Small airway dysfunction in mild asthma: associations with impaired lung function, bronchodilator responsiveness, reduced control, and clinical characteristics.

Small airway dysfunction (SAD) has been implicated in asthma severity and poor control, yet its clinical impact remains underexplored in mild, more controlled asthma. A cross-sectional cohort across asthma severities attending clinics was assessed before enrolment into a longitudinal phenotyping and endotyping study, MAPLE. GINA step 1-3 patients with forced oscillometry (FOT) data (n=95) were assessed against two published SAD cutoffs: 1) “SAD-1” R5-R20>0.07 kPa/L, and 2) “SAD-2” R5-R20>1.0 kPa/L and AX≥1.0 kPa/L. Clinical characteristics, demographics, flares/exacerbations, medications, spirometry, methacholine responsiveness (AHR), bronchodilator responsiveness, AIRQ, ACQ, atopy, FeNO, and blood eosinophils, were compared in those with and without SAD. Among the 95 patients (median age 28, BMI 26, 41% female, 72% white Caucasian, no current smokers), 27% were GINA step 1, 24% step 2, 48% step 3, and 12% had poor control (ACQ-6≥1.5). SAD was present in 20-37% (SAD-2 and SAD-1, respectively) and was associated with lower FEV1 (p<0.001) and FEV1/FVC (p<0.05,p<0.001), greater bronchodilator responsiveness (p<0.05,p=0.072), higher eosinophils (p<0.05,p=0.053) and higher BMI (p<0.05), and had worse control (ACQ-6, not significant). Notably, SAD was present in 13-30% (SAD-2 and SAD-21, respectively) of those with normal central airway function (FEV1%pred≥80% and FEV1/FVC≥70%). These findings underscore the clinical relevance of SAD in milder, more controlled asthma, a population less researched to date. Longitudinal investigation of SAD will provide additionally insights into progression and stability of endotypes.