title: Bronchodilator Response in FVC Is Larger and More Relevant Than in FEV1in Severe Airflow Obstruction.
abstract: 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.
  
  
  
  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.
  
  
  
  Change (Δ) in FEV1and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV1was significantly lower in African Americans. In 1,106 subjects with low FEV1(200-1,621 mL) the FEV1increased 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.
  
  
  
  Expressing FEV1responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1or 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.
authors.affiliation: 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.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Quanjer
authors.affiliation: Department of Pulmonary, Critical Care and Sleep Medicine, St. Louis University School of Medicine, St. Louis, MO.
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Ruppel
authors.affiliation: HUNT Research Center, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Langhammer
authors.affiliation: Department of Pulmonary, Critical Care and Sleep Medicine, St. Louis University School of Medicine, St. Louis, MO.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Krishna
authors.affiliation: Department of Pulmonary Diseases, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Mertens
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Ane
authors.initials: A
authors.lastname: Johannessen
authors.affiliation: Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Ana M B
authors.initials: AMB
authors.lastname: Menezes
authors.affiliation: Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Wehrmeister
authors.affiliation: Sleep Clinic, National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Perez-Padilla
authors.affiliation: Respiratory Physiology Laboratory, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Swanney
authors.affiliation: UBC James Hogg Research Laboratories, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Wan C
authors.initials: WC
authors.lastname: Tan
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourbeau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000402:Airway Obstruction / Q000175:diagnosis* / Q000503:physiopathology; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001993:Bronchodilator Agents; D002170:Canada; D002648:Child; D002675:Child, Preschool; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D007843:Latin America; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009520:New Zealand; D009664:Norway; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States; D014797:Vital Capacity / Q000502:physiology*; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents
keywords: airways obstruction; asthma; bronchodilator responsiveness; chronic obstructive pulmonary disease; respiratory physiology