title: Acute bronchodilator responsiveness and health outcomes in COPD patients in the UPLIFT trial.
abstract: BACKGROUND
  Debate continues as to whether acute bronchodilator responsiveness (BDR) predicts long-term outcomes in COPD. Furthermore, there is no consensus on a threshold for BDR.
  
  
  METHODS
  At baseline and during the 4-year Understanding Potential Long-term Improvements in Function with Tiotropium (UPLIFT®) trial, patients had spirometry performed before and after administration of ipratropium bromide 80 mcg and albuterol 400 mcg. Patients were split according to three BDR thresholds: ≥ 12% + ≥ 200 mL above baseline (criterion A), ≥ 15% above baseline (criterion B); and ≥ 10% absolute increase in percent predicted FEV1 values (criterion C). Several outcomes (pre-dose spirometry, exacerbations, St. George's Respiratory Questionnaire [SGRQ] total score) were assessed according to presence or absence of BDR in the treatment groups.
  
  
  RESULTS
  5783 of 5993 randomized patients had evaluable pre- and post-bronchodilator spirometry at baseline. Mean age (SD) was 64 (8) years, with 75% men, mean post-bronchodilator FEV1 1.33 ± 0.44 L (47.6 ± 12.7% predicted) and 30% current smokers. At baseline, 52%, 66%, and 39% of patients had acute BDR using criterion A, B, and C, respectively. The presence of BDR was variable at follow-up visits. Statistically significant improvements in spirometry and health outcomes occurred with tiotropium regardless of the baseline BDR or criterion used.
  
  
  CONCLUSIONS
  A large proportion of COPD patients demonstrate significant acute BDR. BDR in these patients is variable over time and differs according to the criterion used. BDR status at baseline does not predict long-term response to tiotropium. Assessment of acute BDR should not be used as a decision-making tool when prescribing tiotropium to patients with COPD.
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA. hanania@bcm.tmc.edu
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.forename: Amir
authors.initials: A
authors.lastname: Sharafkhaneh
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.forename: Ted
authors.initials: T
authors.lastname: Lystig
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
authors.forename: Donald
authors.initials: D
authors.lastname: Tashkin
mesh_terms: D000368:Aged; D000420:Albuterol / Q000008:administration & dosage*; D000068600:Albuterol, Ipratropium Drug Combination; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D000068600:Albuterol, Ipratropium Drug Combination; D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D009241:Ipratropium; D000420:Albuterol; D000069447:Tiotropium Bromide