, decrease need for invasive mechanical ventilation, reduce number of complications and also lessen hospital mortality. The main complications found were: facial skin erythema, claustrophobia, nasal congestion, face pain, eye irritation, aspiration pneumonia, hypotension, pneumothorax, aerophagia, hypercapnia, gastric insufflation, vomit, bronchoaspiration, morning headaches, face injuries, air embolism and, last but not least, discomfort of the patient. Noninvasive mechanical ventilation can be more effective in patients with moderate-severe exacerbations of COPD and these complications can be minimized by an adequate interface also by the contribution of the physiotherapist experience.

  5. Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Sean H Ling

    2009-06-01

    Full Text Available Sean H Ling, Stephan F van EedenJames Hogg iCAPTURE Centre for Pulmonary and Cardiovascular Research and Heart and Lung Institute, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary. Strong epidemiological evidence suggests that exposure to particulate matter (PM air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD resulting in increased morbidity and mortality. However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD. The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces. Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease. This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD.Keywords: chronic obstructive pulmonary disease, particulate matter, air pollution, alveolar macrophage

  6. Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease

    Directory of Open Access Journals (Sweden)

    K. Sakamoto

    2009-06-01

    Full Text Available The clinical course of patients with idiopathic pulmonary fibrosis (IPF is generally marked by a decline in pulmonary function over time, although recently there is increasing recognition that fatal deterioration from acute exacerbation can occur at any stage. The patient described in the present case study was a 65-yr-old male who presented with exertional dyspnoea and fever of 2 weeks' duration. He had no history of chronic lung disease or physiological or radiological hallmarks of pre-existing disease. He underwent surgical lung biopsy and the histological examination showed a background pattern of usual interstitial pneumonia (UIP with a pattern of focal acute diffuse alveolar damage (DAD in the area where normal lung architecture was preserved. It is notable that the pathological diagnosis of this rapidly progressive interstitial pneumonia was DAD on UIP, which is typically seen in acute exacerbations of IPF. Unusual findings on high-resolution computed tomography scan were also noted. We presume that in this case acute exacerbation developed in the very early course of IPF. Given the possibility that similar cases may have arisen among patients diagnosed with acute interstitial pneumonia or acute respiratory distress syndrome, the histopathology of rapidly progressive interstitial pneumonia may need to be revisited.

  7. Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

    Science.gov (United States)

    Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

    2017-11-24

    Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Antiplatelet effect of aspirin in patients with coronary artery disease.

    Science.gov (United States)

    Grove, Erik Lerkevang

    2012-09-01

    Cardiovascular disease is the number one cause of death globally, and atherothrombosis is the underlying cause of most cardiovascular events. Several studies have shown that antiplatelet therapy, including aspirin (acetylsalicylic acid), reduces the risk of cardiovascular events and death. However, it is well-known that many patients experience cardiovascular events despite treatment with aspirin, often termed "aspirin low-responsiveness". This fact has caused considerable debate: does biochemical aspirin low-responsiveness have prognostic value? Can low-responders be reliably identified? And if so, should antithrombotic treatment be changed? Is the whole discussion of antiplatelet drug response merely a result of low compliance? Compliance should be carefully optimised, before evaluating the pharmacological effect of a drug. It is well-known that cardiovascular disease is multifactorial, and, therefore, total risk reduction is not feasible. Aetiological factors to the variable platelet inhibition by aspirin seem to include genetic factors, pharmacological interactions, smoking, diabetes mellitus, and increased platelet turnover. It is a captivating thought that antiplatelet therapy may be improved by individually tailored therapy based on platelet function testing. Ongoing studies are challenging the current one-size-fits-all dosing strategy, but the preceding evaluation of platelet function assays has not been adequate. The overall objective of this thesis was to evaluate the reproducibility of and aggreement between a number of widely used platelet function tests and to explore the importance of platelet turnover for the antiplatelet effect of aspirin in patients with coronary artery disease. In the intervention studies (studies 1, 3, and 4), optimal compliance was confirmed by measurements of serum thromboxane, which is the most sensitive assay to confirm compliance with aspirin. In study 1, platelet function tests widely used to measure the antiplatelet effect

  9. Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; García-Rodríguez, L A; Sørensen, H T

    2013-01-01

    Background:Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting.Methods:We used...... exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential...... confounders.Results:A total of 2688 glioma cases and 18 848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin...

