Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD.
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].
Berton
Danilo C
DC
Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil. dcberton@gmail.com
Reis
Michel
M
Siqueira
Ana Cristina B
AC
Barroco
Adriano C
AC
Takara
Luciana S
LS
Bravo
Daniela M
DM
Andreoni
Solange
S
Neder
J Alberto
JA
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
D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide