BACKGROUND:Asthma remission is a feasible treatment goal. However, remission definitions vary, and predictive biomarkers remain underexplored. METHODS:We conducted a post hoc analysis of ATLANTIS (NCT02123667), a multinational prospective study including 684 adult asthmatics. Remission was defined by 3-component (3C) and 4-component (4C) criteria. 3C remission included: (1) ACQ-6 < 1.5, (2) no maintenance oral corticosteroids, (3) no exacerbations. An absolute decline < 10% in pre-bronchodilator FEV1% predicted, was added for the 4C definition. Multivariate logistic regression identified remission predictors. A novel Low Disease Activity (LDA) score was developed using factor analysis of five clinical variables (ACQ-6, FeNO, BEC, and FEV1) including an innovative small airways dysfunction questionnaire tool (SADT). Nasal transcriptomics were analysed for differential gene expression and pathway enrichment and were replicated in U-BIOPRED (NCT01976767) using sputum transcriptomics. U-BIOPRED was included only to study omics replication of remission pathways identified in ATLANTIS. FINDINGS:Remission occurred in 48% (3C) and 45% (4C) of patients. Predictors included male sex, better lung function, fewer previous exacerbations, and higher SADT (fewer small airways symptoms). LDA identified milder disease and was associated with remission [OR 3C 4.43 (2.80, 7.10) and 4C 3.46 (2.23, 5.43)], improved QoL [OR 2.07 (1.65, 2.60)], and fewer future exacerbations [OR 0.43 (0.22, 0.85)]. Transcriptomic analyses revealed remission-associated upregulation of interleukin 4/13 signalling and downregulation of coagulation pathways, in both ATLANTIS and U-BIOPRED. INTERPRETATION:SAD was associated with reduced asthma remission. A novel LDA tool demonstrated clinical utility in stratifying prospective asthma risk. Key immunologic and haemostatic pathways may underpin remission, offering potential targets for future intervention.

BACKGROUND:In real-world chronic obstructive pulmonary disease (COPD) care, poor adherence often leads to treatment discontinuations. Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transiently increasing exacerbation risk; but evidence for long-acting muscarinic antagonists (LAMA) withdrawal remains limited. METHODS:We performed a post hoc analysis of the 52-week, double-blind, Effect of Indacaterol Glycopyrronium versus Fluticasone Salmeterol on COPD Exacerbations trial that compared long-acting beta-2 agonist (LABA)+LAMA with LABA+ICS in 3362 patients with moderate-to-severe COPD and exacerbation history. Potential withdrawal effects after discontinuing LAMA or ICS were suggested by monthly exacerbation incidence plots during the first quarter of follow-up. Participants were stratified by their baseline use of these therapies, and outcomes were compared between the first and subsequent quarters among those who continued versus discontinued each treatment. Multivariable mixed-effects models assessed differences in exacerbation rates, with temporal variation in treatment effects interpreted as indicative of withdrawal effects. RESULTS:Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use). This observation was not confirmed for severe exacerbations, likely due to low event count. In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance. Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count. CONCLUSION:Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials. TRIAL REGISTRATION NUMBER:NCT01782326.

Up to 40% of patients with COPD have evidence of elevated eosinophil counts ≥ 300 cells/mL at some point during their disease. Blood eosinophil counts (BECs) are a biomarker that can identify patients with COPD and type 2 inflammation who are candidates for add-on inhaled corticosteroids (ICS) or biologic therapy. Evidence from real-world and clinical trial data shows variation in BECs over time in patients with COPD and type 2 inflammation. This How I Do It article discusses factors that can influence eosinophil counts, reviews how the use of historical eosinophil counts can inform treatment decisions, and provides practical considerations for identifying underlying type 2 inflammation in patients with COPD in the clinic. Currently, there is no consensus on what constitutes "low" or "high" BEC in COPD or the frequency or number of eosinophil measurements needed to effectively guide disease management. Based on our experience from the clinic and available literature, we propose 4 broad phenotypic groups of patients with COPD: those with BECs predominantly ≥ 300 cells/μL, intermittently ≥ 300 cells/μL, within an intermediate range of 100 to 300 cells/μL, and those with BECs predominantly < 100 cells/μL. Identifying these patterns can help with more precise stratification for pharmacologic interventions, such as adding inhaled corticosteroids or biologic therapies. Although single BEC measurements are easy to obtain and often sufficient to identify patients with COPD and high levels of type 2 inflammation, when interpreted alongside clinical characteristics, repeated BECs may be able to support a more personalized approach to COPD care.

