Lung Health Study II
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: 
      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.
    

Detailed description: 
      BACKGROUND:

      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 will 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.

      DESIGN NARRATIVE:

      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 forced expiratory volume at one second (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 dose 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, a counter that recorded but did not display 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.
    

Intervention name(s): triamcinolone; Placebo
Intervention type(s): Drug; Other
Intervention description(s): 1200 micrograms of triamcinolone in daily divided doses; Placebo
Other intervention name(s): Azmacort
Intervention MeSH terms: Triamcinolone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment