Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate-severe asthma.

Science.gov (United States)

Han, Jennifer; Nguyen, John; Kim, Yuna; Geng, Bob; Romanowski, Gale; Alejandro, Lawrence; Proudfoot, James; Xu, Ronghui; Leibel, Sydney

2018-04-19

Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. There is a statistically significant increase of 0.369 kg/m 2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m 2 in the low dose group (p BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m 2 per year (p BMI trajectory (p BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

Clinical Characteristics of Fungal Sensitization in Children with Allergic Respiratory Diseases

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Pınar Uysal

2016-08-01

Full Text Available Objective: The aim of the study was to evaluate the prevelance of fungal sensitization among school-aged children with allergic respiratory diseases who attended our outpatient clinic and to evaluate its clinical impact on disease severity. Materials and Methods: Children with allergic symptoms during mould season, who attended our outpatient clinic between January 2014 and August 2015, were evaluated for allergic respiratory diseases. Skin prick testing with fungal and other commercial standardized solutions of aeroallergens was performed in all children. Spirometry was performed in children with asthma. Serum total immunoglobulin E (IgE and aeroallergen specific IgE (sIgE levels were measured. Results: A total of 112 children were included in the study. The prevelance of fungal sensitization was 6.4%. Alternaria alterna was the most common fungal allergen in both mono and polysensitized groups (p=0.002, p=0.004, respectively. Alternaria alterna sensitization was significantly higher in patients with persistent allergic rhinitis compared to those with intermittant allergic rhinitis (p=0.002. The patients with mild asthma were mostly monosensitized (p=0.003, but cases with severe asthma (SA were polysensitized (p=0.007. In polysensitized cases, Alternaria alterna and Cladosporium spp. coexistance was the most common combination compared to other fungal combinations (p<0.001. The sensitivity rate of sIgE was found to be 88%. In spirometric analysis, forced expiratory volume in 1 second (FEV1 and FEV1/forced vital capacity values were lower in polysensitized children with asthma and in children with asthma coexisting allergic rhinitis compared to children with allergic rhinitis only (p=0.004, p=0.001, respectively. Conclusion: The most common fungal allergen was Alternaria alterna in children with mono or polysensitization. Polysensitization with fungal allergens was closely associated with SA and lower spirometric parameters.

Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma

OpenAIRE

Elabras Filho, José; Mello, Fernanda Carvalho de Queiroz; Lupi, Omar; Bica, Blanca Elena Rios Gomes; Papi, José Angelo de Souza; França, Alfeu Tavares

2016-01-01

ABSTRACT Objective: To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. Methods: This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma ba...

The airway microbiome in patients with severe asthma: Associations with disease features and severity.

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Huang, Yvonne J; Nariya, Snehal; Harris, Jeffrey M; Lynch, Susan V; Choy, David F; Arron, Joseph R; Boushey, Homer

2015-10-01

Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. We sought to evaluate relationships between the bronchial microbiome and features of severe asthma. Bronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41). In patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index (P PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01), sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values (per square millimeter, P = .07). Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5), an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria. No taxa were associated with a TH2-related epithelial gene expression signature, but expression of TH17-related genes was associated with Proteobacteria. Patients with severe asthma compared with healthy control subjects or patients with mild-to-moderate asthma were significantly enriched in Actinobacteria, although the largest differences

Severe asthma in childhood

International Nuclear Information System (INIS)

Ciznar, P.

2013-01-01

Patients with severe asthma are clinically, physiologically and biologically a heterogeneous group. About half of children referred for medical examination for severe asthma have true severe, therapy resistant asthma. The rest of referred patients have difficult to treat asthma. Symptoms persist mostly due to drug non-compliance, inappropriate inhalation technique, persistent environmental exposures or co-morbid conditions. Compared with adults have children more frequently atopic form of severe asthma. This is associated with eosinophilia in peripheral blood and sensitization to inhaled allergens. The IgE levels are high. Therapy of co-morbidities and improvement of treatment compliance lead in most cases to full asthma control. Proportion of children will benefit from biologics like anti-IgE monoclonal antibody, administered by subcutaneous injections in 2 to 4 week intervals. By this therapy it is not only possible to suppress symptoms, but also decrease the total steroid dose and the risk of adverse effects associated with its long-term administration. By achieving a full asthma control we lower future risk of exacerbations and probably improve long-term prognosis of disease, frequently persisting for the rest of life. (author)

Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma

NARCIS (Netherlands)

Scicchitano, R; Aalbers, R; Ukena, D; Manjra, A; Fouquert, L; Centanni, S; Boulet, LP; Naya, IP; Hultquist, C

Objectives:This study evaluated the efficacy and safety of a novel asthma management strategy - budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy*) - compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

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Lambert, Katrina A; Prendergast, Luke A; Dharmage, Shyamali C; Tang, Mimi; O'Sullivan, Molly; Tran, Thomas; Druce, Julian; Bardin, Philip; Abramson, Michael J; Erbas, Bircan

2017-10-11

It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

[Predictive factors associated with severity of asthma exacerbations].

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Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

2008-01-01

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

The real world effect of omalizumab add on therapy for patients with moderate to severe allergic asthma: The ASTERIX Observational study.

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Mohit Bhutani

Full Text Available Omalizumab is a non-steroidal medication indicated for the treatment of poorly controlled moderate-to-severe allergic asthmatics. This observational study examines the "real world" effectiveness of omalizumab in this population.This is a one year open-label observational study that compared clinical outcomes including total oral corticosteroid use, exacerbation history, measures of quality of life and inflammation in patients with moderate-to-severe allergic asthma, who were prescribed omalizumab as part of their treatment with the year prior to therapy.A total of 99 patients were enrolled at 25 sites in Canada. During the study period, the mean total annual OCS dose was reduced from 2301.5 mg (prednisone equivalents in the year prior to omalizumab to 1130.0 mg (p<0.0001. There was a 71% reduction in asthma exacerbations and 56% of patients on omalizumab remained exacerbation free when compared to the year prior to study entry. Associated with this was reduced health care utilization. There were significant improvements in the Asthma Control Questionnaire (ACQ and Asthma Quality of Life questionnaire (AQLQ Patients with an elevated FeNO at baseline showed a better response to treatment. No new safety issues were identified during the study period.Our study demonstrates that in "real world" clinical practice, after initiating omalizumab, there is a reduction in total OCS use and exacerbation frequency in patients with moderate-to-severe allergic asthma. Patients on treatment reported improved asthma control and quality of life. FeNO may be a useful biomarker to identify patients who may benefit with omalizumab treatment.

Serum YKL-40 and assessment of severity of bronchial asthma in ...

African Journals Online (AJOL)

EL-HAKIM

YKL-40 and asthma severity. 95. Table 1. Characteristics of the studied groups. Variable. Control. (n=15). Mild-Moderate asthma. (n=15). Severe asthma. (n=15). Age (yrs) mean±SD. 7.7±4.7. 6.6±4.9. 3.3±2.7. Gender (male); n (%). 10 (67%). 9 (60%). 8 (50%). PAS score. 0-4 (normal). 5-7 (mild attack). 8-11(moderate).

The real world effect of omalizumab add on therapy for patients with moderate to severe allergic asthma: The ASTERIX Observational study.

Science.gov (United States)

Bhutani, Mohit; Yang, William H; Hébert, Jacques; de Takacsy, Frederica; Stril, Jean-Louis

2017-01-01

Omalizumab is a non-steroidal medication indicated for the treatment of poorly controlled moderate-to-severe allergic asthmatics. This observational study examines the "real world" effectiveness of omalizumab in this population. This is a one year open-label observational study that compared clinical outcomes including total oral corticosteroid use, exacerbation history, measures of quality of life and inflammation in patients with moderate-to-severe allergic asthma, who were prescribed omalizumab as part of their treatment with the year prior to therapy. A total of 99 patients were enrolled at 25 sites in Canada. During the study period, the mean total annual OCS dose was reduced from 2301.5 mg (prednisone equivalents) in the year prior to omalizumab to 1130.0 mg (pomalizumab remained exacerbation free when compared to the year prior to study entry. Associated with this was reduced health care utilization. There were significant improvements in the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life questionnaire (AQLQ) Patients with an elevated FeNO at baseline showed a better response to treatment. No new safety issues were identified during the study period. Our study demonstrates that in "real world" clinical practice, after initiating omalizumab, there is a reduction in total OCS use and exacerbation frequency in patients with moderate-to-severe allergic asthma. Patients on treatment reported improved asthma control and quality of life. FeNO may be a useful biomarker to identify patients who may benefit with omalizumab treatment.

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

Science.gov (United States)

Boita, Monica; Heffler, Enrico; Omedè, Paola; Bellocchia, Michela; Bussolino, Claudia; Solidoro, Paolo; Giorgis, Veronica; Guerrera, Francesco; Riva, Giuseppe; Brussino, Luisa; Bucca, Caterina; Rolla, Giovanni

2018-01-01

Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity. © 2018 S. Karger AG, Basel.

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database

Directory of Open Access Journals (Sweden)

Lee H

2016-04-01

prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD.Methods: Patients with mild-to-moderate COPD (≥40 years were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012 and were linked to the national health insurance reimbursement database to obtain medical service utilization records.Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6% had severe exacerbations over the 6 years (0.012/person-year. Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001. A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002–2.77, P=0.049. In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD.Conclusion: In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients. Keywords: bronchial asthma, chronic obstructive pulmonary disease, acute exacerbation

CYTOLOGICAL AND MORPHOMETRIC ESTIMATE OF THE INFLAMMATION AMONG THE CHILDREN, SUFFERING FROM MODERATELY SEVERE BRONCHIAL ASTHMA

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T.R. Dulina

2007-01-01

Full Text Available The search for the new noninvasive and information methods to estimate the intensity of the inflammatory processes during the bronchial asthma is an important task for the modern medicine, pediatrics, in particular. We have examined 20 children, suffering from moderately severe bronchial asthma in remission. patients underwent the induction of the sputum by means of nail hypertonic solution, bronchoscopic examination along with the sampling of the lavage fluid and bronchial biopsy, cytometry of the induced sputum and bronchoalveolar lavage fluid, morphometric examination of the biopsy samples of bronchi walls, determination of the nitric oxide contents in the expired air. We revealed high self descriptiveness of the cytological characteristics of the induced sputum. High percentage of neutrophiles and eosinophiles in the induced sputum disclosed during remission of the bronchial asthma, as well as thickness increase of the basilemma, ratio distortion of the ciliated and cyathiform cells in the favor of the latter, especially along with the high nitric oxide contents in the expired air indicate the continuous persistence in the allergic respiratory inflammation.Key words: induced sputum, bronchial asthma, children.

Environmental and Personal Factors Related to Asthma Severity among Children: Hospital Based Study, Egypt

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Omaima Ibrahim AboElkheir

2016-09-01

Full Text Available Background: Childhood asthma is a complex disorder in which many environmental and personal factors play a role. However, the contribution of these factors to asthma severity is poorly understood. This study aims to determine the relationship between environmental exposures, personal factors and asthma severity among asthmatic children. Methods: This cross-sectional hospital based study was conducted on 180 asthmatic children; they were divided into mild, moderate and severe asthma according to forced expiratory volume in first second. Environmental factors (indoor and outdoor, food allergy, history of other allergic diseases, family history of allergic disorders, time trend of attacks as well as asthma outcome were reported. Results: Children with severe asthma were younger than those with mild or moderate asthma. Severe asthma was significantly linked to family history of allergy, presence of co-morbid allergic diseases, fish, egg and milk allergy, as well as exposure to passive smoking (73.7% and poor housing conditions. Also, it was significantly linked to presence of unauthorized factories in residential area (31.6 %, p=0.001. As well as, contact with pets (42.1%. Children with severe asthma had more limitations of physical activities (73.7%, missed school days (81.5%, with poor school performance (p=0.04 than those with mild moderate or asthma. Conclusion: Severe asthma was linked to female gender and younger age, co-morbid allergic diseases, family history of atopy and food allergy. It was higher among children residing in places with unauthorized factories and living in substandard housing condition. Children with severe asthma had poor asthma outcome.

Atopy, but not obesity is associated with asthma severity among children with persistent asthma.

Science.gov (United States)

Lu, Kim D; Phipatanakul, Wanda; Perzanowski, Matthew S; Balcer-Whaley, Susan; Matsui, Elizabeth C

2016-12-01

Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma. A cross-sectional analysis of 832 children and adolescents, age range 5-17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA. Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step. Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States.

Poor Executive Functions among Children with Moderate-into-Severe Asthma: Evidence from WCST Performance.

Science.gov (United States)

Taha, Haitham

2017-01-01

Executive functions (EFs) measures of 27 asthmatic children, with general learning difficulties, were tested by using the Wisconsin card sorting test (WCST), and were compared to the performances of 30 non-asthmatic children with general learning difficulties. The results revealed that the asthmatic group has poor performance through all the WCST psychometric parameters and especially the perseverative errors one. The results were discussed in light of the postulation that poor EFs could be associated with the learning difficulties of asthmatic children. Neurophysiological framework has been suggested to explain the etiology of poor EFs among children with moderate into severe asthma.

Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review.

Science.gov (United States)

Corren, Jonathan; Kavati, Abhishek; Ortiz, Benjamin; Colby, Jennifer A; Ruiz, Kimberly; Maiese, Brett A; Cadarette, Sarah M; Panettieri, Reynold A

2017-07-01

There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma. The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinical trials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. Studies that evaluated omalizumab use in patients omalizumab RCTs. Overall, the mean rate of annual exacerbations was significantly lower after 6 months to 2 years of treatment with omalizumab in both RCTs and RWS. In two RCTs and three RWS, inhaled corticosteroid use was significantly reduced in patients who used omalizumab. Similar reductions in the use of rescue medication were also observed in the RCTs and RWS on omalizumab. Real-world evidence demonstrated improvement in forced expiratory volume in the first second of expiration (% predicted) in patients treated with omalizumab as well as significant improvement in the level of asthma control observed over 1 year. There also was evidence that omalizumab treatment reduced health care resource utilization, including fewer hospitalizations, emergency department visits, and unscheduled medical visits. Safety outcomes in all five RWS showed no new safety signals and demonstrated that omalizumab was well tolerated. Overall, RCT evidence strongly supported omalizumab efficacy and safety as add-on treatment in children 6 to 11 years old with moderate-to-severe persistent allergic asthma. RWS data confirmed these findings in an extended patient population of children and adolescents that is more generalizable to the actual day-to-day management of these patients.

Efficacy of omalizumab (Xolair®) in patients with moderate to severe predominately chronic oral steroid dependent asthma in Taiwan: a retrospective, population-based database cohort study.

Science.gov (United States)

Chen, Hao-Cheng; Huang, Chien-Da; Chang, Erin; Kuo, Han-Pin

2016-01-08

Omalizumab (Xolair®), a recombinant monoclonal anti-IgE antibody, has demonstrated efficacy in clinical trials conducted in patients with moderate to severe persistent allergic asthma. We aimed to investigate the efficacy, discontinuation and medical resource utilization of omalizumab in the real-life setting in Taiwan. This study was a retrospective, population-based database cohort study using the Taiwan NHIRD from 2007 to 2011 assessing the efficacy of omalizumab therapy over 4 months on changes in asthma medication, asthma control, frequency of exacerbations and hospitalization rates at baseline and after omalizumab discontinuation. There was a reduction in asthma medication post omalizumab therapy and severe exacerbations and hospitalizations from baseline (31.2%, n = 282) to the end of follow-up (11.8%, n = 144, p omalizumab, the cost of ER medical expenses decreased from New Taiwan dollars (NTD) 3934 at 2 months to NTD 2860 at 12 months. Patients who received omalizumab therapy for over 4 months were more likely to reduce the use of other asthma medications and less likely to experience an asthma exacerbation, ER visits, and hospitalization, even after the discontinuation of omalizumab. These data suggest that omalizumab has efficacy in improving health outcomes in patients with moderate to severe predominately chronic oral steroid dependent asthma in the real-life setting in Taiwan.

Management of severe asthma: targeting the airways, comorbidities and risk factors.

Science.gov (United States)

Gibson, Peter G; McDonald, Vanessa M

2017-06-01

Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA. © 2017 Royal Australasian College of Physicians.

Dupilumab in the management of moderate-to-severe asthma: the data so far

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Barranco P

2017-09-01

Full Text Available Pilar Barranco,1 Elsa Phillips-Angles,2 Javier Dominguez-Ortega,1 Santiago Quirce1 1Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ, CIBER de Enfermedades Respiratorias (CIBERES, Madrid, Spain; 2Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ, Madrid, Spain Abstract: Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem – with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies – particularly, selective targeted monoclonal antibodies (mAbs. It is noteworthy that in approximately 50% of these patients, there is strong evidence of the pathogenic role of T helper type-2 (Th2 cytokines, such as interleukin (IL-4 and IL-13, orchestrating the eosinophilic and allergic inflammatory processes. Among the recently developed antiasthma biologic drugs, the mAb dupilumab is very promising given its ability to inhibit the biological effects of both IL-4 and IL-13. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future. Keywords: dupilumab, asthma, interleukin-4, interleukin-13, monoclonal antibodies, treatment

Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma.

Science.gov (United States)

Elabras, José; Mello, Fernanda Carvalho de Queiroz; Lupi, Omar; Bica, Blanca Elena Rios Gomes; Papi, José Angelo de Souza; França, Alfeu Tavares

2016-01-01

To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma based on the Global Initiative for Asthma criteria: mild asthma (MA), comprising patients with mild intermittent or persistent asthma; and moderate or severe asthma (MSA). We determined the serum levels of staphylococcal toxin-specific IgE antibodies, comparing the results and performing a statistical analysis. The study included 142 patients: 72 in the MA group (median age = 46 years; 59 females) and 70 in the MSA group (median age = 56 years; 60 females). In the sample as a whole, 62 patients (43.7%) presented positive results for staphylococcal toxin-specific IgE antibodies: staphylococcal enterotoxin A (SEA), in 29 (20.4%); SEB, in 35 (24.6%); SEC, in 33 (23.2%); and toxic shock syndrome toxin (TSST), in 45 (31.7%). The mean serum levels of IgE antibodies to SEA, SEB, SEC, and TSST were 0.96 U/L, 1.09 U/L, 1.21 U/L, and 1.18 U/L, respectively. There were no statistically significant differences between the two groups in terms of the qualitative or quantitative results. Serum IgE antibodies to SEA, SEB, SEC, and TSST were detected in 43.7% of the patients in our sample. However, neither the qualitative nor quantitative results showed a statistically significant association with the clinical severity of asthma. Determinar a presença de anticorpos IgE específicos para superantígenos estafilocócicos e o grau de sensibilização mediada por esses, assim como se esses estão associados à gravidade da asma em pacientes adultos. Estudo transversal incluindo asmáticos adultos em acompanhamento ambulatorial em

Alternaria leaf spot in Michigan and fungicide sensitivity issues

Science.gov (United States)

Since 2010 there has been an increase in identification of Alternaria leaf spot on sugar beet in Michigan and other growing regions in the US and Canada. In 2016, the disease was severe enough to cause economic losses in the Michigan growing region. Michigan isolates from sugar beet were examined ...

The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts

NARCIS (Netherlands)

Fleming, Louise; Murray, Clare; Bansal, Aruna T.; Hashimoto, Simone; Bisgaard, Hans; Bush, Andrew; Frey, Urs; Hedlin, Gunilla; Singer, Florian; van Aalderen, Wim M.; Vissing, Nadja H.; Zolkipli, Zaraquiza; Selby, Anna; Fowler, Stephen; Shaw, Dominick; Chung, Kian Fan; Sousa, Ana R.; Wagers, Scott; Corfield, Julie; Pandis, Ioannis; Rowe, Anthony; Formaggio, Elena; Sterk, Peter J.; Roberts, Graham; Tariq, Kamran; Dennison, Patrick; Behndig, Annelie F.; Lutter, Rene; Wagener, Ariane; van Drunen, Kees; Hekking, Pieter-Paul; Brinkman, Paul; Zwinderman, Koos; Mores, Nadia; Santini, Giuseppe; Valente, Salvatore; Rossios, Christos; Gibeon, David; Hoda, Uruj; Rocha, João Pedro Carvalho da Purificação; Sogbesan, Adesimbo; Gent, Julaiha; Menzies-Gow, Andrew; Campagna, Davide; Bigler, Jeannette; Boedigheimer, Michael J.; Yu, Wen; Hu, Xugang; Fichtner, Klaus; Nething, Katja

2015-01-01

U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches. A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53

Co-morbidities in severe asthma

DEFF Research Database (Denmark)

Porsbjerg, Celeste; Menzies-Gow, Andrew

2017-01-01

Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma...... to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical...... impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD...

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

DEFF Research Database (Denmark)

Shaw, Dominick E; Sousa, Ana R; Fowler, Stephen J

2015-01-01

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe...... asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations...

Comparison of six-minute walk test in children with moderate/severe asthma with reference values for healthy children

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Lívia Barboza de Andrade

Full Text Available OBJECTIVE:to compare physical performance and cardiorespiratory responses in the six-minute walk test (6MWT in asthmatic children with reference values for healthy children in the same age group, and to correlate them with intervening variables.METHODS:this was a cross-sectional, prospective study that evaluated children with moderate/severe asthma, aged between 6 and 16 years, in outpatient follow-up. Demographic and spirometric test data were collected. All patients answered the pediatric asthma quality of life (QoL questionnaire (PAQLQ and level of basal physical activity. The 6MWT was performed, following the American Thoracic Society recommendations. Comparison of means was performed using Student's t-test and Pearson's correlation to analyze the 6MWT with study variables. The significance level was set at 5%.RESULTS:40 children with moderate or severe asthma were included, 52.5% males, 70% with normal weight and sedentary. Mean age was 11.3 ± 2.1 years, mean height was 1.5 ± 0.1 m, and mean weight was 40.8 ± 12.6 Kg. The mean distance walked in the 6MWT was significantly lower, corresponding to 71.9% ± 19.7% of predicted values; sedentary children had the worst values. The difference between the distance walked on the test and the predicted values showed positive correlation with age (r = 0.373, p = 0.018 and negative correlation with cardiac rate at the end of the test (r = -0.518, p < 0.001. Regarding QoL assessment, the values in the question about physical activity limitations showed the worst scores, with a negative correlation with walked distance difference (r = -0.311, p = 0.051.CONCLUSIONS:asthmatic children's performance in the 6MWT evaluated through distance walked is significantly lower than the predicted values for healthy children of the same age, and is directly influenced by sedentary life style.

Household mold and dust allergens: Exposure, sensitization and childhood asthma morbidity

International Nuclear Information System (INIS)

Gent, Janneane F.; Kezik, Julie M.; Hill, Melissa E.; Tsai, Eling; Li, De-Wei; Leaderer, Brian P.

2012-01-01

Background: Few studies address concurrent exposures to common household allergens, specific allergen sensitization and childhood asthma morbidity. Objective: To identify levels of allergen exposures that trigger asthma exacerbations in sensitized individuals. Methods: We sampled homes for common indoor allergens (fungi, dust mites (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1) and cockroach (Bla g 1)) for levels associated with respiratory responses among school-aged children with asthma (N=1233) in a month-long study. Blood samples for allergy testing and samples of airborne fungi and settled dust were collected at enrollment. Symptoms and medication use were recorded on calendars. Combined effects of specific allergen sensitization and level of exposure on wheeze, persistent cough, rescue medication use and a 5-level asthma severity score were examined using ordered logistic regression. Results: Children sensitized and exposed to any Penicillium experienced increased risk of wheeze (odds ratio [OR] 2.12 95% confidence interval [CI] 1.12, 4.04), persistent cough (OR 2.01 95% CI 1.05, 3.85) and higher asthma severity score (OR 1.99 95% CI 1.06, 3.72) compared to those not sensitized or sensitized but unexposed. Children sensitized and exposed to pet allergen were at significantly increased risk of wheeze (by 39% and 53% for Fel d 1>0.12 μg/g and Can f 1>1.2 μg/g, respectively). Increased rescue medication use was significantly associated with sensitization and exposure to Der p 1>0.10 μg/g (by 47%) and Fel d 1>0.12 μg/g (by 32%). Conclusion: Asthmatic children sensitized and exposed to low levels of common household allergens Penicillium, Der p 1, Fel d 1 and Can f 1 are at significant risk for increased morbidity. - Highlights: ► Few studies address concurrent allergen exposures, sensitization and asthma morbidity. ► Children with asthma were tested for sensitivity to common indoor allergens. ► Homes were sampled for these allergens and asthma

Asthma Is More Severe in Older Adults

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Dweik, Raed A.; Comhair, Suzy A.; Bleecker, Eugene R.; Moore, Wendy C.; Peters, Stephen P.; Busse, William W.; Jarjour, Nizar N.; Calhoun, William J.; Castro, Mario; Chung, K. Fan; Fitzpatrick, Anne; Israel, Elliot; Teague, W. Gerald; Wenzel, Sally E.; Love, Thomas E.; Gaston, Benjamin M.

2015-01-01

Background Severe asthma occurs more often in older adult patients. We hypothesized that the greater risk for severe asthma in older individuals is due to aging, and is independent of asthma duration. Methods This is a cross-sectional study of prospectively collected data from adult participants (N=1130; 454 with severe asthma) enrolled from 2002 – 2011 in the Severe Asthma Research Program. Results The association between age and the probability of severe asthma, which was performed by applying a Locally Weighted Scatterplot Smoother, revealed an inflection point at age 45 for risk of severe asthma. The probability of severe asthma increased with each year of life until 45 years and thereafter increased at a much slower rate. Asthma duration also increased the probability of severe asthma but had less effect than aging. After adjustment for most comorbidities of aging and for asthma duration using logistic regression, asthmatics older than 45 maintained the greater probability of severe asthma [OR: 2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma continued to increase in men, but not in women. Conclusions Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma. PMID:26200463

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

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Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

2017-06-01

Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

Sensitization predicts asthma development among wheezing toddlers in secondary healthcare.

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Boersma, Nienke A; Meijneke, Ruud W H; Kelder, Johannes C; van der Ent, Cornelis K; Balemans, Walter A F

2017-06-01

Some wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain. This study examines the predictive value of sensitization to inhalant allergens among wheezing toddlers in secondary healthcare for the development of asthma at school age (≥6 years). Preschool children (1-3 years) who presented with wheezing in secondary healthcare were screened on asthma at school age with the International Study of Asthma and Allergies in Childhood questionnaire. The positive and negative predictive value (PPV and NPV) of specific IgE to inhalant allergens (cut-off concentration 0.35 kU/L) and several non-invasive variables from a child's history (such as hospitalization, eczema, and parental atopy) were calculated. The additional predictive value of sensitization when combined with non-invasive predictors was examined in multivariate analysis and by ROC curves. Of 116 included children, 63% developed asthma at school age. Sensitization to inhalant allergens was a strong asthma predictor. The odds ratio (OR), PPV and NPV were 7.4%, 86%, and 55%, respectively. Eczema (OR 3.4) and hospital admission (OR 2.6) were significant non-invasive determinants. Adding sensitization to these non-invasive predictors in multivariate analysis resulted in a significantly better asthma prediction. The area under the ROC curve increased from 0.70 with only non-invasive predictors to 0.79 after adding sensitization. Sensitization to inhalant allergens is a strong predictor of school age asthma in secondary healthcare and has added predictive value when combined with non-invasive determinants. Pediatr Pulmonol. 2017;52:729-736. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma

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Charleston Ribeiro Pinto

2013-06-01

Full Text Available OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx associated with the use of inhaled corticosteroids (ICSs in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5% were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5% were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5% reported at least one adverse effect, and 131 (65.5% had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5% and 154 (77.0% of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here.

Household mold and dust allergens: Exposure, sensitization and childhood asthma morbidity

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Gent, Janneane F., E-mail: janneane.gent@yale.edu [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Kezik, Julie M., E-mail: julie.colburn@yale.edu [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Hill, Melissa E., E-mail: melissa.hill@yale.edu [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Tsai, Eling, E-mail: tsai.umiami@gmail.com [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Li, De-Wei, E-mail: DeWei.Li@ct.gov [Connecticut Agricultural Experiment Station, Valley Laboratory, 153 Cook Hill Road, Windsor, CT 06095 (United States); Leaderer, Brian P., E-mail: brian.leaderer@yale.edu [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States)

2012-10-15

Background: Few studies address concurrent exposures to common household allergens, specific allergen sensitization and childhood asthma morbidity. Objective: To identify levels of allergen exposures that trigger asthma exacerbations in sensitized individuals. Methods: We sampled homes for common indoor allergens (fungi, dust mites (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1) and cockroach (Bla g 1)) for levels associated with respiratory responses among school-aged children with asthma (N=1233) in a month-long study. Blood samples for allergy testing and samples of airborne fungi and settled dust were collected at enrollment. Symptoms and medication use were recorded on calendars. Combined effects of specific allergen sensitization and level of exposure on wheeze, persistent cough, rescue medication use and a 5-level asthma severity score were examined using ordered logistic regression. Results: Children sensitized and exposed to any Penicillium experienced increased risk of wheeze (odds ratio [OR] 2.12 95% confidence interval [CI] 1.12, 4.04), persistent cough (OR 2.01 95% CI 1.05, 3.85) and higher asthma severity score (OR 1.99 95% CI 1.06, 3.72) compared to those not sensitized or sensitized but unexposed. Children sensitized and exposed to pet allergen were at significantly increased risk of wheeze (by 39% and 53% for Fel d 1>0.12 {mu}g/g and Can f 1>1.2 {mu}g/g, respectively). Increased rescue medication use was significantly associated with sensitization and exposure to Der p 1>0.10 {mu}g/g (by 47%) and Fel d 1>0.12 {mu}g/g (by 32%). Conclusion: Asthmatic children sensitized and exposed to low levels of common household allergens Penicillium, Der p 1, Fel d 1 and Can f 1 are at significant risk for increased morbidity. - Highlights: Black-Right-Pointing-Pointer Few studies address concurrent allergen exposures, sensitization and asthma morbidity. Black-Right-Pointing-Pointer Children with asthma were tested for sensitivity to common indoor allergens

Alternaria section Alternaria: Species, formae speciales or pathotypes'

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Woudenberg, J.H.C.; Seidl, M.F.; Groenewald, J.Z.; de Vries, M .; Stielow, B.; Thomma, B.P.H.J.; Crous, P.W.

2015-01-01

The cosmopolitan fungal genus Alternaria consists of multiple saprophytic and pathogenic species. Based on phylogenetic and morphological studies, the genus is currently divided into 26 sections. Alternaria sect. Alternaria contains most of the small-spored Alternaria species with concatenated

Alternaria section Alternaria: Species, formae speciales or pathotypes?

NARCIS (Netherlands)

Woudenberg, J.H.C.; Seidl, M.F.; Groenewald, J.Z.; Vries, de M.; Stielow, J.B.; Thomma, B.; Crous, P.W.

2015-01-01

The cosmopolitan fungal genus Alternaria consists of multiple saprophytic and pathogenic species. Based on phylogenetic and morphological studies, the genus is currently divided into 26 sections. Alternaria sect. Alternaria contains most of the small-spored Alternaria species with concatenated

Current concepts of severe asthma

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Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

2016-01-01

The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

The effect of various breathing exercises (pranayama in patients with bronchial asthma of mild to moderate severity

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Saxena Tarun

2009-01-01

Full Text Available Background/Aim: The incidence of bronchial asthma is on increase. Chemotherapy is helpful during early course of the disease, but later on morbidity and mortality increases. The efficacy of yoga therapy though appreciated is yet to be defined and modified. Aim: To study the effect of breathing exercises ( pranayama in patients with bronchial asthma of mild to moderate severity. Materials and Methods: Fifty cases of bronchial asthma (Forced Expiratory Volume in one second (FEV1 > 70% were studied for 12 weeks. Patients were allocated to two groups: group A and group B (control group. Patients in group A were treated with breathing exercises (deep breathing, Brahmari , and Omkara , etc. for 20 minutes twice daily for a period of 12 weeks. Patients were trained to perform Omkara at high pitch (forceful with prolonged exhalation as compared to normal Omkara . Group B was treated with meditation for 20 minutes twice daily for a period of 12 weeks. Subjective assessment, FEV1%, and Peak Expiratory Flow Rate (PEFR were done in each case initially and after 12 weeks. Results: After 12 weeks, group A subjects had significant improvement in symptoms, FEV1, and PEFR as compared to group B subjects. Conclusion: Breathing exercises ( pranayama , mainly expiratory exercises, improved lung function subjectively and objectively and should be regular part of therapy.

Investigating the Possibility to Individualize Asthma Attack Therapy Based on Attack Severity and Patient Characteristics

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Sárkány Zoltán

2016-03-01

Full Text Available Introduction: The objective of this study was to investigate with the help of a computerized simulation model whether the treatment of an acute asthma attack can be individualized based on the severity of the attack and the characteristics of the patient. Material and Method: A stochastic lung model was used to simulate the deposition of 1 nm - 10 μm particles during a mild and a moderate asthma attack. Breathing parameters were varied to maximize deposition, and simulation results were compared with those obtained in the case of a severe asthma attack. In order to investigate the effect of height on the deposition of inhaled particles, another series of simulations was carried out with identical breathing parameters, comparing patient heights of 155 cm, 175 cm and 195 cm. Results: The optimization process yielded an increase in the maximum deposition values of around 6-7% for each type of investigated asthma attack, and the difference between attacks of different degree of severity was around 5% for both the initial and the optimized values, a higher degree of obstruction increasing the amount of deposited particles. Conclusions: Our results suggest that the individualization of asthma attack treatment cannot be based on particles of different size, as the highest deposited fraction in all three types of attacks can be obtained using 0.01 μm particles. The use of a specific set of breathing parameters yields a difference between a mild and a moderate, as well as a moderate and a severe asthma attack of around 5%.

Severe bronchial asthma in children: the role of clinical and anamnestic indices in diagnosis verification

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Kolyubakina L.V.

2016-03-01

Full Text Available The paper presents comparative analysis of results of clinical and anamnestic examination of children depending on the asthma severity. Severe asthma in schoolchildren relative to moderate phenotype characterized by birth overweight, more burdened individual allergic history, highly infectious index, drug or combined (medication, food and household allergies, seasonal exacerbations (mainly from November to March, what associated with the trigger role of ARVI and meteorological factors, inadequate asthma control during standard basic therapy.

Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics.

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Konradsen, Jon R; Nordlund, Björn; Onell, Annica; Borres, Magnus P; Grönlund, Hans; Hedlin, Gunilla

2014-03-01

Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. Children with severe asthma had lower asthma control (p Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Serum IL-33 Is Elevated in Children with Asthma and Is Associated with Disease Severity.

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Bahrami Mahneh, Sedigheh; Movahedi, Masoud; Aryan, Zahra; Bahar, Mohammad Ali; Rezaei, Arezou; Sadr, Maryam; Rezaei, Nima

2015-01-01

The role of IL-33, a member of the IL-1 family, in airway hyperresponsiveness and asthma has still to be fully understood. This study is aimed at investigating serum IL-33 in children with asthma and its association with asthma severity. This age- and sex-matched case-control study comprised 61 children with asthma and 63 healthy controls. The mean age of the participants was 9.21 years (range: 6-14). Serum IL-33 was measured using ELISA and was compared between children with asthma and controls. In addition, the association of serum IL-33 with asthma severity was investigated. The level of serum IL-33 was significantly higher in children with asthma than in controls (15.17 ± 32.3 vs. 0.61 ± 2.16 pg/ml; p = 0.028). It was significantly increased proportionately to asthma severity, namely 9.92 ± 30.26 pg/ml in children with mild asthma, 13.68 ± 29.27 pg/ml in children with moderate asthma and 31.92 ± 41.45 pg/ml in children with severe asthma (p = 0.026). Serum IL-33 is increased in children with asthma and is associated with disease severity. © 2016 S. Karger AG, Basel.

Mechanisms of aspirin-sensitive asthma

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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

IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis.

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Irene Mittermann

Full Text Available Atopic dermatitis (AD is a complex chronic inflammatory disease where allergens can act as specific triggering factors.To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens.Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53 and moderate AD (n = 126. As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins.IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1 and house dust mite (rDer p 4 and 10, to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD.We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.

IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis.

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Mittermann, Irene; Wikberg, Gustav; Johansson, Catharina; Lupinek, Christian; Lundeberg, Lena; Crameri, Reto; Valenta, Rudolf; Scheynius, Annika

2016-01-01

Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.

Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma

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Rossios, Christos; Pavlidis, Stelios; Hoda, Uruj; Kuo, Chih-Hsi; Wiegman, Coen; Russell, Kirsty; Sun, Kai; Loza, Matthew J.; Baribaud, Frederic; Durham, Andrew L.; Ojo, Oluwaseun; Lutter, Rene; Rowe, Anthony; Bansal, Aruna; Auffray, Charles; Sousa, Ana; Corfield, Julie; Djukanovic, Ratko; Guo, Yike; Sterk, Peter J.; Chung, Kian Fan; Adcock, Ian M.

2018-01-01

Sputum analysis in asthmatic patients is used to define airway inflammatory processes and might guide therapy. We sought to determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared with nonsmoking patients with mild/moderate asthma. Induced

Concordance of opinions between patients and physicians and their relationship with symptomatic control and future risk in patients with moderate-severe asthma.

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Crespo-Lessmann, Astrid; Plaza, Vicente; González-Barcala, Francisco-Javier; Fernández-Sánchez, Toni; Sastre, Joaquín

2017-01-01

Differences between the opinions of patients and physicians on the impact of asthma are common. We hypothesised that patient-physician discordance may negatively affect asthma outcome. A total of 2902 patients (61% women, mean age 47 years) with moderate-severe asthma and 231 physicians participated in a prospective study. At the baseline visit, data on demographics, clinical variables, degree of asthma control according to the Asthma Control Test (ACT), basic spirometry and the Hospital Anxiety and Depression Scale (HADS) were collected and an ad hoc questionnaire was completed that allowed the degree of concordance between doctors and patients to be assessed. A scheduled telephone call after 3 months was used to elicit the ACT score and the future risk of asthma. At the final visit at 6 months, the following data were recorded: ACT score, spirometry, HADS score and an ad hoc questionnaire to assess the agreement between the doctor and the patient. Changes in study variables according to patient-physician concordance or discordance were analysed. The rate of patient-physician discordance was 27.2%, with overestimation of disease impact by the physician in 12.3% and underestimation in 14.9%. Patient-physician opinion discordance, particularly in the case of physicians underestimating the impact of asthma, showed worse results with statistically significant differences in ACT score, a higher percentage of patients with poor asthma control and lower HADS scores. The need for hospital and emergency department admissions was also higher. Patient-physician opinion discordance may be contributing to lower symptomatic control and increased future risk, with a higher impact when physicians underestimate the impact of asthma on their patients.

cFLIP expression is altered in severe corticosteroid-resistant asthma

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Dennis Lazarev

2014-12-01

Full Text Available Dysregulation of alternative splicing of mRNA precursors is known to contribute to numerous human diseases. In this study we carried out the first systematic search for asthma-associated changes in alternative splicing events, using a model of Aspergillus fumigatus (A. fumigatus-sensitized mice and an exon junction microarray to detect potential changes in alternative splicing. One of the sensitization-associated changes identified in the search was a shift in alternative splicing of the mRNA encoding cFLIP, a modulator of the caspase-mediated extrinsic apoptosis pathway. Expanding these studies to human asthma patients, we discovered a significant decrease in the expression of both cFLIP isoforms in severe corticosteroid-resistant asthmatics. Although it is unclear whether these changes were due solely to differences in alternative splicing, these findings provide evidence that dysregulation of the extrinsic apoptosis pathway is part of the underlying immunopathogenesis of severe refractory asthma.

Managing problematic severe asthma: beyond the guidelines.

