Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function. No drug has been shown conclusively to reduce this decline.


OBJECTIVE
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.


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).
Tufts University School of Medicine, Pulmonary and Critical Care Division, Caritas-St Elizabeth's Medical Center, Boston, MA 02135-2997, USA. bcelli@copdnet.org
Bartolomé R
BR
Celli
Nicola E
NE
Thomas
Julie A
JA
Anderson
Gary T
GT
Ferguson
Christine R
CR
Jenkins
Paul W
PW
Jones
Jørgen
J
Vestbo
Katharine
K
Knobil
Julie C
JC
Yates
Peter M A
PM
Calverley
D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D015992:Body Mass Index; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D016019:Survival Analysis
D000730:Androstadienes; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol