History Of Asthma Exacerbations Research Articles

Lebrikizumab in Uncontrolled Asthma: Reanalysis in a Well-Defined Type 2 Population

LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting IL-13 in patients with uncontrolled asthma. Failure to demonstrate efficacy may have been related to patient selection in those trials. To assess the efficacy in a well-defined subpopulation of patients with elevated blood eosinophil counts and a minimum number of prior asthma exacerbations. We performed an additional analysis in a subpopulation of patients with elevated FeNO and prior exacerbations. Adult (LI and LII) and adolescent patients (aged 12-17 years weighing ≥40 kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125 mg, n= 832; or 37.5 mg, n= 829) or placebo (n= 833) subcutaneously every 4 weeks. Post hoc analysis of the annualized adjusted exacerbation rate (AER) was performed in a subpopulation of patients with baseline blood eosinophils of 300 cells/μL or greater and history of one or more exacerbations. In this subpopulation, there were 227 patients in the placebo group, 222 in the lebrikizumab 37.5-mg group, and 217 in the lebrikizumab 125-mg group. We summarized safety in patients who received at least one dose of lebrikizumab using adverse events. Lebrikizumab significantly reduced AER compared with placebo in adults (AER reduction: 125 mg [38%]; and 37.5 mg [41%]) and adolescents (AER reduction:125 mg [59%]; 37.5 mg [64%]) with baseline blood eosinophils of 300 cells/μL or greater and one or more exacerbations. Most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. Lebrikizumab significantly reduced asthma exacerbations in a subpopulation of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation.

Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis.

Current guidelines recommend a higher-dose inhaled corticosteroids (ICS) or adding a long-acting muscarinic antagonist (LAMA) when asthma is not controlled with medium-dose (MD) ICS/long-acting beta2-agonist (LABA) combination therapy. To assess the effectiveness and safety of dual (ICS/LABA) and triple therapies (ICS/LABA/LAMA) compared with each other and with varying doses of ICS in adolescents and adults with uncontrolled asthma. We searched multiple databases for pre-registered randomised controlled trials (RCTs) of at least 12 weeks of study duration from 2008 to 18 February 2022. We searched studies, including adolescents and adults with uncontrolled asthma who had been treated with, or were eligible for, MD-ICS/LABA, comparing dual and triple therapies. We excluded cluster- and cross-over RCTs. We conducted a systematic review and network meta-analysis according to the previously published protocol. We used Cochrane's Screen4ME workflow to assess search results and Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. The primary outcome was steroid-requiring asthma exacerbations and asthma-related hospitalisations (moderate to severe and severe exacerbations). We included 17,161 patients with uncontrolled asthma from 17 studies (median duration 26 weeks; mean age 49.1 years; male 40%; white 81%; mean forced expiratory volume in 1 second (MEF 1)1.9 litres and 61% predicted). The quality of included studies was generally good except for some outcomes in a few studies due to high attrition rates. Medium-dose (MD) and high-dose (HD) triple therapies reduce steroid-requiring asthma exacerbations (hazard ratio (HR) 0.84 [95% credible interval (CrI) 0.71 to 0.99] and 0.69 [0.58 to 0.82], respectively) (high-certainty evidence), but not asthma-related hospitalisations, compared to MD-ICS/LABA. High-dose triple therapy likely reduces steroid-requiring asthma exacerbations compared to MD triple therapy (HR 0.83 [95% CrI 0.69 to 0.996], [moderate certainty]). Subgroup analyses suggest the reduction in steroid-requiring exacerbations associated with triple therapies may be only for those with a history of asthma exacerbations in the previous year but not for those without. High-dose triple therapy, but not MD triple, results in a reduction in all-cause adverse events (AEs) and likely reduces dropouts due to AEs compared to MD-ICS/LABA (odds ratio (OR) 0.79 [95% CrI 0.69 to 0.90], [high certainty] and 0.50 [95% CrI 0.30 to 0.84], [moderate certainty], respectively). Triple therapy results in little to no difference in all-cause or asthma-related serious adverse events (SAEs) compared to dual therapy (high certainty). The evidence suggests triple therapy results in little or no clinically important difference in symptoms or quality of life compared to dual therapy considering the minimal clinically important differences (MCIDs) and HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA. Medium-dose and HD triple therapies reduce steroid-requiring asthma exacerbations, but not asthma-related hospitalisations, compared to MD-ICS/LABA especially in those with a history of asthma exacerbations in the previous year. High-dose triple therapy is likely superior to MD triple therapy in reducing steroid-requiring asthma exacerbations. Triple therapy is unlikely to result in clinically meaningful improvement in symptoms or quality of life compared to dual therapy considering the MCIDs. High-dose triple therapy, but not MD triple, results in a reduction in all-cause AEs and likely reduces dropouts due to AEs compared to MD-ICS/LABA. Triple therapy results in little to no difference in all-cause or asthma-related SAEs compared to dual therapy. HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA, although long-term safety of higher rather than MD- ICS remains to be demonstrated given the median duration of included studies was six months. The above findings may assist deciding on a treatment option when asthma is not controlled with MD-ICS/LABA.