A biomarker panel that improves chronic obstructive pulmonary disease (COPD) diagnosis, even in the presence of confounding factors such as asthma and smoking, is of great importance. Label-free proteomic analysis was conducted in four groups (10 subjects each): COPD patients, asthma patients, smoker controls, and non-smoker controls. A total of 1,469 proteins were identified in the 40 serum samples, of which 29 were differentially expressed in the COPD group ( p < 0.05 and > 2.0-fold change) compared with asthma and control groups. Five differentially expressed proteins (DEPs) stood out in volcano plots and heatmaps: ubiquitin carboxyl-terminal hydrolase 31 (USP31), RING finger protein 10 (RNF10) and transforming acidic coiled-coil containing protein 2 (TACC2) differentiated COPD from both control groups and asthma patients, while mitogen-activated protein 3-kinase 10 (MAP3K10) and collagen type V alpha 1 chain (COL5A1) differentiated COPD from healthy controls. Logistic regression models with 5-fold cross-validation, based on this protein set, achieved over 80% accuracy in diagnosing COPD. DEPs were explored for pathway enrichment using Reactome and Protein Analysis THrough Evolutionary Relationships (PANTHER), revealing pathways related to COPD pathophysiology. Knowledge of these alterations is important for identifying novel biomarkers to aid diagnosis and therapeutic strategies, contributing to precision medicine in COPD.

The current standard of maintenance care for patients with moderate-to-severe asthma is the use of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) medications; some patients may also require additional therapies including long-acting muscarinic antagonists or biologics to establish disease control. Presently, there is a striking discrepancy between the positive outcomes reported in randomised clinical trials (RCTs) of these therapies and real-world outcomes that may be independent of treatment adherence. Patients with asthma included in RCTs are selected using stringent eligibility criteria, for example they have never been heavy smokers. Because current recommendations rely on results from such exclusive RCTs, this calls into question the extent to which these recommendations are applicable in daily practice. Therefore, generalising information from RCTs can be a difficult task for a number of reasons, including differences between ICS/LABAs, varied responses to medications among patients and the limited time busy general practitioners have to bridge the care gaps that exist. Factors in choosing a desirable ICS/LABA may include (a) considerations in clinical decision-making; (b) differences in pharmacokinetic and pharmacodynamic properties of ICS/LABA molecules, therapeutic index; (c) individual patient factors which may influence or facilitate successful adherence to treatment; (d) ease of inhaler use; (e) underlying inflammation; and (f) balancing efficacy and long-term safety, including adverse events and long-term exacerbation risk, based on data from both RCTs and real-world evidence. This review article discusses factors that healthcare professionals may utilise when selecting an ICS/LABA treatment for their patients, by considering data from RCTs and real-world evidence in addition to geographical/environmental, personal, and disease factors, which may also influence the decision process, such as availability and affordability. This article outlines treatments used to control moderate-to-severe asthma. Data from clinical trials and real-world studies were included. Current asthma medicines include combinations that reduce inflammation and open the airways: inhaled corticosteroids with long-acting β2-agonists (ICS/LABAs) plus other treatments for some individuals. Since there are many available combinations of ICS/LABAs (molecules and devices), selecting the most appropriate option requires important considerations from both patient and physician perspectives. In this paper, authors discuss these combinations alongside other important considerations, with the aim of encouraging doctors and patients to work together to choose the most appropriate treatment. Firstly, differences between ICS/LABA molecules mean they could have different effects in individual patients. This review discusses how physicians might identify these effects using different measures within the body. Secondly, findings from clinical trials and from patients in the ‘real world’, comparing specific ICS/LABA treatments, were discussed. Thirdly, balancing the safety of ICS/LABA treatments was explored along with how physicians can minimise the risk of side effects. Finally, individual patient requirements and preferences were explored, as these are important factors when doctors are deciding which inhaler device patients should have. This may help to ensure patients take the medicine as prescribed. This review demonstrates the importance of considering several factors when choosing the most appropriate inhaled medication. It highlights the need to focus on reducing underlying inflammation to prevent future asthma attacks (exacerbations) and minimising side effects. This can assist patients in achieving their long-term disease management goals and supporting continued treatment adherence.