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Pike, Katharine C; Levy, Mark L; Moreiras, John; Fleming, Louise

2018-04-01

This review discusses issues related to managing problematic severe asthma in children and young people. A small minority of children have genuinely severe asthma symptoms which are difficult to control. Children with genuinely severe asthma need investigations and treatments beyond those described within conventional guidelines. However, the majority of children with poor symptom control despite high-intensity treatment achieve improvement in their asthma control once attention has been paid to the basics of asthma management. Basic asthma management requires optimisation of inhaler technique and treatment adherence, avoidance of environmental triggers and self-management education. It is also important that clinicians recognise risk factors that predispose patients to asthma exacerbations and potentially life-threatening attacks. These correctable issues need to be tackled in partnership with children and young people and their families. This requires a coordinated approach between professionals across healthcare settings. Establishing appropriate infrastructure for coordinated asthma care benefits not only those with problematic severe asthma, but also the wider asthma population as similar correctable issues exist for children with asthma of all severities. Investigation and management of genuine severe asthma requires specialist multidisciplinary expertise and a systematic approach to characterising patients' asthma phenotypes and delivering individualised care. While inhaled corticosteroids continue to play a leading role in asthma therapy, new treatments on the horizon might further support phenotype-specific therapy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Induced sputum nitrite levels correlate with clinical asthma parameters in children aged 7-18 years with mild to moderate persistent asthma

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Devki Nandan

2016-01-01

Full Text Available Purpose: The objective of this study is to measure levels of nitrites in induced sputum in children with asthma and correlate it with clinical asthma parameters. Method: This prospective observational study was done in PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi, on 91 children aged 7-18 years with mild and moderate persistent asthma. Patients were specifically evaluated for five clinical parameters of asthma (i.e. Days of acute exacerbations, use of salbutamol as rescue medication, emergency visits, nights with cough, days of school absence and induced sputum nitrite levels was done at the time of enrollment and 3 months after treatment with inhaled budesonide. Results: The mean age of subjects was 10.79 ± 2.563yrs. Six (6.59% patients were not able to perform induced sputum, eighty five (93.41% patients were suitable for data analysis. There was significant reduction in sputum nitrite levels from 33.42 ± 22.04nmol/ml at enrollment to 11.72 ± 5.61 nmol/ml (P < 0.0005 after 3 months of inhaled budesonide therapy. Significant positive correlation was found between reduction in sputum nitrite level and control of asthma symptoms: Days of acute exacerbations(r value = 0.548, P value = 0.0001, Days of salbutamol use as rescue medication (r value = 0.431, P value =< 0.0001, Number of emergency visits(r value = 0.414, P value = 0.0001, Nights with cough (r value = 0.259, P value = 0.0169, Days of school absence(r value = 0.411, P value = 0.0001. Sputum nitrite levels were significantly higher in moderate persistent asthmatics as compared to mild at the time of enrollment (P < 0.0005, which shows that induced sputum nitrite levels correlate with asthma severity. Conclusions: This study confirms that nitrites in induced sputum correlate well with clinical asthma parameters and asthma severity in children and is a simple, non invasive, and cheap method which can be used as a parameter for monitoring of asthma.

Comparing high altitude treatment with current best care in Dutch children with moderate to severe atopic dermatitis (and asthma): study protocol for a pragmatic randomized controlled trial (DAVOS trial).

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Fieten, Karin B; Zijlstra, Wieneke T; van Os-Medendorp, Harmieke; Meijer, Yolanda; Venema, Monica Uniken; Rijssenbeek-Nouwens, Lous; l'Hoir, Monique P; Bruijnzeel-Koomen, Carla A; Pasmans, Suzanne G M A

2014-03-26

About 10 to 20% of children in West European countries have atopic dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome also consists of allergic asthma, allergic rhinitis and food allergy. Treatment approaches for atopic dermatitis and asthma include intermittent anti-inflammatory therapy with corticosteroids, health education and self-management training. However, symptoms persist in a subgroup of patients. Several observational studies have shown significant improvement in clinical symptoms in children and adults with atopic dermatitis or asthma after treatment at high altitude, but evidence on the efficacy when compared to treatment at sea level is still lacking. This study is a pragmatic randomized controlled trial for children with moderate to severe AD within the atopic syndrome. Patients are eligible for enrolment in the study if they are: diagnosed with moderate to severe AD within the atopic syndrome, aged between 8 and 18 years, fluent in the Dutch language, have internet access at home, able to use the digital patient system Digital Eczema Center Utrecht (DECU), willing and able to stay in Davos for a six week treatment period. All data are collected at the Wilhelmina Children's Hospital and DECU. Patients are randomized over two groups. The first group receives multidisciplinary inpatient treatment during six weeks at the Dutch Asthma Center in Davos, Switzerland. The second group receives multidisciplinary treatment during six weeks at the outpatient clinic of the Wilhelmina Children's Hospital, Utrecht, the Netherlands. The trial is not conducted as a blind trial. The trial is designed with three components: psychosocial, clinical and translational. Primary outcomes are coping with itch, quality of life and disease activity. Secondary outcomes include asthma control, medication use, parental quality of life, social and emotional wellbeing of the child and translational parameters. The results of this trial will provide

Omalizumab in Japanese children with severe allergic asthma uncontrolled with standard therapy.

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Odajima, Hiroshi; Ebisawa, Motohiro; Nagakura, Toshikazu; Fujisawa, Takao; Akasawa, Akira; Ito, Komei; Doi, Satoru; Yamaguchi, Koichi; Katsunuma, Toshio; Kurihara, Kazuyuki; Kondo, Naomi; Sugai, Kazuko; Nambu, Mitsuhiko; Hoshioka, Akira; Yoshihara, Shigemi; Sato, Norio; Seko, Noriko; Nishima, Sankei

2015-10-01

Omalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng/ml (target level of suppression). Thirty-eight Japanese children (6-15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg/day fluticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open-label study. The geometric mean serum free IgE level at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were significantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p omalizumab decreased free IgE levels to less than 25 ng/mL. Omalizumab improved asthma control and was well-tolerated, as well. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

A review of omalizumab for the management of severe asthma.

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Lin, Ching-Hsiung; Cheng, Shih-Lung

2016-01-01

Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating immunoglobulin E, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be focused on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response, as well as extending its indications.

The management of adults and children with moderate severity ...

African Journals Online (AJOL)

Moderate severity asthma occurs in approximately 10 to 15% of patients with chronic reversible airway obstruction and is de- fined by more than four daytime symptoms per week, more than four night time symptoms per month and peak expiratory flow rates of between 60 and 80% of predicted values. Currently ...

Relevance of Cat and Dog Sensitization by Skin Prick Testing in Childhood Eczema and Asthma.

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Hon, Kam Lun; Tsang, Kathy Yin Ching; Pong, Nga Hin Henry; Leung, Ting Fan

2017-01-01

Household animal dander has been implicated as aeroallergen in childhood atopic diseases. Many parents seek healthcare advice if household pet keeping may be detrimental in atopic eczema (AE), allergic rhinitis and asthma. We investigated if skin sensitization by cat/dog dander was associated with disease severity and quality of life in children with AE. Demographics, skin prick test (SPT) results, disease severity (Nottingham eczema severity score NESS), Children Dermatology Life Quality Index (CDLQI), blood IgE and eosinophil counts of a cohort of AE patients were reviewed. 325 AE patients followed at a pediatric dermatology clinic were evaluated. Personal history of asthma was lowest (20%) in the dog-dander-positive-group but highest (61%) in bothcat- and-dog-dander-positive group (p=0.007). Binomial logistic regression ascertained that catdander sensitization was associated with increasing age (adjusted odds ratio [aOR], 1.056; 95% Confidence Interval [CI], 1.006 to 1.109; p=0.029), dust-mite sensitization (aOR, 4.625; 95% CI, 1.444 to 14.815; p=0.010), food-allergen sensitization (aOR, 2.330; 95% CI, 1.259 to 4.310; p=0.007) and keeping-cat-ever (aOR, 7.325; 95% CI, 1.193 to 44.971; p=0.032); whereas dogdander sensitization was associated with dust-mite sensitization (aOR, 9.091; 95% CI, 1.148 to 71.980; p=0.037), food-allergen sensitization (aOR, 3.568; 95% CI, 1.341 to 9.492; p=0.011) and keeping-dog-ever (aOR, 6.809; 95% CI, 2.179 to 21.281; p=0.001). However, neither cat nor dog sensitization were associated with asthma, allergic rhinitis, parental or sibling atopic status, disease severity or quality of life. Physicians should advise parents that there is no direct correlation between AE severity, quality of life, asthma or allergic rhinitis with cutaneous sensitization to cats or dogs. Sensitized patients especially those with concomitant asthma and severe symptoms may consider non-furry alternatives if they plan to have a pet. Highly sensitized

Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers.

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Murray, Clare S; Foden, Philip; Sumner, Helen; Shepley, Elizabeth; Custovic, Adnan; Simpson, Angela

2017-07-15

Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation. To evaluate the use of house dust mite-impermeable bedding and its impact on severe asthma exacerbations in children. We randomized mite-sensitized children with asthma (ages 3-17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings. Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36-0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26-0.56] vs. placebo, 0.52 [0.35-0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58-1.17; P = 0.28). Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children. Clinical trial registered with www.isrctn.com (ISRCTN 69543196).

Alternaria redefined

NARCIS (Netherlands)

Woudenberg, J.H.C.; Groenewald, J.Z.; Binder, M.; Crous, P.W.

2013-01-01

Alternaria is a ubiquitous fungal genus that includes saprobic, endophytic and pathogenic species associated with a wide variety of substrates. In recent years, DNA-based studies revealed multiple non-monophyletic genera within the Alternaria complex, and Alternaria species clades that do not always

Asthma symptoms improvement in moderate persistent asthma patients with gastroesophageal reflux disease (GERD: the role of proton-pump inhibitor

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Agus D. Susanto

2008-09-01

Full Text Available This study aimed to evaluate effect of proton pump inhibitor (esomeprazole on asthma symptoms, use of inhaled bronchodilator and peak expiratory flow rate (PEFR in moderate persistent asthma with gastroesofageal refluks disease (GERD. This randomized single blind, controlled clinical trial study was conducted at Persahabatan Hospital, Jakarta from July 2004 until October 2005. Samples were moderate persistent asthma patients with GERD. GERD is diagnosed GERD symptoms and proof of oesophagitis from endoscopy and or histapatologic examination from oesophagus biopsy. Phase 1:2 week run-in period patient received inhaled budesonide 2x200 ug/day. Phase 2: patient randomised to receive inhaled budesonide 2 x 400 ug/day with esomeprazole 40 mg/day or without esomeprazole (control group for 8 weeks. Phase 3: 4 week wash out period, patient receive inhaled budesonide 2 x 200 ug/day. Diary cards were assessed at run-in periode, after treatment 4 weeks, 8 weeks and wash out. There were 32 patients (23 female and 9 male completed the study. Mean total asthma symptoms score daily were significantly decreased on esomeprazole vs without esomeprazole after 8 weeks (-2.29 vs -0.90; p < 0.05. Mean use of inhaled bronchodilator was significantly decreased on esomeprazole vs without esomeprazole after 8 weeks (-1.09 vs -0.42; p < 0.05. Morning and evening PEFR improved higher on esomeprazole than without esomeprazol but were not significantly difference. In conclusion, administration esomeprazole 40 mg daily improved asthma symptoms and lower the use of inhaled bronchodilator in moderate persistent asthma patients with GERD. (Med J Indones 2008; 17: 169-74Keywords: Asthma symptoms, inhaled bronchodilator, moderate persistent asthma, GERD, esomeprazole

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

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Naik, Srilata Puru; P A, Mahesh; B S, Jayaraj; Madhunapantula, SubbaRao V; Jahromi, Sarah Raeiszadeh; Yadav, Manish Kumar

2017-08-01

Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p asthma (p asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV 1 improvement after 2 months of ICS+LABA. Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

Omalizumab therapy for children and adolescents with severe allergic asthma.

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Romano, Ciro

2015-01-01

Omalizumab, a therapeutic humanized monoclonal antibody specific for human IgE, was introduced in clinical practice more than a decade ago as an add-on therapy for moderate-to-severe allergic asthma in patients aged ≥12 years. Omalizumab has been demonstrated to be effective in adults with uncontrolled persistent asthma, with an excellent safety profile. In simple terms, omalizumab works by inhibiting the allergic cascade, that is, by neutralization of the circulating free IgE. This leads to reduction in the quantity of cell-bound IgE, downregulation of high-affinity IgE receptors, and, eventually, prevention of mediator release from effector cells. Evidence is far less abundant on the role of omalizumab in pediatric asthma. Although efficacy and safety of omalizumab in children and adolescents with uncontrolled, persistent allergic asthma has been recognized as well, further studies are needed to clarify a number of open questions in this specific patient population.

Children with problematic severe asthma: A biopsychosocial perspective

NARCIS (Netherlands)

Verkleij, M.

2016-01-01

This thesis focuses on problematic severe asthma in children and its treatment from a biopsychosocial perspective. Asthma is a chronic inflammatory disease of the airways. In children with problematic severe asthma, asthma is not under control despite optimal medical treatment. Asthma control is the

Assessment of asthma severity in adults with ever asthma: A continuous score.

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Lucia Calciano

Full Text Available In epidemiological studies, continuous measures of asthma severity should be used to catch the heterogeneity of phenotypes. This study aimed at developing and validating continuous measures of asthma severity in adult patients with ever asthma from the general population, to be used in epidemiological studies.Respiratory symptoms, anti-asthmatic treatment and lung function were measured on 520 patients with ever asthma aged 20-64 years from the general Italian population (GEIRD study; 2007/2010. The variables that represent the same dimension of asthma severity were identified through an exploratory factor analysis and were summarized through a multiple factor analysis.Only respiratory symptoms and anti-asthmatic treatment were summarized in a continuous score (STS. STS ranges from 0 (no symptoms/treatment to 10 (maximum symptom frequency and treatment intensity. STS was positively correlated with the Global Initiative for Asthma classification of asthma severity computed on the 137 cases with a doctor's diagnosis (Spearman's coefficient = 0.61, p-value<0.0001 (concurrent validity. Furthermore, using a cohort of 1,097 European asthmatics (ECRHS II study; 1999/2002, increasing STS levels at baseline (1991/1993 were positively associated with long-term outcomes (hospitalization and lost workdays for breathing problems, asthma attack frequency and use of asthma controllers (predictive validity. Finally, the STS scores computed from the GEIRD and ECRHS II data were comparable (Lin's coefficient = 0.95, p-value<0.0001 (replication analysis.STS is a valid and replicable measure of asthma severity in adults, which could be used in association studies.

Toxigenic Alternaria species from Argentinean blueberries.

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Greco, M; Patriarca, A; Terminiello, L; Fernández Pinto, V; Pose, G

2012-03-15

Blueberries are traditionally consumed in North America, some European countries and Japan. In Argentina, the blueberry crop is profitable because production starts in November, when the northern hemisphere lacks fresh fruit. Fungal contaminants can grow and produce mycotoxins in fresh fruit. The aims of this work were to identify the main genera of the mycobiota of blueberries grown in Argentina and to determine the toxicogenic potential, pathogenicity and host specificity of the species isolated. The genus Alternaria was the main component of the blueberry mycobiota (95%); minor proportions of Phoma spp. (4%) and Penicillium spp. (1%) were also isolated. According to their sporulation patterns, 127 Alternaria isolates belonged to the Alternaria tenuissima species-group, 5 to the Alternaria alternata species-group and 2 to the Alternaria arborescens species-group. The last mentioned species-group was not isolated at 5°C. Of the 134 isolates, 61% were toxicogenic in autoclaved rice; 97% of these produced alternariol (AOH) in a range from 0.14 to 119.18 mg/kg, 95% produced alternariol methylether (AME) in a range from 1.23 to 901.74 mg/kg and 65% produced tenuazonic acid (TA) in a range from 0.13 to 2778 mg/kg. Fifty two isolates co-produced the three mycotoxins. According to the size of the lesion that they caused on blueberries, the isolates were classified as slightly pathogenic, moderately pathogenic and very pathogenic. No significant differences in pathogenicity were found on different blueberry varieties. In this work, high incidence and toxicogenic potential of the Alternaria isolates from blueberries were demonstrated. Thus, more studies should be done to evaluate the health risk posed by the presence of the Alternaria toxins in blueberries and in the manufactured by-products. Copyright © 2012 Elsevier B.V. All rights reserved.

Air pollution and asthma severity in adults

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Rage, Estelle; Siroux, Valérie; Künzli, Nino; Pin, Isabelle; Kauffmann, Francine

2009-01-01

Objectives There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. Methods Asthma severity over the last 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The 4-class severity score integrated clinical events and type of treatment. The 5-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991–1995. The second consisted in spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). Results Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O3-8hr) and the number of days (O3-days) with 8-hour ozone averages above 110 μg.m−3 (for a 36-day increase, equivalent to the inter quartile range, in O3-days, odds ratio (95% confidence interval) 2.22 (1.61–3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO2. Both exposure assessment methods and severity scores resulted in very similar findings. SO2 correlated with severity but reached statistical significance only for the model based assignment of exposure. Conclusions The observed associations between asthma severity and air pollution, in particular O3, support the hypothesis that air pollution at levels far below current standards increases asthma severity. PMID:19017701

Fragrance materials in asthma: a pilot study using a surrogate aerosol product.

Science.gov (United States)

Vethanayagam, Dilini; Vliagoftis, Harissios; Mah, Dennell; Beach, Jeremy; Smith, Ladd; Moqbel, Redwan

2013-11-01

Many household products contain fragrances. Little is known about exposure to fragrances on human health, particularly within the airways. This study aimed to evaluate how common household fragrance products (i.e. air fresheners, cleaning products) affect people with asthma, who frequently report sensitivity to these products. Many of these products have volatile organic compounds or semi-volatile organic compounds. This study evaluated nine fragrance materials in an aerosol formulation to assess effects on airway physiology, airway inflammation and symptom perception in normal controls and those with asthma. The effects of fragrances were evaluated in people without asthma, people with mild asthma and people with moderate asthma in a four-way crossover placebo-controlled study. Subjects were exposed twice to a fragranced aerosol and twice to a placebo aerosol (15 and 30 min each). Subjects completed a questionnaire for 29 symptoms during and up to 3 h after each exposure scenario. Spirometry was performed prior to and 3 h post-exposure; sputum induction was conducted 3 h post-exposure. Nasal symptoms showed the greatest frequency of response in all three subject groups, and moderate asthmatics reported the greatest symptom severity and symptom types. No significant differences were noted in physiology or cellular inflammation. A trend for increased symptoms was noted in moderate asthmatics, suggesting that asthma severity may play a factor in fragrance sensitivity.

The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

Science.gov (United States)

Rojanasarot, Sirikan; Carlson, Angeline M

2018-04-01

The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma.

Science.gov (United States)

Iribarren, Carlos; Rahmaoui, Abdelkader; Long, Aidan A; Szefler, Stanley J; Bradley, Mary S; Carrigan, Gillis; Eisner, Mark D; Chen, Hubert; Omachi, Theodore A; Farkouh, Michael E; Rothman, Kenneth J

2017-05-01

EXCELS, a postmarketing observational cohort study, was a commitment to the US Food and Drug Administration to assess the long-term safety of omalizumab in an observational setting, focusing predominantly on malignancies. The aim of this study was to examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS. Patients (≥12 years of age) with moderate to severe allergic asthma and who were being treated with omalizumab (n = 5007) or not (n = 2829) at baseline were followed up for ≤5 years. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATEs), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, and unstable angina. A prespecified analysis of the end point of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events. At baseline, the 2 cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus the non-omalizumab group (50% vs 23%). Omalizumab-treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1,000 person years [PYs]) than did non-omalizumab-treated patients (8.1 per 1,000 PYs). The ATE rates per 1,000 PYs were 6.66 (101 patients/15,160 PYs) in the omalizumab cohort and 4.64 (46 patients/9,904 PYs) in the non-omalizumab cohort. After control for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91-1.91). This observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus the non-omalizumab cohort. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Mechanical ventilation for severe asthma.

Science.gov (United States)

Leatherman, James

2015-06-01

Acute exacerbations of asthma can lead to respiratory failure requiring ventilatory assistance. Noninvasive ventilation may prevent the need for endotracheal intubation in selected patients. For patients who are intubated and undergo mechanical ventilation, a strategy that prioritizes avoidance of ventilator-related complications over correction of hypercapnia was first proposed 30 years ago and has become the preferred approach. Excessive pulmonary hyperinflation is a major cause of hypotension and barotrauma. An appreciation of the key determinants of hyperinflation is essential to rational ventilator management. Standard therapy for patients with asthma undergoing mechanical ventilation consists of inhaled bronchodilators, corticosteroids, and drugs used to facilitate controlled hypoventilation. Nonconventional interventions such as heliox, general anesthesia, bronchoscopy, and extracorporeal life support have also been advocated for patients with fulminant asthma but are rarely necessary. Immediate mortality for patients who are mechanically ventilated for acute severe asthma is very low and is often associated with out-of-hospital cardiorespiratory arrest before intubation. However, patients who have been intubated for severe asthma are at increased risk for death from subsequent exacerbations and must be managed accordingly in the outpatient setting.

GENE EXPRESSION DYNAMICS IN PATIENTS WITH SEVERE THERAPY-RESISTANT ASTHMA DURING TREATMENT PERIOD

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Ye. S. Kulikov

2014-01-01

Full Text Available Introduction: The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma in dynamic during treatment period.Methods: Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip. Cluster analysis was performed.Results and conclusion: According to our data several mechanisms of therapy resistance may be considered: increased levels of nitric oxide and beta2-agonists nitration, dysregulation of endogenous steroids secretion and involvement in the pathogenesis of Staphylococcus aureus. Absence of suppression of gene expression KEGG-pathway “asthma" may reflect the low efficiency or long period of anti-inflammatory therapy effect realization.

[The degree of asthma severity in children and the level of maternal anxiety and depression].

Science.gov (United States)

Witkowska-Płusa, Urszula

2015-02-01

Care for sick children most often falls to mothers, which may affect their mental state, causing the states of depression and anxiety. The aim of this study was to determine the relationship between the severity of asthma in children and the level of anxiety and depression in mothers, taking into account the importance of the material status of the family, the educational level of the mothers, the presence of critical events, as well as the coexistence of allergic diseases in other family members. The study included 60 mothers of children with bronchial asthma. Age of mothers in the investigated families was on average 37.28 +/- 6.24 years, and most had a high school education (55.0%) or higher (28.3%). 16.7% of mothers and 8.3% fathers suffered from asthma. 13.3% of mothers of children with asthma were brought child alone. To assess the level of anxiety the inventory for measuring state and trait anxiety (STAI - State Trait Anxiety Inventory) developed by Spielberger, Gorsuch'a and Lushene'a was applied. To determine the changes in depressive the Beck Depression Inventory (BDI - Beck Depression Inventory questionnaire) was used. The Student's t test was included for two independent populations and a comparison of the results obtained in the questionnaire for diagnosing the level of anxiety and depression. For other parameters the correlation coefficient r-Pearson rank and Kendall's tau were performed. Mothers of children with moderate asthma compared to mothers of children with mild asthma had higher levels of anxiety (both state and properties), and also a slightly higher level of depression. Maternal age was connected positively and moderately strongly with the number held by children (r = 0.380; p = 0.003) and age of a child with asthma (r = 0.613, p = 0.0005). The duration of the child's disease was associated positively and moderately strongly with the level of state anxiety mother (X-1) (r = 0.345; p = 0.007) and a bit less and also positively with the

A Patient Advocate to facilitate access and improve communication, care, and outcomes in adults with moderate or severe asthma: Rationale, design, and methods of a randomized controlled trial

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Apter, Andrea J.; Morales, Knashawn H.; Han, Xiaoyan; Perez, Luzmercy; Huang, Jingru; Ndicu, Grace; Localio, Anna; Nardi, Alyssa; Klusaritz, Heather; Rogers, Marisa; Phillips, Alexis; Cidav, Zuleyha; Schwartz, J. Sanford

2017-01-01

Few interventions to improve asthma outcomes have targeted low-income minority adults. Even fewer have focused on the real-world practice where care is delivered. We adapted a patient navigator, here called a Patient Advocate (PA), a term preferred by patients, to facilitate and maintain access to chronic care for adults with moderate or severe asthma and prevalent co-morbidities recruited from clinics serving low-income urban neighborhoods. We describe the planning, design, methodology (informed by patient and provider focus groups), baseline results, and challenges of an ongoing randomized controlled trial of 312 adults of a PA intervention implemented in a variety of practices. The PA coaches, models, and assists participants with preparations for a visit with the asthma clinician; attends the visit with permission of participant and provider; and confirms participants’ understanding of what transpired at the visit. The PA facilitates scheduling, obtaining insurance coverage, overcoming patients’ unique social and administrative barriers to carrying out medical advice and transfer of information between providers and patients. PA activities are individualized, take account of comorbidities, and are generalizable to other chronic diseases. PAs are recent college graduates interested in health-related careers, research experience, working with patients, and generally have the same race/ethnicity distribution as potential participants. We test whether the PA intervention, compared to usual care, is associated with improved and sustained asthma control and other asthma outcomes (prednisone bursts, ED visits, hospitalizations, quality of life, FEV1) relative to baseline. Mediators and moderators of the PA-asthma outcome relationship are examined along with the intervention’s cost-effectiveness. PMID:28315481

Examining the unmet need in adults with severe asthma

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M. R. Partridge

2007-09-01

Full Text Available Asthma currently affects an estimated 300 million people worldwide and the number is expected to rise to 400 million by 2025. Asthma morbidity remains high and the economic burden is significant. Approximately 20% of patients have severe persistent asthma. As patients with severe asthma often have a variety of conditions that may coexist with or be mistaken for asthma, careful diagnosis and management are essential, and adhering to a protocol for investigations is helpful. For patients with severe persistent asthma, the Global Initiative for Asthma 2005 guidelines recommend the use of high-dose inhaled corticosteroids in combination with a long-acting beta2-agonist, with one or more additional controller medications if required (step 4 therapy. However, recent studies have shown that asthma remains inadequately controlled in many patients with severe asthma, despite treatment in accordance with guidelines. Patients with severe asthma have the highest healthcare utilisation and mortality, and there is clearly an unmet need for the effective and safe treatment of patients with severe persistent allergic asthma who remain symptomatic despite optimised standard treatment. The latest guidelines suggest that omalizumab may address this unmet need.

Acute severe asthma presenting in late pregnancy.

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Holland, S M; Thomson, K D

2006-01-01

Asthma is the commonest pre-existing medical condition to complicate pregnancy. Acute severe asthma in pregnancy is rare, but poses difficult problems. In particular, the decision about when and where to deliver the fetus is complex, since maternal response to asthma treatment is unpredictable. We report the successful management of a parturient presenting with acute severe asthma at 37 weeks' gestation. The controversies involved and the importance of adopting a multi-disciplinary team approach to optimise maternal and neonatal outcomes are discussed.

Sensitivities of baseline isolates and boscalid-resistant mutants of Alternaria alternata from pistachio to fluopyram, penthiopyrad, and fluxapyroxad

NARCIS (Netherlands)

Avenot, H.F.; Biggelaar, van den H.; Morgan, D.P.; Moral, J.; Joosten, M.H.A.J.; Michailides, T.J.

2014-01-01

Resistance of Alternaria alternata to boscalid, the first succinate dehydrogenase inhibitor (SDHI) fungicide labeled on pistachio, has become a common occurrence in California pistachio orchards and affects the performance of this fungicide. In this study, we established the baseline sensitivities

Severe asthma and acute attacks: diagnosis and management in ...

African Journals Online (AJOL)

Patients who continue to have symptoms with frequent attacks of asthma despite being adherent to treatment with multiple asthma medications, have severe asthma. Severe asthma has significant implications for the affected individual and utilise a disproportionate share of the health care costs associated with asthma.

Working while unwell: Workplace impairment in people with severe asthma.

Science.gov (United States)

Hiles, Sarah A; Harvey, Erin S; McDonald, Vanessa M; Peters, Matthew; Bardin, Philip; Reynolds, Paul N; Upham, John W; Baraket, Melissa; Bhikoo, Zaheerodin; Bowden, Jeffrey; Brockway, Ben; Chung, Li Ping; Cochrane, Belinda; Foxley, Gloria; Garrett, Jeffrey; Hew, Mark; Jayaram, Lata; Jenkins, Christine; Katelaris, Constance; Katsoulotos, Gregory; Koh, Mariko S; Kritikos, Vicky; Lambert, Marina; Langton, David; Rivero, Alexis Lara; Marks, Guy B; Middleton, Peter G; Nanguzgambo, Aldoph; Radhakrishna, Naghmeh; Reddel, Helen; Rimmer, Janet; Southcott, Anne Marie; Sutherland, Michael; Thien, Francis; Wark, Peter Ab; Yang, Ian A; Yap, Elaine; Gibson, Peter G

2018-04-20

Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. To compare workplace productivity - absenteeism and presenteeism - and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. The Severe Asthma Web-based Database (SAWD) is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18 to 88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (pworkplace. Improving asthma control and mental health may be important targets for optimising workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role of serum eosinophil cationic protein as a biological marker to assess the severity of bronchial asthma

International Nuclear Information System (INIS)

Begum, A.; Sattar, H.; Miah, R.A.; Saleh, A.A.; Hassan, R.; Salam, A

2012-01-01

Objective: The study was carried out to evaluate the role of serum eosinophil cationic protein (ECP) as a biological marker for the diagnosis and to assess the severity of bronchial asthma. Methodology: This observational cross-sectional study was conducted among 70 bronchial asthma patients and 45 disease controls (tuberculosis-15, chronic obstructive pulmonary disease-15, interstitial lung disease-15) enrolled from patients attending the outpatient department of the National Institute of Disease of the Chest and Hospital (NIDCH), Dhaka, Bangladesh during July 2010 to June 2011. Global Initiative of Asthma Management and Prevention (GINA) criteria were followed for selection of both atopic and non-atopic patients with intermittent or persistent (mild, moderate and severe) asthma. Serum level of eosinophil cationic protein (ECP), IgE, forced expiratory volume in 1 second (FEV 1% predicted) and circulatory eosinophil (CE) count were estimated. Results: Mean serum ECP level (28.8 +- 42.9 vs. 6.82 +- 3.5 ng/mL; P<0.001), IgE level (383.59 - 225.3 vs. 135 +- 131.8 IU/mL; P<0.001) and percent circulatory eosinophil count (9.95 +- 3.7 vs. 5.95 +- 1.4; P<0.024) were all found significantly raised among asthma patients than disease controls but % FEV1 was equivocal. All grades of persistent asthma patients had significantly (P<0.025 and P<0.002) higher mean ECP level than intermittent cases but serum IgE level and CE count did not differ significantly. FEV1 % predicted correlated well among moderate and severe persistent asthma but was equivocal for intermittent and mild persistent cases. Conclusion: This study has reinforced that serum eosinophil cationic protein is a dependable biological marker with more discriminatory power over other indicators for bronchial asthma and to assess its severity. (author)

Severe exacerbations and decline in lung function in asthma

DEFF Research Database (Denmark)

O'Byrne, Paul M; Pedersen, Søren; Lamm, Carl Johan

2009-01-01

RATIONALE: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. OBJECTIVES: To determine whether severe asthma exacerbations...... with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. MEASUREMENTS AND MAIN RESULTS: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable...... of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). CONCLUSIONS: Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses...

A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation

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N. Ringdal

1996-01-01

Full Text Available In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP 800 μg daily, administered as a powder via the Diskhaler®, and budesonide (BUD 1600 μg daily, administered using the Turbuhaler®, in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP (p = 0.003, with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04, diurnal PEF variation (p = 0.03 and percentage predicted PEF (p = 0.003, as well as forced expiratory volume (p = 0.008, forced vital capacity (p = 0.02 and PEF (p = 0.005 measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP. In summary, FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily.

Craniocervical posture and hyoid bone position in children with mild and moderate asthma and mouth breathing.

Science.gov (United States)

Chaves, Thaís Cristina; de Andrade e Silva, Tatiana Simões; Monteiro, Solange Aparecida Caldeira; Watanabe, Plauto Christopher Aranha; Oliveira, Anamaria Siriani; Grossi, Débora Bevilaqua

2010-09-01

The objective of the present study was to assess the craniocervical posture and the positioning of the hyoid bone in children with asthma who are mouth breathers compared to non-asthma controls. The study was conducted on 56 children, 28 of them with mild (n=15) and moderate (n=13) asthma (14 girls aged 10.79+/-1.31 years and 14 boys aged 9.79+/-1.12 years), matched for sex, height, weight and age with 28 non-asthma children who are not mouth breathers. The sample size was calculated considering a confidence interval of 95% and a prevalence of 4% of asthma in Latin America. Eighteen variables were analyzed in two radiographs (latero-lateral teleradiography and lateral cervical spine radiography), both obtained with the head in a natural position. The independent t-test was used to compare means values and the chi-square test to compare percentage values (pasthma than in control children (106.38+/-7.66 vs. 111.21+/-7.40, p=0.02) and the frequency of asthma children with an absent or inverted hyoid triangle was found to be significantly higher compared to non-asthma children (36% vs. 7%, p=0.0001). The values of the inclination angles of the superior cervical spine in relation to the horizontal plane were significantly higher in moderate than in mild asthma children (CVT/Hor: 85.10+/-7.25 vs. 90.92+/-6.69, p=0.04 and C1/Hor: 80.93+/-5.56 vs. 85.00+/-4.20, p=0.04). These findings revealed that asthma children presented higher head extension and a higher frequency of changes in hyoid bone position compared to non-asthma children and that greater the asthma severity greater the extension of the upper cervical spine. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

A study of asthma severity in adult twins

DEFF Research Database (Denmark)

Thomsen, Simon Francis; van der Sluis, Sophie; Kyvik, Kirsten Ohm

2012-01-01

Introduction: The tendency to develop asthma runs in families, but whether the severity of asthma symptoms is inherited is not known. Objectives: The aim of this study was to examine whether genetic factors influence the variation in the severity of asthma. Methods: Of a sample of 21 133 adult......, and markers of airway impairment and allergy were measured. Results: After adjusting for confounders, genetic factors explained 24% (10%-37%), P = 0.0004, of the variation in overall asthma symptom severity, whereas non-shared environment accounted for the remaining 76% of the variation. A significant genetic...

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

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Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

2016-06-01

Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression.

Science.gov (United States)

Woodruff, Prescott G; Dolganov, Gregory M; Ferrando, Ronald E; Donnelly, Samantha; Hays, Steven R; Solberg, Owen D; Carter, Roderick; Wong, Hofer H; Cadbury, Peggy S; Fahy, John V

2004-05-01

Bronchial hyperresponsiveness in mild to moderate asthma may result from airway smooth muscle cell proliferation or acquisition of a hypercontractile phenotype. Because these cells have not been well characterized in mild to moderate asthma, we examined the morphometric and gene expression characteristics of smooth muscle cells in this subgroup of patients with asthma. Using bronchial biopsies from 14 subjects with mild to moderate asthma and 15 control subjects, we quantified smooth muscle cell morphology by stereology and the expression of a panel of genes related to a hypercontractile phenotype of airway smooth muscle, using laser microdissection and two-step real-time polymerase chain reaction. We found that airway smooth muscle cell size was similar in both groups, but cell number was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of smooth muscle in the submucosa was increased 50-83% (p 0.1). We conclude that airway smooth muscle proliferation is a pathologic characteristic of subjects with mild to moderate asthma. However, smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene expression changes of a hypercontractile phenotype observed in vitro.

Association of pediatric asthma severity with exposure to common household dust allergens

International Nuclear Information System (INIS)

Gent, Janneane F.; Belanger, Kathleen; Triche, Elizabeth W.; Bracken, Michael B.; Beckett, William S.; Leaderer, Brian P.

2009-01-01

Background: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. Objective: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. Methods: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. Results: Der p 1 house dust mite allergen concentration of 2.0 μg/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 μg/g and OR 2.55 95% CI 1.13, 5.73 for ≥10.0 μg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). Conclusion: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

Association of pediatric asthma severity with exposure to common household dust allergens

Energy Technology Data Exchange (ETDEWEB)

Gent, Janneane F., E-mail: janneane.gent@yale.edu [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Belanger, Kathleen [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Triche, Elizabeth W. [Brown University, Department of Community Health/Epidemiology, Providence, RI (United States); Bracken, Michael B. [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Beckett, William S. [Mount Auburn Hospital, Department of Internal Medicine, Cambridge, MA (United States); Leaderer, Brian P. [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States)

2009-08-15

Background: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. Objective: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. Methods: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. Results: Der p 1 house dust mite allergen concentration of 2.0 {mu}g/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 {mu}g/g and OR 2.55 95% CI 1.13, 5.73 for {>=}10.0 {mu}g/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). Conclusion: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

Science.gov (United States)

Yii, A C A; Tan, J H Y; Lapperre, T S; Chan, A K W; Low, S Y; Ong, T H; Tan, K L; Chotirmall, S H; Sterk, P J; Koh, M S

2017-09-01

Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently

An algorithmic approach for the treatment of severe uncontrolled asthma

Science.gov (United States)

Zervas, Eleftherios; Samitas, Konstantinos; Papaioannou, Andriana I.; Bakakos, Petros; Loukides, Stelios; Gaga, Mina

2018-01-01

A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute asthma patients, they are responsible for more than half of asthma-related healthcare costs. Here, we review a definition for severe asthma and present all therapeutic options currently available for these severe asthma patients. Moreover, we suggest a specific algorithmic treatment approach for the management of severe, difficult-to-treat asthma based on specific phenotype characteristics and biomarkers. The diagnosis and management of severe asthma requires specialised experience, time and effort to comprehend the needs and expectations of each individual patient and incorporate those as well as his/her specific phenotype characteristics into the management planning. Although some new treatment options are currently available for these patients, there is still a need for further research into severe asthma and yet more treatment options. PMID:29531957

Assessment of problematic severe asthma in children

DEFF Research Database (Denmark)

Carlsen, K. C. L.; Hedlin, G.; Bush, A.

2011-01-01

Assessment of problematic severe asthma in children should be performed in a stepwise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessm......Assessment of problematic severe asthma in children should be performed in a stepwise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi......-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps...... in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small...

Mechanisms Mediating Pediatric Severe Asthma and Potential Novel Therapies

Directory of Open Access Journals (Sweden)

Aldara Martin Alonso

2017-07-01

Full Text Available Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling. Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma. However, limitations of its use include ineligibility for approximately one-third of patients because of serum IgE levels outside the recommended range and lack of clinical efficacy in a further one-third. Pediatric severe asthma is thus markedly heterogeneous, but our current understanding of the different mechanisms underpinning various phenotypes is very limited. We know that there are distinctions between the factors that drive pediatric and adult disease since pediatric disease develops in the context of a maturing immune system and during lung growth and development. This review summarizes the current data that give insight into the pathophysiology of pediatric severe asthma and will highlight potential targets for novel therapies. It is apparent that in order to identify novel treatments for pediatric severe asthma, the challenge of undertaking mechanistic studies using age appropriate experimental models and airway samples from children needs to be accepted to allow a targeted approach of personalized medicine to be achieved.

A review of omalizumab for the management of severe asthma

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Lin CH

2016-07-01

Full Text Available Ching-Hsiung Lin,1–3 Shih-Lung Cheng4,5 1Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, Republic of China; 2Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan, Republic of China; 3School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan, Republic of China; 5Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli City, Taoyuan County, Taiwan, Republic of China Abstract: Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating immunoglobulin E, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be focused on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response, as well as extending its indications. Keywords: severe asthma, IgE, omalizumab, exacerbation, chronic idiopathic urticarial, inhaled corticosteroid

Risk factors for death in patients with severe asthma

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Andréia Guedes Oliva Fernandes

2014-08-01

Full Text Available OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4. Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality.

Mismatch between asthma symptoms and spirometry: implications for managing asthma in children.

