Small Airway Dysfunction Is an Independent Exacerbation Risk Biomarker in the Mild, Well-Controlled Patient With Asthma: A Frequently Unrecognized High-Risk Phenotype

TY - JOUR

T1 - Small Airway Dysfunction Is an Independent Exacerbation Risk Biomarker in the Mild, Well-Controlled Patient With Asthma

T2 - A Frequently Unrecognized High-Risk Phenotype

AU - Galant, Stanley P.

AU - Cottini, Marcello

AU - Berti, Alvise

AU - Comberiati, Pasquale

AU - Lombardi, Carlo

AU - Menzella, Francesco

AU - Ventura, Laura

AU - Chan, Rory

N1 - Copyright: © 2025 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

PY - 2025/10

Y1 - 2025/10

N2 - Background: Although current guidelines for asthma diagnosis and management have proven relatively successful, many patients with asthma continue to experience poor asthma control and exacerbations. This may be due to a failure to recognize that patients with mild, well-controlled asthma commonly have small airway dysfunction (SAD), which is associated with a significant exacerbation risk. Objective: We aimed to better characterize how well SAD, determined by impulse oscillometry, is associated with prior exacerbations in the Global Initiative for Asthma–defined mild, well-controlled asthma phenotype.Methods: In 170 adults with mild, well-controlled asthma, we determined the presence of SAD by impulse oscillometry metrics of peripheral airway resistance between 5 and 20 Hz and peripheral airway reactance as the area under the reactance curve at cut points of 0.10 kPa/L per second and 1.0 kPa/L, respectively. We also assessed the associations among SAD, FEV 1, FeNO, blood eosinophilia, and extra-fine inhaled corticosteroids (ICS) with prior exacerbations. A multivariate analysis evaluated which variables were independently associated with prior exacerbations.Results: Small airway dysfunction was present in 27.6% of the population, and prior exacerbations in 34.1%. Exacerbations were greater in those with SAD (82.9% vs 15.4%; P < .001) and lower in those receiving extra-fine ICS (27.7% vs 55.3%; P < .05). Small airway dysfunction and extra-fine ICS were both independently associated with prior exacerbations; SAD increased and extra-fine ICS decreased exacerbation risk.Conclusions: In the patient with mild, well-controlled asthma, SAD and prior exacerbations are common. Small airway dysfunction and extra-fine ICS are respectively independently associated with increased or decreased exacerbations. Detecting SAD could result in early extra-fine ICS intervention, potentially preventing future exacerbations in this phenotype.

AB - Background: Although current guidelines for asthma diagnosis and management have proven relatively successful, many patients with asthma continue to experience poor asthma control and exacerbations. This may be due to a failure to recognize that patients with mild, well-controlled asthma commonly have small airway dysfunction (SAD), which is associated with a significant exacerbation risk. Objective: We aimed to better characterize how well SAD, determined by impulse oscillometry, is associated with prior exacerbations in the Global Initiative for Asthma–defined mild, well-controlled asthma phenotype.Methods: In 170 adults with mild, well-controlled asthma, we determined the presence of SAD by impulse oscillometry metrics of peripheral airway resistance between 5 and 20 Hz and peripheral airway reactance as the area under the reactance curve at cut points of 0.10 kPa/L per second and 1.0 kPa/L, respectively. We also assessed the associations among SAD, FEV 1, FeNO, blood eosinophilia, and extra-fine inhaled corticosteroids (ICS) with prior exacerbations. A multivariate analysis evaluated which variables were independently associated with prior exacerbations.Results: Small airway dysfunction was present in 27.6% of the population, and prior exacerbations in 34.1%. Exacerbations were greater in those with SAD (82.9% vs 15.4%; P < .001) and lower in those receiving extra-fine ICS (27.7% vs 55.3%; P < .05). Small airway dysfunction and extra-fine ICS were both independently associated with prior exacerbations; SAD increased and extra-fine ICS decreased exacerbation risk.Conclusions: In the patient with mild, well-controlled asthma, SAD and prior exacerbations are common. Small airway dysfunction and extra-fine ICS are respectively independently associated with increased or decreased exacerbations. Detecting SAD could result in early extra-fine ICS intervention, potentially preventing future exacerbations in this phenotype.

KW - Asthma

KW - Exacerbations

KW - Small airway dysfunction

UR - https://www.scopus.com/pages/publications/105012537358

U2 - 10.1016/j.jaip.2025.07.002

DO - 10.1016/j.jaip.2025.07.002

M3 - Article

C2 - 40651715

SN - 2213-2198

VL - 13

SP - 2686-2691.e2

JO - The Journal of Allergy and Clinical Immunology: In Practice

JF - The Journal of Allergy and Clinical Immunology: In Practice

IS - 10

ER -