  10. Current Knowledge and Management of Hypersensitivity to Aspirin and NSAIDs.

    Science.gov (United States)

    Laidlaw, Tanya M; Cahill, Katherine N

    Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most common culprits of drug-induced hypersensitivity reactions, and can lead to a wide array of adverse effects. The accurate and timely diagnosis of aspirin and NSAID-induced hypersensitivity reactions is important for both patient safety and for the initiation of appropriate disease-specific management and treatment. Because there are no reliably validated in vitro tests available, aspirin and NSAID challenges are considered to be the criterion standard for the diagnosis of these hypersensitivity reactions, though in some patients the diagnosis can be made on the basis of a clear clinical history. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. High-pressure polymorphism of acetylsalicylic acid (aspirin): Raman spectroscopy

    Science.gov (United States)

    Crowell, Ethan L.; Dreger, Zbigniew A.; Gupta, Yogendra M.

    2015-02-01

    Micro-Raman spectroscopy was used to elucidate the high-pressure polymorphic behavior of acetylsalicylic acid (ASA), an important pharmaceutical compound known as aspirin. Using a diamond anvil cell (DAC), single crystals of the two polymorphic phases of aspirin existing at ambient conditions (ASA-I and ASA-II) were compressed to 10 GPa. We found that ASA-I does not transform to ASA-II, but instead transforms to a new phase (ASA-III) above ∼2 GPa. It is demonstrated that this transformation primarily introduces structural changes in the bonding and arrangement of the acetyl groups and is reversible upon the release of pressure. In contrast, a less dense ASA-II shows no transition in the pressure range studied, though it appears to exhibit a disordered structure above 7 GPa. Our results suggest that ASA-III is the most stable polymorph of aspirin at high pressures.

  12. Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

    Science.gov (United States)

    Gao, Lin; Sun, Jihong; Li, Yuzhen

    2011-08-01

    The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

  13. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  14. Epidural Hematoma Following Interlaminar Epidural Injection in Patient Taking Aspirin.

    Science.gov (United States)

    Sanders, Rebecca A; Bendel, Markus A; Moeschler, Susan M; Mauck, William D

    2018-01-09

    We present a case report of a patient who developed an epidural hematoma following an interlaminar epidural steroid injection with no risk factors aside from old age and aspirin use for secondary prevention. A 79-year-old man developed an epidural hematoma requiring surgical treatment following an uncomplicated interlaminar epidural steroid injection performed for neurogenic claudication. In the periprocedural period, he continued aspirin for secondary prophylaxis following a myocardial infarction. For patients taking aspirin for primary or secondary prophylaxis, the American Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation guidelines for spine and pain procedures recommend a shared assessment and risk stratification when deciding to hold the medication for intermediate-risk neuraxial procedures. Cases such as this serve to highlight the importance of giving careful consideration to medical optimization of a patient even when a low- or intermediate-risk procedure is planned.

