Lung Health Study (LHS) I and III
Condition: Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 3

Summary: 
      In the Lung Health Study I, 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.

      In the Lung Health Study III, 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 (FEV1) in men and women with early chronic obstructive
      lung disease who have been followed prospectively for 12 to 15 years.
    

Detailed description: 
      BACKGROUND:

      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.

      DESIGN NARRATIVE:

      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.
    

Intervention name(s): smoking cessation; ipratropium
Intervention type(s): Behavioral; Drug
Intervention MeSH terms: Ipratropium
Allocation: Randomized
Masking: Double
Primary purpose: Prevention