BACKGROUND:To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. METHODS:Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4 h (AUC0-4h) after nebulised 99mTc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV1 (litres), 15 min post dose (95% confidence intervals [CI]: lower limit >-10%, upper limit >0%). Both studies assessed safety. RESULTS:In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC0-4h geometric mean ratio [90% CI]: 1.00 [0.99, 1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV1 at 15 min: -0.37% [HFA-152a] vs -0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [-3.61, 4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. CONCLUSION:HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.

Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs) have shared risk factors and mechanisms. CVDs are highly prevalent in COPD patients. Additionally, the risk of suffering a cardiovascular (CV) event is increased following an exacerbation and remains elevated for months afterwards. This link between exacerbations and increased CV risk further highlights the importance of preventing exacerbations. Clinical management during and after exacerbations regarding the prevention of CV events remains to be optimised. CV events occur in patients with COPD who have not previously been diagnosed with CVD. Conventional CV risk tools have historically underestimated the risk of CV events in patients with COPD. All patients with COPD should be investigated for CVDs and markers of CV risk should be assessed at the time of COPD exacerbations. Improving survival in COPD depends on reducing the risk of exacerbations, particularly severe exacerbations, addressing identified CV risk factors and managing CVDs when identified according to guidelines.

RATIONALE:Blood eosinophil count (BEC) is a biomarker indicating type 2 inflammation in patients with chronic obstructive pulmonary disease (COPD), but can be variable. OBJECTIVES:Evaluate mepolizumab efficacy in patients with COPD with variability of BEC patterns. METHODS:Data were pooled from the phase 3, randomized, double-blind, placebo-controlled METREX (NCT02105948), METREO (NCT02105961), and MATINEE (NCT04133909) trials. Patients receiving mepolizumab 100 mg or placebo were included. These trials documented historical BEC (within 12 months before randomization) for all patients. Outcomes included annualized rates of moderate or severe exacerbations, and exacerbations requiring an emergency department (ED) visit and/or hospitalization. Outcomes were assessed in subgroups based on BEC values in the 12 months before randomization, at screening, and at baseline. MEASUREMENTS AND MAIN RESULTS:Annualized rates of moderate or severe exacerbations were reduced, or trended toward reduction, with mepolizumab versus placebo in patients with type 2 inflammation characteristics, including those with BEC ≥300 cells/µL at any pre-randomization timepoint (21% reduction), persistently elevated BECs (12%-27% reduction), and -variable BECs over time (22%-36% reduction). Across various subgroups with elevated BEC, starting from ≥150 cells/µL, mepolizumab reduced exacerbations requiring ED visit and/or hospitalization. Patients with persistently low BEC (<150 cells/µL) experienced no benefit with mepolizumab. CONCLUSIONS:Mepolizumab improved exacerbation-related outcomes in patients with COPD and type 2 inflammation, characterized by both consistently and intermittently elevated BEC. Persistent BEC elevation is not required to identify treatable eosinophilic phenotypes in COPD.

