A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo.
BACKGROUND
There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1).


METHODS
The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking.


RESULTS
There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers.


CONCLUSIONS
We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.
Soriano
Joan B
JB
Program of Epidemiology and Clinical Research, Fundació Caubet-CIMERA Illes Balears, International Centre for Advanced Respiratory Medicine, Bunyola, Mallorca, Illes Balears, Spain. Electronic address: jbsoriano@caubet-cimera.es.
Sin
Don D
DD
James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, BC, Canada.
Zhang
Xuekui
X
James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, BC, Canada.
Camp
Pat G
PG
James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, BC, Canada.
Anderson
Julie A
JA
Department of Statistics, GlaxoSmihKline R&D, Greenford, Middlesex, UK.
Anthonisen
Nick R
NR
Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Buist
A Sonia
AS
Department of Medicine, Oregon Health and Science University, Portland, OR.
Burge
P Sherwood
PS
Department of Respiratory Medicine, Heartlands Hospital NHS Trust, Birmingham, UK.
Calverley
Peter M
PM
Department of Medicine, University Hospital Aintree, Liverpool, UK.
Connett
John E
JE
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN.
Petersson
Stefan
S
Department of Statistics, AstraZeneca R&D, Lund, Sweden.
Postma
Dirkje S
DS
Department of Pulmonology, University of Groningen, the Netherlands.
Szafranski
Wojciech
W
Department of Lung Diseases, Voivodeship Specialist Hospital, Radom, Poland.
Vestbo
Jørgen
J
North West Lung Centre, South Manchester University Hospital NHS Trust, Wythenshawe Hospital, Manchester, UK.
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D016540:Smoking Cessation; D015996:Survival Rate
D000305:Adrenal Cortex Hormones