Philip H Quanjer1, Gregg L Ruppel2, Arnulf Langhammer3, Abhishek Krishna2, Frans Mertens4, Ane Johannessen5, Ana M B Menezes6, Fernando C Wehrmeister6, Rogelio Perez-Padilla7, Maureen P Swanney8, Wan C Tan9, Jean Bourbeau10. 1. 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. 2. Department of Pulmonary, Critical Care and Sleep Medicine, St. Louis University School of Medicine, St. Louis, MO. 3. HUNT Research Center, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. 4. Department of Pulmonary Diseases, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands. 5. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. 6. Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil. 7. Sleep Clinic, National Institute of Respiratory Diseases, Mexico City, Mexico. 8. Respiratory Physiology Laboratory, Christchurch Hospital, Christchurch, New Zealand. 9. UBC James Hogg Research Laboratories, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. 10. Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada.
Abstract
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.
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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