title: Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD.
abstract: BACKGROUND
  It is currently unclear whether the additive effects of a long-acting beta(2)-agonist (LABA) and the antimuscarinic tiotropium bromide (TIO) on resting lung function are translated into lower operating lung volumes and improved exercise tolerance in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  On a double-blind and cross-over study, 33 patients (FEV(1) = 47.4 +/- 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 microg twice-daily (FOR) plus TIO 18 microg once-daily or FOR plus placebo (PLA). Inspiratory capacity (IC) was obtained on constant-speed treadmill tests to the limit of tolerance (Tlim).
  
  
  RESULTS
  FOR-TIO was superior to FOR-PLA in increasing post-treatment FEV(1) and Tlim (1.34 +/- 0.42 L vs. 1.25 +/- 0.39 L and 124 +/- 27% vs. 68 +/- 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Deltaisotime-rest = -0.27 +/- 0.40 L vs. -0.45 +/- 0.36 L, p < 0.05). In addition, end-expiratory lung volume (% total lung capacity) was further reduced with FOR-TIO (p < 0.05). Of note, patients showing greater increases in Tlim with FOR-TIO (16/26, 61.6%) had more severe airways obstruction and lower exercise capacity at baseline. Improvement in Tlim with FOR-TIO was also related to larger increases in FEV(1) (p < 0.05).
  
  
  CONCLUSIONS
  Compared to FOR monotherapy, FOR-TIO further improved effort-induced dynamic hyperinflation and exercise endurance in patients with moderate-to-severe COPD. These beneficial consequences were more likely to be found in severely-disabled patients with larger resting functional responses to the combination therapy.
  
  
  BACKGROUND
  Clinicaltrials.gov Identifier: NCT00680056 [ClinicalTrials.gov].
authors.affiliation: Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil. dcberton@gmail.com
authors.forename: Danilo C
authors.initials: DC
authors.lastname: Berton
authors.forename: Michel
authors.initials: M
authors.lastname: Reis
authors.forename: Ana Cristina B
authors.initials: AC
authors.lastname: Siqueira
authors.forename: Adriano C
authors.initials: AC
authors.lastname: Barroco
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Takara
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Bravo
authors.forename: Solange
authors.initials: S
authors.lastname: Andreoni
authors.forename: J Alberto
authors.initials: JA
authors.lastname: Neder
mesh_terms: D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000503:physiopathology; D004983:Ethanolamines / Q000008:administration & dosage*; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D000069447:Tiotropium Bromide; D014109:Total Lung Capacity / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide