Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity in the United States, affecting nearly 10 million persons. COPD accounts for 60,000 deaths yearly and ranks as the fourth leading cause of death. If current trends continue, it may become the nation's fourth or even third leading cause of death by the year 2000.
Epidemiological studies consistently indicated that smoking was the over-whelming risk factor for accelerated decline in pulmonary function and subsequent development of COPD. Furthermore, evidence from several studies indicated that the rate of decline in pulmonary function approached a more normal rate of decline upon cessation of cigarette smoking.
Another presumed risk factor for accelerated decline in pulmonary function was the presence of hyperreactive airways, although it was not clear whether the mere presence of hyperreactive airways contributed to the accelerated decline, or whether the decline resulted from the reaction of the airways to various irritants over a long period of time. It is possible that if the hyperreactive airway was kept non-reactive by pharmacological means over a period of years, the expected abnormal decline might be lessened. This effect might be enhanced by the cessation of cigarette smoking.
Although the evidence was strong that smoking and hyperreactive airways were risk factors for COPD, it had not been demonstrated whether removal of risk factors at a stage when mild dysfunction had already occurred would effectively modify the course of COPD.
Lung Health Study I
Randomized and controlled. Cigarette smokers with evidence of airways obstruction underwent baseline testing that included spirometric responses to isoproterenol and methacholine and were then randomly assigned to one of three groups: a no intervention or usual care group; a group receiving a smoking cessation program and bronchodilator therapy; a group receiving a smoking cessation program and a placebo bronchodilator. The placebo/bronchodilator therapy was double-blind. The smoking intervention consisted of an intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with a continuing five-year maintenance program to minimize relapse. The bronchodilator consisted of ipratropium bromide prescribed three times daily, two puffs per time, from a metered-dose inhaler. All groups were followed yearly for five years. The primary endpoint was the rate of change of FEV1. Respiratory morbidity was a secondary endpoint. Recruitment began in November 1986 and was completed in January 1989. The clinical phase of the trial ended in April 1994. The study continues under contract N01-HR-46002 through September, 2004 for data analysis and dissemination of research results.
Lung Health Study III
Beginning in fiscal year 1998, all surviving participants of LHS I are invited to participate in the long-term followup. The study will determine, using an intent-to-treat analysis, whether the LHS I smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment. The study will also estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history. Studies will be conducted on the role of other factors such as gender, airways reactivity, weight gain, and co-morbidities in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. A determination will also be made as to whether the improvement in lung function and reduction in respiratory symptoms associated with smoking cessation result in improved health-related quality of life (HRQL) and less depression over an extended follow-up period. The LHS III, an investigator initiated long-term follow-up study, is not an NIH- defined clinical trial.