Oscillometry bronchodilator response testing identifies distinct pathophysiological phenotypes: a post hoc analysis of the ATLANTIS study
13 affiliations
- 1National Heart and Lung Institute, NIHR Imperial Biomedical Research Centre, Imperial College London, London, UK.
- 2Data Science Institute, Imperial College London, London, UK.
- 3Institute for Lung Health, National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester College of Life Sciences, University of Leicester, Leicester, UK.
- 4General Practitioners Research Institute, Groningen, The Netherlands.
- 5Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
- 6Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.
- 7Chiesi Farmaceutici S.p.A., Parma, Italy.
- 8LungenClinic Grosshansdorf, Grosshansdorf, Germany.
- 9Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
- 10Christian-Albrechts University of Kiel, Kiel, Germany.
- 11Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
- 12University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK.
- 13Medicines Evaluation Unit, an IQVIA business, Manchester, UK.
Abstract
Background
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.Methods
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.Results
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).Interpretation
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.
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BibTeX
@article{quek2026oscillometry,
title = {{Oscillometry bronchodilator response testing identifies distinct pathophysiological phenotypes: a post hoc analysis of the ATLANTIS study}},
author = {Eleanor Quek and Oliver Pitts and Franz Aaron Clemeno and Janwillem W H Kocks and Bianca Beghe and Monica Kraft and Ulrica Scaffidi Argentina and Alberto Papi and Klaus F Rabe and Maarten van den Berge and Dave Singh and Christopher Brightling and Salman Siddiqui},
journal = {ERJ open research},
year = {2026},
month = nov,
doi = {10.1183/23120541.00314-2026},
url = {https://europepmc.org/article/PMC/PMC13725841},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oscillometry bronchodilator response testing identifies distinct pathophysiological phenotypes: a post hoc analysis of the ATLANTIS study
AU - Eleanor Quek
AU - Oliver Pitts
AU - Franz Aaron Clemeno
AU - Janwillem W H Kocks
AU - Bianca Beghe
AU - Monica Kraft
AU - Ulrica Scaffidi Argentina
AU - Alberto Papi
AU - Klaus F Rabe
AU - Maarten van den Berge
AU - Dave Singh
AU - Christopher Brightling
AU - Salman Siddiqui
PY - 2026
DA - 2026/11/01
JO - ERJ open research
DO - 10.1183/23120541.00314-2026
UR - https://europepmc.org/article/PMC/PMC13725841
AB - Background 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.Methods 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.Results 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).Interpretation 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.
SN - 2312-0541
ER -