@article{Portacci:2026:10.1183/13993003.00150-2026,
author = {Portacci, A and Ventura, L and Menzella, F and Poto, R and Berti, A and Lombardi, C and Comberiati, P and Carpagnano, GE and Diamant, Z and Adcock, IM and Lipworth, B and Usmani, O and Cottini, M and Chan, R},
doi = {10.1183/13993003.00150-2026},
journal = {Eur Respir J},
title = {Small Airway Dysfunction May Mediate the Association Between Body Mass Index and Severe Asthma Exacerbations.},
url = {http://dx.doi.org/10.1183/13993003.00150-2026},
year = {2026}
}

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TY  - JOUR
AB  - BACKGROUND: Obesity is associated with poorer asthma outcomes and an increased risk of exacerbations, but the underlying mechanisms remain incompletely understood. Small airway dysfunction (SAD) may represent a key mechanistic link between excess body weight and adverse asthma outcomes. METHODS: In this multicenter observational study, adult patients with asthma underwent clinical characterization, spirometry and impulse oscillometry (IOS). SAD was defined using a composite criterion based on peripheral airway resistance (R5-20), reactance area (AX) and the ratio of peripheral to total airway resistance (R5-20)/R5. Associations between body mass index (BMI), SAD and severe asthma exacerbations were assessed using multivariable regression models. Non-linear relationships were explored using generalized additive models and mediation analyses quantified the contribution of SAD to the obesity-exacerbation association. FINDINGS: Among 1169 patients, IOS-defined SAD was significantly more prevalent in individuals with BMI≥30kg·m-2. Increasing BMI was associated with worse oscillometric parameters (p<0.0001), following a non-linear pattern with steeper deterioration beyond BMI values of approximately 28-30kg·m-2. SAD was independently associated with obesity (adjusted OR 2.11, 95% CI 1.56-2.86) and with severe asthma exacerbations in the previous year (adjusted OR 2.01, 95% CI 1.53-2.65, both p<0.0001). Mediation analyses showed that SAD accounted for 26%-41% of the association between obesity and exacerbation risk (p=0.004 and 0.03). Spirometric indices provided limited additional information. INTERPRETATION: Oscillometry-defined small airways dysfunction (SAD) represents a non-linear functional trait underlying the association between obesity and severe asthma exacerbations, supporting its clinical relevance in obese patients with asthma and identifying SAD as a potential treatable trait.
AU  - Portacci,A
AU  - Ventura,L
AU  - Menzella,F
AU  - Poto,R
AU  - Berti,A
AU  - Lombardi,C
AU  - Comberiati,P
AU  - Carpagnano,GE
AU  - Diamant,Z
AU  - Adcock,IM
AU  - Lipworth,B
AU  - Usmani,O
AU  - Cottini,M
AU  - Chan,R
DO  - 10.1183/13993003.00150-2026
PY  - 2026///
TI  - Small Airway Dysfunction May Mediate the Association Between Body Mass Index and Severe Asthma Exacerbations.
T2  - Eur Respir J
UR  - http://dx.doi.org/10.1183/13993003.00150-2026
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42167779
ER  - 

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