Science.gov (United States)

Schifano, Elizabeth D; Hollenbach, Jessica P; Cloutier, Michelle M

2014-11-01

To examine the concordance between spirometry and asthma symptoms in assessing asthma severity and beginning therapy by the general pediatrician. Between 2008 and 2012, spirometry testing was satisfactorily performed in 894 children (ages 5-19 years) whose asthma severity had been determined by their pediatrician using asthma guideline-based clinical criteria. Spirometry-determined asthma severity using national asthma guidelines and clinician-determined asthma severity were compared for concordance using weighted Kappa coefficients. Thirty percent of participants had clinically determined intermittent asthma; 32%, 33%, and 5% had mild, moderate, and severe, persistent asthma, respectively. Increasing disease severity was associated with decreases in the forced expiratory volume in 1 second/forced vital capacity (FVC) ratio (P spirometry-determined severity. Concordance was 0.16 (95% CI 0.10, 0.23), and when adjusted for bias and prevalence, was 0.20 (95% CI 0.17, 0.23). When accounting for age, sex, exposure to smoke, and insurance type, only spirometry-determined asthma severity was a significant predictor of agreement (P spirometry-determined severity increased. Concordance between spirometry and asthma symptoms in determining asthma severity is low even when guideline-based clinical assessment tools are used. Because appropriate therapy reduces asthma morbidity and is guided by disease severity, results from spirometry testing could better guide pediatricians in determining appropriate therapy for their patients with asthma. Copyright © 2014 Elsevier Inc. All rights reserved.

Performance of a novel clinical score, the Pediatric Asthma Severity Score (PASS), in the evaluation of acute asthma.

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Gorelick, Marc H; Stevens, Molly W; Schultz, Theresa R; Scribano, Philip V

2004-01-01

To evaluate the reliability, validity, and responsiveness of a new clinical asthma score, the Pediatric Asthma Severity Score (PASS), in children aged 1 through 18 years in an acute clinical setting. This was a prospective cohort study of children treated for acute asthma at two urban pediatric emergency departments (EDs). A total of 852 patients were enrolled at one site and 369 at the second site. Clinical findings were assessed at the start of the ED visit, after one hour of treatment, and at the time of disposition. Peak expiratory flow rate (PEFR) (for patients aged 6 years and older) and pulse oximetry were also measured. Composite scores including three, four, or five clinical findings were evaluated, and the three-item score (wheezing, prolonged expiration, and work of breathing) was selected as the PASS. Interobserver reliability for the PASS was good to excellent (kappa = 0.72 to 0.83). There was a significant correlation between PASS and PEFR (r = 0.27 to 0.37) and pulse oximetry (r = 0.29 to 0.41) at various time points. The PASS was able to discriminate between those patients who did and did not require hospitalization, with area under the receiver operating characteristic curve of 0.82. Finally, the PASS was shown to be responsive, with a 48% relative increase in score from start to end of treatment and an overall effect size of 0.62, indicating a moderate to large effect. This clinical score, the PASS, based on three clinical findings, is a reliable and valid measure of asthma severity in children and shows both discriminative and responsive properties. The PASS may be a useful tool to assess acute asthma severity for clinical and research purposes.

Cost-effectiveness analysis of a state funded programme for control of severe asthma

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Loureiro Sebastião

2007-05-01

Full Text Available Abstract Background Asthma is one of the most common chronic diseases and a major economical burden to families and health systems. Whereas efficacy of current therapeutical options has been clearly established, cost-effectiveness analysis of public health interventions for asthma control are scarce. Methods 81 patients with severe asthma (12–75 years joining a programme in a reference clinic providing free asthma medication were asked retrospectively about costs and events in the previous 12 months. During 12 months after joining the programme, information on direct and indirect costs, asthma control by lung function, symptoms and quality of life were collected. The information obtained was used to estimate cost-effectiveness of the intervention as compared to usual public health asthma management. Sensitivity analysis was conducted. Results 64 patients concluded the study. During the 12-months follow-up within the programme, patients had 5 fewer days of hospitalization and 68 fewer visits to emergency/non scheduled medical visits per year, on average. Asthma control scores improved by 50% and quality of life by 74%. The annual saving in public resources was US$387 per patient. Family annual income increased US$512, and family costs were reduced by US$733. Conclusion A programme for control of severe asthma in a developing country can reduce morbidity, improve quality of life and save resources from the health system and patients families.

Therapeutic interventions in severe asthma.

Science.gov (United States)

Canonica, Giorgio Walter; Senna, Gianenrico; Mitchell, Patrick D; O'Byrne, Paul M; Passalacqua, Giovanni; Varricchi, Gilda

2016-01-01

The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy. Omalizumab, an anti-IgE antibody, has been the only biologic treatment available on the market for severe asthma during the last decade. It prevents the linkage of the IgE and the receptors, thereby inhibiting mast cell degranulation. In clinical practice omalizumab significantly reduced the asthma exacerbations as well as the concomitant use of oral glucocorticoids. In the "Th2-high asthma" phenotype, the hallmarks are increased levels of eosinophils and other markers (such as periostin). Because anti-IL-5 in this condition plays a crucial role in driving eosinophil inflammation, this cytokine or its receptors on the eosinophil surface has been studied as a potential target for therapy. Two different anti-IL-5 humanized monoclonal antibodies, mepolizumab and reslizumab, have been proven effective in this phenotype of asthma (recently they both came on the market in the United States), as well as an anti-IL-5 receptor alpha (IL5Rα), benralizumab. Other monoclonal antibodies, targeting different cytokines (IL-13, IL-4, IL-17 and TSLP) are still under evaluation, though the preliminary results are encouraging. Finally, AIT, Allergen Immunotherapy, a prototype of Precision Medicine, is considered, also in light of the recent evidences of Sublingual Immunotherapy (SLIT) tablet efficacy and safety in mite allergic asthma patients. Given the high costs of these therapies

Socio-economic disadvantage, quality of medical care and admission for acute severe asthma.

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Kolbe, J; Vamos, M; Fergusson, W

1997-06-01

In asthma, socio-economic and health care factors may operate by a number of mechanisms to influence asthma morbidity and mortality. To determine the quality of medical care including the patient perception of the doctor-patient relationship, and the level of socio-economic disadvantage in patients admitted to hospital with acute severe asthma. One hundred and thirty-eight patients (15-50 years) admitted to hospital (general ward or intensive care unit) with acute asthma were prospectively assessed using a number of previously validated instruments. The initial subjects had severe asthma on admission (pH = 7.3 +/- 0.2, PaCO2 = 7.1 +/- 5.0 kPa, n = 90) but short hospital stay (3.7 +/- 2.6 days). Although having high morbidity (40% had hospital admission in the last year and 60% had moderate/severe interference with sleep and/or ability to exercise), they had indicators of good ongoing medical care (96% had a regular GP, 80% were prescribed inhaled steroids, 84% had a peak flow meter, GP measured peak flow routinely in 80%, 52% had a written crisis plan and 44% had a supply of steroids at home). However, they were severely economically disadvantaged (53% had experienced financial difficulties in the last year, and for 35% of households the only income was a social security benefit). In the last year 39% had delayed or put off GP visit because of cost. Management of the index attack was compromised by concern about medical costs in 16% and time off work in 20%. Patients admitted to hospital with acute asthma have evidence of good quality on-going medical care, but are economically disadvantaged. If issues such as financial barriers to health care are not acknowledged and addressed, the health care services for asthmatics will not be effectively utilised and the current reductions in morbidity and mortality may not be maintained.

Risk factors for hospitalization among adults with asthma: the influence of sociodemographic factors and asthma severity

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Eisner Mark D

2000-12-01

Full Text Available Abstract Background The morbidity and mortality from asthma have markedly increased since the late 1970s. The hospitalization rate, an important marker of asthma severity, remains substantial. Methods In adults with health care access, we prospectively studied 242 with asthma, aged 18–50 years, recruited from a random sample of allergy and pulmonary physician practices in Northern California to identify risk factors for subsequent hospitalization. Results Thirty-nine subjects (16% reported hospitalization for asthma during the 18-month follow-up period. On controlling for asthma severity in multiple logistic regression analysis, non-white race (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1–8.8 and lower income (OR, 1.1 per $10,000 decrement; 95% CI, 0.9–1.3 were associated with a higher risk of asthma hospitalization. The severity-of-asthma score (OR, 3.4 per 5 points; 95%, CI 1.7–6.8 and recent asthma hospitalization (OR, 8.3; 95%, CI, 2.1–33.4 were also related to higher risk, after adjusting for demographic characteristics. Reliance on emergency department services for urgent asthma care was also associated with a greater likelihood of hospitalization (OR, 3.2; 95% CI, 1.0–9.8. In multivariate analysis not controlling for asthma severity, low income was even more strongly related to hospitalization (OR, 1.2 per $10,000 decrement; 95% CI, 1.02–1.4. Conclusion In adult asthmatics with access to health care, non-white race, low income, and greater asthma severity were associated with a higher risk of hospitalization. Targeted interventions applied to high-risk asthma patients may reduce asthma morbidity and mortality.

Pharmacokinetics, pharmacodynamics and clinical efficacy of omalizumab for the treatment of asthma.

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Luu, Maxime; Bardou, Marc; Bonniaud, Philippe; Goirand, Françoise

2016-12-01

Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered: This drug evaluation summarizes published data on pharmacokinetic and pharmacodynamic properties of omalizumab, on clinical efficacy and safety, including real-world evidence, and provides a medico-economic evaluation of the drug. Expert opinion: Omalizumab represents an efficient therapeutic option for the management of patients with uncontrolled moderate/severe allergic asthma. It provides a significant reduction in the asthma exacerbation rate with a steroid-sparing effect, an improvement in quality of life in adults and adolescents, despite a lack of evidence about its efficacy specifically in severe allergic asthma. Clinical trials have demonstrated its efficacy in the pediatric population but further real-life evidence is expected to better characterize long-term effects in this population. There is still some debate about the optimal treatment duration but, to date, it is recommended not to stop the treatment as cessation has resulted in symptom recurrence. Omalizumab is an expensive treatment, but a key therapeutic option when used for uncontrolled severe allergic asthma.

Sensitization predicts asthma development among wheezing toddlers in secondary healthcare

NARCIS (Netherlands)

Boersma, Nienke A.; Meijneke, Ruud W.H.; Kelder, Johannes C.; van der Ent, Cornelis K.; Balemans, Walter A.F.

2017-01-01

Introduction: Some wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain. Aim: This study examines the predictive value of sensitization to inhalant allergens among wheezing

The level of diagnostic assessment in severe asthma

DEFF Research Database (Denmark)

von Bulow, Anna; Backer, Vibeke; Bodtger, Uffe

2017-01-01

INTRODUCTION: Systematic assessment of patients with severe asthma is pivotal to decide which patients are eligible to new biological therapies. However, the level of diagnostic work-up in patients with severe asthma is only poorly investigated. AIMS & OBJECTIVES: To describe the diagnostic work-...

Patterns of aeroallergen sensitization predicting risk for asthma in preschool children with atopic dermatitis.

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Calamelli, Elisabetta; Ricci, Giampaolo; Neri, Iria; Ricci, Lorenza; Rondelli, Roberto; Pession, Andrea; Patrizi, Annalisa

2015-06-01

Atopic dermatitis (AD) is a chronic inflammatory skin disorder mostly affecting young children. Although several studies aimed to identify the risk factors for asthma in AD children, many aspects still need to be clarified. The aim of this study was to investigate the possible risk factors for asthma at school age in 99 children with early-onset and IgE-mediated AD. All children performed clinical evaluation and total and specific IgE assay for a panel of inhalant and food allergens at two different times (t1 and t2) during preschool, and asthma diagnosis was assessed at one follow-up visit (t3) at school age. At t3, 39% of children had developed asthma. Of the variables compared, the sensitization to more than one class of inhalant allergens at t2 (mean age = 30 months) was associated with asthma, with grass (OR = 3.24, p = 0.020) and cat sensitization (OR = 2.74, p = 0.043) as independent risk factors. The sensitization pattern of a child with early-onset AD, also within the first 2-3 years of life, can reflect his risk to develop asthma. Therefore, testing these children for the more common allergens during this time frame should be recommended to predict the evolution of atopic diseases.

Overlap of obstructive sleep apnea and bronchial asthma: Effect on asthma control

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Mohamed Zidan

2015-04-01

Conclusion: A high index of suspicion is warranted for the overlap of OSA and asthma, particularly in the presence of obesity, GERD, and in patients with severe asthma. Individualized therapy addressing these moderating factors is warranted for optimal health outcomes. Recognition and treatment of OSA in asthmatics is an important element in improving asthma control.

Pathway discovery using transcriptomic profiles in adult-onset severe asthma

DEFF Research Database (Denmark)

Hekking, Pieter-Paul; Loza, Matt J; Pavlidis, Stelios

2017-01-01

in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung...... injury were less enriched in adult-onset severe asthma. CONCLUSIONS: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma....

Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population.

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Berenguer, Anabela Gonçalves; Fernandes, Ana Teresa; Oliveira, Susana; Rodrigues, Mariana; Ornelas, Pedro; Romeira, Diogo; Serrão, Tânia; Rosa, Alexandra; Câmara, Rita

2014-09-04

Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold). In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Allergy sensitization and asthma among 13-14 year old school ...

African Journals Online (AJOL)

EB

Allergy sensitization and asthma among 13-14 year old school children in Nigeria. Oluwole O1 ... Identified asthma cases were matched to controls. Allergy skin tests ..... lower risk of asthma than those with low birth order because exposure to ...

The Role of Sensitization to Allergen in Asthma Prediction and Prevention

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Maria Moustaki

2017-07-01

Full Text Available The burden of asthma in childhood is considerable worldwide, although some populations are much more affected than others. Many attempts have been made by different investigators to identify the factors that could predict asthma development or persistence in childhood. In this review, the relation between atopic sensitization as an indicator of allergy and asthma in childhood will be discussed. Cross sectional studies, carried out in different countries, failed to show any firm correlation between asthma and atopic sensitization. Birth cohort mainly of infants at high risk for asthma and case–control studies showed that atopic sensitization was a risk factor for current asthma in children older than 6 years. In general, clear relations are observed mostly in affluent Western countries, whereas in less affluent countries, the picture is more heterogeneous. For the prediction of asthma development or persistence in school age children, other prerequisites should also be fulfilled such as family history of asthma and wheezing episodes at preschool age. Despite the conductance of different studies regarding the potential role of allergen avoidance for the primary prevention of childhood asthma, it does not seem that this approach is of benefit for primary prevention purposes. However, the identification of children at risk for asthma is of benefit as these subjects could be provided with the best management practices and with the appropriate secondary prevention measures.

Effectiveness of Evidence-Based Asthma Interventions.

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Kennedy, Suzanne; Bailey, Ryan; Jaffee, Katy; Markus, Anne; Gerstein, Maya; Stevens, David M; Lesch, Julie Kennedy; Malveaux, Floyd J; Mitchell, Herman

2017-06-01

Researchers often struggle with the gap between efficacy and effectiveness in clinical research. To bridge this gap, the Community Healthcare for Asthma Management and Prevention of Symptoms (CHAMPS) study adapted an efficacious, randomized controlled trial that resulted in evidence-based asthma interventions in community health centers. Children (aged 5-12 years; N = 590) with moderate to severe asthma were enrolled from 3 intervention and 3 geographically/capacity-matched control sites in high-risk, low-income communities located in Arizona, Michigan, and Puerto Rico. The asthma intervention was tailored to the participant's allergen sensitivity and exposure, and it comprised 4 visits over the course of 1 year. Study visits were documented and monitored prospectively via electronic data capture. Asthma symptoms and health care utilization were evaluated at baseline, and at 6 and 12 months. A total of 314 intervention children and 276 control children were enrolled in the study. Allergen sensitivity testing (96%) and home environmental assessments (89%) were performed on the majority of intervention children. Overall study activity completion (eg, intervention visits, clinical assessments) was 70%. Overall and individual site participant symptom days in the previous 4 weeks were significantly reduced compared with control findings (control, change of -2.28; intervention, change of -3.27; difference, -0.99; P asthma in these high-need populations. Copyright © 2017 by the American Academy of Pediatrics.

Effect of asthma severity on symptom perception in childhood asthma

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A.L.B. Cabral

2002-03-01

Full Text Available Individual ability to perceive airway obstruction varies substantially. The factors influencing the perception of asthma are probably numerous and not well established in children. The present study was designed to examine the influence of asthma severity, use of preventive medication, age and gender on the association between respiratory symptoms (RS and peak expiratory flow (PEF rates in asthmatic children. We followed 92 asthmatic children, aged 6 to 16 years, for five months. Symptom scores were recorded daily and PEF was measured twice a day. The correlations among variables at the within-person level over time were analyzed for each child and for the pooled data by multivariate analysis. After pooling the data, there was a significant (P<0.05 correlation between each symptom and PEF; 60% of the children were accurate perceivers (defined by a statistically significant correlation between symptoms and PEF across time for diurnal symptoms and 37% for nocturnal symptoms. The accuracy of perception was independent of asthma severity, age, gender or the use of preventive medication. Symptom perception is inaccurate in a substantial number of asthmatic children, independently of clinical severity, age, gender or use of preventive medication. It is not clear why some asthmatic patients are capable of accurately perceiving the severity of airway obstruction while others are not.

Allergy sensitization and asthma among 13-14 year old school ...

African Journals Online (AJOL)

Background: The prevalence of asthma and role of atopy in asthma among children has not been clearly defined in Nigeria. Objective: To determine the prevalence of asthma and investigate risk factors related to allergy sensitization among urban and rural school children in southwest Nigeria. Methods: Validated ISAAC ...

The usefulness of the mannitol challenge test for asthma

DEFF Research Database (Denmark)

Porsbjerg, Celeste; Sverrild, Asger; Backer, Vibeke

2013-01-01

The mannitol test was developed as an easy-to-use, safe, standardized bronchial challenge test for diagnosing asthma in a wide range of clinical settings. The mannitol test has a moderate sensitivity and will only detect approximately 60% of asthma cases. Hence, a negative mannitol test cannot be......-inflammatory therapy. In this review, the current knowledge on the usefulness of the mannitol in a clinical setting as well as in clinical trials is presented and outstanding questions on the usefulness of the test are discussed.......The mannitol test was developed as an easy-to-use, safe, standardized bronchial challenge test for diagnosing asthma in a wide range of clinical settings. The mannitol test has a moderate sensitivity and will only detect approximately 60% of asthma cases. Hence, a negative mannitol test cannot...... be used to rule out asthma. The advantage of the mannitol test is a high specificity. In an individual with symptoms suggestive of asthma, a positive test indicates a high likelihood of asthma with ongoing airway inflammation and seems useful for detecting asthma requiring regular anti...

Bronchial Thermoplasty in Severe Asthma: Best Practice Recommendations from an Expert Panel.

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Bonta, Peter I; Chanez, Pascal; Annema, Jouke T; Shah, Pallav L; Niven, Robert

2018-01-01

Bronchial thermoplasty (BT) is a bronchoscopic treatment for patients with severe asthma who remain symptomatic despite optimal medical therapy. In this "expert best practice" paper, the background and practical aspects of BT are highlighted. Randomized, controlled clinical trials have shown BT to be safe and effective in reducing severe exacerbations, improving quality of life, and decreasing emergency department visits. Five-year follow-up studies have provided evidence of the functional stability of BT-treated patients with persistence of a clinical benefit. The Global Initiative for Asthma (GINA) guidelines state that BT can be considered as a treatment option for adult asthma patients at step 5. Patient selection for BT requires close collaboration between interventional pulmonologists and severe asthma specialists. Key patient selection criteria for BT will be reviewed. BT therapy is delivered in 3 separate bronchoscopy sessions at least 3 weeks apart, covering different regions of the lung separately. Patients are treated with 50 mg/day of prednisolone or equivalent for 5 days, starting treatment 3 days prior to the procedure. The procedure is performed under moderate-to-deep sedation or general anesthesia. At bronchos-copy a single-use catheter with a basket design is inserted through the instrument channel and the energy is delivered by a radiofrequency (RF) generator (AlairTM Bronchial Thermoplasty System). BT uses temperature-controlled RF energy to impact airway remodeling, including a reduction of excessive airway smooth muscle within the airway wall, which has been recognized as a predominant feature of asthma. The treatment should be performed in a systemic manner, starting at the most distal part of the (sub)segmental airway, then moving proximally to the main bronchi, ensuring that the majority of the airways are treated. In general, 40-70 RF activations are provided in the lower lobes, and between 50 and 100 activations in the upper lobes combined

Development of a questionnaire to evaluate asthma control in Japanese asthma patients.

Science.gov (United States)

Tohda, Yuji; Hozawa, Soichiro; Tanaka, Hiroshi

2018-01-01

The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients. A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated. The intra-class correlation coefficients (ICCs) were within the range of 0.55-0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were -0.78, -0.78, and 0.77, respectively, showing a significant correlation (p asthma control status in a higher number of patients. UMIN000016589. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

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Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

2013-09-01

Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Copyright © 2013 Wiley Periodicals, Inc.

Assessment of variations in control of asthma over time.

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Combescure, C; Chanez, P; Saint-Pierre, P; Daurès, J P; Proudhon, H; Godard, P

2003-08-01

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Comparative efficacy of inhaled ciclesonide, budesonide, and fluticasone in mild to moderately persistent bronchial asthma

OpenAIRE

Tamoghna Maiti; Syed Mohammed Naser; Amrita Panda; Sekhar Mandal; Sonai Mandal; Tanmoy Gangopadhyay; Parvin Banu

2014-01-01

Background: Bronchodilators and glucocorticoids have been proven to be very effective and safe in asthma treatment, which recommend the use of steroids and beta2-agonist (long or short acting) as the first line of treatment in of asthma. This study was aimed to compare the efficacy of three different inhaled corticosteroids ciclesonide, budesonide, and fluticasone in bronchial asthma. Methods: A total of 30 patients with mild to moderately persistent bronchial asthma was selected as per th...

Severe asthma: anti-IgE or anti-IL-5?

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Evgenia Papathanassiou

2016-11-01

Full Text Available Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator. Anti-IgE (omalizumab and anti-IL-5 (mepolizumab antibodies are biological agents that interfere in different steps of the Th2 inflammatory cascade and are licensed in severe asthma. Both exhibit a favourable clinical outcome as they reduce exacerbation rate and improve asthma control and quality of life, while mepolizumab also induces an oral steroid sparing effect. Nevertheless, it is still questionable which agent is more suitable in the management of severe allergic asthma since no comparable studies have been conducted. Omalizumab's established effectiveness in clinical practice over a long period is complemented by a beneficial effect on airway remodelling process mediated mainly through its impact on eosinophils and other parameters strongly related to eosinophilic inflammation. However, it is possible that mepolizumab through nearly depleting eosinophils could have a similar effect on airway remodelling. Moreover, to date, markers indicative of the patient population responding to each treatment are unavailable although baseline eosinophils and exacerbation rate in the previous year demonstrate a predictive value regarding anti-IL-5 therapy effectiveness. On the other hand, a better therapeutic response for omalizumab has been observed when low forced expiratory volume in 1 sec, high-dose inhaled corticosteroids and increased IgE concentrations are present. Consequently, conclusions are not yet safe to be drawn based on

Comparative Genomics of Pathogens Causing Brown Spot Disease of Tobacco: Alternaria longipes and Alternaria alternata.

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Yujie Hou

Full Text Available The genus Alternaria is a group of infectious/contagious pathogenic fungi that not only invade a wide range of crops but also induce severe allergic reactions in a part of the human population. In this study, two strains Alternaria longipes cx1 and Alternaria alternata cx2 were isolated from different brown spot lesions on infected tobacco leaves. Their complete genomes were sequenced, de novo assembled, and comparatively analyzed. Phylogenetic analysis revealed that A. longipes cx1 and A. alternata cx2 diverged 3.3 million years ago, indicating a recent event of speciation. Seventeen non-ribosomal peptide synthetase (NRPS genes and 13 polyketide synthase (PKS genes in A. longipes cx1 and 13 NRPS genes and 12 PKS genes in A. alternata cx2 were identified in these two strains. Some of these genes were predicted to participate in the synthesis of non-host specific toxins (non-HSTs, such as tenuazonic acid (TeA, alternariol (AOH and alternariol monomethyl ether (AME. By comparative genome analysis, we uncovered that A. longipes cx1 had more genes putatively involved in pathogen-plant interaction, more carbohydrate-degrading enzymes and more secreted proteins than A. alternata cx2. In summary, our results demonstrate the genomic distinction between A. longipes cx1 and A. altenata cx2. They will not only improve the understanding of the phylogenetic relationship among genus Alternaria, but more importantly provide valuable genomic resources for the investigation of plant-pathogen interaction.

Prevalence of IgE sensitization in Danish children with suspected asthma

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Hoffmann-Petersen, Benjamin; Høst, Arne; Larsen, Kirsten Toksvig

2013-01-01

OBJECTIVE: The aim of this article was to estimate the prevalence of IgE sensitization in Danish children with suspected asthma and to characterize the pattern of sensitization. STUDY DESIGN: We performed a cross-sectional study including 1744 children from 0 to 15 yr suspected of asthma who were...... referred to pediatric outpatient clinics in the region of southern Denmark from 2003 to 2005. The children were subjected to an extensive questionnaire-based interview, clinical examination, and both skin prick testing (SPT) and IgE measurements for 17 allergens. RESULTS: Asthma was confirmed in 1024...... of the 1744 children. Among the children in whom the asthma diagnosis was confirmed, sensitization to one or more of the 17 allergens tested was found in 67.5% by either SPT or s-IgE ≥ class 2. Sensitization to any food allergen was found in 31.1%, to any outdoor allergen in 36.2%, and to any indoor allergen...

Relationships between severity of chronic rhinosinusitis and nasal polyposis, asthma, and atopy

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Pearlman, Aaron N.; Chandra, Rakesh K.; Chang, Dennis; Conley, David B.; Peters, Anju Tripathi; Grammer, Leslie C.; Schleimer, Robert T.; Kern, Robert C.

2013-01-01

Background The effect of comorbid conditions such as asthma and atopy on the severity of chronic rhinosinusitis (CRS) and the presence of nasal polyps (NPs) remains an area of investigation. We sought to elucidate the relationship among these entities. Methods The study population included 106 consecutive patients who were referred to a multidisciplinary, university-based allergy and sinus clinic that underwent computed tomography (CT) scan, skin-prick testing, and had CRS. Data were analyzed to determine Lund-MacKay score (LMS), presence of NPs, asthma status, and sensitivity to seven classes of aeroallergens. Results Skin tests were positive in 52 cases and negative in 54 cases. Although, there was no statistical relationship between LMS and atopic status in the entire group, among the asthmatic subgroup, mean LMS was greater in nona topic asthmatic patients than in atopic asthmatic patients. Asthmatic patients had a higher LMS than nonasthmatic patients (p 10 (p = 0.0236) and had more severe maxillary sinus involvement (p = 0.0391). Conclusion These data indicate a strong relationship between CRS severity, as measured by LMS, and chronic airway inflammatory diseases, asthma, and NPs. The association between LMS and atopic status appears weak. The present study suggests that CRS is an inflammatory disease that occurs independently of systemic IgE-mediated pathways. PMID:19401038

RItA: The Italian severe/uncontrolled asthma registry.

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Maio, S; Baldacci, S; Bresciani, M; Simoni, M; Latorre, M; Murgia, N; Spinozzi, F; Braschi, M; Antonicelli, L; Brunetto, B; Iacovacci, P; Roazzi, P; Pini, C; Pata, M; La Grasta, L; Paggiaro, P; Viegi, G

2018-03-01

The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV 1 % pred of 75.1%, median values of 300/mm 3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Point-of-care blood eosinophil count in a severe asthma clinic setting.

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Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

2017-07-01

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Age-Specific Characteristics of Inpatients with Severe Asthma Exacerbation

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Kiyoshi Sekiya

2013-01-01

Conclusions: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.

Use of inhaled corticosteroids in pediatric asthma

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Bisgaard, H

1997-01-01

to normal when introduced for moderately severe asthma. This finding highlights the need to improve treatment strategy in pediatric asthma. The natural progression of persistent asthma may lead to loss of lung function and chronic bronchial hyperreactivity for children and adults. There is evidence...

Severe bronchial asthma in children: a review of novel biomarkers used as predictors of the disease

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Uwaezuoke SN

2018-01-01

Full Text Available Samuel N Uwaezuoke, Adaeze C Ayuk, Joy N Eze Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria Abstract: Severe asthma or therapy-resistant asthma in children is a heterogeneous disease that affects all age-groups. Given its heterogeneity, precision in diagnosis and treatment has become imperative, in order to achieve better outcomes. If one is thus able to identify specific patient phenotypes and endotypes using the appropriate biomarkers, it will assist in providing the patient with more personalized and appropriate treatment. However, there appears to be a huge diagnostic gap in severe asthma, as there is no single test yet that accurately determines disease phenotype. In this paper, we review the published literature on some of these biomarkers and their possible role in bridging this diagnostic gap. We also highlight the cellular and molecular mechanisms involved in severe asthma, in order to show the basis for the novel biomarkers. Some markers useful for monitoring therapy and assessing airway remodeling in the disease are also discussed. A review of the literature was conducted with PubMed to gather baseline data on the subject. The literature search extended to articles published within the last 40 years. Although biomarkers specific to different severe asthma phenotypes have been identified, progress in their utility remains slow, because of several disease mechanisms, the variation of biomarkers at different levels of inflammation, changes in relying on one test over time (eg, from sputum eosinophilia to blood eosinophilia, and the degree of invasive tests required to collect biomarkers, which limits their applicability in clinical settings. In conclusion, several biomarkers remain useful in recognizing various asthma phenotypes. However, due to disease heterogeneity, identification and utilization of ideal and defined biomarkers in severe asthma are still inconclusive. The development of novel

Functional significance of air trapping detected in moderate asthma

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Laurent, F.; Latrabe, V.; Raherison, C.; Marthan, R.; Tunon-de-Lara, J.M.

2000-01-01

The aim of this study was to evaluate bronchial and lung abnormalities in patients suffering from moderate asthma as defined by international guidelines, with special attention to air trapping on CT in comparison with that detected in smoking and non-smoking normal subjects. Twenty-two patients classified as moderate asthma and control subjects including healthy volunteers, smokers (n = 10) or non-smokers (n = 12) were prospectively explored by high-resolution CT (HRCT) performed at suspended full inspiration and expiration. The same expiratory protocol was performed 15 min after inhalation of 200 μg of salbutamol. Patients underwent pulmonary function tests within the same week and bronchodilator response was assessed following inhalation of salbutamol. Abnormalities of bronchi and lung parenchyma on inspiratory CT and air trapping on expiratory CT, in dependent and non-dependent areas, were assessed and scored semi-quantitatively by two independent observers. Comparison of score mean values between the different groups was performed using Mann-Whitney test and Spearman correlation between CT findings and pulmonary function tests were calculated. Mosaic perfusion was observed in 23 % of asthmatics. Air-trapping scores were significantly higher in asthmatic patients than in non-smoking control subjects (p = 0.003), but not than in smokers. This difference was ascribed to non-dependent zones of the lung for which air-trapping scores were also higher in asthmatic patients (p = 0.003) and in smoking subjects (p = 0.004) than in normal controls. In the asthmatic group, a significant positive correlation was found between airways resistance and bronchial dilatation score (p = 0.01), and between small airways obstruction index and mosaic perfusion score (p = 0.05). In addition, both FEV1 and reversibility of small airways obstruction values correlated with air-trapping score (p = 0.03 and p = 0.007, respectively). No change could be detected in air-trapping score

Clinical experience with Omalizumab in a Portuguese severe asthma unit

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S. Alfarroba

2014-03-01

Full Text Available Background: It is widely recognized that asthma control is not always possible in patients with very severe asthma despite available treatment. The aim of this study was to evaluate the efficacy of Omalizumab on asthma control as an add‐on therapy in patients from the “Severe Asthma Outpatient Service” of Pulido Valente Hospital in Lisbon, Portugal. Methods: A retrospective study was conducted to assess asthma control by the ACT score and by GINA classification, frequency and severity of exacerbations, medication use and pulmonary function in patients treated with Omalizumab. Clinical information was collected from medical records from the start of treatment and at 6‐, 12‐ and 24‐month follow‐ups. Results: 26 patients started the treatment with Omalizumab, and all (100% were classified by GINA with uncontrolled asthma prior to treatment. Mean ACT score was 11.5. All the patients had treatment with fixed‐dose ICS and LABA and 34.6% also had an anti‐cholinergic inhaler. 42.3% of patients were also treated with oral glucocorticosteroids for control. Patients reported an average of 1.8 moderate and 3.1 severe exacerbations/year. Statistical differences were found at 6‐month follow‐up in most end‐points: GINA score improved: 60.9% of patients with partially controlled asthma and only 39.1% with uncontrolled asthma (Wilcoxon 0.00; ACT score improved to 19.52 (Wilcoxon 0.00; mean FEV1 improved to 76.7% (Wilcoxon 0.025; the proportion of patients requiring oral glucocorticosteroid therapy reduced to 17.4% (Wilcoxon 0.014; and the number of moderate and severe exacerbations also decreased to 1.04 and 1.83 respectively (Wilcoxon 0.007; Wilcoxon 0.002 respectively. Conclusions: The current analysis shows evidence that omalizumab is successful in improving asthma control as an add‐on therapy GINA step 5 treatment. Resumo: Introdução: Está bem documentado que o controlo de asma nem

The effectiveness of the treatment of severe exercise-induced asthma in schoolchildren

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M.N. Garas

2017-03-01

Full Text Available Background. Bronchial asthma is one of the most common chronic multifactorial diseases of the lungs. At least 10–12 % of patients with bronchial asthma are suffering from a severe form of the disease. One aspect of inadequate severe asthma control is its phenotypic heterogeneity, interest of experts increases to the problem of exercise-induced asthma. The purpose of the study was to increase efficiency of treatment for severe exercise-induced asthma in schoolchildren based on the analysis of the attack dynamics and to achieve disease control according to main inflammatometric and spirometric indices. Materials and methods. We examined 46 children with severe persistent bronchial asthma, in particular, 15 schoolchildren suffering from severe exercise-induced asthma, the second clinical group (comparison one consisted of 31 children suffering from severe type of the disease, with no signs of exercise-induced bronchoconstriction. Basic therapy effectiveness was determined prospectively by assessing the disease control using AST-test with an interval of 3 months. The severity of bronchial obstruction syndrome in patients on admission to hospital during exacerbation was assessed by score scale. Airway hyperresponsiveness was evaluated according to the results of bronchoprovocation with histamine. Results. Children of I clinical group had more significant manifestations of bronchial obstruction during the week of inpatient treatment than the comparison group of patients, including significantly more severe manifestations of bronchial obstruction were verified on 1st and 7th day of hospitalization. Due to the analysis of basic therapy effectiveness, only a quarter of I clinical group patients and a larger part of schoolchildren in comparison group achieved the partial control after a 3-month course of anti-inflammatory treatment. Eosinophilic inflammation was observed in most children with severe exercise-induced asthma (60.1 % and in 47.2 % of

B-Glucan exacerbates allergic asthma independent of fungal ...

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BackgroundAllergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity.ObjectiveWe sought to determine the mechanism by which fungi affect asthma development and severity.MethodsWe integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity.ResultsWe report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc−/− mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity.ConclusionOur data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. To describe th

DNA methylation levels associated with race and childhood asthma severity.

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Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

2017-10-01

Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

Job strain and the risk of severe asthma exacerbations

DEFF Research Database (Denmark)

Heikkilä, K; Madsen, I E H; Nyberg, S T

2014-01-01

BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations...... in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe...... asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years...

Changes in asthma control, work productivity, and impairment with omalizumab: 5-year EXCELS study results.

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Zazzali, James L; Raimundo, Karina P; Trzaskoma, Benjamin; Rosén, Karin E; Schatz, Michael

2015-01-01

Asthma poses a significant disease burden worldwide. Current guidelines emphasize achieving and maintaining asthma control. To describe longitudinal changes of asthma control and asthma-related work, school, and activity impairment for patients with moderate-to-severe asthma treated with omalizumab and those who did not receive omalizumab in a real-world setting. This study used 5 years of data from patients ages ≥12 years old with moderate-to-severe persistent allergic asthma who were enrolled in the Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma observational study. Asthma control was assessed with the Asthma Control Test for 5 years, and asthma-related work, school, and activity impairment was measured with the Work Productivity/Activity Impairment-Asthma questionnaire for the first 2 years. The percentage of patients treated with omalizumab (n = 4930) and with well-controlled asthma (Asthma Control Test score, >20) increased from 45% at baseline to 61% at month 60, and it was 49% (baseline) and 67% (month 60) for the non-omalizumab-treated cohort (n = 2779). For new starters to omalizumab (n = 576), the percentage with well-controlled asthma increased from 25% at baseline to 51% at month 6, and to 60% at month 60. Patients in the omalizumab-treated cohort and those in the non-omalizumab-treated cohort experienced a reduction in asthma-related work, school, and activity impairment. The amount of improvement in asthma control achieved and the reduction in asthma-related work, school, and activity impairment were similar, regardless of asthma severity. On average, patients in the Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma observational study who initiated omalizumab experienced clinically significant improvement in asthma control, which was observed within 6 months and persisted for 5 years.

Novel targets of omalizumab in asthma.

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Sattler, Caroline; Garcia, Gilles; Humbert, Marc

2017-01-01

Omalizumab is a recombinant humanized anti-IgE monoclonal antibody approved in the US for moderate to severe persistent allergic asthma (severe persistent asthma in the European Union), uncontrolled despite treatment with inhaled corticosteroids and long-acting beta2 agonists. It reduces asthma exacerbations, symptoms, oral corticosteroid doses, and improves quality of life. Omalizumab may have an antiviral effect when used as a preventive therapy for fall exacerbations in children and teenagers. Two proof-of-concept studies have evaluated omalizumab in nonatopic asthma and showed that it is safe and possibly efficacious in some patients. Omalizumab has been successfully studied as add-on to specific immunotherapy in moderate allergic asthma. Its safety in pregnancy has been assessed in the EXPECT registry. Case series also report positive effects in cases of allergic bronchopulmonary aspergillosis, and in nasal disorders frequently associated with asthma. Last, omalizumab may have corticosteroid-sparing effect in a subset of patients with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). Recent studies argue in favor of positive effects of omalizumab beyond its current indications in asthma. Well-designed studies are needed in order to demonstrate the safety and efficacy of omalizumab in these possible novel indications.

In vitro sensitivity of Alternaria solani to conventional fungicides and a biofungicide based on tea tree essential oil

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Miloš Stepanović

2015-01-01

Full Text Available A study of in vitro sensitivity of five Alternaria solani isolates to cooper-oxychloride, chlorothalonil, difenoconazole, pyraclostrobin and a biofungicide based on tea tree essential oil was carried out. The isolates were obtained from infected tomato leaves collected from five different locations in Serbia. The tested isolates showed the highest sensitivity to pyraclostrobin with EC50 values ranging from 0.0014 to 0.0041 μg ml-1. The EC50 values of difenoconazole were 0.018-0.037 μg ml-1, chlorothalonil 2.99-4.54 μg ml-1, and cooper-oxychloride 13.27-15.63 μg ml-1. All tested A. solani isolates were the least sensitive to tea tree oil (1323.97-3307.08 μg l-1.

An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma.

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Simone Accordini

Full Text Available Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD study (www.geird.org, 326 subjects (aged 20-64 with ever asthma were identified from the general population in Verona (Italy between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes was analysed. A symptom and treatment score (STS and pre-bronchodilator FEV1% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV1% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR. SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4 was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04, whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r(2 = 0.94 in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09. Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1 or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever

Influence of β(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol.

