TY - JOUR
T1 - Bronchodilator responsiveness and future chronic airflow obstruction
T2 - a multinational longitudinal study
AU - Knox-Brown, Ben
AU - Algharbi, Fahad
AU - Mulhern, Octavia
AU - Potts, James
AU - Harrabi, Imed
AU - Janson, Christer
AU - Nielsen, Rune
AU - Agarwal, Dhiraj
AU - Malinovschi, Andrei
AU - Juvekar, Sanjay
AU - Denguezli, Miriam
AU - Gislason, Thorarinn
AU - Ahmed, Rana
AU - Nafees, Asaad
AU - Koul, Parvaiz A.
AU - Obaseki, Daniel
AU - Anand, Mahesh Padukudru
AU - Loh, Li Cher
AU - Dias, Herminia Brites
AU - Rodrigues, Fatima
AU - Mannino, David
AU - Elbiaze, Mohammed
AU - Elrhazi, Karima
AU - Mejza, Filip
AU - Devereux, Graham
AU - Franssen, Frits M. E.
AU - El Sony, Asma
AU - Wouters, Emiel
AU - Al Ghobain, Mohammed
AU - Mortimer, Kevin
AU - Rashid, Abdul
AU - Osman, Rashid
AU - Studnicka, Michael
AU - Cardoso, Joao
AU - Burney, Peter
AU - Amaral, Andre F. S.
AU - BOLD Collaborative Research Group
PY - 2025/3/1
Y1 - 2025/3/1
N2 - Background Bronchodilator responsiveness testing is mainly used for diagnosing asthma. We aimed to investigate whether it is associated with progression to chronic airflow obstruction over time. Methods The multinational Burden of Obstructive Lung Disease cohort study surveyed adults, aged 40 years and above, at baseline and followed them up after a mean of 9.1 years. Recruitment took place between January 2, 2003 and December 26, 2016. Follow-up measurements were collected between January 29, 2019 and October 24, 2021. On both occasions, study participants provided information on respiratory symptoms, health status and several environmental and lifestyle exposures. They also underwent pre- and post-bronchodilator spirometry. We defined bronchodilator responsiveness at baseline using the American Thoracic Society and European Respiratory Society (ATS/ERS) 2022 definition, and the presence of chronic airflow obstruction at follow-up as a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) less than the lower limit of normal. We used multi-level regression models to estimate the association between baseline bronchodilator responsiveness and incident chronic airflow obstruction. We stratified analyses by gender and performed a sensitivity analysis in never smokers. Findings We analysed data from 3701 adults with 56% being women. Compared to those without bronchodilator responsiveness at baseline, those with bronchodilator responsiveness had 36% increased risk of developing chronic airflow obstruction (RR: 1.36, 95%CI 1.04, 1.80). This effect was stronger in women (RR: 1.45, 95%CI 1.09, 1.91) than men (RR: 1.07, 95%CI 0.51, 2.24). Never smokers with bronchodilator responsiveness also were at greater risk of incident chronic airflow obstruction (RR: 1.48, 95%CI 1.01, 2.20). Interpretation Bronchodilator responsiveness appears to be a risk factor for incident chronic airflow obstruction. It is important that future studies in other large population-based cohorts replicate these findings. Funding National Heart and Lung Institute, UK Medical Research Council, and Wellcome Trust. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
AB - Background Bronchodilator responsiveness testing is mainly used for diagnosing asthma. We aimed to investigate whether it is associated with progression to chronic airflow obstruction over time. Methods The multinational Burden of Obstructive Lung Disease cohort study surveyed adults, aged 40 years and above, at baseline and followed them up after a mean of 9.1 years. Recruitment took place between January 2, 2003 and December 26, 2016. Follow-up measurements were collected between January 29, 2019 and October 24, 2021. On both occasions, study participants provided information on respiratory symptoms, health status and several environmental and lifestyle exposures. They also underwent pre- and post-bronchodilator spirometry. We defined bronchodilator responsiveness at baseline using the American Thoracic Society and European Respiratory Society (ATS/ERS) 2022 definition, and the presence of chronic airflow obstruction at follow-up as a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) less than the lower limit of normal. We used multi-level regression models to estimate the association between baseline bronchodilator responsiveness and incident chronic airflow obstruction. We stratified analyses by gender and performed a sensitivity analysis in never smokers. Findings We analysed data from 3701 adults with 56% being women. Compared to those without bronchodilator responsiveness at baseline, those with bronchodilator responsiveness had 36% increased risk of developing chronic airflow obstruction (RR: 1.36, 95%CI 1.04, 1.80). This effect was stronger in women (RR: 1.45, 95%CI 1.09, 1.91) than men (RR: 1.07, 95%CI 0.51, 2.24). Never smokers with bronchodilator responsiveness also were at greater risk of incident chronic airflow obstruction (RR: 1.48, 95%CI 1.01, 2.20). Interpretation Bronchodilator responsiveness appears to be a risk factor for incident chronic airflow obstruction. It is important that future studies in other large population-based cohorts replicate these findings. Funding National Heart and Lung Institute, UK Medical Research Council, and Wellcome Trust. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
KW - Spirometry
KW - Asthma
KW - Epidemiology
KW - COPD
KW - Bronchodilator
KW - SEX-DIFFERENCES
KW - LUNG-FUNCTION
KW - MOUSE MODEL
KW - COUNTRIES
KW - ADULTS
KW - ASTHMA
U2 - 10.1016/j.eclinm.2025.103123
DO - 10.1016/j.eclinm.2025.103123
M3 - Article
SN - 2589-5370
VL - 81
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 103123
ER -