Anti-inflammatory therapies for cystic fibrosis-related lung disease

Cystic fibrosis (CF) is an autosomal recessive disease affecting many organ systems. In the lung, the underlying ion transport defect in CF establishes a perpetuating cycle of impaired airway clearance, chronic endobronchial infection, and exuberant inflammation. The interrelated nature of these components of CF lung disease makes it likely that the most effective therapeutic strategies will include treatments of each of these. This chapter reviews the preclinical and clinical data focused on ways to better understand and particularly to limit inflammation in the CF airway. Anti-inflammatories are an attractive therapeutic target in CF with a proven ability to decrease the rate of decline in lung function. However, the inherent complexity of the inflammatory response combined with the obvious dependency on this response to contain infection and the side effect profiles of common anti-inflammatories have made identifying the most suitable agents challenging. Research continues to discover impairments in signaling events in CF that may contribute to the excessive inflammation seen clinically. Concurrent with these findings, promising new therapies are being evaluated to determine which agents will be most effective and well tolerated. Available data from studies commenced over the last two decades, which have generated both encouraging and disappointing results, are reviewed below.