Bronchodilator responsiveness and future chronic airflow obstruction: a multinational longitudinal study

Knox-Brown B 1 , Algharbi F 1 , Mulhern O 1 , Potts J 1 , Harrabi I 2 , Janson C 3 Show all authors , Nielsen R 4 , Agarwal D 5 , Malinovschi A 6 , Juvekar S 5 , Denguezli M 7 , Gíslason T 8 , Ahmed R 9 , Nafees A 10 , Koul PA 11 , Obaseki D 12 , Anand MP 13 , Loh LC 14 , Dias HB 15 , Rodrigues F 16 , Mannino D 17 , Elbiaze M 18 , El Rhazi K 19 , Mejza F 20 , Devereux G 21 , Franssen FME 22 , El Sony A 9 , Wouters E 22 , Al Ghobain M 23 , Mortimer K 24 , Rashid A 14 , Osman R 9 , Studnicka M 25 , Cardoso J 26 , Burney P 1 , Amaral AFS 1 , BOLD Collaborative Research Group

Affiliations 

  • 1 National Heart and Lung Institute, Imperial College London, London, UK
  • 2 Ibn El Jazzar Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia
  • 3 Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
  • 4 Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
  • 5 Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India
  • 6 Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden
  • 7 Université de Sousse, Faculté de Médecine de Sousse, LR19ES09, Sousse 4000, Tunisia
  • 8 Faculty of Medicine, University of Iceland, Reykjavík, Iceland
  • 9 The Epidemiological Laboratory, Khartoum, Sudan
  • 10 Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan
  • 11 Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J&K, India
  • 12 Obafemi Awolowo University, Ile-Ife, Osun, Nigeria
  • 13 Department of Respiratory Medicine JSS Medical College, JSSAHER, India
  • 14 RCSI and UCD Malaysia Campus, Penang, Malaysia
  • 15 Escola Superior de Tecnologia da Saúde de Lisboa, Politécnico de Lisboa (Lisbon School of Health Technology, Polytechnic of Lisbon), Lisbon, Portugal
  • 16 Pulmonology Department, Santa Maria Local Health Unit, Lisbon, Portugal
  • 17 University of Kentucky, Lexington, KY, USA
  • 18 Faculté de Médecine et de Pharmacie et de Médecine dentaire Fès, Morocco
  • 19 Epidemiology and Research in Health Sciences Laboratory, Faculty of Medicine, Pharmacy and Dentistry, Sidi Mohamed Ben Abdillah University, Morocco
  • 20 Centre for Evidence Based Medicine, 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland
  • 21 Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK
  • 22 Maastricht University Medical Centre, Maastricht, the Netherlands
  • 23 King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  • 24 University of Cambridge, Cambridge, UK
  • 25 Department of Pulmonary Medicine, Paracelsus Medical University, Salzburg, Austria
  • 26 Pulmonology Department, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
EClinicalMedicine, 2025 Mar;81:103123.
PMID: 40083442 DOI: 10.1016/j.eclinm.2025.103123

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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