Chest
Volume 131, Issue 3, March 2007, Pages 682-689
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Original Research: COPD
A Pooled Analysis of FEV1Decline in COPD Patients Randomized to Inhaled Corticosteroids or Placebo

https://doi.org/10.1378/chest.06-1696Get rights and content

Abstract

Background:There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1.

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 FEV1decline 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 FEV1of 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 FEV1decline (−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 FEV1during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV1with 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 FEV1among those who completed these randomized clinical trials.

Section snippets

Materials and Methods

The methods of the Inhaled Steroids Effect Evaluation in COPD study13have been reported. Briefly, we pooled data from all seven RCTs in which stable patients with COPD were randomly assigned to receive ICSs or placebo for at least 12 months. These trials included the Lung Health Study (LHS)-2,14the Copenhagen City Lung Study (CCLS),15Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE),16ERS Study on COPD (EUROSCOP),17the Trial of Inhaled Steroids and Long Acting β2-Agonists,18and

Demographic and Clinical Characteristics

There were 3,911 COPD participants randomized to receive ICSs or placebo who had three of more measurements of FEV1. Of these, 29.2% were women(Table 1). Within all COPD participants analyzed in this pooled analysis, men were older, more frequently obese, and more likely to be current smokers than were women (p < 0.05) [Table 2]. Regarding COPD severity measured by FEV1, men had on average a higher FEV1in absolute terms, but a lower FEV1in terms of percent predicted than women (p < 0.05).

Treatment Effect (ICS vs Placebo in FEV1Decline Data)

In the

Discussion

The most important finding of the present study, which was conducted with primary individual-based data and was adjusted by major demographic and clinical characteristics, was that ICS therapy in COPD patients did not affect the rate of decline in FEV1among those who completed these randomized clinical trials. ICS therapy only produced significant but small improvements in FEV1over the first 6 months of therapy, an effect that was most pronounced in female ex-smokers. Beyond this time frame,

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  • Cited by (0)

    Interdisciplinary Capacity Enhancement: Bridging Excellence in Respiratory Disease and Gender Studies (ICEBERGS), which is supported by funding from Canadian Institutes of Health Research (IGH/ICRH), the Canadian Lung Association, and the Heart and Stroke Foundation of Canada (http://www.icebergs.ubc.ca).

    Dr. Soriano was an employee of GlaxoSmithKline, a manufacturer of respiratory drugs, up to 2005. Dr. Sin has received honoraria for speaking engagements from AstraZeneca and GlaxoSmithKline, and has received consultancy fees and research funding from GlaxoSmithKline. Dr. Anderson is currently an employee of GlaxoSmithKline, a manufacturer of respiratory drugs. Dr. Anthonisen and Dr. Buist are members of a respiratory advisory board for GlaxoSmithKline. Dr. Calverley has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Petersson is currently an employee of AstraZeneca, a manufacturer of respiratory drugs. Dr. Postma has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Vestbo has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Drs. Zhang, Camp, Burge, Connett, and Szafranski have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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

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