  15. Regular use of aspirin and pancreatic cancer risk

    Directory of Open Access Journals (Sweden)

    Mahoney Martin C

    2002-09-01

    Full Text Available Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. Methods In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs with 95% confidence intervals (CIs. Results Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39. No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. Conclusions These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

  16. The effectiveness of aspirin for migraine prophylaxis: a systematic review.

    Science.gov (United States)

    Baena, Cristina Pellegrino; D'Amico, Raíssa Campos; Slongo, Helena; Brunoni, André Russowsky; Goulart, Alessandra Carvalho; Benseñor, Isabela

    2017-01-01

    Many researchers have suggested that aspirin prevents migraines. However, the evidence is unclear. The aim of this study was to analyze the available evidence on the effect of aspirin as a migraine prophylactic. Systematic review, conducted at the Pontifícia Universidade Católica do Paraná, Brazil, and at the University of São Paulo, Brazil. We performed electronic searches in the databases of MEDLINE/PubMed, Embase, WEB OF SCIENCE, the World Health Organization, CENTRAL and OpenGrey, and we also searched manually for interventional studies published before April 2016 that compared the effects of aspirin with a control, in adults. Two authors independently extracted data on the publication, population recruited, intervention (aspirin dosage, follow-up and combined treatment) and main outcomes (frequency, severity and duration of migraine). We evaluated the quality of the studies using the Cochrane risk-of-bias tool. Our search retrieved 1,098 references, of which 8 met the selection criteria for this systematic review. The total population was 28,326 participants (18-64 years old); most (96%) were men. The dosage varied from 50 to 650 mg/day across the studies. The risk of bias was generally low or unclear. The only outcome for which most of the studies included (6/8) reported a significant reduction was frequency of migraine, which was reduced at an aspirin dosage of at least 325 mg/day. Aspirin can reduce the frequency of migraines. However, the optimal dosage is unclear.

  17. The effectiveness of aspirin for migraine prophylaxis: a systematic review

    Directory of Open Access Journals (Sweden)

    Cristina Pellegrino Baena

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Many researchers have suggested that aspirin prevents migraines. However, the evidence is unclear. The aim of this study was to analyze the available evidence on the effect of aspirin as a migraine prophylactic. DESIGN AND SETTING: Systematic review, conducted at the Pontifícia Universidade Católica do Paraná, Brazil, and at the University of São Paulo, Brazil. METHODS: We performed electronic searches in the databases of MEDLINE/PubMed, Embase, WEB OF SCIENCE, the World Health Organization, CENTRAL and OpenGrey, and we also searched manually for interventional studies published before April 2016 that compared the effects of aspirin with a control, in adults. Two authors independently extracted data on the publication, population recruited, intervention (aspirin dosage, follow-up and combined treatment and main outcomes (frequency, severity and duration of migraine. We evaluated the quality of the studies using the Cochrane risk-of-bias tool. RESULTS: Our search retrieved 1,098 references, of which 8 met the selection criteria for this systematic review. The total population was 28,326 participants (18-64 years old; most (96% were men. The dosage varied from 50 to 650 mg/day across the studies. The risk of bias was generally low or unclear. The only outcome for which most of the studies included (6/8 reported a significant reduction was frequency of migraine, which was reduced at an aspirin dosage of at least 325 mg/day. CONCLUSION: Aspirin can reduce the frequency of migraines. However, the optimal dosage is unclear.

  18. [Aspirin in primary and secondary prevention of colorectal carcinomas].

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard

    2013-11-01

    Observational but also some randomized trials suggest that regular long-term use of aspirin (acetylsalicylic acid) might reduce the risk of colorectal carcinomas by 15-40%. The efficacy appears to be increased with longer duration of treatment, i.e. beyond 5-10 years, but not with increasing doses. Aspirin at 75-100 mg daily appears to be sufficient in both primary as well as secondary prevention of recurrent tumors in sensitive persons, including prevention of distant metastases. The pharmacological mode of aspirin action is unclear as is the question whether only one or more sites of action exist. In any case, the mechanism(s) in charge should work at aspirin plasma levels of 10 microM or less which is the maximum concentration to be expected after antiplatelet doses. Inhibition of COX-1 and/or COX-2 is most likely involved. Follow-up reactions, such as inhibition of platelet-dependent thromboxane formation and action, release of storage products such as VEGF or sphingosine-1-phosphate and acetylation of COX-2 with subsequent generation of antioncogenic lipid mediators, such as lipoxins, are also possible. There is not much likelihood for "direct" actions of aspirin, shown in vitro at concentrations of 5 mM and more, which uncouple oxidative phosphorylation and paralyse the cell energy metabolism. benefit/risk profile, specifically regarding severe or fatal bleedings (GI-tract, cerebral). Accordingly, the actual German guideline "colorectal carcinoma" does not recommend aspirin use for prophylactic purposes. What is strongly needed are definitions of risk patients in terms of biomarkers or genetic profiling as well as data from long-term prospective randomized trials--both are underway.

