Inflammation and Cystic Fibrosis Pulmonary Disease
Inflammation plays a primary role in the pathogenesis of cystic fibrosis (CF)-related lung disease. Controlling the inflammatory process with antiinflammatory therapy may slow the progression of pulmonary disease and thereby decrease morbidity. Despite potential benefits of antiinflammatory therapy, both the decision to treat and selection of the most appropriate therapeutic agent are controversial. Although oral corticosteroids are associated with reduced progression of pulmonary disease, the risk of clinically significant adverse effects limits long-term therapy. Clinical studies with inhaled corticosteroids failed to report positive effects on reducing airway inflammation. Based on available clinical data, routine therapy with these agents should be limited to patients with asthma or steroid-responsive wheezing. High-dosage ibuprofen has a beneficial effect on reducing the annual rate of decline in pulmonary function in patients with mild lung disease. Whereas initial results are encouraging, they do not support routine ibuprofen therapy in all patients with CF. However, as advocated by the Cystic Fibrosis Foundation, high-dosage ibuprofen may be considered in children 5-12 years of age with a baseline forced expiratory volume of 60% predicted or greater.

Cystic fibrosis (CF), the most common, lethal, genetic disorder in Caucasians, is a multisystem disease affecting approximately 30,000 people in the United States. Chronic obstructive pulmonary disease, the primary complication of CF, is responsible for more than 90% of disease-related morbidity and mortality in these patients. The etiology of CF pulmonary disease is multi-factorial, involving a continuous cycle of airway obstruction, chronic infection, and excessive local inflammation that leads to development of end-stage bronchiectasis. Specifically, defective ion (Na, Cl) and water transport across pulmonary epithelia, a consequence of mutations in the CF gene, results in formation of abnormally viscous airway secretions. Presence of thickened secretions impairs mucociliary clearance and contributes to airway obstruction. Chronic bacterial colonization, primarily with Pseudomonas aeruginosa, and recurrent acute exacerbations stimulate an excessive inflam-matory response. Persistence of local inflammation further alters lung integrity and worsens airway obstruction. Although inflammation is well established as a primary pathophysiologic event in CF pulmonary disease, its pathogenesis and clinical management are controversial.