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Background: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma., Objective: This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854)., Methods: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV 1 ) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV 1 at week 12)., Results: The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by week 2 and then gradually to week 52 in patients treated with dupilumab versus placebo; Eos, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with the change in biomarkers in either treatment group. The change from baseline in pre-BD FEV 1 at week 52 was inversely associated with the fold change in FeNO in both groups, with a significant difference between the dupilumab and placebo curves (P = .014), and was positively associated with the fold change in Eos in both groups (P = .022)., Conclusions: Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed a predictive value for lung function improvement; for FeNO, this was specific to the dupilumab treatment arm., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The natural history of many chronic diseases is characterized by periods of increased disease activity, commonly referred to as flare-ups or exacerbations. Accurate characterization of the burden of these exacerbations is an important research objective., Methods: The purpose of this work was to develop a statistical framework for nuanced characterization of the three main features of exacerbations: their rate, duration, and severity, with interrelationships among these features being a particular focus. We jointly specified a zero-inflated accelerated failure time regression model for the rate, an accelerated failure time regression model for the duration, and a logistic regression model for the severity of exacerbations. Random effects were incorporated into each component to capture heterogeneity beyond the variability attributable to observed characteristics, and to describe the interrelationships among these components., Results: We used pooled data from two clinical trials in asthma as an exemplary application to illustrate the utility of the joint modeling approach. The model fit clearly indicated the presence of heterogeneity in all three components. A novel finding was that the new therapy reduced not just the rate but also the duration of exacerbations, but did not have a significant impact on their severity. After controlling for covariates, exacerbations among more frequent exacerbators tended to be shorter and less likely to be severe., Conclusions: We conclude that a joint modeling framework, programmable in available software, can provide novel insights about how the rate, duration, and severity of episodic events interrelate, and enables consistent inference on the effect of treatments on different disease outcomes. Trial registration Ethics approval was obtained from the University of British Columbia Human Ethics Board (H17-00938)., (© 2023. The Author(s).)

New therapeutic options for severe asthma have recently emerged, mostly in the form of monoclonal antibodies ("biologicals") targeting relevant inflammatory pathways. Currently available agents target different aspects of "Type 2" immunity, and their indications often include overlapping patient groups. We present a round-table discussion that took place during the Annual Meeting of the Respiratory Effectiveness Group (REG), on the reasoning behind the use of different add-on medications for severe asthma, and crucially, on selection strategies. The proposed rational is based on current evidence, including real-life studies, as well as on the appreciation of the relevant complexities. Direct head-to-head comparisons of biologicals are lacking; therefore, algorithms for initial choice and potential switch between agents should be based on understanding the key characteristics of different options and the development of a clear plan with predefined targets and shared decision-making, in a structured way., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

This review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients' quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe., (Copyright ©ERS 2015.)

Background: Patients with a history of asthma-related hospitalizations are at high risk of readmission and generally consume a large amount of health-care resources. It is not clear if the secondary care provided by specialists after an episode of asthma-related hospitalization is associated with better outcomes compared with the primary care provided by general practitioners., Methods: Using population-based administrative health data from the province of British Columbia, Canada, we created a propensity-score-matched cohort of individuals who received primary vs secondary care in the 60 days after discharge from asthma-related hospitalization. Total direct asthma-related medical costs (primary outcome) and health service use and measures of medication adherence (secondary outcomes) were compared for the next 12 months., Results: Two thousand eighty-eight individuals were equally matched between the primary and secondary care groups. There was no difference in the direct asthma-related costs (difference $567; 95% CI, -$276 to $1,410) and rate of readmission (rate ratio [RR] = 1.06; 95% CI, 0.85-1.32) between the secondary and the primary care groups. Patients under secondary care had a higher rate of asthma-related outpatient service use (RR = 1.22; 95% CI, 1.11-1.35) but a lower rate of short-acting β-agonist dispensation (RR = 0.91; 95% CI, 0.85-0.98). The proportion of days covered with a controller medication was higher among the secondary care group (difference of 3.2%; 95% CI, 0.4%-6.0%)., Conclusions: Compared with those who received only primary care, patients who received secondary care showed evidence of more appropriate treatment. Nevertheless, there were no differences in the costs or the risk of readmission. Adherence to asthma medication in both groups was poor, indicating the need for raising the quality of care provided by generalists and specialists alike.