Background:Macrolide antibiotics have immunomodulatory activity and when taken chronically reduce exacerbations of COPD. However, chronic use can cause bacterial resistance. EP395 (glasmacinal), a novel macrolide, is being developed as a treatment to reduce exacerbations of COPD without inducing antimicrobial resistance. Methods:In this double-blind, placebo-controlled, phase 2a trial (NCT05572333), patients (≥45 years old, diagnosed with COPD for ≥2 years and stable on at least one maintenance inhaled therapy) were randomised (2:1) to EP395 or placebo daily for 12 weeks. The primary objective was safety, with key secondary objectives assessing pharmacodynamic effects of EP395. Results:A total of 61 patients were randomised (42 EP395, 19 placebo). A 12-week course of EP395 was well tolerated: no serious adverse events were considered related to EP395, and adverse events occurred in similar proportions in both groups (64.3% EP395, 63.2% placebo). Four patients were withdrawn due to adverse events (three EP395, one placebo). Sputum neutrophil elastase and myeloperoxidase, mediators of neutrophil activation, were reduced with EP395 (treatment difference (log scale): neutrophil elastase -0.415 ng·mL-1, 95% CI -0.787 to -0.043 ng·mL-1, p=0.030; myeloperoxidase -0.282 ng·mL-1, 95% CI -0.640 to 0.076 ng·mL-1, p=0.119). Relative changes in neutrophil elastase and myeloperoxidase from baseline with EP395 were 66% and 75%, respectively, of those observed with placebo. Exploratory 16S rRNA sequencing of sputum showed EP395 had no detectable effect on the lung microbiome, including the proportion of pathogenic Proteobacteria species. Conclusion:In patients with stable COPD, EP395 for 12 weeks was well tolerated, demonstrated selective anti-inflammatory activity and had no detectable effect on the lung microbiome.

Dave Singh,1 Nicolas Roche,2,3 Libo Wu,4 Hosein Sadafi,5 Jan De Backer,6,7 Navid Monshi Tousi,5 Jonathan Marshall8 1Respiratory Research Group, University of Manchester, Medicines Evaluation Unit, Manchester University National Health Service Foundation Trust, Manchester, UK; 2Department of Respiratory Medicine, Hospital Cochin, APHP Centre, Paris, France; 3Universit&eacute; Paris Cit&eacute;, Institut Cochin, U1016, Paris, France; 4Product Development Operations, AstraZeneca, Durham, NC, USA; 5Department of Computational Engineering, FLUIDDA NV, Kontich, Belgium; 6FLUIDDA NV, Kontich, Belgium; 7Department of Respiratory Medicine, University of Antwerp, Antwerp, Belgium; 8Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UKCorrespondence: Jonathan Marshall, Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CV2 0AA, UK, Tel +44 (0)20 3749 5000, Email jonathan.marshall1@astrazeneca.com

BACKGROUND:Randomised controlled trials (RCTs) of COPD management assess heterogeneous outcomes with diverse instruments and often omit those important to patients and healthcare professionals, limiting interpretability and comparability. This review aimed to identify the outcomes and instruments used in phase III/IV COPD maintenance management RCTs and assess their consistency. METHODS:We systematically reviewed all phase III/IV RCTs registered on ClinicalTrials.gov between 2010 and 2025 evaluating COPD maintenance management. Outcomes and measurement instruments were extracted from registry entries and categorised using the COMET (Core Outcome Measures in Effectiveness Trials) taxonomy. Registered outcomes from a random 10% sample were compared with the corresponding publications to assess concordance. Outcome frequencies were summarised across intervention types and sponsor categories. RESULTS:43 unique outcomes were identified across 240 eligible RCTs. Physiological (89.5%), clinical (85.0%) and life impact outcomes (63.8%) were most frequently assessed, whereas resource use (39.6%), safety (36.7%) and mortality (16.7%) outcomes were less commonly reported. Only lung function (76.3%) and health-related quality of life (57.5%) appeared in over half of the trials. Exacerbations were reported in 40.4% of studies, while several patient-prioritised outcomes, particularly activities of daily living (5.4%) and exercise tolerance (18.3%), were infrequently assessed. Industry-sponsored RCTs more often reported lung function, resource use and adverse events; non-industry trials more frequently included biomarkers. Concordance between registered and published outcomes was acceptable (79.7%), although safety outcomes and instruments were sometimes under-reported. CONCLUSION:COPD maintenance management RCTs show substantial heterogeneity and incomplete assessment of patient-prioritised outcomes. An internationally representative, multi-stakeholder core outcome set is urgently needed to improve consistency and patient-centred evaluation in future trials.

