• Philip H Quanjer, Gregg L Ruppel, Arnulf Langhammer, Abhishek Krishna, Frans Mertens, Ane Johannessen, MenezesAna M BAMBPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil., Fernando C Wehrmeister, Rogelio Perez-Padilla, Maureen P Swanney, Wan C Tan, and Jean Bourbeau.
• Department of Pulmonary Diseases, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands; Department of Pediatrics-Pulmonary Diseases, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands. Electronic address: pquanjer@gmail.com.
• Chest. 2017 May 1; 151 (5): 1088-1098.

BackgroundRecommendations 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.MethodsBDR 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.ResultsChange (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.ConclusionsExpressing 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.Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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