|Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review
|Singh J M, Palda V A, Stanbrook M B, Chapman K R
To determine whether corticosteroids are of demonstrable benefit to patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). The adverse effects of systemic steroid therapy were reviewed separately.
For the evaluation of effectiveness, MEDLINE was searched from 1966 to February 2002) using the MeSH terms 'steroids', 'obstructive lung disease', 'respiratory insufficiency', and the textword 'exacerbation'. The search was limited to clinical trials conducted in humans and published in the English language; publications that included the subject heading 'asthma' were excluded. The Cochrane Library was searched using the headings 'obstructive lung disease', 'respiratory insufficiency' and 'exacerbation'. The bibliographies of the retrieved articles were examined for further references.
For the evaluation of adverse effects, a limited search was undertaken to identify clinical trials and review articles that were indexed in MEDLINE, using the keywords 'steroids-adverse effects' and 'obstructive lung disease'. The search was limited to English-language papers.
Study designs of evaluations included in the review
For the evaluation of effectiveness, only published placebo-controlled, randomised controlled trials (RCTs) were considered for inclusion. Publications in abstract form were also included. Any study design was considered for the evaluation of adverse effects.
Specific interventions included in the review
Any systemic corticosteroids were considered for inclusion. The specific drugs examined by the included studies were intravenous methylprednisolone (40, 100 or 125 mg, or 0.05 mg/kg) with or without oral prednisone, intravenous hydrocortisone (100 mg) followed by oral prednisone, oral prednisone (60, 40 and 20 mg used together), and oral prednisolone (30 mg, or either 2.5 or 0.3 mg/kg).
Participants included in the review
For the evaluation of effectiveness, only studies that included patients with COPD (diagnosed using any criteria) exacerbations were considered for inclusion. For the evaluation of adverse effects, populations other than those with COPD who were not immunosuppressed were also considered. The populations in the included studies were in-patients, out-patients or emergency department patients.
Outcomes assessed in the review
No a priori inclusion criteria referring to the outcome measures were reported. The primary outcome measures used by the included effectiveness studies were treatment failure (death, intubation, therapeutic intensification), forced expiratory volume in 1 second (FEV1), symptom score, hospital stay and clinical failure rate.
How were decisions on the relevance of primary studies made?
The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.
Assessment of study quality
The quality of the studies was assessed using generic criteria, which were adapted to include some COPD-specific factors. The criteria included: an adequate randomisation resulting in the assembly of comparable groups; maintenance of comparable groups by attention to attrition, crossover, compliance, and contamination; clinically important loss to follow-up; a clear definition of the interventions; important outcomes were assessed (in a blinded fashion); the measurement methods used were equal, reliable, and valid; and the analysis used was intention to treat. The type of diagnostic criterion used was also incorporated into the quality assessment. The studies were rated as 'good', 'fair' or 'poor' according to the methodology of the U.S. Preventive Services Task Force (see Other Publications of Related Interest).
There was no specific quality assessment of the studies evaluating adverse effects. The study quality was assessed and independently verified by two reviewers.
The data were extracted and independently verified by two reviewers. The type of data extracted was information relating to study quality, and factors specific to COPD that might have an important effect on the results. The following data were presented in summary tables: reference details, the number of patients, quality assessment rating, intervention, primary outcome measure, results, comments, and quality assessment (confounding factors, power, intention-to-treat analysis, and adequate follow-up).
For the evaluation of adverse effects, any numerical information related to steroid use was extracted.
Methods of synthesis
How were the studies combined?
The studies were pooled in a narrative in which the conclusions were based on the strength of the evidence; good-quality studies were considered to provide stronger evidence than fair, and fair-quality studies to provide stronger evidence than poor-quality studies.
How were differences between studies investigated?
Differences between the studies were considered in a narrative summary.
Results of the review
Eight RCTs (678 patients) were included for the evaluation of effectiveness. It was unclear how many studies were reviewed for the assessment of adverse effects.
Two studies were of good quality, three were deemed to be fair, and four were of poor quality.
Five studies (2 good, 2 fair and 1 poor quality) found that a significant improvement in FEV1 (greater than 20%) was associated with steroid administration. One published study and two study abstracts did not find a significant improvement in spirometric measures with corticosteroid administration.
Health care measures.
Two studies (good quality) found an improvement in clinically relevant outcomes, i.e. a reduction in treatment failure and hospital stay.
Regimen of systemic corticosteroid administration.
The benefit from corticosteroid administration was evident within the first 5 days of therapy (good-quality evidence), and it lasted for at least the 5 days of therapy (fair-quality evidence). No published studies comparing parental corticosteroids with oral steroids in the treatment of COPD exacerbations were found.
There was evidence from good-quality RCTs that steroid use results in an increase in the incidence of hyperglycaemia and potentially life-threatening infections (among patients receiving very high doses for 8 weeks). There was evidence to suggest that the administration of systemic corticosteroids to patients with COPD exacerbations has deleterious effects on bone mineral density, and this effect is likely to be dose-dependent.
Short courses of systemic corticosteroids in acute exacerbations of COPD have been shown to improve spirometric outcomes (good-quality evidence) and clinical outcomes (good-quality evidence).
This review addressed an appropriate question using fairly broad inclusion and exclusion criteria. The literature search was not very comprehensive as it only included two databases and only English language papers were considered for inclusion. For the evaluation of adverse effects, any study design was considered for inclusion, yet the literature search was limited to clinical trials and review articles indexed in MEDLINE. It was not stated how the studies were assessed for relevancy. Two reviewers independently extracted the data and assessed the validity of the included studies. Relevant data for the included studies of effectiveness were presented in tabular format, but the actual summary results (i.e. a measure of the size of the effect) were not presented, only p-values or whether the results were statistically significant. Assessing the overall effect of the intervention using a 'vote counting' system without taking into account the actual effect size, confidence interval and direction for individual studies, only provides a very crude overview that may be misleading and loses information. Information relating to the studies reviewed for adverse effects was unclear.
Implications of the review for practice and research
Practice: The authors did not state any implications for practice.
Research: The authors state that further research is needed to characterise the optimal dose, route and duration of treatment, and the long-term risks of therapy.
Singh J M, Palda V A, Stanbrook M B, Chapman K R. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review. Archives of Internal Medicine 2002; 162(22): 2527-2536
Other publications of related interest
U.S. Preventive Services Task Force. Preventative Services News. Rockville (MD): Agency for Healthcare Research and Quality; 2000.
Subject indexing assigned by NLM
Acute Disease; Administration, Oral; Adrenal Cortex Hormones /administration & Aged; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydrocortisone /administration & Male; Methylprednisolone /administration & Middle Aged; Prednisolone /administration & Prednisone /administration & Prognosis; Pulmonary Disease, Chronic Obstructive /diagnosis /drug therapy /mortality; Randomized Controlled Trials as Topic; Recurrence; Severity of Illness Index; Spirometry; Survival Rate; Treatment Outcome; dosage; dosage; dosage; dosage; dosage
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.