Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2026
Small airway dysfunction: A key predictor of exacerbation risk in adolescents with mild, well-controlled asthma.
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Comberiati Pasquale, Cottini Marcello, Ventura Laura, Lombardi Carlo, Chan Rory, Berti Alvise, Wandalsen Gustavo, Pelaia Corrado, Munblit Daniel, Menzella Francesco, Landi Massimo, Peroni Diego, Galant Stanley
Аннотация
BACKGROUND: Mild asthma is considered a low-risk condition because symptoms are infrequent and lung function is preserved. However, severe exacerbations may still occur in such patients. Small airway dysfunction (SAD) is recognized as an important contributor to exacerbation risk, even in adults with mild asthma. Less is known in adolescents, a vulnerable population because of transition-related issues.
OBJECTIVE: To investigate whether SAD, identified by impulse oscillometry, is associated with prior exacerbations in adolescents with Global Initiative for Asthma (GINA)-defined mild asthma, good symptom control, and normal spirometry.
METHODS: SAD was determined by the concomitant presence of abnormal z-score values for peripheral airway resistance between 5 and 20 Hz (R5-R20) and the area under the reactance curve (>+1.645) and peripheral airway reactance at 5 Hz (<-1.645). Associations between SAD, fractional exhaled nitric oxide (FeNO), and blood eosinophil count (BEC) with previous exacerbations were assessed using multivariable logistic regression.
RESULTS: SAD was present in 28% of participants. Adolescents with SAD exhibited higher type-2 inflammatory biomarkers and significantly more frequent exacerbations than those without SAD (79% vs 20%, P < .0001). In multivariable analysis, SAD, FeNO greater than or equal to 25 parts per billion, and BEC greater than or equal to 300 cells/μL were independently associated with previous exacerbations; SAD remained an independent predictor even after adjusting for both elevated FeNO and BEC (adjusted odds ratio, 5.07; 95% CI, 1.52-18.43; P = .008). Mediation analysis suggested that SAD significantly mediated the association between type-2 inflammation and exacerbations.
CONCLUSION: Among adolescents with mild, controlled asthma and normal spirometry, impulse oscillometry-defined SAD is strongly associated with exacerbation susceptibility. Objective assessment of peripheral airway function may help refine risk stratification in this population.
OBJECTIVE: To investigate whether SAD, identified by impulse oscillometry, is associated with prior exacerbations in adolescents with Global Initiative for Asthma (GINA)-defined mild asthma, good symptom control, and normal spirometry.
METHODS: SAD was determined by the concomitant presence of abnormal z-score values for peripheral airway resistance between 5 and 20 Hz (R5-R20) and the area under the reactance curve (>+1.645) and peripheral airway reactance at 5 Hz (<-1.645). Associations between SAD, fractional exhaled nitric oxide (FeNO), and blood eosinophil count (BEC) with previous exacerbations were assessed using multivariable logistic regression.
RESULTS: SAD was present in 28% of participants. Adolescents with SAD exhibited higher type-2 inflammatory biomarkers and significantly more frequent exacerbations than those without SAD (79% vs 20%, P < .0001). In multivariable analysis, SAD, FeNO greater than or equal to 25 parts per billion, and BEC greater than or equal to 300 cells/μL were independently associated with previous exacerbations; SAD remained an independent predictor even after adjusting for both elevated FeNO and BEC (adjusted odds ratio, 5.07; 95% CI, 1.52-18.43; P = .008). Mediation analysis suggested that SAD significantly mediated the association between type-2 inflammation and exacerbations.
CONCLUSION: Among adolescents with mild, controlled asthma and normal spirometry, impulse oscillometry-defined SAD is strongly associated with exacerbation susceptibility. Objective assessment of peripheral airway function may help refine risk stratification in this population.