Allergy in severe asthma.

Science.gov (United States)

Del Giacco, S R; Bakirtas, A; Bel, E; Custovic, A; Diamant, Z; Hamelmann, E; Heffler, E; Kalayci, Ö; Saglani, S; Sergejeva, S; Seys, S; Simpson, A; Bjermer, L

2017-02-01

It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma

NARCIS (Netherlands)

Westerhof, Guus A.; de Groot, Jantina C.; Amelink, Marijke; de Nijs, Selma B.; ten Brinke, Anneke; Weersink, Els J.; Bel, Elisabeth H.

2016-01-01

Persistent eosinophilic airway inflammation is an important driver for asthma exacerbations in non-smokers with asthma. Whether eosinophilic inflammation is also a predictor of asthma exacerbations in (ex)smokers is not known. The aim was to investigate factors associated with frequent exacerbations

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

Exacerbations of asthma during pregnancy

DEFF Research Database (Denmark)

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

2016-01-01

Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal...... that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care...... to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome....

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

A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Sleiman, Patrick; Nielsen, Kasper

2014-01-01

Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6......1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin......-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes....

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection.

Science.gov (United States)

Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

2008-05-30

Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). Our data suggest an association between acute atypical infection and a more severe AEBA.

[The Chinese experts' consensus on the evaluation and management of asthma exacerbation].

Science.gov (United States)

2018-01-01

Asthma exacerbations can do a lot of harm to the patients and consume large amounts of medical resources. This consensus is based on the domestic and foreign guidelines and literatures to standardize the evaluation and management of asthma exacerbations in China. Asthma exacerbations are characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing or chest tightness and progressive decrease in lung function, and usually require modification of treatment. Recognizing risk factors and triggering factors of asthma exacerbations is helpful for the prevention and long-term management. Evaluation of asthma exacerbations is based on symptoms, lung function, and arterial blood gas. Management is stratified according to the severity of disease. Different regimens to treat asthma exacerbations are discussed in this consensus. Glucocorticoids should be used properly. Overuse of antibiotics should be avoided. Management of life-threatening asthma is discussed separately. Special attention should be paid in some special respects, such as asthma during peri-operation period, gestation period, and childhood. Diagnosis and management of complications are also of great significance and are discussed in details.

Asthma Exacerbations and Unconventional Natural Gas Development in the Marcellus Shale

Science.gov (United States)

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

2017-01-01

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

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

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection

Directory of Open Access Journals (Sweden)

Pappalettera Maria

2008-05-01

Full Text Available Abstract Background Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA. The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. Methods We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4–8 weeks. Results Fifty-eight patients completed the study. Acute atypical infections (AAI was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 ± 104 L/min vs 276 ± 117 p = 0.02 and persisted until visit 2 (FEV1% 76.30 ± 24.54 vs FEV1% 92.91 ± 13.89, p = 0.002. Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38–13.32. Conclusion Our data suggest an association between acute atypical infection and a more severe AEBA.

Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults

DEFF Research Database (Denmark)

Bjerregaard, Asger; Laing, Ingrid A; Poulsen, Nadia

2017-01-01

BACKGROUND: In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response...... occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. METHODS: Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum...... in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo...

Determinants of low risk of asthma exacerbation during pregnancy

DEFF Research Database (Denmark)

Ali, Z; Nilas, L; Ulrik, C S

2018-01-01

of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital since 2007. Assessment of asthma control, adjustment of treatment, spirometry and measurement of exhaled nitric oxide (FENO) were performed, and baseline characteristics and exacerbation history were collected at enrolment. Determinants of low......: Clinically stable asthma at enrolment, together with no history of previous exacerbations and no prescribed controller medication, is a determinant of low risk of an asthma exacerbation during pregnancy, which may guide clinicians in individualizing surveillance of asthma during pregnancy.......BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management...

Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.

Science.gov (United States)

Meltzer, Eli O; Busse, William W; Wenzel, Sally E; Belozeroff, Vasily; Weng, Haoling H; Feng, JingYuan; Chon, Yun; Chiou, Chiun-Fang; Globe, Denise; Lin, Shao-Lee

2011-01-01

Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial. To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation. This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma. At baseline, patients had an ACQ score ≥1.5. Exacerbations were defined as requirement for systemic corticosteroids. A Cox proportional hazards model was used, with ACQ score as the time-dependent covariate. The analysis was repeated for individual components of the ACQ. Each 1-point increase in ACQ was associated with a 50% increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the following 2-week period. Evaluation of individual ACQ components also demonstrated a similar trend, though each to a lesser degree than the full composite ACQ. Although based on a retrospective analysis, with small number of exacerbations, these findings support the utility of the composite ACQ score measurement to predict risk of future exacerbation in clinical trials and clinical practice. The composite ACQ score measurement was found to be a better predictor of future risk than individual ACQ components. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Right ventricular function during acute exacerbation of severe equine asthma.

Science.gov (United States)

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.

Asthma exacerbations: risk factors for hospital readmissions.

Science.gov (United States)

Gonzalez-Barcala, F-J; Calvo-Alvarez, U; Garcia-Sanz, M-T; Garcia-Couceiro, N; Martin-Lancharro, P; Pose, A; Carreira, J-M; Moure-Gonzalez, J-D; Valdes-Cuadrado, L; Muñoz, X

2018-02-01

The aim of our study is to analyse hospital readmissions due to asthma, as well as the factors associated with their increase. We carried out a retrospective study including all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The data were gathered by two members of the research team, by reviewing the clinical records. The first hospital admission of each patient was included for this study. An early readmission (ER) was defined as that which occurred in the following 15 days after hospital discharge and late readmission (LR) to that occurring from 16 days after discharge. This study included 2166 hospital admissions and 1316 patients, with a mean age of 62.6 years. Of the 1316 patients analysed, 36 (2.7%) had one ER and 313 (23.8%) one LR. The only factor independently associated with a higher probability of an ER was poor lung function. A higher probability of LR was associated with a greater severity of the asthma (OR: 17.8, for severe asthma versus intermittent asthma), to have had any hospital admission in the previous year (OR: 3.5) and the use of a combination of ICS-LABA as maintenance treatment. About 25% of the patients in our area admitted to hospital due to asthma exacerbation had repeat episodes of hospitalisation.

Detection of rhinovirus-associated asthma exacerbations using ...

African Journals Online (AJOL)

Ehab

between common viral respiratory infections and asthma exacerbations. Respiratory viruses have ... positive Rhinovirus RT-PCR test and 4 (50%) of the HRV positive patients were of the ... reaction volume was 50 µl, and the reaction mixture contained 0.9 ..... significance in asthma exacerbation and airway remodeling.

Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

Directory of Open Access Journals (Sweden)

Alun L Edwards

1996-01-01

Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

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.

CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids

DEFF Research Database (Denmark)

Dahlin, Amber; Denny, Joshua; Roden, Dan M

2015-01-01

Inhaled corticosteroids (ICS) are the most effective controller medications for asthma, and variability in ICS response is associated with genetic variation. Despite ICS treatment, some patients with poor asthma control experience severe asthma exacerbations, defined as a hospitalization or emerg...

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.

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)

The impact of asthma medication guidelines on asthma controller use and on asthma exacerbation rates comparing 1997-1998 and 2004-2005.

Science.gov (United States)

Rank, Matthew A; Liesinger, Juliette T; Ziegenfuss, Jeanette Y; Branda, Megan E; Lim, Kaiser G; Yawn, Barbara P; Shah, Nilay D

2012-01-01

The relationship between asthma controller medication use and exacerbation rates over time is unclear at the population level. To estimate the change in asthma controller medication use between 2 time periods as measured by the controller-to-total asthma medication ratio and its association with changes in asthma exacerbation rates between 1997-1998 and 2004-2005. The study design was a cross-sectional population-level comparison between individuals from 1997-1998 and 2004-2005. Study participants were individuals aged 5 to 56 years identified as having asthma in the Medical Expenditure Panel Survey (MEPS). The main outcome measures were a controller-to-total asthma medication ratio greater than 0.5 and asthma exacerbation rates (dispensing of systemic corticosteroid or emergency department visit/hospitalization for asthma) in 1997-1998 compared with 2004-2005. The proportion of individuals with a controller-to-total asthma medication ratio greater than 0.5, when adjusted for other demographic factors, has improved by 16.1% (95% CI: 10.8%, 21.3%) for all individuals from 1997-1998 to 2004-2005. Annual asthma exacerbation rates did not change significantly in any group from 1997-1998 to 2004-2005 (0.27/year to 0.23/year). African American and Hispanic individuals with asthma had higher asthma exacerbation rates and a lower proportion with a controller-to-total asthma medication ratio greater than 0.5 than whites in both 1997-1998 and 2004-2005; however, these differences were not statistically significant. An increase in asthma controller-to-total medication ratio in a sample reflective of the US population was not associated with a decreased asthma exacerbation rate comparing 1997-1998 and 2004-2005. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study

DEFF Research Database (Denmark)

Vedel-Krogh, Signe; Nielsen, Sune Fallgaard; Lange, Peter

2017-01-01

BACKGROUND: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated...... with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS: From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during...... with blood eosinophil counts >0.29 × 10(9)/L (highest tertile) vs individuals with blood eosinophil counts

Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

International Nuclear Information System (INIS)

Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

2012-01-01

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

Energy Technology Data Exchange (ETDEWEB)

Schneider, Brent C. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); Constant, Stephanie L. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Patierno, Steven R. [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); GW Cancer Institute, The George Washington University, Washington, DC 20037 (United States); Jurjus, Rosalyn A. [Department of Anatomy and Regenerative Biology, The George Washington University, Washington, DC 20037 (United States); Ceryak, Susan M., E-mail: phmsmc@gwumc.edu [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States)

2012-02-15

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

Predicting an asthma exacerbation in children 2 to 5 years of age

DEFF Research Database (Denmark)

Swern, A.S.; Tozzi, C.A.; Knorr, B.

2008-01-01

BACKGROUND: Asthma exacerbations in young children are prevalent. Identification of symptoms or other factors that are precursors of asthma exacerbations would be useful for early treatment and prevention. OBJECTIVES: To determine whether diary symptoms and beta2-agonist use before an exacerbation...... could predict an asthma exacerbation in children 2 to 5 years of age. METHODS: Post hoc analyses were conducted on data collected in a study of 689 patients 2 to 5 years of age with asthma symptoms, randomly assigned to montelukast, 4 mg, or placebo daily for 12 weeks. During the study, 196 patients had...... of an exacerbation. These methods predicted 149 (66.8%) of the exacerbations with a very low false-positive rate of 14.2%. CONCLUSIONS: No individual symptom was predictive of an imminent asthma exacerbation, but a combination of increased daytime cough, daytime wheeze, and nighttime beta2-agonist use 1 day before...

Fine particulate pollution and asthma exacerbations.

Science.gov (United States)

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

2017-12-19

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

Postpartum airway responsiveness and exacerbation of asthma during pregnancy

DEFF Research Database (Denmark)

Ali, Zarqa; Nilas, Lisbeth; Ulrik, Charlotte Suppli

2017-01-01

, diffusing capacity for carbon monoxide, bronchial responsiveness to inhaled mannitol, and inflammatory characteristics in induced sputum. Obtained data were analyzed in relation to exacerbation status during pregnancy. The PD15 is defined as the cumulative administered dose causing a 15% decline in forced......BACKGROUND: Airway responsiveness and inflammation are associated with the clinical manifestations of asthma and the response to pharmacological therapy. OBJECTIVE: To investigate if airway responsiveness and inflammatory characteristics are related to asthma exacerbations during pregnancy....... MATERIALS AND METHODS: In women with asthma who were prescribed controller medication and monitored closely during pregnancy, the risk of exacerbations was analyzed in relation to postpartum measures of fractional exhaled nitric oxide (FENO), skin prick test reactivity, static and dynamic lung volumes...

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

Directory of Open Access Journals (Sweden)

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

Predicting asthma exacerbations using artificial intelligence.

Science.gov (United States)

Finkelstein, Joseph; Wood, Jeffrey

2013-01-01

Modern telemonitoring systems identify a serious patient deterioration when it already occurred. It would be much more beneficial if the upcoming clinical deterioration were identified ahead of time even before a patient actually experiences it. The goal of this study was to assess artificial intelligence approaches which potentially can be used in telemonitoring systems for advance prediction of changes in disease severity before they actually occur. The study dataset was based on daily self-reports submitted by 26 adult asthma patients during home telemonitoring consisting of 7001 records. Two classification algorithms were employed for building predictive models: naïve Bayesian classifier and support vector machines. Using a 7-day window, a support vector machine was able to predict asthma exacerbation to occur on the day 8 with the accuracy of 0.80, sensitivity of 0.84 and specificity of 0.80. Our study showed that methods of artificial intelligence have significant potential in developing individualized decision support for chronic disease telemonitoring systems.

Proximity to Industrial Food Animal Production and Asthma Exacerbations in Pennsylvania, 2005-2012.

Science.gov (United States)

Rasmussen, Sara G; Casey, Joan A; Bandeen-Roche, Karen; Schwartz, Brian S

2017-03-31

The research on industrial food animal production (IFAP) and asthma exacerbations in the United States has relied on small sample sizes and/or self-reported outcomes. We assessed associations of proximity to large-scale and densely stocked swine and dairy/veal IFAP with three types of asthma exacerbations: hospitalizations, emergency encounters, and oral corticosteroid (OCS) medication orders from Geisinger Clinic in Pennsylvania. We used a diagnosis code ( International Classification of Diseases, 9th Revision, Clinical Modification code 493.x) and medication orders from electronic health records to identify these exacerbations among asthma patients ( n = 35,269) from 2005-2012. We compared residential proximity to swine or dairy/veal IFAP (dichotomized as <3 miles (4.8 km) or ≥3 miles) among asthma patients with and without exacerbations and estimated odds ratios using multilevel logistic regression. In adjusted models, proximity to IFAP was associated (odds ratio (95% confidence interval)) with OCS orders (1.11 (1.04-1.19)) and hospitalizations (1.29 (1.15-1.46)), but not emergency encounters (1.12 (0.91-1.37)). This study contributes to growing evidence that IFAP may impact health, in this case clinically-documented asthma exacerbations. No prior study has evaluated the association of IFAP and clinically-documented asthma exacerbations in the United States.

Risk Factors for Asthma Exacerbation and Treatment Failure in Adults and Adolescents with Well-Controlled Asthma during Continuation and Step Down Therapy.

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DiMango, Emily; Rogers, Linda; Reibman, Joan; Gerald, Lynn B; Brown, Mark; Sugar, Elizabeth A; Henderson, Robert; Holbrook, Janet T

2018-06-04

Although national and international guidelines recommend reduction of asthma controller therapy or 'step-down" therapy in patients with well controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. Characteristics associated with subsequent exacerbations during step-down therapy have not been well defined. The effect of environmental tobacco smoke (ETS) exposure on risk of treatment failure during asthma step down therapy has not been reported. To identify baseline characteristics associated with treatment failure and asthma exacerbation during maintenance and guideline-based step-down therapy. The present analysis uses data collected from a completed randomized controlled trial of optimal step-down therapy in patients with well controlled asthma taking moderate dose combination inhaled corticosteroids/long acting beta agonists. Participants were 12 years or older with physician diagnosed asthma and were enrolled between December 2011 and May 2014. An Emergency Room visit in the previous year was predictive of a subsequent treatment failure (HR 1.53 (1.06, 2.21 CI). For every 10% increase in baseline forced expiratory volume in one second percent predicted, the hazard for treatment failure was reduced by 14% (95% CI: 0.74-0.99). There was no difference in risk of treatment failure between adults and children, nor did duration of asthma increase risk of treatment failure. Age of asthma onset was not associated with increased risk of treatment failure. Unexpected emergency room visit in the previous year was the only risk factor significantly associated with subsequent asthma exacerbations requiring systemic corticosteroids. Time to treatment failure or exacerbation did not differ in participants with and without self-report of ETS exposure. The present findings can help clinicians identify patients more likely to develop treatment failures and exacerbations and who may therefore

P2X7-Regulated Protection from Exacerbations and Loss of Control Is Independent of Asthma Maintenance Therapy

Science.gov (United States)

Manthei, David M.; Seibold, Max A.; Ahn, Kwangmi; Bleecker, Eugene; Boushey, Homer A.; Calhoun, William J.; Castro, Mario; Chinchili, Vernon M.; Fahy, John V.; Hawkins, Greg A.; Icitovic, Nicolina; Israel, Elliot; Jarjour, Nizar N.; King, Tonya; Kraft, Monica; Lazarus, Stephen C.; Lehman, Erik; Martin, Richard J.; Meyers, Deborah A.; Peters, Stephen P.; Sheerar, Dagna; Shi, Lei; Sutherland, E. Rand; Szefler, Stanley J.; Wechsler, Michael E.; Sorkness, Christine A.; Lemanske, Robert F.

2013-01-01

Rationale: The function of the P2X7 nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied. Objectives: To evaluate the association between P2X7, asthma exacerbations, and incomplete symptom control in a more diverse population. Methods: A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X7 pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently. Measurements and Main Results: A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting β2-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2–6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1–9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV1 reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase. Conclusions: P2X7 pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy. PMID:23144325

Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma.

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Esquivel, Ann; Busse, William W; Calatroni, Agustin; Togias, Alkis G; Grindle, Kristine G; Bochkov, Yury A; Gruchalla, Rebecca S; Kattan, Meyer; Kercsmar, Carolyn M; Khurana Hershey, G; Kim, Haejin; Lebeau, Petra; Liu, Andrew H; Szefler, Stanley J; Teach, Stephen J; West, Joseph B; Wildfire, Jeremy; Pongracic, Jaqueline A; Gern, James E

2017-10-15

Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal. To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma. In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression. RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84). In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).

Managing problematic severe asthma: beyond the guidelines.

Science.gov (United States)

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.

Burden of Obesity on Pediatric Inpatients with Acute Asthma Exacerbation in the United States.

Science.gov (United States)

Okubo, Yusuke; Nochioka, Kotaro; Hataya, Hiroshi; Sakakibara, Hiroshi; Terakawa, Toshiro; Testa, Marcia

Obesity and asthma are common health problems in the United States. The objective of this study was to evaluate the clinical and economic burdens of obesity on hospitalized children with acute asthma exacerbation in 2012. Hospital discharge records of patients aged 2 to 18 years with a diagnosis of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data were compiled by the Agency for Healthcare Research and Quality. The discharge records were weighted to estimate the number of hospitalizations because of asthma exacerbations in the United States. To classify whether the patient was obese or not, we used the International Classification of Diseases, Ninth Revision, Clinical Modification code 278.0x. We compared the odds of using noninvasive or invasive mechanical ventilation, mean total charges for inpatient service, and length of hospital stay between obese and nonobese patients. A total of 74,338 patient discharges were extracted. Of these, 3,494 discharges were excluded because of chronic medical conditions. Using discharge weight variables, we estimated a total of 100,157 hospitalizations with asthma exacerbations among children aged between 2 and 18 years in 2012. Obesity was significantly associated with higher odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared with nonobesity. These findings suggest that obesity is a significant risk factor of severe asthma exacerbation that requires mechanical ventilation, and obesity is an economically complicating factor. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effects of seasonal smog on asthma and COPD exacerbations requiring emergency visits in Chiang Mai, Thailand.

Science.gov (United States)

Pothirat, Chaicharn; Tosukhowong, Apiwat; Chaiwong, Warawut; Liwsrisakun, Chalerm; Inchai, Juthamas

2016-12-01

Seasonal smog produces particulate matters that are less than 10 microns in diameter (PM₁₀), which are known to have several impacts on the respiratory system. This study was to determine the association of an increased PM10 level due to seasonal smog in Chiang Mai and emergency visits for asthma and chronic obstructive pulmonary disease (COPD) exacerbations. A retrospective cross-sectional study was conducted between the months of January and March from 2006 until 2009. The association of an increased PM₁₀ level and the daily number of asthma and COPD exacerbations were analyzed using a generalized linear model; a Poisson regression model was fit to the number of daily emergency visits using predictor variables: lags of PM10, day of the week, and time. There were a total of 917 emergency visits for acute exacerbations of asthma and COPD, with a median of 2 visits per day (range 0-10). The median PM₁₀ level during the same interval was 64.5 microgram per cubic meter (μg/m3) (16-304). For every 10 μg/m3 rise in PM10 concentration, there was a lag time of 6 days for asthma exacerbations [Adjusted relative risk (RR)=1.020; 95% confident interval (CI), 1.001-1.040; (p=0.014)], 7 days for COPD exacerbations [RR=1.030; 95%CI, 1.010-1.050 (p=0.024)] and 7 days for all exacerbations [RR=1.030 95%CI, 1.010-1.040 (p<0.001)]. This study confirms the effect of increasing PM₁₀ concentrations from seasonal smog on asthma and COPD exacerbations. However, there was an approximately 1 week lag time between the elevated PM₁₀ levels and time to emergency visits due to disease exacerbation.

Risk factors for asthma exacerbation in patients presenting to an ...

African Journals Online (AJOL)

Conclusion: Lack of corticosteroid use and upper respiratory tract infections are ... Key words: Asthma, asthma exacerbations, risk factors, corticosteroids ..... recall bias may be a limitation. ... obstructive picture on spirometry were included as.

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

DEFF Research Database (Denmark)

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

2005-01-01

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parall...

Rapid vs Maintenance Vitamin D Supplementation in Deficient Children With Asthma to Prevent Exacerbations.

Science.gov (United States)

Alansari, Khalid; Davidson, Bruce L; Yousef, Khalid Ibrahim; Mohamed, Abdel Nasser H; Alattar, Imad

2017-09-01

Whether vitamin D reduces clinically important exacerbations of childhood asthma remains uncertain. We compared rapid to maintenance vitamin D repletion analyzed by baseline vitamin D level. Children presenting to the ED with moderate-to-severe asthma exacerbations and vitamin D levels ≤ 25 ng/mL underwent masked randomization, and then open dosing to either IM+oral (the latter daily) therapy or daily oral-only therapy, and were followed for 12 months. The primary outcome was patient-initiated unplanned visits for asthma exacerbations, examined two ways: cumulative proportions with an exacerbation, and average exacerbation frequency. As this was a nutrient study, we analyzed treatment groups by quartile of baseline vitamin D level, collecting repeat levels and clinical observations at 3, 6, 9, and 12 months after enrollment. One hundred and sixteen patients in the IM+oral cohort vs 115 in the oral-only cohort had similar mean (SD) baseline levels: 15.1 (5.4) vs 15.8 (5.2) ng/mL (range, 3-25 ng/mL). There was no difference in the primary outcome over the entire 12-month observation period. However, rapid IM+oral supplementation significantly reduced unplanned visits for asthma exacerbations for children with baseline levels of 3 to 11 ng/mL during the initial 3 months: the relative exacerbation rate for the IM+oral cohort compared with the oral-only cohort at 3 months was 0.48 (95% CI, 0.28-0.89; P = .008); average exacerbation frequency per child analysis, relative rate 0.36 (95% CI, 0.13-0.87; P = .017). Otherwise, there were no significant differences between groups. Rapid compared to maintenance vitamin D supplementation for children with the lowest levels resulted in short- but not long-term reduction in asthma exacerbations. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Serum eosinophil cationic protein levels can be useful for predicting acute exacerbation of asthma

Directory of Open Access Journals (Sweden)

Mitsuhiro Kamimura

1998-01-01

Full Text Available We report on a case in which five consecutive exacerbations of asthma were monitored by following serum eosinophil cationic protein (ECP levels. The serum ECP level correlated well with each exacerbation and tended to increase even before the exacerbations of asthma became apparent. This case shows that serum levels of ECP can be useful markers of disease activity and may also be predictive markers for acute exacerbation.

Prevalence and pattern of asthma exacerbation in children seen at ...

African Journals Online (AJOL)

2016-01-15

Jan 15, 2016 ... asthma. Aim: To determine the prevalence and pattern of acute exacerbation of asthma in ... cost to health care systems and seriously diminish the quality of life of .... also from USA, 2% of all outpatient visits and 2.3% of.

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

DEFF Research Database (Denmark)

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

2011-01-01

and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most...... and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02505.x. ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections...

Effectiveness of school-based family asthma educational programs in quality of life and asthma exacerbations in asthmatic children aged five to 18: a systematic review.

Science.gov (United States)

Walter, Helen; Sadeque-Iqbal, Fatema; Ulysse, Rose; Castillo, Doreen; Fitzpatrick, Aileen; Singleton, Joanne

2016-11-01

Asthma is a common, chronic, non-communicable respiratory disease that affects millions of children worldwide. Asthma exacerbations can range from mild to severe and can have an unfavorable impact on the quality of life of children and their caregivers. Asthma exacerbations often result in absenteeism from school or work, activity intolerance and emergency hospital visits. One strategy to address this health issue in an attempt to improve health outcomes is school-based asthma educational programs. A review of the literature revealed that previous systematic reviews have examined similar topics on the effectiveness of school-based asthma educational programs that have included collaborative efforts between parents and schools. No systematic reviews were found that examined the effectiveness of school-based asthma educational programs that exclusively included children and their caregivers. Research has not been systematically reviewed to determine the effectiveness of a school-based asthma educational program within a familial context. To identify the best available evidence on the effectiveness of school-based family asthma educational programs that exclusively included both children and caregivers on the quality of life and number of asthma exacerbations of children aged five to 18 years with a clinical diagnosis of asthma. Children aged five to 18 years of any gender, race or ethnicity with a clinical diagnosis of asthma and their caregivers. School-based family asthma educational programs. Randomized controlled trials. Quality of life and the number of asthma exacerbations measured by either missed days from school or work, and/or physical activity intolerance, and/or emergency hospital visits. The search strategy aimed to find both published and unpublished studies from inception of the database to August 21, 2015. Quantitative papers selected for retrieval were assessed by two independent reviewers for methodological validity before inclusion in the review

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

Directory of Open Access Journals (Sweden)

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.

The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma

Directory of Open Access Journals (Sweden)

Tomomitsu Miyasaka

2018-01-01

Full Text Available Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a “neuropsychiatry phenotype” in asthma.

Risk factors for asthma exacerbation in patients presenting to an ...

African Journals Online (AJOL)

Background: Asthma exacerbations are caused by a variety of risk factors. Reducing exposure to these risk factors improves the control of asthma and reduces medication needs. Knowledge of the particular risk factors is essential in formulating controlling and treatment protocols. This study set out to determine the risk ...

Exacerbations in adults with asthma: A systematic review and external validation of prediction models

NARCIS (Netherlands)

Loymans, Rik J. B.; Debray, Thomas P. A.; Honkoop, Persijn J.; Termeer, Evelien H.; Snoeck-Stroband, Jiska B.; Schermer, Tjard R. J.; Assendelft, Willem J. J.; Timp, Merel; Chung, Kian Fan; Sousa, Ana R.; Sont, Jaap K.; Sterk, Peter J.; Reddel, Helen K.; ter Riet, Gerben

2018-01-01

Several prediction models assessing future risk of exacerbations in adult patients with asthma have been published. Applicability of these models is uncertain because their predictive performance has often not been assessed beyond the population in which they were derived. This study aimed to

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.

Can a school-based hand hygiene program reduce asthma exacerbations among elementary school children?

Science.gov (United States)

Gerald, Joe K.; Zhang, Bin; McClure, Leslie A.; Bailey, William C.; Harrington, Kathy F.

2012-01-01

Background Viral upper respiratory infections have been implicated as a major cause of asthma exacerbations among school age children. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections but, effective hand washing practices are difficult to establish in schools. Objectives This randomized controlled trial evaluated whether a standardized regimen of hand washing plus alcohol-based hand sanitizer could reduce asthma exacerbations more than schools’ usual hand hygiene practices. Methods This was a two year, community-based, randomized controlled crossover trial. Schools were randomized to usual care then intervention (Sequence 1) or intervention then usual care (Sequence 2). Intervention schools were provided with alcohol-based hand sanitizer, hand soap, and hand hygiene education. The primary outcome was the proportion of students experiencing an asthma exacerbation each month. Generalized estimating equations were used to model the difference in the marginal rate of exacerbations between sequences while controlling for individual demographic factors and the correlation within each student and between students within each school. Results 527 students with asthma were enrolled among 31 schools. The hand hygiene intervention did not reduce the number of asthma exacerbations as compared to the schools’ usual hand hygiene practices (p=0.132). There was a strong temporal trend as both sequences experienced fewer exacerbations during Year 2 as compared to Year 1 (phand hygiene behaviors and resources in usual care schools. Therefore, these results should be viewed cautiously. PMID:23069487

RItA: The Italian severe/uncontrolled asthma registry.

Science.gov (United States)

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.

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.

Noninvasive ventilation for acute exacerbations of asthma: A systematic review of the literature.

Science.gov (United States)

Green, Elyce; Jain, Paras; Bernoth, Maree

2017-11-01

Asthma is a chronic disease characterised by reversible airway obstruction caused by bronchospasm, mucous and oedema. People with asthma commonly experience acute exacerbations of their disease requiring hospitalisation and subsequent utilisation of economic and healthcare resources. Noninvasive ventilation has been suggested as a treatment for acute exacerbations of asthma due to its ability to provide airway stenting, optimal oxygen delivery and decreased work of breathing. This paper is a systematic review of the available published research focused on the use of noninvasive ventilation for the treatment of acute exacerbations of asthma to determine if this treatment provides better outcomes for patients compared to standard medical therapy. Database searches were conducted using EBSCOhost, MEDLINE and PubMed. Search terms used were combinations of 'noninvasive ventilation', 'BiPAP', 'CPAP', 'wheez*' and 'asthma'. Articles were included if they were research papers focused on adult patients with asthma and a treatment of noninvasive ventilation, and were published in full text in English. Included articles were reviewed using the National Health and Medical Research Council (Australia) evidence hierarchy and quality appraisal tools. There were 492 articles identified from the database searches. After application of inclusion/exclusion criteria 13 articles were included in the systematic review. Studies varied significantly in design, endpoints and outcomes. There was a trend in better outcomes for patients with acute asthma who were treated with noninvasive ventilation compared to standard medical therapy, however, the variability of the studies meant that no conclusive recommendations could be made. More research is required before noninvasive ventilation can be conclusively recommended for the treatment of acute exacerbations of asthma. Copyright © 2017 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status

DEFF Research Database (Denmark)

Kerstjens, Huib A M; Moroni-Zentgraf, Petra; Tashkin, Donald P

2016-01-01

performed in parallel in patients with severe symptomatic asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, time to first severe exacerbation, time to first episode of asthma worsening, and seven-question Asthma Control Questionnaire responder rate were......BACKGROUND: Many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic...... asthma. OBJECTIVE: To determine whether the efficacy of tiotropium add-on therapy is dependent on patients' baseline characteristics. METHODS: Two randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat(®) 5 μg add-on to ICS plus a LABA were...

Hourly differences in air pollution on the risk of asthma exacerbation

International Nuclear Information System (INIS)

Kim, Jayeun; Kim, Ho; Kweon, Jung

2015-01-01

We investigated the association between hourly differences in air pollution and asthma exacerbation in Korea using asthma-related emergency department data and verified seasonality and demographic modifiers with an hourly temporal resolution. We applied time-stratified case-crossover adjusted for weather and influenza; the lag was stratified as 1–6, 7–12, 13–18, 19–24, 25–48, and49–72 h. Odds ratios (95% confidence interval) per interquartile range increase were 1.05 (1.00–1.11) after 1–6 h for PM 10–2.5 and 1.10 (1.04–1.16) after 19–24 h for O 3 . Effect size was 1.14 (1.06–1.22) at a 1–6 h lag in spring for PM 10–2.5 , and 1.25 (1.03–1.51) at a 25–48 h lag in winter for O 3 . O 3 effects were age- and low socio-economic status-modified at a 7–12 h lag [1.25 (1.04–1.51)]. Increased PM 10–2.5 and O 3 increased the risk of asthma exacerbation; the effect of PM 10–2.5 was most immediate. - Highlights: • We examined hourly differences in air pollution levels and asthma exacerbation risk. • Increased PM 10–2.5 and O 3 levels increased the risk of asthma exacerbation. • The effect of PM 10–2.5 was more immediate than other pollutants. • The effect of O 3 was modified by age and socio-economic status. • O 3 has a longer lag effect, particularly in winter. - Hourly increments of PM 10–2.5 and O 3 induced an increased risk of asthma-related emergency room visits, and the effect of PM 10–2.5 was most immediate

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...

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.

Response to omalizumab in patients with severe allergic asthma

DEFF Research Database (Denmark)

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...

IL-33 promotes the migration and proliferation of circulating fibrocytes from patients with allergen-exacerbated asthma

International Nuclear Information System (INIS)

Bianchetti, Lorenza; Marini, Maurizio A.; Isgrò, Mirko; Bellini, Alberto; Schmidt, Matthias; Mattoli, Sabrina

2012-01-01

Highlights: ► IL-33 is considered a new therapeutic target for reducing inflammation in asthma. ► This study shows that IL-33 is a potent chemoattractant for fibrocytes in asthma. ► IL-33 also promotes fibrocyte proliferation without reducing collagen production. ► The study uncovers a novel non-inflammatory, profibrotic function of IL-33. -- Abstract: The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthma by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in 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.

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.

IL-33 promotes the migration and proliferation of circulating fibrocytes from patients with allergen-exacerbated asthma

Energy Technology Data Exchange (ETDEWEB)

Bianchetti, Lorenza, E-mail: lbianchetti@avail-research.com [Avail Biomedical Research Institute, Basel (Switzerland); Laboratory of Cytopathology and Cytogenetics, Italian ABR Operative Unit, Milan (Italy); Marini, Maurizio A., E-mail: mam.marini@yahoo.com [Multispecialty Outpatient Clinic and Diagnostic Center, Milan (Italy); Isgro, Mirko, E-mail: m.isgro@vtxmail.ch [Avail Biomedical Research Institute, Basel (Switzerland); Laboratory of Cytopathology and Cytogenetics, Italian ABR Operative Unit, Milan (Italy); Bellini, Alberto, E-mail: abellini@avail-research.com [Avail Biomedical Research Institute, Basel (Switzerland); Schmidt, Matthias, E-mail: mschmidt@avail-research.com [Avail Biomedical Research Institute, Basel (Switzerland); Mattoli, Sabrina, E-mail: smattoli@avail-research.com [Avail Biomedical Research Institute, Basel (Switzerland)

2012-09-14

Highlights: Black-Right-Pointing-Pointer IL-33 is considered a new therapeutic target for reducing inflammation in asthma. Black-Right-Pointing-Pointer This study shows that IL-33 is a potent chemoattractant for fibrocytes in asthma. Black-Right-Pointing-Pointer IL-33 also promotes fibrocyte proliferation without reducing collagen production. Black-Right-Pointing-Pointer The study uncovers a novel non-inflammatory, profibrotic function of IL-33. -- Abstract: The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthma by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in asthma.

Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

Science.gov (United States)

Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

2011-01-01

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

Asthma in inner city children: recent insights: United States.

Science.gov (United States)

Dutmer, Cullen M; Kim, Haejin; Searing, Daniel A; Zoratti, Edward M; Liu, Andrew H

2018-04-01

Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016-2017) advances in the understanding of asthma in US inner city children. Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.

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

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

Directory of Open Access Journals (Sweden)

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.

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.

Severe angina pectoris in asthma attack: a case report.

Science.gov (United States)

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.

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

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

Directory of Open Access Journals (Sweden)

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

[Role of serum S1P levels during asthma attack in the evaluation of asthma severity].

Science.gov (United States)

Zhao, Yunwei; Xu, Yiqin; Li, Shuang; Wei, Yu; Wang, Chunling

2017-09-01

To observe the changes of serum sphingosine-1-phosphate (S1P) level in asthmatic patients with different severity of bronchial asthma, and to explore the evaluation value of S1P on the severity of asthma. A prospective observational study was conducted. Fifty-two patients with asthma admitted to Department of Respiratory Medicine of the First Affiliated Hospital of Jiamusi University from November 2015 to January 2017 were enrolled. According to the severity of the disease, the patients were divided into mild, moderate and severe groups. In the same period, 25 healthy subjects were served as healthy control group. All the subjects got the peripheral venous blood collection in the morning fasting, the level of serum S1P was determined by enzyme linked immunosorbent assay (ELISA), the peripheral blood eosinophil (EOS) was counted, and the pulmonary function test was performed. The correlation among the parameters was analyzed by Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted, and the value of serum S1P on evaluating the severity of asthma was analyzed. Fifty-two asthma patients were enrolled, including 17 patients of the mild, 19 of the moderate, and 16 of the severe. Compared with the healthy control group, serum S1P level and peripheral blood EOS in different degree asthma groups were significantly increased, and forced expiratory volume in 1 second (FEV1) was decreased significantly; and with asthma exacerbations, serum S1P levels and peripheral blood EOS were gradually increased [mild, moderate and severe S1P (nmol/L) were 1 537.0±120.3, 1 980.7±149.5, 2 202.2±117.2 (F = 274.624, P = 0.001); EOS (×10 9 /L) were 0.13±0.06, 0.20±0.07, 0.37±0.14 , respectively (F = 44.093, P = 0.001)], and FEV1 was decreased gradually [mild, moderate and severe were 0.89±0.05, 0.63±0.06, 0.42±0.10, respectively (F = 159.756, P = 0.001)]. Correlation analysis showed that there were significant positive correlations between serum S1P

Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review.

Science.gov (United States)

Zheng, Xue-Yan; Xu, Yan-Jun; Guan, Wei-Jie; Lin, Li-Feng

2018-04-01

Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations.

Advances in asthma 2015: Across the lifespan.

Science.gov (United States)

Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2016-08-01

In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

Science.gov (United States)

Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

2017-11-01

Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

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

Science.gov (United States)

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

Linking Asthma Exacerbation and Air Pollution Data: A Step Toward Public Health and Environmental Data Integration

Science.gov (United States)

Faruque, Fazlay; Finley, Richard; Marshall, Gailen; Brackin, Bruce; Li, Hui; Williams, Worth; Al-Hamdan, Mohammad; Luvall, Jeffrey; Rickman, Doug; Crosson, Bill

2006-01-01

Studies have shown that reducing exposure to triggers such as air pollutants can reduce symptoms and the need for medication in asthma patients. However, systems that track asthma are generally not integrated with those that track environmental hazards related to asthma. Tlvs lack of integration hinders public health awareness and responsiveness to these environmental triggers. The current study is a collaboration between health and environmental professionals to utilize NASA-derived environmental data to develop a decision support system (DSS) for asthma prediction, surveillance, and intervention. The investigators link asthma morbidity data from the University of Mississippi Medical Center (UMMC) and Mississippi Department of Health (MDH) with air quality data from the Mississippi Department of Environmental Quality (MDEQ) and remote sensing data from NASA. Daily ambient environmental hazard data for PM2.5 and ozone are obtained from the MDEQ air quality monitoring locations and are combined with remotely sensed data from NASA to develop a state-wide spatial and time series profile of environmental air quality. These data are then used to study the correlation of these measures of air quality variation with the asthma exacerbation incidence throughout the state over time. The goal is to utilize these readily available measures to allow real-time risk assessment for asthma exacerbations. GeoMedStat, a DSS previously developed for biosurveillance, will integrate these measures to monitor, analyze and report the real-time risk assessment for asthma exacerbation throughout the state.

Asthma and obesity

DEFF Research Database (Denmark)

Ulrik, Charlotte S

2016-01-01

PURPOSE OF REVIEW: Obesity has significant negative impact on asthma control and risk of exacerbations. The purpose of this review is to discuss recent studies evaluating the effects of weight reduction on asthma control in obese adults. RECENT FINDINGS: Clinical studies have shown that weight...... reduction in obese patients is associated with improvements in symptoms, use of controller medication, and asthma-related quality of life together with a reduction in the risk for severe exacerbations. Furthermore, several studies have also revealed improvements in lung function and airway responsiveness...... reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Weight reduction should be a cornerstone in the management of obese patients with asthma....

Effect of long-acting beta2 agonists on exacerbation rates of asthma in children

DEFF Research Database (Denmark)

Bisgaard, Hans

2003-01-01

The purpose of this analysis was to examine the effect of long-acting beta(2)-adrenoceptor agonists (LABAs) on the asthma exacerbation rate in pediatric patients. Randomized controlled trials (RCT) that included the use of LABAs to treat symptoms of pediatric asthma in children on inhaled cortico...

A review of omalizumab for the management of severe asthma

Directory of Open Access Journals (Sweden)

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

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

NARCIS (Netherlands)

Loymans, Rik J. B.; Gemperli, Armin; Cohen, Judith; Rubinstein, Sidney M.; Sterk, Peter J.; Reddel, Helen K.; Jüni, Peter; ter Riet, Gerben

2014-01-01

To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Systematic review and network meta-analysis using Bayesian statistics. Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate.

Increased ultrafine particles and carbon monoxide concentrations are associated with asthma exacerbation among urban children

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Evans, Kristin A.; Halterman, Jill S.; Hopke, Philip K.; Fagnano, Maria; Rich, David Q.

2014-01-01

Objectives Increased air pollutant concentrations have been linked to several asthma-related outcomes in children, including respiratory symptoms, medication use, and hospital visits. However, few studies have examined effects of ultrafine particles in a pediatric population. Our primary objective was to examine the effects of ambient concentrations of ultrafine particles on asthma exacerbation among urban children and determine whether consistent treatment with inhaled corticosteroids could attenuate these effects. We also explored the relationship between asthma exacerbation and ambient concentrations of accumulation mode particles, fine particles (≤ 2.5 micrograms [μm]; PM2.5), carbon monoxide, sulfur dioxide, and ozone. We hypothesized that increased 1 to 7 day concentrations of ultrafine particles and other pollutants would be associated with increases in the relative odds of an asthma exacerbation, but that this increase in risk would be attenuated among children receiving school-based corticosteroid therapy. Methods We conducted a pilot study using data from 3–10 year-old children participating in the School-Based Asthma Therapy trial. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the relative odds of a pediatric asthma visit treated with prednisone (n=96 visits among 74 children) associated with increased pollutant concentrations in the previous 7 days. We re-ran these analyses separately for children receiving medications through the school-based intervention and children in a usual care control group. Results Interquartile range increases in ultrafine particles and carbon monoxide concentrations in the previous 7 days were associated with increases in the relative odds of a pediatric asthma visit, with the largest increases observed for 4-day mean ultrafine particles (interquartile range=2088 p/cm3; OR=1.27; 95% CI=0.90–1.79) and 7-day mean carbon monoxide (interquartile range=0.17 ppm; OR=1.63; 95

Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma.

Science.gov (United States)

Kato, Masahiko; Suzuki, Kazuo; Yamada, Yoshiyuki; Maruyama, Kenichi; Hayashi, Yasuhide; Mochizuki, Hiroyuki

2015-09-01

Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged asthma in patients childhood asthma. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

Science.gov (United States)

Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang; Lynch, David A; Strand, Matthew J; van Beek, Edwin J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

2018-02-01

Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. ClinicalTrials.gov; No. NCT00608764; https

Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma.

Science.gov (United States)

Youroukova, Vania M; Dimitrova, Denitsa G; Valerieva, Anna D; Lesichkova, Spaska S; Velikova, Tsvetelina V; Ivanova-Todorova, Ekaterina I; Tumangelova-Yuzeir, Kalina D

2017-06-01

Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms. To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters. Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included. All underwent clinical assessment, anthropometric measurements, skin prick testing, standard spirometry and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum total IgE and periostin levels were determined. Two-step cluster approach, hierarchical clustering method and k-mean analysis were used for identification of the clusters. We have identified four clusters. Cluster 1 (n=14) - late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) - late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity, eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma. Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment.

Science.gov (United States)

Turner, Steve; Francis, Ben; Vijverberg, Susanne; Pino-Yanes, Maria; Maitland-van der Zee, Anke H; Basu, Kaninika; Bignell, Lauren; Mukhopadhyay, Somnath; Tavendale, Roger; Palmer, Colin; Hawcutt, Daniel; Pirmohamed, Munir; Burchard, Esteban G; Lipworth, Brian

2016-07-01

The Gly-to-Arg substitution at the 16 position (rs1042713) in the β2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of β2-receptors. We sought to undertake a meta-analysis to test the hypothesis that there is an interaction between the A allele of rs1042713 (Arg16 amino acid) and long-acting β-agonist (LABA) exposure for asthma exacerbations in children. Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). A history of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined. Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P = .0021) for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n = 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n = 354) or ICSs plus LABAs plus LTRAs (n = 569). The use of a LABA but not an LTRA as an "add-on controller" is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood

DEFF Research Database (Denmark)

Bisgaard, Hans; Bønnelykke, Klaus; Sleiman, Patrick M A

2009-01-01

RATIONALE: An asthma predisposition locus on chromosome 17q12-q21 has recently been replicated in different ethnic groups. OBJECTIVES: To characterize the asthma and atopy phenotypes in early childhood that associate with the 17q12-21 locus. METHODS: The single nucleotide polymorphism (SNP), rs......7216389, was genotyped in 376 of 411 children from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort born to mothers with asthma together with 305 mothers and 224 fathers. Nineteen additional SNPs in the region were genotyped in the children. Investigator-diagnosed clinical...... of wheeze (hazard ratio 1.64 [1.05-2.59], P value = 0.03), asthma (hazard ratio, 1.88 [1.15-3.07], P = 0.01), and acute severe exacerbations (hazard ratio 2.66 [1.58-4.48], P value = 0.0002). The effect on wheeze and asthma was observed for early onset but not late onset of disease. The increased risk...

A review of omalizumab for the management of severe asthma.

Science.gov (United States)

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.

Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment.

Science.gov (United States)

Magnan, A; Bourdin, A; Prazma, C M; Albers, F C; Price, R G; Yancey, S W; Ortega, H

2016-09-01

We performed post hoc analyses to evaluate the effect of humanized monoclonal antibody mepolizumab in patients with severe eosinophilic asthma previously treated with omalizumab. Data were collected from two randomized double-blind, placebo-controlled studies: MENSA (NCT01691521: 32-week treatment phase) and SIRIUS (NCT01691508: 24-week treatment phase). Active treatment was 75 mg intravenous mepolizumab (MENSA) or 100 mg subcutaneous mepolizumab (MENSA, SIRIUS). Patients had evidence of eosinophilic inflammation ≥150 cells/μl (at screening) or ≥300 cells/μl (during the previous year). Primary outcomes were the rate of exacerbations (MENSA) and the percentage reduction in oral corticosteroid (OCS) dose (SIRIUS). Other outcomes included lung function (forced expiratory volume in 1 s and morning peak expiratory flow), Asthma Control Questionnaire (ACQ-5), St George's Respiratory Questionnaire (SGRQ) scores, and safety. Overall, 576 patients were included from MENSA and 135 from SIRIUS, with 13% and 33% previously receiving omalizumab, respectively. In MENSA, mepolizumab reduced the rate of exacerbations by 57% (prior omalizumab) and 47% (no prior omalizumab) vs placebo. In SIRIUS, reductions in OCS use were comparable regardless of prior omalizumab use. Despite reducing chronic OCS use, mepolizumab also resulted in similar reductions in exacerbation rate relative to placebo in both subgroups. Asthma control and quality of life improved with mepolizumab vs placebo in both studies independent of prior omalizumab use, as shown by ACQ-5 and SGRQ scores. Adverse events were also comparable irrespective of prior omalizumab use. These post hoc analyses indicate that patients with severe eosinophilic asthma respond positively to mepolizumab regardless of prior use of omalizumab. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Pneumomediastinum from a severe asthma attack.

Science.gov (United States)

Hashim, Taimoor; Chaudry, Ayesha H; Ahmad, Khurram; Imhoff, Jennifer; Khouzam, Rami

2013-07-01

Spontaneous pneumomediastinum is a rare complication of an asthma exacerbation characterized by chest pain, dyspnea, neck swelling, and subcutaneous emphysema. Although the condition is usually benign and treatment is primarily supportive, surgical intervention may be needed if the patient develops hemodynamic or respiratory failure.

Excessive gestational weight gain in first trimester is a risk factor for exacerbation of asthma during pregnancy

DEFF Research Database (Denmark)

Ali, Zarqa; Nilas, Lisbeth; Ulrik, Charlotte Suppli

2018-01-01

BACKGROUND: Acute exacerbation during pregnancy is the most important risk factor for an unfavorable outcome of pregnancy in women with asthma. OBJECTIVE: We sought to identify pregnancy-related risk factors for acute exacerbations of asthma during pregnancy. METHODS: Since 2007, all pregnant women...... referred to give birth at Hvidovre Hospital, Denmark, have been offered participation in the prospective Management of Asthma during Pregnancy (MAP) program. Women were included in the present analysis if they fulfilled the following criteria: (1) diagnosed with asthma, (2) prescribed at least rescue...... bronchodilator, and (3) had the first visit to the respiratory outpatient clinic within the first 18 weeks of pregnancy. Data were analyzed using multiple logistic regression models with backward stepwise elimination (Proc Logistic procedure in SAS). RESULTS: Over an 8-year study period, a total of 1283...

Participation of CD161(+) and invariant natural killer T cells in pediatric asthma exacerbations.

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Carpio-Pedroza, Juan C; Vaughan, Gilberto; del Rio-Navarro, Blanca E; del Río-Chivardí, Jaime M; Vergara-Castañeda, Arely; Jiménez-Zamudio, Luis A; Morales-Flores, Amelia; Rodríguez-Moreno, Guadalupe; Ruiz-Tovar, Karina; Fonseca-Coronado, Salvador; Gonçalves Rossi, Livia M; Escobar-Gutiérrez, Alejandro

2013-01-01

Asthma has been defined as a disease of chronic airway inflammation in which many cells and cellular products participate with variable degrees of airflow obstruction and hyperresponsiveness that lead to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Prominent among these cellular elements are two cell types referred to as the invariant natural killer T (iNKT) cells and a subpopulation of T cells expressing the molecule CD161, which are both thought to play a role in the pathogenesis of asthma. Although the presence of iNKT and other CD161(+) cells in murine models has been associated with asthma, relatively few studies have been performed in the adult patient with asthma that have been often conflicting and even fewer studies are available in children. The present study was performed to investigate the peripheral blood frequencies of iNKT and CD161(+) T cells in children with asthma. A total of 35 children, 19 stable asthmatic patients, 6 who had experienced an asthmatic attack within 24 hours and had not received any treatment, and 10 healthy controls, aged 6-12 years, were enrolled in the study. iNKT and CD161(+) T-cell frequencies in blood were measured together with quantitative levels of IL-4 and interferon (IFN) γ using a cytofluorimetric approach. The results show that iNKT cells are increased in pediatric asthmatic patients undergoing exacerbations of asthma. These cells also produced less IFN-γ and more IL-4 than children with stable asthma and in healthy control children. These results suggest that iNKT cells might participate in the development of the asthmatic exacerbations. The increased production of IL-4 in conjunction with the decrease of IFN-γ may be mechanistically responsible, at least partially, for the heightening of the immunologic response leading to the asthmatic attack in children. Knowledge of these interactive mechanisms involving the iNKT cell and our understanding of its role in the exacerbation of

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.

Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations.

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Teach, Stephen J; Gill, Michelle A; Togias, Alkis; Sorkness, Christine A; Arbes, Samuel J; Calatroni, Agustin; Wildfire, Jeremy J; Gergen, Peter J; Cohen, Robyn T; Pongracic, Jacqueline A; Kercsmar, Carolyn M; Khurana Hershey, Gurjit K; Gruchalla, Rebecca S; Liu, Andrew H; Zoratti, Edward M; Kattan, Meyer; Grindle, Kristine A; Gern, James E; Busse, William W; Szefler, Stanley J

2015-12-01

Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms. Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

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.

Confirmatory spirometry for adults hospitalized with a diagnosis of asthma or chronic obstructive pulmonary disease exacerbation

Science.gov (United States)

2012-01-01

Background Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation. Methods Multi-center study of four academic healthcare institutions. Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation. Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data. Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations. Results There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings. Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality. Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease. Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007). Conclusions Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation. Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese

Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis.

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Whittington, Melanie D; McQueen, R Brett; Ollendorf, Daniel A; Tice, Jeffrey A; Chapman, Richard H; Pearson, Steven D; Campbell, Jonathan D

2017-02-01

Adding mepolizumab to standard treatment with inhaled corticosteroids and controller medications could decrease asthma exacerbations and use of long-term oral steroids in patients with severe disease and increased eosinophils; however, mepolizumab is costly and its cost effectiveness is unknown. To estimate the cost effectiveness of mepolizumab. A Markov model was used to determine the incremental cost per quality-adjusted life year (QALY) gained for mepolizumab plus standard of care (SoC) and for SoC alone. The population, adults with severe eosinophilic asthma, was modeled for a lifetime time horizon. A responder scenario analysis was conducted to determine the cost effectiveness for a cohort able to achieve and maintain asthma control. Over a lifetime treatment horizon, 23.96 exacerbations were averted per patient receiving mepolizumab plus SoC. Avoidance of exacerbations and decrease in long-term oral steroid use resulted in more than $18,000 in cost offsets among those receiving mepolizumab, but treatment costs increased by more than $600,000. Treatment with mepolizumab plus SoC vs SoC alone resulted in a cost-effectiveness estimate of $386,000 per QALY. To achieve cost effectiveness of approximately $150,000 per QALY, mepolizumab would require a more than 60% price discount. At current pricing, treating a responder cohort yielded cost-effectiveness estimates near $160,000 per QALY. The estimated cost effectiveness of mepolizumab exceeds value thresholds. Achieving these thresholds would require significant discounts from the current list price. Alternatively, treatment limited to responders improves the cost effectiveness toward, but remains still slightly above, these thresholds. Payers interested in improving the efficiency of health care resources should consider negotiations of the mepolizumab price and ways to predict and assess the response to mepolizumab. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All

Effects of procalcitonin-guided treatment on antibiotic use and need for mechanical ventilation in patients with acute asthma exacerbation: Meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Wanis H. Ibrahim

2017-12-01

Full Text Available Objective: The primary outcome was to determine whether serum procalcitonin-guided antibiotic therapy can reduce antibiotic exposure in patients with an acute exacerbation of asthma presenting to the primary care facility or emergency department, or during hospital admission. The secondary outcome was the need for mechanical ventilation. Methods: An extensive literature search was performed to identify randomized controlled clinical trials (published in English that compared serum procalcitonin-guided antibiotic therapy versus antibiotic use according to physician’s discretion for adult participants with mild, moderate, or severe acute asthma exacerbations. Results: Four randomized controlled trials evaluating 457 patients were included in this meta-analysis, with significant homogeneity observed among these studies. Procalcitonin-based protocols decreased antibiotic prescriptions (relative risk 0.58, 95% confidence interval 0.50–0.67. The conclusion regarding the difference between the two groups in the need for mechanical ventilation (relative risk 1.10, 95% confidence interval 0.62–1.94 was guarded due to inadequate power and the potential for type II error. The overall quality of evidence was also limited by the lack of double-blinding. Conclusions: These data suggest a potential benefit for the use of serum procalcitonin in guiding antibiotic therapy in patients with an acute asthma exacerbation and advocates the need for more randomized controlled trials. Keywords: Procalcitonin, Asthma, Antibiotic, Exacerbation, Guided

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...

Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations

DEFF Research Database (Denmark)

Silkoff, Philip E; Flavin, Susan; Gordon, Robert

2017-01-01

BACKGROUND: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. OBJECTIVE: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157......, respectively, and were then inoculated with HRV-16 within 72 hours. All subjects were monitored for respiratory symptoms, lung function, and nasal viral load. The primary end point was maximal decrease in FEV1 during 10 days after inoculation. RESULTS: In asthmatic patients (n = 63) CNTO3157 provided......: In summary, CNTO3157 was ineffective in attenuating the effect of HRV-16 challenge on lung function, asthma control, and symptoms in asthmatic patients but suppressed cold symptoms in healthy subjects. Other approaches, including blockade of multiple pathways or antiviral agents, need to be sought...

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

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

Science.gov (United States)

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.

Allergy in severe asthma

NARCIS (Netherlands)

Del Giacco, Stefano R.; Bakirtas, A.; Bel, E.; Custovic, A.; Diamant, Z.; Hamelmann, E.; Heffler, E.; Kalayci, O.; Saglani, S.; Sergejeva, S.; Seys, S.; Simpson, A.; Bjermer, Leif

It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps

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.

Hospitals' Patterns of Use of Noninvasive Ventilation in Patients With Asthma Exacerbation.

Science.gov (United States)

Stefan, Mihaela S; Nathanson, Brian H; Priya, Aruna; Pekow, Penelope S; Lagu, Tara; Steingrub, Jay S; Hill, Nicholas S; Goldberg, Robert J; Kent, David M; Lindenauer, Peter K

2016-03-01

Limited data are available on the use of noninvasive ventilation in patients with asthma exacerbations. The objective of this study was to characterize hospital patterns of noninvasive ventilation use in patients with asthma and to evaluate the association with the use of invasive mechanical ventilation and case fatality rate. This cross-sectional study used an electronic medical record dataset, which includes comprehensive pharmacy and laboratory results from 58 hospitals. Data on 13,558 patients admitted from 2009 to 2012 were analyzed. Initial noninvasive ventilation (NIV) or invasive mechanical ventilation (IMV) was defined as the first ventilation method during hospitalization. Hospital-level risk-standardized rates of NIV among all admissions with asthma were calculated by using a hierarchical regression model. Hospitals were grouped into quartiles of NIV to compare the outcomes. Overall, 90.3% of patients with asthma were not ventilated, 4.0% were ventilated with NIV, and 5.7% were ventilated with IMV. Twenty-two (38%) hospitals did not use NIV for any included admissions. Hospital-level adjusted NIV rates varied considerably (range, 0.4-33.1; median, 5.2%). Hospitals in the highest quartile of NIV did not have lower IMV use (5.4% vs 5.7%), but they did have a small but significantly shorter length of stay. Higher NIV rates were not associated with lower risk-adjusted case fatality rates. Large variation exists in hospital use of NIV for patients with an acute exacerbation of asthma. Higher hospital rates of NIV use does not seem to be associated with lower IMV rates. These results indicate a need to understand contextual and organizational factors contributing to this variability. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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...

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.

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

Directory of Open Access Journals (Sweden)

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

The effectiveness of school-based family asthma educational programs on the quality of life and number of asthma exacerbations of children aged five to 18 years diagnosed with asthma: a systematic review protocol.

Science.gov (United States)

Walter, Helen; Sadeque-Iqbal, Fatema; Ulysse, Rose; Castillo, Doreen; Fitzpatrick, Aileen; Singleton, Joanne

2015-10-01

$655 million was spent on asthma for 2008-09.Asthma is a chronic respiratory disease that affects millions of people of all ethnicities, ages and genders worldwide. The pathophysiology of asthma is multifaceted, and is characterized by restriction of airflow into and out of the lungs, airway inflammation with increased mucus production, and bronchial hyper-reactivity caused by exposure to environmental irritants and chemicals, often referred to as triggers, which in some cases are modifiable. Asthma triggers include respiratory infections, weather changes, stress, excitement, exercise and other physical activities, allergic hypersensitivity reactions, food additives, animal dander, dust mites, cockroaches, outdoor and indoor pollutants, certain medications and cigarette smoke. Asthma is characterized by recurrent, episodic, reversible symptoms often referred to as asthma exacerbations, or asthma attacks. Asthma symptoms include coughing, shortness of breath, chest tightness and wheezing that most frequently occur at night or in the early morning. Asthma symptoms vary in severity and frequency in affected individuals, and can occur several times a day or week. Asthma symptoms may be mild, moderate, or severe, and are classified according to presenting symptoms and quantitative measurements of lung function using a peak expiratory flow meter (PEF), or of forced expiratory volume in one second (FEV1). Asthma symptoms can be so severe that, if left untreated, death can occur.Exacerbations of asthma symptoms often result in school and work absenteeism, activity intolerance and emergency hospital visits for asthma. Nocturnal asthma exacerbations frequently cause sleeplessness, which may result in daytime fatigue. Asthma symptoms can interfere and disrupt activities of daily life, and can have an unfavorable impact on the quality of life for people with the disease, including children and their caregivers. For this review, quality of life represents how well the asthmatic

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.

[Features of Autonomic Response in Children with Bronchial Asthma in the Period of Exacerbation].

Science.gov (United States)

Lebedenko, A A; Semernik, O E

2015-01-01

Asthma is one of the urgent problems of modern pediatrics, but neuroregulation mechanisms underlying this disease have not been fully disclosed so far. The autonomic interaction assessment in patients with bronchial asthma is important to understand the pathogenesis and prognosis of the disease. The aim of this study was to investigate features of autonomic response in children with asthma in the period of exacerbation. The autonomic nervous system ANS) of 82 children aged 6 to 18 years old with asthma in the period of exacerbation were investigated. The spectral analysis of the heart rate variability and the correlation rhythmography method (skaterography) were used to assess the ANS state. Investigations were carried out at rest and after clinoorthostatic test. Non-respiratory (slow) waves reflecting (be degree of activity of humoral and neural canals of heart rate central regulation were dominated at the spectrogram of 72 (87.80%) children experiencing asthma attack; more than half of patients (58.53%) had predominantly very low-frequency component (VLF%) in the range of fluctuation rate that indicated (the influence of neurohumoral regulation. A significant increase in vagosympathetic balance coefficient (LE/HF) was recorded after clinoorthostatic test indicating the activation of the sympathetic nervous system. According to the correlation rhytlimnography data, a considerable scattering of scattergraphy points was detected in patients in (the baseline state that indicated the predominant influence of parasympathetic nervous system. After the clinoorthostatic test, on the contrary, we observed the of the scattergraphy cloud that could indicate sympathicotonia. The imbalance of the autonomic nervous system in the form of activation of the sympathetic amid neurohumoral regulation department was found in children with asthma.

Asthma Is More Severe in Older Adults

Science.gov (United States)

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

Svær asthma bronchiale

DEFF Research Database (Denmark)

von Bülow, Anna; Backer, Vibeke; Porsbjerg, Celeste

2015-01-01

Severe asthma is defined by persistent symptoms and frequent exacerbations despite intensive asthma therapy. The prevalence is estimated to be 5-10% of all asthmatics. Severe asthma is responsible for a major burden of illness including low quality of life and a disproportionate use of health......-care resources. The clinical assessment of severe asthma must include verification of the correct diagnosis, adherence to medication, excluding differential diagnosis and identification and treatment of aggravating co-morbidities and trigger factors....

Psychopathology in difficult asthma

NARCIS (Netherlands)

Prins, L.C.; van Son, M.J.M.; Keimpema, A.R.; van Ranst, D; Pommer, A; Meijer, J.W.; Pop, V.J.M.

2015-01-01

OBJECTIVE: Within the asthma population, difficult asthma (DA) is a severe condition in which patients present with frequent exacerbations, hospitalizations and emergency room visits. The identification and treatment of psychopathology is included in the management of DA. Psychopathology is supposed

Budesonide/formoterol maintenance and reliever therapy in adolescent patients with asthma

DEFF Research Database (Denmark)

Jorup, Carin; Lythgoe, Dan; Bisgaard, Hans

2018-01-01

Asthma control is often suboptimal in adolescents, but few studies have evaluated asthma treatments in this population.This post hoc analysis assessed the efficacy and safety of budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (MART) for treatment of persistent asthma in adolescent...... (age 12-17 years) subgroups within six randomised, double-blind trials. The primary end-point was time to first severe exacerbation. Secondary end-points included number of severe exacerbations, asthma-related symptoms, night-time awakenings, morning peak expiratory flow, forced expiratory volume in 1...... s, as-needed medication use and five-item asthma control questionnaire scores.In adolescents (n=1847), BUD/FORM MART was similar to or more effective than comparators across each of the studies in reducing the risk of a first severe exacerbation (hazard ratios (HR) BUD/FORM MART versus comparators 0...

Current concepts of severe asthma

Science.gov (United States)

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

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

Science.gov (United States)

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.

Fixed versus variable practice for teaching medical students the management of pediatric asthma exacerbations using simulation.

Science.gov (United States)

Drummond, David; Truchot, Jennifer; Fabbro, Eleonora; Ceccaldi, Pierre-François; Plaisance, Patrick; Tesnière, Antoine; Hadchouel, Alice

2018-02-01

Simulation-based trainings represent an interesting approach to teach medical students the management of pediatric asthma exacerbations (PAEs). In this study, we compared two pedagogical approaches, training students once on three different scenarios of PAEs versus training students three times on the same scenario of PAE. Eighty-five third-year medical students, novice learners for the management of PAEs, were randomized and trained. Students were assessed twice, 1 week and 4 months after the training, on a scenario of PAE new to both groups and on scenarios used during the training. The main outcome was the performance score on the new scenario of PAE at 1 week, assessed on a checklist custom-designed for the study. All students progressed rapidly and acquired excellent skills. One week after the training, there was no difference between the two groups on all the scenarios tested, including the new scenario of PAE (median performance score (IQR) of 8.3 (7.4-10.0) in the variation group versus 8.0 (6.0-10.0) in the repetition group (p = 0.16)). Four months later, the performance of the two groups remained similar. Varying practice with different scenarios was equivalent to repetitive practice on the same scenario for novice learners, with both methods leading to transfer and long-term retention of the skills acquired during the training. What is known: • Simulation-based trainings represent an interesting approach to teach medical students the management of pediatric asthma exacerbations. • It is unclear whether students would benefit more from repetitive practice on the same scenario of asthma exacerbation or from practice on different scenarios in terms of transfer of skills. What is new: • An individual 30-min training on the management of pediatric asthma exacerbations using simulation allows transfer and long-term retention of the skills acquired. • Varying practice with different scenarios is equivalent to repetitive practice on the same

Can mean platelet volume be used as a biomarker for asthma?