Background: Recent evidence suggests that the use of leukotriene receptor antagonists (LTRAs) in addition to inhaled corticosteroids (ICSs) in asthmatic patients provides comparable benefits to the addition of long-acting β-agonists (LABAs) to ICSs., Objective: We sought to compare, in a unified framework, adherence, outcomes, and costs associated with ICS+LTRA versus ICS+LABA as step-up therapies for asthma., Methods: Using the administrative databases of British Columbia, Canada (years 1997-2007), we created a propensity score-matched sample of asthmatic patients (12-45 years old) receiving ICS+LTRA therapy versus ICS+LABA therapy after a period of monotherapy with an ICS. We compared the outcomes using 2 analyses: an intention-to-treat (ITT) analysis that followed subjects for a fixed period of 2 years and an uninterrupted treatment analysis that followed subjects for as long as they continuously dispensed their index medications., Results: The matched cohort consisted of 1032 subjects in each group (mean age at entry, 27.4 years; 52.5% female). Adherence, which was defined as the proportion of days covered, was higher in the ICS+LABA group compared with the ICS+LTRA group. In both the ITT and uninterrupted treatment analyses, use of ICS+LTRA therapy was associated with more asthma-related outpatient visits, asthma-related medication dispensations, and dispensation of reliever medications. Dispensation of oral corticosteroids and rate of asthma exacerbations were higher in the ICS+LTRA group in the uninterrupted treatment analysis but not in the ITT analysis., Conclusions: In a real-world clinical setting subjects were more adherent to ICS+LABA therapy than ICS+LTRA therapy. ICS+LABA therapy seems to be more effective than ICS+LTRA therapy in the management of asthma, regardless of adherence., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS)., Objective: To determine whether noneosinophilic, steroid-naive asthmatic subjects show an improvement in asthma control, asthma symptoms and spirometry after four weeks of treatment with ICS, and whether they further benefit from the addition of a long-acting beta-2 agonists to ICS., Methods: A randomized, double-blind, placebo-controlled, multicentre study comparing the efficacy of placebo versus inhaled fluticasone propionate 250 mcg twice daily for four weeks in mildly uncontrolled, steroid-naive asthmatic subjects with a sputum eosinophil count of 2% or less. This was followed by an open-label, four-week treatment period with fluticasone propionate 250 mcg⁄salmeterol 50 mcg, twice daily for all subjects., Results: After four weeks of double-blind treatment, there was a statistically significant and clinically relevant improvement in the mean (± SD) Asthma Control Questionnaire score in the ICS-treated group (n = 6) (decrease of 1.0 ± 0.5) compared with the placebo group (n = 6) (decrease of 0.09 ± 0.4) (P = 0.008). Forced expiratory volume in 1 s declined in the placebo group (-0.2 ± 0.2 L) and did not change in the ICS group (0.04 ± 0.1 L) after four weeks of treatment (P = 0.02). The open-label treatment with fluticasone propionate 250 mcg⁄salmeterol 50 mcg did not produce additional improvements in those who were previously treated for four weeks with inhaled fluticasone alone., Conclusion: A clinically important and statistically significant response to ICS was observed in mildly uncontrolled noneosinophilic asthmatic subjects.

Background: Asthma is difficult to diagnose in children and at times misdiagnosis of an infection can occur. However, little is known about the magnitude and patterns of antibiotic consumption in children with asthma relative to those without asthma., Methods: Using population-based data, 128,872 children were identified with at least 6 years of follow-up. The adjusted rate-ratio (RR) of antibiotics dispensed to asthmatic as compared to non-asthmatic children was determined., Results: At age six, the RR of antibiotic consumption for asthmatics compared to non-asthmatics varied between, 1.66 to 2.32, depending on the year of asthma diagnosis. Of the 18,864 children with asthma at ages 2-8, 52% (n = 9,841) had antibiotics dispensed in the 6 months prior to their index date of asthma diagnosis. The RR of antibiotic consumption in the 1 month prior to asthma diagnosis compared to 5 months prior was 1.66 (95% CI 1.60-1.71). The RR was lower in males compared to females (1.58 vs 1.77), and lower in those who received antibiotics in the first year of life relative to those that did not (1.60 vs. 1.76)., Conclusions: There is higher antibiotic consumption in children with asthma compared to those without asthma. The pattern of antibiotic use suggests that diagnosis guidelines are difficult to follow in young children leading to misdiagnosis and over treatment with antibiotics.

