disease, since both diagnostic practices and access to care might vary across our widely dispersed sites. Nonetheless this is stan- dard practice for developing reference equations for lung func- tion.25 Also, we would note that only 4% of our healthy never smokers met criteria for GOLD stage 2 or higher COPD, suggesting that the results would be unlikely to change much by excluding these individuals, and indeed we conﬁrmed this for tables 2 and 3 (data not shown). Second, because the distribution of BDRs are continuous and unimodal as had been shown in clinical studies8 9 15 and population studies,18e20 the cutoff value for a ‘positive’ response in all studies, including ours, remained somewhat arbitrary.35 Third, we used 200 mg of salbutamol/albuterol instead of higher doses as an extra precaution because it was a ﬁeld study and involved home visits in many sites. While GOLD guidelines recommended 400 mg, many published clinical studies have used different types and doses of drugs as summarised in the recent paper on broncho- dilator reversibility by Hanania et al.26 Lastly, we demonstrated the effect of acute reversibility due to bronchodilator in one setting but not its reproducibility on repeated testing and also not the long-term reversibility due to anti-inﬂammatory drugs. Hence, a lack of a response to bronchodilator testing in one setting may not preclude a clinical response to bronchodilating or anti-inﬂammatory therapy.10 24 In conclusion, the results from this study add new worldwide data on the distribution of bronchodilator response and airway reversibility. The reference values derived from healthy individ- uals addressed the reference gap in BDR. The values agreed well with the current guideline cutoffs for a signiﬁcant BDR, were discriminative for different subpopulations and strengthen the applicability of these measures for global interpretation in bronchodilator testing. Acknowledgements BOLD wishes to acknowledge the contributions of Georg Harnoncourt of the ndd Corporation and Paul Enright for their assistance with spirometry training and quality control during the study. Contributors WT and WMV had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. WT and WMV contributed to data analysis and writing the manuscript. BL, DMM, AJ, EN-M, FM, PB, TG and SB contributed to writing and revising the manuscript. Funding The BOLD initiative has been funded in part by unrestricted educational grants to the Operations Center (http://www.boldcopd.org) from ALTANA, Aventis, AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Merck, Novartis, Pﬁzer, Schering-Plough, Sepracor, and University of Kentucky. Additional local support for BOLD clinical sites was provided by: Boehringer Ingelheim China (GuangZhou, China); Turkish Thoracic Society, Boehringer-Ingelheim, and Pﬁzer (Adana, Turkey); Altana, Astra-Zeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck Sharpe & Dohme, Novartis, Salzburger Gebietskrankenkasse, and Salzburg Local Government (Salzburg, Austria); Research for International Tobacco Control, the International Development Research Centre, the South African Medical Research Council, the South African Thoracic Society GlaxoSmithKline Pulmonary Research Fellowship, and the University of Cape Town Lung Institute (Cape Town, South Africa); and Landsp´ıtali-University Hospital-Scientiﬁc Fund, GlaxoSmithKline Iceland, and AstraZeneca Iceland (Reykjavik, Iceland); GlaxoSmithKline Pharmaceuticals, Polpharma, Ivax Pharma Poland, AstraZeneca Pharma Poland, ZF Altana Pharma, Pliva Krak´ow, Adamed, Novartis Poland, Linde Gaz Polska, Lek Polska, Tarchominskie Zakłady Farmaceutyczne Polfa, Starostwo Proszowice, Skanska, Zasada, Agencja Mienia Wojskowego w Krakowie, Telekomunikacja Polska, Biernacki, Biogran, Amplus Bucki, Skrzydlewski, Sotwin, and Agroplon (Cracow, Poland); Boehringer-Ingelheim, and Pﬁzer Germany (Hannover, Germany); the Norwegian Ministry of Health’s Foundation for Clinical Research, and Haukeland University Hospital’s Medical Research Foundation for Thoracic Medicine (Bergen, Norway); AstraZeneca, Boehringer-Ingelheim, Pﬁzer, and GlaxoSmithKline (Vancouver, Canada); Marty Driesler Cancer Project (Lexington, Kentucky, USA); Altana, Boehringer Ingelheim (Phil), GlaxoSmithKline, Pﬁzer, Philippine College of Chest Physicians, Philippine College of Physicians, and United Laboratories (Phil) (Manila, Philippines); Air Liquide Healthcare P/L, AstraZeneca P/L, Boehringer Ingelheim P/L, GlaxoSmithKline Australia P/L, Pﬁzer Australia P/L (Sydney, Australia); UK Department of Health’s Policy Research Programme (London, UK); Swedish Heart-Lung Foundation, the Swedish Heart and Lung Association, and GlaxoSmithKline (Uppsala, Thorax 2012;67:718e726. doi:10.1136/thoraxjnl-2011-201445 R e s p i r a t o r y e p i d em i o l o g y Sweden). The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Competing interests WMV, ASB, TG, BL, ENM and WCT received funding for the BOLD study Operations Center and/or other research from unrestricted educational grants from GlaxoSmithKline, Pﬁzer, Boehringer Ingelheim, AstraZeneca, ALTANA, Novartis, Merck, Chiesi, Schering Plough, and Sepracor. Several authors have served on advisory boards for GlaxoSmithKline (ASB), ALTANA (ASB), Merck (ASB, WMV), Novartis (ASB). Several authors have participated in COPD workshops funded by Merck (WMV), AstraZeneca (ASB, TG), Pﬁzer (TG), GlaxoSmithKline (ASB, TG, WMV) and Telacris (WCT). All other authors declare they have no conﬂict of interest. Ethics approval Institutional Ethics Review Board at each study site. Provenance and peer review Not commissioned; externally peer reviewed. 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