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Giubergia, Verónica; Gravina, Luis; Castaños, Claudio; Chertkoff, Lilien

2013-03-01

New evidence suggests that different β(2)-adrenergic receptor (β2AR) polymorphisms may influence asthma control in patients receiving long-acting β(2)agonists (LABAs) as regular therapy. To determine the influence of β2AR polymorphisms on asthma exacerbations in children with severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs regularly. Ninety-seven children with severe asthma were genotyped for polymorphisms of β2AR at codons 16 and 27. The number of severe exacerbations, the time of first asthma exacerbation, and the number of hospitalizations during 12 months were assessed. Changes on pulmonary function from the beginning to the end of the study were also evaluated. The number of overall asthma exacerbations and the proportion of children with these events were similar among β2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position 27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was similar among individuals carrying different β2AR polymorphisms. No β2AR genotype association was found in relation to the number of hospitalizations. Longitudinal analysis of forced expiratory volume in 1 second from baseline to the end of the study also showed no differences among β2AR genotypes at position 16 or 27. No association was observed among the 3 most common haplotypes (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of participants with asthmatic crisis or with the overall number of exacerbations. β2AR polymorphisms were not associated with an increased risk of having asthma exacerbations or lung function decline in a population of Argentinian children with severe asthma receiving ICS and LABAs regularly. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Early-life sensitization to hen's egg predicts asthma and rhinoconjunctivitis at 14 years of age

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Christiansen, Elisabeth Soegaard; Kjaer, Henrik Fomsgaard; Eller, Esben

2017-01-01

to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. RESULTS: Both transient and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99(1.41-11.32) and 5.95(1.78-19.92)) and RC...... (aOR 2.94(1.19-7.28) and 6.18(1.86-20.53)) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to HDM had increased risk of asthma (aOR 3.80(1.17-12.41)) at 14 years. CONCLUSIONS: Early transient and persistent IgE sensitization to hen......'s egg was associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years. This article is protected by copyright. All rights reserved....

Alt a 1 allergen homologs from Alternaria and related taxa: analysis of phylogenetic content and secondary structure.

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Hong, Soon Gyu; Cramer, Robert A; Lawrence, Christopher B; Pryor, Barry M

2005-02-01

A gene for the Alternaria major allergen, Alt a 1, was amplified from 52 species of Alternaria and related genera, and sequence information was used for phylogenetic study. Alt a 1 gene sequences evolved 3.8 times faster and contained 3.5 times more parsimony-informative sites than glyceraldehyde-3-phosphate dehydrogenase (gpd) sequences. Analyses of Alt a 1 gene and gpd exon sequences strongly supported grouping of Alternaria spp. and related taxa into several species-groups described in previous studies, especially the infectoria, alternata, porri, brassicicola, and radicina species-groups and the Embellisia group. The sonchi species-group was newly suggested in this study. Monophyly of the Nimbya group was moderately supported, and monophyly of the Ulocladium group was weakly supported. Relationships among species-groups and among closely related species of the same species-group were not fully resolved. However, higher resolution could be obtained using Alt a 1 sequences or a combined dataset than using gpd sequences alone. Despite high levels of variation in amino acid sequences, results of in silico prediction of protein secondary structure for Alt a 1 demonstrated a high degree of structural similarity for most of the species suggesting a conservation of function.

Mode of dendritic cell activation: the decisive hand in Th2/Th17 cell differentiation. Implications in asthma severity?

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Vroman, Heleen; van den Blink, Bernt; Kool, Mirjam

2015-02-01

Asthma is a heterogeneous chronic inflammatory disease of the airways, with reversible airflow limitations and airway remodeling. The classification of asthma phenotypes was initially based on different combinations of clinical symptoms, but they are now unfolding to link biology to phenotype. As such, patients can suffer from a predominant eosinophilic, neutrophilic or even mixed eosinophilic/neutrophilic inflammatory response. In adult asthma patients, eosinophilic inflammation is usually seen in mild-to-moderate disease and neutrophilic inflammation in more severe disease. The underlying T cell response is predominated by T helper (Th) 2, Th17, or a mixed Th2/Th17 cell immune response. Dendritic cells (DCs) are "professional" antigen presenting cells (APCs), since their principal function is to present antigens and induce a primary immune response in resting naive T cells. DCs also drive the differentiation into distinctive Th subsets. The expression of co-stimulatory molecules and cytokines by DCs and surrounding cells determines the outcome of Th cell differentiation. The nature of DC activation will determine the expression of specific co-stimulatory molecules and cytokines, specifically needed for induction of the different Th cell programs. Thus DC activation is crucial for the subsequent effector Th immune responses. In this review, we will discuss underlying mechanisms that initiate DC activation in favor of Th2 differentiation versus Th1/Th17 and Th17 differentiation in the development of mild versus moderate to severe asthma. Copyright © 2014 Elsevier GmbH. All rights reserved.

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

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Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-12-01

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Epidemiology of dark leaf spot caused by Alternaria brassicicola and Alternaria brassicae in organic seed production of cauliflower

NARCIS (Netherlands)

Köhl, J.; Tongeren, van C.A.M.; Groenenboom-de Haas, B.H.; Hoof, van R.A.; Driessen, R.; Heijden, van der L.

2010-01-01

In organic seed production of Brassica vegetables, infections by Alternaria brassicicola and A. brassicae can cause severe losses of yield and seed quality. Four field experiments with or without artificial inoculation with A. brassicicola were conducted in organically managed seed-production crops

Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

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Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

2017-04-01

To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.

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Jin, Peng; Andiappan, Anand Kumar; Quek, Jia Min; Lee, Bernett; Au, Bijin; Sio, Yang Yie; Irwanto, Astrid; Schurmann, Claudia; Grabe, Hans Jörgen; Suri, Bani Kaur; Matta, Sri Anusha; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Sun, Liangdan; Zhang, Xuejun; Liu, Hong; Zhang, Furen; Larbi, Anis; Xu, Xin; Poidinger, Michael; Liu, Jianjun; Chew, Fook Tim; Rotzschke, Olaf; Shi, Li; Wang, De Yun

2015-06-01

Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR. We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR. Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays. The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood. A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Studying the Effects of Fasting during Ramadan on Pulmonary Functioning Test and Asthma Severity

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Seyyed Hassan Adeli

2015-03-01

Full Text Available Background and Objectives: Studies have shown that fasting can have an impact on the course and severity of chronic diseases. There are a few studies on the association of fasting and asthma. Therefore, this study has been conducted with the purpose of examining the effects of fasting on asthma severity and pulmonary functioning tests. Methods: 30 patients with asthma who attended a pulmonology clinic in Qom were enrolled in this study. The severity of patients’ asthma has been studied by questionnaire and spirometry of pulmonary functioning in the month of Shaban, Ramadan and Shawwal. The results of Asthma Control Questionnaire and the pulmonary functioning tests in three months have been compared. Results: The average age of patients was 43.42 years and 43.3% of patients were males. The Average score for asthma severity questionnaire in three months were 20.4, 21 and 20.17 respectively. Statistically, there haven’t been any significant differences between the results of pulmonary functioning test and asthma severity before Ramadan (Shaban, during Ramadan and after that (Shawwal. Conclusion: The findings of this study showed that fasting in patients with asthma has no effect on pulmonary function and asthma severity.

Non-invasive ventilation in severe asthma attack, its possibilities and problems.

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Murase, K; Tomii, K; Chin, K; Niimi, A; Ishihara, K; Mishima, M

2011-06-01

Asthma attack is characterized by episodic attacks of cough, dyspnea and wheeze occurring due to bronchoconstriction, airway hyperresponsiveness and mucous hypersecretion. Although nationwide clinical guidelines have been published to establish the standard care of asthma, choices in the treatment of fatal asthma attacks remain of clinical significance. Especially, in a severe asthma attack, despite the application of conventional medical treatment, respiratory management is critical. Even though non-invasive ventilation (NIV) has been shown to be effective in a wide variety of clinical settings, reports of NIV in asthmatic patients are scarce. According to a few prospective clinical trials reporting promising results in favour of the use of NIV in a severe asthma attack, a trial of NIV prior to invasive mechanical ventilation seems acceptable and may benefit patients by decreasing the need for intubation and by supporting pharmaceutical treatments. Although selecting the appropriate patients for NIV use is a key factor in successful NIV application, how to distinguish such patients is quite controversial. Larger high quality clinical trails are urgently required to confirm the benefits of NIV to patients with severe asthma attack. In this article, we focus on the body of evidence supporting the use of NIV in asthma attacks and discuss its advantages as well its problems.

Benralizumab: a unique IL-5 inhibitor for severe asthma

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Tan LD

2016-04-01

Full Text Available Laren D Tan,1 Jennifer M Bratt,2 Dorottya Godor,3 Samuel Louie,2 Nicholas J Kenyon2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 2Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, USA; 3School of Medicine, Semmelweis University, Budapest, Hungary Abstract: The presence of eosinophilic inflammation is a characteristic feature of chronic and acute inflammation in asthma. An estimated 5%–10% of the 300 million people worldwide who suffer from asthma have a severe form. Patients with eosinophilic airway inflammation represent approximately 40%–60% of this severe asthmatic population. This form of asthma is often uncontrolled, marked by refractoriness to standard therapy, and shows persistent airway eosinophilia despite glucocorticoid therapy. This paper reviews personalized novel therapies, more specifically benralizumab, a humanized anti-IL-5Rα antibody, while also being the first to provide an algorithm for potential candidates who may benefit from anti-IL-5Rα therapy. Keywords: asthma, eosinophils, asthma treatments, benralizumab, IL-5, IL-5Rα, MEDI-563

Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma.

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Phipatanakul, Wanda; Mauger, David T; Sorkness, Ronald L; Gaffin, Jonathan M; Holguin, Fernando; Woodruff, Prescott G; Ly, Ngoc P; Bacharier, Leonard B; Bhakta, Nirav R; Moore, Wendy C; Bleecker, Eugene R; Hastie, Annette T; Meyers, Deborah A; Castro, Mario; Fahy, John V; Fitzpatrick, Anne M; Gaston, Benjamin M; Jarjour, Nizar N; Levy, Bruce D; Peters, Stephen P; Teague, W Gerald; Fajt, Merritt; Wenzel, Sally E; Erzurum, Serpil C; Israel, Elliot

2017-06-01

Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids. To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations. A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV 1 . Adult asthma groups exhibited a small but significant mean FEV 1 % predicted improvement after TA (SA group mean difference, 3.4%; 95% confidence interval, 2.2-4.7%; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV 1 and worse asthma control as compared with NONSA after TA. In children, after TA only prebronchodilator FEV 1 distinguished SA from NONSA. A total of 21% of adults with SA and 20% of children with SA achieved greater than or equal to 10% improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA. One in five patients with SA exhibit greater than or equal to 10% improvement in FEV 1 with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www

Omalizumab Treatment Response in a Population With Severe Allergic Asthma and Overlapping COPD.

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Maltby, Steven; Gibson, Peter G; Powell, Heather; McDonald, Vanessa M

2017-01-01

Asthma and COPD are common airway diseases. Individuals with overlapping asthma and COPD experience increased health impairment and severe disease exacerbations. Efficacious treatment options are required for this population. Omalizumab (anti-IgE) therapy is effective in patients with severe persistent asthma, but limited data are available on efficacy in populations with overlapping asthma and COPD. Data from the Australian Xolair Registry were used to compare treatment responses in individuals with asthma-COPD overlap with responses in patients with severe asthma alone. Participants were assessed at baseline and after 6 months of omalizumab treatment. We used several different definitions of asthma-COPD overlap. First, we compared participants with a previous physician diagnosis of COPD to participants with no COPD diagnosis. We then made comparisons based on baseline lung function, comparing participants with an FEV 1 80% predicted after bronchodilator use. In the population with an FEV 1 Omalizumab treatment markedly improved asthma control and health-related quality of life in all populations assessed based on the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. Omalizumab treatment did not improve lung function (FEV 1 , FVC, or FEV 1 /FVC ratio) in populations that were enriched for asthma-COPD overlap (diagnosis of COPD or FEV 1  omalizumab improves asthma control and health-related quality of life in individuals with severe allergic asthma and overlapping COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful in the management of severe asthma with COPD overlap. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

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Ono, Emiko; Dutile, Stefanie; Kazani, Shamsah; Wechsler, Michael E.; Yang, Jun; Hammock, Bruce D.; Douda, David Nobuhiro; Tabet, Yacine; Khaddaj-Mallat, Rayan; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric; Martin, Richard; Sutherland, E. Rand; Castro, Mario; N. Jarjour, Nizar; Israel, Elliot

2014-01-01

Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. Objectives: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. Methods: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte–platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. Measurements and Main Results: 8-Isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r = −0.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte–platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor–induced increases in leukocyte–platelet aggregates (70.8% inhibition [LXA4 100 nM], 78.3% inhibition [15-epi-LXA4 100 nM]) and 15-epi-LXA4 markedly inhibited tumor necrosis factor-α–induced increases in bronchial contraction. Conclusions: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach

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

the 12 UNGD-outcome associations had increasing odds ratios across quartiles. Our findings were robust to increasing levels of covariate control and in sensitivity analyses that included evaluation of some possible sources of unmeasured confounding. Conclusions and Relevance Residential UNGD activity metrics were statistically associated with increased odds of mild, moderate, and severe asthma exacerbations. Whether these associations are causal awaits further investigation, including more detailed exposure assessment. PMID:27428612

Monograph on alternaria diseases of crucifers. Technical bulletin No. 1994-6E

Energy Technology Data Exchange (ETDEWEB)

Verma, P R

1994-12-31

The brassicas include an important group of oilseed crops such as canola and commercial vegetables such as cabbage and broccoli. Infection by species of the fungus Alternaria causes severe yield losses to those crops. This document compiles the most recent information on fundamental and applied knowledge of Alternaria species infecting Brassicaceae crops and weeds. It includes a review of the symptoms, geographical distribution, yield losses, and disease assessment methods of infections from the four most widely distributed species of Alternaria; information on the characteristics of the pathogen, its host range, disease cycle, process of infection, epidemiology, fine structures and electron microscopy, resistance, and phytotoxins; and techniques for disease infection and management. The document concludes with an evaluation of future strategies and priorities in the management of Alternaria diseases.

Inhaled budesonide for adults with mild-to-moderate asthma: a randomized placebo-controlled, double-blind clinical trial

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Ana Luisa Godoy Fernandes

2001-09-01

Full Text Available CONTEXT: Budesonide is an inhaled corticosteroid with high topical potency and low systemic activity recommended in the treatment of chronic asthma. OBJECTIVE: This study was conducted to determine the efficacy and safety of inhaled budesonide via a breath-activated, multi-dose, dry-powder inhaler. TYPE OF STUDY: Multicenter randomized parallel-group, placebo-controlled, double-blind, clinical trial. SETTING: Multicenter study in the university units. PARTICIPANTS: Adult patients with mild-to-moderate asthma that was not controlled using bronchodilator therapy alone. PROCEDURES: Comparison of budesonide 400 µg administered twice daily via a breath-activated, multi-dose, dry-powder inhaler with placebo, in 43 adult patients (aged 15 to 78 years with mild-to-moderate asthma (FEV1 71% of predicted normal that was not controlled using bronchodilator therapy alone. MAIN MEASUREMENTS: Efficacy was assessed by pulmonary function tests and asthma symptom control (as perceived by the patients and the use of rescue medication. RESULTS: Budesonide 400 µg (bid was significantly more effective than placebo in improving morning peak expiratory flow (mean difference: 67.9 l/min; P < 0.005 and FEV1 (mean difference: 0.60 l; P < 0.005 over the 8-week treatment period. Onset of action, assessed by morning peak expiratory flow, occurred within the first two weeks of treatment. CONCLUSIONS: Budesonide via a breath-activated, multi-dose, dry-powder inhaler results in a rapid onset of asthma control, which is maintained over time and is well tolerated in adults with mild-to-moderate asthma.

Lower prevalence and greater severity of asthma in hot and dry climate

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Marco Aurélio de Valois Correia Junior

Full Text Available Abstract Objective: To estimate asthma prevalence, severity, and associated factors in adolescents who live in a low relative humidity environment. Methods: In this cross-sectional study, adolescents aged 13-14 years from the city of Petrolina located in the Brazilian semiarid region answered the International Study of Asthma and Allergies in Childhood (ISAAC questionnaire. The possible explanatory variables of the study were gender, family income, mother's education, smokers in the household, parental history of asthma, personal history of allergic rhinitis or atopic dermatitis, and physical activity level. Poisson regression analysis was used to assess the association between asthma and the explanatory variables. Results: A total of 1591 adolescents participated in the study, of whom 49.7% were male. The prevalence of active asthma, severe asthma, and physician-diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with asthma missed more school days than their peers (33 vs. 22 days/year; p < 0.03. Associated factors that remained significant after adjustment were history of asthma in parents (PR = 2.65, p < 0.001 and personal diagnosis of allergic rhinitis (PR = 1.96, p < 0.001 and/or atopic dermatitis (PR = 2.18, p < 0.001. Conclusion: Asthma prevalence in this low-humidity environment was lower, but more severe than those reported in other Brazilian cities. The dry climate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population.

ANTI-IGE THERAPY FOR SEVERE ASTHMA IN CHILDREN: TWO-YEAR TRIAL

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T.Yu. Kulichenko

2010-01-01

Full Text Available The article summarizes a two-year experience of treating children and adolescents with severe uncontrolled atopic asthma using Omalizumab. This treatment facilitated to achieve full asthma control in 70% of patients and partial control in 30% of patients. Anti-Ig Etherapy contributes to reduce the frequency of asthma relapses 77%, and the number of those seeking emergency medical treatment, particularly no need for in-patient asthma care. Thanks to treatment, lung function parameters improve, particularly in children with low bronchial patency parameters even after administration of broncholytics. Thanks to treatment with omalizumab, the dosage of inhalant glucocorticosteroids is reduced 1.5 to 2.5 times in 75% patients. Treatment tolerance in all children is satisfactory, no serious adverse events associated with the medication or any system side effects are registered in patients. Anti-IgE therapy is a good alternative to use of high and ultra-high doses of inhalant glucocorticosteroids in children with severe atopic asthma. Key words: omalizumab, anti-IgE-antibodies, treatment-resistant asthma, atopic asthma, treatment, children, adolescents, asthma control. (Pediatric Pharmacology. – 2010; 7(3:57-65

Induction of mutant resistant to alternaria blotch of apple by gamma-ray irradiation

International Nuclear Information System (INIS)

Yoshioka, Toji; Ito, Yuji; Masuda, Tetsuo

2000-01-01

Apple cultivars resistant to Alternaria blotch disease have been produced by cross-breeding, but it is difficult to produce resistance by crossing without changing the properties of cultivar because the gene composition of the cultivar tree is almost heterozygous. This study aimed to investigate the resistant mutation in Alternaria blotch susceptible and semiresistant cultivars. The resistance to Alternaria blotch pathogen or AM toxin is classified into the following three groups: 1) highly sensitive group including Indo, Redgold and Starking delicious, 2) semi-resistant group including Fuji, Orin and Golden delicious and 3) resistant group including Gala and Tsugaru. After gamma ray exposure of 80 Gy (at 5 Gy/hour), AM-toxin insensitive clones were selected in the VM 6 generation. These selected mutants could be rooted and habituated under field conditions. The degree of disease resistance was assessed by AM toxin treatment and Alternaria blotch fungi spore inoculation test. The leaves of these mutants were changed to variegated at high temperature, suggesting that some mutation related to chloroplast might have occurred. Alternaria blotch resistant strains could be produced by exposing to γray and selecting with AM toxin in shoot-tip culture system, but the functional effects of the AM toxin in Alternaria blotch and also the mechanism in the mutant lines were still unclear. (M.N.)

Outcome of short-term hospitalization for children with severe asthma.

Science.gov (United States)

Weinstein, A G; Faust, D S; McKee, L; Padman, R

1992-07-01

This study presents results of a family-centered, short-term residential program in which medical, behavioral, and treatment assessments were provided to the child with severe asthma and the family. After a median stay of 15 days, forty-four consecutively admitted children with severe asthma achieved a 93% reduction in hospital days (median, 7 hospital days for the year before treatment versus median 0 hospital days per patient per year at 20 1/2-month follow-up; p less than 0.001) and an 81% reduction in emergency care (median, 4 visits for the year previously versus median, 0.4 visits per patient per year at follow-up; p less than 0.01). There was also a significant reduction in corticosteroid bursts and improvement in FEV1. Unique to this program was mandatory family participation focusing on the child's and family's adaptation to severe asthma and development of family-specific interventions to promote compliance with the treatment regimen. Child and family functioning was assessed at admission and follow-up. Hospital use at follow-up was greater for children from dysfunctional families. Families demonstrating difficulties in disciplining the child with asthma required more hospital days both before admission and at follow-up. Short-term hospitalization for children with severe asthma is associated with significant improvement in pulmonary morbidity when the family of the child is included in assessment and treatment.

Patient and physician evaluation of the severity of acute asthma exacerbations

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Atta J.A.

2004-01-01

Full Text Available We studied the ability of patients not experienced in the use of peak expiratory flow meters to assess the severity of their asthma exacerbations and compared it to the assessment of experienced clinicians. We also evaluated which data of physical examination and medical history are used by physicians to subjectively evaluate the severity of asthma attacks. Fifty-seven adult patients (15 men and 42 women, with a mean (± SD age of 37.3 ± 14.5 years and 24.0 ± 17.9 years of asthma symptoms with asthma exacerbations were evaluated in a University Hospital Emergency Department. Patients and physicians independently evaluated the severity of the asthma attack using a linear scale. Patient score, physician score and forced expiratory volume at the first second (FEV1 were correlated with history and physical examination variables, and were also considered as dependent variables in multiple linear regression models. FEV1 correlated significantly with the physician score (rho = 0.42, P = 0.001, but not with patient score (rho = 0.03; P = 0.77. Use of neck accessory muscles, expiratory time and wheezing intensity were the explanatory variables in the FEV1 regression model and were also present in the physician score model. We conclude that physicians evaluate asthma exacerbation severity better than patients and that physician's scoring of asthma severity correlated significantly with objective measures of airway obstruction (FEV1. Some variables (the use of neck accessory muscles, expiratory time and wheezing intensity persisted as explanatory variables in physician score and FEV1 regression models, and should be emphasized in medical schools and emergency settings.

Patient and physician evaluation of the severity of acute asthma exacerbations

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J.A. Atta

2004-09-01

Full Text Available We studied the ability of patients not experienced in the use of peak expiratory flow meters to assess the severity of their asthma exacerbations and compared it to the assessment of experienced clinicians. We also evaluated which data of physical examination and medical history are used by physicians to subjectively evaluate the severity of asthma attacks. Fifty-seven adult patients (15 men and 42 women, with a mean (± SD age of 37.3 ± 14.5 years and 24.0 ± 17.9 years of asthma symptoms with asthma exacerbations were evaluated in a University Hospital Emergency Department. Patients and physicians independently evaluated the severity of the asthma attack using a linear scale. Patient score, physician score and forced expiratory volume at the first second (FEV1 were correlated with history and physical examination variables, and were also considered as dependent variables in multiple linear regression models. FEV1 correlated significantly with the physician score (rho = 0.42, P = 0.001, but not with patient score (rho = 0.03; P = 0.77. Use of neck accessory muscles, expiratory time and wheezing intensity were the explanatory variables in the FEV1 regression model and were also present in the physician score model. We conclude that physicians evaluate asthma exacerbation severity better than patients and that physician's scoring of asthma severity correlated significantly with objective measures of airway obstruction (FEV1. Some variables (the use of neck accessory muscles, expiratory time and wheezing intensity persisted as explanatory variables in physician score and FEV1 regression models, and should be emphasized in medical schools and emergency settings.

Predicting hospitalization in children with acute asthma.

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Buyuktiryaki, A Betul; Civelek, Ersoy; Can, Demet; Orhan, Fazıl; Aydogan, Metin; Reisli, Ismail; Keskin, Ozlem; Akcay, Ahmet; Yazicioglu, Mehtap; Cokugras, Haluk; Yuksel, Hasan; Zeyrek, Dost; Kocak, A Kadir; Sekerel, Bulent E

2013-05-01

Acute asthma is one of the most common medical emergencies in children. Appropriate assessment/treatment and early identification of factors that predict hospitalization are critical for the effective utilization of emergency services. To identify risk factors that predict hospitalization and to compare the concordance of the Modified Pulmonary Index Score (MPIS) with the Global Initiative for Asthma (GINA) guideline criteria in terms of attack severity. The study population was composed of children aged 5-18 years who presented to the Emergency Departments (ED) of the tertiary reference centers of the country within a period of 3 months. Patients were evaluated at the initial presentation and the 1(st) and 4(th) hours. Of the 304 patients (median age: 8.0 years [interquartile range: 6.5-9.7]), 51.3% and 19.4% required oral corticosteroids (OCS) and hospitalization, respectively. Attack severity and MPIS were found as predicting factors for hospitalization, but none of the demographic characteristics collected predicted OCS use or hospitalization. Hospitalization status at the 1(st) hour with moderate/severe attack severity showed a sensitivity of 44.1%, specificity of 82.9%, positive predictive value of 38.2%, and negative predictive value of 86.0%; for MPIS ≥ 5, these values were 42.4%, 85.3%, 41.0%, and 86.0%, respectively. Concordance in prediction of hospitalization between the MPIS and the GINA guideline was found to be moderate at the 1(st) hour (κ = 0.577). Attack severity is a predictive factor for hospitalization in children with acute asthma. Determining attack severity with MPIS and a cut-off value ≥ 5 at the 1(st) hour may help physicians in EDs. Having fewer variables and the ability to calculate a numeric value with MPIS makes it an easy and useful tool in clinical practice. Copyright © 2013 Elsevier Inc. All rights reserved.

The Differences in Serum Quantitative Specific IgE Levels Induced by Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis Sensitization in Intermittent and Persistent Allergic Asthma

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Agus Joko Susanto

2018-01-01

Full Text Available Background: house dust mites (HDM are an important inhalant allergen in allergic asthma. However, molecular diagnostic study of specific IgE to HDM allergens has not been done in Indonesia. In addition, the association of quantitative specific IgE measurement with asthma severity has not been investigatedd. This study aimed to investigate the difference of serum quantitative specific IgE levels induced by Dermatophagoides (D. pteronyssinus, D. farinae and Blomia tropicalis sensitization in intermittent and persistent allergic asthma. Methods: this was a cross-sectional study on adult allergic asthma patients who were invited for serum specific IgE testing. This study was a part of a larger study within the Division of Allergy and Immunology, Cipto Mangunkusumo Hospital. Asthma severity was defined based on Global Initiative on Asthma (GINA 2015 criteria and were grouped as intermittent or persistent. Quantitative specific IgE testing was done on blood serum using a multiple allergosorbent test (Polycheck Allergy, Biocheck GmbH, Munster, Germany. The HDM allergens tested were D. pteronyssinus, D. farinae, and Blomia tropicalis. Difference between two groups were analyze using Mann-Whitney test. Results: a total of 87 subjects were enrolled in this study; 69 (79.3% were women. Mean patients’ age was 40, 2 years. Sixty-three (72.4% subjects had asthma and allergic rhinitis. Fifty-eight (66.7% subjects were classified as persistent asthma. The prevalence of sensitization was 62.1% for D. farinae, 51.7% for D. pteronyssinus, and 48.3% for Blomia tropicalis. The median of specific IgE levels were significantly higher in persistent asthma compares to intermittent asthma induced by D. farinae (median 1.30 vs. 0.0 kU/L; p=0.024 and B. tropicalis (median 0.57 vs. 0.0 kU/L; p=0.015 sensitization. Level of Specific IgE  D. pteronyssinus was also to be higher in persistent asthma than the level measured in intermittent asthma (0.67 vs. 0.00 kU/L; p=0

Fungi of genus Alternaria occurring on tomato

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Joanna Marcinkowska

2013-12-01

Full Text Available Tomato early blight in central Poland was caused by Alternaria solani (A. porri f. sp., solani and A. alernata (A. tenuis. A. alternata was isolated more often than A. solani. All isolates of A. solani in controlled conditions killed tomato seedlings, while pathogenic isolates of A. alternata caused only slight seedling blight. In greenhouse tests A. solani proved to be strongly pathogenic for leaves and stems of tomato but A. alternata was weakly pathogenic. The latter species attacked only injured fruits while, A. solanicould penetrate through undamaged peel of fruits. Both of these species caused the same type of symptoms; the differences consisted only in intensification of disease symptoms. During 1974 and 1975 field tomatoes were moderately attacked by early blight. Thebest development of this disease occurred by the turn of August and September. Determinate variety 'New Yorker' was distinguished by more severe infection of stem parts of tomato whereas the fruits of a stock variety 'Apollo' were more strongly attacked.

Body composition in severe refractory asthma: comparison with COPD patients and healthy smokers.

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Markos Minas

Full Text Available BACKGROUND: Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA on fat free mass (FFM has not been investigated. METHODOLOGY AND PRINCIPAL FINDINGS: 213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements and spirometry were performed. Differences in fat free mass index (FFMI between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3-18.3-19.5(18.4-21.5, p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I-III COPD and comparable to those of stage IV COPD patients [18.0(17.3-18.3-18.8(17.8-20.1, p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS and daily use of oral corticosteroids (OCS. In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used. CONCLUSIONS AND SIGNIFICANCE: SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.

Admission predictability of children with acute asthma

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Maan Alherbish

2018-01-01

CONCLUSIONS: Decision of admission could be made to many children with moderate-to-severe acute asthma at the 2nd h of ED stay based on their total PAS. OS and RR should be part of any scoring system to evaluate acute asthma in children.

Lower prevalence and greater severity of asthma in hot and dry climate.

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Correia Junior, Marco Aurélio de Valois; Sarinho, Emanuel Sávio Cavalcanti; Rizzo, José Angelo; Sarinho, Silvia Wanick

To estimate asthma prevalence, severity, and associated factors in adolescents who live in a low relative humidity environment. In this cross-sectional study, adolescents aged 13-14 years from the city of Petrolina located in the Brazilian semiarid region answered the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The possible explanatory variables of the study were gender, family income, mother's education, smokers in the household, parental history of asthma, personal history of allergic rhinitis or atopic dermatitis, and physical activity level. Poisson regression analysis was used to assess the association between asthma and the explanatory variables. A total of 1591 adolescents participated in the study, of whom 49.7% were male. The prevalence of active asthma, severe asthma, and physician-diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with asthma missed more school days than their peers (33 vs. 22 days/year; pclimate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Spirometry Findings Following Treatment with Oral and Inhalant Corticosteroids in Mild to Moderate Asthma Exacerbation in Children

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Nemat Bilan

2014-12-01

Full Text Available Introduction:  Asthma exacerbation is common in children. Treatment with oral corticosteroids (OCS and inhaled corticosteroids are suggested for asthma exacerbation. It is shown that inhaled corticosteroids has similar outcome in reducing asthma symptoms compared to OCS. But few studies have evaluated the pulmonary function changes in these two treatments. In this study, we evaluated the changes in pulmonary function tests in children with mild-to-moderate asthma exacerbation receiving oral prednisolone and inhaled Budesonide. Methods and Materials: Forty-four children with mild-to-moderate asthma exacerbation were randomly assigned to receive oral prednisolone (2 mg/kg or Budesonide spray (2 puffs every 12 hours, each puff contains 200 microgram Budesonide using a spacer for one week. The first dose of the treatment was given in the emergency department. Children were followed for seven days and spirometry findings before and after treatment were evaluated. Results: There was no significant difference between pulmonary function tests before and after treatment between groups. Children receiving oral prednisolone had significantly more improvement in PEF (p=0.01. There was significant improvement in all respiratory parameters after treatment in both groups (p

Severe angina pectoris in asthma attack: a case report.

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Nabavizadeh, Seyed Hesamedin; Farahbakhsh, Nazanin; Fazel, Ali; Mosavat, Fereshteh; Anushiravani, Amir

2016-06-01

Asthma is a chronic inflammatory disorder of the airways related to the obstruction of reversible airflow. Asthma presents as recurrent attacks of cough and dyspnea. Poor control causes recurrent admissions to the ICU, and mortality is related to poor drug compliance and follow-up. Angina pectoris is a syndrome of recurrent chest discomfort related to myocardial ischemia. The presence of these two disorders rarely has been reported. We reported a 12-year-old boy who was referred with exacerbation of asthma and developed angina pectoris during hospitalization. He had labored breathing and diffuse wheezing. During treatment of the asthma, the patient developed severe chest pain due to shunt formation and coronary hypoxia, caused by the sole administration of ventolin, since oxygen had been disconnected. After receiving appropriate therapy, both his asthma and angina recovered, and, to date, he has not experienced angina pectoris again.

Asthma Severity in patients initiating controller monotherapy versus combination therapy.

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Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

2011-04-01

Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

Natural occurrence of mycotoxins and toxigenic capacity of Alternaria strains from mouldy peppers

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da Cruz Cabral, Lucía; Terminiello, Laura; Fernández Pinto, Virginia

2016-01-01

Sweet pepper (Capsicum annuum) is an important crop cultivated worldwide, with Argentina being one of the major producers in South America. The fruit is susceptible to several fungal diseases, leading to severe economic losses for producers. In this study, Alternaria was found as the prevalent...... genus in mouldy peppers (50% fruits infected). Morphological identification revealed that all 64 Alternaria isolates belonged to small-spored species, most of them corresponding to A. tenuissima, A. arborescens and A. alternata species-groups. Their secondary metabolite profile was evaluated in vitro......; alternariols were synthesized by most of the isolates (91% for alternariol and 92% for alternariol monomethyl ether). A high number of Alternaria spp. also produced tenuazonic acid (64%), altenuene (84%) and tentoxin (72%). In addition, damaged pepper fruits were analysed for the presence of tenuazonic acid...

Large-spored Alternaria pathogens in section Porri disentangled

NARCIS (Netherlands)

Woudenberg, J H C; Truter, M; Groenewald, J Z; Crous, P W

The omnipresent fungal genus Alternaria was recently divided into 24 sections based on molecular and morphological data. Alternaria sect. Porri is the largest section, containing almost all Alternaria species with medium to large conidia and long beaks, some of which are important plant pathogens

Large-spored Alternaria pathogens in section Porri disentangled

NARCIS (Netherlands)

Woudenberg, J.H.C.; Truter, M.; Groenewald, J.Z.; Crous, P.W.

2014-01-01

The omnipresent fungal genus Alternaria was recently divided into 24 sections based on molecular and morphological data. Alternaria sect. Porri is the largest section, containing almost all Alternaria species with medium to large conidia and long beaks, some of which are important plant pathogens

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

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Suzy A A Comhair

2011-05-01

Full Text Available Environmental tobacco smoke (ETS has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown.In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD, a potential oxidative target of ETS that is negatively associated with asthma severity.From 2002-2006, 654 asthmatics (non-severe 366, severe 288 were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage.ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.

Indoor environmental exposures for children with asthma enrolled in the HEAL study, post-Katrina New Orleans.

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Grimsley, L Faye; Chulada, Patricia C; Kennedy, Suzanne; White, LuAnn; Wildfire, Jeremy; Cohn, Richard D; Mitchell, Herman; Thornton, Eleanor; El-Dahr, Jane; Mvula, Mosanda M; Sterling, Yvonne; Martin, William J; Stephens, Kevin U; Lichtveld, Maureen

2012-11-01

Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma. The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma. The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children's beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA. More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m3, respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 µg/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations. Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans.

Large-spored Alternaria pathogens in section Porri disentangled

OpenAIRE

Woudenberg, J.H.C.; Truter, M.; Groenewald, J.Z.; Crous, P.W.

2014-01-01

The omnipresent fungal genus Alternaria was recently divided into 24 sections based on molecular and morphological data. Alternaria sect. Porri is the largest section, containing almost all Alternaria species with medium to large conidia and long beaks, some of which are important plant pathogens (e.g. Alternaria porri, A. solani and A. tomatophila). We constructed a multi-gene phylogeny on parts of the ITS, GAPDH, RPB2, TEF1 and Alt a 1 gene regions, which, supplemented with morphological an...

Serum total and free carnitine levels in children with asthma.

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Asilsoy, Suna; Bekem, Ozlem; Karaman, Ozkan; Uzuner, Nevin; Kavukçu, Salih

2009-02-01

Serum carnitine is decreased in recurrent pulmonary infections. We aimed to evaluate serum carnitine levels in asthmatic children. Study group consisted of children with stable asthma and those with acute asthma attacks, while control group included healthy children. Attack severity was determined by the pulmonary score system. Total and free carnitine levels were studied in one blood sample from the control group and stable asthmatics and in two samples from children with acute asthma exacerbation during and after the attack. All the 40 patients in the study group had moderate asthma including 30 with acute attack (13 mild and 17 moderate) and 10 with stable asthma. Carnitine levels were significantly lower in acute attack asthmatics than in the stable asthmatics and controls, while there was no significant difference between the latter two groups. Carnitine levels were not different between asthmatics with mild and moderate attack, and were similar during and after an acute attack. Serum carnitine levels decrease in children with moderate asthma during exacerbation of asthma and shortly thereafter. Further studies are needed to evaluate the effect of carnitine treatment on serum carnitine level.

Examining Profiles of Family Functioning in Pediatric Asthma: Longitudinal Associations With Child Adjustment and Asthma Severity.

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Al G Hriwati, Nour; Winter, Marcia A; Everhart, Robin S

2017-05-01

Identify profiles of functioning in families of children with asthma and examine whether profile membership predicts subsequent child mental and physical well-being. Primary caregivers and children ( N  = 1,030) from the Childhood Asthma Management Program completed questionnaires assessing family functioning and child adaptation at five time points. Asthma severity was also assessed via spirometry. Latent profile analyses identified a four-profile solution as best fitting the data: cohesive, permissive, controlling/disengaged, and controlling/enmeshed families. Distal outcome analyses using Bolck-Croon-Hagenaars techniques suggested that children from families that were more cohesive had fewer internalizing and externalizing symptoms. These associations remained stable across time. Family profiles did not differ with regards to child asthma severity. Results highlight the importance of looking beyond the effects of distinct components of family functioning and instead using pattern-based approaches. Recommendations for incorporating screenings and services for families in pediatric care settings are provided. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Is asthma associated with cognitive impairments? A meta-analytic review.

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Irani, Farzin; Barbone, Jordan Mark; Beausoleil, Janet; Gerald, Lynn

2017-12-01

Asthma is a chronic disease with significant health burden and socioeconomic and racial/ethnic disparities related to diagnosis and treatment. Asthma primarily affects the lungs, but can impact brain function through direct and indirect mechanisms. Some studies have suggested that asthma negatively impacts cognition, while others have failed to identify asthma-related cognitive compromise. We aimed to conduct a meta-analysis of cognition in individuals with asthma compared to that in healthy controls. We also examined the impact of some key potential moderators. Data on cognitive outcome measures and sociodemographic, illness-related, and study-related variables were extracted from studies reporting cognitive test performance in individuals with asthma compared to that in controls. There was no evidence of publication bias. A random-effects model examining differences in task performance between 2017 individuals with asthma and 2131 healthy controls showed significant effects in the small to medium range. Cognitive deficits associated with asthma were global, with strongest effects on broader measures involving academic achievement and executive functioning, but with additional impact on processing speed, global intellect, attention, visuospatial functioning, language, learning, and memory. Severity of asthma was a key moderator, with greatest cognitive deficits associated with severe asthma. Cognitive burden was also greatest in asthma patients who were younger, males, from low socioeconomic backgrounds, and from racial/ethnic minorities. Effects were independent of type of population (child versus adult), type of study (norm-referenced versus control-referenced), or reported use of oral or inhaled corticosteroid medications. There is cognitive burden associated with asthma, particularly among vulnerable groups with severe asthma. This could be due to increased risk of intermittent cerebral hypoxia in severe asthma. The clinical need to assess cognition in

Potencial de pseudomonas spp. fluorescentes para biocontrole de alternaria ricini em mamoneira Potential of fluorescent pseudomonas spp. For biological control of alternaria ricini on castorbean

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Francisco de A.G. da Silva

1998-06-01

Full Text Available The potential of fluorescent Pseudomonas spp. to control Alternaria leaf spot on castorbean, caused by Alternaria ricini, was studied under greenhouse conditions. Two periods for antagonist applications were tested: 48h before and simultaneously to the pathogen inoculation. Among the antagonists tested JA4 and BJ22 were the most effectives showing disease severity reduction of 20.9% and 17.8% respectively, when applied simultaneously. The effect of Pseudomonas spp. on the micelial growth and sporulation was also studied throughout three different methods (funel, streak and celophane. Inhibition of micelial growth and sporulation was observed. There was no correlation between in vitro and in vivo data. Antibiosis was showed as a mode of action for Pseudomonas spp. in relation to Alternaria ricini. Ultrastructural studies confirmed the inhibition of spore germination by the bacteria.

