Stable chronic obstructive pulmonary disease.(Statistical Data Included)

This review is taken from Issue 1 of Clinical Evidence, a new information resource for clinicians published by BMJ Publishing Group. The compendium will be updated and expanded every six months. Future issues of Clinical Evidence will cover respiratory stimulants, DNAse, [[Alpha].sub.1] antitrypsin augmentation, and vaccination against influenza and streptococcus.

Background

Definition: Chronic obstructive pulmonary disease (COPD) is characterised by airflow obstruction caused by chronic bronchitis, emphysema, or both. Emphysema is defined as abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. Chronic bronchitis is defined as chronic cough, mucus production, or both, for at least three months for at least two successive years where other causes of chronic cough have been excluded.[1]

Incidence/prevalence: Chronic obstructive pulmonary disease characteristically affects middle aged and elderly people. It is one of the leading causes of morbidity and mortality worldwide. In the United States it affects about 14 million people and is the fourth leading cause of death. Both morbidity and mortality are rising. Estimated prevalence in the United States has risen by 41% since 1982, and age adjusted death rates rose by 71% between 1966 and 1985. This contrasts with the decline over the same period in age adjusted mortality from all causes, which fell by 22%, and from cardiovascular diseases, which fell by 45%.[1]

Aetiology: Chronic obstructive pulmonary disease is largely preventable. The main cause is exposure to cigarette smoke. The disease is rare in lifetime non-smokers (reported in 5% in one large study[2]), in whom exposure to environmental tobacco smoke will explain at least some of the airways obstruction.[3] Other proposed aetiological factors include airway hyperresponsiveness,[4, 5] ambient air pollution,[6] and allergy.[7]

Prognosis: The airflow obstruction in chronic obstructive pulmonary disease is usually progressive in people who continue to smoke. This results in early disability and shortened survival. Stopping smoking reverts decline in lung function to values of non-smokers.[8] Many patients will use medication chronically for the rest of their lives, with the need for increased doses and additional drugs during exacerbations.

Aims: To alleviate symptoms, to prevent exacerbations, to preserve optimal lung function, and to improve activities of daily living and quality of life.[9]

Outcomes: Survival; short and long term changes in lung function (including changes in forced expiratory volume in one second ([FEV.sub.1])); exercise tolerance; frequency, severity, and duration of exacerbations; symptom scores for dyspnoea; and quality of life. There are now two well validated quality of life questionnaires for chronic obstructive pulmonary disease.[10 11]

Methods

This review deals only with maintenance treatment in stable chronic obstructive pulmonary disease, and not with treatment of acute exacerbations. A Clinical Evidence search was performed in July 1998. Where we found no systematic reviews, we searched for RCTs. Because we were interested in maintenance treatment, we did not include single dose or single day cumulative dose response trials.

Questions: What are the short and long term effects of maintenance treatment in stable chronic obstructive pulmonary diseases?

Option: Inhaled anticholinergic drugs

Trials using a range of methods found that anticholinergic drugs achieve short term bronchodilation and relieve symptoms in people with chronic obstructive pulmonary disease. One large randomised controlled trial (RCT) found no evidence that maintenance treatment with inhaled anticholinergic drugs improved long term prognosis.

Benefits

We found no systematic review of the benefits of treatment with inhaled anticholinergic drugs.

Short term treatment: We found no major RCTs comparing ipratropium bromide versus placebo in chronic obstructive pulmonary disease. The many small, placebo controlled trials used different end points. Most included at least some measure of airways obstruction and found a significant effect of ipratropium bromide.[12-15]

Maintenance treatment: We found one RCT (lung health study) in 5887 men and women smokers (aged 35-60 years) with spirometric signs of early chronic obstructive pulmonary disease ([FEV.sub.1] 75% predicted).[8] Three interventions were compared over a five year period: usual care; an intensive 12 session smoking cessation programme combining behaviour modification and use of nicotine gum; and the same smoking intervention programme plus ipratropium bromide three times daily. The addition of ipratropium bromide had no significant effect on decline in [FEV.sub.1]. Decline in [FEV.sub.1] was significantly slower in participants who stopped smoking than in the group that received usual care.

Harms

In the …