Risk Factors for Exacerbations in School-Age Children with Asthma

Introduction: Awareness of risk factors for asthma exacerbation can reduce the morbidity and mortality of the disease. The current study aimed to investigate the risk factors associated with current asthma exacerbations in school-age children. Methods: This study enrolled children who were admitted to a tertiary outpatient paediatric allergy and asthma department and were diagnosed with asthma. Patients and their caregivers underwent an interviewer-administered questionnaire, which obtained information regarding the demographic features and parameters to determine environmental exposures along with previous disease history. Laboratory examinations, including complete blood count with differential, total IgE levels, skin prick tests, and pulmonary function tests, were also performed. Results: A total of 431 children (288 male, 66.8%) with a median age (interquartile range) of 8.1 (6.3–11.2) years were included, among whom 265 (61.5%) had aeroallergen sensitization. Asthma was controlled, partially controlled, and uncontrolled in 154 (35.7%), 53 (12.3%), and 143 (33.2%) patients, respectively. A total of 81 patients (18.8%) experienced asthma exacerbation. Multivariate logistic regression analysis revealed that a history of asthma exacerbation within the last year (odds ratio [confidence interval]) (20.73 [9.95–43.20]; p < 0.001), a shorter asthma duration (<2.5 years) (2.58 [1.44–4.61]; p = 0.001), and a lack of regular controller therapy (4.12 [1.54–10.98]; p = 0.005) were associated with current asthma exacerbation. Discussion/Conclusion: Awareness of risk factors for asthma exacerbation may help physicians treat school-age children with asthma by providing prompt and rational interventions in order to prevent asthma exacerbations.

Optimal follow-up period after switching to another inhaled corticosteroid/long-acting β2 agonist in patients with asthma: A retrospective study using Japanese administrative claims data.

Switching inhalation devices is a reasonable option if problems with control, adherence, or inhalation technique occur in patients with asthma treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA). However, evidence to determine the extent to which the carefully monitored period persists after switching is insufficient. In this study, we aimed to investigate the duration of the carefully monitored period after switching to another ICS/LABA. This retrospective study used claims data from Japanese health insurance associations from May 2014 to April 2019. A total of 1,951 patients who switched to another ICS/LABA during the study period were selected for analysis. The relative risk of the first exacerbation after switching was calculated for each four-week interval after the switch compared with that before the switch in a self-controlled case series design. We further assessed patient background associated with exacerbations during the follow-up period. In the primary analysis, the risk of asthma exacerbation compared to the control period was derived from a conditional logistic regression model, which showed a significant decrease immediately after the switch (1 to 4 weeks, Odds ratio [OR] 0.37, 95% confidence interval [CI] 0.26–0.54). Subsequently, the risk increased again and was not significantly different from the control period until week 32 (OR 0.55, 95% CI 0.29–1.04). In a sensitivity analysis among patients with a history of exacerbations, up to week 20 was the period of no continuous risk reduction (OR 0.84, 95% CI 0.41–1.70). In the secondary analysis, chronic rhinosinusitis, sleep disorders, and a history of asthma exacerbation were significantly associated with asthma exacerbation. The incidence of exacerbation remained high for approximately 4 to 7 months after patients with asthma switched to another ICS/LABA. Therefore, these patients should be carefully monitored for at least 4 to 7 months and should be re-assessed at an earlier point in time, if necessary.

