Fixed airway obstruction and bronchodilator responsiveness phenotypes in severe asthma population from SANI registry
- PMID: 41173502
- PMCID: PMC12581063
- DOI: 10.1136/bmjresp-2024-002992
Fixed airway obstruction and bronchodilator responsiveness phenotypes in severe asthma population from SANI registry
Abstract
Background: Data on asthma with fixed airway obstruction (FAO) are heterogeneous due to different and misleading definitions. Describing the FAO phenotype has significant implications for severe asthma (SA) comprehension.
Objective: To characterise SA patients with FAO in the Severe Asthma Network in Italy (SANI) registry at baseline, and to compare with those with reversible airway obstruction (bronchodilator responsiveness, BDR). The potential for re-evaluating FAO or BDR in the follow-up was explored.
Methods: FAO was defined as a forced expiratory volume in the first second (FEV1)/forced vital capacity ratio < Lower Limit of Normal (LNN) after a bronchodilator test with an increase in FEV1 of <12% or 200 mL, compared with BDR and no airway obstruction (no-AO). Clinical reported outcomes, including asthma control (ACT), quality of life (AQLQ) and exacerbations (AEs) were collected. The effect of demographic, clinical and biohumoral variables on FAO, BDR and no-AO groups at baseline and during the follow-up was estimated.
Results: Among 354 patients, 190 (53.7%) reported AO with 116 (60.1%) resulting in FAO. The overall FAO rate at enrolment was 32.8%. Compared with BDR, FAO patients had better asthma control (34.5% vs 20.3%, p=0.004), a higher ACT (17.4 vs 15.2, p=0.005) and AQLQ (4.6 vs 3.8, p=0.001) score. FAO patients were less likely to visit the emergency room or be hospitalised than BDR (p=0.050), with no difference in AEs. The effect of airway calibre on fractional exhaled nitric oxide is more likely to cause its lower level within FAO compared with BDR (29.5 vs 46.0 ppb, p=0.04) than a lower T2 burden. A variation from FAO to BDR or no-AO was associated with the Global Initiative for Asthma classification (step 4 vs 5: HR 3.58 (95% CI 1.16 to 11.03)) and the age of asthma onset (30-39 vs <20 years: HR 3.94 (95% CI 1.09 to 14.30)) CONCLUSION: Stratifying SA patients from the SANI registry reveals an FAO phenotype that expresses different clinical outcomes and biological markers compared to BDR. Over time, FAO may be reversible in late-onset SA with less inhaled corticosteroid treatment.
Keywords: Asthma; Asthma Mechanisms; Pulmonary Disease, Chronic Obstructive; Respiratory Function Test.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
Conflict of interest statement
Competing interests: GG reports fee as speaker for AstraZeneca; FB received financial grants from AstraZeneca Financial grants from AstraZeneca, Chiesi Farmaceutici S.p.A and Insmed Inc.; he worked as a paid consultant for Menarini and Zambon; and received speaker fees from AstraZeneca, Chiesi Farmaceutici S.p.A., GlaxoSmithKline, Guidotti, Grifols, Insmed Inc., Menarini, Novartis AG, Sanofi-Genzyme, Viatris Inc., Vertex Pharmaceuticals and Zambo; GWC reports having received research grants as well as being lecturer or having received advisory board fees from: A. Menarini, Allergy Therapeutics, AstraZeneca, Chiesi Farmaceutici, Faes, Firma, Guidotti-Malesci, Glaxo Smith Kline, Hal Allergy, Innovacaremd, Novartis, OmPharma, RedMaple, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes-Greer, Uriach Pharma, ThermoFisher, Valeas; EH received a research grant from GlaxoSmith&Kline, and fees for lectures from Sanofi, Regeneron, GlaxoSmith&Kline, AstraZeneca, Novartis, Chiesi, Stallergenes-Greer; and declares fees for advisory boards participation from Sanofi, Regeneron, Glaxo Smith Kline, AstraZeneca, Novartis, Chiesi, Almirall, Celltrion Healthcare, Bosch; PP received advisory board fees from Chiesi Farmaceutici, Glaxo Smith Kline and Sanofi, and fees for educational activities from: AstraZeneca, Chiesi Farmaceutici, Glaxo Smith Kline, Guidotti and Sanofi; IS and VB report no conflicts of interest; FLMR: reports grants, personal fees and other compensation from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Novartis, and personal fees and grants to support scientific research from Sanofi; MM reports grants from Astra-Zeneca, Glaxo Smith Kline and Sanofi-Genzyme.
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