Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Long-acting β2-agonists and inhaled corticosteroids reduce exacerbations in chronic obstructive pulmonary disease


ACP J Club. 2004 May-Jun;140:58. doi:10.7326/ACPJC-2004-140-3-058

Clinical Impact Ratings

GIM/FP/GP: 5 stars

Hospitalists: 5 stars

Pulmonology: 6 stars

GIM/FP/GP: 5 stars

Hospitalists: 5 stars

Pulmonology: 6 stars

Source Citation

Sin DD, McAlister FA, Man SF, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease: scientific review. JAMA. 2003;290:2301-12. [PubMed ID: 14600189]



What are the effects of commonly used treatments for chronic obstructive pulmonary disease (COPD) on patient outcomes?

Data sources

Studies were identified by searching MEDLINE (1980 to 1 May 2002) and the Cochrane Database of Systematic Reviews, reviewing bibliographies of published articles, and contacting experts.

Study selection and assessment

Studies were selected if they were English-language, randomized, controlled trials (RCTs) with ≥ 3 months of follow-up in adults with COPD and assessed long-acting (LA) β2-agonists (β2As); LA inhaled anticholinergics (tiotropium); combined short-acting (SA) β2As and SA anticholinergics; inhaled corticosteroids; combined inhaled corticosteroids and LAβ2As; pulmonary rehabilitation (with ≥ 6-wk follow-up); long-term nocturnal noninvasive mechanical ventilation; domiciliary oxygen therapy; or disease management (any combination of patient education, enhanced follow-up, and self-management sessions). Analysis was restricted to RCTs with blinded {only drug interventions where placebo was possible}* ascertainment of outcomes, complete or near-complete {> 90%}* follow-up data, and well-balanced baseline characteristics in treatment and control groups.


COPD exacerbations and mortality.

Main results

The results are summarized in the Table.


In patients with chronic obstructive pulmonary disease, long-acting (LA) β2-agonists (β2As) and inhaled corticosteroids, with and without LAβ2As, reduce exacerbations, but not mortality.

*Information provided by author.

Sources of funding: Canadian Institutes of Health Research and Alberta Heritage Foundation for Medical Research.

For correspondence: Dr. D.D. Sin, James Hogg iCAPTURE Center for Pulmonary and Cardiovascular Research, Vancouver, British Columbia, Canada. E-mail

Table. Summary of efficacy data for interventions for chronic obstructive pulmonary disease†

Comparisons RRR/RRI (95% CI)
Exacerbation Mortality
LAβ2A vs placebo RRR 21% (10 to 31) RRR 24% (−48 to 61)‡
Tiotropium vs placebo RRR 26% (11 to 38) NA
Tiotropium vs LAβ2A RRR 7% (−8 to 20)‡ NA
Tiotropium vs ipratropium RRR 22% (5 to 37) NA
SAβ2A + anticholinergic vs SAβ2A RRR 32% (9 to 49) RRI 18% (−66 to 308)‡
SAβ2A + anticholinergic vs ipratropium RRI 4% (−35 to 68)‡ RRI 256% (−41 to 2053)‡
Inhaled corticosteroids vs placebo RRR 24% (20 to 28) RRR 22% (−5 to 42)‡
Inhaled corticosteroids + LAβ2A vs placebo RRR 30% (22 to 38) RRR 48% (−34 to 80)‡
Inhaled corticosteroids + LAβ2A vs LAβ2A RRR 20% (10 to 29) NA
Inhaled corticosteroids + LAβ2A vs inhaled corticosteroids RRR 10% (−2 to 20)‡ NA
Pulmonary rehabilitation vs control (usual care, placebo, or education) NA RRR 10% (−24 to 35)‡
Supplemental oxygen vs usual care (patients with resting PaO2 < 60 mm Hg sea level) NA RRR 39% (18 to 54)
Supplemental oxygen vs usual care (patients with resting PaO2≥ 60 mm Hg sea level) NA RRI 16% (−15 to 58)‡
Disease management vs usual care NA RRR 37% (−4 to 62)‡

†SAβ2A = short-acting β2-agonist; LAβ2A = long-acting β2-agonist; NA = not assessed. Other abbreviations defined in Glossary; RRR, RRI, and CI calculated from data in article.
‡Not significant.


The review by Sin and colleagues covers a wide range of treatments for COPD. Breadth is achieved at the expense of detail, but the authors provide a useful overview. A major criticism of respiratory medicine has been the absence of large, long-term studies, unlike the field of cardiology.

In the controversial area of inhaled corticosteroid therapy for COPD, an attempt was made to rectify this paucity with several reasonably large studies that lasted ≥ 3 years. These studies provided some important answers, but still left unanswered questions. 2 meta-analyses (1, 2) published in 2003 found a slower decline in FEV1 with inhaled corticosteroids compared with placebo, but the difference was < 10 mL/y, and the authors came to opposite conclusions on the importance of the finding. These meta-analyses included more studies than the review by Sin and colleagues, but the lack of available details makes comparisons difficult.

Recent studies of COPD have concentrated on clinically relevant outcomes, such as exacerbations, quality of life, and admissions, although definitions of exacerbations vary. LAβ2As, tiotropium, and inhaled corticosteroids all reduce exacerbations by 20% to 30% relative to placebo. The added benefits of combination therapies on various endpoints are difficult to extricate and need further study. Corticosteroids seem to add to the effect of LAβ2As. The results provide a good case for LAβ2As or tiotropium in patients with more than mild COPD and inhaled corticosteroids in patients with more severe disease.

Good evidence exists on the benefits of rehabilitation in the short to medium term, although there is uncertainty on how to maintain the initial benefit, and many countries have difficulty providing adequate respiratory rehabilitation programs. Smoking cessation and long-term oxygen therapy are the only treatments that significantly improve the natural history and life expectancy of persons with COPD.

P. John Rees, MD
Guy’s, King’s and St Thomas’ School of Medicine
London, England, UK


1. Highland KB, Strange C, Heffner JE. Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis. Ann Intern Med. 2003;138:969-73. [PubMed ID: 12809453]

2. Sutherland ER, Allmers H, Ayas NT, Venn AJ, Martin RJ. Inhaled corticosteroids reduce the progression of airflow limitation in chronic obstructive pulmonary disease: a meta-analysis. Thorax. 2003;58:937-41. [PubMed ID: 14586043]