Combined Large and Small Airway Obstruction Is Associated With Increased Exacerbation Frequency and Poorer Symptom Control in Persistent Asthma

Background: Spirometry remains central to the assessment of asthma but may fail to detect small airways dysfunction (SAD), which contributes to considerable symptoms and exacerbation risk. Objective: We investigated whether integrating oscillometry with spirometry improves physiological phenotyping and risk stratification in asthma. Methods: In this retrospective, multicenter study, data from 1497 adults with asthma were analyzed from the Oscillometry Asthma Registry. SAD was defined using the ratio of resistance heterogeneity between 5 and 20 Hz to resistance at 5 Hz ≥19% and airflow obstruction as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <70%. Participants were categorized into 4 mutually exclusive groups: (1) group 1—normal oscillometry and normal spirometry, (2) group 2—abnormal oscillometry with normal spirometry, (3) group 3—normal oscillometry with abnormal spirometry, and (4) group 4—abnormal oscillometry and abnormal spirometry. Associations with symptom control, exacerbations, and type 2 inflammatory biomarkers were assessed using multivariable logistic regression. Results: For ≥1 exacerbation, the adjusted odds ratios (aORs) (95% confidence intervals) for group 4 were as follows: versus group 1, 3.19 (2.31, 4.42); versus group 2, 1.99 (1.46, 2.74); and versus group 3, 1.59 (1.07, 2.37). Corresponding aOR values for group 3 were as follows: versus group 2, 1.26 (0.85, 1.86), and versus group 1, 2.01 (1.37, 2.94). The aOR for ≥1 exacerbation for group 2 versus group 1 was 1.60 (1.18, 2.16). Results were similar when using FEV1/FVC