  19. Aspirin use among adults in the U.S.: results of a national survey.

    Science.gov (United States)

    Williams, Craig D; Chan, Andrew T; Elman, Miriam R; Kristensen, Alyson H; Miser, W Fred; Pignone, Michael P; Stafford, Randall S; McGregor, Jessina C

    2015-05-01

    The use of aspirin in patients without cardiovascular disease remains controversial. Patients' understanding of the risks and benefits of aspirin likely contribute to the decision of whether or not to use aspirin regularly. The purpose of this study is to assess patients' knowledge of aspirin and identify factors contributing to regular use. A survey of U.S. adults aged 45-75 years was performed to ascertain aspirin use and factors that may be associated with use. Multivariate logistic regression was used to identify predictors of current use of aspirin among those with a primary prevention indication. The survey was completed in 2012 with data analysis performed in 2013. Among 2,509 respondents, 52% reported current aspirin use. Among 2,039 respondents without a history of cardiovascular disease, current use of aspirin was 47%. Regular use of aspirin for primary prevention was associated with the presence of major cardiovascular disease risk factors (OR=3.0, 95% CI=2.4, 3.7), high self-assessed knowledge of aspirin (OR=9.1, 95% CI=5.2, 15.7), and having discussed aspirin therapy with a provider (OR=25.9, 95% CI=19.7, 34.1). Several markers of healthy lifestyle choices were also associated with regular use. After multivariate analysis, the strongest independent predictor of regular aspirin use was having discussed aspirin therapy with a provider (OR=23.79, 95% CI=17.8, 31.5). Approximately half of the nationwide survey of U.S. adults reported regular aspirin use. Among those with a primary prevention indication, having discussed aspirin with a provider was the strongest predictor of regular use. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Platelet-rich fibrin/aspirin complex promotes alveolar bone regeneration in periodontal defect in rats.

    Science.gov (United States)

    Du, J; Mei, S; Guo, L; Su, Y; Wang, H; Liu, Y; Zhao, Z; Wang, S; Liu, Y

    2018-02-01

    The efficacy and outcomes of aspirin in local defects and the use of platelet-rich fibrin (PRF) in periodontal defects were investigated. Whether the PRF/aspirin complex is a suitable scaffold and delivery system to carry sustained-release aspirin/salicylic acid to promote periodontal bone regeneration was determined. PRF and PRF/aspirin complex were prepared. The concentrations of aspirin/salicylic acid released from the PRF/aspirin complex were calculated at 37°C. Periodontal ligament mesenchymal cells were cultured on six-well plates with PRF or PRF/aspirin complex gel to analyze proliferation and migration. The alveolar bone between the inferior buccal mesial root and anterior buccal distal root of the first maxillary molar was removed in 15 rats randomly divided into three groups: no treatment, PRF or PRF/aspirin complex. Twelve weeks post-transplantation, 2D/3D micro-computed tomography and histomorphometric technique were used for quantitative analyses. The PRF/aspirin complex provided a sustained-release aspirin/salicylic acid. Peak concentrations occurred 4 hours after transplantation and were sustained to 48 hours at 37°C; the total concentration of released aspirin/salicylic acid was 83.5 mg/mL, respectively. The sustained-release promoted the proliferation and migration of periodontal ligament mesenchymal cells. Micro-computed tomography and histological data showed that both the PRF and PRF/aspirin complex enhanced periodontal bone formation (P<.05). Moreover, the new bone formation was two times greater in the PRF/aspirin complex group than the PRF group. Aspirin/salicylic acid could be sustained-released from PRF/aspirin complex, which could inhibit inflammation and improve the function of mesenchymal cells. The data might provide a new safe and easy clinical therapeutic strategy to promote periodontal bone reparation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Effect of ELOM-080 on exacerbations and symptoms in COPD patients with a chronic bronchitis phenotype – a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial

