Improved peripheral airway reactance is associated with clinical remission after biologic therapy in severe asthma

BACKGROUND: Small airways dysfunction (SAD) is increasingly recognized as a treatable trait in severe asthma and may influence the likelihood of achieving clinical remission. OBJECTIVE: To investigate whether oscillometry-defined SAD parameters were associated with remission after biologic or standard-of-care treatment. METHODS: Data from 237 adults with Global Initiative for Asthma-defined severe asthma were retrospectively collected at a tertiary specialist center. A total of 127 individuals received add-on biologic therapy (benralizumab, dupilumab, or tezepelumab) and 110 received standard of care alone. Spirometry, oscillometry, fractional exhaled nitric oxide, blood eosinophil count, exacerbation frequency, and Asthma Control Questionnaire (ACQ) scores were collected. Three-component remission (3CR; no exacerbations, no maintenance oral corticosteroids, and ACQ < 1.5) and four-component remission (4CR; 3CR plus stable lung function defined as forced expiratory volume in 1 second) were assessed. Multivariable logistic regression was used to identify predictors of remission, adjusted for age, sex, body mass index, inhaled corticosteroid dose, and smoking status. RESULTS: Biologic therapy significantly improved lung function, oscillometry indices, type 2 biomarkers, exacerbation frequency, and ACQ scores. In the biologics group, 50.4% achieved 3CR and 34.6% achieved 4CR, compared with 42.6% and 25.0%, respectively, in the standard-of-care group. Baseline fractional exhaled nitric oxide greater than or equal to 25 parts per billion and greater than or equal to 50 parts per billion were associated with higher odds of achieving remission after biologic therapy. An improvement in forced expiratory volume in 1 second greater than or equal to 100 mL was strongly associated with both 3CR and 4CR. More importantly, improvement in the oscillometry-derived area under the reactance curve greater than or equal to 0.65 kPa/L, corresponding to the minimal clinically important difference, was significantly associated with 4CR (adjusted odds ratio, 2.61 [1.02-6.65]; P < .05). In the standard-of-care group (3CR: 42.6%; 4CR: 25%), a higher baseline area under the reactance curve greater than or equal to 1.0 kPa/L was associated with a lower likelihood of achieving 3CR (adjusted odds ratio, 0.36 [0.14-0.93]; P < .05). CONCLUSION: Improvements in peripheral airway compliance measured using oscillometry are associated with clinical remission in severe asthma after biologic therapy. These findings support SAD as an important physiological correlate and a potential treatable trait in achieving asthma remission.