Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study
- Wan C Tan1,
- William M Vollmer2,
- Bernd Lamprecht3,
- David M Mannino4,
- Anamika Jithoo5,
- Ewa Nizankowska-Mogilnicka6,
- Filip Mejza6,
- Thorarinn Gislason7,
- Peter G J Burney5,
- A Sonia Buist8,
- 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;
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.
- Received 30 November 2011
- Accepted 25 March 2012
- Published Online First 29 April 2012
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 (ΔFEV1); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV1i); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV1p). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVCi); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVCp). 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.
- Bronchodilator response
- COPD epidemiology
- COPD exacerbations
- respiratory measurement
- asthma epidemiology
- clinical epidemiology
- occupational lung disease
- tobacco and the lung
- COPD mechanisms
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 Landspítali-University Hospital-Scientific Fund, GlaxoSmithKline Iceland, and AstraZeneca Iceland (Reykjavik, Iceland); GlaxoSmithKline Pharmaceuticals, Polpharma, Ivax Pharma Poland, AstraZeneca Pharma Poland, ZF Altana Pharma, Pliva Kraków, Adamed, Novartis Poland, Linde Gaz Polska, Lek Polska, Tarchomińskie 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, 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.
Data sharing statement Data sharing is available via the BOLD process (through Peter Burney; e mail: ).
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