    OpenAIRE

    Beeh KM; Beier J; Candler H; Wittig T

    2016-01-01

    Kai-Michael Beeh,1 Jutta Beier,1 Henning Candler,2 Thomas Wittig2 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2G. Pohl-Boskamp GmbH & Co KG, Hohenlockstedt, Germany Background: Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease (COPD) long-term management. Recently, a more tailored treatment approach has been proposed, in particular for two well-established clinical phenotypes, frequent exacerbators and ...

  2. Is co-morbidity taken into account in the antibiotic management of elderly patients with acute bronchitis and COPD exacerbations?

    Science.gov (United States)

    Bont, Jettie; Hak, Eelko; Birkhoff, Christine E; Hoes, Arno W; Verheij, Theo J M

    2007-09-01

    Guidelines on acute lower respiratory tract infections recommend restrictive use of antibiotics, however, in patients with relevant co-morbid conditions treatment with antibiotics should be considered. Presently, it is unknown whether GPs adhere to these guidelines and target antibiotic treatment more often at patients with risk-elevating conditions. We assessed whether in elderly primary care patients with acute bronchitis or exacerbations of chronic pulmonary disease (COPD), antibiotics are more often prescribed to patients with risk-elevating co-morbid conditions. Using the Utrecht GP research database, we analysed 2643 episodes in patients of 65 years of age or older with a GP-diagnosed acute bronchitis or exacerbation of COPD. Multivariable logistic regression analysis was applied to determine independent determinants of antibiotic use. Antibiotic prescribing rates were high in both acute bronchitis (84%) and in exacerbations of COPD (53%). In acute bronchitis, only age was an independent determinant of antibiotic use [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.003-1.048], whereas in exacerbations of COPD antibiotics were more often prescribed to male patients (OR 1.3, 95% CI 1.0-1.5), patients with diabetes (OR 1.7, 95% CI 1.1-2.4) and heart failure (OR 1.3, 95% CI 1.0-1.7). Dutch GPs prescribe antibiotics in the majority of elderly patients with acute bronchitis and in half of the episodes of exacerbations of COPD. Tailoring their antibiotic treatment according to the presence or absence of high-risk co-morbid conditions could help GPs in improving antibiotic use in patients with respiratory tract infections in primary care.

  3. Risk factors predict frequent hospitalization in patients with acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Wei X

    2017-12-01

    Full Text Available Xia Wei,1,2,* Zhengquan Ma,2,* Nan Yu,3 Jingting Ren,2 Chenwang Jin,1 Jiuyun Mi,2 Meijuan Shi,1 Libin Tian,2 Yanzhong Gao,4 Youmin Guo1 1Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Respiratory Medicine, The Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 3Department of Radiology, The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Shaanxi, 4Department of Radiology, The Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Purpose: COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited. This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.Patients and methods: This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016. During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE group, while the others were grouped into the infrequent exacerbation (IE group. The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.Results: Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1/forced vital capacity (FVC (P=0.005, FEV1%pred (P=0.002, maximal mid-expiratory flow (MMEF25–75%pred (P=0.003, and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA (P=0.03 and higher resonant frequency (Fres; P=0.04. According to generations of bronchi, the percentage of the wall area

  4. Lights and shadows of non-invasive mechanical ventilation for chronic obstructive pulmonary disease (COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Jose Luis Lopez-Campos