Advances in asthma in 2016: Designing individualized approaches to management.

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Anderson, William C; Apter, Andrea J; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2017-09-01

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Factors associated with allergen sensitizations in patients with asthma and/or rhinitis in China.

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Li, Jing; Huang, Ying; Lin, Xiaoping; Zhao, Deyu; Tan, Guolin; Wu, Jinzhun; Zhao, Changqing; Zhao, Jing; Spangfort, Michael D; Lai, Xuxin; Zhong, Nanshan

2012-01-01

Allergen sensitization is influenced by genetic and environmental factors; however, the factors related to sensitizations in patients with rhinitis and asthma in China are largely unknown. This study investigated the factors associated with allergen sensitizations in patients with asthma and rhinitis in China. A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from four regions of China. Patients completed a standardized questionnaire related to respiratory and allergic symptoms, family history of allergic diseases, smoking history, environmental exposure, and eating behaviors. They underwent skin-prick tests (SPTs) with 13 common aeroallergens. Blood samples were collected from 2268 of patients for specific IgE (sIgE) measurements against 16 common aeroallergens. Patients with both asthma and rhinitis had higher prevalence of SPT and sIgE positivity to most allergens than those with asthma or rhinitis alone (p history of allergic rhinitis, air-conditioner usage, sleeping on a mattress, and frequently eating meat were associated with increased risk of SPT and sIgE positivity. Using air-conditioner and sleeping on a mattress were further found to be associated with sIgE positivity to mites and molds. However, increased age and fish, fruit, and raw vegetable intake decreased the risk of SPT and sIgE positivity. Family history of allergic rhinitis, male gender, using an air conditioner, sleeping on a mattress, and frequent meat consumption are risk factors for allergen sensitizations, whereas increased age and frequent fish, fruit, and raw vegetable consumption may protect patients with asthma and/or rhinitis from developing sensitizations in China.

Omalizumab: Clinical Use for the Management of Asthma

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Neil C. Thomson

2012-01-01

Full Text Available Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β 2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduces IgE mediated airway inflammation and its effect on airway remodeling is under investigation. Recent long-term clinical trials confirm the benefits of omalizumab in reducing exacerbations and symptoms in adults and in children with moderate to severe allergic asthma. No clinical or immunological factor consistently predicts a good therapeutic response to omalizumab in allergic asthma. In responders, the duration of treatment is unclear. The main adverse effect of omalizumab is anaphylaxis, although this occurs infrequently. Preliminary data from a five-year safety study has raised concerns about increased cardiovascular events and a final report is awaited. Clinical trials are in progress to determine whether omalizumab has efficacy in the treatment of non-allergic asthma.

Application of the asthma phenotype algorithm from the Severe Asthma Research Program to an urban population.

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Paru Patrawalla

Full Text Available Identification and characterization of asthma phenotypes are challenging due to disease complexity and heterogeneity. The Severe Asthma Research Program (SARP used unsupervised cluster analysis to define 5 phenotypically distinct asthma clusters that they replicated using 3 variables in a simplified algorithm. We evaluated whether this simplified SARP algorithm could be used in a separate and diverse urban asthma population to recreate these 5 phenotypic clusters.The SARP simplified algorithm was applied to adults with asthma recruited to the New York University/Bellevue Asthma Registry (NYUBAR to classify patients into five groups. The clinical phenotypes were summarized and compared.Asthma subjects in NYUBAR (n = 471 were predominantly women (70% and Hispanic (57%, which were demographically different from the SARP population. The clinical phenotypes of the five groups generated by the simplified SARP algorithm were distinct across groups and distributed similarly to those described for the SARP population. Groups 1 and 2 (6 and 63%, respectively had predominantly childhood onset atopic asthma. Groups 4 and 5 (20% were older, with the longest duration of asthma, increased symptoms and exacerbations. Group 4 subjects were the most atopic and had the highest peripheral eosinophils. Group 3 (10% had the least atopy, but included older obese women with adult-onset asthma, and increased exacerbations.Application of the simplified SARP algorithm to the NYUBAR yielded groups that were phenotypically distinct and useful to characterize disease heterogeneity. Differences across NYUBAR groups support phenotypic variation and support the use of the simplified SARP algorithm for classification of asthma phenotypes in future prospective studies to investigate treatment and outcome differences between these distinct groups.Clinicaltrials.gov NCT00212537.

Infection with Mycoplasma pneumoniae is not related to asthma control, asthma severity, and location of airway obstruction

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Khalil Ansarin,Siavoush Abedi,Reza Ghotaslou

2010-12-01

Full Text Available Khalil Ansarin1, Siavoush Abedi1, Reza Ghotaslou1, Mohammad Hossein Soroush1, Kamyar Ghabili1, Kenneth R Chapman21Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Asthma and Airway Centre, Toronto Western Hospital, University Health Network, Toronto, ON, CanadaBackground: Mycoplasma pneumoniae is an organism that reportedly has a strong relationship to asthma. However, asthma severity and location of airway obstruction have not been compared between asthmatic patients with and without evidence for remote mycoplasma infection.Objectives: The aim of this research was to study the relationship between previous M. pneumoniae infections in asthmatic patients and presence of any predilection for the involvement of central or peripheral airways, the severity of the disease, and asthma control.Methods: Sixty-two patients with asthma were assessed by a validated asthma control test (ACT. All patients underwent spirometry and lung volume studies by body plethysmography. The forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, total lung capacity (TLC, residual volume (RV, and functional residual capacity (FRC were measured. An oropharyngeal swab was obtained for polymerase chain reaction analysis to detect the mycoplasma antigen. Moreover, blood samples were obtained to measure the titration of antimycoplasma immunoglobulin M (IgM and IgG antibodies. The asthmatic patients with a positive IgG for mycoplasma and negative PCR and negative IgM antibody were considered to have remote history of mycoplasma infection. The relationship between the asthma control using ACT score and pulmonary function variables were compared in patients with and without evidence for remote mycoplasma infection.Results: The incidence of postnasal drip was higher among the patients with asthma who had no evidence for remote mycoplasma infection (61.3% vs 32%, P = 0.035. The median ACT score was 16.5 (11–22 and

Lower prevalence and greater severity of asthma in hot and dry climate

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Marco Aurélio de Valois Correia Junior

2017-03-01

Conclusion: Asthma prevalence in this low‐humidity environment was lower, but more severe than those reported in other Brazilian cities. The dry climate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population.

Restyling Alternaria

NARCIS (Netherlands)

Woudenberg, J.H.C.

2015-01-01

The omnipresent dematiaceous hyphomycete genus Alternaria is associated with a wide variety of substrates including seeds, plants, agricultural products, humans, soil and even the atmosphere. It includes saprophytic, endophytic and pathogenic species, among which multiple plant

Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma.

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Patelis, A; Janson, C; Borres, M P; Nordvall, L; Alving, K; Malinovschi, A

2014-03-01

We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population-based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization. FeNO, airway responsiveness, blood eosinophil count (B-Eos) and IgE sensitization to food allergens and aeroallergens were determined in 408 subjects with asthma, aged 10-34 years. Asthmatics had higher prevalence of IgE sensitization against all allergens than controls (P < 0.001). Mite, pollen, furry animal, mould and food sensitizations were each associated with increased FeNO, airway responsiveness and B-Eos in asthmatics. IgE sensitization to mould, furry animals and food allergens was independently related to FeNO (all P < 0.05) after adjustment for age, sex, height, smoking history and medication. IgE sensitization to mould (P < 0.001) and furry animals (P = 0.02) was related to airway responsiveness in a similar model. Finally, IgE sensitization to mould (P = 0.001), furry animals (P < 0.001) and food allergens (P < 0.001) was independently related to B-Eos. Independent effects of IgE sensitization to aeroallergens (furry animals and mould) and food allergens were found on both local and systemic markers of inflammation in asthma. The finding regarding food IgE sensitization is novel, and a clinical implication might be that even food sensitization must be assessed to fully understand inflammation patterns in asthma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Large-spored Alternaria pathogens in section Porri disentangled.

Science.gov (United States)

Woudenberg, J H C; Truter, M; Groenewald, J Z; Crous, P W

2014-09-01

The omnipresent fungal genus Alternaria was recently divided into 24 sections based on molecular and morphological data. Alternaria sect. Porri is the largest section, containing almost all Alternaria species with medium to large conidia and long beaks, some of which are important plant pathogens (e.g. Alternaria porri, A. solani and A. tomatophila). We constructed a multi-gene phylogeny on parts of the ITS, GAPDH, RPB2, TEF1 and Alt a 1 gene regions, which, supplemented with morphological and cultural studies, forms the basis for species recognition in sect. Porri. Our data reveal 63 species, of which 10 are newly described in sect. Porri, and 27 species names are synonymised. The three known Alternaria pathogens causing early blight on tomato all cluster in one clade, and are synonymised under the older name, A. linariae. Alternaria protenta, a species formerly only known as pathogen on Helianthus annuus, is also reported to cause early blight of potato, together with A. solani and A. grandis. Two clades with isolates causing purple blotch of onion are confirmed as A. allii and A. porri, but the two species cannot adequately be distinguished based on the number of beaks and branches as suggested previously. This is also found among the pathogens of Passifloraceae, which are reduced from four to three species. In addition to the known pathogen of sweet potato, A. bataticola, three more species are delineated of which two are newly described. A new Alternaria section is also described, comprising two large-spored Alternaria species with concatenate conidia.

Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

Science.gov (United States)

Green, Benjamin J; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B; Kehagia, Valia; Lau, Laurie; Carroll, Mary P; Bruce, Kenneth D; Howarth, Peter H

2014-01-01

Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that

Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta(2) agonist and steroid response

NARCIS (Netherlands)

Vonk, Judith M.; Postma, Dirkje S.; Maarsingh, Harm; Bruinenberg, Marcel; Koppelman, Gerard H.; Meurs, Herman

Rationale Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta(2) agonists. Objectives We investigated the association between arginase 1

The application of subset correspondence analysis to address the problem of missing data in a study on asthma severity in childhood.

Science.gov (United States)

Hendry, G; North, D; Zewotir, T; Naidoo, R N

2014-09-28

Non-response in cross-sectional data is not uncommon and requires careful handling during the analysis stage so as not to bias results. In this paper, we illustrate how subset correspondence analysis can be applied in order to manage the non-response while at the same time retaining all observed data. This variant of correspondence analysis was applied to a set of epidemiological data in which relationships between numerous environmental, genetic, behavioural and socio-economic factors and their association with asthma severity in children were explored. The application of subset correspondence analysis revealed interesting associations between the measured variables that otherwise may not have been exposed. Many of the associations found confirm established theories found in literature regarding factors that exacerbate childhood asthma. Moderate to severe asthma was found to be associated with needing neonatal care, male children, 8- to 9-year olds, exposure to tobacco smoke in vehicles and living in areas that suffer from extreme air pollution. Associations were found between mild persistent asthma and low birthweight, and being exposed to smoke in the home and living in a home with up to four people. The classification of probable asthma was associated with a group of variables that indicate low socio-economic status. Copyright © 2014 John Wiley & Sons, Ltd.

Innate lymphoid cells and asthma.

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Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

2014-04-01

Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Adding formoterol to budesonide in moderate asthma - health economic results from the FACET study

NARCIS (Netherlands)

Andersson, F; Stahl, E; Barnes, PJ; Lofdahl, CG; O'Byrne, PM; Pauwels, RA; Postma, DS; Tattersfield, AE; Ullman, A

The FACET (Formoterol and Corticosteroid Establishing Therapy) study established that there is a clear clinical benefit in adding formoterol to budesonide therapy in patients who have persistent symptoms of asthma despite treatment with low to moderate doses of an inhaled corticosteroid. We combined

Fevipiprant in the treatment of asthma.

Science.gov (United States)

White, Christobelle; Wright, Adam; Brightling, Christopher

2018-02-01

Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. It competitively and reversibly antagonises the prostaglandin D2 receptor 2 (DP2) expressed on inflammatory and structural cells. Areas covered: We reviewed fevipiprant's mode of action and efficacy against other current and emerging pharmacological interventions for moderate-to-severe asthma. We undertook a literature review using the PubMed/Medline database, the U.S. National Library of Medicine's Clinical Trials website and from manufacturers' press releases with the search terms: 'QAW039', 'Fevipiprant', 'CRTH2 antagonists', 'DP2', 'DP1', 'monoclonal antibody', 'eosinophil' with 'asthma' plus the names of individual drugs. Three Phase 2 trials have been conducted and three Phase 3 trials (NCT02563067, NCT03052517, NCT02555683) are in progress. To date Fevipiprant's greatest success has been in targeting severe eosinophilic asthma. Expert opinion: Fevipiprant presents the possibility of a new orally active therapy for asthma. If successful in phase 3 trials it will have an enormous impact on the treatment paradigm for asthma and will potentially widen access for pre-biologic treatment to a larger population.

Association of Body Mass Index with Asthma Severity and Pulmonary Function among Asthmatic Children

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Rasuol Nasiri Kalmarzi

2016-09-01

Full Text Available Background Asthma is a chronic inflammatory disease in respiratory system and obesity is another inflammatory disease which incidence rate is increasing. Although, many studies have been conducted on severity of asthma and its relationship with obesity, but different results have been obtained. This study aimed to determine a relationship between asthma severity, Body Mass Index (BMI and pulmonary function in Kurdistan province, Iran. Materials and Methods: In this cross sectional study 90 asthmatic patients referred to referral hospital in Kurdistan, North West of Iran, were selected by simple random method. BMI was calculated by dividing weight by height.Pulmonary Function Test (PFT and bronchial-stimulation-test were used for confirmation and investigation of asthma severity. Data were analyzed using SPSS-15 and Chi-square and spearman correlation coefficient tests. Results: Relationship between BMI and severity of asthma (mild, medium and severe was evaluated, there was a relationship and positive relationship between them (P

Decreasing asthma morbidity

African Journals Online (AJOL)

1994-12-12

Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

Omalizumab: Clinical Use for the Management of Asthma

OpenAIRE

Thomson, Neil C.; Chaudhuri, Rekha

2012-01-01

Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β 2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduce...

[Severe uncontrolled asthma in patients over 75 years old: Treatment with omalizumab].

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Romand, P; Kelkel, E; Saint-Raymond, C; Glas, N; Caillaud, D; Devouassoux, G

2016-05-01

With an aging population and an increase in the prevalence of asthma, this disease is becoming more common in the elderly. Nevertheless, the management of severe asthma can be complex, due to an increased risk of uncontrolled disease in patients over 65 years old and partly to the inherent characteristics of old age: comorbidities, underestimation of the role of allergies, poor adherence, difficulties with inhalation devices, etc. We report two cases of women over 75 with severe persistent allergic asthma not controlled by high doses of inhaled corticosteroids and long-acting beta-2-agonists in whom treatment with omalizumab was initiated. Following treatment with omalizumab a decrease in the number and severity of exacerbations, improved asthma control and dose reduction or discontinuation of systemic corticosteroids were observed. The tolerance of omalizumab was good in both cases. Omalizumab is to be considered an effective and well-tolerated therapeutic option for elderly patients with inadequately controlled severe allergic asthma. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Alternaria Leaf Spot on Mealycup Sage (Salvia farinacea Benth.) Caused by Alternaria alternata (Fr.) Keissler

OpenAIRE

Hiromitsu, NEGISHI; Kazuo, SUYAMA; Faculty of Agriculture,Tokyo University of Agriculture; Faculty of Agriculture,Tokyo University of Agriculture

2002-01-01

In June 1995, a disease causing round to irregular-shaped, water-soaked, brown to blackish brown spots on mealycup sage (Salvia farinacea Benth.) was found in Atsugi-shi, Kanagawa Prefecture, Japan. The symptoms were seen only on leaves, not on neither flower petals or stems. The disease was also found in Setagaya-ku, Tokyo, Memambetsu-cho, Hokkaido and Shimoda-shi and Matsuzaki-cho, Shizuoka. An Alternaria sp. was frequently isolated from these diseased plants. The isolates were severely pat...

Appropriate selection for omalizumab treatment in patients with severe asthma?

DEFF Research Database (Denmark)

Nygaard, Leo; Henriksen, Daniel Pilsgaard; Madsen, Hanne

2017-01-01

Background: Omalizumab improves asthma control in patients with uncontrolled severe allergic asthma; however, appropriate patient selection is crucial. Information in this field is sparse. Objective: We aimed to estimate whether potential omalizumab candidates were appropriately selected according...... to guidelines, and the clinical effect of omalizumab treatment over time. Design: We performed a retrospective observational study on adult patients with asthma treated with omalizumab during 2006-2015 at the Department of Respiratory Medicine at Odense University Hospital (OUH), Denmark. Data were obtained...... from the Electronic Patient Journal of OUH and Odense Pharmaco-Epidemiological Database. Guideline criteria for omalizumab treatment were used to evaluate the appropriateness of omalizumab candidate selection, and the Asthma Control Test (ACT) to assess the clinical effects of omalizumab at weeks 16...

The presence of Alternaria spp. on the seed of Apiaceae plants and their influence on seed emergence

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Bulajić Aleksandra

2009-01-01

Full Text Available Considerable damping-off of the seedlings of several commercial Apiaceae plant species was observed in Serbia. The infection of a total of 48 seed samples of nine vegetable and spice plants with phytopathogenic Alternaria spp. was established using the deep-freeze-blotter method. Identification of Alternaria species was performed using both conventional methods and PCR. Four different plant-pathogenic Alternaria species were detected in Serbia: A. dauci, A. radicina, A. petroselini, and A. alternata, all of which caused reduction of carrot, parsley, parsnip, and celery seed emergence. Alternaria dauci, A. radicina, and A. petroselini were relatively more aggressive compared to A. alternata. Substantial seed infection levels and strong influence of Alternaria spp. on seed emergence indicated that production of Apiaceae seed needs to be improved in order to obtain pathogen-free seed.

Quality of Life in Children With Asthma: A Developmental Perspective.

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Miadich, Samantha A; Everhart, Robin S; Borschuk, Adrienne P; Winter, Marcia A; Fiese, Barbara H

2015-08-01

The current study investigated whether factors associated with quality of life (QOL) in children with asthma (e.g., family functioning, asthma routines, asthma severity) differed by child age. Participants included 192 children with asthma (5-12 years) and their caregivers. Both children and caregivers completed questionnaires at an initial research session. Family functioning was determined from a mealtime observation that occurred in family homes. Child age moderated the association between asthma severity and child QOL and between routine burden and QOL in children with asthma. Post hoc probing analyses revealed that among older children, QOL levels were lower in the presence of worse asthma severity and more routine burden. Findings suggest that associations between asthma severity, routine burden, and QOL may differ by child age. Treatment programs and health-care recommendations addressing QOL in children with asthma may need to be tailored to address differences in factors associated with QOL by child age. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hyperspectral and thermal imaging of oilseed rape (Brassica napus response to fungal species of the genus Alternaria.

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Piotr Baranowski

Full Text Available In this paper, thermal (8-13 µm and hyperspectral imaging in visible and near infrared (VNIR and short wavelength infrared (SWIR ranges were used to elaborate a method of early detection of biotic stresses caused by fungal species belonging to the genus Alternaria that were host (Alternaria alternata, Alternaria brassicae, and Alternaria brassicicola and non-host (Alternaria dauci pathogens to oilseed rape (Brassica napus L.. The measurements of disease severity for chosen dates after inoculation were compared to temperature distributions on infected leaves and to averaged reflectance characteristics. Statistical analysis revealed that leaf temperature distributions on particular days after inoculation and respective spectral characteristics, especially in the SWIR range (1000-2500 nm, significantly differed for the leaves inoculated with A. dauci from the other species of Alternaria as well as from leaves of non-treated plants. The significant differences in leaf temperature of the studied Alternaria species were observed in various stages of infection development. The classification experiments were performed on the hyperspectral data of the leaf surfaces to distinguish days after inoculation and Alternaria species. The second-derivative transformation of the spectral data together with back-propagation neural networks (BNNs appeared to be the best combination for classification of days after inoculation (prediction accuracy 90.5% and Alternaria species (prediction accuracy 80.5%.

Childhood asthma-predictive phenotype.

Science.gov (United States)

Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

2014-01-01

Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma

DEFF Research Database (Denmark)

Virchow, Johann Christian; Backer, Vibeke; Kuna, Piotr

2016-01-01

moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events. RESULTS: Among 834 randomized...... in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13...... corticosteroid (ICS) reduction period. DESIGN, SETTINGS, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products...

Omalizumab in children with uncontrolled allergic asthma: Review of clinical trial and real-world experience.

Science.gov (United States)

Chipps, Bradley E; Lanier, Bob; Milgrom, Henry; Deschildre, Antoine; Hedlin, Gunilla; Szefler, Stanley J; Kattan, Meyer; Kianifard, Farid; Ortiz, Benjamin; Haselkorn, Tmirah; Iqbal, Ahmar; Rosén, Karin; Trzaskoma, Benjamin; Busse, William W

2017-05-01

Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Influence of Health Education on Family Management of Childhood Asthma.

Science.gov (United States)

Brazil, Kevin; McLean, Leslie; Abbey, David; Musselman, Carol

1997-01-01

Differences in asthma management among families with a child who has moderate to severe asthma were examined when they participated in an in-patient versus a day-camp program. Two broad categories of outcome were examined: illness and self-management skills. Findings and observations regarding children's feelings about asthma are discussed.…

Association between severe asthma and changes in the stomatognathic system.

Science.gov (United States)

Carvalho-Oliveira, Mayra; Salles, Cristina; Terse, Regina; D'Oliveira, Argemiro

2016-01-01

To describe orofacial muscle function in patients with severe asthma. This was a descriptive study comparing patients with severe controlled asthma (SCA) and severe uncontrolled asthma (SUA). We selected 160 patients, who completed a sociodemographic questionnaire and the 6-item Asthma Control Questionnaire (ACQ-6), as well as undergoing evaluation of orofacial muscle function. Of the 160 patients evaluated, 126 (78.8%) and 34 (21.2%) presented with SCA and SUA, respectively, as defined by the Global Initiative for Asthma criteria. Regardless of the level of asthma control, the most frequent changes found after evaluation of muscle function were difficulty in chewing, oronasal breathing pattern, below-average or poor dental arch condition, and difficulty in swallowing. When the sample was stratified by FEV1 (% of predicted), was significantly higher proportions of SUA group patients, compared with SCA group patients, showed habitual open-mouth chewing (24.8% vs. 7.7%; p de controle da asma grave, as alterações mais frequentes observadas na avaliação miofuncional foram problemas de mastigação, padrão de respiração oronasal, estado de conservação da arcada dentária médio ou ruim e problemas na deglutição. Quando a amostra foi estratificada pelo VEF1 (% do previsto), os resultados foram significativamente maiores no grupo AGNC que no grupo AGC quanto a mastigação habitual com boca aberta (24,8% vs. 7,7%; p de água com dificuldade (33,7% vs. 17,3%; p de voz (81,2% vs. 51,9%; p resultados do grupo AGNC foram significativamente maiores que no grupo AGC quanto à deglutição de pão com dificuldade (66,6% vs. 26,6%; p de alterações do sistema estomatognático parece ser alta em adultos com asma grave independentemente do nível de controle da doença. No grupo AGNC, algumas dessas alterações foram significativamente mais frequentes que no grupo AGC.

Perceived exercise limitation in asthma: The role of disease severity, overweight, and physical activity in children.

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Westergren, Thomas; Berntsen, Sveinung; Lødrup Carlsen, Karin C; Mowinckel, Petter; Håland, Geir; Fegran, Liv; Carlsen, Kai-Håkon

2017-02-01

Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA). The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/m 2 or above at 18 years), exercise-induced bronchoconstriction (forced expiratory volume in one-second (FEV 1 ) pre- and post-exercise), methacholine bronchial challenge (severe BHR; provocative dose causing ≥20% decrease in FEV 1 ≤ 1 μmol), and asthma severity score (dose of controller medication and exacerbations last 12 months). Multivariate logistic regression analyses were conducted to assess associations with perceived EL. In the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEV 1 post-exercise (OR: 1.48 (1.10, 1.98)) and overweight (OR: 2.15 (1.13, 4.08) and 2.53 (1.27, 5.03)) explained 9.7% and 8.4% of perceived EL, respectively. Perceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Smoke-free air laws and asthma prevalence, symptoms, and severity among nonsmoking youth.

Science.gov (United States)

Dove, Melanie S; Dockery, Douglas W; Connolly, Gregory N

2011-01-01

We investigated the association between smoke-free laws and asthma prevalence, symptoms, and severity among nonsmoking youth (aged 3-15 years). We examined data from the 1999-2006 National Health and Nutrition Examination Survey, a cross-sectional survey designed to monitor the health and nutritional status of the US population. Survey locations were dichotomized as having or not having at least 1 smoke-free workplace, restaurant, or bar law at the county or state level that covered the entire county population. Asthma prevalence was assessed as self-reported current asthma and as ever having asthma with current symptoms. Asthmatic symptoms included persistent wheeze, chronic night cough, and wheeze-medication use. We also examined asthma severity (asthma attack or emergency-department visit for asthma) and persistent ear infection. Smoke-free laws were not associated with current asthma but were significantly associated with lower odds of asthmatic symptoms (odds ratio [OR]: 0.67 [95% confidence interval (CI): 0.48-0.93]) among nonsmoking youth. The association between smoke-free laws and ever having asthma with current symptoms approached significance (OR: 0.74 [95% CI: 0.53-1.03]). Smoke-free laws were associated with lower odds of asthma attacks (OR: 0.66 [95% CI: 0.28-1.56]) and emergency-department visits for asthma (OR: 0.55 [95% CI: 0.27-1.13]), although these results were not statistically significant. Our results suggest that smoke-free laws reduce asthmatic symptoms, including persistent wheeze, chronic night cough, and wheeze-medication use in nonsmoking youth.

Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Directory of Open Access Journals (Sweden)

Tabatabaian F

2018-04-01

Full Text Available Farnaz Tabatabaian, Dennis K Ledford Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA Abstract: Asthma is a heterogeneous syndrome with numerous underlining molecular and inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes. Multiple therapies targeting severe asthma with type 2 (T2 high inflammation are or soon will be available. T2 high inflammation is defined as inflammation associated with atopy or eosinophilia or an increase in cytokines associated with T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody and the first biologic therapy approved for moderate–severe allergic asthma. Despite the specificity of biologic therapies like omalizumab, clinical response is variable, with approximately 50% of treated patients achieving the primary outcome. A prior identification of the ideal candidate for therapy would improve patient outcomes and optimize the use of health care resources. As the number of biologic therapies for asthma increases, the goal is identification of biomarkers or clinical phenotypes likely to respond to a specific therapy. This review focuses on potential biomarkers and clinical history that may identify responders to omalizumab therapy for asthma. Keywords: severe persistent asthma, asthma phenotype and endotype, T2 high inflammation, omalizumab, asthma biomarkers, eosinophils, fractional exhaled nitric oxide, IgE

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma.

Science.gov (United States)

Singhania, Akul; Wallington, Joshua C; Smith, Caroline G; Horowitz, Daniel; Staples, Karl J; Howarth, Peter H; Gadola, Stephan D; Djukanović, Ratko; Woelk, Christopher H; Hinks, Timothy S C

2018-02-01

Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3 + T cells from sputum and BAL were obtained from healthy subjects (n = 19) and patients with asthma (mild, moderate, and severe asthma; n = 46). Gene expression was assessed using Affymetrix HT HG-U133 + PM GeneChips, and results were validated by real-time quantitative PCR. In the epithelium, IL-13 response genes (POSTN, SERPINB2, and CLCA1), mast cell mediators (CPA3 and TPSAB1), inducible nitric oxide synthase, and cystatins (CST1, CST2, and CST4) were upregulated in mild asthma, but, except for cystatins, were suppressed by corticosteroids in moderate asthma. In severe asthma-with predominantly neutrophilic phenotype-several distinct processes were upregulated, including neutrophilia (TCN1 and MMP9), mucins, and oxidative stress responses. The majority of the disease signature was evident in sputum T cells in severe asthma, where 267 genes were differentially regulated compared with health, highlighting compartmentalization of inflammation. This signature included IL-17-inducible chemokines (CXCL1, CXCL2, CXCL3, IL8, and CSF3) and chemoattractants for neutrophils (IL8, CCL3, and LGALS3), T cells, and monocytes. A protein interaction network in severe asthma highlighted signatures of responses to bacterial infections across tissues (CEACAM5, CD14, and TLR2), including Toll-like receptor signaling. In conclusion, the activation of innate immune pathways in the airways suggests that activated T cells may be driving neutrophilic inflammation and steroid-insensitive IL-17 response in severe asthma.

Current asthma deaths among adults in Japan

Directory of Open Access Journals (Sweden)

Tsugio Nakazawa

2004-01-01

Full Text Available Recent asthma deaths were examined from yearly reports of the Ministry of Health, Labor and Welfare of Japan and from reports published by the Japan Asthma Death Investigation Committee on 811 deaths over the period 1992–2000. The rate and number of recent asthma deaths in Japan have been decreasing rapidly. Most asthma deaths were of patients aged 70–90 years and there has been a marked trend for increased asthma deaths in the elderly. As for the circumstances surrounding the deaths, sudden death, unstable sudden aggravation and intermittent aggravation were mainly noted. Respiratory infections, fatigue and stress were the major courses of fatal attacks contributing to deaths due to asthma. Many of the patients who died from asthma had been diagnosed as having as moderate to severe asthma and many had non-atopic asthma. There are some reports that suggest that the recent decrease in asthma deaths in Japan is correlated with the use of inhaled cortico- steroids.

How should treatment approaches differ depending on the severity of asthma?

Science.gov (United States)

Kupczyk, Maciej; Kuna, Piotr

2017-12-01

Asthma is nowadays regarded as a syndrome of various overlapping phenotypes with defined clinical characteristics, different underlying inflammatory mechanisms, identifiable genetic background, environmental risk factors and possible biomarkers. There are no doubts that due to the diversity of asthma, a 'one size fits all' management of the disease is no longer valid. Areas covered: Nowadays asthma management is based on the control of the disease, and the goals of asthma treatment are defined as good symptom control, decreased future risk of exacerbations, fixed airflow limitation, and side-effects of treatment. Alternative strategies for adjusting asthma treatment such as sputum or exhaled nitric oxide guided protocols have been evaluated and despite some effectiveness, are regarded as impractical in every-day clinical conditions. Further studies in the field of asthma phenotypes/endotypes and biomarkers are warranted with the main goal to define which of those possible subgroups will be useful in clinical practice in regards to the potential allocation of successful treatment. Expert commentary: Despite the availability of guidelines on the diagnosis and management of asthma, it seems that the disease is still not optimally controlled. Addressing unmet needs in every day care, improving education, adherence/compliance and inhalation technique may significantly improve asthma control across all severities of the disease.

The effect of omalizumab on small airway inflammation as measured by exhaled nitric oxide in moderate-to-severe asthmatic patients.

Science.gov (United States)

Pasha, M Asghar; Jourd'heuil, David; Jourd'heuil, Francis; Mahon, Lori; Romero, Francisco; Feustel, Paul J; Evans, Mary; Smith, Thomas; Mitchell, Jesse; Gendapodi, Pradeep; Demeyere-Coursey, Kelly C; Townley, Robert G

2014-01-01

Measurement of fractional nitric oxide concentration in exhaled breath (FENO) is a simple, noninvasive method to evaluate eosinophilic airway inflammation. Nitric oxide (NO) arising from peripheral small airways/alveoli (alveolar NO concentration [CalvNO]) can be estimated using multiple flow rates and a two-compartment model of the airways and alveoli. Omalizumab, a monoclonal anti-IgE antibody, is approved for the treatment of allergic asthma and also has been shown to decrease FENO levels. This study investigates the effects of omalizumab, when added to an inhaled corticosteroid (ICS) ± long-acting beta-adrenergic agonist (LABA) treatment, on peripheral small airway/alveolar inflammation reflected by FENO measurements at higher flow rates. We hypothesized that compared with placebo, omalizumab would decrease CalvNO levels in asthmatic patients on ICS ± LABA. Forty-two patients with moderate-to-severe asthma were randomly assigned 2:1 to either omalizumab (n = 29) or placebo treatment (n = 13) for 16 weeks. Selection criteria included moderate-to-severe asthmatic patients on an ICS ± LABA, positive skin test to one or more perennial allergen, screening FENO of >13 ppb, and a baseline IgE of 30-700 IU/mL. FENO measured at multiple flow rates was used to calculate CalvNO over the course of 16 weeks. FENO levels decrease with increasing flow rates (p < 0.05 repeated measures ANOVA) but no differences between the placebo and treatment groups in overall CalvNO levels or in the changes of CalvNO with time were found. Omalizumab did not lower the CalvNO, which could have been caused by the initial low CalvNO in this asthmatic population. The model used may not be completely sufficient and/or sensitive enough to detect small changes in CalvNO.

Therapy with omalizumab for patients with severe allergic asthma improves asthma control and reduces overall healthcare costs.

LENUS (Irish Health Repository)

Costello, R W

2012-02-01

BACKGROUND: Patients with asthma who have persistent symptoms despite treatment with inhaled steroids and long-acting beta agonists are considered to have severe asthma. Omalizumab is a monoclonal antibody directed against IgE, which is used as an add-on treatment for patients who have severe persistent allergic asthma. AIMS: The aim of this study was to assess the clinical benefit and healthcare utilisation of patients who responded to omalizumab therapy and to establish an overall cost implication. METHODS: This was an observational retrospective cohort study designed to investigate the effect of omalizumab on exacerbations of asthma before and after 6 months of treatment in Irish patients. RESULTS: Centres who had treated patients with severe allergic asthma for the 6 months prior and post omalizumab treatment were audited with a standardised assessment tool. Sixty-three (32 male) patients were studied. In the 6 months prior to omalizumab 41 of 63 (66%) had been hospitalised, and this fell to 15 of 63 (24%), p < 0.0001 in the 6 months after treatment was started. Hospital admissions reduced from 2.4 +\\/- 0.41 to 0.8 +\\/- 0.37 and the mean number of bed days occupied was reduced from 16.6 +\\/- 2.94 to 5.3 +\\/- 2.57 days, p < 0.001. The number of oral corticosteroid doses used fell from 3.1 +\\/- 0.27 to 1.2 +\\/- 0.17, p < 0.001. The overall cost saving per omalizumab responder patients for 6 months was 834. CONCLUSIONS: Six months therapy with omalizumab reduced the number of bed days, the number of hospitalisations and the use of oral corticosteroids compared to the 6 months prior to commencement. Despite the cost of the additional therapy there were overall savings in health costs.

Novel monoclonal treatments in severe asthma

DEFF Research Database (Denmark)

Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste

2017-01-01

articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies. RESULTS: Of the 37 studies investigating biological treatments of asthma, 5 were on the effects of anti-IgE (omalizumab); 12 on anti-IL-5; 8...... TSLP, IL-9, and TNF-α lacked convincing effectiveness. CONCLUSION: Research on the biological treatment of asthma shows promising results. While anti-IgE (omalizumab) has been used in the treatment of asthma for some years, anti-IL-5 has recently been approved for use. The efficacy of results of other...... large studies with a longer duration is needed to draw a firm conclusion. Such studies should not only focus on clinical outcomes, but also consider asthma-related quality of life. Knowledge on the asthma phenotypes and identification of biomarkers associated with these will be useful for physicians...

Asthma exacerbations during the first trimester of pregnancy and congenital malformations: revisiting the association in a large representative cohort.

Science.gov (United States)

Blais, Lucie; Kettani, Fatima-Zohra; Forget, Amélie; Beauchesne, Marie-France; Lemière, Catherine

2015-07-01

We previously reported an increased prevalence of any congenital malformation among women experiencing moderate-to-severe asthma exacerbations during the first trimester of pregnancy, based on a study in which 90.1% of the cohort of women were social welfare recipients. This study re-examined the association between asthma exacerbations and congenital malformations in a new large representative cohort of asthmatic pregnant women. A cohort of 36 587 pregnancies in asthmatic women was reconstructed from Québec Province administrative databases (1998-2009). Occurrences of asthma exacerbations during the first trimester of pregnancy were assessed and categorised into severe, moderate and no such exacerbations. For comparison, we also considered moderate and severe asthma exacerbations combined. Congenital malformations were identified using diagnoses recorded in the hospitalisation database. Generalised estimation equations were used to estimate adjusted ORs of congenital malformations. The prevalence of any congenital malformation was 19.1%, 11.7% and 12.0% among women with severe, moderate and no such exacerbations during the first trimester, respectively. The adjusted OR for all malformations was 1.64 (95% CI 1.02 to 2.64) when women with severe exacerbations were compared with those in the reference group, while no association was seen for moderate exacerbations. Also, no association was observed between cases of moderate and severe asthma exacerbations combined and any congenital malformation. Only severe asthma exacerbations were found to significantly increase the risk of congenital malformations in this representative study. Previous studies possibly overestimated the risk because they were based mainly on women at a lower socioeconomic status. 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.

Serum resistin as an asthma marker and predictor of inhaled corticosteroid response in bronchial asthma in children

Directory of Open Access Journals (Sweden)

Hassan M. Al-Asy

2017-07-01

Conclusions: From these results we can conclude that resistin can be considered as a marker of asthma and its severity and high resistin levels can predict favourable anti-inflammatory effect of inhaled glucocorticoids suggesting that resistin may be a marker of steroid-sensitive genotype in asthma in children.

Alternaria resistance of Brassicae campestris L. improved by induced mutations

International Nuclear Information System (INIS)

Das, M.L.; Rahman, A.

1989-01-01

Full text: Seeds of 'YS 52', a cultivar susceptible to Alternaria brassicae (Berk.) Sacc., were exposed to gamma rays (30-90 kR). Eight more resistant mutants were selected in M3 and subjected to further field evaluation. The best mutant '17-5-83' appeared resistant and gave 44% higher yield than the parent, mutant '70-7-82' was found to be moderately resistant and gave a yield 21% higher than the parent. The yield increases seem to be connected with plant architecture changes. (author)

Alternaria Toxins: Potential Virulence Factors and Genes Related to Pathogenesis

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Mukesh Meena

2017-08-01

Full Text Available Alternaria is an important fungus to study due to their different life style from saprophytes to endophytes and a very successful fungal pathogen that causes diseases to a number of economically important crops. Alternaria species have been well-characterized for the production of different host-specific toxins (HSTs and non-host specific toxins (nHSTs which depend upon their physiological and morphological stages. The pathogenicity of Alternaria species depends on host susceptibility or resistance as well as quantitative production of HSTs and nHSTs. These toxins are chemically low molecular weight secondary metabolites (SMs. The effects of toxins are mainly on different parts of cells like mitochondria, chloroplast, plasma membrane, Golgi complex, nucleus, etc. Alternaria species produce several nHSTs such as brefeldin A, tenuazonic acid, tentoxin, and zinniol. HSTs that act in very low concentrations affect only certain plant varieties or genotype and play a role in determining the host range of specificity of plant pathogens. The commonly known HSTs are AAL-, AK-, AM-, AF-, ACR-, and ACT-toxins which are named by their host specificity and these toxins are classified into different family groups. The HSTs are differentiated on the basis of bio-statistical and other molecular analyses. All these toxins have different mode of action, biochemical reactions and signaling mechanisms to cause diseases. Different species of Alternaria produced toxins which reveal its biochemical and genetic effects on itself as well as on its host cells tissues. The genes responsible for the production of HSTs are found on the conditionally dispensable chromosomes (CDCs which have been well characterized. Different bio-statistical methods like basic local alignment search tool (BLAST data analysis used for the annotation of gene prediction, pathogenicity-related genes may provide surprising knowledge in present and future.

