surface and a majority of staining in the air space (alveolar cells and macrophages) with some 
reaction noted in distal airways. DNA/RNA analysis of all tissues is underway. 
III. Experimental Design 
I II. A. Patient selection 
A total of 10 patients with cystic fibrosis will be recruited from Michigan, Indiana, and Illinois 
by contacting in person, by telephone, and by letter: 1) CF Center Directors, and 2) Physicians 
specializing in pulmonary medicine or other specialties who are known to be active in providing 
care for patients with cystic fibrosis. The list of physicians will be obtained from CF Center 
Directors. 
Entry into the study will be contingent upon fulfilling the following criteria: 
Inclusion Criteria 
1 . Proven diagnosis of cystic fibrosis. Proof will consist of documentation of both: 
a) Sweat sodium or chloride > 60 mEq/l by the pilocarpine iontophoresis method or 
cystic fibrosis genotype 
b) Clinical manifestations of cystic fibrosis. 
2. Age: ^ 18 years old. 
3. Gender: Males or females. Only patients who have no chance of procreating will be 
entered into the study. In the unlikely event that participation in the study induces 
germline mutations, these alterations will not be passed onto future generations. 
Males are eligible if they have documented azospermia Over 95% of males with cystic 
fibrosis have congenital atrophy of the vas deferens and would thus fulfill this criterion. 
Females are eligible if they are documented to have had bilateral tubal ligations or a 
hysterectomy. 
4. Severity of disease: To be eligible, a patient must be in adequate clinical condition to 
safely undergo the planned procedures, i.e. bronchoscopies. An acceptable reserve will 
be defined as having a clinical condition such that the estimated 2 year survival is > 
50%. Using the study of Kerem et al. [Kerem, 1992], patients will be considered to 
have a greater than 50% chance of two year survival if they fulfill all of the following: 
a) FEVi ^ 30% predicted 
b ) PaC>2 > 55 mmHg while breathing room air 
c) PaC02 < 50 mmHg while breathing room air 
Although the disease severity criteria have been selected to avoid entering patients with 
near terminal pulmonary disease, the intent nevertheless is to study those with at least 
moderate to severe lung disease and a substantially shortened predicted survival. To 
Recombinant DNA Research, Volume 16 
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