Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD.
OBJECTIVE
To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD.


METHODS
This was a randomized, double-blind, parallel-group study.


METHODS
Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal.


METHODS
Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50.


RESULTS
A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50.


CONCLUSIONS
We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.
O'Donnell
Denis E
DE
Queen's University, Kingston, ON, Canada. odonnell@post.queensu.ca
Sciurba
Frank
F
Celli
Bartolome
B
Mahler
Donald A
DA
Webb
Katherine A
KA
Kalberg
Chris J
CJ
Knobil
Katharine
K
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000730:Androstadienes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004417:Dyspnea / Q000503:physiopathology; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D010807:Physical Endurance / Q000187:drug effects* / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D000068299:Salmeterol Xinafoate; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000068299:Salmeterol Xinafoate; D000420:Albuterol