Directory of Open Access Journals (Sweden)

Hikmet Tekin Nacaroglu

2016-06-01

Full Text Available Introduction : Platelets play important roles in airway inflammation and are activated in inflammatory lung diseases, including asthma. Aim :We evaluated the mean platelet volume (MPV, used as a marker of platelet activation, in asthmatic patients during asymptomatic periods and exacerbations compared to healthy controls to determine whether MPV can be used as an indicator of inflammation. Material and methods :Our patient group consisted of95 children with exacerbation of asthma who were admitted to our allergy clinic. The control group consisted of 100 healthy children matched for age, gender, and ethnicity. Mean platelet volume values of the patient group obtained during exacerbation of asthma were compared to those of the same group during the asymptomatic period and with the control group. We investigated factors that can affect the MPV values of asthma patients, including infection, atopy, immunotherapy treatment, and severity of asthma exacerbation. Results :The patient group consisted of 50 (52.6% boys and 45 (47.4% girls with a mean age of 125 ±38 months old. Mean MPV values in the exacerbation period, the healthy period, and in the control group were 8.1 ±0.8 fl, 8.1 ±1.06 fl, and 8.2 ±0.9 fl, respectively; there were no significant differences between groups (p > 0.05. The severity of asthma, severity of asthma exacerbation, immunotherapy, coinfection, eosinophil count, and IgE level also had no effect on MPV (p > 0.05. Conclusions : Although platelets play a rolein the pathophysiology of asthma, MPV measurement is insufficient to detect inflammation through platelets

The Prevalence of Severe Asthma and Low Asthma Control Among Danish Adults

DEFF Research Database (Denmark)

von Bülow, Anna; Kriegbaum, Margit; Backer, Vibeke

2014-01-01

asthma, the extent of asthma control, and contact with specialist care. METHODS: A descriptive cross-sectional register study was performed. By using a nationwide prescription database, we identified current patients with asthma (age, 18-44 years) in 2010. Severity was classified as severe versus mild......-moderate asthma according to the level of antiasthma treatment. We investigated prescription drug use, hospitalizations, emergency department visits, and outpatient clinic visits according to severity. RESULTS: Among a nationwide population, we identified 61,583 current patients with asthma. Based on the level...... asthma and low asthma control were not managed by specialist care. Patients with severe asthma with specialist contact more frequently had impaired asthma control compared with subjects not treated by a specialist (44.4% vs 33.1%, P

Risk factors precipitating exacerbations in adult asthma patients ...

African Journals Online (AJOL)

Background: Research into asthma is proceeding at an unprecedented rate and yet we live with a disease that escalates in prevalence and severity, ... Data from Australia, Canada and Spain report that acute asthma accounted for 1 to 12% of all adult .... budesonide inhalers, oral theophylline, long-acting β2-agonists and.

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.

Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults

DEFF Research Database (Denmark)

Bjermer, Leif; Bisgaard, Hans; Bousquet, Jean

2003-01-01

OBJECTIVES: To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. Design and setting A 52 week, two period, double blind, multicentre trial during which pa...

Psychopathology in difficult asthma : Review

NARCIS (Netherlands)

Prins, L.C.J.; van Son, M.A.C.; van Keimpema, A.R.J.; van Ranst, D.; Antonissen-Pommer, A.M.; Meijer, J.W.G.; Pop, V.J.M.

2015-01-01

Objective: Within the asthma population, difficult asthma (DA) is a severe condition in which patients present with frequent exacerbations, hospitalizations and emergency room visits. The identification and treatment of psychopathology is included in the management of DA. Psychopathology is supposed

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

Science.gov (United States)

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

Understanding mild persistent asthma in children

DEFF Research Database (Denmark)

Bisgaard, Hans; Szefler, Stanley J

2005-01-01

Limitations in asthma prevalence studies and difficulties in diagnosing pediatric asthma lead to uncertainty over the full extent of mild persistent asthma in children and adolescents. Although recent surveys have reported that the majority of pediatric patients with asthma in the United States...... and Europe have symptoms consistent with mild disease, these surveys have limitations in design. Thus, the true prevalence of mild asthma remains unknown. It is unclear whether children with mild persistent asthma progress to more severe asthma, but the risk of severe asthma exacerbations seems...... to be unrelated to the symptom severity. Clinical studies restricted to pediatric patients with mild asthma are limited, but available data do suggest substantial morbidity of mild persistent asthma in this population and support inhaled corticosteroid intervention. There is a need for further investigation...

Acute respiratory failure in asthma

OpenAIRE

Soubra Said; Guntupalli Kalapalatha

2005-01-01

Although asthma is a condition that is managed in the outpatient setting in most patients, the poorly controlled and severe cases pose a major challenge to the health-care team. Recognition of the more common insidious and the less common rapid onset "acute asphyxic" asthma are important. The intensivist needs to be familiar with the factors that denote severity of the exacerbation. The management of respiratory failure in asthma, including pharmacologic and mechanical ventilation, are discus...

The effectiveness of newly developed written asthma action plan in improvement of asthma outcome in children.

Science.gov (United States)

Lakupoch, Kingthong; Manuyakorn, Wiparat; Preutthipan, Aroonwan; Kamalaporn, Harutai

2017-09-17

Providing asthma education about controller medication use and appropriate management of asthma exacerbation are the keys to improving the disease outcome. Many asthma guidelines recommend that physicians provide written asthma action plan (WAAP) to all of their asthmatic patients. However, the benefit of WAAP is unclear. Thus, we have created a new WAAP which is simplified in Thai and more user friendly. To determine the effectiveness of the newly developed asthma action plan in management of children with asthma. Asthmatic children who meet inclusion criteria all received the WAAP and they were followed up for 6 months with measurement of outcome variables, such as asthma exacerbation that required emergency room visit, unscheduled OPD visit, admission and school absence in order to compare with the past 6 months before receiving the WAAP. The analyzed outcomes of forty-nine children show significantly reduced emergency room visit (P-value 0.005), unscheduled OPD visit (P-value 0.046), admission days (P-value 0.026) and school absence days (P-value 0.022). Well controlled group and mild severity group were not the factors that contribute to decreased emergency room visit but step up therapy may be the co-factor to decreased ER visit. The results of this study suggest that the provision of newly developed WAAP is useful for improving self-care of asthma patients and reducing asthma exacerbation.

Serological neo-epitope extracellular matrix related markers reflecting collagen or elastin degradation are elevated in a mouse model of allergic asthma exacerbation

NARCIS (Netherlands)

Weckmann, M.; Rønnow, S.; Bülow-Sand, J.M.; Wegmann, M.; Lunding, L.; Burgess, J.; Bahmer, T.; Leeming, D.J.; Kopp, M.V.

2018-01-01

Asthma is a chronic inflammatory disease, characterized by symptoms including increased mucus production, reversible airway obstruction and lung inflammation: all of which are exaggerated during asthma exacerbations. Extracellular matrix remodeling is associated with the release of ECM protein

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

Directory of Open Access Journals (Sweden)

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.

Herbal Medicine Cordyceps sinensis Improves Health-Related Quality of Life in Moderate-to-Severe Asthma

Directory of Open Access Journals (Sweden)

Ningqun Wang

2016-01-01

Full Text Available Moderate-to-severe asthma has a substantial impact on the health-related quality of life (HR-QOL of the patients. Cordyceps sinensis is a traditional Chinese medicine that is evaluated clinically for the treatment of many diseases, such as chronic allograft nephropathy, diabetic kidney disease, and lung fibrosis. In order to investigate the effects of Cordyceps sinensis on patients with moderate-to-severe persistent asthma, 120 subjects were randomized to receive Corbin capsule containing Cordyceps sinensis for 3 months (treatment group, n=60, whereas the control group (n=60 did not receive treatment with Corbin capsule. Inhaled corticosteroid and as-needed β-agonists were used in the treatment of both groups. HR-QOL was measured with the Juniper’s Asthma Quality of Life Questionnaire (AQLQ. The incidence of asthma exacerbation, pulmonary function testing, and serum measurements of inflammatory mediators were also evaluated. The results showed that the treatment group indicated a significant increase in AQLQ scores and lung function compared with the control group. The expression levels of the inflammation markers IgE, ICAM-1, IL-4, and MMP-9 in the serum were decreased and IgG increased in the treatment group compared with the control group. Therefore, the conclusion was reached that a formulation of Cordyceps sinensis improved the HR-QOL, asthma symptoms, lung function, and inflammatory profile of the patients with moderate-to-severe asthma. This trial is registered with ChiCTR-IPC-16008730.

Herbal Medicine Cordyceps sinensis Improves Health-Related Quality of Life in Moderate-to-Severe Asthma.

Science.gov (United States)

Wang, Ningqun; Li, Jie; Huang, Xiaobo; Chen, Wenqiang; Chen, Yujing

2016-01-01

Moderate-to-severe asthma has a substantial impact on the health-related quality of life (HR-QOL) of the patients. Cordyceps sinensis is a traditional Chinese medicine that is evaluated clinically for the treatment of many diseases, such as chronic allograft nephropathy, diabetic kidney disease, and lung fibrosis. In order to investigate the effects of Cordyceps sinensis on patients with moderate-to-severe persistent asthma, 120 subjects were randomized to receive Corbin capsule containing Cordyceps sinensis for 3 months (treatment group, n = 60), whereas the control group ( n = 60) did not receive treatment with Corbin capsule. Inhaled corticosteroid and as-needed β -agonists were used in the treatment of both groups. HR-QOL was measured with the Juniper's Asthma Quality of Life Questionnaire (AQLQ). The incidence of asthma exacerbation, pulmonary function testing, and serum measurements of inflammatory mediators were also evaluated. The results showed that the treatment group indicated a significant increase in AQLQ scores and lung function compared with the control group. The expression levels of the inflammation markers IgE, ICAM-1, IL-4, and MMP-9 in the serum were decreased and IgG increased in the treatment group compared with the control group. Therefore, the conclusion was reached that a formulation of Cordyceps sinensis improved the HR-QOL, asthma symptoms, lung function, and inflammatory profile of the patients with moderate-to-severe asthma. This trial is registered with ChiCTR-IPC-16008730.

Clinical experience with Omalizumab in a Portuguese severe asthma unit

Directory of Open Access Journals (Sweden)

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

Participation of Antidiuretic Hormone (ADH) in Asthma Exacerbations Induced by Psychological Stress via PKA/PKC Signal Pathway in Airway-Related Vagal Preganglionic Neurons (AVPNs).

Science.gov (United States)

Hou, Lili; Zhu, Lei; Zhang, Min; Zhang, Xingyi; Zhang, Guoqing; Liu, Zhenwei; Li, Qiang; Zhou, Xin

2017-01-01

Present study was performed to examine whether ADH was implicated in psychological stress asthma and to explore the underlying molecular mechanism. We not only examined ADH levels in the cerebrospinal fluid (CSF) via radioimmunoassay, but also measured ADH receptor (ADHR) expression in airway-related vagal preganglionic neurons (AVPNs) through real-time PCR in all experimental mice. Western blotting was performed to evaluate the relationship between ADH and PKA/PKC in psychological stress asthma. Finally, the role of PKA/PKC in psychological stress asthma was analyzed. Marked asthma exacerbations were noted owing to significantly elevated levels of ADH and ADHR after psychological stress induction as compared to OVA alone (asthma group). ADHR antagonists (SR-49095 or SR-121463A) dramatically lowered higher protein levels of PKAα and PKCα induced by psychological stress as compared to OVA alone, suggesting the correlation between ADH and PKA/PKC in psychological stress asthma. KT-5720 (PKA inhibitor) and Go-7874 (PKC inhibitor) further directly revealed the involvement of PKA/PKC in psychological stress asthma. Some notable changes were also noted after employing PKA and PKC inhibitors in psychological stress asthma, including reduced asthmatic inflammation (lower eosinophil peroxidase (EPO) activity, myeloperoxidase (MPO) activity, immunoglobulin E (IgE) level, and histamine release), substantial decrements in inflammatory cell counts (eosinophils and lymphocytes), and decreased cytokine secretion (IL-6, IL-10, and IFN-γ), indicating the involvement of PKA/PKC in asthma exacerbations induced by psychological stress. Our results strongly suggested that ADH participated in psychological stress-induced asthma exacerbations via PKA/PKC signal pathway in AVPNs. © 2017 The Author(s)Published by S. Karger AG, Basel.

Novel targets of omalizumab in asthma.

Science.gov (United States)

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.

Does pre-hospital telephone communication with a clinician result in more appropriate medication administration by parents during childhood asthma exacerbations?

Science.gov (United States)

Garro, A C; Fearon, D; Koinis-Mitchell, D; McQuaid, E L

2009-11-01

The National Heart, Lung and Blood Institute asthma guidelines recommend that parents communicate with a clinician during childhood asthma exacerbations when symptoms worsen or do not improve with initial therapy. This study tested the hypothesis that communication by parents with a clinician before an Emergency Department visit was associated with more appropriate medication administration for children with asthma exacerbations. This was a retrospective cohort study using data gathered from parents of children presenting with an asthma exacerbation to the emergency department. The communicating cohort included parents who communicated by telephone with a clinician during the exacerbation and the non-communicating cohort included parents who did not. Multivariate logistic regression models were used to test three hypotheses; communication with a clinician is associated with (1) administration of short-acting beta-agonists (SABAs), (2) increased dosing frequency of SABAs, and (3) administration of an oral corticosteroid. A total of 199 subjects were enrolled, with 104 (52.3%) in the communicating and 95 (47.7%) in the non-communicating cohort. There was an association between communication and provider practice type, with children who received routine care from a private practice provider more likely to communicate with the clinician than children in hospital-based clinics or community health centers (Adjusted OR 1.9, 95% CI 1.0-3.7). Impoverished children and children insured by Medicaid were less likely to communicate with a clinician (controlling for provider type). Parents who communicated with a clinician were more likely to administer a SABA (adjusted OR 3.6, 95% CI 1.3-9.4) and an oral corticosteroid (adjusted OR 3.3, 95% CI 1.3-8.4) but were not more likely to administer a SABA with increased dosing frequency (adjusted OR 0.9, 95% CI 0.5-1.6). Parents of children with asthma exacerbations who communicated with clinicians were more likely to administer SABAs

Outcomes of Noninvasive and Invasive Ventilation in Patients Hospitalized with Asthma Exacerbation.

Science.gov (United States)

Stefan, Mihaela S; Nathanson, Brian H; Lagu, Tara; Priya, Aruna; Pekow, Penelope S; Steingrub, Jay S; Hill, Nicholas S; Goldberg, Robert J; Kent, David M; Lindenauer, Peter K

2016-07-01

Little is known about the effectiveness of noninvasive ventilation for patients hospitalized with asthma exacerbation. To assess clinical outcomes of noninvasive (NIV) and invasive mechanical ventilation (IMV) and examine predictors for NIV use in patients hospitalized with asthma. This was a retrospective cohort study at 97 U.S. hospitals using an electronic medical record database. We developed a hierarchical regression model to identify factors associated with the choice of initial ventilation and used the Laboratory Acute Physiological Score to adjust for differences in the severity of illness. We assessed the outcomes of patients treated with initial NIV or IMV in a propensity-matched cohort. Among 13,930 subjects, 73% were women and 54% were white. The median age was 53 years. Overall, 1,254 patients (9%) required ventilatory support (NIV or IMV). NIV was the initial ventilation method for 556 patients (4.0%) and IMV for 668 (5.0%). Twenty-six patients (4.7% of patients treated with NIV) had to be intubated (NIV failure). The in-hospital mortality was 0.2, 2.3, 14.5, and 15.4%, and the median length of stay was 2.9, 4.1, 6.7, and 10.9 days among those not ventilated, ventilated with NIV, ventilated with IMV, and with NIV failure, respectively. Older patients were more likely to receive NIV (odds ratio, 1.06 per 5 yr; 95% confidence interval [CI], 1.01-1.11), whereas those with higher acuity (Laboratory Acute Physiological Score per 5 units: odds ratio, 0.85; 95% CI, 0.82-0.88) and those with concomitant pneumonia were less likely to receive NIV. In a propensity-matched sample, NIV was associated with a lower inpatient risk of dying (risk ratio, 0.12; 95% CI, 0.03-0.51) and shorter lengths of stay (4.3 d less; 95% CI, 2.9-5.8) than IMV. Among patients hospitalized with asthma exacerbation and requiring ventilatory support (NIV or IMV), more than 40% received NIV. Although patients successfully treated with NIV appear to have better outcomes than those treated

Acute bronchial asthma

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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.

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

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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.

COPD exacerbations by disease severity in England

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Merinopoulou E

2016-04-01

Full Text Available Evie Merinopoulou,1 Mireia Raluy-Callado,1 Sreeram Ramagopalan,1 Sharon MacLachlan,1 Javaria Mona Khalid2 1Real-World Evidence, Evidera, 2Takeda Development Centre Europe Ltd, London, UK Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2013.Methods: Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013 were exacerbation rates and resource utilization (general practitioner visits, hospital admissions.Results: From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85 for GOLD A to 2.51 (95% CI: 2.47–2.55 for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93 for GOLD A to 7.44 (95% CI: 7.31–7.61 for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39 to more symptoms (GOLD B: 0.52, GOLD D: 0.84.Conclusion: Patients in the most severe category (GOLD D experienced nearly three times the number of exacerbations and COPD

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.

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.

The Airway Microbiome in 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

2015-01-01

Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions

Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology

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Jenkins Cathy A

2010-03-01

Full Text Available Abstract Background Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV1 (criterion validity and change of %FEV1 (responsiveness during treatment in pediatric patients with acute asthma exacerbations. Methods We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV1, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests. Results We studied 219 subjects (median age 9 years; male 62%; African-American 56%. Correlation of PEP with %FEV1 demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30 and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09 and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07. PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17, but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P Conclusions PEP demonstrates criterion validity and responsiveness in correlations with %FEV1. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition

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

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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.

Biologic Therapy and Asthma.

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Viswanathan, Ravi K; Busse, William W

2018-02-01

Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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.

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

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.

Defining asthma and assessing asthma outcomes using electronic health record data: a systematic scoping review.

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Al Sallakh, Mohammad A; Vasileiou, Eleftheria; Rodgers, Sarah E; Lyons, Ronan A; Sheikh, Aziz; Davies, Gwyneth A

2017-06-01

There is currently no consensus on approaches to defining asthma or assessing asthma outcomes using electronic health record-derived data. We explored these approaches in the recent literature and examined the clarity of reporting.We systematically searched for asthma-related articles published between January 1, 2014 and December 31, 2015, extracted the algorithms used to identify asthma patients and assess severity, control and exacerbations, and examined how the validity of these outcomes was justified.From 113 eligible articles, we found significant heterogeneity in the algorithms used to define asthma (n=66 different algorithms), severity (n=18), control (n=9) and exacerbations (n=24). For the majority of algorithms (n=106), validity was not justified. In the remaining cases, approaches ranged from using algorithms validated in the same databases to using nonvalidated algorithms that were based on clinical judgement or clinical guidelines. The implementation of these algorithms was suboptimally described overall.Although electronic health record-derived data are now widely used to study asthma, the approaches being used are significantly varied and are often underdescribed, rendering it difficult to assess the validity of studies and compare their findings. Given the substantial growth in this body of literature, it is crucial that scientific consensus is reached on the underlying definitions and algorithms. Copyright ©ERS 2017.

The burden of severe asthma in childhood and adolescence

DEFF Research Database (Denmark)

Fleming, Louise; Murray, Clare; Bansal, Aruna T

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...... in the severe wheeze cohort. Almost all participants in each cohort were atopic and had a normal body mass index. Asthma-related quality of life, as assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), was worse...... and mild/moderate cohorts were clinically very similar. Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life that is associated with poor control and airflow limitation: a very different phenotype from adult severe asthma. In-depth phenotyping...

Usefulness of modified Pulmonary Index Score (mPIS) as a quantitative tool for the evaluation of severe acute exacerbation in asthmatic children.

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Koga, Takeshi; Tokuyama, Kenichi; Itano, Atsushi; Morita, Eiji; Ueda, Yutaka; Katsunuma, Toshio

2015-04-01

Acute exacerbation of asthma is divided qualitatively into mild, moderate, and severe attacks and respiratory failure. This system is, however, not suitable for estimating small changes in respiratory condition with time and for determining the efficacy of treatments, because it has a qualitative, but not quantitative nature. To evaluate the usefulness of quantitative estimation of asthma exacerbation, modified Pulmonary Index Score (mPIS) values were measured in 87 asthmatic children (mean age, 5.0 ± 0.4 years) during hospitalization. mPIS was calculated by adding the sum of scores for 6 items (scores of 0-3 were given for each item). These consisted of heart rate, respiratory rate, accessory muscle use, inspiratory-to-expiratory flow ratio, degree of wheezing, and oxygen saturation in room air. Measurements were made at visits and at hospitalization and were then made twice a day until discharge. mPIS values were highly correlated among raters. mPIS values at visits were 9.1 ± 0.1 and 12.6 ± 0.4 in subjects with moderate and severe attacks, respectively (p asthma attacks, including the determination of a treatment plan, and prediction of the period of hospitalization in admitted patients, although prospective studies would be required to establish our hypothesis. Copyright © 2014 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Self-hypnosis for anxiety associated with severe asthma: a case report

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Anbar Ran D

2003-07-01

Full Text Available Abstract Background Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations. Case Presentation The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy. Conclusions This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma.

Montelukast for the high impact of asthma exacerbations in Venezuela: a practical and valid approach for Latin America?

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Capriles Hulett, Arnaldo; Yibirin, Maria Gonzalez; Garcia, Amaris; Hurtado, Dollys

2014-01-01

Asthma affects mainly Venezuela's urban and poor majority. Exacerbations bring about a high demand in health services, thus becoming a significant public health problem. In general, asthma control programs (GINA) with use of inhaled steroid medications have proven effective, although their implementation in real life remains cumbersome. Montelukast could be a useful and practical tool for these deprived socioeconomic sectors. This real-life pilot study was conducted in a prospective, double blinded, placebo-controlled manner with randomized and parallel groups. Asthmatics that had never used leukotriene modifiers were recruited and followed-up every three months. The main outcome was the number of exacerbations meriting use of nebulized bronchodilators administered by the health care system. Eighty-eight asthmatic patients were enrolled, between children and adults. Groups were comparable in: demographic data, previous use of other medications, ACT scores, pulmonary functions (Wright Peak Flow meter), allergy status (Skin Prick Test) as well as adherence to the prescribed Montelukast treatment. By an intention to treat (ITT), a total of 64 patients were included for analysis. For the three and six months time points the difference between placebo and Montelukast was found to be significant (p asthma treatment.

