Respiratory epidemiology ORIGINAL ARTICLE Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study Wan C Tan,1 William M Vollmer,2 Bernd Lamprecht,3 David M Mannino,4 Anamika Jithoo,5 Ewa Nizankowska-Mogilnicka,6 Filip Mejza,6 Thorarinn Gislason,7 Peter G J Burney,5 A Sonia Buist,8 for the BOLD Collaborative Research Group* 1UBC James Hogg Research Laboratories, Providence Heart and Lung Institute, St Paul’s Hospital, University of British Columbia, Vancouver, Canada 2Kaizer Permanente, Center for Health Research, Portland, Oregon, USA 3Department of Pulmonary Medicine, Paracelsus Private Medical University Salzburg, Salzburg, Austria 4Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, Kentucky, USA 5Department of Respiratory Epidemiology and Public Health, Imperial College London, London, UK 6Department of Respiratory Diseases, Jagiellonian University Medical College, Krakow, Poland 7Department of Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland 8Oregon Health and Science University, Portland, Oregon, USA Correspondence to Dr Wan Tan, University of British Columbia, UBC iCapture Centre for CardioPulmonary Research, St Paul’s Hospital, Rm 166, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6; wan.tan@hli.ubc.ca *The BOLD Collaborative Research Group members are listed in appendix 1. Received 30 November 2011 Accepted 25 March 2012 Published Online First 29 April 2012 This paper is freely available online under the BMJ Journals unlocked scheme, see http:// thorax.bmj.com/site/about/ unlocked.xhtml 718 ABSTRACT Rationale Criteria for a clinically signiﬁcant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. Methods 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airﬂow obstruction. Results In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (DFEV1); 12.0% (11.2% to 12.8%) change relative to initial value (%DFEV1i); and 10.0% (9.5% to 10.5%) change relative to predicted value (%DFEV1p). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (DFVC); 10.5% (8.9% to 12.0%) change relative to initial value (DFVCi); and 9.2% (7.9% to 10.5%) change relative to predicted value (DFVCp). The proportion who exceeded the above threshold values in the subgroup with spirometrically deﬁned Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV1/FVC <0.7 and FEV1% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV1-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. Conclusions The results provide reference values for bronchodilator responses worldwide that conﬁrm guideline estimates for a clinically signiﬁcant level of BDR in bronchodilator testing. INTRODUCTION Airway responsiveness to a bronchodilator is widely performed in most clinical respiratory function laboratories throughout the world. Bronchodilator response (BDR) is used to predict a patient’s response to bronchodilator treatment, to establish best attainable lung function, and in clinical trials, to rule in or rule out asthma and chronic obstruc- tive pulmonary disease (COPD).1e5 Although much has been learned about BDR, there continues to be confusion about its clinical usefulness,6 7 its Key messages What is the key question? < What is the distribution of bronchodilator response in healthy populations worldwide? What is the bottom line? < We have generated global population-based thresholds for bronchodilator reversibility testing. Why read on? < The article provides new insights into global bronchodilator response and reversibility. pathophysiological basis, its expression8e10 and its determinants.11 There is also a lack of consensus on the criteria for a signiﬁcant or increased BDR.12 13 One obstacle is the lack of agreement on how the response should be expressed.8e10 12 Another is paucity of normative reference data derived from healthy general populations, as has been recommended by the American Thoracic Society (ATS)12 and the European Respiratory Society (ERS) guidelines.13 The most common recommendation of a ‘cut-off ’ of 12% change in FEV1 from baseline for signiﬁcant bronchial responsiveness has been derived from patients with obstructive lung disease.8 9 14e17 It is conceivable that these cut-offs may not reﬂect the spectrum of responsiveness in a healthy general population.12 To date, the information derived from general populations is patchy,18e20 and none comes from non-Western countries. A better under- standing of the worldwide distribution of BDR in health and disease would be helpful for developing global criteria for BDR for clinical use and research. In this paper we report the BDR in terms of changes in forced expiratory volume in 1 s (FEV1) and in forced vital capacity (FVC), measured in population-based samples from 14 country sites that participated in the Burden of Obstructive Lung Disease (BOLD) study.21 22 The focus in this descriptive report is the distribution of BDR in healthy populations, with comparison in subpop- ulations with chronic airway obstruction. From these, we generated the 95th percentiles and tested Thorax 2012;67:718e726. doi:10.1136/thoraxjnl-2011-201445