Factors Associated with Asthma Exacerbations During Pregnancy

Asthma exacerbations during pregnancy are associated with adverse pregnancy outcomes. The aim of this study was to establish factors associated with asthma exacerbations during pregnancy. We obtained data from three cohorts of pregnant women with asthma recruited in eastern Australia (2004-2019; n= 1461). Severe exacerbations were defined as episodes of asthma requiring hospitalization, an emergency department visit, or prescription of oral corticosteroids after enrollment. Baseline information on potential risk factors included demographic characteristics, asthma characteristics (eg, lung function, asthma triggers, asthma control, medication use), pregnancy factors (eg, fetal sex, parity, antenatal care type), and other maternal factors (body mass index, smoking status, mental health). Backward stepwise logistic regression and Akaike information criterion were used to determine the best-fitting model. A total of 135 participants experienced a severe exacerbation during pregnancy (9.2%). Medium to high ICS dose was most strongly associated with severe asthma exacerbations (adjusted odds ratio= 3.20; 95% confidence interval, 1.85-5.53). Worse asthma control, possession of a written action plan, and a history of asthma exacerbations in the year preceding pregnancy were associated with an increased rate of exacerbations. Asthma exacerbations before pregnancy and more severe asthma at the beginning of pregnancy were associated with an increased rate of exacerbations during pregnancy. Despite Global Initiative for Asthma step 3 and 4 treatment and optimal management including a written asthma action plan, there is still a significant asthma burden in a group of women at high risk for severe exacerbations in pregnancy.

Influence of seasonal changes on asthma exacerbation in a sudan savanna region: An analysis of 87 cases

Background:Asthma accounts for 1 out of every 250 deaths worldwide. Many of these deaths are preventable as they occur as a result of suboptimal long-term medical care and delay in seeking help during severe exacerbation. It is believed that increased concentrations of dust, high winds, low temperatures, and low humidity may cause exacerbation of asthma.Objective:The aim of this study is to assess seasonal variation in asthma exacerbation among patients attending Usmanu Danfodiyo University Teaching Hospital, Sokoto.Materials and Methods:Eighty-seven patients aged 16 years and above with physician-diagnosed asthma were selected by systematic random sampling. Clinical information was obtained from each participant about history of asthma exacerbation and health-care utilization. Meteorological data were obtained from the Nigerian Meteorological Agency corresponding to period of patient's recruitment.Results:Eighty-seven patients comprising 60 females and 27 males aged 32.1 ± 10.8 years participated in the study. Among the study participants, 50.6%, 28.7%, and 20.7% had exacerbation during harmattan, rainy, and dry (hot) seasons, respectively. Correlation analysis shows a significant negative relationship between temperature and asthma exacerbation (r = −0.372, P < 0.01).Conclusion:This study shows that asthma exacerbation is most frequent during the harmattan season and low temperature is associated with its exacerbation.

Once-daily mometasone plus indacaterol versus mometasone or twice-daily fluticasone plus salmeterol in patients with inadequately controlled asthma (PALLADIUM): a randomised, double-blind, triple-dummy, controlled phase 3 study

Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β2-adrenoceptor agonists (LABA) are considered safe and efficacious in asthma management. Most available FDCs require twice-daily dosing to achieve optimum therapeutic effect. The objective of the PALLADIUM study was to assess the efficacy and safety of once-daily FDC of mometasone furoate plus indacaterol acetate (MF-IND) versus mometasone furoate (MF) monotherapy in patients with inadequately controlled asthma. This 52-week, double-blind, triple-dummy, parallel-group, phase 3 study recruited patients from 316 centres across 24 countries. Patients aged 12 to 75 years with a documented diagnosis of asthma for at least 1 year, percentage of predicted FEV1 of 50-85%, and an Asthma Control Questionnaire 7 score of at least 1·5 despite treatment with medium-dose or high-dose ICS or low-dose ICS plus LABA were included. A history of asthma exacerbations was not a study requirement. Participants were randomily assigned (1:1:1:1:1) via interactive response technology to receive one of the following treatments for 52 weeks: high-dose MF-IND (320 μg, 150 μg) or medium-dose MF-IND (160 μg, 150 μg) once daily via Breezhaler; high-dose MF (800 μg [400 μg twice daily]) or medium-dose MF (400 μg once daily) via Twisthaler; or high-dose fluticasone propionate-salmeterol xinafoate (FLU-SAL; 500 μg, 50 μg) twice daily via Diskus. Participants received placebo via inhalation through the Breezhaler, Twisthaler, or Diskus devices in the mornings and evenings, as appropriate. The primary endpoint was improvement in trough FEV1 with high-dose and medium-dose MF-IND versus respective MF doses from baseline at 26 weeks, analysed in the full analysis set by means of a mixed model for repeated measures. High-dose MF-IND once daily was compared with high-dose FLU-SAL twice daily for non-inferiority on improving trough FEV1 at week 26 with a margin of -90 mL using mixed model for repeated measures as one of the secondary endpoints. Safety was assessed in all patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02554786, and is completed. Between Dec 29, 2015, and May 4, 2018, 2216 patients were randomly assigned (high-dose MF-IND, n=445; medium-dose MF-IND, n=439; high-dose MF, n=442; medium-dose MF, n=444; high-dose FLU-SAL, n=446), of which 1973 (89·0%) completed the study treatment and 234 (10·6%) prematurely discontinued study treatment. High-dose MF-IND (treatment difference [Δ] 132 mL [95% CI 88 to 176]; p<0·001) and medium-dose MF-IND (Δ 211 mL [167 to 255]; p<0·001) showed superiority in improving trough FEV1 over corresponding MF doses from baseline at week 26. High-dose MF-IND was non-inferior to high-dose FLU-SAL in improving trough FEV1 from baseline at week 26 (Δ 36 mL [-7 to 80]; p=0·101). Overall, the incidence of adverse events was similar across the treatment groups. Once-daily FDC of ICS and LABA (MF-IND) significantly improved lung function over ICS monotherapy (MF) at week 26; high-dose MF-IND was non-inferior to twice-daily combination of ICS and LABA (high-dose FLU-SAL) for improvement in trough FEV1. The combination of MF-IND provides a novel once-daily dry powder option for asthma control. Novartis Pharmaceuticals.

Risk factors for asthma exacerbation among Hajj pilgrims: a case study from DKI Jakarta, Indonesia

BACKGROUND Hajj pilgrims are prone to asthma exacerbation because of the high transmission rate of respiratory infections, severe environmental factors, and high-intensity activities during the Hajj. Well-controlled asthma status and preventive efforts prior to the Hajj could reduce such exacerbations. This research aimed to determine the risk factors of asthma exacerbation during the Hajj to help establish preventive measures.&#x0D; METHODS Participants were evaluated at community health centers (puskesmas) through history taking, physical examination, and spirometry. The risk factors examined included a history of exacerbation one year before the Hajj, obesity, comorbidities (e.g., diabetes mellitus, hypertension, coronary heart disease), lung function, smoking, fitness level, and influenza vaccination. Asthma exacerbation while in Saudi Arabia was determined through direct observations by authors and physicians assigned to Hajj pilgrim groups and analysis of data obtained from questionnaires distributed to the pilgrims before their departure. Odds ratios (OR) were calculated using logistic regression.&#x0D; RESULTS Among 68 pilgrims with asthma, exacerbation occurred in 27 (40%) pilgrims. Risk of asthma exacerbation was significantly increased in the pilgrims with a history of exacerbation one year before the Hajj (OR = 4.27; 95% confidence interval [CI] = 1.156–15.829; p = 0.029) and obesity grade II (OR = 4.02; 95% CI = 1.151–14.097; p = 0.029). Other factors, including smoking, comorbidities, lung function, fitness level, obesity grade I, and influenza vaccination, were not significantly related to exacerbation.&#x0D; CONCLUSIONS Obesity grade II and history of asthma exacerbation one year before the Hajj are strong factors for asthma exacerbation during Hajj pilgrims.

The safety of mepolizumab for the treatment of asthma

ABSTRACTIntroduction: Asthma is an airway disease characterized by airway inflammation. It is associated with significant morbidity, mortality, and costs to the healthcare system and society. Interleukin-5 (IL-5) was identified for its role in eosinophil development, maturation, and survival in tissues, which has been related to disease severity and airway eosinophilia.Areas covered: In this review, we will present the pharmacokinetics and dynamics of mepolizumab in addition to efficacy and safety data.Expert Opinion: Mepolizumab is novel, new, first-in-class therapy targeting IL-5. It has been found to be particularly effective in the management of patients with asthma whose peripheral blood eosinophil count is at a well-defined cut point within the normative range. This easily available biomarker, along with a history of asthma exacerbations, has translated into a clinically significant reduction in asthma exacerbations and the dose of oral corticosteroids in patients who previously have been prednisone-dependent. The pivotal studies indicate that mepolizumab was well tolerated, with the most frequently reported adverse events being headache, nasopharyngitis, worsening of asthma, and local injection reactions. These study investigators did not report any deaths or anaphylaxis related to mepolizumab.

Positioning of Long-Acting Muscarinic Antagonists in the Management of Asthma.

Despite a range of efficacious therapies for asthma, including inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), a significant proportion of patients have poor asthma control and retain a risk of future worsening of their symptoms. Long-acting muscarinic antagonist (LAMA) bronchodilators offer a well-tolerated, efficacious, and cost-effective add-on to a patient's treatment. Of the LAMAs currently under investigation or available for the treatment of asthma, evidence from a comprehensive clinical trial program in adults and children shows that once-daily treatment with tiotropium provides benefits for patients with uncontrolled asthma despite the use of ICS and LABAs. Tiotropium is included in the Global Initiative for Asthma (GINA) strategy document as an add-on therapy option for patients at Step 4 or 5 with a history of asthma exacerbations. Tiotropium Respimat® has demonstrated safety and efficacy in patients with a range of disease severities, ages, and phenotypes. This review describes the evidence for the use of LAMA as add-on therapy for patients with asthma who remain uncontrolled despite the use of ICS and LABA treatments.

Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials

In phase 2 trials, lebrikizumab, an anti-interleukin-13 monoclonal antibody, reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma, particularly in those with high concentrations of type 2 biomarkers (eg, periostin or blood eosinophils). We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication. Adult patients with uncontrolled asthma, pre-bronchodilator FEV1 40-80% predicted, and stable background therapy were randomly assigned (1:1:1) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg, or placebo subcutaneously, once every 4 weeks. Randomisation was stratified by screening serum periostin concentration, history of asthma exacerbations within the last 12 months, baseline asthma medications, and country. The primary efficacy endpoint was the rate of asthma exacerbations over 52 weeks in biomarker-high patients (periostin ≥50 ng/mL or blood eosinophils ≥300 cells per μL), analysed with a Poisson regression model corrected for overdispersion with Pearson χ2 that included terms for treatment group, number of asthma exacerbations within the 12 months before study entry, baseline asthma medications, geographic region, screening periostin concentration, and blood eosinophil counts as covariates. Both trials are registered at ClinicalTrials.gov, LAVOLTA I, number NCT01867125, and LAVOLTA II, number NCT01868061. 1081 patients were treated in LAVOLTA I and 1067 patients in LAVOLTA II. Over 52 weeks, lebrikizumab reduced exacerbation rates in biomarker-high patients in the 37·5 mg dose group (rate ratio [RR] 0·49 [95% CI 0·34-0·69], p<0·0001) and in the 125 mg dose group (RR 0·70 [0·51-0·95], p=0·0232) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in biomarker-high patients in both dose groups versus placebo in LAVOLTA II (37·5 mg: RR 0·74 [95% CI 0·54-1·01], p=0·0609; 125 mg: RR 0·74 [0·54-1·02], p=0·0626). Pooling both studies, the proportion of patients who experienced treatment-emergent adverse events (79% [1125 of 1432 patients] for both lebrikizumab doses vs 80% [576 of 716 patients] for placebo), serious adverse events (8% [115 patients] for both lebrikizumab doses vs 9% [65 patients] for placebo), and adverse events leading to study drug discontinuation (3% [49 patients] for both lebrikizumab doses vs 4% [31 patients] for placebo) were similar between lebrikizumab and placebo. The following serious adverse events were reported in the placebo-controlled period: one event of aplastic anaemia and five serious adverse events related to raised concentrations of eosinophils in patients treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo group. Lebrikizumab did not consistently show significant reduction in asthma exacerbations in biomarker-high patients. However, it blocked interleukin-13 as evidenced by the effect on interleukin-13-related pharmacodynamic biomarkers, and clinically relevant changes could not be ruled out. F Hoffmann-La Roche.

Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma

BackgroundLong-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.MethodsWe randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis.ResultsAmong the 6208 patients, 27 patients in the fluticasone–salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone–salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone–salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone–salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01).ConclusionsIn this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344.)

Leading causes of bronchial asthma exacerbation

Introduction: Bronchial asthma is one of the most common chronic respiratory diseases. The frequency of occurrence differs from country to country, ranging from 1-18%.Purpose: The purpose of this study was to investigate the causes leading to exacerbation of bronchial asthma.Material and Methods: Α prospective observational study. The studied sample consisted of 82 patients who attended the emergency department or hospitalized in pulmonary clinics of Athens General Hospital, due to exacerbation of bronchial asthma. For data collection a specific registration form was used. Data analysis was performed with the statistical package Statistical Package for Social Sciences (SPSS).Results: Twenty two patients (26.8%) were male. The majority of patients (37.8%, n=31) were aged 46-65 years old. There were no statistically significant differences among patients admitted to the hospital for asthma exacerbation, during the last year and factors such as smoking, type of occupation, place of residence and pet ownership. Statistically significant correlation was found between patients who were trained for taking their medication, those who comply with medical orders and history of asthma exacerbation during the last year, (p&lt;0.05).Conclusions: Patients suffering from bronchial asthma education is an integral part of disease prevention and treatment strategies with a view to comply with medication treatment.

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

BackgroundProtease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied.MethodsWe recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry.ResultsSubjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations.ConclusionsPAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

Small airway dysfunction by impulse oscillometry in asthmatic patients with normal forced expiratory volume in the 1st second values

Small airways are relevant to the pathophysiology of asthma. We investigated whether in asthmatic patients with normal forced expiratory volume in the 1st second (FEV(1)) values, impulse oscillometry system (IOS), as a measure of small airway function, contributed additional information to spirometry either at baseline or after bronchodilator, and whether it was related to the disease control. The fall in resistance from 5 to 20 Hz (R5-R20) and reactance at 5 Hz (X5) by IOS and spirometry measures of small airway function (forced expiratory flow at 25-75% [FEF(25-75)] and forced vital capacity/slow inspiratory vital capacity [FVC/SVC]) at baseline and after 400 micrograms of salbutamol were prospectively measured in 33 asthmatic patients (18 women; age range, 18-66 years). Disease control was assessed by the Asthma Control Test (ACT). R5-R20 but not X5 values were significantly related to FEF(25-75) and FVC/SVC values (p < 0.05 for both correlations). When the bronchodilator response was assessed, no correlation was found among IOS and spirometry changes. ACT scores were related to R5-R20, FEF(25-75), and FVC/SVC values (p < 0.01 for all correlations). In asthmatic patients with normal FEV(1) values, R5-R20 values were related to spirometry measures of small airway function. However, when the bronchodilator response was assessed, IOS and spirometry provided quite different results. Moreover, small airway dysfunction, as assessed by IOS and spirometry, was associated with poor disease control and history of asthma exacerbations. The results of this study confirm the value of IOS, as an investigative tool, and suggest that in asthmatic patients with normal FEV(1) values and poor disease control, small airway function should be investigated.