Effects of Alternaria alternata f.sp. lycopersici toxins on pollen

NARCIS (Netherlands)

Bino, R.J.; Franken, J.; Witsenboer, H.M.A.; Hille, J.; Dons, J.J.M.

1988-01-01

Effects of the phytotoxic compounds (AAL-toxins) isolated from cell-free culture filtrates of Alternaria alternata f.sp. lycopersici on in vitro pollen development were studied. AAL-toxins inhibited both germination and tube growth of pollen from several Lycopersicon genotypes. Pollen from

Cutaneous sarcoidosis in a patient with severe asthma treated with omalizumab

Science.gov (United States)

Yung, Samuel; Han, Duhyun; Lee, Jason K

2015-01-01

Omalizumab, a monoclonal anti-immunoglobulin E antibody, has been used as an effective treatment for severe asthma associated with atopy over the past decade. Sarcoidosis is an idiopathic granulomatous disorder in which first-line treatment is usually glucocorticoids. To the authors’ knowledge, the present report describes the first case of an association between omalizumab therapy and revelation of cutaneous sarcoidosis with the withdrawal of systemic glucocorticoids. A 56-year-old woman with severe allergic asthma dependent on oral prednisone initiated omalizumab treatment. As her symptoms of asthma improved over the course of a year, her prednisone was gradually tapered. After being off glucocorticoids, she developed skin nodules that had biopsy characteristics of sarcoidosis. The present case illustrates the need to monitor closely for potential unmasking of glucocorticoid-responsive conditions when transitioning from systemic glucocorticoids to omalizumab therapy. PMID:26401982

Acute asthma severity identification of expert system flow in emergency department

Science.gov (United States)

Sharif, Nurul Atikah Mohd; Ahmad, Norazura; Ahmad, Nazihah; Desa, Wan Laailatul Hanim Mat

2017-11-01

Integration of computerized system in healthcare management help in smoothening the documentation of patient records, highly accesses of knowledge and clinical practices guideline, and advice on decision making. Exploit the advancement of artificial intelligent such as fuzzy logic and rule-based reasoning may improve the management of emergency department in terms of uncertainty condition and medical practices adherence towards clinical guideline. This paper presenting details of the emergency department flow for acute asthma severity identification with the embedding of acute asthma severity identification expert system (AASIES). Currently, AASIES is still in preliminary stage of system validation. However, the implementation of AASIES in asthma bay management is hope can reduce the usage of paper for manual documentation and be a pioneer for the development of a more complex decision support system to smoothen the ED management and more systematic.

Control of moderate-to-severe asthma with randomized ciclesonide doses of 160, 320 and 640 μg/day

Directory of Open Access Journals (Sweden)

Pedersen SE

2017-03-01

Full Text Available Søren E Pedersen,1 Niyati Prasad,2 Udo-Michael Goehring,3 Henrik Andersson,4 Dirkje S Postma5 1Pediatric Research Unit, Kolding Hospital, University of Southern Denmark, Kolding, Denmark; 2Vertex, Phase IV & Global Strategy, London, UK; 3Vifor Pharma Ltd, Clinical Research & Biometrics, Glattbrugg, Switzerland; 4Swedish Social Insurance Agency, Government Offices of Sweden, Stockholm, Sweden; 5Department of Pulmonology, Griac Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Background: The inhaled corticosteroid (ICS ciclesonide (Cic, controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use. Patients and methods: In a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 μg/day. After a single-blind, 3-week baseline period with Cic 160 µg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 μg/day (double-blind period during which forced expiratory volume in 1 second (FEV1, exacerbations and Asthma Control Questionnaire (ACQ scores were measured. Results: Treatment with all the three doses was associated with significant improvements in ACQ scores, FEV1 and asthma symptoms (P<0.01. There were no statistically significant differences between the three doses. The results of the primary end point analysis showed a numerical improvement in the ACQ score with Cic 640 μg/day compared with Cic 160 μg/day (least square [LS] mean: -0.122; two-sided P-value: 0.30. Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 μg/day compared

The dynamics of the fungal aerospores Alternaria sp. and Cladosporium sp. in Parisian atmospheric air, in France

Science.gov (United States)

Brezoczki, V. M.

2016-08-01

The bioallergens occurring naturally in the atmospheric air are microorganisms, pollen grains, plant seeds, leaf and stem scrap, or their protein molecules. The presence of various airborne fungal spores determines a high allergenic potential for public health. This effect is due to the high number of produced spores, which under favourable meteorological conditions (dry weather and wind) reach the surrounding air. This paper traces the dynamics of two types of fungi, Alternaria sp and Cladosporium sp, fungi which can be found outdoors, in the surrounding air, as well as indoors, inside houses (especially the conidia of Cladosporium sp). The effects of these fungal spores on human health are varies, ranging from seasonal allergies (hay fever, rhinitis, sinusitis etc.) to sever afflictions of the respiratory system, onset of asthma, disfunctionalities of the nervous systems, of the immune system, zymoses etc. The monitoring of the dynamics of the aerospores Alternaria sp and Cladosporium sp was carried out between 2010 and 2013, over a period of 42 weeks during one calendar year, from February to the end of September, in the surrounding air in the French capital, Paris. The regional and global climate and meteorological conditions are directly involved in the occurrence and development of fungi colonies, the transportation and dispersion of fungal spores in the atmospheric air, as well as in the creation of the environment required for the interaction of chemical and biological components in the air. Knowledge of the dynamics of the studied fungal aerospores, coupled with climate and meteorological changes, offers a series of information on the magnitude of the allergenic potential these airborne spores can determine. Legal regulations in this domain set the allergen risk threshold for the Alternaria sp aerospores at 3500 ÷ 7000 spores/m3 air/week, and for the Cladosporium sp aerospores at 56,000 spores/m3 air/week. Besides these regulations there exist a series of

Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

DEFF Research Database (Denmark)

Bush, A; Pedersen, S; Hedlin, G

2011-01-01

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided......, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both...

Aspirin desensitization in aspirin-sensitive asthma: failure to maintain a desensitized state during prolonged therapy.

Science.gov (United States)

Dankner, R E; Wedner, H J

1983-11-01

A patient with a history of asthma induced by acetylsalicylic acid (ASA) was found to be ASA sensitive when orally challenged with ASA. She was successfully desensitized using incremental doses of ASA given orally and maintained on ASA or other nonsteroidal antiinflammatory (NSAI) agents for the treatment of arthritis. After 6 months of uninterrupted therapy the patient developed asthmatic symptoms that were related to ASA and NSAI drug therapy. Although desensitization may be achieved in patients with ASA-sensitive asthma, sensitivity may recur despite continuous therapy.

Novel monoclonal treatments in severe asthma.

Science.gov (United States)

Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste; Backer, Vibeke

2017-12-01

To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." Only articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies. Of the 37 studies investigating biological treatments of asthma, 5 were on the effects of anti-IgE (omalizumab); 12 on anti-IL-5; 8 on anti-IL-13; 5 on anti-IL-4R-α; 3 on anti-IL-9; one on TNF-α; one on anti-IL-2R-α; one on TSLP (Thymic Stromal Lymphopoietin); and one on OX40L. Sample sizes ranged from 3 to 943 participants. Studies of therapies targeting IgE, IL-2, IL4R-α, IL-5, and IL-13 showed some efficacy, whereas those targeting TSLP, IL-9, and TNF-α lacked convincing effectiveness. Research on the biological treatment of asthma shows promising results. While anti-IgE (omalizumab) has been used in the treatment of asthma for some years, anti-IL-5 has recently been approved for use. The efficacy of results of other large studies with a longer duration is needed to draw a firm conclusion. Such studies should not only focus on clinical outcomes, but also consider asthma-related quality of life. Knowledge on the asthma phenotypes and identification of biomarkers associated with these will be useful for physicians considering the right treatment for the asthma patient.

Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma

NARCIS (Netherlands)

Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

2015-01-01

Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 +/- A 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

Science.gov (United States)

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma

Defining moderate asthma exacerbations in clinical trials based on ATS/ERS joint statement

DEFF Research Database (Denmark)

Virchow, J Christian; Backer, Vibeke; de Blay, Frédéric

2015-01-01

from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline and/or d) visit to the emergency room/trial site for asthma treatment not requiring systemic corticosteroids. CONCLUSION: A clinically and patient-relevant, operational definition of moderate exacerbations......BACKGROUND: Exacerbations are a key outcome in clinical research, providing patient-relevant information about symptomatic control, health state and disease progression. Generally considered as an episode of (sub)acute deterioration of respiratory symptoms, a precise, clinically useful definition...... is needed for use in clinical trials. AIM AND METHODS: Focussing on moderate exacerbations, this opinion piece reviews landmark trials and current guidelines to provide a practical definition of a moderate exacerbation. Specifically, we adapt the ATS/ERS consensus statement of terminology Reddel et al...

Mannose binding lectin (MBL levels predict lung function decline in severe asthma

Directory of Open Access Journals (Sweden)

Ilonka. H. van Veen

2006-12-01

Full Text Available There is increasing evidence that activation of the complement system in asthma contributes to ongoing inflammation, tissue damage and airway remodeling. Mannose binding lectin (MBL is a pattern recognition molecule that serves as the key mediator of the lectin pathway of complement activation. MBL levels are genetically determined and vary widely amongst individuals. In the present study we hypothesized that high MBL levels in asthma are associated with increased loss of lung function over time, as a consequence of inflammatory tissue damage. We measured serum MBL levels by ELISA in 68 patients with severe asthma and prospectively determined the change in post-bronchodilator (pb FEV1 over a mean period of 5.7 years. The relationship between MBL and change in pbFEV1 (FEV1 was analysed using (multiple regression analysis and corrected for possible confounders (age, sex, age of onset, asthma duration, and pbFEV1. The median (range MBL level was 332 (10.8-3587 ng·ml–1. MBL was significantly associated with FEV1 (p<0.04. Patients with a high MBL level (332 ng·ml–1 had an increased risk of lung function decline compared to those with low MBL levels (OR (CI: 3.16 (1.14-8.79, p = 0.027; the excess decline being 42 ml·yr–1 (p = 0.01. We conclude that a high MBL level is associated with an increased decline in lung function in patients with severe asthma. MBL might provide a clue towards better understanding of the pathophysiology of ongoing inflammation and subsequent decline in lung function of patients with severe asthma.

[Prevalence of sensitization to allergens in school children with asthma residents from Guadalajara metropolitan area].

Science.gov (United States)

Alcalá-Padilla, Guadalupe; Bedolla-Barajas, Martín; Kestler-Gramajo, Amanda; Valdez-López, Francisco

2016-01-01

Allergic sensitization is dependent on the geographical and climatic conditions in each region; therefore, identify agents most commonly sensitized children with asthma is important for planning prevention measures. To determine the prevalence of the sensitization to allergens in children with asthma. This cross-sectional and prolective study includes children from ages 6 to 14, who have asthma, attended for the first time in an allergy service. The patients were recruited consecutively between the months of January 1st 2014 to December 31st 2014. The frequency of the allergen sensitization was estimated. This study included 186 children, the median age was 7 years olds, the male group was 104/186 (55.9%) The median of the positive results was 5 and monosensitized were 47/186 (2.2%). The most common category of allergens was the indoor (90.3%), then trees (71.0%), and finally the fungi (9.7%). Individually, the house dust mites were more common in between the interior allergens, followed by the epithelial; in the tree pollen were oaks (31.7%) and ashes (28.0%), in weeds was mugwort (21.5%), in grasses was Zea mays (18.3%) and in the fungi was Cladosporium spp. (6.5%). The high prevalence of the sensitization to house dust mites and epithelial in children with asthma, stimulates to implement methods of environmental control for contributing a better control of the disease.

Cost-effectiveness of budesonide Turbuhaler in the treatment of mild-to-moderate asthma in Japan

Directory of Open Access Journals (Sweden)

Terumasa Miyamoto

1999-01-01

Full Text Available Asthma therapy including inhaled corticosteroids (ICS has been shown to be effective in many parts of the world, but its use is still limited in Japan. A 6-week, randomized, placebo-controlled, clinical trial was therefore undertaken to assess the efficacy of the ICS budesonide Turbuhaler (budesonide administered via the dry-powder inhaler Turbuhaler in patients in Japan with mild-to-moderate asthma. Prior to, and during, the study, all concomitant medications, except corticosteroid preparations, were allowed (i.e. all pre-study medication was to be maintained throughout the study. In total, 218 patients randomized to receive budesonide Turbuhaler 200 μg/day (n = 53, 400 μg/day (n = 55, 800 μg/day (n = 57 or placebo (n = 53 were included in the analysis. Due to the increased demand and interest for health economic data in Japan, this retrospective cost-effectiveness analysis reports on the economic impact of budesonide Turbuhaler compared with placebo (i.e. usual care, based on this clinical trial. At each dosage, budesonide Turbuhaler was significantly more effective than the placebo, according to the number of symptom-free and episode-free days. The number of emergency visits, days of lost production and days of hospitalization were all lower in the budesonide Turbuhaler groups, leading to significantly (P < 0.05 reduced total health-care and productivity costs compared with placebo. These findings were generally stable to sensitivity analysis. However, this reduction in costs will obviously have to be compared with the acquisition cost of budesonide Turbuhaler (which was excluded in the analysis as a price had not been determined when it becomes available on the market. Budesonide Turbuhaler, while improving the health of patients, could thus have a considerable impact on the costs of treating asthma in Japan, by shifting large hospital care costs towards relatively small out-patient medication costs.

Cluster analysis of obesity and asthma phenotypes.

Directory of Open Access Journals (Sweden)

E Rand Sutherland

Full Text Available Asthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC. Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype.In a cohort of clinical trial participants (n = 250, minimum-variance hierarchical clustering was used to identify clinical and inflammatory biomarkers important in determining disease cluster membership in mild and moderate persistent asthmatics. In a subset of participants, GC sensitivity was assessed via expression of GC receptor alpha (GCRα and induction of MAP kinase phosphatase-1 (MKP-1 expression by dexamethasone. Four asthma clusters were identified, with body mass index (BMI, kg/m(2 and severity of asthma symptoms (AEQ score the most significant determinants of cluster membership (F = 57.1, p<0.0001 and F = 44.8, p<0.0001, respectively. Two clusters were composed of predominantly obese individuals; these two obese asthma clusters differed from one another with regard to age of asthma onset, measures of asthma symptoms (AEQ and control (ACQ, exhaled nitric oxide concentration (F(ENO and airway hyperresponsiveness (methacholine PC(20 but were similar with regard to measures of lung function (FEV(1 (% and FEV(1/FVC, airway eosinophilia, IgE, leptin, adiponectin and C-reactive protein (hsCRP. Members of obese clusters demonstrated evidence of reduced expression of GCRα, a finding which was correlated with a reduced induction of MKP-1 expression by dexamethasoneObesity is an important determinant of asthma phenotype in adults. There is heterogeneity in expression of clinical and inflammatory biomarkers of asthma across obese individuals

Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma

NARCIS (Netherlands)

Verkleij, Marieke; van de Griendt, E-J.; Colland, V.; Van Loey, N.E.E.; Beelen, A.; Geenen, R.

2015-01-01

Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in

Therapy with omalizumab for patients with severe allergic asthma improves asthma control and reduces overall healthcare costs.

LENUS (Irish Health Repository)

Costello, R W

2011-05-11

BACKGROUND: Patients with asthma who have persistent symptoms despite treatment with inhaled steroids and long-acting beta agonists are considered to have severe asthma. Omalizumab is a monoclonal antibody directed against IgE, which is used as an add-on treatment for patients who have severe persistent allergic asthma. AIMS: The aim of this study was to assess the clinical benefit and healthcare utilisation of patients who responded to omalizumab therapy and to establish an overall cost implication. METHODS: This was an observational retrospective cohort study designed to investigate the effect of omalizumab on exacerbations of asthma before and after 6 months of treatment in Irish patients. RESULTS: Centres who had treated patients with severe allergic asthma for the 6 months prior and post omalizumab treatment were audited with a standardised assessment tool. Sixty-three (32 male) patients were studied. In the 6 months prior to omalizumab 41 of 63 (66%) had been hospitalised, and this fell to 15 of 63 (24%), p < 0.0001 in the 6 months after treatment was started. Hospital admissions reduced from 2.4 ± 0.41 to 0.8 ± 0.37 and the mean number of bed days occupied was reduced from 16.6 ± 2.94 to 5.3 ± 2.57 days, p < 0.001. The number of oral corticosteroid doses used fell from 3.1 ± 0.27 to 1.2 ± 0.17, p < 0.001. The overall cost saving per omalizumab responder patients for 6 months was 834. CONCLUSIONS: Six months therapy with omalizumab reduced the number of bed days, the number of hospitalisations and the use of oral corticosteroids compared to the 6 months prior to commencement. Despite the cost of the additional therapy there were overall savings in health costs.

Which functional parameters can help differentiate severe asthma from COPD?

Directory of Open Access Journals (Sweden)

Ricardo Marques Dias

2010-03-01

Full Text Available The aim of this study was to identify the respiratory function parameters that help in the accurate diagnosis of asthma and COPD. We studied 20 asthma and 30 COPD patients who underwent lung function tests including spirometry and plethysmography both with bronchodilator test and diffusion with carbon monoxide (DLCO. The tests were performed according to International Guidelines (ATS/ERS. The asthma patients were younger (mean age = 48 than those in the COPD group (mean age = 59 and this group also had more female patients (65% than the COPD group (40%. The results showed a more severe obstruction in the asthma group: FEV1/FVC = 59% versus 66% for COPD. There was also a greater bronchodilator response as shown by changes in absolute and percentage values for FEV1 in the asthma group. Average DLCO values were normal in the asthma group (103%P and lower in the COPD (69%. In plethysmography the asthma group had a higher residual volume (%P and a higher airway resistance. We concluded that many functional parameters were useful in distinguishing the asthma and COPD groups. In individual analysis, DLCO was the parameter which best aided in an accurate diagnosis in both groups, with a higher specificity for COPD. The bronchodilator response measured by changes in FEV1 showed a higher sensitivity for asthma. Thus, these two tests are highlighted in the differential diagnosis of obstructive diseases. Resumo: Com o objectivo de identificar parâmetros funcionais respiratórios que contribuam para o diagnóstico diferencial entre asma e DPOC, estudámos 20 asmáticos e 30 bronquíticos, com ou sem enfisema, com os exames usuais de função pulmonar: espirografia, pletismografia e DLCO, pré e pós-broncodilatação para os dois primeiros exames. Os grupos apresentam diferenças significativas na sua constituição. Os asmáticos são mais jovens, média de 48 anos, contra 59 anos no grupo com DPOC, e o

Response to omalizumab in patients with severe allergic asthma

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Zierau, Louise; Walsted, Emil Schwarz; Thomsen, Simon Francis

2017-01-01

INTRODUCTION: Omalizumab is a humanized monoclonal anti-IgE antibody, which is widely used for patients with severe uncontrolled asthma. Treatment with omalizumab is known to decrease the number of exacerbations and GETE score (Global Evaluation of Treatment Effectiveness) - but little is known...

Prevalence, severity and determinations of asthma in Danish five-year-olds

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Hermann, Christian; De Fine Olivarius, Niels; Høst, Arne

2006-01-01

regarding respiratory symptoms and our own questions on sociodemography and tobacco exposure. RESULTS: "Wheeze ever" was reported in 38.3%, "doctor-diagnosed asthma ever" in 10.5%, "childhood bronchitis ever" in 30.0%, "current wheeze" (3 episodes) in 3.......9% of the children. Current wheeze was associated with male gender (OR 1.63, 95% CI 1.35-1.96), low parental post-primary education (OR 1.29, 95% CI 1.02-1.63 for or =3 y) and current maternal smoking (OR 1.69, 95% CI 1.39-2.04). "Severe current wheeze" was recognized as asthma in six and childhood......BACKGROUND: The prevalence of asthma and wheeze is increasing. AIM: To study the annual and cumulative prevalence of asthma and wheeze in 5-y-old Danish children. METHODS: We obtained data on 3052 (82.0% of eligible) Danish children by a postal parental questionnaire including ISAAC questions...

Control of moderate-to-severe asthma with randomized ciclesonide doses of 160, 320 and 640 μg/day

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Pedersen, Søren E.; Prasad, Niyati; Goehring, Udo Michael

2017-01-01

Background: The inhaled corticosteroid (ICS) ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 μg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-te...... additional effect. Patients who experience more than one exacerbation per year may benefit from higher doses; however, further studies are necessary to confirm this. All Cic doses were well tolerated....

High Resolution Computed Tomography in Asthma 

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Nabil Maradny

2012-03-01

Full Text Available  Objectives: High-resolution computed tomography (HRCT can detect the structural abnormalities in asthma. This study attempts to correlate these abnormalities with clinical and pulmonary function test (PFT data.Methods: Consecutive stable asthma patients attending Mubarak Al Kabeer Hospital, Kuwait, were subjected to HRCT during a six month period from July 2004 to December 2004, after initial evaluation and PFT.Results: Of the 28 cases, sixteen (57.1�20had moderate, 6 (21.4�20had mild and 6 (21.4�20had severe persistent asthma. Thirteen (46.4�20patients had asthma for 1 to 5 years and 12 (42.9�20were having asthma for >10 years. Bronchial wall thickening (57.1� bronchiectasis (28.6� mucoid impaction (17.9� mosaic attenuation (10.7� air trapping (78.6�20and plate like atelectasis (21.4�20were noted. Bronchial wall thickening (p=0.044 and bronchiectasis (p=0.063 were most prevalent in males. Ten (35.7�20patients exhibited mild, 9 (32.1�20had moderate and 3 (10.7�20had severe air trapping. The difference in Hounsfield units between expiratory and inspiratory slices (air trapping when correlated with percent-predicted FEV1 in right upper (r=0.25;p=0.30, left upper (r=0.20; p=0.41, right mid (r=0.15; p=0.53, left mid (r=-0.04; p=0.60, right lower (r=0.04; p=0.86 and left lower zones (r=-0.13; p=0.58 showed no relation. The same when correlated as above with the percent predicted FEF 25-75 did not show any significant association. The presence of air trapping was compared with sex (p=0.640, nationality (p=1.000, disease duration (p=1.000 and severity of symptoms (p=0.581.Conclusion: Abnormal HRCT findings are common in asthma; however, air trapping when present was not related to the duration or severity of the illness or to the FEV1.

Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma.

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Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

2015-09-01

Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in previous research, scores on the Parenting Stress Index in mothers and fathers of the children with problematic severe asthma were low. Higher parenting stress was associated with higher levels of internalizing and externalizing behavioral problems in children (Child Behavior Checklist). Higher parenting stress in mothers was also associated with higher airway inflammation (FeNO). Thus, although parenting stress was suggested to be low in this group, higher parenting stress, especially in the mother, is associated with more airway inflammation and greater child behavioral problems. This indicates the importance of focusing care in this group on all possible sources of problems, i.e., disease exacerbations and behavioral problems in the child as well as parenting stress.

Anti-IgE: lessons from clinical trials in patients with severe allergic asthma symptomatic despite optimised therapy

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R. Buhl

2007-09-01

Full Text Available The efficacy of omalizumab has been extensively investigated in clinical trials in patients with severe persistent allergic (pre-treatment total immunoglobulin E 30–700 IU·mL–1 asthma including the Investigation of Omalizumab in Severe Asthma Treatment (INNOVATE study, which enrolled patients with inadequately controlled severe persistent allergic asthma despite receiving high-dose inhaled corticosteroid in combination with a long-acting beta2-agonist, and also additional controller medication if required. In the INNOVATE study, add-on omalizumab significantly reduced clinically significant exacerbation rates by 26% (0.68 versus 0.91, severe exacerbation rates by 50% (0.24 versus 0.48 and emergency visit rates by 44% (0.24 versus 0.43 and significantly improved asthma-related quality of life (QoL compared with placebo. In a pooled analysis of data from seven studies, add-on omalizumab significantly reduced asthma exacerbation rates by 38% (0.91 versus 1.47 and total emergency visits by 47% (0.332 versus 0.623. In addition, omalizumab significantly improved QoL versus current asthma therapy in a pooled analysis of data from six studies. Omalizumab has demonstrated a good safety and tolerability profile in completed phase-I, -II and -III studies involving >7,500 patients with asthma, rhinitis or related conditions. Omalizumab represents a major advance for the treatment of severe persistent allergic asthma that is inadequately controlled despite treatment with inhaled corticosteroids and a long-acting beta2-agonist.

Phenotypes of asthma in low-income children and adolescents: cluster analysis

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Anna Lucia Barros Cabral

Full Text Available ABSTRACT Objective: Studies characterizing asthma phenotypes have predominantly included adults or have involved children and adolescents in developed countries. Therefore, their applicability in other populations, such as those of developing countries, remains indeterminate. Our objective was to determine how low-income children and adolescents with asthma in Brazil are distributed across a cluster analysis. Methods: We included 306 children and adolescents (6-18 years of age with a clinical diagnosis of asthma and under medical treatment for at least one year of follow-up. At enrollment, all the patients were clinically stable. For the cluster analysis, we selected 20 variables commonly measured in clinical practice and considered important in defining asthma phenotypes. Variables with high multicollinearity were excluded. A cluster analysis was applied using a twostep agglomerative test and log-likelihood distance measure. Results: Three clusters were defined for our population. Cluster 1 (n = 94 included subjects with normal pulmonary function, mild eosinophil inflammation, few exacerbations, later age at asthma onset, and mild atopy. Cluster 2 (n = 87 included those with normal pulmonary function, a moderate number of exacerbations, early age at asthma onset, more severe eosinophil inflammation, and moderate atopy. Cluster 3 (n = 108 included those with poor pulmonary function, frequent exacerbations, severe eosinophil inflammation, and severe atopy. Conclusions: Asthma was characterized by the presence of atopy, number of exacerbations, and lung function in low-income children and adolescents in Brazil. The many similarities with previous cluster analyses of phenotypes indicate that this approach shows good generalizability.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.

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Richgels, Phoebe K; Yamani, Amnah; Chougnet, Claire A; Lewkowich, Ian P

2017-11-01

Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. We sought to determine whether maternal HDM exposure influences asthma development in offspring. Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, T H 2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, T H 2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by

Sub-optimal patient and physician communication in primary care consultations: its relation to severe and difficult asthma

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Moffat, M.; Cleland, J.; Van der Molen, T.; Price, D.

2006-01-01

Introduction: Asthma control can be influenced by a range of non-medical issues, including psychosocial factors. Little is known about the views of patients, particularly those with severe and/or difficult asthma, towards their asthma control and their asthma-related primary care consultations. Aims

Successful Use of Extracorporeal Life Support after Double Traumatic Tracheobronchial Injury in a Patient with Severe Acute Asthma

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Xavier Valette

2011-01-01

Full Text Available We report the case of an asthmatic patient with blunt trachea and left main bronchus injuries who developed acute severe asthma after surgical repair. Despite medical treatment and ventilatory support, asthma persisted with high airway pressures and severe respiratory acidosis. We proposed venovenous extracorporeal life support for CO2 removal which allowed arterial blood gas normalization and airway pressures decrease. Extracorporeal life support was removed on day five after medical treatment of acute severe asthma. So we report the successful use of extracorporeal life support for operated double blunt tracheobronchial injury with acute severe asthma.

4-month omalizumab efficacy outcomes for severe allergic asthma: the Dutch National Omalizumab in Asthma Registry

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Snelder, S. M.; Weersink, E. J. M.; Braunstahl, G. J.

2017-01-01

Background: Omalizumab is licensed as add-on therapy for patients with severe allergic asthma. Response is in most studies scored by the physician's global evaluation of treatment effectiveness (GETE). A good clinical and validated parameter for treatment response is currently missing. Also, there

Pathogenic, morphological and molecular characteristics of Alternaria Tenuissima from soybean

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Jasnić Stevan M.

2011-01-01

Full Text Available During 2008 and 2009 phytopathological isolations were done from soybean plants and seed samples from several localities in Serbia. A total of 19 isolates of Alternaria spp. were isolated, 13 from the seed and 3 from both leaf and stem. In order to determine and characterize isolates, cultural, morphological, molecular and pathogenic characteristics were thoroughly investigated. The slowest growth of the examined isolates was noted on Malt agar (MA with average colony diameter of 42.9 mm after 7 days of incubation. On other two media (V8 and PCA, colony growth was uniform and faster, with average diameter of 66.8 mm and 66.1 mm, respectively. Isolates of fungi form unbranched or poorly branched conidial chains on short unbranched conidiophores. Conidia are dark in colour, multicellular with transverse and longitudinal septae. They are of different size regarding the place of formation in the chain. Based on these characteristics, the tested isolates were determined as Alternaria tenuissima. Molecular identification with sequencing of ITS1-5.8S-ITS2 rDNA verified that investigated isolates belong to Alternaria tenuissima group. Pathogenicity test proved that all isolates were more or less virulent to soybean seed (12.5% to 40% of rotten seeds, while pathogenicity on plants was poorly expressed.

Anaesthesia in aspirin-induced asthma.

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Celiker, V; Basgül, E

2003-01-01

The triad of bronchial asthma, nasal polyposis, and intolerance to aspirin and aspirin-like chemicals are designated aspirin-induced asthma (AIA) or Samter's syndrome. The exact mechanism of the disease is unknown but it is thought to be a disorder of arachidonic acid metabolism. These patients are frequently referred to allergy clinics for preoperative evaluation for possible anesthetic agent sensitivity, requiring anesthesia for nasal polypectomy or several other reasons. Anesthetists must be aware of their pulmonary dysfunction, because the anesthetic management of asthma requires a specific approach. Marked cross-sensitivity with NSAIDs, which may also precipitate severe bronchospasm and adverse reactions, is the main problem faced by anesthetists in postoperative pain management. This article discusses the relationship between AIA and anesthesia. We also present our experience with 47 patients diagnosed with AIA between 1991 and 2003 in the department of chest diseases and adult allergy unit who underwent surgery requiring general anesthesia. In conclusion, preoperative evaluation of these patients and collaboration between the allergists and anesthesiologists is essential to prevent preoperative, perioperative and postoperative complications.

An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

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Norris Reinero, Carol R; Decile, Kendra C; Berghaus, Roy D; Williams, Kurt J; Leutenegger, Christian M; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2004-10-01

Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Lower prevalence and greater severity of asthma in hot and dry climate

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Marco Aurélio de Valois Correia Junior

2017-03-01

Full Text Available Objective: To estimate asthma prevalence, severity, and associated factors in adolescents who live in a low relative humidity environment. Methods: In this cross-sectional study, adolescents aged 13–14 years from the city of Petrolina located in the Brazilian semiarid region answered the International Study of Asthma and Allergies in Childhood (ISAAC questionnaire. The possible explanatory variables of the study were gender, family income, mother's education, smokers in the household, parental history of asthma, personal history of allergic rhinitis or atopic dermatitis, and physical activity level. Poisson regression analysis was used to assess the association between asthma and the explanatory variables. Results: A total of 1591 adolescents participated in the study, of whom 49.7% were male. The prevalence of active asthma, severe asthma, and physician-diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with asthma missed more school days than their peers (33 vs. 22 days/year; p < 0.03. Associated factors that remained significant after adjustment were history of asthma in parents (PR = 2.65, p < 0.001 and personal diagnosis of allergic rhinitis (PR = 1.96, p < 0.001 and/or atopic dermatitis (PR = 2.18, p < 0.001. Conclusion: Asthma prevalence in this low-humidity environment was lower, but more severe than those reported in other Brazilian cities. The dry climate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population. Resumo: Objetivo: Estimar a prevalência, a gravidade e os fatores associados à asma em adolescentes que vivem em uma região de baixa umidade relativa do ar. Métodos: Estudo transversal em adolescentes de 13 e 14 anos do semiárido brasileiro. Os

Benralizumab in the treatment of severe asthma: design, development and potential place in therapy

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Pelaia C

2018-03-01

Full Text Available Corrado Pelaia,1 Alessandro Vatrella,2 Andrea Bruni,1 Rosa Terracciano,3 Girolamo Pelaia1 1Department of Medical and Surgical Sciences, Section of Respiratory Diseases, “Magna Græcia” University of Catanzaro, Catanzaro, Italy; 2Department of Medicine, Surgery and Dentistry, Section of Respiratory Diseases, University of Salerno, Salerno, Italy; 3Department of Health Sciences, “Magna Græcia” University of Catanzaro, Catanzaro, Italy Abstract: Asthma is a widespread and heterogeneous inflammatory disease of the airways, which is characterized by several different phenotypes and endotypes. In particular, eosinophilic airway inflammation is a common pathologic trait of both allergic and nonallergic asthma. The key cytokine responsible for maturation, activation, recruitment, and survival of eosinophils is interleukin (IL-5, which is mainly produced by T helper 2 (Th2 lymphocytes and group 2 innate lymphoid cells. Therefore, for uncontrolled patients with severe eosinophilic asthma, who are not fully responsive to corticosteroids, IL-5 represents a very important molecular target for add-on biological therapies. Among these new treatments, anti-IL-5 monoclonal antibodies such as mepolizumab and reslizumab have been developed and clinically evaluated. Furthermore, benralizumab is currently the only available biologic drug that specifically binds to the IL-5 receptor, thus preventing the interaction with its ligand and the consequent pro-inflammatory effects. The effectiveness of benralizumab in improving severe eosinophilic asthma has been well-documented by many randomized controlled trials. Keywords: IL-5, IL-5 receptor, severe eosinophilic asthma, benralizumab

Dysfunctional breathing phenotype in adults with asthma - incidence and risk factors

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Agache Ioana

2012-09-01

Full Text Available Abstract Background Abnormal breathing patterns may cause characteristic symptoms and impair quality of life. In a cross-sectional survey 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing (DB, more likely to be female and younger, with no differences for severity of asthma. No clear risk factors were demonstrated for DB in asthma, nor the impact of asthma medication was evaluated. The objective of this study was to describe the DB phenotype in adults with asthma treated in a specialised asthma centre. Methods Adult patients aged 17–65 with diagnosed asthma were screened for DB using the Nijmegen questionnaire (positive predictive score >23 and confirmed by progressive exercise testing. The following were evaluated as independent risk factors for DB in the multiple regression analysis: female sex; atopy, obesity, active smoker, moderate/severe rhinitis, psychopathology, GERD, arterial hypertension; severe asthma, asthma duration > 5 years, lack of asthma control, fixed airway obstruction, fast lung function decline, frequent exacerbator and brittle asthma phenotypes; lack of ICS, use of LABA or LTRA. Results 91 adults with asthma, mean age 35.04 ±1.19 years, 47(51.65% females were evaluated. 27 (29.67% subjects had a positive screening score on Nijmegen questionnaire and 16(17.58% were confirmed by progressive exercise testing as having DB. Independent risk factors for DB were psychopathology (p = 0.000002, frequent exacerbator asthma phenotype (p = 0.01 and uncontrolled asthma (p Conclusion Dysfunctional breathing is not infrequent in asthma patients and should be evaluated in asthma patients presenting with psychopathology, frequent severe asthma exacerbations or uncontrolled asthma. Asthma medication (ICS, LABA or LTRA had no significant relation with dysfunctional breathing.

Efficacy of long-term omalizumab therapy in patients with severe asthma.

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Saji, Junko; Yamamoto, Takahito; Arai, Motonaka; Mineshita, Masamichi; Miyazawa, Teruomi

2017-03-01

The efficacy of omalizumab, an anti-immunoglobulin E (IgE) antibody, has been studied in patients with severe bronchial asthma. We conducted a study to evaluate, on the basis of both objective and subjective measures, the efficacy of omalizumab as a long-term therapy in patients with severe and persistent asthma. Omalizumab was administered subcutaneously every two or four weeks. The results of pulmonary function tests, Asthma Control Test (ACT) and Asthma Health Questionnaire (AHQ)-33 scores, the dosage of methylprednisolone during the 12-month treatment period, and the number of emergency visits prior to the start of treatment with omalizumab were compared in patients pre- and post-treatment with omalizumab. Fourteen patients were enrolled in the study between June 2010 and February 2012. Ten patients completed the study. With omalizumab treatment, there was no improvement in lung function; however, the number of emergency visits (19.3 before treatment vs. 1.2 after treatment, p=0.020) and the dosage of methylprednisolone (871.5mg before treatment vs. 119.0mg after treatment, p=0.046) decreased significantly. ACT and AHQ-33 scores at 16 weeks after treatment were significantly better than baseline scores. Four patients continued treatment with omalizumab for four years, and a reduction in their corticosteroid usage was noted. Long-term omalizumab therapy in our patients was found to significantly reduce corticosteroid usage and the number of emergency visits. Long-term omalizumab therapy was effective and might have potential to reduce the frequency of asthma exacerbations. The trial has not been registered because it is not an intervention study. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

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Suzuki, Cibele; Lopes da Silva, Nilceia; Kumar, Praveen; Pathak, Purnima; Ong, Siew Hwa

2017-08-01

Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross

Handgrip strength test as a complementary tool in monitoring asthma in daily clinical practice in children.

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Latorre-Román, Pedro Ángel; Navarro-Martínez, Ana Vanesa; Mañas-Bastidas, Alfonso; García-Pinillos, Felipe

2014-12-01

The aim of this study was to demonstrate that handgrip strength test can discriminate the presence/absence of asthma and between intermittent and moderate persistent asthma in children. 140 children (70 healthy and 70 with asthma) completed the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and performed the handgrip strength test. Forty-eight hours later, subjects performed spirometry. The results showed Handgrip strength was significantly lower (pstrength test was a predictive factor for asthma (cut-off at 16.84 kg) and for severity of pathology (cut-off at 15.06 kg). Handgrip strength was reduced in children with asthma. Handgrip strength was positively associated with lung capacity and quality of life. The fact that the handgrip strength test was able to discriminate between presence/absence of asthma and between intermittent and moderate persistent asthma in children suggested that this test could be used as a complementary tool in the monitoring of asthma in daily clinical practice.

Active Video Game Exercise Training Improves the Clinical Control of Asthma in Children: Randomized Controlled Trial

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Gomes, Evelim L. F. D.; Carvalho, Celso R. F.; Peixoto-Souza, Fabiana Sobral; Teixeira-Carvalho, Etiene Farah; Mendonça, Juliana Fernandes Barreto; Stirbulov, Roberto; Sampaio, Luciana Maria Malosá; Costa, Dirceu

2015-01-01

Objective The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with moderate to severe asthma. Design A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing (Bruce protocol) and lung function. Results No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p video game had a positive impact on children with asthma in terms of clinical control, improvementin their exercise capacity and a reductionin pulmonary inflammation. Trial Registration Clinicaltrials.gov NCT01438294 PMID:26301706

Active Video Game Exercise Training Improves the Clinical Control of Asthma in Children: Randomized Controlled Trial.

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Gomes, Evelim L F D; Carvalho, Celso R F; Peixoto-Souza, Fabiana Sobral; Teixeira-Carvalho, Etiene Farah; Mendonça, Juliana Fernandes Barreto; Stirbulov, Roberto; Sampaio, Luciana Maria Malosá; Costa, Dirceu

2015-01-01

The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with moderate to severe asthma. A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing (Bruce protocol) and lung function. No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p video game had a positive impact on children with asthma in terms of clinical control, improvement in their exercise capacity and a reduction in pulmonary inflammation. Clinicaltrials.gov NCT01438294.

Blood lipid levels associate with childhood asthma, airway obstruction, bronchial hyperresponsiveness, and aeroallergen sensitization

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Vinding, Rebecca K; Stokholm, Jakob; Chawes, Bo Lund Krogsgaard

2016-01-01

-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured at ages 5 to 7 years in the Copenhagen Prospective Studies on Asthma in Childhood2000 at-risk birth cohort. Asthma and allergic rhinitis were diagnosed based on predefined algorithms at age 7 years along......BACKGROUND: Studies of children's blood lipid profiles in relation to asthma are few, and the results are ambiguous. OBJECTIVE: We sought to examine whether the lipid profile is associated with concurrent asthma, altered lung function, and allergic sensitization in children. METHODS: High...... associated with concurrent asthma (adjusted odds ratio [aOR], 1.93; 95% CI, 1.06-3.55; P = .03) and airway obstruction: 50% of forced expiratory flow (aβ coefficient, -0.13 L/s; 95% CI, -0.24 to -0.03 L/s; P = .01) and specific airway resistance (aβ coefficient, 0.06 kPa/s; 95% CI, 0.00-0.11 kPa/s; P = .05...

