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

Ben Knox-Brown et al. EClinicalMedicine. .

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.

Keywords: Asthma; Bronchodilator; COPD; Epidemiology; Spirometry.

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Conflict of interest statement

DM declares being a consultant to and receiving royalties from GlaxoSmithKline, AstraZeneca, and the COPD Foundation (royalty payments are up to date) and acting as an expert witness for Schlesinger Law Firm, outside of the submitted work. RN reports grants and personal fees from AstraZeneca and GlaxoSmithKline and grants from Boehringer Ingelheim and Novartis, outside of the submitted work. FR reports grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. FF reports consulting fees from Sanofi and MSD, as well as personal and institutional fees from Sanofi, AstraZeneca, Chiesi, GSK and Pfizer, outside of the submitted work. AA reports research grants from the COLT foundation outside of the submitted work. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study flow diagram showing the inclusion and exclusion of participant data from Burden of Obstructive Lung Disease (BOLD) study.
Fig. 2
Fig. 2
Proportion progressing to chronic airflow obstruction by gender and WHO region. Ref: Reference population with no self-reported asthma and no evidence of bronchodilator responsiveness and no chronic airflow obstruction (CAO) at baseline; BDR: responsiveness according to ATS/ERS 2022 definition-change of >10% relative to the predicted value for FEV1 or FVC. Chronic airflow obstruction defined if post-bronchodilator FEV1/FVC was less than the lower limit of normal (LLN) according to reference equations for European Americans in The Third National Health and Nutrition Survey (NHANES III). African region includes: Nigeria, Benin, Malawi. European region includes: Estonia, Iceland, Kyrgyzstan, Norway, and Sweden. South-East Asia includes: Indian sites. Western Pacific includes: Philippines.
Fig. 3
Fig. 3
Incidence rates of chronic airflow obstruction per 1000 person-years. Error bars represent 95% confidence interval. Ref: Reference population with no self-reported asthma and no evidence of bronchodilator responsiveness and no chronic airflow obstruction at baseline; BDR+: Bronchodilator Responsiveness ATS/ERS 2022 definition: change of >10% relative to the predicted value for FEV1 or FVC; Asthma ever: if participants answered yes to “Has a doctor or other health care provider ever told you that you have asthma, asthmatic bronchitis or allergic bronchitis?” in the core questionnaire Chronic airflow obstruction defined if post-bronchodilator FEV1/FVC was less than the lower limit of normal (LLN) according to reference equations for European Americans in The Third National Health and Nutrition Survey (NHANES III).
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