The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1. Secondary outcomes are the development of respiratory and nonrespiratory morbidity and mortality. After screening 73,694 cigarette smokers, aged 35 to 60 years, 5,887 participants were randomized into three equal groups: usual care, smoking intervention with daily use of a metered-dose inhaler with ipratropium bromide, and smoking intervention with inhalation of placebo. Eligible participants had a ratio of FEV1 to forced vital capacity (FVC) of 70 percent or less, were free of known life-limiting conditions, expressed willingness to enter the intervention program if so randomized, and gave written informed consent prior to entry into the trial. Spirometry, methacholine challenge, and questionnaires were strictly standardized within and across centers. The purpose of this report is to describe the characteristics of randomized participants at the time of entry into the study. For both sexes, three measures of lung function-average cross-sectional FEV1/FVC ratio, FEV1, and FEV1 percentage of predicted normal-showed slight downward trends for each successively older 5-year age cohort. The increase in FEV1 after isoproterenol was 15 percent or more in only 2.4 percent of men and 2.8 percent of women. A positive response to methacholine (defined as a fall in FEV1 of >20 percent from baseline at concentrations up to 25 mg/ml) occurred in 63 percent of men and 87 percent of women. The cross-sectional prevalences of cough, phlegm, wheeze on most days or nights, and shortness of breath were 49 percent, 43 percent, 32 percent, and 43 percent, respectively. Respiratory symptoms were reported by a higher proportion of participants in the younger age groups than in the older age groups. Participants who reported cough, phlegm, and/or wheeze averaged lower FEV1 percent predicted and higher probability of positive response to methacholine than participants who did not. Shortness of breath appeared to be significantly associated with lower lung function and higher reactivity in men but not in women. The initial goal of identifying a population of men and women at elevated risk for development of COPD appears to have been attained.
Bibliographical noteFunding Information:
The Salt Lake City Center of the University of Utah has been assisted by the Clinical Research Center, Public Health Research grant No. M01-RR00064 from the National Center for Research Resources.