Identification, characterization and mycotoxigenic ability of Alternaria spp. causing core rot of apple fruit in Greece.

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Ntasiou, Panagiota; Myresiotis, Charalampos; Konstantinou, Sotiris; Papadopoulou-Mourkidou, Euphemia; Karaoglanidis, George S

2015-03-16

Alternaria core rot is a major postharvest disease of apple fruit in several countries of the world, including Greece. The study was conducted aiming to identify the disease causal agents at species level, investigate the aggressiveness of Alternaria spp. isolates and the susceptibility of different apple varieties and determine the mycotoxigenic potential of Alternaria spp. isolates from apple fruit. Seventy-five Alternaria spp. isolates obtained from apple fruit showing core rot symptoms were identified as either Alternaria tenuissima or Alternaria arborescens at frequencies of 89.3 and 11.7%, respectively, based on the sequence of endopolygalacturonase (EndoPG) gene. Artificial inoculations of fruit of 4 different varieties (Fuji, Golden Delicious, Granny Smith and Red Delicious) and incubation at two different temperatures (2 and 25°C) showed that fruit of Fuji variety were the most susceptible and fruit of Golden Delicious the most resistant to both pathogens. In addition, the production of 3 mycotoxins, alternariol (AOH), alternariol monomethyl ether (AME) and tentoxin (TEN) was investigated in 30 isolates of both species. Mycotoxin determination was conducted both in vitro, on artificial nutrient medium and in vivo on artificially inoculated apple fruit, using a high performance liquid chromatography with diode array detector (HPLC-DAD). The results showed that most of the isolates of both species were able to produce all the 3 metabolites both in vivo and in vitro. On apple fruit A. tenuissima isolates produced more AOH than A. arborescens isolates, whereas the latter produced more TEN than the former. Such results indicate that Alternaria core rot represents a major threat of apple fruit production not only due to quantitative yield losses but also for qualitative deterioration of apple by-products. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Inhibition of spore germination of Alternaria tenuis by sulfur dioxide

Energy Technology Data Exchange (ETDEWEB)

Couey, H.M.

1962-08-01

As a part of a continuing study of SO/sub 2/ fumigation of table grapes, the effect of SO/sub 2/ on spores of an isolate of A. tenuis Auct. causing decay of table grapes was determined. The amount of SO/sub 2/ required to inhibit completely spore germination depended on availability of moisture and the temperature. At 20/sup 0/C, wet spores required 20-min exposure to 100 ppm SO/sub 2/ to prevent germination, but spores equilibrated at 90% relative humidity (RH) required 10-min exposure to 1000 ppm SO/sub 2/. Dry spores at 60% RH were unaffected by a 20-min exposure to 4000 ppm SO/sub 2/. Increasing the temperature in the range 5-20/sup 0/C increased effectiveness of the SO/sub 2/ treatment. A comparison of Alternaria with Botrytis cinerea Fr. (studied earlier) showed that wet spores of these organisms were about equally sensitive to SO/sub 2/, but that dry Alternaria spores were more resistant to SO/sub 2/ than dry Botrytis spores under comparable conditions.

[Control of asthma symptoms and cellular markers of inflammation in induced sputum in children and adolescents with chronic asthma].

Science.gov (United States)

Ciółkowski, Janusz; Stasiowska, Barbara; Mazurek, Henryk

2009-03-01

After the GINA 2006 publication, asthma therapy is based on control of symptoms. However there are suggestions of monitoring of airway inflammation. Aim of the study was to compare clinical criteria of asthma control with cellular markers of lower airway inflammation in induced sputum in a group of young asthmatics. To assess relationship between sputum eosinophilia, asthma severity and spirometry. A group of 154 young patients with chronic asthma (8-21 years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum induction was effective in 121 patients (78%), and in this group control of clinical symptoms was assessed according to GINA 2006 criteria. Asthma was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p = 0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p 3%) was observed in 24.4% of patients with controlled asthma and in 61.5% with uncontrolled asthma (p astma than in patients with moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/- 23.3% vs 81.7 +/- 23.1%; p = 0.004). In this study of young asthmatics, control of asthma symptoms was observed in 67.8% of patients. However, cellular markers of lower airway inflammation were present in 1/4 of patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more important that FEV1 for estimating control of asthma. Improvement of asthma control scoring is needed as well as availability of simple methods of inflammation monitoring.

Antigenic characteristics as taxonomic criterion of differentiation of Alternaria spp., pathogenic for carrot and parsley

Directory of Open Access Journals (Sweden)

Bulajić Aleksandra R.

2007-01-01

Full Text Available Identification of Alternaria genus species is a very complicated process which demands broadly designed investigations and studying of great number of properties which together can be considered as satisfying taxonomic criteria. The main objective of these investigations was examining the possibilities of applying the antigenic characteristics of Alternaria spp. phytopathogenic fungi as a taxonomic criterion, as well as introducing the serological methods for their identification. Conducting the examination of Alternaria spp., pathogenic for Apiaceae plants in Serbia, several isolates were obtained and identified as Alternaria radicina, A. petroselini, A. dauci and A. alternata, based on the conventional mycological methods and host range, as well as on molecular detection and partial characterization. The investigation included 12 isolates from plant leaves, seeds and soil which were pathogenic mainly to carrot and parsley and were identified as A. radicina, A. petroselini, A. dauci and A. alternate. Investigated isolates were compared with each other, as well as with standard isolates for the mentioned species (a total of 5 isolates, originating from USA and EU. During the investigation of serological characteristics of Alternaria spp. firstly a polyclonal antiserum was prepared against one isolate from Serbia identified as A. dauci. This antiserum was specific to Alternaria genus while there was no reaction with antigens from other phytopathogenic fungi genera (Fusarium, Rhizoctonia and Agaricus. Antiserum titer, determined by slide agglutination test, was 1/32. Antigenic characteristics of Alternaria genus fungi were examined by Electro-Blot-Immunoassay serological method (EBIA, Western blot, i.e. their protein profiles were compared. Investigated Alternaria spp. isolates showed different protein band profiles in gel and on nitrocellulose paper, and the observed differences were in complete correlation with the results of the previous

An integrated model of environmental factors in adult asthma lung function and disease severity: a cross-sectional study

Directory of Open Access Journals (Sweden)

Katz Patricia P

2010-05-01

Full Text Available Abstract Background Diverse environmental exposures, studied separately, have been linked to health outcomes in adult asthma, but integrated multi-factorial effects have not been modeled. We sought to evaluate the contribution of combined social and physical environmental exposures to adult asthma lung function and disease severity. Methods Data on 176 subjects with asthma and/or rhinitis were collected via telephone interviews for sociodemographic factors and asthma severity (scored on a 0-28 point range. Dust, indoor air quality, antigen-specific IgE antibodies, and lung function (percent predicted FEV1 were assessed through home visits. Neighborhood socioeconomic status, proximity to traffic, land use, and ambient air quality data were linked to the individual-level data via residential geocoding. Multiple linear regression separately tested the explanatory power of five groups of environmental factors for the outcomes, percent predicted FEV1 and asthma severity. Final models retained all variables statistically associated (p Results Mean FEV1 was 85.0 ± 18.6%; mean asthma severity score was 6.9 ± 5.6. Of 29 variables screened, 13 were retained in the final model of FEV1 (R2 = 0.30; p 2 = 0.16; p 1 as an independent variable to the severity model further increased its explanatory power (R2 = 0.25. Conclusions Multivariate models covering a range of individual and environmental factors explained nearly a third of FEV1 variability and, taking into account lung function, one quarter of variability in asthma severity. These data support an integrated approach to modeling adult asthma outcomes, including both the physical and the social environment.

Induced resistance in tomato fruit by γ-aminobutyric acid for the control of alternaria rot caused by Alternaria alternata.

Science.gov (United States)

Yang, Jiali; Sun, Cui; Zhang, Yangyang; Fu, Da; Zheng, Xiaodong; Yu, Ting

2017-04-15

The study investigated the effect of γ-aminobutyric acid (GABA) on the control of alternaria rot in tomato fruit and the possible mechanism involved. Our results showed exogenous GABA could stimulate remarkable resistance to the alternaria rot, while it had no direct antifungal activity against Alternaria alternata. Moreover, the activities of antioxidant enzymes, including peroxidase, superoxide dismutase and catalase, along with the expression of these corresponding genes, were significantly induced in the GABA treatment. The obtained data suggested GABA induced resistance against the necrotrophic pathogen A. alternata, at least in part by activating antioxidant enzymes, restricting the levels of cell death caused by reactive oxygen species. Meanwhile, the key enzyme genes of GABA shunt, GABA transaminase and succinic-semialdehyde dehydrogenase, were found up-regulated in the GABA treatment. The activation of the GABA shunt might play a vital role in the resistance mechanism underpinning GABA-induced plant immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new perspective on concepts of asthma severity and control

NARCIS (Netherlands)

D.R. Taylor; E.D. Bateman (Eric); L.P. Boulet; H.A. Boushey; W.W. Busse; T.B. Casale (Thomas); P. Chanez; P.L. Enright (Paul); P.G. Gibson; J.C. de Jongste (Johan); H.A. Kerstjens; S.C. Lazarus; M.L. Levy (Mark); P. O'byrne; M.R. Partridge; I.D. Pavord; M.R. Sears; P.J. Sterk (Peter); S.W. Stoloff; S.J. Szefler; S.D. Sullivan (Sean); M.D. Thomas; S.E. Wenzel; H.K. Reddel

2008-01-01

textabstractConcepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European

A new perspective on concepts of asthma severity and control

NARCIS (Netherlands)

Taylor, D. R.; Bateman, E. D.; Boulet, L.-P.; Boushey, H. A.; Busse, W. W.; Casale, T. B.; Chanez, P.; Enright, P. L.; Gibson, P. G.; de Jongste, J. C.; Kerstjens, H. A. M.; Lazarus, S. C.; Levy, M. L.; O'Byrne, P. M.; Partridge, M. R.; Pavord, I. D.; Sears, M. R.; Sterk, P. J.; Stoloff, S. W.; Szefler, S. J.; Sullivan, S. D.; Thomas, M. D.; Wenzel, S. E.; Reddel, H. K.

2008-01-01

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society

A new perspective on concepts of asthma severity and control

NARCIS (Netherlands)

Taylor, D. R.; Bateman, E. D.; Boulet, L-P.; Boushey, H. A.; Busse, W. W.; Casale, T. B.; Chanez, P.; Enright, P. L.; Gibson, P. G.; de Jongste, J. C.; Kerstjens, H. A. M.; Lazarus, S. C.; Levy, M. L.; O'Byrne, P. M.; Partridge, M. R.; Pavord, I. D.; Sears, M. R.; Sterk, P. J.; Stoloff, S. W.; Szefler, S. J.; Sullivan, S. D.; Thomas, M. D.; Wenzel, S. E.; Reddel, H. K.

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society

Dysfunction of Right Heart in Attack Period of Bronchial Asthma in Children

Directory of Open Access Journals (Sweden)

V.А. Kondratiev

2015-11-01

Full Text Available There were performed Doppler echocardiography investigations of functional state of the right heart in 42 children aged 5–17 years old in attack period of bronchial asthma of moderate to severe degree. Changes of intra-cardiac hemodynamics of the right heart in children in attack period of bronchial asthma were characterized by disturbance of systolic and diastolic function of the right ventricle and right atrium. Combined systolic-diastolic variant of the right ventricle dysfunction was typical for attack period of bronchial asthma in children and developed in 95.5 % of cases. Elevation of pressure in pulmonary artery was typical and significantly more often occurred in severe asthma attack, herewith pulmonary hypertension of the second degree predominated.

Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood

KAUST Repository

Al-Garawi, A; Fattouh, R; Botelho, F; Walker, T D; Goncharova, S; Moore, C-L; Mori, M; Erjefalt, J S; Chu, D K; Humbles, A A; Kolbeck, R; Stampfli, M R; O'Byrne, P M; Coyle, A J; Jordana, M

2011-01-01

The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We

Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children.

Science.gov (United States)

Jochmann, Anja; Artusio, Luca; Jamalzadeh, Angela; Nagakumar, Prasad; Delgado-Eckert, Edgar; Saglani, Sejal; Bush, Andrew; Frey, Urs; Fleming, Louise J

2017-12-01

International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma.Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period.93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21-99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups.Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic. Copyright ©ERS 2017.

Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

Science.gov (United States)

Nakamoto, Keitaro; Watanabe, Masato; Sada, Mitsuru; Inui, Toshiya; Nakamura, Masuo; Honda, Kojiro; Wada, Hiroo; Mikami, Yu; Matsuzaki, Hirotaka; Horie, Masafumi; Noguchi, Satoshi; Yamauchi, Yasuhiro; Koyama, Hikari; Kogane, Toshiyuki; Kohyama, Tadashi; Takizawa, Hajime

2016-01-01

Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. PMID:27776186

A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma

NARCIS (Netherlands)

Wenzel, Sally E.; Barnes, Peter J.; Bleecker, Eugene R.; Bousquet, Jean; Busse, William; Dahlén, Sven-Erik; Holgate, Stephen T.; Meyers, Deborah A.; Rabe, Klaus F.; Antczak, Adam; Baker, James; Horvath, Ildiko; Mark, Zsuzsanna; Bernstein, David; Kerwin, Edward; Schlenker-Herceg, Rozsa; Lo, Kim Hung; Watt, Rosemary; Barnathan, Elliot S.; Chanez, Pascal; Chanez, P.; Tunon-de-Lara, M.; Antczak, A.; Pierzchala, W.; Bukowczan, Z.; Trawinska, E.; Baker, J.; Wenzel, S. E.; Katial, R.; Bernstein, D.; Kerwin, E.; Bensch, G.; Castro, M.; Noonan, M.; Nayak, A.; Chupp, G.; Kline, J.; Busse, W.; Kavuru, M. S.; Lang, D.; Wolfe, R.; Baughman, R.; Korenblat, P.; Mansfield, L.; Bleecker, E.; Lisberg, E.; Liu, M.; Panettieri, R.; Spangenthal, S.; Bel, E. H.

2009-01-01

RATIONALE: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. OBJECTIVES: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.

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

Food and nutrition insecurity: a marker of vulnerability to asthma symptoms.

Science.gov (United States)

Ribeiro-Silva, Rita de Cássia; Oliveira-Assis, Ana Marlúcia; Junqueira, Samuel Badaró; Fiaccone, Rosemeire Leovigildo; Dos Santos, Sandra Maria Chaves; Barreto, Maurício Lima; de Jesus Pinto, Elizabete; da Silva, Luce Alves; Rodrigues, Laura Cunha; Alcantara-Neves, Neuza Maria

2014-01-01

To evaluate the association between food and nutrition insecurity and asthma in children from Latin America. Cross-sectional study. São Francisco do Conde, Bahia, north-eastern Brazil. The study included 1307 children aged 6-12 years from public elementary schools. Asthma symptoms were collected using a questionnaire that was translated and adapted from the International Study of Asthma and Allergies in Childhood, phase III. The diagnosis of asthma was determined based on reports of wheezing in the previous 12 months. The Brazilian Food Insecurity Scale was used to identify food insecurity. We also obtained demographic, socio-economic and anthropometric information for each participant. We used multivariate logistic regression analyses to assess the associations of interest. Of the children surveyed, 10·4% had a history of wheezing and 64·5% had some degree of food and nutrition insecurity. We found a positive dose-response relationship and statistically significant associations of asthma with moderate (OR = 1·71, 95% CI 1·01, 2·89) and severe (OR = 2·51, 95% CI 1·28, 4·93) food and nutrition insecurity. The results show that moderate and severe food and nutrition insecurity are markers of vulnerability to wheezing. It is important to note that the results of studies in this field have potential implications for social policies that promote food security. Further studies to identify the mechanisms involved in the relationship between food and nutrition insecurity and asthma are needed.

Asthma control during the year after bronchial thermoplasty

DEFF Research Database (Denmark)

Cox, Gerard; Thomson, Neil C.; Rubin, Adalberto S.

2007-01-01

scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed....... RESULTS: The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements......-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment. CONCLUSIONS: Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].)....

Episodes of asthma during pregnancy – link with a viral infection and treatment approaches

Directory of Open Access Journals (Sweden)

Pertseva T.A.

2014-06-01

Full Text Available Bronchial asthma (BA is the most common respiratory disease in pregnancy. About 20% of pregnant women experience asthma exacerbations of varying severity, while 5.8 % of them require hospitalization. Objective: to study asthma course during pregnancy by determining clinical and functional cha¬racteristics of the disease, taking into account presence of exacerbations and adherence to basic therapy (BT. Materials and methods: The study included 35 pregnant females (Me ± SD aged 31±5,28 years, gestational age – 34±6,69 weeks. Anamnestic and physical data, spirometry and assessment of asthma control using Control Asthma Test were conducted. Results: In the study group 71% of pregnant women suffered from aggravation of varying severity deve¬loping on the background of symptoms of respiratory tract infection. Here with commitment to BT before and during pregnancy significantly did not differ. Inconsistency of BT to severity of the disease in 25% of women with mild and in 36% with moderate asthma course was detected.

Respiratory allergy to moth: the importance of sensitization to Bombyx mori in children with asthma and rhinitis.

Science.gov (United States)

Araujo, Laura M L; Rosário Filho, Nelson A; Riedi, Carlos A

2014-01-01

this study aimed to prepare a silkworm moth (Bombyx mori) antigenic extract and to perform skin prick tests with this extract in patients with allergic respiratory diseases; to evaluate serum specific immunoglobulin E (IgE) to Bombyx mori using ImmunoCAP® system and to report the frequency of positivity between the two methods and with clinical data. this was a cross-sectional study with 99 children and adolescents diagnosed with asthma and/or allergic rhinitis, who had skin reactivity to at least one of the six aeroallergens tested. Clinical data were evaluated: skin prick tests with Bombyx mori in-house extract, and total and specific IgE analysis using ImmunoCAP® were performed. the frequency of Bombyx mori specific IgE was found to be 52.5% and 60% using the skin prick test and ImmunoCAP®, respectively. An association between a positive skin test for Bombyx mori and the presence of allergic rhinitis, atopic dermatitis, and urticaria was observed, but the same was not true for asthma or allergic conjunctivitis. There was no relation with the severity of asthma or rhinitis symptoms. a high frequency of sensitization to Bombyx mori was observed in a selected population of patients with respiratory allergic diseases in the city of Curitiba, state of Paraná, Brazil. The extract prepared from the wings of this moth species is effective in demonstrating this sensitivity. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Disorders of cardiac hemodynamic in attack period of bronchial asthma in children

Directory of Open Access Journals (Sweden)

Kondratiev V.А.

2016-05-01

Full Text Available By dopplerechocardiography method there was studied functional state of cardiac ventricles and character of hemodynamic disorders in 48 patients aged 5-17 years in attack period of moderately-severe and severe bronchial asthma. Group of comparison included 40 healthy peers. Disorders of central and peripheral hemodynamic in attack period of bronchial asthma in children were accompanied both by systolic and diastolic dysfunction of the left and right heart ventricles, herewith right ventricle was functioning in the mode of hyperdynamic, and left one – in the mode of hypodynamic. Combined systolic-diastolic variant of dysfunction both of right and left ventricles was developing in 58,3% of patients with moderately-severe and in 91,6% of patients with severe bronchial asthma. In the attack period of bronchial asthma in children equal directionality of systolic and diastolic dysfunction of heart ventricles was developing; this was characterized by synchronization of their function. Assessment of functional interaction of the ventricles under conditions of severe asthma attack showed direct and high (r=0,67 correlative interaction between finding of Tei index of the left and right ventricles, which characterize their systolic function; this, under conditions of increased hemodynamic pre-loading testified to compensatory increase of systolic interaction of ventricles. Direct and high (r=0,69 correlative interaction between time indices of isovolumic relaxation of the left and right ventricles, characterizing their diastolic function, testified to compensatory increase of diastolic interaction of ventricles under conditions of increase of hemodynamic post-loading. Imbalance of central and peripheral link of hemodynamic in attack period of bronchial asthma in children testified to development of cardiac insufficiency, which was compensated predominantly at the expense of increase of heart contractions rate.

Acute bronchial asthma

Directory of Open Access Journals (Sweden)

Susanna Ramuscello

2007-04-01

Full Text Available Asthma is one of the main causes of morbidity worldwide. It affects some 300 million individuals and has risen over the past 20 years, especially in the paediatric population. Asthma is a chronic inflammation of the airways, subject to periodic exacerbations, characterised by coughing and progressive dyspnoea. Clinical conditions may vary greatly, ranging from moderate exacerbation with an increase in nocturnal awakening and a less than 20% reduction in the flow peak, through to severe respiratory insufficiency that requires immediate intubation of the airways. Pharmacological treatment envisages a step approach that aims to obtain and maintain control over the symptoms, taking into consideration the effectiveness of the treatment available, potential side effects and cost. β2-agonists and corticosteroids are the drugs of election for both maintenance therapy and for treating exacerbations. Other therapeutic devices may prove useful in particular cases. One fundamental key point in treatment over time is the cooperation between patient and attending doctor. The latest review of the Global Initiative for Asthma (GINA guidelines was published in 2006.

The concentration of kynurenine in rat model of asthma.

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Barbara Mroczko

2008-06-01

Full Text Available Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN. To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC. In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01. In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma.

Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

NARCIS (Netherlands)

Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

2015-01-01

In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

Self-management program in treatment of asthma

Directory of Open Access Journals (Sweden)

Milenković Branislava

2007-01-01

Full Text Available Introduction. Recently published national and international guidelines stress the importance of self-management in asthma. They have recommended that self-management plans should be an essential part of the long-term management of asthmatic patients. These plans essentially focus on the early recognition of unstable or deteoriorating asthma, by monitoring peak flow or symptoms. Objective. The aim of our one-year study was to compare the efficacy of peak-flow based self-management of asthma with traditional treatment. Method. Sixty clinically stable adult patients with mild and moderate persistent asthma were randomly allocated to peakflow based self-management (Group A, n=30 or to conventional treatment (Group B, n=30, with no significant difference between groups in terms of age, sex distribution and initial lung function. The recorded measurements were: lung function, asthma exacerbations, unscheduled ambulatory care facilities (hospital-based emergency department, consultations with general practitioner or pulmonologist, courses of oral prednisolone, courses of antibiotics, days off work. Results. There was a significant difference between groups in number of asthma exacerbations (p<0.05, unscheduled visits to ambulatory care facilities (p<0.005, days off work (p<0.0001, courses of oral prednisolone (p<0.001 and antibiotics (p<0.05. At the final visit, there was a significant improvement in some measurements of asthma severity in group A (reduced unscheduled visits for ambulatory care, reduced treatment requirements for oral corticosteroids and antibiotics, reduced days off work, but a lack of statistical difference in lung function and the maintenance-inhaled corticosteroid dose. There was no significant change in group B. Conclusion. These results suggest that peak-flow based self management is more effective than traditonal treatment in mild and moderate persistent asthma. .

Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis

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Carla Bisaccioni

2009-01-01

Full Text Available OBJECTIVES: Severe asthma is found in approximately 10% of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD, nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma. METHODS: We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 2008. Symptoms of rhinitis and gastroesophageal reflux disease were evaluated as well as intolerance to nonsteroidal anti-inflammatory drugs. We evaluated the results of esophagogastroduodenoscopy, videolaryngoscopy and CT scans of the chest in order to confirm gastroesophageal reflux disease, nasal polyposis, vocal cord dysfunction and bronchiectasis. RESULTS: We evaluated 245 patients. Rhinitis symptoms were present in 224 patients (91.4%; 18 (7.3% had intolerance to nonsteroidal anti-inflammatory drugs, and 8 (3.3% had nasal polyposis. Symptoms of gastroesophageal reflux disease were reported for 173 (70.6% patients, although the diagnosis of gastroesophageal reflux disease was confirmed based on esophagogastroduodenoscopy or laryngoscopy findings in just 58 (33.6% patients. Vocal cord dysfunction was suspected in 16 (6.5% and confirmed through laryngoscopy in 4 (1.6%. The patient records provided CT scans of the chest for 105 patients, and 26 (24.8% showed bronchiectasis. DISCUSSION: Rhinitis and gastroesophageal reflux disease were the most common comorbidities observed, in addition to bronchiectasis. Therefore, in patients with severe asthma, associated diseases should be investigated as the cause of respiratory symptoms and uncontrolled asthma.

Right ventricular function during acute exacerbation of severe equine asthma.

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Decloedt, A; Borowicz, H; Slowikowska, M; Chiers, K; van Loon, G; Niedzwiedz, A

2017-09-01

Pulmonary hypertension has been described in horses with severe equine asthma, but its effect on the right ventricle has not been fully elucidated. To evaluate right ventricular structure and function after a 1-week period of pulmonary hypertension secondary to acute exacerbation of severe equine asthma. Prospective study. A clinical episode of severe equine asthma was induced experimentally in six susceptible horses. Examinations in remission and on day 7 of the clinical episode included a physical examination with clinical scoring, echocardiography, arterial blood gas measurements, venous blood sampling for cardiac biomarkers, intracardiac pressure measurements, right ventricular and right atrial myocardial biopsies, airway endoscopy and bronchoalveolar lavage. After 1 month of recovery, physical examination, echocardiography and cardiac biomarker analysis were repeated. Echocardiographic and pressure measurements were compared with those in 10 healthy control horses. All horses developed clinical signs of acute pulmonary obstruction. Right heart pressures increased significantly. Altered right ventricular function could be detected by tissue Doppler and speckle tracking echocardiography. Cardiac troponin concentrations did not increase significantly, but were highly elevated in one horse which exercised in the paddock prior to sampling. Focal neutrophil infiltration was present in two myocardial samples. Even in remission, asthmatic horses showed a thicker right ventricular wall, an increased left ventricular end-systolic eccentricity index at chordal level and decreased right ventricular longitudinal strain compared with controls. The induced clinical episode was rather mild and the number of horses was limited because of the invasive nature of the study. Pulmonary obstruction in asthmatic horses induces pulmonary hypertension with right ventricular structural and functional changes. © 2017 EVJ Ltd.

Obesity and Asthma

DEFF Research Database (Denmark)

Juel, Caroline Trunk-Black; Ulrik, Charlotte Suppli

2013-01-01

Asthma is more prevalent in obese compared with normal weight subjects. Our aim has been to review current knowledge of the impact of obesity on asthma severity, asthma control, and response to therapy.Several studies have shown that overweight and obesity is associated with more severe asthma...... and impaired quality of life compared with normal weight individuals. Furthermore, obesity is associated with poorer asthma control, as assessed by asthma control questionnaires, limitations in daily activities, breathlessness and wheezing, use of rescue medication, unscheduled doctor visits, emergency...... department visits, and hospitalizations for acute asthma. Studies of the impact of a high body mass index (BMI) on response to asthma therapy have, however, revealed conflicting results. Most studies show that overweight and obesity is associated with less favorable response to asthma therapy with regard...

Phagocytosis, bacterial killing, and cytokine activation of circulating blood neutrophils in horses with severe equine asthma and control horses.

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Vanderstock, Johanne M; Lecours, Marie-Pier; Lavoie-Lamoureux, Annouck; Gottschalk, Marcelo; Segura, Mariela; Lavoie, Jean-Pierre; Jean, Daniel

2018-04-01

OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of circulating blood neutrophils in horses with severe equine asthma and control horses and to determine whether circulating blood neutrophils in horses with severe equine asthma have an increase in expression of the proinflammatory cytokine tumor necrosis factor (TNF)-α and the chemokine interleukin (IL)-8 and a decrease in expression of the anti-inflammatory cytokine IL-10 in response to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses. PROCEDURES Circulating blood neutrophils were isolated from horses with severe equine asthma and control horses. Phagocytosis was evaluated by use of flow cytometry. Bactericidal activity of circulating blood neutrophils was assessed by use of Streptococcus equi and Streptococcus zooepidemicus as targets, whereas the cytokine mRNA response was assessed by use of a quantitative PCR assay. RESULTS Circulating blood neutrophils from horses with severe equine asthma had significantly lower bactericidal activity toward S zooepidemicus but not toward S equi, compared with results for control horses. Phagocytosis and mRNA expression of TNF-α, IL-8, and IL-10 were not different between groups. CONCLUSIONS AND CLINCAL RELEVANCE Impairment of bactericidal activity of circulating blood neutrophils in horses with severe equine asthma could contribute to an increased susceptibility to infections.

Development of a novel severe triple allergen asthma model in mice which is resistant to dexamethasone and partially resistant to TLR7 and TLR9 agonist treatment.

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Matthias J Duechs

Full Text Available Severe asthma is characterised by persistent inflammation, hyperreactivity and remodeling of the airways. No efficient treatment is available, this is particularly the case for steroid resistant phenotypes. Our aim therefore was to develop a preclinical model showing characteristics of severe human asthma including steroid insensitivity. Mice were first sensitized with ovalbumin, extracts of cockroach or house dust mite followed by a challenge period of seven weeks. Further to this, an additional group of mice was sensitized with all three allergens and then challenged with allergen alternating weekly between allergens. All three allergens applied separately to the mice induced comparably strong Th2-type airway inflammation, airway hyperreactivity and airway remodeling, which was characterised by fibrosis and increased smooth muscle thickness. In contrast, application of all three allergens together resulted in a greater Th2 response and increased airway hyperreactivity and a stronger albeit not significant remodeling phenotype compared to using HDM or CRA. In this triple allergen model dexamethasone application, during the last 4 weeks of challenge, showed no suppressive effects on any of these parameters in this model. In contrast, both TLR7 agonist resiquimod and TLR9 agonist CpG-ODN reduced allergen-specific IgE, eosinophils, and collagen I in the lungs. The TLR9 agonist also reduced IL-4 and IL-5 whilst increasing IFN-γ and strongly IL-10 levels in the lungs, effects not seen with the TLR7 agonist. However, neither TLR agonist had any effect on airway hyperreactivity and airway smooth muscle mass. In conclusion we have developed a severe asthma model, which is steroid resistant and only partially sensitive to TLR7 and TLR9 agonist treatment. This model may be particular useful to test new potential therapeutics aiming at treating steroid resistant asthma in humans and investigating the underlying mechanisms responsible for steroid

Sensivity of Jordanian Isolates of Alternaria solani to Manchotane

OpenAIRE

K.I. Al-Mughrabi

2004-01-01

Early blight of potato, caused by Alternaria solani, poses a significant risk to potato crops worldwide. Fifty A. solani isolates representing a population were collected from the Jordan Valley, purified, and tested for their sensitivity to the fungicide mancothane. The isolates were tested against a series of concentrations of 0, 0.1, 1, 10, 100, and 1000 mg mancothane ml-1 in 5% sodium dodecyl sulfate (SDS). Some A. solani isolates tolerated up to 1000 mg mancothane ml-1. Isolat...

EVALUATION OF THE ROLE OF INTERLEUKIN-8 (IL -8), SOLUBLE INTERCELLULAR ADHESION MOLECULE-1(SICAM-1) AND EOSINOPHIL CATIONIC PROTEIN (ECP) IN PATHOGENESIS OF BRONCHIAL ASTHMA

International Nuclear Information System (INIS)

EL-NASHAR, N.A.; MOSTAFA, A.M.E.; AHMED, S.M.; ABDEL-LATIF, A.

2008-01-01

Bronchial asthma remains a leading cause of chronic illness in children. Current theories of the pathogenesis of asthma suggest that airway inflammation is an important determinant of bronchial hyperactivity .The interaction of several inflammatory cells, soluble mediators and adhesion molecules may be important determinants of asthma. Since a better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease, this study was designed to investigate the contribution of these markers to airway inflammation. The present study included 25 children with asthma and 15 control children. The asthma cases were 18 males and 7 females ( mean age= 9.36 ± 2.16 years). According to the severity of asthma, patients were classified as mild (n=10), moderate (n=9) and severe (n=6) asthma. They were further classified into allergic asthmatics (extrinsic atopic, n=10) and non-allergic (intrinsic asthmatics, n=15). Estimations of serum levels of IL-8, sICAM-1(by ELISA) and ECP (by flouroimmunoassay) were done. The results of this study revealed that serum levels of IL-8 were significantly higher in asthmatics than in controls. Also, serum levels of it were significantly higher in cases with severe and cases with moderate asthma than in cases with mild asthma. Serum levels of sICAM-1 were significantly higher in asthmatic than in control children, in severe than in moderate, and in both than in mild asthma cases. Levels of ECP were significantly higher in asthmatics than in controls. Also, serum levels of it were related to asthma severity. Furthermore, the three biomarkers showed higher expression in allergic asthmatics versus non- allergies. There were positive correlations of IL-8, sICAM-1, ECP and IgE with each other in asthmatic children that may indicate interaction of these markers in regulation and persistence of inflammatory cascade in asthma through different mechanisms. In

Characterization of Alternaria strains from Argentinean blueberry, tomato, walnut and wheat

DEFF Research Database (Denmark)

Andersen, Birgitte; Nielsen, Kristian Fog; Fernández Pinto, Virginia

2015-01-01

of the chemical potential. Four strains belonged to the Alternaria infectoria sp.-grp., 6 to the Alternaria arborescens sp.-grp., 6 showed a sporulation pattern similar to that of “M” according to Simmons, 1 to that of Alternaria vaccinii, and the remaining 70 constituted a diverse group belonging...... sporulation pattern “M” were only isolated from tomatoes. Otherwise, no clear association between substrate and identity could be found. The analyses in the study show that at least 75% of the Argentinean strains are able to produce potential mycotoxins....

[Determination of the profiles of secondary metabolites characteristic of Alternaria strains isolated from tomato].

Science.gov (United States)

Benavidez Rozo, Martha Elizabeth; Patriarca, Andrea; Cabrera, Gabriela; Fernández Pinto, Virginia E

2014-01-01

Many Alternaria species have been studied for their ability to produce bioactive secondary metabolites, such as tentoxin (TEN), some of which have toxic properties. The main food contaminant toxins are tenuazonic acid, alternariol (AOH), alternariol monomethyl ether (AME), altenuene, and altertoxins i, ii and iii. To determine the profiles of secondary metabolites characteristic of Alternaria strains isolated from tomato for their chemotaxonomic classification. The profiles of secondary metabolites were determined by HPLC MS. The Alternaria isolates obtained from spoiled tomatoes belong, according to their morphological characteristics, to the species groups Alternaria alternata, Alternaria tenuissima and Alternaria arborescens, with A. tenuissima being the most frequent. The most frequent profiles of secondary metabolites belonging to the species groups A. alternata (AOH, AME, TEN), A. tenuissima (AOH, AME, TEN, tenuazonic acid) and A. arborescens (AOH, AME, TEN, tenuazonic acid) were determined, with some isolates of the latter being able to synthesize AAL toxins. Secondary metabolite profiles are a useful tool for the differentiation of small spored Alternaria isolates not easily identifiable by their morphological characteristics. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Asthma history, job type and job changes among US nurses.

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Dumas, Orianne; Varraso, Raphaëlle; Zock, Jan Paul; Henneberger, Paul K; Speizer, Frank E; Wiley, Aleta S; Le Moual, Nicole; Camargo, Carlos A

2015-07-01

Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. The Nurses' Health Study II is a prospective study of US female nurses enrolled in 1989 (ages 24-44 years). Job status and asthma were assessed in biennial (1989-2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. The analytic cohort included 98 048 nurses. Compared with nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio 0.73 (95% CI 0.63 to 0.86)) and emergency room/inpatient units (0.89 (0.82 to 0.97)). During a 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (HR 1.13 (1.07 to 1.18)), especially among those with more severe asthma (HR for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared with intermittent asthma, p trend: 0.004). Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses. 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.

Micromycetes sensitiveness to heavy metals

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O. N. Korinovskaya

2011-07-01

Full Text Available The sensitivity of 33 micromycete species to nitric compounds of copper, lead, zinc, nickel and cadmium has been determined. Absidia butleri Lendn, Mortierella vanesae Dixon-Stewart, Cunninghamella echinulata Thaxte, Curvularia tuberculata Jain, Cladosporium cladosporiodes (Fresen G. A. de Vries and Fusarium solani (C. Mart. Appel et Wollenw are sensitive to minimal content of the heavy metals (0.75 of maximum permissible concentration (MPC in the growth medium. At the same time Trixoderma longibrachiatiim Rifai, Alternaria alternatа (Fr. Keissl and Penicillium sp. 4 demonstrated moderate growth under maximal concentration (50 MPC. It is determined that minimal content of the heavy metals in the initial stage of influence (up to 48 h promotes growth of only Fusarium oxysporum E. F. Sm. et Swingle, while retards growth of the other species.

Increased body mass index predicts severity of asthma symptoms but not objective asthma traits in a large sample of asthmatics

DEFF Research Database (Denmark)

Bildstrup, Line; Backer, Vibeke; Thomsen, Simon Francis

2015-01-01

AIM: To examine the relationship between body mass index (BMI) and different indicators of asthma severity in a large community-based sample of Danish adolescents and adults. METHODS: A total of 1186 subjects, 14-44 years of age, who in a screening questionnaire had reported a history of airway...... symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore height and weight, skin test reactivity, lung function, and airway responsiveness were measured...

Th17 immunity in children with allergic asthma and rhinitis: a pharmacological approach.

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Giusy Daniela Albano

Full Text Available Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss, nasal wash (NW and plasma (P from Healthy Controls (HC and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested "in vitro" on IL-17A, RORγ(t and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of 12 weeks of treatment with Budesonide and Formoterol was tested "in vivo" in T-lymphocytes from mild-moderate asthma/persistent rhinitis patients. IL-17A was increased in Ss, NW and P from children with mild-moderate asthma compared with intermittent and HC. In cultured T-lymphocytes IL-17A and RORγ(t expression were higher in mild-moderate asthma/persistent rhinitis than in mild-moderate asthma/intermittent rhinitis, while FOXP3 was reduced. Budesonide with Formoterol reduced IL-17A and RORγ(t, while increased FOXP3 in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis, and reduced the IL-8 release mediated by IL-17A present in NW and Ss from mild-moderate asthma/persistent rhinitis in nasal and bronchial epithelial cells. Finally, Budesonide with Formoterol reduced IL-17A levels in P and Ss, CD4(+IL-17A(+T-cells, in naïve children with mild-moderate asthma/persistent rhinitis after 12 weeks of treatment. Th17 mediated immunity may be involved in the airway disease of children with allergic asthma and allergic rhinitis. Budesonide with Formoterol might be a useful tool for its therapeutic control.

[A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

Science.gov (United States)

Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

2009-08-01

A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis.

Science.gov (United States)

Arasi, Stefania; Costa, Stefano; Magazzù, Giuseppe; Ieni, Antonio; Crisafulli, Giuseppe; Caminiti, Lucia; Chiera, Fernanda; Vaccaro, Mario; Del Giudice, Michele Miraglia; Pajno, Giovanni Battista

2016-03-22

Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. We present herein the case of a 13-year-old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases.

Differentiation of Alternaria infectoria and Alternaria alternata based on morphology, metabolite profiles, and cultural characteristics

DEFF Research Database (Denmark)

Andersen, Birgitte; Thrane, Ulf

1996-01-01

Some small-spored species belonging to the genus Alternaria Nees have been studied according to their chemical, morphological, and cultural characteristics. A data matrix was constructed based on a combination of characters. Cluster analysis of the combined data set showed good resolution of two...

Sevoflurane therapy for life-threatening acute severe asthma: a case report.