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

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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.

Outdoor fungi and child asthma health service attendances.

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Tham, Rachel; Dharmage, Shyamali C; Taylor, Philip E; Katelaris, Constance H; Vicendese, Don; Abramson, Michael J; Erbas, Bircan

2014-08-01

Asthma is a significant global public health issue. Severe asthma exacerbations can be triggered by environmental factors and require medical care from health services. Although it is known that fungal exposure may lead to allergic sensitization, little is understood about its impact on asthma exacerbations. This review aims to examine whether outdoor fungi play a significant role in child asthma exacerbations. Systematic search of seven electronic databases and hand searching for peer-reviewed studies published in English, up to 31 August 2013. Inclusion criteria were study population aged asthma, attended a health service; outdoor fungi exposure was reported. Quality and risk of bias assessments were conducted. Due to significant heterogeneity, meta-analysis was not conducted. Of the 1896 articles found, 15 were eligible. Findings were not consistent, possibly due to methodological variations in exposure classifications, statistical methods and inclusion of confounders. Cross-sectional studies found no or weak associations. All but one time series studies indicated an association that varied between fungal species. Increasing evidence indicates that asthmatic children are susceptible to asthma exacerbations when exposed to outdoor fungal spores. There is limited understanding of the contributions of different fungal species. Research is needed to investigate interactions of outdoor fungi with pollen, air pollutants and respiratory viruses. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Mepolizumab for Treating Severe Eosinophilic Asthma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

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Bermejo, Iñigo; Stevenson, Matt; Cooper, Katy; Harnan, Sue; Hamilton, Jean; Clowes, Mark; Carroll, Christopher; Harrison, Tim; Saha, Shironjit

2018-02-01

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company (GlaxoSmithKline) that manufactures mepolizumab (Nucala ® ) to submit evidence on the clinical and cost effectiveness of mepolizumab for the treatment of severe eosinophilic asthma. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent evidence review group (ERG). The ERG produced a review of the evidence for the clinical and cost effectiveness of mepolizumab as add-on to standard of care (SoC) compared with SoC and omalizumab, based upon the company's submission to NICE. The clinical-effectiveness evidence in the company's submission was based predominantly on three randomised controlled trials (DREAM, MENSA and SIRIUS) comparing add-on mepolizumab with placebo plus SoC. The relevant population was defined in terms of degree of asthma severity (four or more exacerbations in the previous year and/or dependency on maintenance oral corticosteroids [mOCS]) and degree of eosinophilia (a blood eosinophil count of ≥ 300 cells/µl in the previous year) based on post hoc subgroup analyses of the pivotal trials. Other subpopulations were considered throughout the appraisal, defined by different eosinophil measurements, number of exacerbations and dependency (or lack thereof) on mOCS. Statistically significant reductions in clinically significant exacerbations were observed in patients receiving mepolizumab compared with SoC meta-analysed across MENSA and DREAM in the modified intention-to-treat (ITT) population (rate ratio [RR] 0.51; 95% confidence interval [CI] 0.42-0.62) as well as in the relevant population (RR 0.47; 95% CI 0.36-0.62). In terms of quality of life, differences on the St. George's Respiratory Questionnaire in MENSA for add-on subcutaneous mepolizumab 100 mg vs. placebo were 7 and 7.5 units in the modified ITT and

Acute severe asthma presenting in late pregnancy.

Science.gov (United States)

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.

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.

Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives

Directory of Open Access Journals (Sweden)

Konstantinos Samitas

2015-12-01

Full Text Available Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes.

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

Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma.

Science.gov (United States)

Tajiri, T; Matsumoto, H; Gon, Y; Ito, R; Hashimoto, S; Izuhara, K; Suzukawa, M; Ohta, K; Ono, J; Ohta, S; Ito, I; Oguma, T; Inoue, H; Iwata, T; Kanemitsu, Y; Nagasaki, T; Niimi, A; Mishima, M

2016-10-01

Omalizumab, a humanized anti-IgE monoclonal antibody, has demonstrated efficacy in patients with severe allergic asthma. However, treatment responses vary widely among individuals. Despite a lack of data, free serum IgE levels following omalizumab treatment have been proposed as a marker of treatment responsiveness. In this prospective, observational study, we assessed the utility of biomarkers of type 2 inflammation in predicting omalizumab treatment responses, as determined by the absence of asthma exacerbation during the first year of treatment. Free serum IgE levels were monitored for 2 years to examine their association with baseline biomarker levels and the number of exacerbations. We enrolled thirty patients who had been treated with omalizumab for at least 1 year, of whom 27 were treated for 2 years. Baseline serum periostin levels and blood eosinophil counts were significantly higher in patients without exacerbations during the first year of treatment than in patients with exacerbations. Baseline serum periostin levels, but not eosinophil counts, were negatively associated with free serum IgE levels after 16 or 32 weeks of treatment. Reduced free serum IgE levels during treatment from those at baseline were associated with reduced exacerbation numbers at 2 years. In 14 patients who continued to have exacerbations during the first year of treatment, exacerbation numbers gradually and significantly decreased over the 2-year study period, with concurrent significant reductions in free serum IgE levels. Baseline serum periostin levels and serum free IgE levels during treatment follow-up may be useful in evaluating responses to omalizumab treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cost-Effectiveness of Bronchial Thermoplasty, Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma.

Science.gov (United States)

Zafari, Zafar; Sadatsafavi, Mohsen; Marra, Carlo A; Chen, Wenjia; FitzGerald, J Mark

2016-01-01

Bronchial thermoplasty (BT) is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy. To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA. A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]). A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs) and exacerbations as the outcomes. For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER) of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP) of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI) was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%. Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes cost

Cost-Effectiveness of Bronchial Thermoplasty, Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma.

Directory of Open Access Journals (Sweden)

Zafar Zafari

Full Text Available Bronchial thermoplasty (BT is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy.To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA.A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]. A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs and exacerbations as the outcomes.For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%.Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes

Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey

Science.gov (United States)

Price, David; Fletcher, Monica; van der Molen, Thys

2014-01-01

Background: Asthma is one of the most common chronic diseases in the world, and previous studies have reported low levels of control. Recent developments in the availability and use of online sources of information about asthma might add to patients’ knowledge and help improve control. Aims: To investigate whether asthma control has improved by assessing levels of symptoms, exacerbations and Global Initiative for Asthma-defined control in a real-life population of patients who use the Internet and social media, as well as evaluate patient perception of control and attitudes to asthma. Methods: Online surveys were conducted among 8,000 patients with asthma (aged 18–50 years, ⩾2 prescriptions in the previous 2 years, use of social media) from 11 European countries. Results: Levels of asthma control were low: 45% of respondents had uncontrolled asthma. Acute exacerbations were common: 44% of respondents reported having used oral steroids for asthma in the previous 12 months, 24% had visited an emergency department and 12% had been hospitalised. More than 80% of respondents (overall, and among those with a history of exacerbations) considered their asthma to be controlled. Of those who had an exacerbation requiring oral steroids, 75% regarded their asthma as not serious. Conclusions: Asthma control in Europe remains poor; symptoms and exacerbations are common. Many patients regard their asthma as controlled and not serious despite experiencing symptoms and exacerbations. There is a need to assess patients’ control, risk and inhaler technique, and to ensure that patients are prescribed, and take, appropriate treatments. PMID:24921985

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 

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.

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...

Indoor combustion and asthma.

Science.gov (United States)

Belanger, Kathleen; Triche, Elizabeth W

2008-08-01

Indoor combustion produces both gases (eg, nitrogen dioxide, carbon monoxide) and particulate matter that may affect the development or exacerbation of asthma. Sources in the home include both heating devices (eg, fireplaces, woodstoves, kerosene heaters, flued [ie, vented] or nonflued gas heaters) and gas stoves for cooking. This article highlights the recent literature examining associations between exposure to indoor combustion and asthma development and severity. Since asthma is a chronic condition affecting both children and adults, both age groups are included in this article. Overall, there is some evidence of an association between exposure to indoor combustion and asthma, particularly asthma symptoms in children. Some sources of combustion such as coal stoves have been more consistently associated with these outcomes than other sources such as woodstoves.

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

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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.

Comparison of Psychological, Quality of Life, Work-Limitation, and Socioeconomic Status Between Patients With Occupational Asthma and Work-Exacerbated Asthma.

Science.gov (United States)

Lipszyc, Joshua C; Silverman, Frances; Holness, Dorothy Linn; Liss, Gary M; Lavoie, Kim L; Tarlo, Susan M

2017-07-01

The aim of this study was to compare psychological status, quality of life (QoL), work limitation, and socioeconomic status between patients with occupational asthma (OA) and work-exacerbated asthma (WEA). The following questionnaires were administered to participants: Beck anxiety and depression (II) inventories, Marks' Asthma Quality of Life Questionnaire, and Work Limitations Questionnaire. Cross-sectional analyses between OA and WEA subgroups were completed. There were 77 participants. WEA subjects had a trend to higher anxiety scores (OA = 9.2 ± 8.0, WEA = 12.8 ± 8.3, P = 0.07, Cohen d = 0.4). Depression scores trended higher for those with WEA (OA = 9.6 ± 10.3, WEA = 13.4 ± 13.5, P = 0.2, Cohen d = 0.3). QoL was comparable between groups. WEA subjects had fewer work limitations (N = 50, OA = 25.1 ± 27.3, WEA = 20.6 ± 24.4, P = 0.56, Cohen d = 0.3) and OA subjects were more likely to have reduced income. In a tertiary clinic, there were some modest differences for specific variables between OA and WEA subjects that may help inform management.

Variation of Asthma Symptoms Perception | Lutfi | Sudan Journal of ...

African Journals Online (AJOL)

Background: Asthmatic patients may perceive their symptoms inadequately putting them at a risk of a fatal attack because the severity of an exacerbation may be underestimated. The present study is intended to detect if disease duration affects the perception of asthma symptoms. The relation between asthma activity and ...

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

Japanese Guideline for Childhood Asthma

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Toshiyuki Nishimuta

2011-01-01

JAGL differs from the Global Initiative for Asthma Guideline (GINA in that the former emphasizes long-term management of childhood asthma based on asthma severity and early diagnosis and intervention at <2 years and 2–5 years of age. However, a management method, including step-up or step-down of long-term management agents based on the status of asthma symptoms, is easy to understand and thus JAGL is suitable for routine medical treatment. JAGL also introduced treatment and management using a control test for children, recommending treatment and management aimed at complete control through avoiding exacerbation factors and appropriate use of antiinflammatory agents.

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

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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.

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.

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.

Mild, Moderate, Severe Asthma: What Do Grades Mean?

Science.gov (United States)

... that arise by making this kind of distinction. What Really Matters Is Control, Not Severity It turns out that asthma severity ... Asthma” make a strong point that the overall control of your child’s asthma is really what is most important, not what the severity level ...

Impact and prevention of severe exacerbations of COPD: a review of the evidence

Science.gov (United States)

Halpin, David MG; Miravitlles, Marc; Metzdorf, Norbert; Celli, Bartolomé

2017-01-01

Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. PMID:29062228

Use of Antibiotics during pregnancy increases the risk of Asthma in early childhood

DEFF Research Database (Denmark)

Stensballe, Lone Graff; Simonsen, Jacob; Jensen, Signe Marie

2013-01-01

OBJECTIVES: To investigate the hypothesis that mother's use of antibiotics in pregnancy could influence asthma and eczema in early life. STUDY DESIGN: Subjects were included from the Copenhagen Prospective Study on Asthma in Childhood cohort of children born of mothers with asthma (N = 411). Severe...... verified eczema. All children were followed to age 5 years in a cohort study design. RESULTS: The Copenhagen Prospective Study on Asthma in Childhood data showed increased risk of asthma exacerbation (hazard ratio 1.98 [95% CI 1.08-3.63]) if mothers had used antibiotics during third trimester. The Danish...... asthma exacerbations and eczema were diagnosed by research unit physicians. Replication was sought in children from the Danish National Birth Cohort (N = 30 675). Asthma outcomes were hospitalization and use of inhaled corticosteroids. Eczema was defined by an algorithm developed from cases of clinically...

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

Directory of Open Access Journals (Sweden)

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.

Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark

DEFF Research Database (Denmark)

Backer, V.; Harving, H.; Soes-Petersen, U.

2008-01-01

leading to admission. Material and methods: In a retrospective design, we audited the hospital records of all patients aged 18-40 years admitted to five Danish university hospitals with an acute exacerbation of asthma in 2004. Results: We found records covering 323 asthmatic patients (186 women). Before...

Pollen exposure and hospitalization due to asthma exacerbations: daily time series in a European city

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Osborne, Nicholas J.; Alcock, Ian; Wheeler, Benedict W.; Hajat, Shakoor; Sarran, Christophe; Clewlow, Yolanda; McInnes, Rachel N.; Hemming, Deborah; White, Mathew; Vardoulakis, Sotiris; Fleming, Lora E.

2017-10-01

Exposure to pollen can contribute to increased hospital admissions for asthma exacerbation. This study applied an ecological time series analysis to examine associations between atmospheric concentrations of different pollen types and the risk of hospitalization for asthma in London from 2005 to 2011. The analysis examined short-term associations between daily pollen counts and hospital admissions in the presence of seasonal and long-term patterns, and allowed for time lags between exposure and admission. Models were adjusted for temperature, precipitation, humidity, day of week, and air pollutants. Analyses revealed an association between daily counts (continuous) of grass pollen and adult hospital admissions for asthma in London, with a 4-5-day lag. When grass pollen concentrations were categorized into Met Office pollen `alert' levels, `very high' days (vs. `low') were associated with increased admissions 2-5 days later, peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days. Increased admissions were also associated with `high' versus `low' pollen days at a 3-day lag. Results from tree pollen models were inconclusive and likely to have been affected by the shorter pollen seasons and consequent limited number of observation days with higher tree pollen concentrations. Future reductions in asthma hospitalizations may be achieved by better understanding of environmental risks, informing improved alert systems and supporting patients to take preventive measures.

Summary of the 2008 BTS/SIGN British Guideline on the management of asthma.

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Levy, Mark L; Thomas, Mike; Small, Iain; Pearce, Linda; Pinnock, Hilary; Stephenson, Paul

2009-01-01

The 2008 BTS/SIGN British Guideline on the management of asthma provides comprehensive updated evidence-based guidance on asthma management for healthcare professionals. This primary care-focussed summary has been produced to aid dissemination and implementation of the key guideline messages into primary care. The section on diagnosis emphasises the new integrated symptom-based approach with clinicians using their deductive skills to determine the probability that the patient has asthma. The various tools used for monitoring asthma are discussed. There are sections on both non-pharmacological and pharmacological management of chronic asthma in adults and children. Treatment options for children are subdivided into the under-5s and children aged 5-12 years. Poor asthma control is manifested by exacerbations and acute asthma. Personalised asthma action plans for guided self management should be provided and used when levels of asthma control change. There are sections on difficult asthma and the treatment of exacerbations and acute severe asthma. Various outcome measures for auditing the quality of asthma care are discussed.

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-...

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.

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....

Impact and prevention of severe exacerbations of COPD: a review of the evidence

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Halpin DMG

2017-10-01

Full Text Available David MG Halpin,1 Marc Miravitlles,2 Norbert Metzdorf,3 Bartolomé Celli4 1Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 2Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 3Respiratory Medicine, Boehringer Ingelheim Pharma GmBH & Co KG, Ingelheim am Rhein, Germany; 4Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA Abstract: Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. Keywords

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

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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.

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.

Omalizumab in the management of patients with allergic (IgE-mediated asthma

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Thomas Sandström

2009-05-01

Full Text Available Thomas SandströmDepartment of Respiratory Medicine and Allergy, University Hospital, Umeå, SwedenAbstract: Immunoglobulin E (IgE is central to the pathophysiology of allergic asthma. Omalizumab, an anti-IgE monoclonal antibody, binds to the FcεRI binding site on free IgE. As a result, circulating free IgE is reduced, IgE is prevented from attaching to mast cells and basophils, and FcεRI receptor expression is down-regulated. The inflammatory response to allergens and the acute and chronic effector phases of allergic inflammation are thereby attenuated. In clinical trials in adults and adolescents, omalizumab reduced asthma exacerbations, severe asthma exacerbations, inhaled corticosteroid requirements, and emergency visits, as well as significantly improving asthma-related quality of life, morning peak expiratory flow and asthma symptom scores in patients with severe allergic (IgE-mediated asthma. Results from clinical trials in children (< 12 years are consistent with those in the adult population. It is difficult to predict which patients will respond to omalizumab. Responders to omalizumab should be identified after a 16-week trial of therapy using the physician’s overall assessment. When treatment is targeted to these responders, omalizumab provides a cost-effective therapy for inadequately controlled severe allergic (IgE-mediated asthma. Long-term therapy with omalizumab shows the potential for disease-modification in asthma. Ongoing studies are also evaluating the use of omalizumab in other non-asthma IgE-mediated conditions.Keywords: omalizumab, IgE, allergic asthma

Outpatient Management of Asthma in Children

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André Schultz

2013-01-01

Full Text Available The principal aims of asthma management in childhood are to obtain symptom control that allows individuals to engage in unrestricted physical activities and to normalize lung function. These aims should be achieved using the fewest possible medications. Ensuring a correct diagnosis is the first priority. The mainstay of asthma management remains pharmacotherapy. Various treatment options are discussed. Asthma monitoring includes the regular assessment of asthma severity and asthma control, which then informs decisions regarding the stepping up or stepping down of therapy. Delivery systems and devices for inhaled therapy are discussed, as are the factors influencing adherence to prescribed treatment. The role of the pediatric health care provider is to establish a functional partnership with the child and their family in order to minimize the impact of asthma symptoms and exacerbations during childhood.

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

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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.

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.

The effects of aminophylline infusion in the treatment of children with acute asthma exacerbation. Evaluation with 81mKr ventilation scintigraphy

International Nuclear Information System (INIS)

Matsubara, Yasuko; Shimada, Takao

1998-01-01

The use of intravenous aminophylline in the treatment of children with acute asthma remains controversial. Most authors suggest that aminophylline be used with caution because of its poor efficacy with adverse reactions and instead recommend other drugs, such as β 2 -adrenergic agonists and glucocorticoids. However other studies have reported the benefits of aminophylline, and current Japanese guidelines for the management of asthma recommend its use. Here, we have evaluated the efficacy of aminophylline infusion in children with acute asthma exacerbations. Twenty children with acute asthma exacerbations were given an infusion of 5 mg/kg of aminophylline over 5 minutes, 30 minutes after the same volume of normal saline had been infused as a control. 81m Kr ventilation scintigraphy was done sequentially, and lung function was measured with spirometry before and after each infusion. Side effects were also evaluated with a questionnaire. Ventilation images obtained with 81m Kr scintigraphy, which initially showed widespread ventilatory defects caused by bronchoconstriction, decreased 54.9% after aminophylline infusion (p 81m Kr bolus inhalation procedure, also showed significant improvement (p<0.0001). These improvement were accompanied by improvements in lung function as assessed with forced expiratory volume in 1 second (p<0.01) and maximum expiratory flow rates at 25% (p<0.001) and 50% (p<0.001). No serious adverse reactions were recognized in any subjects. Our results show that aminophylline is a useful bronchodilator which decreased ventilatory imbalance and improves lung function in both central and peripheral airways. (author)

Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy.

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Brusselle, Guy; Canvin, Janice; Weiss, Sivan; Sun, Shawn X; Buhl, Roland

2017-07-01

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies. This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines. Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL -1 ) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in 1 s (FEV 1 ) and patient-reported outcomes. Of 953 patients, 69% (n=657) and 11% (n=106) were receiving Step 4 and Step 5 therapy, respectively. Compared with placebo, reslizumab reduced exacerbation rates by 53% (95% CI 0.36-0.62) and 72% (95% CI 0.15-0.52), in Step 4 and Step 5 groups respectively. By study end, reslizumab increased FEV 1 in Step 4 and Step 5 groups by 103 mL (95% CI 52-154 mL) and 237 mL (95% CI 68-407 mL), respectively. Reslizumab also improved patient-reported outcomes compared with placebo in both groups. Reslizumab reduces exacerbation rates and improves lung function and patient-reported outcomes in patients with eosinophilic asthma receiving therapy per Steps 4 and 5 of the GINA guidelines.

Features of Atopic Reactivity in Schoolchildren with Severe Bronchial Asthma

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U.I. Marusyk

2014-11-01

Full Text Available The study involved 30 students with severe bronchial asthma and 30 children with moderate to severe course. Patients with severe bronchial asthma revealed a clear tendency to increase the relative content of interleukin 4 in peripheral blood, which indirectly indicates the severity of inflammation in the bronchi. Almost every second child suffering from severe bronchial asthma reported an increase in the concentration of immunoglobulin E (more than 545.3 IU/ml, and the odds ratio was 1.9 (95% CI 1.1–3.4. In the group of patients with severe bronchial asthma, cases of increased skin sensitivity to household allergens were significantly more frequent compared to the second group. Thus, the size of hyperemia over 15.0 mm was recorded in 81.5 % of children of the first group and only in 51.9 % of persons (Pϕ < 0.05 in the second one. Clinical and epidemiological risk and diagnostic value of individual indicators of atopic reactivity were determined to verify the phenotype of severe bronchial asthma.

Harsh parent-child conflict is associated with decreased anti-inflammatory gene expression and increased symptom severity in children with asthma.

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Ehrlich, Katherine B; Miller, Gregory E; Chen, Edith

2015-11-01

Asthma is a chronic respiratory disorder that affects over 7 million children in the United States. Evidence indicates that family stressors are associated with worsening of asthma symptoms, and some research suggests that these stressful experiences engender changes in children's immune systems in ways that exacerbate airway inflammation and contribute to both acute and chronic asthma symptoms. We examined the association between observed experiences of parent-child conflict and the expression of signaling molecules involved in the transduction of anti-inflammatory signals that regulate airway inflammation and obstruction. Fifty-seven children and their parents participated in a conflict task, and coders rated interactions for evidence of harsh and supportive behaviors. Children reported on their perceptions of parental support and reported on their daily asthma symptoms for 2 weeks. We collected peripheral blood in children to measure leukocyte expression of messenger RNA for the glucocorticoid receptor and the β2-adrenergic receptor. Analyses revealed that harsh conflict behaviors were associated with decreased expression of both messenger RNAs and more severe asthma symptoms. Neither supportive behaviors nor perceived parental support was associated with gene expression or asthma symptoms. These findings suggest that harsh interactions with parents are associated with downregulation of key anti-inflammatory signaling molecules and difficulties breathing in children with asthma. Children with asthma who are also victims of maltreatment may be particularly susceptible to transcriptional changes in immune cells that could worsen asthma over time.