    2015-01-01

    Full Text Available Despite the overwhelming evidence justifying the use of non-invasive ventilation (NIV for providing ventilatory support in chronic obstructive pulmonary disease (COPD exacerbations, recent studies demonstrated that its application in real-life settings remains suboptimal. European clinical audits have shown that 1 NIV is not invariably available, 2 its availability depends on countries and hospital sizes, and 3 numerous centers declare their inability to provide NIV to all of the eligible patients presenting throughout the year. Even with an established indication, the use of NIV in acute respiratory failure due to COPD exacerbations faces important challenges. First, the location and personnel using NIV should be carefully selected. Second, the use of NIV is not straightforward despite the availability of technologically advanced ventilators. Third, NIV therapy of critically ill patients requires a thorough knowledge of both respiratory physiology and existing ventilatory devices. Accordingly, an optimal team-training experience, the careful selection of patients, and special attention to the selection of devices are critical for optimizing NIV outcomes. Additionally, when applied, NIV should be closely monitored, and endotracheal intubation should be promptly available in the case of failure. Another topic that merits careful consideration is the use of NIV in the elderly. This patient population is particularly fragile, with several physiological and social characteristics requiring specific attention in relation to NIV. Several other novel indications should also be critically examined, including the use of NIV during fiberoptic bronchoscopy or transesophageal echocardiography, as well as in interventional cardiology and pulmonology. The present narrative review aims to provide updated information on the use of NIV in acute settings to improve the clinical outcomes of patients hospitalized for COPD exacerbations.

  5. The aspirin story - from willow to wonder drug.

    Science.gov (United States)

    Desborough, Michael J R; Keeling, David M

    2017-06-01

    The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century. © 2017 John Wiley & Sons Ltd.

  6. Aspirin for Prophylaxis Against Venous Thromboembolism After Orthopaedic Oncologic Surgery.

    Science.gov (United States)

    Mendez, Gregory M; Patel, Yash M; Ricketti, Daniel A; Gaughan, John P; Lackman, Richard D; Kim, Tae Won B

    2017-12-06

    Patients who undergo orthopaedic oncologic surgical procedures are at increased risk of developing a venous thromboembolism (VTE). Guidelines from surgical societies are shifting to include aspirin as a postoperative VTE prophylactic agent. The purpose of this study was to review our experience using aspirin as postoperative VTE prophylaxis for orthopaedic oncologic surgical procedures. This study was a retrospective review of patients diagnosed with a primary malignant soft-tissue or bone tumor or metastatic carcinoma. Demographic information, histopathologic diagnosis, VTE history, surgical procedure, and VTE prophylaxis were analyzed. VTE rates in the overall and prophylactic-specific cohorts were recorded and compared. A total of 142 distinct surgical procedures in 130 patients were included. VTE prophylaxis with aspirin was used after 103 procedures, and non-aspirin prophylaxis was used after 39. In 33 cases, imaging was used to investigate for VTE because of clinical signs and symptoms. VTE developed after 7 (4.9%) of the 142 procedures. There were 6 deep venous thromboses (DVTs) and 1 pulmonary embolism, and 2 of the VTEs presented in patients with a VTE history. VTE developed in 2.9% (3) of the 103 aspirin cases and 10.3% (4) of the 39 non-aspirin cases. No patient in the aspirin group who had been diagnosed with metastatic carcinoma, malignant soft-tissue sarcoma, lymphoma, or multiple myeloma developed a VTE. Risk factors for VTE development included diabetes mellitus (odds ratio [OR] = 10.40, 95% confidence interval [CI] = 1.61 to 67.30), a history of VTE (OR = 7.26, 95% CI = 1.19 to 44.25), postoperative transfusion (OR = 34.50, 95% CI = 3.94 to 302.01), and estimated blood losses of 250 mL (OR = 1.50, 95% CI = 1.11 to 2.03), 500 mL (OR = 2.26, 95% CI = 1.23 to 4.13), and 1,000 mL (OR = 5.10, 95% CI = 1.52 to 17.04). Aspirin may be a suitable and effective option for VTE chemoprophylaxis in patients treated with orthopaedic oncologic surgery, especially

  7. Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial.

