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Original Research: Pulmonary Physiology |

Bronchodilator Response in FVC Is Larger and More Relevant Than in FEV1 in Severe Airflow Obstruction

Philip H. Quanjer, MD, PhD; Gregg L. Ruppel, MEd; Arnulf Langhammer, MD, PhD; Abhishek Krishna, MD; Frans Mertens, BICT; Ane Johannessen, PhD; Ana M.B. Menezes, MD; Fernando C. Wehrmeister, PhD; Rogelio Perez-Padilla, MD; Maureen P. Swanney, PhD; Wan C. Tan, MD; Jean Bourbeau, MD
Author and Funding Information

FUNDING/SUPPORT: J. B. reports grants from AstraZeneca, Boehringer Ingelheim, the Canadian Respiratory Research Network, Novartis, and GlaxoSmithKline for the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, and grants from Takeda, Pfizer, and Grifols outside the submitted work. A. L. reports that the HUNT lung study was partly funded by Astra-Zeneca Norway and the Norwegian Research Council. The Nord-Trøndelag Health Study (the HUNT study) is a collaboration between the HUNT Research Center (Faculty of Medicine, Norwegian University of Science and Technology), the Nord-Trøndelag County Council, the Central Norway Health Authority, and the Norwegian Institute of Public Health. The PLATINO study was funded by Boehringer Ingelheim and by the Latin-American Thoracic Association (ALAT). A. M. B. M. reports grants from Boehringer Ingelheim GmbH during the conduct of the PLATINO study, and personal fees from AstraZeneca outside the submitted work. W. C. T. reports grants from the Canadian Institute of Health Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners Astra Zeneca Canada Ltd, Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc, Nycomed Canada Inc, and Pfizer Canada Ltd for conducting the longitudinal population-based CanCOLD study on COPD.

aDepartment of Pulmonary Diseases, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands

bDepartment of Pediatrics-Pulmonary Diseases, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands

cDepartment of Pulmonary, Critical Care and Sleep Medicine, St. Louis University School of Medicine, St. Louis, MO

dHUNT Research Center, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway

eDepartment of Global Public Health and Primary Care, University of Bergen, Bergen, Norway

fPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil

gSleep Clinic, National Institute of Respiratory Diseases, Mexico City, Mexico

hRespiratory Physiology Laboratory, Christchurch Hospital, Christchurch, New Zealand

iUBC James Hogg Research Laboratories, Providence Heart and Lung Institute, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada

jRespiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada

CORRESPONDENCE TO: Philip H. Quanjer, MD, PhD, Kervel 19, 7443 GT Nijverdal, The Netherlands


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(5):1088-1098. doi:10.1016/j.chest.2016.12.017
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Background  Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment.

Methods  BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV1, FVC, and FEV1/FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score.

Results  Change (Δ) in FEV1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1,106 subjects with low FEV1 (200-1,621 mL) the FEV1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. ΔFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction.

Conclusions  Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.

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