Fibrosis Quistica

State of the Art
Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis
Ronald L. Gibson, Jane L. Burns, and Bonnie W. Ramsey
Department of Pediatrics, University of Washington School of Medicine, Children’s Hospital, and Regional Medical Center, Seattle, Washington

This comprehensive State of the Art review summarizes the current published knowledge base regarding thepathophysiology and microbiology of pulmonary disease in cystic fibrosis (CF). The molecular basis of CF lung disease including the impact of defective cystic fibrosis transmembrane regulator (CFTR) protein function on airway physiology, mucociliary clearance, and establishment of Pseudomonas aeruginosa infection is described. An extensive review of the microbiology of CF lung disease withparticular reference to infection with P. aeruginosa is provided. Other pathogens commonly associated with CF lung disease including Staphylococcal aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and atypical mycobacteria are also described. Clinical presentation and assessment of CF lung disease including diagnostic microbiology and other measures of pulmonary healthare reviewed. Current recommendations for management of CF lung disease are provided. An extensive review of antipseudomonal therapies in the settings of treatment for early P. aeruginosa infection, maintenance for patients with chronic P. aeruginosa infection, and treatment of exacerbation in pulmonary symptoms, as well as antibiotic therapies for other CF respiratory pathogens, are included. Inaddition, the article discusses infection control policies, therapies to optimize airway clearance and reduce inflammation, and potential future therapies. Keywords: cystic fibrosis, Pseudomonas aeruginosa, airway disease, cystic fibrosis transmembrane conductance regulator, antibiotics

Clinical Assessment in the Management of CF Lung Disease Monitoring Pulmonary Health Status DiagnosticMicrobiology Current Antibiotic Therapies Prevention of Chronic P. aeruginosa Infection Maintenance Therapy Treatment of Pulmonary Exacerbation Treatment of Other Emerging Pathogens Immunotherapy Infection Control in CF Pulmonary Disease Transmissibility of CF Pathogens Consensus Recommendations Current Therapies to Optimize Airway Clearance and Reduce Inflammation Optimizing Airway Clearance and ASLHydration Bronchodilators Antiinflammatory Therapy Diagnosis and Treatment of ABPA Future Therapies for CF Pulmonary Disease Gene Transfer Therapy Pharmacologic Approaches New Approaches to Treating P. aeruginosa Infection The cystic fibrosis (CF) scientific community has orchestrated a focused, multidisciplinary effort to understand the molecular basis of this disorder and at the same time improveclinical care for patients with CF. After identification of the CF gene in 1989, the 1990s was a decade associated with rapid expansion of knowledge regarding the structure and function of the CF gene product, CF transmembrane conductance regulator (CFTR) protein. The previous State of the Art assessment of CF in 1996 (1) provided a comprehensive review focusing on significant advances in scientificunderstanding of the CFTR gene. As we enter the 21st century, both laboratory and clinical investigators are applying this knowledge toward elucidating the critical factors that initiate chronic endobronchial bacterial infection in this genetic disorder and are using this knowledge to develop novel and effective therapies. This State of the Art focuses on the current understanding of the impact ofabnormal CFTR function on airway surface liquid (ASL) that initiates a pathophysiologic cascade leading to progressive lung disease. The role of chronic endobronchial bacterial infection with pathogens such as Pseudomonas aeruginosa and the resultant intense neutrophilic inflammatory response, pathognomonic for this lung disease, will be reviewed. In addition, current and future therapies to...