Chest
Volume 130, Issue 3, September 2006, Pages 647-656
Journal home page for Chest

Original Research: COPD
Effect of Fluticasone Propionate/Salmeterol on Lung Hyperinflation and Exercise Endurance in COPD

https://doi.org/10.1378/chest.130.3.647Get rights and content

Study objective

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

Design

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

Patients

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

Interventions

Patients were randomized to FSC 250/50; salmeterol, 50 μg; 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 ≤ 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.

Conclusion

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.

Section snippets

Subjects

Subjects included clinically stable patients ≥ 40 years old with a diagnosis of COPD21; a cigarette smoking history ≥ 10 pack-years; a prealbuterol FEV1 < 70% of predicted; an FEV1/FVC ratio ≤ 0.70; a functional residual capacity (FRC) ≥ 120% of predicted normal; a baseline dyspnea index (BDI) score < 7; and the ability to complete a work rate of 20 W during an incremental cycle cardiopulmonary exercise test (CPET) at the screening visit. Exclusion criteria included a current diagnosis of

Subject Characteristics

A total of 185 patients were randomized to treatment with FSC 250/50 (n = 62), salmeterol (n = 59), or placebo (n = 64), and 176 patients completed the study. Five of the nine patients who withdrew were in the placebo group, with one patient and three patients in the salmeterol and FSC 250/50 groups, respectively. Demographic, smoking history, dyspnea, lung function, and exercise values at screening are shown in Table 1. Patients had moderate-to-severe COPD, with mean FEV1 values of 39.5 to

DISCUSSION

The results of this study demonstrate that treatment with FSC 250/50 twice daily for 8 weeks resulted in reduced lung hyperinflation at rest, as shown by significant reductions in postdose evaluations of FRC and RV; a reduction in hyperinflation during exercise, as shown by a significant increase in resting and exercise IC, and in Vt and V˙e; and a significant improvement in exercise endurance time when compared with placebo.

The magnitude of decrease in static lung volumes observed with

ACKNOWLEDGEMENT

We wish to acknowledge the contributions of the following investigators: P. Amelung, MD, Baltimore, MD; D. Berry, MD, Bellingham, WA; C. Cooper, MD, Los Angeles, CA; D. Doherty, MD, Lexington, KY; J. Donohue, MD, Chapel Hill, NC; G. Ferguson, MD, Livonia, MI; C. Fogarty, MD, Spartanburg, SC; N. Hanania, Houston, TX; M. Kaye, MD, Minneapolis, MN; B. Make, MD, Denver, CO; E. Robinette Jr, MD, Abingdon, VA; W. Stringer, MD, Torrence, CA; R. ZuWallack, MD, Hartford, CT; J Leech, MD, Ottawa, ON,

REFERENCES (41)

  • O Diaz et al.

    Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest

    Eur Respir J

    (2000)
  • MJ Belman et al.

    Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (1996)
  • FJ Martinez et al.

    Lung volume reduction improves dyspnea, dynamic hyperinflation, and respiratory muscle function

    Am J Respir Crit Care Med

    (1997)
  • DE O'Donnell et al.

    Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms

    Am J Respir Crit Care Med

    (1997)
  • S Rennard et al.

    Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey

    Eur Respir J

    (2002)
  • RA Pauwels et al.

    Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary

    Am J Respir Crit Care Med

    (2001)
  • ML Ayers et al.

    Effectiveness of salmeterol versus ipratropium bromide on exertional dyspnoea in COPD

    Eur Respir J

    (2001)
  • WDC Man et al.

    Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD

    Thorax

    (2004)
  • DE O'Donnell et al.

    Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (1999)
  • DE O'Donnell et al.

    Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD

    Eur Respir J

    (2004)
  • Cited by (198)

    • The Pathophysiology of Dyspnea and Exercise Intolerance in Chronic Obstructive Pulmonary Disease

      2019, Clinics in Chest Medicine
      Citation Excerpt :

      Several intervention studies have shown that therapies that reduce EELV (resting and dynamic) or counterbalance its negative effects on the inspiratory muscles are associated with reduced dyspnea and improved exercise tolerance. These include bronchodilators of every class,60,61,154–156 bullectomy,157,158 surgical or endoscopic lung volume reduction, and continuous positive airway pressure or inspiratory pressure assist.141,142 Bronchodilators, inspiratory muscle training, and combined interventions are reviewed here.

    View all citing articles on Scopus

    These data have been presented in part at the 2005 Annual meeting of the American College of Chest Physicians in Montreal, QC, Canada; October 29 to November 3, 2005.

    Drs. O'Donnell, Sciurba, Celli, and Mahler have served as consultants and Speaker's Bureau members for GlaxoSmithKline and have received research grants from GlaxoSmithKline. Dr. Kalberg and Dr. Knobil are employees of GlaxoSmithKline.

    This study was funded by GlaxoSmithKline.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    View full text