the airways become damaged, culminating in bronchiectasis. Although the dis- 
ease is primarily based in the airways, the mucus obstruction, inflammation 
and infection commonly extends to the peribronchiolar alveolar structures, 
causing fibrosis and alveolar destruction. In the late stages of the disease, 
the lung is markedly deranged with dilated and sometimes stenosed airways, 
emphysema, and peribronchiolar and interstitial alveolar inflammation and 
fibrosis (6) . 
Infection plays a prominent role in the pathogenesis of the derangements of 
the lung in CF. The infection is primarily endobronchial and is chronic, with 
acute exacerbations. The most common organisms involved are Hemophilus influ- 
enzae . Staphylococcus aureus . and Pseudomonas aeruginosa . The fact that the 
infection is confined to the lung argues strongly that the host defense prob- 
lems permitting the infection are local rather than systemic (5,8). The patho- 
biologic processes permitting chronic infection of the airways are not fully 
understood, but may involve abnormalities in the volume, physical properties 
and/or characteristics of mucus in the respiratory tract (9). In addition, the 
dysfunctional and/or damaged airway epithelial cells may permit organisms such 
as P. aeruginosa to adhere to the epithelium, permitting chronic colonization 
( 10 ). ' 
Concomitant with the infection is chronic intense inflammation of the airways 
that is dominated by neutrophils. Mononuclear phagocytes and lymphocytes play 
a lesser role. Sputum and lavage fluid analyses of CF patients reveal large 
concentrations of inflammatory mediators, particularly neutrophil proteases 
(11). Bacterial proteases, including Pseudomonas elastase are present, but to 
a far lesser extent (12). Concomitant with the response to the infection, 
inflammatory cells in the local milieu are chronically releasing large amounts 
of oxidants (13). Together, the mediators released by the inflammatory cells 
overwhelm the normal anti-inflammatory defense screen of the epithelial sur- 
face, and interfere with local host defense processes in the airways (11,13). 
The inflammatory mediators also exaggerate epithelial cell secretion (14), 
thus perpetuating the increased mucus production that characterizes the dis- 
ease. Consequent to this chronic, overwhelming inflammation, there is progres- 
sive damage to the epithelium culminating in the bronchiectasis and other 
permanent derangements of the lung that characterize CF. 
The clinical manifestations of CF reflect the progressive derangements to the 
airways (1). Early in the disease there is cough, together with respiratory 
tract infection. The sputum becomes thick and purulent. There is a long period 
of chronic bronchitis with acute exacerbations. Eventually, the permanent 
derangements of the respiratory tract cause symptoms of shortness of breath. 
The cycles of chronic and acute infection eventually culminate in limitation 
of activity, weight loss, and end- stage lung disease with hypoxemia, pulmonary 
hypertension, cor pulmonale and death (1,15). 
1.2 Current Therapy. Outpatient therapy includes frequent postural drainage 
and chest percussion, aerosolized DNase, administration of antibiotics, and 
bronchodilators . Most clinicians agree regarding the benefits of postural 
drainage and chest percussion; some advocate it for all patients while others 
reserve it for those with copious sputum production. Some centers advocate 
continuous antibiotic therapy while others reserve antibiotics for documented 
infections. Aerosolized DNase has recently been approved for therapy and its 
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