Background: Long-acting ss(2)-agonists are an established controller medication in asthma. BI 1744 is a novel L\long-acting ss(2)-agonist with a preclinical profile that suggests 24-hour bronchodilation and bronchoprotection may be achieved., Objective: To examine the bronchoprotective effects of single doses of BI 1744 against methacholine provocation in subjects with mild asthma., Methods: Thirty-one subjects with mild asthma were randomized to receive single doses of BI 1744 (2, 5, 10, 20 microg) or placebo on separate days according to a double-blind, 5-way crossover design. Methacholine challenges were performed at 30 minutes and at 4, 8, 24, and 32 hours after each single dose of medication, and the results were expressed as PC(20) FEV(1)., Results: All doses of BI 1744 produced statistically significant increases in the methacholine PC(20) compared with placebo as long as 32 hours. The mean (geometric SEM) methacholine PC(20) 24 hours after dosing with placebo was 1.73 (1.13) mg/mL, which increased after 2 microg to 3.86 (1.14) mg/mL, after 5 microg to 5.67 (1.14) mg/mL, after 10 microg to 9.42 (1.13) mg/mL, and after 20 microg to 13.71 (1.14) mg/mL (all P < .0001). After 32 hours, the methacholine PC(20) value remained significantly increased for all doses. No safety or tolerability concerns were identified., Conclusion: BI 1744 provides significant bronchoprotection against inhaled methacholine for up to 32 hours after single-dose administration.

Long-acting beta-agonists are a pillar of therapy for many patients with asthma because they are the preferred add-on therapy to inhaled corticosteroids. However, a recent meta-analysis documented a substantial increase in severe exacerbations requiring hospital admission and life-threatening asthma exacerbations in patients treated with long-acting beta-agonists. A careful evaluation of this meta-analysis raises several concerns about its applicability to current practice. Pivotal trials evaluating the benefit of adding long-acting beta-agonists to inhaled corticosteroids were not included. The authors of the current paper call for physicians to continue their usual practice of using long-acting beta-agonists as adjunctive therapy, as well as for an independent meta-analysis of individual patients using inhaled corticosteroids and long-acting beta-agonists concomitantly.

Presents the summary of recommendations from the Canadian Asthma Consesus Guidelines 2003 and Canadian Pediatric Asthma Consensus Guidelines, 2003. Definition of asthma; General management and diagnosis of asthma; Prevention strategies and pharmacotherapy; Inhaled devices for the treatment of asthma.

Aetiology/risk factors Most people with asthma are atopic; exposure to certain stimuli initiates inflammation and structural changes in airways, causing airway hyperresponsiveness and variable airflow obstruction, which in turn cause most asthma symptoms. Stimuli include environmental allergens, occupational sensitising agents, and respiratory viral infections. Prognosis About 10.20% of people presenting to the emergency department with asthma are admitted to hospital. Of these, fewer than 10% receive mechanical ventilation, although previous ventilation is associated with a 19-fold increased risk of ventilation for a subsequent episode. It is unusual for people to die unless they have had respiratory arrest before reaching hospital. One prospective study of 939 people discharged from emergency care found that 17% (95% confidence interval 14% to 20%) had relapsed by two weeks. Aims To minimise or eliminate symptoms; to maximise lung function; to prevent exacerbations; to minimise the need for medication; to minimise adverse effects of treatment; and to provide enough information and support to facilitate self management of asthma. Outcomes Symptoms (daytime and nocturnal); lung function (PEFR and forced expiratory volume in one second (FEV1)); need for rescue medication such as inhaled beta 2 agonists; variability of flow rates; activities of daily living; adverse effects of treatment. [ABSTRACT FROM AUTHOR]

Interpretation: Despite the widespread distribution of guidelines for asthma pharmacotherapy, inappropriate use of asthma medications persists (specifically excessive use of inhaled short-acting B-agonists combined with underuse of inhaled corticosteroids). Not only are patients who use medication inappropriately at higher risk for fatal or near-fatal asthma attacks, but, as shown in this study, they use significantly more health care resources than patients with appropriate medication use. [ABSTRACT FROM AUTHOR]

Dupilumab 200 mg reduced the annualized exacerbation rate by 46.4%, while dupilumab 300 mg did not show treatment effect vs PBO in adolescents, although the unadjusted exacerbation rate was 0.46 for dupilumab 300 mg and 0.76 for PBO. B CLINICAL IMPLICATIONS: b Dupilumab may benefit lung function and severe exacerbation rates in adolescents with uncontrolled moderate-to-severe asthma. [Extracted from the article]