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

BACKGROUND: Small airways dysfunction (SAD) is increasingly recognised 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 following biologic or standard-of-care treatment. METHODS: Data from 237 adults with GINA-defined severe asthma were retrospectively collected at a tertiary specialist centre. 127 received add on biologic therapy (Benralizumab, Dupilumab or Tezepelumab) and 110 received standard of care alone. Spirometry, oscillometry, fractional exhaled nitric oxide (FeNO), blood eosinophil count (BEC), exacerbation frequency and Asthma Control Questionnaire (ACQ) scores were collected. Three component remission (3CR: no exacerbations, no maintenance OCS,ACQ <1.5) and four component remission (4CR: 3CR plus stable lung function defined as FEV₁) were assessed. Multivariable logistic regression was used to identify predictors of remission, adjusted for age, sex, BMI, ICS 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 FeNO ≥25ppb and ≥50ppb were associated with higher odds of achieving remission following biologic therapy. An improvement in FEV₁ ≥100mL was strongly associated with both 3CR and 4CR. Importantly, improvement in oscillometry-derived area under the reactance curve (AX) ≥0.65kPa/L, corresponding to the minimal clinically important difference, was significantly associated with 4CR (adjusted OR 2.61 [1.02-6.65], p<0.05). In the standard-of-care group (3CR: 42.6%; 4CR: 25%), higher baseline AX ≥1.0 kPa/L was associated with a lower likelihood of achieving 3CR (adjusted OR 0.36 [0.14-0.93], p<0.05). CONCLUSION: Improvements in peripheral airway compliance measured using oscillometry are associated with clinical remission in severe asthma following biologic therapy. These findings support SAD as an important physiological correlate and potential treatable trait in achieving asthma remission.