    Science.gov (United States)

    Rodés-Cabau, Josep; Masson, Jean-Bernard; Welsh, Robert C; Garcia Del Blanco, Bruno; Pelletier, Marc; Webb, John G; Al-Qoofi, Faisal; Généreux, Philippe; Maluenda, Gabriel; Thoenes, Martin; Paradis, Jean-Michel; Chamandi, Chekrallah; Serra, Vicenç; Dumont, Eric; Côté, Mélanie

    2017-07-10

    The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. Few data exist on the optimal antithrombotic therapy following TAVR. This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE

  8. Hemorrhagic Cholecystitis in an Elderly Patient Taking Aspirin and Cilostazol

    Directory of Open Access Journals (Sweden)

    David S. Morris

    2008-06-01

    Full Text Available Hemorrhage is a rare complication of acute cholecystitis. Patients who develop this complication often are receiving anticoagulation therapy or have a pathologic coagulopathy. We present a case of an elderly patient who developed hemorrhagic cholecystitis while taking aspirin and cilostazol, a phosphodiesterase inhibitor. The patient underwent an emergent abdominal exploration. A large, blood-filled gallbladder was found along with a large hematoma between the liver and gallbladder. We also briefly review the literature regarding hemorrhagic cholecystitis, hemorrhage into the biliary tree, and hemorrhage as a complication of aspirin and phosphodiesterase inhibitor therapy.

  9. Optimizing the use of aspirin for cardiovascular prevention.

    Science.gov (United States)

    Casado-Arroyo, Rubén; Sostres, Carlos; Lanas, Angel

    2013-06-01

    This article describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin at doses used for cardiovascular prevention and provides specific management recommendations for optimal use in clinical practice. The paper highlights practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, concomitant treatment with other NSAIDs, and strategies for the prevention of gastrointestinal toxicity. Specifically, we revise the benefits and hazards in different clinical settings to help the clinician in the decision-making process for individuals who have different risks for cardiovascular and gastrointestinal bleeding events.

  10. Pidotimod activity against chronic bronchitis exacerbations.

    Science.gov (United States)

    Ciaccia, A

    1994-12-01

    The efficacy of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in the management of infectious exacerbations of chronic bronchitis was evaluated in a double-blind, placebo-controlled study in parallel groups over 5 months (60 days of treatment and 90 days of follow-up). The study enrolled 580 patients, of whom 514 could be evaluated. The pidotimod group had fewer and shorter infectious episodes, fewer days of antibiotic therapy and fewer days unable to undertake normal activities. The difference vs. placebo was significant during the follow-up period and, in those subjects with a less severe history, during the treatment period also. Pidotimod was well tolerated.

  11. Role of antileukotrienes in acute asthma exacerbations

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2012-04-01

    Full Text Available Acute asthma exacerbations are one of the most frequent reasons to visit the emergency department or general practitioner. Although current standard treatments for acute asthma – including supplemental oxygen, short-acting β2-agonists, systemic corticosteroids and anticholinergics – are quite effective in most patients, they are inadequate for rapid and sustained improvement in a significant proportion. The antileukotrienes, a relatively new class of drugs, have a role in the treatment of chronic asthma. Their relatively rapid onset of action after endovenous or oral administration and their additive effect to β2-agonists led to the hypothesis that they might be of benefit in acute asthma. This review examines the efficacy of antileukotrienes in the treatment of acute asthma.

  12. [Treatment of multiple sclerosis symptoms and exacerbations].

    Science.gov (United States)

    Prieto González, José María

    2014-12-01

    In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Exacerbating factors of itch in atopic dermatitis