Small airway dysfunction: A key predictor of exacerbation risk in adolescents with mild, well-controlled asthma.

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.