Background:Higher blood eosinophil counts are associated with greater lung function decline in patients with COPD, and a relationship between higher sputum eosinophil counts and greater emphysema has been reported. The aim of the current study was to investigate a role for eosinophils in alveolar septal damage, which may contribute to emphysema and lung function decline in COPD patients. Methods:We quantified Luna positive alveolar septal eosinophil counts (ASEC) in peripheral lung tissue blocks from 48 COPD patients versus 27 smokers and 15 nonsmokers and examined the relationship between eosinophil numbers and alveolar tissue damage using histology techniques. Results:The numbers of ASEC were greater in COPD compared to controls (p≤0.02), and there was a significant correlation between ASEC and alveolar septal damage in a subgroup of COPD patients (rho=0.4, p=0.03). Conclusion:This association suggests a role for eosinophils in the pathogenesis of emphysema in a subset of COPD.

Malnutrition is often overlooked as an extrapulmonary comorbidity in chronic obstructive pulmonary disease (COPD) and there is limited information regarding the nutritional status of younger individuals with mild-to-moderate disease in outpatient settings. We assessed energy and protein intakes in mild-to-moderate COPD patients compared to a group of healthy non-smoking individuals (HNS). COPD patients and HNS were recruited; anthropometric measurements were assessed via BMI and bioelectrical impedance, while nutritional intake was assessed using a 7-day food diary and the EPIC-Norfolk Food Frequency Questionnaire (FFQ). Low fat-free mass index (FFMI) was defined as (a) < 15 kg/m2 for females and < 17 kg/m2 for males (Schols in Eur Respir J 44:1504–1520, 2014) or (b) adjusted for age, sex and BMI (Wei et al. in Front Endocrinol 14:1185221, 2023). 21 COPD participants and 15 HNS were recruited with a median age of 58.0 and 57.0, respectively [IQR: 55.0–63.0 and 50.0–60.0]. A significantly greater proportion of individuals with COPD had a low FFMI when using age-sex-BMI adjusted criteria (23.8 vs. 0.0

RATIONALE:Disease stability in chronic obstructive pulmonary disease (COPD) is a low disease activity state proposed as a treatment target. OBJECTIVES:Characterize COPD stability as a composite endpoint. METHODS:Post hoc analyses were carried out on IMPACT and FULFIL (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] vs dual therapies) and MATINEE/METREX/METREO (mepolizumab added onto triple therapy). Stability was defined as "no moderate/severe exacerbations and no worsening from baseline in COPD Assessment Test (CAT) and FEV1." We assessed whether achieving stability at week 28 was prognostic of subsequent outcomes (time to first on-treatment moderate/severe exacerbation and time to all-cause mortality [ACM]) after week 28 (IMPACT). Bayesian joint modeling evaluated the probability of achieving stability (IMPACT). MEASUREMENTS AND MAIN RESULTS:Stability was achieved with FF/UMEC/VI by 22% of patients in IMPACT (week 52) and by 46% of patients in FULFIL (week 24); stability was achieved with mepolizumab + triple therapy by 18% of patients in MATINEE/METREX/METREO (week 52). Patients were more likely to achieve stability with triple vs dual therapy and with mepolizumab vs placebo. Many individuals achieving stability had clinically meaningful improvements in CAT and FEV1. Patients achieving stability at week 28 (vs patients who were not stable) had a 45.7% reduction in the risk of moderate/severe exacerbations and a 51.7% reduction in the risk of ACM after week 28. Bayesian joint modeling demonstrated a mean (SD) posterior probability of stability: 25.60% (0.66) at week 52 (FF/UMEC/VI). CONCLUSIONS:Our data provide further evidence for disease stability as an achievable COPD treatment target that predicts long-term clinical benefits in exacerbations and mortality.

