title: Effects of tiotropium on hyperinflation and treadmill exercise tolerance in mild to moderate chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Bronchodilator therapy represents a potentially valuable therapeutic option to increase exercise tolerance and enhance lung function in mild to moderate chronic obstructive pulmonary disease (COPD).
  
  
  OBJECTIVE
  To determine effects of tiotropium on pulmonary hyperinflation and exercise tolerance in patients with symptomatic Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and 2 COPD who experienced inspiratory capacity decrease greater than or equal to 100 ml during incremental and constant work rate treadmill exercise.
  
  
  METHODS
  This 22-week, randomized, double-blind, two-period crossover study evaluated the efficacy of once-daily tiotropium bromide (18 μg) versus placebo in patients with GOLD 1 and 2 COPD. Primary endpoint was between-group (tiotropium vs. placebo) difference in inspiratory capacity at isotime (i.e., at the time the shortest test ended) during constant work rate treadmill exercise from baseline to the end of a 6-week treatment period. Key secondary endpoints included differences in exercise duration and exertional dyspnea. Safety was assessed by recording adverse events.
  
  
  RESULTS
  Study population comprised 48 patients with GOLD 1 COPD and 78 patients with GOLD 2 COPD. Resting inspiratory capacity significantly improved with tiotropium versus placebo in the overall (P < 0.0001), GOLD 1 (P = 0.0183), and GOLD 2 (P < 0.0001) groups. Isotime inspiratory capacity was significantly enhanced during exercise in the overall (P = 0.0087) and GOLD 2 (P = 0.0494) groups after tiotropium versus placebo. Tiotropium versus placebo significantly enhanced exercise duration in the GOLD 2 group (P = 0.0070) but not in the GOLD 1 or overall patient groups. In the overall group, increase in exercise duration seen with tiotropium was well correlated with the increase in isotime inspiratory capacity (r = 0.463, P < 0.0001).
  
  
  CONCLUSIONS
  Resting and exercise hyperinflation were ameliorated by bronchodilator therapy with tiotropium in the overall GOLD 1 plus 2 COPD group. Exercise tolerance was enhanced in GOLD 2, but not GOLD 1, COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01072396).
authors.affiliation: 1 Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.forename: François
authors.initials: F
authors.lastname: Maltais
authors.forename: Janos
authors.initials: J
authors.lastname: Porszasz
authors.forename: Frank
authors.initials: F
authors.lastname: Albers
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Deng
authors.forename: Ahmar
authors.initials: A
authors.lastname: Iqbal
authors.forename: Heather A
authors.initials: HA
authors.lastname: Paden
authors.forename: Denis E
authors.initials: DE
authors.lastname: O'Donnell
mesh_terms: D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D007320:Inspiratory Capacity / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
keywords: Global Initiative for Chronic Obstructive Lung Disease; chronic obstructive pulmonary disease; dynamic hyperinflation; dyspnea; inspiratory capacity