Lung Health Studies I & II

Lung Health Study I

Principal Investigator: Richard. E Kanner, M.D.

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Subjects: Men and Women who were cigarette smokers and between ages of 35 and 60

Total Enrollment: 650 Subjects

Objectives:

To determine the effects of Special Care, compared to Usual Care, on rate of decline in pulmonary function in a group of cigarette smokers identified as having mild abnormalities in pulmonary function
To determine if participants with chronic obstructive pulmonary disease, who were assigned to inhaled corticosteroids had a lower rate of decline in lung function and lower incidence of respiratory morbidity compared to participants assigned to placebo.

To determine the long-term effects of smoking cessation and continued smoking, on cardiopulmonary morbidity, mortality, and the rate of decline in the one second forced expiratory volume in men and women with early chronic obstructive lung disease who have been followed prospectively for 12 to 15 years.

Results:

Participants in the two smoking intervention groups showed significantly smaller declines in FEV1 than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small non-cumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of study. The authors concluded that an aggressive smoking intervention program significantly reduced the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator resulted in a relatively small improvement in FEV1 that appeared to be reversed after the drug was discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1. Additionally, the study showed that lung function decline in the patients treated with the inhaled corticosteroid was statistically no different from that in the placebo group. Corticosteroid use did, however, result in 25 percent fewer respiratory symptoms and nearly 50 percent fewer outpatient visits for respiratory problems. However, after three years, bone density in the hip and back was lower in the corticosteroid group.

Lung Health Study II

Principal Investigator: Richard. E Kanner, M.D.

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Subjects: Men and Women, ages 40 to 69, with FEV1/FVC 70 percent and FEV1 that was 30 to 90 percent predicted

Total Enrollment: 105 subjects

Objective:

To determine if participants with chronic obstructive pulmonary disease, who were assigned to inhaled corticosteroids has a lower rate of decline in lung function and lower incidence of respiratory morbidity compared to participants assigned to placebo

Details:

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States and a major cause of morbidity, is a spectrum of chronic lung diseases including clinical diagnoses of chronic bronchitis, emphysema, and combinations of both. Varying degrees of bronchoreactivity occur over the entire spectrum. Asthma and COPD have many features in common. Distinction is usually dependent on clinical features and clinical course. The diagnosis of asthma did not exclude a patient from the designation of COPD for this study, although criteria for exclusion include recent (within six months) use of inhaled or oral steroid with the intent of excluding most of those who are clearly predominantly bronchospastic. The morbid anatomy of COPD is well described and includes many features of acute and chronic inflammation. There is well supported evidence in the literature that this inflammatory process may be an important pathogenetic mechanism in the development of emphysema. On this basis, the rationale for the use of corticosteroids is well justified. There are various published studies suggesting that inhaled steroids reduce bronchial lavage markers of inflammation, variously influence short-term bronchial hyperreactivity, improve lung function acutely or short-term, and slow rate of decline in lung function. Most studies have asked for improvement rather than stability. However, despite the studies which do not support these contentions and the lack of long-term information, inhaled steroids in COPD are becoming widely used in clinical practice. It was the intent of this clinical trial to assess the long-term efficacy of this treatment before such therapy became an accepted community practice, making it impractical or impossible to conduct a clinical trial.

Protocol Entry Criteria: Men and women, ages 40 to 69, with FEV1/FVC 70 percent and FEV1 that was 30 to 90 percent predicted

Design:

Subjects were recruited from the Lung Health Study I and randomized to 1200 micrograms of triamcinolone in daily divided doses or to placebo. Pulmonary function was evaluated every six months. Bronchial activity was tested at baseline, at nine months, and at three-and-a-half years using a methacholine inhalation challenge. Mean duration of follow-up was 40 months. The primary outcome measure was the rate of decline in pulmonary function as assessed by the post-bronchodilator FEV1 value. Other outcome measures included death, respiratory symptoms, quality of life, side-effects and toxicity, adherence, bronchial hyperreactivity, atopic status, and smoking status. Recruitment was initiated in November 1994 and ended November 28, 1995 to allow 3.5 to 4.5 years of follow-up through April, 1999. The investigators initiated a doser monitor (puff counter) protocol at nine of the centers among the fair to satisfactory compliers (4 to 9 puffs versus the ideal of 12 puffs per day) to test whether a memory aid would enhance inhaler compliance. Consenting participants were randomized to Group 1 who could see the display on the puff counter for 12 months or to Group 2 who had no counter for three months, and a counter with display for six months. There were a bone densitometry and adrenal suppression ancillary studies, funded by Rhone-Poulenc-Rorer, to assess the effect of inhaled corticosteroids on bone density and adrenal function.

Study Type: Interventional, Treatment, Randomized, Placebo Control

Status: Completed

Beginning in 1998, all surviving participants of LSH I were invited to participate in the long-term follow-up, LHS III

Objectives: The overall objectives of Lung Health Study III is to determine the long-term effects of smoking cessation, and continued smoking, on cardiopulmonary morbidity, mortality and the rate of decline of FEV1 in men and women with early COPD who have been followed prospectively for 12-15 years.

Status: completed