Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study.

Abstract

RATIONALE:

Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function. No drug has been shown conclusively to reduce this decline.

OBJECTIVES:

In a post hoc analysis of the Toward a Revolution in COPD Health (TORCH) study, we investigated the effects of combined salmeterol 50 microg plus fluticasone propionate 500 microg, either component alone or placebo, on the rate of post-bronchodilator FEV(1) decline in patients with moderate or severe COPD.

METHODS:

A randomized, double-blind, placebo-controlled study was conducted from September 2000 to November 2005 in 42 countries. Of 6,112 patients from the efficacy population, 5,343 were included in this analysis.

MEASUREMENTS AND MAIN RESULTS:

Spirometry was measured every 24 weeks for 3 years. There were 26,539 on-treatment observations. The adjusted rate of decline in FEV(1) was 55 ml/year for placebo, 42 ml/year for salmeterol, 42 ml/year for fluticasone propionate, and 39 ml/year for salmeterol plus fluticasone propionate. Salmeterol plus fluticasone propionate reduced the rate of FEV(1) decline by 16 ml/year compared with placebo (95% confidence interval [CI], 7-25; P < 0.001). The difference was smaller for fluticasone propionate and salmeterol compared with placebo (13 ml/year; 95% CI, 5-22; P = 0.003). Rates of decline were similar among the active treatment arms. FEV(1) declined faster in current smokers and patients with a lower body mass index, and varied between world regions. Patients who exacerbated more frequently had a faster FEV(1) decline.

CONCLUSIONS:

Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline of FEV(1) in patients with moderate-to-severe COPD, thus slowing disease progression. Clinical trial (GSK Study Code SCO30003) registered with www.clinicaltrials.gov (NCT00268216).

• Authors: Bartolomé R Celli, Nicola E Thomas, Julie A Anderson, Gary T Ferguson, Christine R Jenkins, Paul W Jones, Jørgen Vestbo, Katharine Knobil, Julie C Yates, Peter M A Calverley
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 178 Issue 4 Pg. 332-8 (Aug 15 2008) ISSN: 1535-4970 [Electronic] United States
• PMID: 18511702 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Bronchodilator Agents
• Salmeterol Xinafoate
• Fluticasone
• Albuterol

Topics

• Administration, Inhalation
• Aged
• Albuterol (administration & dosage, analogs & derivatives)
• Androstadienes (administration & dosage)
• Body Mass Index
• Bronchodilator Agents (administration & dosage)
• Disease Progression
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Fluticasone
• Follow-Up Studies
• Forced Expiratory Volume (drug effects)
• Humans
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (diagnosis, drug therapy, mortality)
• Risk Factors
• Salmeterol Xinafoate
• Smoking (adverse effects)
• Spirometry
• Survival Analysis