Steroid use in COPD

Summarized by Robert W. Griffith, MD
October 11, 1999 (Reviewed: January 21, 2005)

Introduction

Chronic obstructive pulmonary disease (COPD) is characterized by persistent slowing of the airflow during expiration in patients who do not have more specific conditions such as asthma, bronchiectasis or cystic fibrosis. It is sometimes diagnosed as chronic bronchitis or emphysema, or both. The degree of emphysema present and the severity of airflow obstruction do not correlate well. However, emphysema is an important cause of airflow obstruction, and probably basic to the condition, with exacerbations produced by a flare-up in the inflammatory component - bronchitis.

The principal symptom of COPD is dyspnea, which is usually accompanied by wheezing and excessive sputum production. The dyspnea is sometimes difficult to distinguish from that seen in other cardio-respiratory disorders. However, the clinical signs are familiar to most physicians, and, when accompanied by the appropriate radiological findings, are usually diagnostic.

COPD is primarily a disease of cigarette smokers, and abandoning this habit is a major preventive step. Other risk factors include passive exposure to cigarette smoke, increasing age, and genetic factors, which include atopy.

An active inflammatory process contributes to a more rapid decline in maximum airflow, and such exacerbations of severe COPD carry a very poor prognosis -- although 90% of patients may recover from hospitalization, half will die within two years. Six months after hospitalization only 25% of patients can report a "good" to "excellent" quality of life. This makes it important to find treatments that will prolong the normalcy of the airway system as long as possible, or restore it as soon as possible after an exacerbation. In this respect, the results of the clinical trial by the UK team from Liverpool, summarized here, are important. The study explored the role of oral steroids in treating exacerbations of COPD, using a prospective, randomized, double-blind, placebo-controlled design. Views on the use of steroids in COPD patients with acute deterioration in airflow vary between UK/Australia/New Zealand respiratory physicians and those in North America.

Method

Patients with COPD attending the emergency room were entered into the study if they had increasing breathlessness, and at least two of the following in the previous 24 hours: increased cough (frequency or severity), increased sputum (volume or purulence), or increased wheezing. Patients had to have had a history of at least 20 pack-years of cigarette smoking and evidence of airflow limitation (initial FEV1 less than 70% of predicted and FEV1/FVC ratio less than 75% ¹). Standard treatment for all patients comprised a nebulized beta-agonist (salbutamol), an anticholinergic (ipratropium bromide), controlled oxygen, and oral or IV antibiotics. Those patients taking inhaled corticosteroids before randomization continued to take them during the study. After acceptance into the study, patients were randomly assigned to take 30 mg prednisone orally every day for 14 days, or identical placebo tablets.

Full clinical and laboratory work-up was done, including spirometry. Symptom scores and spirometry were reported daily during hospitalization, and the time to discharge was noted. Patients were recalled at 6 weeks for repeat spirometry and to assess progress after returning home.

Out of a total of 246 patients screened for the study, 60 met the inclusion criteria. The most common reason for exclusion was previous treatment with oral steroids. Twenty-nine patients were randomly assigned to active treatment and 27 were assigned placebo. Five placebo patients withdrew, as did one corticosteroid patient. Withdraw during Week 1 of the study was significantly greater in the placebo group than in the active treatment group (p=0.034).

Thirty-four men and 16 women comprised the 50 patients who completed study. Their mean age was 67 years, their mean smoking history was 55 pack-years, and 52% were current smokers. At study entry there were no major differences in previous treatment, clinical or laboratory findings between the active and placebo treatment groups.

Results

There were no deaths during the study hospitalization, but 2 patients died before completion of the follow-up at 6 weeks - one from each treatment group. The mean FEV1 after beta-agonist-induced bronchodilation increased more rapidly and to a greater extent in the oral steroid-treated group. Expressed as a percentage of predicted FEV1 after bronchodilation, it rose from 25.7% to 32.2% in the placebo group and from 28.2% to 41.5% in the active treatment group at the time of discharge from hospital. The difference between groups was statistically significant (p<0.0001). Improvement plateaued earlier in the steroid-treated group; by Day 5 patients on steroids had increased their FEV1 after bronchodilation to 92% of that achieved at hospital discharge, compared with only 85% in the placebo group.

Decreases in symptom scores were seen in both treatment groups, with greater improvement in the corticosteroid patients. With regard to adverse events, there were no reported changes in mood, and no episodes of overt gastrointestinal bleeding, but six patients in the corticosteroid group developed transient glycosuria; three active- and two placebo-treated patients complained of heartburn.

The length of hospital stay was analyzed for all 56 patients who entered the study. The median length of stay in patients given oral steroids was seven days, which was significantly shorter than that in those receiving placebo (9 days, p=0.027).

At the 6-week follow-up, percentage predicted FEV1 after bronchodilation was 39.6% in the steroid-treated group and 33.2% for the placebo group; these values were similar to those at hospital discharge. Nine of the corticosteroid patients and 7 of the placebo group had received treatment for exacerbations of COPD in the interval between hospitalization and follow-up. There were no differences in the treatment received between patients from each group within this period.

Comment

This study showed that oral prednisone was able to accelerate the improvement in FEV1 after bronchodilation and shorten the hospital stay of patients with exacerbations of their COPD. However, review 6 weeks later showed that the initial benefit of the steroid did not extend beyond the early stages of recovery from the exacerbation. Although prednisone was given for 14 days in this study, the authors point out that shorter courses might be equally effective.

The findings join those from three other recent studies supporting the role of systemic steroids in the management of acute exacerbations. There is now, therefore, convincing evidence that the somewhat cautious American Thoracic Society Guidelines need to be modified in this direction, to follow more closely those of the British Thoracic Society. ² The long-term use of inhaled steroids and/or systemic steroids in stable COPD patients is still controversial, and further studies are required to determine the best approach for the individual patient.

Source

• Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomized controlled trial. L. Davies, RM. Angus, PMA. Calverley, Lancet, 1999, vol. 354, pp. 456--460

Footnotes
1. FEV1 = forced expiratory volume in 1 second. FVC = forced vital capacity
2. Emerging role of corticosteroids in chronic obstructive pulmonary disease. Editorial. AS. Banner, Lancet, 1999, vol. 354, pp. 440--441

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