Abstract
Background: Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA). Objective: To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA. Methods: We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n = 140; severe, n = 128) and 69 healthy controls from the All Age Asthma Cohort. We evaluated SAD prevalence and its interrelation with risk factors for asthma severity (older age, obesity, and smoking), type 2 inflammation (sputum and blood eosinophils, fractional exhaled nitric oxide), systemic inflammation (high-sensitivity C-reactive protein), asthma control (AC), and PA (accelerometer for 1 week). We applied a clinical model based on structural equation modeling that integrated causal pathways among these clinical variables. Results: The prevalence of SAD ranged from 75% to 90% in patients with severe asthma and from 53% to 64% in mild to moderate asthma. Severe SAD was associated with poor AC and low PA. Structural equation modeling indicated that age, obesity, obesity-related systemic inflammation, T2 inflammation, and smoking are independent predictors of SAD. Small airway dysfunction was the main determinant factor of AC, which in turn affected PA. Obesity affected AC directly and through its contribution to SAD and low PA. In addition, PA had bidirectional associations with obesity, SAD, and AC. Structural equation modeling also indicated interrelations among distal airflow limitation, air trapping, and ventilation heterogeneity. Conclusions: Small airway dysfunction is a highly prevalent key feature of asthma that interrelates a spectrum of distal lung function abnormalities with risk factors for asthma severity, asthma control, and physical activity.
| Original language | English |
|---|---|
| Journal | Journal of Allergy and Clinical Immunology: In Practice |
| Volume | 9 |
| Issue number | 9 |
| Pages (from-to) | 3359-3368.e1 |
| ISSN | 2213-2198 |
| DOIs | |
| Publication status | Published - 09.2021 |
Funding
The All Age Asthma Cohort infrastructure is provided by the participating sites of the German Centre for Lung Research and associated study centers and hospitals. Direct costs of the All Age Asthma Cohort are being paid by project grants from the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), grant no. 82DZL001A4 . Conflicts of interest: F. Trinkmann received travel support from Actelion, Berlin Chemie, Boehringer Ingelheim, Chiesi, Novartis, Mundipharma, and TEVA, as well as speaker or consultation fees from AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, GlaxoSmithKline, Novartis, Roche, and Sanofi-Aventis, all outside the submitted work. E. von Mutius reports personal fees from Pharmaventures, OM Pharma S. A., Springer-Verlag GmbH, Elsevier GmbH and Elsevier Ltd, Peptinnovate Ltd, Turun Yliopisto, Tampereen Yliopisto, Helsingin Yliopisto, European Respiratory Society, Deutsche Pharmazeutische Gesellschaft e V, Massachusetts Medical Society, Chinese University of Hongkong, European Commission, Boehringer Ingelheim International GmbH, Universiteit Utrecht, Faculteit Diergeneeskunde, Universität Salzburg, Georg Thieme Verlag, and Japanese Society of Pediatric Allergy and Clinical Immunology, outside the submitted work. In addition, E. von Mutius has Patent LU101064, “Barn dust extract for the prevention and treatment of diseases” pending, Patent EP2361632, “Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders,” with royalties paid to ProtectImmun GmbH, Patent EP 1411977, “Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases,” licensed to ProtectImmun GmbH, Patent EP1637147 “Stable dust extract for allergy protection,” licensed to ProtectImmun GmbH, and Patent EP 1964570, “Pharmaceutical compound to protect against allergies and inflammatory diseases,” licensed to ProtectImmun GmbH. T. Bahmer reports grants from BMBF ; an unrestricted research grant for the German Center for Lung Research during the conduct of the study; personal fees from AstraZeneca, GlaxoSmithKline, Novartis, and Roche, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