Science.gov (United States)

Ruszkai, Zoltán; Bokrétás, Gergely Péter; Bartha, Péter Töhötöm

2014-10-01

Acute severe asthma is a life-threatening form of bronchial constriction in which the progressively worsening airway obstruction is unresponsive to the usual appropriate bronchodilator therapy. Pathophysiological changes restrict airflow, which leads to premature closure of the airway on expiration, impaired gas exchange, and dynamic hyperinflation ("air-trapping"). Additionally, patients suffering from asthma for a prolonged period of time usually have serious comorbidities. These conditions constitute a challenge during the treatment of this disease. Therapeutic interventions are designed to reduce airway resistance and improve respiratory status. To achieve therapeutic goals, appropriate bronchodilator treatment is indispensable, and mechanical ventilation under adequate sedation may also be required. The volatile anesthetic agent, sevoflurane, meets both criteria; therefore, its use can be beneficial and should be considered. A 67-yr-old Caucasian male presented with acute life-threatening asthma provoked by an assumed upper airway infection and non-steroidal anti-inflammatory drug antipyretics, complicated by chronic atrial fibrillation and hemodynamic instability. Due to frequent premature ventricular contractions, conventional treatment was considered unsafe and discontinued, and sevoflurane inhalation was initiated via the AnaConDa (Anaesthetic Conserving Device). Symptoms of life-threatening bronchospasm resolved, and the patient's respiratory status improved within hours. Adequate sedation was also achieved without any hemodynamic adverse effects. The volatile anesthetic agent, sevoflurane, is used widely in anesthesia practice. Its utility for treatment of refractory bronchospasm has been appreciated for years; however, its administration was difficult within the environment of the intensive care unit due to the need for an anesthesia machine and a scavenging system. The introduction of the AnaConDa eliminates these obstacles and makes the use of

Anti-mite measurements in mite-sensitive adult asthma. A controlled trial.

Science.gov (United States)

Burr, M L; St Leger, A S; Neale, E

1976-02-14

A cross-over controlled trial has been conducted among 32 adult patients with mite-sensitive asthma. The bedclothes and pillows of each subject were laundered and vacuum-cleaned and a plastic cover applied to the mattress for six weeks in an attempt to reduce exposure to mites. No improvement in daily peak-flow reading or drug usage was found in comparison with a control period.

Asthma Research

Science.gov (United States)

EPA is working to explore the role of common air pollutants in the development and exacerbation of asthma at different life stages as well as other environmental and genetic factors that might make a person more sensitive to developing asthma.

Eficiência e custo do controle químico da mancha de alternaria em tangor murcote Efficiency and cost of chemical control of alternaria brown spot

Directory of Open Access Journals (Sweden)

Adimara Bentivoglio Colturato

2009-09-01

Full Text Available A mancha de alternaria, causada por Alternaria alternata f. sp. citri, afeta tangelos Minneola, tangerinas Dancy, tangores Murcote e, menos freqüentemente, tangelos Orlando, tangerinas Novas, Lees e Sunburst. Esta doença causa desfolha grave, queda de frutos e manchas nas frutas. O objetivo deste trabalho foi estabelecer o melhor fungicida e a melhor dose para o controle da mancha marrom de alternaria. O delineamento experimental foi de parcelas subdivididas em blocos, com 10 tratamentos principais e 3 doses (subparcelas, com 5 repetições. Foram feitas 5 aplicações, com intervalo de 15 dias. Os tratamentos foram: azoxystrobin, pyraclostrobin, trifloxystrobin, trifloxystrobin + tebuconazole (2 aplicações seguido de 3 aplicações de mancozeb, difenoconazole, trifloxystrobin + propiconazole, iprodione, trifloxystrobin + propineb (2 aplicações seguido de 3 aplicações de oxicloreto de cobre, oxicloreto de cobre + óleo e testemunha. Simultaneamente foram feitas avaliações de incidência e número de lesões por folha. Ao surgimento dos frutos foram avaliadas a incidência em frutos e a produtividade em Kg/ha. Todos os tratamentos foram superiores à testemunha quanto a produtividade. Entre os produtos utilizados o tratamento com trifloxystrobin + propiconazole foi rentável comparando-se custo e produtividade.Alternaria brown spot, caused by Alternaria alternata sp. citri, attacks with more intensity the Tangelos Minneola, tangerine Dancy, and Murcotts, and with less intensity the tangelos Orlando and the tangerinas Novas, Lees and Sunburst. This disease causes severe defoliation and drop or necrotic spots in the fruits. The aim of this work was to evaluated the chemical control of brown spot, and to define the most appropriate dosage of fungicide to control it. The experimental design was split-spot, with ten treatments and 3 doses of fungicides, with five replicates, the fungicides were: azoxystrobin, pyraclostrobin, trifloxystrobin

Characteristics of asthma attack with long-term management for bronchial asthma.

Science.gov (United States)

Kawahara, Noriko; Hasegawa, Shunji; Hashimoto, Kunio; Matsubara, Tomoyo; Ichiyama, Takashi; Furukawa, Susumu

2009-10-01

There have been no reports on the evaluation of the usefulness of long-term asthma management based on the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2005 (JPGL 2005). The purpose of the present study was to retrospectively investigate the records of 350 patients admitted to Yamaguchi University Hospital who had asthma attacks from January 2006 to June 2008. There were 149 patients who were treated for more than 3 months in accordance with the guideline (long-term management group) and 201 who were not (non-long-term management group). The patients were divided into three age groups: 100 infants, 159 toddlers, and 91 schoolchildren. The onset age of asthma in the long-term management group was earlier than that in the non-long-term management group in toddlers and schoolchildren. The white blood cell counts and C-reactive protein levels were higher in the non-long-term management group in schoolchildren, suggesting the complication of some infections. The severity of asthma in the long-term management group was greater than that in the non-long-term management group among all three age groups. There were no significant differences, however, in the severity of asthma attack at admission between the long-term and non-long-term management groups in the three age groups. Patients who had severe asthma tended to be treated with long-term management, which suggests that long-term asthma management according to JPGL 2005 may reduce the severity of asthma attack at that admission, because the severity of asthma in patients undergoing long-term management correlates with the severity of asthma attack.

Comparative study on the effect of chemicals on Alternaria blight in Indian mustard--a multi-location study in India.

Science.gov (United States)

Meena, P D; Chattopadhyay, C; Kumar, A; Awasthi, R P; Singh, R; Kaur, S; Thomas, L; Goyal, P; Chand, P

2011-05-01

High severity of Altemaria blight disease is a major constraint in production of rapeseed-mustard in India. The aim of this study was to investigate the suppressive potential of chemicals viz., zinc sulphate, borax, sulphur, potash and calcium sulphate, aqueous extracts viz., Eucalyptus globosus (50 g l-1) leaf extract and garlic (Allium sativum) bulb (20 g l-1) extract, cow urine and bio-agents Trichoderma harzianum, Pseudomonas fluorescence in comparison with the recommended chemical fungicide (mancozeb), against foliar disease Alternaria blight of Indian mustard [Brassica juncea (L.) Czern. and Coss] under five different geographical locations of India. Mancozeb recorded the lowest mean severity (leaf: 33.1%; pod: 26.3%) of Alternaria blight with efficacy of garlic bulb extract alone (leaf = 34.4%; pod = 27.3%) or in combination with cow urine (leaf = 34.2%; pod = 28.6%) being statistically at par with the recommended chemical fungicide. Chemicals also proved effective in reducing Alternaria blight severity on leaves and pods of Indian mustard (leaf = 36.3-37.9%; pod = 27.5-30.1%). The effective treatments besides providing significant reduction in disease severity also enabled increase in dry seed yield of the crop (mancozeb = 2052 kg ha-1; garlic = 2006 kg ha-1; control = 1561 kg ha-1).

Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

Directory of Open Access Journals (Sweden)

Woodcock Ashley

2011-12-01

Full Text Available Abstract Background Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD evening and twice-daily (BD regimens of the novel inhaled corticosteroid fluticasone furoate (FF in asthma patients. Methods Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml were randomized to FF or fluticasone propionate (FP regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs and 24-hour urinary cortisol excretion were assessed. Results The intent-to-treat population comprised 147 (FF and 43 (FP patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml; all FF and FP regimens were significantly superior to placebo (p ≤ 0.02. AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02. Conclusions FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose. Trial registration Clinicaltrials.gov; NCT00766090.

Integrating asthma education and smoking cessation for parents: financial return on investment.

Science.gov (United States)

McQuaid, Elizabeth L; Garro, Aris; Seifer, Ronald; Hammond, S Katharine; Borrelli, Belinda

2012-10-01

Caregivers who smoke and have children with asthma are an important group for intervention. Home-based interventions successfully reduce asthma morbidity, yet are costly. This study evaluated the financial return on investment (ROI) of the Parents of Asthmatics Quit Smoking (PAQS) program, a combined asthma education and smoking cessation intervention. Participants included caregivers (n = 224) that smoked, had a child with asthma, and were enrolled in a Medicaid managed care plan. Participants received nurse-delivered asthma education and smoking counseling in three home visits. Program implementation costs were estimated, and healthcare expenses were obtained from insurance claims data 12 months pre- and 12 months post intervention. ROI was calculated for all participants, children <6 years, children 6-18 years, and children with moderate/severe persistent asthma. Total program implementation cost was $34,481. After intervention, there was increased mean annual refills of beta-agonist (0.51 pre, 1.64 post; P < 0.001), and controller medications (0.65 pre, 2.44 post; P < 0.001). Reductions were found in mean annual emergency department visits (0.33 pre, 0.14 post; P < 0.001), hospitalizations (0.23 pre, 0.08 post; P < 0.001), and outpatient visits (2.33 pre, 1.45 post, P < 0.001). The program had negative ROI (-21.8%) for the entire sample. The ROI was positive (+106.9) for children <6 years, negative (-150.3) for children 6-18, and negligible for moderate/severe persistent asthma (+6.9%). PAQS was associated with increased medication use and decreased healthcare utilization. While the overall ROI for PAQS was negative, PAQS had a positive ROI for caregivers of young children with asthma. Copyright © 2012 Wiley Periodicals, Inc.

Animal models of asthma: utility and limitations

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Aun MV

2017-11-01

Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

Characteristics and severity of asthma in children with and without atopic conditions : a cross-sectional study

NARCIS (Netherlands)

Arabkhazaeli, Ali; Vijverberg, Susanne J H; van Erp, Francine C; Raaijmakers, Jan A M; van der Ent, Cornelis K.; Maitland van der Zee, Anke H

2015-01-01

BACKGROUND: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children

Characteristics and severity of asthma in children with and without atopic conditions: A cross-sectional study

NARCIS (Netherlands)

Arabkhazaeli, Ali; Vijverberg, Susanne J. H.; van Erp, Francine C.; Raaijmakers, Jan A. M.; van der Ent, Cornelis K.; Maitland van der Zee, Anke H.

2015-01-01

Background: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children

Pulmonary Function Tests in Emergency Department Pediatric Patients with Acute Wheezing/Asthma Exacerbation

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Kathryn Giordano

2012-01-01

Full Text Available Background. Pulmonary function tests (PFT have been developed to analyze tidal breathing in patients who are minimally cooperative due to age and respiratory status. This study used tidal breathing tests in the ED to measure asthma severity. Design/Method. A prospective pilot study in pediatric patients (3 to 18 yrs with asthma/wheezing was conducted in an ED setting using respiratory inductance plethysmography and pneumotachography. The main outcome measures were testing feasibility, compliance, and predictive value for admission versus discharge. Results. Forty patients were studied, of which, 14 (35% were admitted. Fifty-five percent of the patients were classified as a mild-intermittent asthmatic, 30% were mild-persistent asthmatics, 12.5% were moderate-persistent asthmatics, and 2.5% were severe-persistent. Heart rate was higher in admitted patients as was labored breathing index, phase angle, and asthma score. Conclusions. Tidal breathing tests provide feasible, objective assessment of patient status in the enrolled age group and may assist in the evaluation of acute asthma exacerbation in the ED. Our results demonstrate that PFT measurements, in addition to asthma scores, may be useful in indicating the severity of wheezing/asthma and the need for admission.

Determination of mycotoxin profiles characteristic of Alternaria strains isolated from Malbec grapes

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Vargas Trinidad Andrea

2015-01-01

Full Text Available The world grape production has increased, reaching 751 million quintals (Mql in 2013. Many Alternaria species have been studied for their ability to produce secondary metabolites in foods, some of which have toxic properties with tenu- azonic acid (TA, alternariol (AOH, alternariol methyl ether (AME being the most important ones. The aim was to determine the characteristic mycotoxin production profiles of Alternaria strains isolated from Malbec grapes in the Patagonian region of Argentina. Fifty Alternaria isolates (5 A. alternata, 5 A. arborescens and 40 A. tenuissima were analyzed for the produc- tion of mycotoxins (TA, AOH and AME in autoclaved rice media by High Performance Liquid Chromatography (HPLC. All isolates were found to be producers of mycotoxins; the 100% was producer of TA (0.016–21.031 mg/kg, 98% produced AOH (0.003–0.057 mg/kg and 36% produced AME (0.001–0.133 mg/kg. Thirty-three isolates co-produced the three mycotoxins. In this study, it was demonstrated a high toxigenic potential of Alternaria isolates. Although Alternaria growth on grapes has been amply demonstrated, there are few studies about the incidence their more characteristic mycotoxin sand their toxicogenic capac- ity determination in grapes, wines and derivatives. In addition, mycotoxins studied in this work are not regulated in oenology. Therefore, further studies should be conducted to assess the health risk due to the presence of Alternaria toxins in grapes, wine, grape juice and raisins.

IL-13 and its genetic variants: effect on current asthma treatments.

Science.gov (United States)

Townley, Robert G; Sapkota, Muna; Sapkota, Kiran

2011-12-01

Airway hyperresponsiveness is an essential part of the definition of asthma associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain organic chemicals. Interleukin-13 (IL-13) is implicated as a central regulator in immunoglobulin E (IgE) synthesis, mucus hypersecretion, airway hyperresponsiveness, and fibrosis. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene and asthma and related traits. Single-nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations. Glucocorticoids are anti-inflammatory medications often used as maintenance therapy in acute and chronic asthma; however, some patients with severe asthma are steroid resistant. IL-13 remains elevated in glucocorticoid insensitive asthma but not in glucocorticoid sensitive asthma. Thus targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. This review focuses on the role of IL-13 on airway hyperresponsiveness and corticosteroids resistant asthma both preclinically and clinically. © Discovery Medicine

Determinants of allergic rhinitis in young children with asthma.

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Lise Moussu

Full Text Available BACKGROUND: In the preschool period, allergic rhinitis (AR is infrequent and thus under-diagnosed. However, recent works have highlighted the occurrence of AR in toddlers although the causes of AR in this young population remain unknown. The objective of this study was to identify determinants of AR in young children with asthma. METHODS: We carried out a case-control study of 227 children with active asthma and enrolled in the Trousseau Asthma Program. AR and other allergic diseases (asthma, food allergy and eczema were diagnosed by medical doctors using standardized questionnaires. Parental history of AR and asthma, biological markers of atopy (total IgE, blood eosinophilia, allergic sensitization towards food and aeroallergens and environmental parameters were also collected. RESULTS: Forty one of the children (18.1% had AR. By univariate logistic regression analysis, AR was mainly associated with peanut sensitization (OR = 6.75; p = 0.002; food allergy (OR = 4.31; p = 0.026; mold exposure (OR = 3.81 p<0.01 and parental history of AR (OR = 1.42; p = 0.046. Due to the strong link between food allergy and peanut sensitization three models of multivariate logistic regression were performed and confirmed that AR is associated with peanut sensitization but also food allergy and mold exposure. A random forest analysis was also performed to explain AR. The results reinforced the logistic analysis that peanut sensitization and mold exposure were the principal determinants of AR. CONCLUSIONS & CLINICAL RELEVANCE: These results stress the importance of investigating AR in young children with asthma to potentially diagnose a particularly severe allergic asthmatic phenotype. Moreover, these data evoke the hypothesis that peanut could be an aeroallergen.

Patient profiles and clinical utility of mepolizumab in severe eosinophilic asthma

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Haldar P

2017-06-01

Full Text Available Pranabashis Haldar Respiratory Biomedical Research Unit, Glenfield Hospital, University of Leicester, Leicester, UK Abstract: Mepolizumab (Nucala® is an effective and specific anti-eosinophil molecular therapy that has recently been approved as add-on therapy for the management of severe eosinophilic asthma by the US Food and Drug Administration (FDA, European Medicines Agency (EMA; European Union and more recently National Institute for Health and Care Excellence (NICE; UK. It is one of several molecular therapies in development for this indication and is illustrative of the strategic trajectory for pharmaceutical drug development taken over the past decade in several disease areas. Molecular therapies offer the prospect of improved specificity and effectiveness of biological effect. However, this necessitates a clear understanding of the underlying mechanistic pathways underpinning pathological processes, to inform drug development that yields novel more efficacious treatment options with a better clinical profile than existing agents. For the first time, utilization of molecular therapies in clinical trials is providing a novel in vivo model to characterize the association between specific pathways and clinical disease expression. It is increasingly recognized that asthma exhibits both clinical and pathological heterogeneity. It follows that a one-size-fits-all approach will not be appropriate and cost-effectiveness may only be achieved by identifying responder subgroups. This so-called personalized approach to therapy is being supported by the parallel development of companion biomarkers for clinical application. In this review, the author summarizes the clinical studies, their interpretation and the lessons learnt with mepolizumab that have informed our understanding of the approach to personalized molecular therapy in asthma. Keywords: IL-5, Nucala, exacerbations 

The influence of leptin on Th1/Th2 balance in obese children with asthma

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Doaa Mohammed Youssef

2013-09-01

Full Text Available OBJECTIVE: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. METHODS: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25 and non-obese (n = 25. From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. RESULTS: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. CONCLUSIONS: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.

A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.

Science.gov (United States)

Forno, Erick; Wang, Ting; Yan, Qi; Brehm, John; Acosta-Perez, Edna; Colon-Semidey, Angel; Alvarez, Maria; Boutaoui, Nadia; Cloutier, Michelle M; Alcorn, John F; Canino, Glorisa; Chen, Wei; Celedón, Juan C

2017-10-01

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

Ultrasound Evaluation of Patients with Moderate and Severe Carpal Tunnel Syndrome

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Ali Moghtaderi

2012-01-01

Full Text Available The objective of this study is to determine cut-off points for the crosssectional areas of the median nerve proximal and distal to carpal tunnel in moderate and severe Carpal Tunnel Syndrome (CTS and compare the results of our study with those available in the literature. Forty-three patients with upper limb pain other than CTS and 36 patients with idiopathic CTS enrolled into the study. The diagnosis and categorization of CTS were based on electrophysiologic criteria of the American Academy of Neurology. Median nerve cross-sectional areas were measured. Arithmetic mean values and standard deviation of each variable were measured. Student t-test and chi-squared test were applied to compare continuous and dichotomous variables between CTS and non-CTS control groups. Ultimately the diagnostic performances of the test characteristics including sensitivity, specificity, positive and negative predictive values were measured. Mean cross-sectional area of the nerve is higher in moderate than severe CTS proximal and distal to carpal tunnel. We accepted cut-off points of 11.5 mm2 and 13.5 mm2 for cross-sectional areas of the proximal and distal portions of carpal canal respectively. The sensitivity, specificity, positive and negative predictive values for the proximal inlet are 83%, 90.7%, 65.5% and 55.7%; and for the distal outlet are 36.1%, 93%, 81.2% and 63.4% respectively. We suggest that ultrasound is a good diagnostic modality for patients referred to tertiary care centers which categorized as moderate CTS.

Canadian Economic Evaluation of Budesonide-Formoterol as Maintenance and Reliever Treatment in Patients with Moderate to Severe Asthma

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Elizabeth Miller

2007-01-01

Full Text Available OBJECTIVES: To compare the cost-effectiveness of budesonide-formoterol in a single inhaler used as both maintenance and reliever medication versus clinician-directed titration of salmeterol-fluticasone as maintenance medication, plus salbutamol taken as needed, in controlling asthma in adults and adolescents.

Prevalence of sensitization to allergens in school children with asthma residents from Guadalajara metropolitan area

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Guadalupe Alcalá-Padilla

2016-05-01

Conclusion: The high prevalence of the sensitization to house dust mites and epithelial in children with asthma, stimulates to implement methods of environmental control for contributing a better control of the disease.

Therapy of moderate and severe psoriasis

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Werfel, Thomas

2006-04-01

Full Text Available Objective and methods: This health technology assessment (HTA report synthesises systematically randomized controlled studies (RCT on the therapy of moderate and severe psoriasis vulgaris which were published between 1999 and 2004; it includes some important clinical studies which have been published after 2004 and thus updates the English HTA report by Griffiths et al. [1]. The major objective is the evaluation of the medical effectiveness of different therapeutical approaches and the cost effectiveness with relevance for Germany. Results: The major conclusions from the results of medical RCT on moderate and severe psoriasis vulgaris are: Oral fumarates are effective in the treatment of moderate to severe psoriasis vulgaris. However, fumarates quiet frequently cause moderate side effects. Cyclosporine and methotrexate are both effective in the treatment of severe psoriasis vulgaris. Both substances have a different spectrum of side effects which may limit the individual applicability. Acetritin is only moderately effective in the treatment of severe psoriasis of the plaque type. Calcipotriol or UV-radiation used at the same time can increase the clinical effectiveness of acetritin. Systemic PUVA, balneo-PUVA and UVB therapy are all effective for the treatment of severe psoriasis. The combination of UV therapy with vitamin D3 analogues or with topical steroids is more effective than the treatment with UV radiation alone. Saltwater baths increase the effectiveness of UVB therapy. No RCT on the therapeutical effects of topical tar or of dithranol in combination with UV therapy have been published so far. A continuous therapy with PUVA should not be applied due to its proven photocarcinogenicity. Three substances from the group of biologicals (Efalizumab, Etanercept, and Infliximab are now available in Europe and a further substance (Alefacept is available in the USA for the treatment of moderate to severe psoriasis. All biologicals have been

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

Science.gov (United States)

Meert, Kathleen L; Clark, Jeff; Sarnaik, Ashok P

2007-11-01

1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. Retrospective medical record review. University-affiliated children's hospital. All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. None. Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH 120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

The Association between Asthma and Sleep in Urban Adolescents with Undiagnosed Asthma

Science.gov (United States)

Koinis Mitchell, Daphne; Kopel, Sheryl J.; Williams, Brittney; Cespedes, Amarilis; Bruzzese, Jean-Marie

2015-01-01

Background: We examined associations between asthma and sleep in a sample of inner-city adolescents with asthma-like symptoms who are undiagnosed, and to assess the extent to which youth's report of perceived stress moderates this association. Methods: A total of 349 adolescents (83% girls), with a mean age of 15.8 years, and their primary…

Airway inflammatory response to ozone in subjects with different asthma severity

Energy Technology Data Exchange (ETDEWEB)

Vagaggini, B.; Carnevali, S.; Macchioni, P. [Univ. of Pisa, Cardio-Thoracic Dept., Respiratory patho-physiology (IT)] (and others)

1999-07-01

The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity. Two groups of asthmatic subjects were studied: seven with intermittent mild asthma not requiring regular treatment (group A); and seven with persistent mild asthma requiring regular treatment with inhaled corticosteroids and long-acting {beta}{sub 2}-agonists (group B). All subjects were exposed, in a randomized cross-over design, to air or O{sub 3} (0.26 parts per million (ppm) for 2 h with intermittent exercise); subjects in group B withdrew from regular treatment 72 h before each exposure. Before the exposure, and 1 and 2 h after the beginning of the exposure they performed a pulmonary function test, and a questionnaire was completed to obtain a total symptom score (TSS). Six hours after the end of the exposure, hypertonic saline (HS) sputum induction was conducted. Sputum cell percentages, eosinophil cationic protein (ECP) and interleukin (IL)-8 concentrations in the sputum supernatant were measured. TSS significantly increased and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) significantly decreased after O{sub 3} exposure in comparison with air exposure in group A, whereas no changes were observed in group B except for a significant decrement of FEV1 2 h after the beginning of O{sub 3} exposure. Sputum neutrophil percentage was significantly higher after O{sub 3} exposure than after air exposure in both groups (Group A: 70.2% (28-87) versus 26.6% (8.6-73.2); Group B: 62.1% (25-82.4) versus 27.9% (14.4-54)). IL-8 was higher in sputum supernatant collected 6 h after O{sub 3} exposure than after air, only in group A. No change due to O{sub 3} has been found in sputum eosinophil percentage and ECP concentration in both groups. In conclusion, the degree of airway response to a short-term exposure to ozone is different in subjects with asthma of different severity. The

Fuel to Moderator Ratio Sensitivity Study Using Water Rod Moderator in SCWR Conceptual Core Design

International Nuclear Information System (INIS)

Bae, Seong Man; Kim, Yong Bae; Park, Dong Hwan; Lee, Kwang Ho

2009-01-01

The conceptual operating condition of Super Critical Water-cooled Reactor (SCWR) is above critical point of water, such that the coolant temperature ranges from 280 .deg. C to 510 .deg. C with a pressure of 25MPa. This operating condition makes an SCWR have both merits and demerits when compared with current Light Water Reactors (LWRs). One of the demerits of SCWR is degradation of neutron moderation due to a lower water density from ∼0.1g/cm 3 to ∼0.7g/cm 3 under a high coolant temperature condition. Therefore it is necessary to enhance the moderation capability for SCWR to slow down the fast fission neutrons. Many SCWR designs have a water rod concept as an additional moderator, because water has a good moderation capability. Through reviewing the previous water rod assembly designs, it was identified that a sensitivity study is required to optimize fuel assembly pitch to increase the neutron economy. In this paper, the results of the conceptual assembly design sensitivity study which focuses on the comparison of sensitivity for the fuel pitch to diameter (P/D) ratio using water rod moderator, are presented

Sensivity of Jordanian Isolates of Alternaria solani to Manchotane

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K.I. Al-Mughrabi

2004-04-01

Full Text Available Early blight of potato, caused by Alternaria solani, poses a significant risk to potato crops worldwide. Fifty A. solani isolates representing a population were collected from the Jordan Valley, purified, and tested for their sensitivity to the fungicide mancothane. The isolates were tested against a series of concentrations of 0, 0.1, 1, 10, 100, and 1000 mg mancothane ml-1 in 5% sodium dodecyl sulfate (SDS. Some A. solani isolates tolerated up to 1000 mg mancothane ml-1. Isolates treated with the various concentrations were divided into 5 groups based on the percentage of A. solani growth achieved despite treatment: group 1 comprised isolates with mycelial growth of 0.1– 20.9%; group 2, 21–40.9%; group 3, 41–60.9%; group 4, 61–80.9%; and group 5, 81–100%. Ninety-seven percent of all isolates grew at 0.1 mg mancothane ml-1, 94% at 1 mg ml-1, 86% at 10 mg ml-1, 66% at 100 mg ml-1, and 16% at 1000 mg ml-1. Isolates appeared to be distributed normally at 10 mg mancothane ml-1. Eight isolates were highly resistant to mancothane and grew even at the highest test concentration. An A. solani population collected from potato fields in the Jordan Valley exhibited a moderate level of resistance to mancothane. Growers should be careful and vigilant when using this fungicide to control early blight.

A retrospective analysis of practice patterns in the management of acute asthma attack across Turkey.

Science.gov (United States)

Türktaş, Haluk; Bavbek, Sevim; Misirligil, Zeynep; Gemicioğlu, Bilun; Mungan, Dilşad

2010-12-01

To evaluate patient characteristics and practice patterns in the management of acute asthma attack at tertiary care centers across Turkey. A total of 294 patients (mean age: 50.4 ± 15.1 years; females: 80.3%) diagnosed with persistent asthma were included in this retrospective study upon their admission to the hospital with an acute asthma attack. Patient demographics, asthma control level, asthma attack severity and the management of the attack were evaluated. There was no influence of gender on asthma control and attack severity. In 57.5% of the patients, asthma attack was moderate. Most patients (78.9%) were hospitalized with longer duration evident in the severe attack. Spirometry and chest X-Ray were the most frequent tests (85.4%), while steroids (72.0% parenteral; 29.0% oral) and short-acting beta-agonists (SABA) + anticholinergics (45.5%) were the main drugs of choice in the attack management. Attack severity and pre-attack asthma control level was significantly correlated (p attack asthma was uncontrolled in 42.6% of the patients with severe attack. Most of the patients were on combination of more than one (two in 38.7% and 3-4 in 31.2%) controller drugs before the attack. Providing country specific data on practice patterns in the management of acute asthma attack in a representative cohort in Turkey, prescription of steroids and SABA + anticholinergics as the main drugs of choice was in line with guidelines while the significant relation of pre-attack asthma control to risk/severity of asthma attack and rate/duration of hospitalization seem to be the leading results of the present study. Copyright © 2010 Elsevier Ltd. All rights reserved.

'Real-life' effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review.

Science.gov (United States)

Abraham, I; Alhossan, A; Lee, C S; Kutbi, H; MacDonald, K

2016-05-01

We reviewed 24 'real-life' effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short- and long-term benefit of anti-IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life - thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2-4 years, and the majority of omalizumab-treated patients may benefit for many years. Omalizumab has positive short- and long-term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Linoleic acid metabolite leads to steroid resistant asthma features partially through NF-?B

OpenAIRE

Panda, Lipsa; Gheware, Atish; Rehman, Rakhshinda; Yadav, Manish K.; Jayaraj, B. S.; Madhunapantula, SubbaRao V.; Mahesh, Padukudru Anand; Ghosh, Balaram; Agrawal, Anurag; Mabalirajan, Ulaganathan

2017-01-01

Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15?lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that H...

Occurrence of Leaf Blight on Cosmos Caused by Alternaria cosmosa in Korea

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Jian Xin Deng

2015-03-01

Full Text Available In 2011, a leaf blight disease was observed on cosmos (Cosmos bipinnatus leaves in Nonsan, Korea. The causal pathogen was isolated and identified based on morphological and molecular approaches. Morphological characteristics of the pathogen matched well with the Alternaria cosmosa and also easily distinguishable from Alternaria zinniae reported from cosmos seeds by producing branched beak. Phylogenetically, the pathogen could not be distinguished from A. passiflorae based on the sequence analysis of a combined data set of Alt a1 and gpd genes. However, A. passiflorae was distinguished from the present species by having conidiophores with 4 to 5 conidiogenous loci. The results indicate that the present Alternaria species is A. cosmosa. Pathogenicity tests revealed that the isolate was pathogenic to the leaves of Cosmos bipinnatus. This is the first report of Alternaria blight disease caused by A. cosmosa on cosmos in Korea.

Longterm clinical outcomes of omalizumab therapy in severe allergic asthma: Study of efficacy and safety.

Science.gov (United States)

Mansur, Adel H; Srivastava, Sapna; Mitchell, Verity; Sullivan, Julie; Kasujee, Ismail

2017-03-01

Omalizumab has been shown to be an effective add-on therapy for patients with uncontrolled severe persistent allergic asthma. There has been a steady accumulation of evidence on the long-term effectiveness of omalizumab; however, data on real-life outcomes beyond one year of treatment is limited. In this study, we report on long-term outcomes of omalizumab treatment. We collected data from our severe asthma registry on hospitalisations, exacerbations, corticosteroid sparing, asthma control, lung function, biomarkers and side effects, to determine if the benefit was sustained and treatment was safe on the long term. Forty-five patients [mean age 44.9 years (range 19-69), females 37/45 (82%), mean duration of omalizumab treatment = 60.7 ± 30.9 months (range 23-121) were included in the analysis. We observed a reduction in the annual acute asthma related hospital admissions for the total population from 207 at baseline to 40 on treatment (80.7% reduction), whilst the per patient annual hospitalisations were reduced from a mean of 4.8 to 0.89 post-omalizumab treatment (p omalizumab therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost-Effectiveness Analysis of Omalizumab for the Treatment of Severe Persistent Asthma in Real Clinical Practice in Spain.

Science.gov (United States)

Vennera, María Del Carmen; Valero, Antonio; Uría, Estefany; Forné, Carles; Picado, César

2016-07-01

Omalizumab is a humanized monoclonal antibody that targets circulating immunoglobulin E molecules to treat severe uncontrolled asthma. The aim of this study was to determine the cost effectiveness of omalizumab compared with standard treatment for the control of severe persistent asthma according to data from patients treated in a specialized asthma unit. This was an observational, retrospective, single-center study in the setting of the Pulmonology and Respiratory Allergy Service, Thorax Institute, Hospital Clínic de Barcelona, Barcelona, Spain. Data were collected by review of medical records of 86 uncontrolled severe persistent asthma patients treated with omalizumab from January 2005 to April 2014. Effectiveness was assessed by the reduction in asthma exacerbations and 3-point increases in the Asthma Control Test (ACT) score. The economic evaluation was performed from the societal perspective, including direct health costs (resource use and drug treatments) and indirect costs (disease impact on labor productivity) in 2016 Euros. The time horizon was 12 months before and after the initiation of treatment with omalizumab. Results were expressed using the incremental cost-effectiveness ratio (ICER). Taking into account only direct costs, the ICERs were €1487.46 (95 % confidence interval [CI] 1241.21-1778.34) per exacerbation avoided and €5425.13 (95 % CI 4539.30-6551.03) per 3-point increase in the ACT. When indirect costs were included, the ICERs were €1130.93 (95 % CI 909.08-1392.86) per exacerbation avoided, and €4124.79 (95 % CI 3281.69-5186.73) per 3-point increase in the ACT. The results of this study confirm the effectiveness of the addition of omalizumab to standard therapy in patients with uncontrolled severe persistent asthma.

Comparative effectiveness of mepolizumab and omalizumab in severe asthma: An indirect treatment comparison.

Science.gov (United States)

Cockle, Sarah M; Stynes, Gillian; Gunsoy, Necdet B; Parks, Daniel; Alfonso-Cristancho, Rafael; Wex, Jaro; Bradford, Eric S; Albers, Frank C; Willson, Jenny

2017-02-01

Severe asthma is a heterogeneous disease. Patients with both eosinophilic and allergic asthma phenotypes may be eligible for treatment with mepolizumab and omalizumab. Evidence on the relative effectiveness of these treatments in this 'overlap' population would be informative for clinical and payer decision making. A systematic literature review and indirect treatment comparison (Bayesian framework) were performed to assess the comparative effectiveness and tolerability of mepolizumab and omalizumab, as add-ons to standard of care. Studies included in the primary analysis were double-blind, randomized controlled trials, ≥12 weeks' duration enrolling patients with severe asthma with a documented exacerbation history and receiving high-dose inhaled corticosteroids plus ≥1 additional controller. Two populations were examined: patients potentially eligible for 1) both treatments (Overlap population) and 2) either treatment (Trial population). In the Overlap population, no differences between treatments in clinically significant exacerbations and exacerbations requiring hospitalization were found, although trends favored mepolizumab (rate ratio [RR]:0.66 [95% credible intervals (Crl):0.37,1.19]; 0.19[0.02,2.32], respectively). In the Trial population, mepolizumab treatment produced greater reductions in clinically significant exacerbations (RR:0.63 [95% CrI:0.45,0.89]) but not exacerbations requiring hospitalization compared with omalizumab (RR:0.58 [95% Crl: 0.16,2.13]), although the trend favored mepolizumab. Both treatments had broadly comparable effects on lung function, and similar tolerability profiles. Whilst this analysis has limitations due to a restricted evidence base and residual heterogeneity, it showed that in patients with severe asthma, mepolizumab seems to be at least as effective as omalizumab and that the tolerability profiles of the two treatments did not meaningfully differentiate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence and severity of self-reported asthma in young adults, 1976-2004

DEFF Research Database (Denmark)

Browatzki, A; Ulrik, Charlotte Suppli; Lange, P

2009-01-01

The aim of the present study was to describe the prevalence and severity of asthma in young Danish adults over three decades. Males and females aged 20-35 yrs were sampled from the population of Copenhagen for the three surveys (1976-1978, 1991-1993 and 2001-2004). A total of 3,285 (46% male) sub...... to increase over the last three decades among young Danish adults, and the observed increase in severity seems, at least partly, to be related to the increase in prevalence of obesity.......The aim of the present study was to describe the prevalence and severity of asthma in young Danish adults over three decades. Males and females aged 20-35 yrs were sampled from the population of Copenhagen for the three surveys (1976-1978, 1991-1993 and 2001-2004). A total of 3,285 (46% male...... index, especially >30 kg.m(-2), was associated with a lower percentage predicted FEV1 (pobesity on FEV1. The proportion of smokers declined from 60 to 38% (p

Active Video Game Exercise Training Improves the Clinical Control of Asthma in Children: Randomized Controlled Trial.

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Evelim L F D Gomes

Full Text Available The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with moderate to severe asthma.A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20 or a treadmill group (TG; n = 16. Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO, maximum exercise testing (Bruce protocol and lung function.No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p < 0.05. Although the mean energy expenditure at rest and during exercise training was similar for both groups, the maximum energy expenditure was higher in the VGG.The present findings strongly suggest that aerobic training promoted by an active video game had a positive impact on children with asthma in terms of clinical control, improvement in their exercise capacity and a reduction in pulmonary inflammation.Clinicaltrials.gov NCT01438294.

Visual, instrumental, mycological and mycotoxicological characterization of wheat inoculated with and protected against Alternaria spp.

Directory of Open Access Journals (Sweden)

Janić-Hajnal Elizabet P.

2016-01-01

Full Text Available The aim of this work was to characterize visual properties, instrumentally measured colour properties, field fungi presence and Alternaria toxins levels in wheat samples grown under conditions aimed at inhibition and stimulation of wheat infection with fungi from the Alternaria genus. Experiment was carried out on the wheat treated by fungicide and wheat inoculated by Alternaria spp., while non treated wheat was used as a control. Statistically significant difference was observed between all three treatments using visual scale. Protected wheat samples were significantly different from other samples in terms of all measured colour parameters while inoculated and control wheat samples were significantly different in terms of lightness and dominant wavelength. Identification of field fungi in the all examined wheat samples showed that the dominant mycotoxigenic fungus was Alternaria spp., followed by Fusarium spp. The content of Alternaria toxins in samples of wheat hulls and dehulled kernels point out at higher concentrations of Alternaria toxins in hulls than in dehulled kernels. [Projekat Ministarstvo nauke Republike Srbije, br. III 46001 i br. III 46005

Optimizing the position and use of omalizumab for severe persistent allergic asthma using cost-effectiveness analysis.

Science.gov (United States)

Faria, Rita; McKenna, Claire; Palmer, Stephen

2014-12-01

There has been some controversy on whether the costs of omalizumab outweigh its benefits for severe persistent allergic asthma. This study aimed to resolve the uncertainties and limitations of previous analyses and establish the cost-effectiveness of omalizumab under the list price and Patient Access Scheme (PAS) discounted price for the UK National Health Service. A decision-analytic model was developed to evaluate the long-term cost-effectiveness of omalizumab under the perspective of the National Health Service. Outcomes were expressed as quality-adjusted life-years (QALYs). Patient subgroups were defined post hoc on the basis of data collected in clinical trials: previous hospitalization, on maintenance oral corticosteroids, and three or more previous exacerbations. The incremental cost-effectiveness ratio varied from £30,109 to £57,557 per QALY gained depending on the population considered using the PAS price; incremental cost-effectiveness ratios were over a third higher using the list price. Omalizumab is likely to be cost-effective at the threshold of £30,000 per QALY gained in the severe subgroups if the improvement in health-related quality of life from omalizumab is mapped from an asthma-specific measure to the EuroQol five-dimensional questionnaire (vs. the EuroQol five-dimensional questionnaire directly collected from patients) or asthma mortality refers to death after hospitalization from asthma (vs. asthma-mortality risk in the community). Although the cost-effectiveness of omalizumab is more favorable under the PAS price, it represents good value for money only in severe subgroups and under optimistic assumptions regarding asthma mortality and improvement in health-related quality of life. For these reasons, omalizumab should be carefully targeted to ensure value for money. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Prevalência e gravidade de asma brônquica em adultos obesos com indicação de cirurgia bariátrica Prevalence and severity of asthma in obese adult candidates for bariatric surgery