Association of CHI3L1 in African-Americans with Prior History of Asthma Exacerbations and Stress

Rationale. Asthma exacerbations are influenced by multiple factors including environmental exposures, psychosocial interactions, and genetic variations. Aim. To better understand the correlation between clinical, physiologic, genetic, and psychological dimensions in asthma phenotypes and exacerbations. Methods. Supervised cluster analysis of a previously conducted clinical trial of asthma was used to identify subpopulations with differing exacerbation rates in an African-American study population (n = 475). The clusters were characterized by their clinical characteristics and genetic variations. The genetic analysis (n = 322) compared subgroups across 40 different polymorphisms of 10 genes associated with asthma exacerbations. Results. Four clusters were identified with varying annualized rates of exacerbations. Cluster 1 (n = 272) was represented by subjects with a mean age of 25 years and 52% females. In contrast, cluster 4, most divergent from cluster 1, was represented by subjects with the highest rate of asthma exacerbations (1.18 events per year), was mostly female (>80%), with a mean body mass index of 34, and was distinguished by the report of stress and emotions as the cause for prior exacerbations. Lower lung function and increased rescue medication use was also reported in cluster 4. Additionally, genetic analysis revealed a significant difference in distribution of genotypes among the four clusters for rs4950928, a single nucleotide polymorphism (SNP) located in the promoter region of the CHI3L1, the chitinase 3-like 1 gene encoding YKL-40. Conclusions. African-Americans who reported stress and emotions as a primary historical cause of exacerbations had the highest annualized rate of exacerbation. Further, a significant correlation with the genotypes in CHI3L1/YKL-40 was observed in the context of stress and asthma severity.

Characterization of Asthma Exacerbations in Primary CareUsing Cluster Analysis

Rationale. Patients with a history of asthma exacerbations are at a higher risk for future episodes of severe asthma exacerbations. Characterization of asthma phenotypes could help improve asthma management, including reducing exacerbations. Aim. The aim of this study is to identify distinctive patient characteristics associated with a history of asthma exacerbations using cluster analysis. Methods. We used data assessing asthma control from two cross-sectional surveys of adult and pediatric patients in the primary care setting. A supervised cluster analysis with recursive partitioning approach was applied to identify characteristics that maximized the differences across subgroups. Results. The sample comprised 2205 adults and 2435 children and adolescents with asthma. Key predictors were identified in seven adult clusters including visiting an asthma specialist, number of hours worked, and excessive use of rescue medication. The rate ratio (RR) for having an exacerbation was significantly higher (2.88; 95% confidence interval (CI), 2.46–3.36) in Cluster 7, with more female patients reporting severe disease, high body mass index, sinus infections, gastroesophageal reflux disease, skin allergies, and lower asthma control score. Features identified in the six pediatric clusters included visiting an asthma specialist, missed school days, race/ethnicity, and age. The RR for having an exacerbation was higher in Cluster 6 (2.36; 95% CI, 2.11–2.64), with patients reporting more severe disease, sinus and skin allergies, and lower asthma control score. Conclusions. Identification of specific risk factors can be enhanced by using supervised cluster analysis. This approach allows grouping of patients with unique characteristics to help identify patients at higher risk of exacerbations.

Omalizumab in children with inadequately controlled severe allergic (IgE-mediated) asthma

Background:Many children with severe persistent allergic (IgE-mediated) asthma remain inadequately controlled despite treatment with high-dose inhaled corticosteroids (ICS) plus a long-acting β2-agonist (LABA).Research and design methods:This pre-specified analysis of a randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of omalizumab in children (6–<12 years) with perennial allergen sensitivity, and history of asthma exacerbations and symptoms despite treatment with ICS (fluticasone ≥500 µg · day−1 or equivalent) plus a LABA. Patients received omalizumab (75–375 mg once or twice a month by subcutaneous injection, as determined from dosing tables) or placebo over 52 weeks (24-week fixed-steroid then 28-week adjustable-steroid phases).Results:Out of 246 randomized patients (omalizumab, n = 166; placebo, n = 80), efficacy was analysed in 235 (omalizumab, n = 159; placebo, n = 76). Over the 24-week fixed-steroid phase, omalizumab reduced the rate of clinically significant asthma exacerbations (worsening symptoms requiring doubling of baseline ICS dose and/or systemic steroids) by 34% versus placebo (0.42 vs 0.63, rate ratio 0.662; P = 0.047). Over 52 weeks, the exacerbation rate was reduced by 50% (P < 0.001). Omalizumab had an acceptable safety profile, with no statistically significant (P < 0.05) differences in adverse events observed between omalizumab and placebo.Conclusion:Add-on omalizumab is well-tolerated and reduces exacerbations in children (6–<12 years) with severe persistent allergic asthma, inadequately controlled despite high-dose ICS plus a LABA. It should be noted that the sample size was not based on providing statistical power in the severe subgroup, and no corrections were made for multiple comparisons; however, outcomes consistently favoured omalizumab.Trial registration: ClinicalTrials.gov identifier: NCT00079937.

