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Original Research |

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, B ICT; 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

Financial disclosure

Dr. Bourbeau reports grants from AstraZeneca, Boehringer Ingelheim, Canadian Respiratory Research Network, Novartis, GlaxoSmithKline for the CanCOLD study, and grants from Takeda, Pfizer, Grifols outside the submitted work.

Dr. Langhammer 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 HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology NTNU), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health.

Dr. Menezes reports grants from Boehringer Ingelheim GmbH during the conduct of the PLATINO study, and personal fees from AstraZeneca outside the submitted work.

Dr. Tan reports grants from Canadian Institute of Heath 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., Pfizer Canada Ltd for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD.

AJ, AK, FCW, FM, GLR, MPS, PHQ and RP-P have nothing to declare.

Role of sponsors: This study received no support from sponsors.

Other contributions: The PLATINO study was funded by Boehringer-Ingelheim and by ALAT (Latin-American Thoracic Association).

Department of Pulmonary Diseases and Department of Paediatrics-Pulmonary Diseases, Erasmus Medical Centre, Erasmus University, Rotterdam, Netherlands

Department of Pulmonary, Critical Care and Sleep Medicine, Saint Louis University School of Medicine, St Louis, Missouri, USA

HUNT Research Centre, Department of Public Health and General Practice, The Norwegian University of Science and Technology (NTNU), Levanger, Norway

Department of Pulmonary, Critical Care and Sleep Medicine, Saint Louis University School of Medicine, St Louis, Missouri, USA

Department of Pulmonary Diseases, Erasmus Medical Centre, Erasmus University, Rotterdam, Netherlands

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

Post-graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil

Post-graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil

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

Respiratory Physiology Laboratory, Christchurch Hospital, Christchurch, New Zealand

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

Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montréal, Quebec, Canada

Corresponding author: Philip H. Quanjer, Kervel 19, 7443 GT Nijverdal, The Netherlands.


Copyright 2016, . All Rights Reserved.


Chest. 2017. doi:10.1016/j.chest.2016.12.017
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Published online

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 tests were available from clinical patients in the Netherlands, New Zealand and the USA (N=15,278, 51.7% females) and surveys in Canada, Norway and five Latin-American countries (N=16,250, 54.7% females). BDR in FEV1, FVC and FEV1/ FVC was expressed as absolute change, % baseline, % predicted and z-score.

Results  Change (Δ) in FEV1 and FVC in mL was unrelated to the baseline value but biased towards age, height, sex and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1106 subjects with a low FEV1 (200-1621mL) the FEV1 increased 12-44.7% baseline but <200mL. Expressing BDR as percentage of predicted or z-score attenuated the bias and made the 200mL 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 in z-scores eliminates this artefact and renders the required 200mL 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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