Evaluating symptom burden to characterise, predict, and prevent asthma attacks : a patient-level analysis of randomised trials and translational prospective studies
Ghent University Academic Bibliography (Ghent University)
Abstract
Background: Asthma symptoms often guide assessment and management, yet their prognostic and predictive value remains unclear. We evaluated the extent to which symptom burden measured by the 5-item Asthma Control Questionnaire (ACQ-5) predicts future severe asthma attacks and response to anti-inflammatory therapy. Methods: Primary analyses used the ORACLE2 patient-level meta-analysis (n=6,513) of control arm participants from 22 randomised controlled trials. Additional datasets included the DREAM intravenous mepolizumab arm (n=461); a cross-sectional severe asthma cohort (n=74); and two acute asthma cohorts (PRISMA, biologic-naïve, n=53; BOOST, anti-interleukin-5-treated, n=60). Associations between baseline ACQ-5 and clinical, physiological, and inflammatory profiles, asthma attack risk, and anti-inflammatory treatment responses were examined. Findings: Across five datasets encompassing 7,161 distinct participants, asthma severity, lung function, inflammatory profiles, comorbidities, and ACQ-5 varied widely. The proportion of subjects with high symptom burden (ACQ-5>1.5) ranged from 39% to 100%. Baseline ACQ-5 showed no consistent cross-sectional association with other clinical, physiological, or inflammatory asthma features. Each 0.5-point increase in baseline ACQ-5 was associated with a modest increase in future asthma attacks (adjusted rate ratio [aRR] 1.09, 95%CI 1.06-1.12; ΔR2 =0.02 versus multivariable prediction model without ACQ-5). Baseline ACQ-5 did not alter relative and absolute attack risk reduction from intravenous mepolizumab in DREAM. In contrast, patients with high blood eosinophils and exhaled nitric oxide (FeNO) had the highest relative and absolute risk reduction (2.81 vs 1.17 attacks; aRR 0.38, 95%CI 0.25-0.57). In PRISMA and BOOST, ACQ-5 was not associated with post-corticosteroid lung function change. Across studies, relative and absolute treatment effects showed consistent associations with blood eosinophils and FeNO. Conclusions: In a large patient-level analysis of RCTs and translational prospective studies, we observed limited alignment of symptom burden with other clinical, physiological, or biological features of asthma and modest prognostic value for severe attacks. In contrast, type-2 biomarkers more reliably identified high-risk and treatment-responsive patients. Symptoms may require contextual interpretation to guide anti-inflammatory escalation in asthma.
Authors 29
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Leiden University Medical Center
Affiliation as printed
Department of Biomedical Data Sciences , Leiden University Medical Center , Leiden , The Netherlands;
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Affiliation as printed
Faculté de médecine et des sciences de la santé , Université de Sherbrooke , Sherbrooke , Québec , Canada;
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Université de Sherbrooke · Hospital Universitario San Ignacio
Affiliation as printed
Faculté de médecine et des sciences de la santé , Université de Sherbrooke , Sherbrooke , Québec , Canada;
Pulmonary Unit , Internal Medicine Department , Hospital Universitario San Ignacio , Bogota , Colombia;
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Affiliation as printed
Faculté de médecine et des sciences de la santé , Université de Sherbrooke , Sherbrooke , Québec , Canada;
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University of Leicester · NIHR Leicester Biomedical Research Centre
Affiliation as printed
Department of Respiratory Sciences , Institute for Lung Health , NIHR Respiratory BRC , University of Leicester , Leicester , United Kingdom;
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Affiliation as printed
Faculté de médecine et des sciences de la santé , Université de Sherbrooke , Sherbrooke , Québec , Canada;
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The University of Western Australia · Sir Charles Gairdner Hospital · Institute for Respiratory Health
Affiliation as printed
Department of Respiratory Medicine , Sir Charles Gairdner Hospital , Perth , Australia;
Institute for Respiratory Health and UWA Medical School , University of Western Australia , Perth , Australia;
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Affiliation as printed
Department of Respiratory Medicine , Ghent University Hospital (UZ Ghent) , Ghent , Belgium;
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University of Leicester · NIHR Leicester Biomedical Research Centre
Affiliation as printed
Department of Respiratory Sciences , Institute for Lung Health , NIHR Respiratory BRC , University of Leicester , Leicester , United Kingdom;
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Affiliation as printed
Pulmonary,
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University of Kansas Medical Center
Affiliation as printed
Critical Care and Sleep Medicine , University of Kansas Medical Center , Kansas City , KS , United States;
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Affiliation as printed
Baylor College of Medicine , Houston , TX , United States; Guy's Severe Asthma Centre ,
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Guy's Hospital · University of Leicester · King's College London · NIHR Leicester Biomedical Research Centre
Affiliation as printed
Department of Respiratory Sciences , Institute for Lung Health , NIHR Respiratory BRC , University of Leicester , Leicester , United Kingdom;
School of Immunology & Microbial Sciences , Guy's Hospital , King's College London , London , United Kingdom;
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Affiliation as printed
AstraZeneca , Cambridge , United Kingdom;
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Affiliation as printed
AstraZeneca , Cambridge , United Kingdom;
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Genentech · Regeneron (United States)
Affiliation as printed
Regeneron Pharmaceuticals , Tarrytown , NY , United States;
formerly Genentech , South San Francisco , CA , United States;
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Affiliation as printed
Novartis Healthcare Private Limited , Hyderabad , India;
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Utrecht University · Leiden University Medical Center · University Medical Center Utrecht
Affiliation as printed
Department of Biomedical Data Sciences , Leiden University Medical Center , Leiden , The Netherlands;
Julius Center for Health Sciences and Primary Care , University Medical Center Utrecht , Utrecht , The Netherlands
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Affiliation as printed
Respiratory Medicine Unit and Oxford Respiratory NIHR BRC , Nuffield Department of Medicine , University of Oxford , Oxford , United Kingdom;