Environmental triggers and avoidance in the management of asthma

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Gautier C

2017-03-01

Full Text Available Clarisse Gautier,1 Denis Charpin1,2 1Department of Pulmonology and Allergy, North Hospital, 2Faculty of Medicine, Aix-Marseille University, Marseille, France Abstract: Identifying asthma triggers forms the basis of environmental secondary prevention. These triggers may be allergenic or nonallergenic. Allergenic triggers include indoor allergens, such as house dust mites (HDMs, molds, pets, cockroaches, and rodents, and outdoor allergens, such as pollens and molds. Clinical observations provide support for the role of HDM exposure as a trigger, although avoidance studies provide conflicting results. Molds and their metabolic products are now considered to be triggers of asthma attacks. Pets, dogs, and especially cats can undoubtedly trigger asthmatic symptoms in sensitized subjects. Avoidance is difficult and rarely adhered to by families. Cockroach allergens contribute to asthma morbidity, and avoidance strategies can lead to clinical benefit. Mouse allergens are mostly found in inner-city dwellings, but their implication in asthma morbidity is debated. In the outdoors, pollens can induce seasonal asthma in sensitized individuals. Avoidance relies on preventing pollens from getting into the house and on minimizing seasonal outdoor exposure. Outdoor molds may lead to severe asthma exacerbations. Nonallergenic triggers include viral infections, active and passive smoking, meteorological changes, occupational exposures, and other triggers that are less commonly involved. Viral infection is the main asthma trigger in children. Active smoking is associated with higher asthma morbidity, and smoking cessation interventions should be personalized. Passive smoking is also a risk factor for asthma exacerbation. The implementation of public smoking bans has led to a reduction in the hospitalization of asthmatic children. Air pollution levels have been linked with asthmatic symptoms, a decrease in lung function, and increased emergency room visits and

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.

Repeated irradiations with γ-rays at a dose of 0.5 Gy may exacerbate asthma

International Nuclear Information System (INIS)

Fang, Su-ping; Tago, Fumitoshi; Tanaka, Takashi; Simura, Noriko; Kojima, Shuji; Muto, Yasuko; Goto, Resuke

2005-01-01

We previously showed that 0.5 Gy whole-body γ-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFNγ/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy γ-rays irradiation can improve asthma in an ovalbumin (OVA)-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of γ-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the γ-ray-irradiated group, while that of IFN-γ was significantly lower, resulting in a further decrease of the IFN-γ/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with γ-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures. (author)

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

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

2009-07-01

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

Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

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Wang, Lei; Liang, Rui; Zhou, Ting; Zheng, Jing; Liang, Bing Miao; Zhang, Hong Ping; Luo, Feng Ming; Gibson, Peter G; Wang, Gang

2017-10-01

Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Different innate neutrophil responses in controlled and uncontrolled asthma

NARCIS (Netherlands)

Tang, Francesca; Foxley, Gloria; Gibson, Peter; Burgess, Janette; Baines, Katherine; Oliver, Brian

2015-01-01

Introduction: Respiratory viruses are a major cause of asthma exacerbations. Neutrophilic inflammation occurs during infections and is associated with difficult to treat asthma. The role of neutrophils in viral infections and whether neutrophil dysfunction contributes to exacerbation pathogenesis

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.

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.

Indoor Air Quality and Asthma

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Robert Golden

2017-02-01

Full Text Available Numerous contaminants in indoor air and their potential to cause or exacerbate asthma continue to be a subject of public health concern. Many agents are causally associated with or can exacerbate asthma, particularly in children. For formaldehyde, an established respiratory irritant based on numerous studies, the evidence for an association with asthma is still considered only limited or suggestive. However, there is no evidence that indicates increased sensitivity to sensory irritation to formaldehyde in people often regarded as susceptible such as asthmatics. Acrolein, but not formaldehyde, was significantly associated with asthma in a large cohort of children. This prompted an evaluation of this highly irritating chemical that had never previously been considered in the context of the indoor air/childhood asthma issue. Because acrolein is more potent than formaldehyde as a respiratory irritant and ubiquitous in indoor air, it is plausible that previous studies on potential risk factors and childhood asthma may be confounded by formaldehyde acting as an unrecognized proxy for acrolein.

Spirometry use in children hospitalized with asthma.

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Tan, Chee Chun; McDowell, Karen M; Fenchel, Matthew; Szczesniak, Rhonda; Kercsmar, Carolyn M

2014-05-01

Asthma is the most common chronic disorder of childhood and continues to be a leading cause of pediatric hospital admission. The National Asthma Education and Prevention Program (NAEPP) recommends that spirometry be obtained for asthma patients upon hospital admission, after bronchodilation during the acute phase of asthma symptoms, and at least one additional time before discharge from the hospital. The objectives of this study were to describe the use of spirometry in children hospitalized with asthma and to determine association of pulmonary function with future exacerbations. A retrospective cohort study design was utilized involving review of medical records of children ≥5 years old admitted with asthma to Cincinnati Children's Hospital Medical Center from September 1, 2009 to March 31, 2011. Hospitalization or emergency department (ED) visits were identified by the ICD-9-CM codes of having either a primary diagnosis of asthma (493) or a respiratory illness (460-496) plus a secondary diagnosis of asthma. Asthma re-exacerbation was defined as either having an ED visit or hospitalization for asthma that occurred within 3 months after the index hospitalization. All spirometries were performed in a pediatric pulmonary function laboratory. Among 1,037 admissions included in this study, 89 (8.6%) had spirometry that was recommended by a consulting asthma specialist and usually performed on the day of discharge. Spirometries for forty-five of these patients (54.9%) met all acceptability and repeatability criteria of the American Thoracic Society. Patients who performed acceptable spirometry were significantly older (12.4 ± 3.8 vs. 10.7 ± 3.0 years; P = 0.041). The average forced expiratory volume in the first second (FEV1 ) was 84.4 ± 19.7% predicted; forced vital capacity (FVC) was 98.1 ± 16.0% predicted; FEV1 /FVC was 74.6 ± 9.6%; forced expiratory flow at 25-75% (FEF25-75 ) was 61.2 ± 30.1% predicted. Ten patients (22%) who

Does vitamin d deficiency contribute to the severity of asthma in children and adults

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Ahmed, S.Z.A.; Hameed, K.; Jaleel, A.

2015-01-01

Role of vitamin D in the health of bones has been well established for over decades. It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named t he sunshine vitamin . As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma. (author)

DOES VITAMIN D DEFICIENCY CONTRIBUTE TO THE SEVERITY OF ASTHMA IN CHILDREN AND ADULTS?

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Ahmed, Syed Zaryab; Jaleel, Anila; Hameed, Kamran; Qazi, Salman; Suleman, Ahsan

2015-01-01

Role of vitamin D in the health of bones has been well established for over decades; It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named "the sunshine vitamin". As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma.

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.

Vitamins C and E for asthma and exercise-induced bronchoconstriction.

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Wilkinson, Mark; Hart, Anna; Milan, Stephen J; Sugumar, Karnam

2014-06-17

differences in outcomes were seen when vitamin C and E supplementation versus placebo was provided for participants with asthma, and only one of those studies (160 children) included a paediatric population; the remaining three studies included a combined total of just 46 adults. An additional study considered the question of whether differences in outcomes were noted when vitamin C and E supplementation was compared with placebo for exercise-induced asthma; this trial included only eight participants. The randomisation process of the trials were unclear leading us to downgrade the quality of the evidence. Four of the studies were double blind while the other study was single blind.None of these studies provided data on our two prespecified primary outcome measures: exacerbations and HRQL. Lung function data obtained from the studies were inconclusive. The only studies that provided any suggestion of an effect, and only with some outcomes, were the paediatric study, especially for children with moderate to severe asthma, and the small study on exercise-induced asthma. Even so, this evidence was judged to be at moderate/low quality. Only one study contributed data on asthma symptoms and adverse events, reporting no evidence of an effect of the intervention for symptoms and that one participant in the treatment group dropped out due to cystitis. It is not possible to draw firm conclusions from this review with respect to the comparison of vitamin C and E supplementation versus placebo in the management of asthma or exercise-induced bronchoconstriction. We found only one study relevant to exercise-induced bronchoconstriction; most included participants came from studies designed to assess the effect of vitamin supplementation on the impact of atmospheric pollutants (such as ozone). Evidence is lacking on the comparison of vitamin C and E supplementation versus placebo for asthma with respect to outcomes such as HRQL and exacerbations, which were not addressed by any of the

IgE sensitization and sociodemographic conditions as determinant factors in asthma severity

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Rodrigo Gaviria

2017-12-01

Full Text Available Background: In Latin America there are few data about the factors that influence the control and severity of asthma. Objective: To describe the association between IgE sensitization to intra-home allergens and housing conditions in the severity of asthma. Methods: Sensitization to aero-allergens was evaluated by skin prick test and socio-demographic data by a questionnaire in a population between 6 and 14 years of age with diagnosis of asthma. Asthma control was measured according to spirometric results and to the application of the ACT (Asthma Control Test; the severity and symptom control was evaluated according to the GINA guideline. Results: A total of 150 resident patients from the Aburra Valley (Colombia were included. The median age of participants was 11 years, 95 (63.3 % male. 92 % of the patients resided in the urban area. Mite sensitization was the most prevalent in controlled and uncontrolled patients. Sensitization to cockroach and some poverty conditions were risk factors for asthma severity. Conclusion: Poverty conditions appear to favor the development of severe asthma and in turn IgE sensitization to cockroaches. This sensitization could serve as a biomarker of severity.

Asthma essentials

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Timothy Greene

2013-12-01

Full Text Available Asthma is a chronic, reversible obstructive disease that when in exacerbation can present to the emergency department in a spectrum of severity. Prompt recognition of the potentially severely ill asthmatic requires a careful history and physical exam while considering alternative diagnoses for the presenting symptoms. Early administration of salbutamol and corticosteroids is indicated in almost all patients with other medications such as ipratropium and magnesium and supportive modalities like BiPAP reserved for sicker patients. The global impact of asthma is increasing, especially amongst children. While the benign clinical presentation is most common and mortality has decreased in recent decades due to improved recognition and care, the ubiquity of the condition and frequent lack of regular outpatient management contribute to the disease claiming 250,000 lives worldwide annually. The emergency physician must be prepared to assess and appropriately manage both the young child with a mild wheeze and the adult in respiratory failure.

Risk factors precipitating exacerbations in adult asthma patients ...

African Journals Online (AJOL)

one-third of the direct care costs of asthma are attributable to ED visits ... The setting for this study was the emergency unit, the primary health clinic and the asthma .... diisocyanate or when they were employed in the pharmaceutical, plastics or ...

Approach to asthma in adults

African Journals Online (AJOL)

Introduction. Asthma is a chronic inflammatory disease of the airways, ... of the airway, constriction of the airway via smooth muscle ... Avoiding these factors can help to reduce asthma exacerbations .... Nutritional and exercise-related factors.

Asthma and obesity: does weight loss improve asthma control? a systematic review

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Juel CTB

2012-06-01

Full Text Available Caroline Trunk-Black Juel,1 Zarqa Ali,1 Lisbeth Nilas,2 Charlotte Suppli Ulrik11Respiratory Section, Internal Medicine Unit, 2Department of Obstetrics and Gynaecology, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkAim and methods: Obesity is a major health problem, and obesity is associated with a high incidence of asthma and poor asthma control. The aim of the present paper is to systematically review the current knowledge of the effect on overall asthma control of weight reduction in overweight and obese adults with asthma.Results: Weight loss in obese individuals with doctor-diagnosed asthma is associated with a 48%–100% remission of asthma symptoms and use of asthma medication. Published studies, furthermore, reveal that weight loss in obese asthmatics improves asthma control, and that especially surgically induced weight loss results in significant improvements in asthma severity, use of asthma medication, dyspnoea, exercise tolerance, and acute exacerbations, including hospitalizations due to asthma. Furthermore, weight loss in obese asthmatics is associated with improvements in level of lung function and airway responsiveness to inhaled methacholine, whereas no significant improvements have been observed in exhaled nitric oxide or other markers of eosinophilic airway inflammation.Conclusion: Overweight and obese adults with asthma experience a high symptomatic remission rate and significant improvements in asthma control, including objective measures of disease activity, after weight loss. Although these positive effects of weight loss on asthma-related health outcomes seem not to be accompanied by remission or improvements in markers of eosinophilic airway inflammation, it has potentially important implications for the future burden of asthma.Keywords: asthma, weight loss, diet, bariatric surgery, asthma control

Pulmonary rehabilitation and severe exacerbations of COPD: solution or white elephant?

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William D-C. Man

2015-10-01

Full Text Available Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact.

Management preferences of pediatricians in moderate and severe acute asthma.

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Arga, Mustafa; Bakirtas, Arzu; Catal, Ferhat; Derinoz, Oksan; Topal, Erdem; Demirsoy, M Sadik; Turktas, Ipek

2013-05-01

To assess and compare management preferences of physicians for moderate and severe acute asthma based on case scenarios and to determine the factors influencing their decisions. A questionnaire based on the Global Initiative on Asthma (GINA) guideline and comprising eight questions on management of acute asthma was delivered to participants of two national pediatric congresses. Management of moderate and severe acute asthma cases was evaluated by two clinical case scenarios for estimation of acute attack severity, initial treatment, treatment after 1h, and discharge recommendations. A uniform answer box comprising the possible choices was provided just below the questions, and respondents were requested to tick the answers they thought was appropriate. Four-hundred and eighteen questionnaires were analyzed. All questions regarding moderate and severe acute asthma case scenarios were answered accurately by 15.8% and 17.0% of physicians, respectively. The initial treatment of moderate and severe cases was known by 100.0% and 78.2% of physicians, respectively. Knowledge of the appropriate plan for treatment after 1h was low both for moderate (45.0%) and severe attacks (35.4%). Discharge recommendations were adequate in 32.5% and 70.8% of physicians for moderate and severe attacks, respectively. Multiple logistic regression analysis revealed that working at a hospital with a continuing medical education program was the only significant predictor of a correct response to all questions regarding severe attacks (p = .04; 95%CI, 1.02-3.21). No predictors were found for information on moderate attacks. Pediatricians have difficulty in planning treatment after 1 hour both for moderate and severe asthma attacks. Postgraduate education programs that target physicians in hospitals without continuing medical education facilities may improve guideline adherence.

The effects of aminophylline infusion in the treatment of children with acute asthma exacerbation. Evaluation with {sup 81m}Kr ventilation scintigraphy

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Matsubara, Yasuko; Shimada, Takao [Jikei Univ., Tokyo (Japan). School of Medicine

1998-09-01

The use of intravenous aminophylline in the treatment of children with acute asthma remains controversial. Most authors suggest that aminophylline be used with caution because of its poor efficacy with adverse reactions and instead recommend other drugs, such as {beta}{sub 2}-adrenergic agonists and glucocorticoids. However other studies have reported the benefits of aminophylline, and current Japanese guidelines for the management of asthma recommend its use. Here, we have evaluated the efficacy of aminophylline infusion in children with acute asthma exacerbations. Twenty children with acute asthma exacerbations were given an infusion of 5 mg/kg of aminophylline over 5 minutes, 30 minutes after the same volume of normal saline had been infused as a control. {sup 81m}Kr ventilation scintigraphy was done sequentially, and lung function was measured with spirometry before and after each infusion. Side effects were also evaluated with a questionnaire. Ventilation images obtained with {sup 81m}Kr scintigraphy, which initially showed widespread ventilatory defects caused by bronchoconstriction, decreased 54.9% after aminophylline infusion (p<0.0001). Ventilatory defects, caused by both central and peripheral airway disturbances and confirmed with the {sup 81m}Kr bolus inhalation procedure, also showed significant improvement (p<0.0001). These improvement were accompanied by improvements in lung function as assessed with forced expiratory volume in 1 second (p<0.01) and maximum expiratory flow rates at 25% (p<0.001) and 50% (p<0.001). No serious adverse reactions were recognized in any subjects. Our results show that aminophylline is a useful bronchodilator which decreased ventilatory imbalance and improves lung function in both central and peripheral airways. (author)

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....

Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

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Wei-Lun Tsai

2015-11-01

Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

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.

Fractional exhaled nitric oxide for the management of asthma in adults: a systematic review.

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Essat, Munira; Harnan, Sue; Gomersall, Tim; Tappenden, Paul; Wong, Ruth; Pavord, Ian; Lawson, Rod; Everard, Mark L

2016-03-01

The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults.13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed.Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63-1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43-1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of -0.24 (95% CI -0.56-0.07). No statistically significant differences for health-related quality of life or asthma control were found.FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or inhaled corticosteroid use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most. Copyright ©ERS 2016.

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

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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

Culture-specific programs for children and adults from minority groups who have asthma.

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McCallum, Gabrielle B; Morris, Peter S; Brown, Ngiare; Chang, Anne B

2017-08-22

studies ranged from very low to low. For our primary outcome (asthma exacerbations during follow-up), the quality of evidence was low for all outcomes. In adults, use of a culture-specific programme, compared to generic programmes or usual care did not significantly reduce the number of participants from two studies with 294 participants for: exacerbations with one or more exacerbations during follow-up (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.50 to 1.26), hospitalisations over 12 months (OR 0.83, 95% CI 0.31 to 2.22) and exacerbations requiring oral corticosteroids (OR 0.97, 95% CI 0.55 to 1.73). However, use of a culture-specific programme, improved asthma quality of life scores in 280 adults from two studies (mean difference (MD) 0.26, 95% CI 0.17 to 0.36) (although the MD was less then the minimal important difference for the score). In children, use of a culture-specific programme was superior to generic programmes or usual care in reducing severe asthma exacerbations requiring hospitalisation in two studies with 305 children (rate ratio 0.48, 95% CI 0.24 to 0.95), asthma control in one study with 62 children and QoL in three studies with 213 children, but not for the number of exacerbations during follow-up (OR 1.55, 95% CI 0.66 to 3.66) or the number of exacerbations (MD 0.18, 95% CI -0.25 to 0.62) among 100 children from two studies. The available evidence showed that culture-specific education programmes for adults and children from minority groups are likely effective in improving asthma-related outcomes. This review was limited by few studies and evidence of very low to low quality. Not all asthma-related outcomes improved with culture-specific programs for both adults and children. Nevertheless, while modified culture-specific education programs are usually more time intensive, the findings of this review suggest using culture-specific asthma education programmes for children and adults from minority groups. However, more robust RCTs are needed to

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).

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.

Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

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Cristina B. Barra

Full Text Available Summary Introduction: Oral corticosteroids (OCS are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamic-pituitary-adrenal (HPA axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS trial. Method: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006. Results: In all, 140 children (0.3-15 years old with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29 nor in the last OCS course duration (p=0.20. The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89. Conclusion: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing.

Addressing unmet needs in understanding asthma mechanisms: From the European Asthma Research and Innovation Partnership (EARIP) Work Package (WP)2 collaborators.

Science.gov (United States)

Edwards, Michael R; Saglani, Sejal; Schwarze, Jurgen; Skevaki, Chrysanthi; Smith, Jaclyn A; Ainsworth, Ben; Almond, Mark; Andreakos, Evangelos; Belvisi, Maria G; Chung, Kian Fan; Cookson, William; Cullinan, Paul; Hawrylowicz, Catherine; Lommatzsch, Marek; Jackson, David; Lutter, Rene; Marsland, Benjamin; Moffatt, Miriam; Thomas, Mike; Virchow, J Christian; Xanthou, Georgina; Edwards, Jessica; Walker, Samantha; Johnston, Sebastian L

2017-05-01

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes. Copyright ©ERS 2017.

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.

Leveraging gene-environment interactions and endotypes for asthma gene discovery

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Ober, Carole

2016-01-01

, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs......Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also...... heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes...

Mexican Asthma Guidelines: GUIMA 2017

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Désirée Larenas-Linnemann

2017-04-01

Full Text Available Background: The need for a national guideline, with a broad basis among specialists and primary care physicians was felt in Mexico, to try unifying asthma management. As several high-quality asthma guidelines exist worldwide, it was decided to select the best three for transculturation. Methods: Following the internationally recommended methodology for guideline transculturation, ADAPTE, a literature search for asthma guidelines, published 1-1-2007 through 31-12-2015 was conducted. AGREE-II evaluations yielded 3/40 most suitable for transculturation. Their compound evidence was fused with local reality, patient preference, cost and safety considerations to draft the guideline document. Subsequently, this was adjusted by physicians from 12 national medical societies in several rounds of a Delphi process and 3 face-to-face meetings to reach the final version. Results: Evidence was fused from British Thoracic Society Asthma Guideline 2014, Global Initiative on Asthma 2015, and Guía Española del Manejo del Asma 2015 (2016 updates included. After 3 Delphi-rounds we developed an evidence-based document taking into account patient characteristics, including age, treatment costs and safety and best locally available medication. Conclusion: In cooperation pulmonologists, allergists, ENT physicians, paediatricians and GPs were able to develop an evidence-based document for the prevention, diagnosis and treatment of asthma and its exacerbations in Mexico.

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.

Pattern of vitamin D in patients with chronic obstructive pulmonary diseases and in patients with bronchial asthma

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Essam Gouda

2016-04-01

Conclusion: Vitamin D deficiency was highly prevalent in COPD and bronchial asthma (100% and 50% respectively. Low levels of vitamin D were associated with low FEV1%, frequent exacerbations in patients with COPD and bronchial asthma, and increased COPD severity as assessed by GOLD guidelines. Important statistically significant negative associations between vitamin D level and both asthma control and asthma severity according to GINA classification were also found. Thus it is advised to include vitamin D levels in the routine assessment of patients with bronchial asthma and COPD, as well as studying the importance and clinical impact of oral supplementation of vitamin D in patients with COPD and bronchial asthma should be an important goal of future research.

