Oscillometry bronchodilator response testing identifies distinct pathophysiological phenotypes: a post hoc analysis of the ATLANTIS study

Spirometry with bronchodilator response (BDR) testing is the first-line test for asthma in international guidelines; however, it has been shown to have suboptimal sensitivity for asthma diagnosis and detecting small airways dysfunction. Oscillometry with BDR may identify bronchodilator response in patients with no significant BDR by spirometry. The aims of the present study were to determine whether oscillometry identifies additional BDR in the Assessment of Small Airways Involvement in Asthma (ATLANTIS) study asthma cohort compared to spirometry (ClinicalTrials.gov identifier NCT02123667), and to characterise phenotypic differences between BDR groups.

Baseline data from 518 adults with objectively confirmed asthma enrolled in ATLANTIS were analysed. Differences in clinical, biomarker and physiological characteristics were assessed between BDR groups. A subset with computed tomography (CT) imaging (208 out of 518) and nasal RNA-sequencing data (236 out of 518) underwent CT biomarker and differential gene expression analysis to investigate differences in airway morphology and pathways underlying a small airways bronchodilator responsive phenotype.

Oscillometry detected significant bronchodilator response in an additional 11% of participants not identified by spirometry, although spirometry identified more responders overall. Spirometry-positive BDR-only cases (group 1) had greater airway obstruction and exhaled nitric oxide fraction (p<0.05) compared with oscillometry-only BDR (group 2). Subgroup analysis identified differentially expressed genes related to mitochondrial stress and cell adhesion in group 3 (BDR in both) versus group 1 and reduced luminal area and greater gas trapping on CT imaging (p<0.05).

Oscillometry identified additional bronchodilator-responsive participants beyond spirometry, indicating complementary physiological information. Distinct BDR patterns were associated with differing inflammatory, physiological and structural features, suggesting distinct asthma phenotypes.