Rationale The mechanisms driving epithelial pathology in COPD are steadily being unveiled, confirming a role for inflammation in the disease. This study explored the interleukin (IL)-6/STAT3 axis, previously reported to link inflammation and epithelial-to-mesenchymal transition, two features of COPD at the airway epithelium level. Methods Bronchoalveolar lavage fluid (BALF) and surgical lung tissue were obtained from nonsmoker controls, smokers and COPD patients. The activation of STAT3 and IL-6 levels were measured in these samples. Primary air-liquid interface (ALI) cultures were carried out from nonsmokers, smokers and COPD patients, and IL-6 release and STAT3 mRNA levels were assessed. BEAS-2B cell cultures were exposed to sputum supernatants from COPD patients versus nonsmokers, with and without a pan-gp130 blocking monoclonal antibody. Finally, primary ALI cultures from nonsmokers were exposed to IL-6 versus vehicle and assessed for epithelial-to-mesenchymal transition and cell differentiation. Results IL-6 and Tyr705-phospho-STAT3 levels were increased in samples from COPD patients compared to controls, both in BALF and in the airway epithelium, as well as in ALI cultures. BEAS-2B cells exposed to COPD sputum supernatants displayed STAT3 activation that was inhibited by the pan-gp130 blocking monoclonal antibody. In addition, stimulation of ALI cultures with IL-6 induced increased vimentin expression and fibronectin release and reduced the expression of apical junctional complexes proteins, indicating epithelial-to-mesenchymal transition. Finally, no impact on airway cell differentiation was observed. Conclusions The IL-6/STAT3 axis is activated in the COPD airway epithelium, presumably contributing to epithelial-to-mesenchymal transition.

Background There is growing interest in evaluating the ability of treatments to deliver clinical remission in patients with asthma. We conducted post-hoc analyses of TRIMARAN and TRIGGER, two clinical studies comparing the efficacy and safety of fixed-dose combination beclometasone dipropionate, formoterol fumarate and glycopyrronium (BDP/FF/G: TRIMARAN, 100/6/10 μg; TRIGGER 200/6/10 µg) with BDP/FF (100/6 and 200/6 µg). Methods Clinical remission was defined as: no use of oral corticosteroids over 52 weeks, no occurrence of severe exacerbations over 52 weeks, Asthma Control Questionnaire-5 score <1.5 at Weeks 26, 40 and 52, and pre-dose forced expiratory volume in 1 s at Week 52 equal to, or higher than, the baseline value. Results Of 2291 patients included in these analyses, 598 (26.1%) met the clinical remission definition ( i.e. , met all criteria) at Week 52–315 (27.4%) in TRIMARAN and 283 (24.8%) in TRIGGER. The proportion of patients who achieved clinical remission was higher in the BDP/FF/G group than in the BDP/FF group in both studies (29.4% and 29.6% in TRIMARAN and TRIGGER, respectively, versus 25.4% and 20.0%), with the difference reaching statistical significance in TRIGGER (odds ratio 1.70 [95% confidence interval 1.29, 2.23]; p<0.001) and when data were pooled (29.5% versus 22.7%; 1.44 [1.19, 1.73]; p<0.001). Conclusions Among patients with asthma that was uncontrolled by an inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA) combination prior to study entry, a higher proportion achieved clinical remission by switching to inhaled triple therapy than by continuing ICS/LABA.