Predictors of Uncontrolled Asthma in Adult and Pediatric Patients: Analysis of the Asthma Control Characteristics and Prevalence Survey Studies (ACCESS)

Background. Despite the availability of effective asthma treatments and evidence-based management guidelines focusing on asthma control, many patients have asthma that is inadequately controlled. The objective of this analysis was to identify risk factors for uncontrolled asthma among adult and pediatric patients. Methods. Two cross-sectional surveys assessing asthma control status were conducted between January 25 and May 2, 2008, among adult and pediatric patients with asthma. Participants completed a self-administered questionnaire including demographics, medical history, and current asthma medication use. In addition, participants completed either the Asthma Control Test (ACT) or Childhood ACT (C-ACT). Uncontrolled asthma was defined as a score of ≤19 on the ACT or C-ACT. Multiple logistic regression was used to identify factors related to uncontrolled asthma. Results. A sample of 64 primary care provider sites (35 for adults and 29 for pediatric patients) across the United States enrolled. One study enrolled 2238 adults (aged ≥18 years) and the other 2429 children (aged 4–17 years) with asthma. The patients were visiting their health care provider for a scheduled appointment for any reason. The overall prevalence of uncontrolled asthma was 58% and 46% in adult and pediatric patients, respectively. Multivariate analysis identified predictors of uncontrolled asthma in both adults and children including self-reported asthma severity, lack of adherence, and recent history of cold, flu, or sinus infection. The predictors of uncontrolled asthma seen only in adults were less education, insurance status, current smoker, body mass index (BMI) >30 kg/m2, and history of gastroesophageal symptoms. The predictors of uncontrolled asthma seen only in children were female aged 12–17 years, caregiver unemployment, and history of asthma exacerbation. Conclusions. A high proportion of patients with asthma seen in primary care settings are not well controlled. Recognition of specific predictors can signal who may be at higher risk of uncontrolled asthma and provide the opportunity for early interventions.

Factors associated with severity and exacerbation of asthma: a baseline analysis of the COhort for Reality and Evolution of adult Asthma in Korea (COREA)

Asthma presents with heterogeneous features, and patients show various phenotypes of differing severities. Therefore, it is necessary to define reliable predictable clinical factors that influence severity. To date, few large-scale studies have gathered clinical data on adult asthma patients in Asia. To establish an adult asthma cohort in Korea and to define significant factors associated with asthma severity and exacerbation. Researchers from 11 university hospitals have established an asthma cohort termed the COhort for Reality and Evolution of adult Asthma in Korea (COREA). We classified the severity of asthma into 3 groups: mild, moderate, and severe. In this article, the first analysis of our cohort, we evaluate various clinical factors associated with the severity and exacerbation of asthma using data from 1,260 asthma patients. Physician-evaluated severity of asthma was associated with a history of asthma exacerbation (P < .001), a history of smoking (P < .001), symptom duration (P = .007), and treatment duration (P < .001). It was also significantly correlated with predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) values and FEV1/FVC ratio (all P < .001). Previous exacerbation was associated with smoking (P = .02), predicted FVC and FEV1 values (both P < .001), FEV1/FVC ratio (P = .02), airway hyperresponsiveness (P = .002), and duration of disease (P < .001). Previous exacerbation, duration of disease, and decrease in lung function were important clinical indices associated with asthma severity in the COREA study patients. Our long-term follow-up study is expected to soon yield more accurate and detailed outcomes.