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

Overweight/obesity status in preschool children associates with worse asthma but robust improvement on inhaled corticosteroids.

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Lang, Jason E; Fitzpatrick, Anne M; Mauger, David T; Guilbert, Theresa W; Jackson, Daniel J; Lemanske, Robert F; Martinez, Fernando D; Strunk, Robert C; Zeiger, Robert S; Phipatanakul, Wanda; Bacharier, Leonard B; Pongracic, Jacqueline A; Holguin, Fernando; Cabana, Michael D; Covar, Ronina A; Raissy, Hengameh H; Tang, Monica; Szefler, Stanley J

2018-04-01

Overweight/obesity (OW) is linked to worse asthma and poorer inhaled corticosteroid (ICS) response in older children and adults. We sought to describe the relationships between OW and asthma severity and response to ICS in preschool children. This post hoc study of 3 large multicenter trials involving 2- to 5-year-old children compared annualized asthma symptom days and exacerbations among normal weight (NW) (body mass index: 10th-84th percentiles) versus OW (body mass index: ≥85th percentile) participants. Participants had been randomized to daily ICS, intermittent ICS, or daily placebo. Simple and multivariable linear regression was used to compare body mass index groups. Within the group not treated with a daily controller, OW children had more asthma symptom days (90.7 vs 53.2, P = .020) and exacerbations (1.4 vs 0.8, P = .009) thanNW children did. Within the ICS-treated groups, OW and NW children had similar asthma symptom days (daily ICS: 47.2 vs 44.0 days, P = .44; short-term ICS: 61.8 vs 52.9 days, P = .46; as-needed ICS: 53.3 vs 47.3 days, P = .53), and similar exacerbations (daily ICS: 0.6 vs 0.8, P = .10; short-term ICS: 1.1 vs 0.8 days, P = .25; as-needed ICS: 1.0 vs 1.1, P = .72). Compared with placebo, daily ICS in OW led to fewer annualized asthma symptom days (90.7 vs 41.2, P = .004) and exacerbations (1.4 vs 0.6, P = .006), while similar protective ICS effects were less apparent among NW. In preschool children off controller therapy, OW is associated with greater asthma impairment and exacerbations. However, unlike older asthmatic patients, OW preschool children do not demonstrate reduced responsiveness to ICS therapy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. 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

Self-management program in treatment of asthma

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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. .

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

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

2016-08-18

Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. Among

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

Breastfeeding associated with higher lung function in African American youths with asthma.

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Oh, Sam S; Du, Randal; Zeiger, Andrew M; McGarry, Meghan E; Hu, Donglei; Thakur, Neeta; Pino-Yanes, Maria; Galanter, Joshua M; Eng, Celeste; Nishimura, Katherine Keiko; Huntsman, Scott; Farber, Harold J; Meade, Kelley; Avila, Pedro; Serebrisky, Denise; Bibbins-Domingo, Kirsten; Lenoir, Michael A; Ford, Jean G; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Thyne, Shannon M; Sen, Saunak; Rodriguez-Santana, Jose R; Williams, Keoki; Kumar, Rajesh; Burchard, Esteban G

2017-10-01

In the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1 second (FEV 1 ) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma. As part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21 years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV 1 % predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations. Prevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p asthma exacerbations (p = 0.03) in African Americans only. Breastfeeding was associated with higher FEV 1 % predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Implementation of spacer therapy for acute asthma in children.

LENUS (Irish Health Repository)

Vandeleur, M

2009-09-01

The aim was to develop and implement an evidence based guideline for the treatment of acute asthma using a metered dose inhaler and spacer combination. Children admitted to Cork University Hospital Paediatric Department with acute asthma were identified during two identical 2 month seasonal periods before (2005) and after (2006) implementation of the new guidelines in September 2006. Pre-intervention and post-intervention audits by case note review were performed to determine the impact of and compliance with this evidence-based guideline emphasising patient assessment, spacer delivered bronchodilator and specific discharge criteria. Patients had similar characteristics during the two study periods. There was a raised threshold for admission after guideline implementation with 11\\/52 patients having mild exacerbations in 2006, compared to 21\\/36 in 2005. Duration of admission was less in the post-implementation group for equivalent exacerbation severity e.g. for moderate severity; 28 hours in 2005, 23 hours in 2006. Duration of bronchodilator therapy was shorter in 2006 and more likely to be given by spacer device earlier for equivalent levels of severity e.g. for moderate exacerbations, in 2006 the average length of salbutamol therapy was 18 hours with 12 hours by spacer device, in 2005 the average length of therapy was 25 hours with 3 hours by spacer. There was earlier initiation of oral corticosteroids; the average time to administration was 56 minutes in 2006 and 227 minutes in 2005. There was an improved documentation of asthma education in 2006 e.g. inhaler technique was reviewed in 37\\/52 in 2006, 21\\/35 in 2005 and better use of written action plans.

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

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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.

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.

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

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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.

Single-inhaler combination therapy for maintenance and relief of asthma: a new strategy in disease management.

Science.gov (United States)

Peters, Matthew

2009-01-01

When an adequate standard of asthma control is not achieved with maintenance treatment of inhaled corticosteroids, the addition of a long-acting beta(2)-adrenergic receptor agonist (LABA) bronchodilator is recommended. Using a combination product, salmeterol/fluticasone propionate (Seretide or Advair) or budesonide/formoterol (Symbicort) is preferred for convenience and avoids any risk that LABA might be used as monotherapy. As formoterol has a rapid onset of bronchodilator effect, the budesonide/formoterol combination can be used for both the maintenance and reliever components of asthma treatment (Symbicort SMART) and this is endorsed as an effective treatment by the Global Initiative for Asthma. The efficacy of this approach has been evaluated in a series of well conducted, controlled studies. Current control of asthma symptoms is improved or achieved with reduced total dose administration with Symbicort SMART compared with any reasonable alternate option. In every study, the risk of severe exacerbations was lower with Symbicort SMART than comparator treatment. Patients who benefit to the greatest extent are those with evidence of more severe asthma and greater exacerbation risk. When initiated in suitable patients in conjunction with appropriate education, Symbicort SMART is dominant in pharmacoeconomic terms. Symbicort SMART delivers improved asthma outcomes with lower treatment and social costs than any alternative.

Japanese guidelines for childhood asthma 2017.

Science.gov (United States)

Arakawa, Hirokazu; Hamasaki, Yuhei; Kohno, Yoichi; Ebisawa, Motohiro; Kondo, Naomi; Nishima, Sankei; Nishimuta, Toshiyuki; Morikawa, Akihiro

2017-04-01

The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2017 (JAGL 2017) includes a minor revision of the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. The section on child asthma in JAGL 2017 provides information on how to diagnose asthma between infancy and adolescence (0-15 years of age). It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. This guideline will be of interest to non-specialist physicians involved in the care of children with asthma. JAGL differs from the Global Initiative for Asthma Guideline in that JAGL emphasizes diagnosis and early intervention of children with asthma at asthma control levels, is easy to understand; thus, this guideline is suitable for the routine medical care of children with asthma. JAGL also recommends using a control test in children, so that the physician aims for complete control by avoiding exacerbating factors and appropriately using anti-inflammatory drugs (for example, inhaled corticosteroids and leukotriene receptor antagonists). Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. 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...

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].)....

Asthma and Pregnancy: Possible to prevent complications?- With Special reference to the impact of obesity and type of airwayinflammation

Science.gov (United States)

Ali, Zarqa

2017-12-01

Background Asthma is a serious global health issue and the most prevalent chronic disorder among Danish pregnant women. Exacerbations of asthma during pregnancy have been associated with increased risk of adverse pregnancy and perinatal outcomes, and by that making asthma a potential serious medical condition during pregnancy. Monitoring of asthma every four to six weeks is recommended during pregnancy, although evidence is lacking that following this recommendation will improve pregnancy outcome and, not least, be beneficial for all pregnant women with asthma. Aim The overall aim of the present thesis was to gain more knowledge of the interaction between asthma and pregnancy. The specific research questions were to identify pregnancies with low risk of an exacerbation during pregnancy, to identify risk factors for an exacerbation during pregnancy, and to compare the adverse pregnancy and perinatal outcomes in women without asthma and women with asthma monitored closely as recommended during pregnancy. Methods In study I and II, determinants of pregnancies with low risk of an exacerbation and maternal pregnancy-related risk factors for an exacerbations were investigated in a large prospective cohort study with 1.283 women with asthma. The Management of Asthma during Pregnancy (MAP) was initiated in 2007, and all pregnant women referred to Hvidovre Hospital have since then received an invitation to participate. Women were followed-up every four weeks with assessment of asthma control and adjustment of medication if necessary. In study III, the potential differences in airway hyperresponsiveness and airway inflammation, in participants (n=50) from the MAP cohort, were investigated in a post-partum examination. In study IV, the effect of maternal asthma on obstetrical and perinatal outcomes was investigated in a large case-control study, with 938 cases i.e. women with asthma from the MAP cohort, and 2.778 controls i.e. women without asthma. Results No history of pre

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

Science.gov (United States)

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.

Clinical characteristics of eosinophilic asthma exacerbations

DEFF Research Database (Denmark)

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

2017-01-01

blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction...... at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P...... = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P

Remote versus face-to-face check-ups for asthma.

Science.gov (United States)

Kew, Kayleigh M; Cates, Christopher J

2016-04-18

Evaluation (GRADE) approach. Six studies including a total of 2100 participants met the inclusion criteria: we pooled four studies including 792 people in the main efficacy analyses, and presented the results of a cluster implementation study (n = 1213) and an oral steroid tapering study (n = 95) separately. Baseline characteristics relating to asthma severity were variable, but studies generally recruited people with asthma taking regular medications and excluded those with COPD or severe asthma. One study compared the two types of check-up for oral steroid tapering in severe refractory asthma and we assessed it as a separate question. The studies could not be blinded and dropout was high in four of the six studies, which may have biased the results.We could not say whether more people who had a remote check-up needed oral corticosteroids for an asthma exacerbation than those who were seen face-to-face because the confidence intervals (CIs) were very wide (OR 1.74, 95% CI 0.41 to 7.44; 278 participants; one study; low quality evidence). In the face-to-face check-up groups, 21 participants out of 1000 had exacerbations that required oral steroids over three months, compared to 36 (95% CI nine to 139) out of 1000 for the remote check-up group. Exacerbations that needed treatment in the Emergency Department (ED), hospital admission or an unscheduled healthcare visit all happened too infrequently to detect whether remote check-ups are a safe alternative to face-to-face consultations. Serious adverse events were not reported separately from the exacerbation outcomes.There was no difference in asthma control measured by the Asthma Control Questionnaire (ACQ) or in quality of life measured on the Asthma Quality of Life Questionnaire (AQLQ) between remote and face-to-face check-ups. We could rule out significant harm of remote check-ups for these outcomes but we were less confident because these outcomes are more prone to bias from lack of blinding.The larger implementation study

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

Science.gov (United States)

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.

Asthma Severity in patients initiating controller monotherapy versus combination therapy.

Science.gov (United States)

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.

Allergen aerosol from pollen-nucleated precipitation: A novel thunderstorm asthma trigger

Science.gov (United States)

Beggs, Paul John

2017-03-01

Thunderstorm asthma is the term used to describe epidemics of asthma exacerbation associated with thunderstorms. Most published reports of thunderstorm asthma have come from the United Kingdom, Canada, and Australia, although several studies have been published on the phenomenon in the USA and Europe (particularly Greece and Italy). Such reports usually consider changes in hospital admissions or emergency department attendances for asthma. For example, Celenza et al. (1996) studied an asthma epidemic in London in June 1994 where 40 patients presented to the accident and emergency department of St Mary's Hospital in the 24 hours after a thunderstorm compared to an average of just over 2 asthma presentations per day over the several weeks before and after this event. More recent examples include the 20 patients who presented to an emergency department in Puglia, Italy, for sudden and severe asthmatic symptoms immediately after a thunderstorm in May 2010, where the average daily emergency department presentations for asthma several weeks before and after this event was only 2 to 3 (Losappio et al., 2011); and the 36 emergency department presentations for acute asthma to the Austin Hospital in Melbourne, Australia, on 25 November 2010 immediately after a thunderstorm (with the number of such presentations on days prior to and following the epidemic ranging from 0 to 10) (Howden et al., 2011).

Viral asthma: implications for clinical practice

Directory of Open Access Journals (Sweden)

Roger Menendez

2010-07-01

Full Text Available Roger Menendez1, Michael D Goldman21Allergy and Asthma Center of El Paso, El Paso, TX, USA; 2Pulmonary Division, UCLA Gaffen School of Medicine, Los Angeles, CA, USAAbstract: The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.Keywords: asthma, rhinoviruses, exacerbations, epidemiology, phenotypes, clinical trials

Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

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Vogelmeier CF

2018-04-01

Full Text Available Claus F Vogelmeier,1 Kenneth R Chapman,2 Marc Miravitlles,3 Nicolas Roche,4 Jørgen Vestbo,5 Chau Thach,6 Donald Banerji,6 Robert Fogel,6 Francesco Patalano,7 Petter Olsson,8 Konstantinos Kostikas,7 Jadwiga A Wedzicha9 1Member of the German Center for Lung Research (DZL, Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany; 2Asthma and Airway Centre, University Health Network and University of Toronto, Toronto, ON, Canada; 3Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Service de Pneumologie AP-HP, Cochin Hospital, University Paris Descartes (EA2511, Paris, France; 5Institute of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Novartis Pharma AG, Basel, Switzerland; 8Novartis Sverige AB, Täby, Sweden; 9National Heart and Lung Institute, Imperial College London, London, UK Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY 110/50 µg with twice-daily salmeterol/fluticasone (SFC 50/500 µg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1 moderate/severe exacerbations according to prior exacerbation history and treatment, and 2 types of exacerbations according to health care resource utilization (HCRU during 1-year follow-up. Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75–0.93, ≥2 exacerbations (RR: 0.85, 95% CI: 0.70–1.03 and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74�

Asthma and Adherence to Inhaled Corticosteroids

DEFF Research Database (Denmark)

Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli

2015-01-01

Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, ... prescribed fixed-combination therapy (ICS and long-acting β2 agonists). Good adherence was associated with higher FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations, less use of oral corticosteroids, and lower mortality rate. Overall, 24% of exacerbations and 60% of asthma...

Study of the effect of anti-IgE (omalizumab on serum level of matrix metalloproteinase-9 as a marker of remodeling in severe asthmatic patients

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Nasr Affara

2015-10-01

Conclusion: Omalizumab can reduce asthma exacerbations and improve asthma control and pulmonary function. The reducing effect of omalizumab on metalloproteinase-9 serum level may contribute to decreased airway remodeling in patients with severe asthma.

High incidence of oral corticosteroids prescriptions in children with asthma in early childhood

NARCIS (Netherlands)

Arabkhazaeli, A.; Vijverberg, S.J.H.; Van Der Ent, C. Kors; Raaijmakers, J.A.M.; van der Zee, A.H.

2016-01-01

OBJECTIVE: Severe asthma exacerbations are often treated with short courses of oral corticosteroids (OCS). This study assessed the incidence of OCS being prescribed in asthmatic children of various age groups and calculated their chances of receiving subsequent OCS prescriptions. METHODS:

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

Science.gov (United States)

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

Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

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Amatullah Hajera

2011-02-01

Full Text Available Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA and challenged with nebulized PBS (OVA/PBS or OVA (OVA/OVA for three consecutive days (sub-acute model or 12 weeks (chronic model, which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3, or HEPA-filtered air (FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of

Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium

DEFF Research Database (Denmark)

Farzan, Niloufar; Vijverberg, Susanne J; Andiappan, Anand K

2017-01-01

AIM: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. MATERIALS & METHODS: Investigators of each study participating in PiCA provided data...... corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center...

Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease

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van Geffen WH

2018-04-01

Full Text Available Wouter H van Geffen,1,2 Huib AM Kerstjens2 1Department of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, the Netherlands; 2Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands Background: Static hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD (AECOPD, but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear. Methods: In a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state at least 42 days later: inspiratory capacity (IC, body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea. Results: Forty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05±0.11 L and increased again during resolution by 15.6%±23.1% or 0.28±0.08 L (mean ± standard error of the mean, p<0.01. Testing of metronome-paced changes in IC was feasible, and it decreased by 0.74±0.06 L at admission, similarly to at stable state. Clinical COPD Questionnaire score was 3.7±0.2 at admission and improved by 1.7±0.2 points (p<0.01, and the Borg dyspnea score improved by 2.2±0.5 points from 4.4±0.4 at admission (p<0.01. Conclusion: Static hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase. Keywords: COPD, exacerbations of COPD, static hyperinflation, dynamic hyperinflation, severe acute exacerbations of COPD, COPD exacerbation, chronic obstructive pulmonary disease

SEVERE CHRONIC ALLERGIC (AND RELATED DISEASES: A UNIFORM APPROACH — A MEDALL-GA2LEN-ARIA POSITION PAPER IN COLLABORATION WITH THE WHO COLLABORATING CENTER FOR ASTHMA AND RHINITIS (ENGLISH & RUSSIAN VARIANTS

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J. Bousquet

2011-01-01

Full Text Available Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria, atopic dermatitis in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as co-morbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related diseases for clinical practice, research (including epidemiology, public health purposes, education and the discovery of novel therapies.Key words: IgE, allergy, severity, control, risk, asthma, rhinitis, rhinosinusitis, urticaria, atopic dermatitis.

Guidelines for the management of asthma in adults in South Africa ...

African Journals Online (AJOL)

Statement by a working group of the South African Pulmonology Society. The morbidity and mortality caused by asthma can be attributed to three factors: underassessment of severity, failure on the part of both patients and their medical attendants to initiate treatment promptly, and undertreatment of exacerbations; Moreover ...

Takotsubo cardiomyopathy: A known unknown foe of asthma.

Science.gov (United States)

Kotsiou, Ourania S; Douras, Alexandros; Makris, Demosthenes; Mpaka, Nikoleta; Gourgoulianis, Konstantinos I

2017-10-01

Patients with uncontrolled asthma are at a greater risk of asthma attacks requiring emergency room visits or hospital admissions. Takotsubo cardiomyopathy is potentially a significant complication in a course of status asthmaticus. We describe a 43-year-old female patient who presented with status asthmaticus that was further complicated with takotsubo cardiomyopathy. Recognizing apical ballooning syndrome is challenging in patients with a history of respiratory disease because the symptoms of the last entity may complicate the diagnostic approach. It is difficult to distinguish clinically apical ballooning syndrome from the acute airway exacerbation itself. Both asthma and takotsubo cardiomyopathy share the same clinical presentation with dyspnea and chest tightness. In our patient, the electrocardiographic abnormalities, the rapidly reversible distinctive characteristics of echocardiography, and the modest elevation of serum cardiac biomarkers levels, in combination with the presence of a stress trigger (severe asthma attack), strongly supported the diagnosis of broken heart syndrome. Clinicians should re-evaluate asthma management and be aware of the complications associated with asthma attacks such as stress-induced cardiomyopathy.

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

Effectiveness of asthma education with and without a self-management plan in hospitalized children.

Science.gov (United States)

Espinoza-Palma, Tatiana; Zamorano, Alejandra; Arancibia, Francisca; Bustos, María-Francisca; Silva, Maria José; Cardenas, Consuelo; De La Barra, Pedro; Puente, Victoria; Cerda, Jaime; Castro-Rodriguez, José A; Prado, Francisco

2009-11-01

Background. Formal education in primary care can reduce asthma exacerbations. However, there are few studies in hospitalized children, with none originating in Latin America. Methods. A prospective randomized study was designed to evaluate whether a full education with self-management plan (ESM) was more effective than an education without self-management plan (E) in reducing asthma hospitalization. Children (5 to 15 years of age) who were hospitalized for an asthma attack were divided in two groups. Children in the E group received general instructions based on a booklet. Those in the ESM group received the same booklet plus a self-management guide and a puzzle game that reinforces the lessons learned in the booklet. Patients were interviewed every 3 months, by telephone, for one year. Interviewers recording the number of hospitalizations, exacerbations, and emergency visits for asthma and oral steroid burst uses. Results. From 88 children who met the inclusion criteria, 77 (86%) completed one year of follow-up (41 from E and 36 from ESM group). Overall, after one year, the hospitalization decreased by 66% and the inhaled corticosteroids therapy increased from 36% to 79%. At the end of the study, there was no difference in exacerbations, emergency visits, oral steroid burst uses, or hospitalizations between the two groups. Conclusions. Asthma education with or without a self-management plan during asthma hospitalization were effective in reducing exacerbations, emergency visits, oral steroid burst uses, and future rehospitalizations. This evidence supports the importance of providing a complete asthma education plan in any patient who is admitted for asthma exacerbation.

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

Science.gov (United States)

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.

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.

Clinical characteristics of children and adolescents with severe therapy-resistant asthma in Brazil

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Andrea Mendonça Rodrigues

2015-08-01

Full Text Available AbstractObjective: To describe the clinical characteristics, lung function, radiological findings, and the inflammatory cell profile in induced sputum in children and adolescents with severe therapy-resistant asthma (STRA treated at a referral center in southern Brazil.Methods: We retrospectively analyzed children and adolescents (3-18 years of age with uncontrolled STRA treated with high-dose inhaled corticosteroids and long-acting β2 agonists. We prospectively collected data on disease control, lung function, skin test reactivity to allergens, the inflammatory cell profile in induced sputum, chest CT findings, and esophageal pH monitoring results.Results: We analyzed 21 patients (mean age, 9.2 ± 2.98 years. Of those, 18 (86% were atopic. Most had uncontrolled asthma and near-normal baseline lung function. In 4 and 7, induced sputum was found to be eosinophilic and neutrophilic, respectively; the inflammatory cell profile in induced sputum having changed in 67% of those in whom induced sputum analysis was repeated. Of the 8 patients receiving treatment with omalizumab (an anti-IgE antibody, 7 (87.5% showed significant improvement in quality of life, as well as significant reductions in the numbers of exacerbations and hospitalizations.Conclusions: Children with STRA present with near-normal lung function and a variable airway inflammatory pattern during clinical follow-up, showing a significant clinical response to omalizumab. In children, STRA differs from that seen in adults, further studies being required in order to gain a better understanding of the disease mechanisms.

