title: The effect of bronchodilators on forced vital capacity measurement in patients with idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Forced vital capacity (FVC) is a key measure of disease severity in patients with idiopathic pulmonary fibrosis (IPF) and is an important clinical trial endpoint. We hypothesize that reversible airflow limitation co-exists in a subgroup of patients with IPF, and that bronchodilator use will improve the performance characteristics of FVC.
  
  
  METHODS
  IPF patients with pre and post-bronchodilator spirometry testing performed were identified from two tertiary referral cohorts. The difference between pre and post-bronchodilator FVC (intra-test difference) was calculated. The test characteristics of pre and post-bronchodilator FVC change over time (inter-test difference) were assessed in patients with sequential spirometry, and were used to generate sample size estimates for hypothetical clinical trials using change in FVC as the primary endpoint.
  
  
  RESULTS
  There were 551 patients, contributing 967 unique spirometry tests. The mean intra-test increase in FVC with bronchodilator use was 0.04 L (2.71 vs. 2.75 L, p < 0.001). Reversible airflow limitation (increase in FEV1 or FVC of ≥12% and ≥200 mL) occurred in 9.1% of patients. The inter-test difference in change in FVC over time were equivalent for pre and post-bronchodilator (p = 0.65), leading to similar sample size estimates in a hypothetical clinical trial using change in FVC as the primary endpoint.
  
  
  CONCLUSIONS
  Approximately one in ten patients with IPF has physiological evidence of reversible airflow limitation, and bronchodilator use in these patients may improve the assessment of disease progression based on FVC change over time. Bronchodilator use does not appear to meaningfully impact the precision of FVC as an endpoint in clinical trials.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States. Electronic address: Deborah.Assayag@mail.mcgill.ca.
authors.forename: Deborah
authors.initials: D
authors.lastname: Assayag
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ryerson
authors.affiliation: School of Medicine, University of Modena, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cocconcelli
authors.affiliation: School of Medicine, University of Modena, Modena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tonelli
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Radiology, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Elicker
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Jones
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Koth
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Joyce S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Brett
authors.initials: B
authors.lastname: Ley
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Shum
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wolters
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Harold R
authors.initials: HR
authors.lastname: Collard
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D013147:Spirometry; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology*
chemical_list: D001993:Bronchodilator Agents
keywords: Bronchodilators; Clinical trials; Idiopathic pulmonary fibrosis; Lung function; Spirometry