The treatment of the pulmonary disease in cystic fibrosis has a multifaceted approach. The use 
of antibiotics is a major component of treatment regimens. Although prolonged eradication of 
bacteria from the sputum is rarely accomplished, frequent and sometimes prolonged antibiotic 
therapy helps lower the numbers of bacteria. The development of infection with antibiotic- 
resistant organisms reduces the effectiveness during later stages of the disease. The antibiotics 
are administered orally, intravenously, and/or by aerosol. 
Bronchodilator therapy has been shown to be effective in subgroups of patients with cystic 
fibrosis. Studies of the efficacy of p-agonists [Weintraub and Eschenbacher, 1989], 
anticholinergic agents [Weintraub and Eschenbacher, 1989], and theophylline [Pan et al. t 
1989] demonstrate improved pulmonary function in some patients with the disease. 
Physical maneuvers to promote secretion clearance such as postural drainage with percussion 
have long been a mainstay in the treatment of cystic fibrosis. In some patients, secretion 
clearance can be induced by physical exercise. 
When the disease progresses to the point of significant hypoxemia, supplemental inspired 
oxygen is used in an attempt to delay the onset of cor pulmonale and right heart failure. In the 
last stages of the disease, intratracheal intubation and mechanical ventilation is available. 
However, the prognosis for successful weaning and extubation is very low and many patients 
chose to forego the use of mechanical ventilation [Davis, 1978]. 
Unfortunately, the therapy outlined above is not fully effective. Eventually, the patient's 
respiratory condition progresses leading to death. New therapies are under development to 
improve the life span of patients with cystic fibrosis. These include aerosolized amiloride to 
block excessive sodium reabsorption in the airway and promote hydration of secretions 
[Knowles et al. t 1990]. Topical application of triphosphate nucleotides has been shown to 
activate chloride secretion from cystic fibrosis epithelium [Knowles et al., 1991]. Aerosolized 
antiproteases such as secretory leukocyte protease inhibitor [McElvaney, 1991] and a-1- 
protease inhibitor [Vogelmeier et al., 1991] are being evaluated to see if their use will reduce 
tissue damage caused by protease that is released by bacteria and inflammatory cells. Agents 
such as DNase I are being studied to see if they can promote secretion clearance by reducing the 
viscosity of the mucus [Hubbard et al., 1992]. Anti-inflammatory agents are being evaluated to 
see if suppression of the assumed excessive immune response will reduce the rate of lung 
injury [Auerbach et al., 1985; Rosenstein et al., 1991]. Although one or more of these 
approaches might be efficacious, none of the preliminary studies has shown total reversal of the 
processes that are known to lead eventually to permanent, severe lung injury. 
Lung transplantation has been performed in small numbers of patients with cystic fibrosis 
[Aitken et al., 1992; deLeval et al., 1991; Frist et al., 1991; Shennib et al., 1992]. This 
treatment has the potential for correcting the underlying defect in that the transplanted lung 
appears not to manifest the abnormal electrophysiology characteristic of cystic fibrosis. 
However, severe limitations of donor organ availability have impeded the performance of large 
number of transplants. Although mortality rate is improving following transplantation, the two 
year survival rate still approaches only 50%. 
In summary, survival data indicate that the prognosis for patients alive today with cystic 
fibrosis is much better than 20 years ago. However, the prospect for a normal life span with 
currently available therapies is not good. A rational approach is to correct the cellular defect at 
the site where the most serious pathological process occurs, i.e. within the airways. Successful 
transfection and expression of a normal CFTR gene into airway epithelial cells of patients with 
cystic fibrosis would correct the underlying abnormality. 
The isolation of the gene responsible for CF in 1989 ushered in a new era of research for this 
deadly disease [Rummens et al., 1989; Riordan et al., 1989; Kerem et al., 1989]. Elegant in 
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