Auranofin in the treatment of steroid dependent asthma: a double blind study.

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Nierop, G; Gijzel, W P; Bel, E H; Zwinderman, A H; Dijkman, J H

1992-01-01

BACKGROUND: Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti-inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated. METHODS: A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids. RESULTS: Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable. CONCLUSION: Auranofin provides an effective adjunct to treatment for steroid

New drugs for asthma.

Science.gov (United States)

Colice, Gene L

2008-06-01

The goal of asthma therapy is to reduce symptoms to the extent that patients can lead active, unlimited lives and to minimize concern about exacerbations. Unfortunately, despite advances in our understanding of the pathophysiology of asthma and the existence of consensus asthma-management guidelines, patients with asthma still suffer considerable morbidity and, on rare occasions, death. Part of the reason for suboptimal asthma control is poor adherence, by both providers and patients, to the recommended asthma regimens and guidelines. However, even under the ideal circumstances of a motivated patient and a knowledgeable physician, the available asthma drugs are not effective in all patients at all times. The market for asthma drugs has been dynamic; numerous new products have recently been approved for marketing by the Food and Drug Administration. Unfortunately, the products recently approved and those likely to enter the market soon mostly are either reformulations or combinations of established molecules. Developing new drugs to treat asthma, particularly with novel anti-inflammatory properties, should be a priority.

Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma

NARCIS (Netherlands)

Hellings, P. W.; Vandekerckhove, P.; Claeys, R.; Billen, J.; Kasran, A.; Ceuppens, J. L.

2003-01-01

Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone. This study was aimed to explore the effect of exogenously administered

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

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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

Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications.

Science.gov (United States)

Sandur, V; Murugesh, M; Banait, V; Rathi, P M; Bhatia, S J; Joshi, J M; Kate, A

2014-01-01

The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH 5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH reflux symptom score(RSS) improved from 22.39 ± 14.99 to 1.04 ± 1.07, pulmonary symptom score(PSS) improved from 27.14 ± 7.49 to 13.82 ± 4.21 and night time asthma symptom score(NASS) improved from 6.71 ± 1.80 to 3.04 ± 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 ± 0.57 and 4.14 ± 1.97 to 1.47 ± 0.54 and 5.56 ± 1.72, respectively (p-value 0.00114). PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients.

International trends in admissions and drug sales for asthma.

Science.gov (United States)

Gupta, R; Anderson, H R; Strachan, D P; Maier, W; Watson, L

2006-02-01

To test whether national patterns of asthma drug use, particularly inhaled corticosteroids (ICS), are related to the rate of acute severe asthma exacerbations. The relation of international trends in hospital admissions for asthma with asthma drug sales was examined using country-specific regressions over the period 1990-1999. Pooled estimates of the regression coefficients were calculated using random effects models. Data on asthma admissions and asthma drug sales (including the sub-category ICS) were obtained from 11 countries. There was a negative relationship between falling admissions and rising sales of respiratory drugs and ICS in 9 of these 11 countries. A pooled estimate of the change in asthma admission rate per 10,000 associated with a unit increase in sales rate was -6.3 (95% CI -10.4 - -2.3) for all asthma drugs and -11.2 (95% CI -19.7 - -2.8) for ICS. At the national level, there is good evidence that over the last decade, increased sales of asthma drugs, and ICS in particular, were associated with a decline in rates of hospital admission for asthma. This is consistent with a beneficial effect of increasing use of asthma drugs, but other explanations such as decreasing prevalence could also be responsible.

Work-related asthma

African Journals Online (AJOL)

occupational exposure is 16% and for work-exacerbated asthma around 10%.3,4 ... Mohamed Jeebhay is a Professor of Occupational Medicine at the University of Cape Town. He convenes .... (obtain material safety data sheets. (MSDs) for ...

Genetic associations with viral respiratory illnesses and asthma control in children

DEFF Research Database (Denmark)

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

2016-01-01

of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled...... in the Childhood Origins of Asthma (COAST) birth cohort study. RESULTS: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment...... differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma....

Influences on hospital admission for asthma in south Asian and white adults: qualitative interview study.

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Griffiths, C; Kaur, G; Gantley, M; Feder, G; Hillier, S; Goddard, J; Packe, G

2001-10-27

To explore reasons for increased risk of hospital admission among south Asian patients with asthma. Qualitative interview study using modified critical incident technique and framework analysis. Newham, east London, a deprived area with a large mixed south Asian population. 58 south Asian and white adults with asthma (49 admitted to hospital with asthma, 9 not admitted); 17 general practitioners; 5 accident and emergency doctors; 2 out of hours general practitioners; 1 asthma specialist nurse. Patients' and health professionals' views on influences on admission, events leading to admission, general practices' organisation and asthma strategies, doctor-patient relationship, and cultural attitudes to asthma. South Asian and white patients admitted to hospital coped differently with asthma. South Asians described less confidence in controlling their asthma, were unfamiliar with the concept of preventive medication, and often expressed less confidence in their general practitioner. South Asians managed asthma exacerbations with family advocacy, without systematic changes in prophylaxis, and without systemic corticosteroids. Patients describing difficulty accessing primary care during asthma exacerbations were registered with practices with weak strategies for asthma care and were often south Asian. Patients with easy access described care suggesting partnerships with their general practitioner, had better confidence to control asthma, and were registered with practices with well developed asthma strategies that included policies for avoiding hospital admission. The different ways of coping with asthma exacerbations and accessing care may partly explain the increased risk of hospital admission in south Asian patients. Interventions that increase confidence to control asthma, confidence in the general practitioner, understanding of preventive treatment, and use of systemic corticosteroids in exacerbations may reduce hospital admissions. Development of more sophisticated

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

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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.

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

Majority of never-smokers with airflow limitation do not have asthma: the Copenhagen General Population Study.

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Çolak, Yunus; Afzal, Shoaib; Nordestgaard, Børge G; Lange, Peter

2016-07-01

A substantial proportion of individuals with airflow limitation are never-smokers. However, whether never-smokers with airflow limitation have undiagnosed asthma is unknown. We hypothesised that the majority of never-smokers with respiratory symptoms and airflow limitation but without known asthma have undiagnosed asthma by comparing characteristics and prognosis in never-smokers with airflow limitation and asthma (NS+AFL+A) with never-smokers with airflow limitation but without asthma (NS+AFL-A). Among 94 079 participants aged 20-100 years from the general population, 39 102 (42%) were never-smokers. In this group, 13 719 (35%) reported to have respiratory symptoms of whom 1610 (12%) had airflow limitation. We investigated characteristics and risk of complications (asthma or COPD exacerbations, pneumonias and all-cause mortality) and comorbidities (lung cancer, ischaemic heart disease, myocardial infarction, deep venous thrombosis and PE) during 4.5 years median follow-up. NS+AFL-A compared with NS+AFL+A reported less allergy and respiratory symptoms, and had higher FEV1 and lower levels of eosinophils and IgE in peripheral blood. NS+AFL+A had increased risk of asthma and COPD exacerbations, but not of pneumonias; adjusted HRs in NS+AFL+A compared with NS+AFL-A were 16 (95% CI 3.7 to 73) for asthma exacerbations and 15 (2.8 to 80) for COPD exacerbations. Still, NS+AFL-A had increased risk of COPD exacerbations and pneumonias, but not of asthma exacerbations; adjusted HRs in NS+AFL-A compared with never-smokers without airflow limitation or asthma (NS-AFL-A) were 7.7 (2.8 to 21) for COPD exacerbations and 1.7 (1.3 to 2.3) for pneumonias. Risk of comorbidities or all-cause mortality was not increased in NS+AFL-A or NS+AFL+A compared with NS-AFL-A. Majority of NS+AFL-A do not seem to have undiagnosed asthma and may instead have airflow limitation caused by other risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not

[Warning symptoms of asthma attack and asthma self-management: a national asthma control survey from China].

Science.gov (United States)

Lin, J T; Wang, W Q; Zhou, X; Wang, C Z; Huang, M; Cai, S X; Chen, P; Lin, Q C; Zhou, J Y; Gu, Y H; Yuan, Y D; Sun, D J; Yang, X H; Yang, L; Huo, J M; Chen, Z C; Jiang, P; Zhang, J; Ye, X W; Liu, H G; Tang, H P; Liu, R Y; Liu, C T; Zhang, W; Hu, C P; Chen, Y Q; Liu, X J; Dai, L M; Zhou, W; Huang, Y J; Xu, J Y

2017-08-08

Objective: To investigate warning symptoms of asthma attack and evaluate asthma self-management status of asthma patients in urban China. Methods: A multi-center, cross-sectional, questionnaire-based survey was carried out from 30 general hospitals dispersed in 30 provinces of mainland China (except for Tibet) during Oct 2015 to May 2016. Information of frequency and warning symptoms of asthma attack, the time from warning symptoms to asthma attack, the impact of asthma attack and asthma self-management were collected from asthma patients of outpatient department. Results: Altogether 3 875 asthmatic outpatients were recruited. 78.1% (3 026/3 875) of the patients reported restriction of exercise and daily activities during asthma exacerbation. 82.5% (3 160/3 829) of the patients had warning symptoms before asthma attack, the most common warning symptoms were cough, chest tightness and shortness of breath. The median time from warning symptoms to asthma attack was 2 h, the mean time was 90 h. Only 4.4% (167/3 829) of the patients had definite confidence to control asthma when symptoms deteriorated. 76.7% (2 937/3 828) of the patients used medications to control asthma when asthma symptoms deteriorated. Medication choice: inhaled corticosteroid (ICS) + formoterol 45.8% (1 776/3 875), short-acting beta-agonist (SABA) 23.9% (927/3 875). Conclusions: Most asthma patients have warning symptoms before asthma attack, the most common symptoms are cough, chest tightness and shortness of breath. The proportion of patients conducting effective asthma self-management remains low.

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...

Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia.

Science.gov (United States)

Singh, Shashi P; Chand, Hitendra S; Langley, Raymond J; Mishra, Neerad; Barrett, Ted; Rudolph, Karin; Tellez, Carmen; Filipczak, Piotr T; Belinsky, Steve; Saeed, Ali I; Sheybani, Aryaz; Exil, Vernat; Agarwal, Hemant; Sidhaye, Venkataramana K; Sussan, Thomas; Biswal, Shyam; Sopori, Mohan

2017-05-15

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies. Copyright © 2017 by The American Association of Immunologists, Inc.

The effect of COPD severity and study duration on exacerbation outcome in randomized controlled trials

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Eriksson G

2017-05-01

Full Text Available Göran Eriksson,1 Peter M Calverley,2 Christine R Jenkins,3,4 Antonio R Anzueto,5 Barry J Make,6 Magnus Lindberg,7 Malin Fagerås,7 Dirkje S Postma8 1Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 2Pulmonary and Rehabilitation Research Group, University Hospital Aintree, Liverpool, UK; 3Concord Clinical School, University of Sydney, 4The George Institute for Global Health, Sydney, Australia; 5Department of Pulmonary Medicine and Critical Care, University of Texas Health Sciences Center and South Texas Veterans’ Health Care System, San Antonio, Texas, 6Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado, Denver, Colorado, USA; 7AstraZeneca R&D, Mölndal, Sweden; 8Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, the Netherlands Background: When discontinuation in COPD randomized controlled trials (RCTs is unevenly distributed between treatments (differential dropout, the capacity to demonstrate treatment effects may be reduced. We investigated the impact of the time of differential dropout on exacerbation outcomes in RCTs, in relation to study duration and COPD severity.Methods: A post hoc analysis of 2,345 patients from three RCTs of 6- and 12-month duration was performed to compare budesonide/formoterol and formoterol in moderate, severe, and very severe COPD. Outcomes were exacerbation rate, time-to-first exacerbation, or discontinuation; patients were stratified by disease severity. Outcomes were studied by censoring data monthly from 1 to 12 months.Results: In patients treated with budesonide/formoterol, annualized exacerbation rates (AERs were comparable for each study duration (rate ratio [RR] =0.6. With formoterol, the AER decreased with study duration (RR =1.20 at 1 month to RR =0.86 at 12 months. There was a treatment-related difference in

A Survey of Asthma Management Practices and Implementation of ...

African Journals Online (AJOL)

2017-09-14

Sep 14, 2017 ... the participants regarding knowledge of asthma prevalence, asthma risk factors, and ..... pneumonia which are known to be more common among low birth weight ... poor symptom control and frequent exacerbations.[18] The.

Correlation between Bronchovascular and Cardiovascular Disorders in Children with Bronchial Asthma: Multifacetedness and Inexhaustibility of Problem Study

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T.Ye. Shumna

2014-11-01

Full Text Available Due to tight functional interrelation between respiratory apparatus and blood circulation, exacerbation of bronchial asthma in children is associated with changes of cardiovascular system. Multifacetedness of this problem determines comprehensive approach to examination of children with bronchial asthma, involving most available methods of heart function evaluation: echocardiographic heart study with Doppler sonography and electrocardiography. Of great importance is investigation of systemic and pulmonary hemodynamics and microcirculation in bronchial asthma depending on its clinical course. It was found that children with exacerbation of bronchial asthma were detected with pulmonary hypertension, which had gradual regression after attack alleviation. During the remission stage, hemodynamics disturbances in lesser circulation were present in long-lasting and severe course of disease. However, the increase in the pulmonary blood flow parameters in patients only in the early period after attack can be regarded as a compensatory response from the lesser circulation to the decline in respiratory function indices. Therefore, despite the great achievements of science in the study of pathophysiological mechanisms and clinical features of bronchial asthma at different ages, it is necessary to continue further study of all aspects of bronchial asthma in children, because it is not as well studied as asthma in adults.

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.

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids

Science.gov (United States)

Postma, Dirkje S.; Dekhuijzen, Richard; van der Molen, Thys; Martin, Richard J.; van Aalderen, Wim; Roche, Nicolas; Guilbert, Theresa W.; Israel, Elliot; van Eickels, Daniela; Khalid, Javaria Mona; Herings, Ron M.C.; Overbeek, Jetty A.; Miglio, Cristiana; Thomas, Victoria; Hutton, Catherine; Hillyer, Elizabeth V.

2017-01-01

Purpose Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). Methods This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. Results Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. Conclusions In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS. PMID:28102056

Asthma and PM10

Directory of Open Access Journals (Sweden)

Gilmour M Ian

2000-07-01

Full Text Available Abstract PM10 (the mass of particles present in the air having a 50% cutoff for particles with an aerodynamic diameter of 10 μm is the standard measure of particulate air pollution used worldwide. Epidemiological studies suggest that asthma symptoms can be worsened by increases in the levels of PM10. Epidemiological evidence at present indicates that PM10 increases do not raise the chances of initial sensitisation and induction of disease, although further research is warranted. PM10 is a complex mixture of particle types and has many components and there is no general agreement regarding which component(s could lead to exacerbations of asthma. However pro-inflammatory effects of transition metals, hydrocarbons, ultrafine particles and endotoxin, all present to varying degrees in PM10, could be important. An understanding of the role of the different components of PM10 in exacerbating asthma is essential before proper risk assessment can be undertaken leading to advice on risk management for the many asthmatics who are exposed to air pollution particles.

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

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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

Vitamin D and asthma in children.

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Gupta, Atul; Bush, Andrew; Hawrylowicz, Catherine; Saglani, Sejal

2012-12-01

Vitamin D deficiency and insufficiency are increasingly being recognized in the general population, and have been largely attributed to lifestyle changes (reduced exposure to sunshine due to working indoors or the use of protective clothing and sunscreen; changes in diet) over the last few decades. The musculoskeletal consequences of severe vitamin D deficiency are well established, however, a number of other disorders have now been linked to vitamin D insufficiency, including asthma. There is growing appreciation of the likely importance of vitamin D as a pleiotrophic mediator that contributes to pulmonary health. Children with asthma appear to be at increased risk of vitamin D insufficiency. Epidemiologic data suggest that low serum vitamin D in children with asthma is associated with more symptoms, exacerbations, reduced lung function, increased medication usage and severe disease. In vitro studies have demonstrated that vitamin D enhances steroid responsiveness in adult asthmatics. Vitamin D may play an important role in pulmonary health by inhibiting inflammation, in part through maintaining regulatory T cells, and direct induction of innate antimicrobial mechanisms. More research is required to fully understand the role of vitamin D in the maintenance of airway homeostasis and address the diagnostic and therapeutic implications vitamin D may have in the future of asthma management. This review summarises the current understanding and uncertainties regarding the effect of vitamin D deficiency and insufficiency in children with asthma. Copyright © 2011. Published by Elsevier Ltd.

Association between severe asthma and changes in the stomatognathic system.

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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.

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

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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.

Switching patients from other inhaled corticosteroid devices to the Easyhaler®: historical, matched-cohort study of real-life asthma patients

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Price D

2014-04-01

Full Text Available David Price,1,2 Vicky Thomas,2 Julie von Ziegenweidt,2 Shuna Gould,2 Catherine Hutton,2 Christine King2 1Academic Centre of Primary Care, University of Aberdeen, Aberdeen, UK; 2Research in Real Life, Oakington, Cambridge, UK Purpose: To investigate the clinical and cost effectiveness of switching real-life asthma patients from other types of inhalers to the Easyhaler® (EH for the administration of inhaled corticosteroids (ICS. Patients and methods: Historical, matched-cohort study of 1,958 asthma patients (children and adults treated in UK primary-care practices, using data obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink. Other inhalers (OH included pressurized metered-dose inhalers, breath-actuated inhalers, and dry-powder inhalers, delivering beclomethasone, budesonide, fluticasone, or ciclesonide. Patients remaining on OH unchanged (same drug, dosage, and device; n=979 were matched 1:1 with those switched to the EH (beclomethasone or budesonide at the same or lower ICS dosage (n=979, based on age, sex, year of index patient review/switch, most recent ICS drug, dosage, and device, and the number of severe exacerbations and average daily short-acting β2 agonist (SABA dosage in the preceding year. Clinical outcomes and health care costs were compared between groups for 12 months before and after the switch. Co-primary clinical outcomes were: 1 risk domain asthma control (RDAC – no asthma-related hospitalization, acute oral steroid use, or lower respiratory tract infection (LRTI; 2 exacerbation rate (American Thoracic Society [ATS] definition – where exacerbation is asthma-related hospitalization or acute oral steroid use; 3 exacerbation rate (clinical definition – where exacerbation is ATS exacerbation or LRTI; and 4 overall asthma control (OAC – RDAC plus average salbutamol-equivalent SABA dosage ≤200 μg/day. Non-inferiority (at least equivalence of EH was tested against OH for the

Association between asthma and female sex hormones.

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Baldaçara, Raquel Prudente de Carvalho; Silva, Ivaldo

2017-01-01

The relationship between sex hormones and asthma has been evaluated in several studies. The aim of this review article was to investigate the association between asthma and female sex hormones, under different conditions (premenstrual asthma, use of oral contraceptives, menopause, hormone replacement therapy and pregnancy). Narrative review of the medical literature, Universidade Federal do Tocantins (UFT) and Universidade Federal de São Paulo (Unifesp). We searched the CAPES journal portal, a Brazilian platform that provides access to articles in the MEDLINE, PubMed, SciELO, and LILACS databases. The following keywords were used based on Medical Subject Headings: asthma, sex hormones, women and use of oral contraceptives. The associations between sex hormones and asthma remain obscure. In adults, asthma is more common in women than in men. In addition, mortality due to asthma is significantly higher among females. The immune system is influenced by sex hormones: either because progesterone stimulates progesterone-induced blocking factor and Th2 cytokines or because contraceptives derived from progesterone and estrogen stimulate the transcription factor GATA-3. The associations between asthma and female sex hormones remain obscure. We speculate that estrogen fluctuations are responsible for asthma exacerbations that occur in women. Because of the anti-inflammatory action of estrogen, it decreases TNF-α production, interferon-γ expression and NK cell activity. We suggest that further studies that highlight the underlying physiopathological mechanisms contributing towards these interactions should be conducted.

The association between previous and future severe exacerbations of chronic obstructive pulmonary disease: Updating the literature using robust statistical methodology.

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Sadatsafavi, Mohsen; Xie, Hui; Etminan, Mahyar; Johnson, Kate; FitzGerald, J Mark

2018-01-01

There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course. Previous studies on this topic did not generate causally-interpretable estimates. Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients. Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes. We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events. Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics. 35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up. The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations. This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event. The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality. There was substantial heterogeneity in the individual-specific rate of severe exacerbations. Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile. Using robust statistical methodology that controlled

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

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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

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.

Wireless Sensor-Dependent Ecological Momentary Assessment for Pediatric Asthma mHealth Applications.

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Buonocore, Chris M; Rocchio, Rosemary A; Roman, Alfonso; King, Christine E; Sarrafzadeh, Majid

2017-07-01

Pediatric asthma is a prevalent chronic disease condition that can benefit from wireless health systems through constant symptom management. In this paper, we propose a smart watch based wireless health system that incorporates wireless sensing and ecological momentary assessment (EMA) to determine an individual's asthma symptoms. Since asthma is a multifaceted disease, this approach provides individualized symptom assessments through various physiological and environmental wireless sensor based EMA triggers specific to common asthma exacerbations. Furthermore, the approach described here improves compliance to use of the system through insightful EMA scheduling related to sensor detected environmental and physiological changes, as well as the patient's own schedule. After testing under several real world conditions, it was found that the system is sensitive to both physiological and environmental conditions that would cause asthma symptoms. Furthermore, the EMA questionnaires that were triggered based on these changes were specific to the asthma trigger itself, allowing for invaluable context behind the data to be collected.

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

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Bjerregaard, A; Laing, I A; Backer, V; Sverrild, A; Khoo, S-K; Chidlow, G; Sikazwe, C; Smith, D W; Le Souëf, P; Porsbjerg, C

2017-08-01

The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033). Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies. © 2017 John Wiley & Sons Ltd.

cFLIP expression is altered in severe corticosteroid-resistant asthma

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