The EPIC Observational Study will serve as a freestanding epidemiologic study of the risk factors for and clinical impact of initial Pa acquisition and anti-pseudomonal therapy. Defining the risk factors for Pa acquisition can potentially allow for preventive measures and identification of high-risk populations requiring closer monitoring. Despite rigorous data collection, previous studies have been limited by small sample sizes and by conduct at one or two centers. This study will include a much larger sample size from many more centers than previous studies. It will thus provide for more generalizable results and more precise risk estimates for previously identified risk factors for Pa acquisition, and it will allow for exploration of novel risk factors not included in earlier studies. Better understanding of the clinical outcomes associated with Pa acquisition and the outcomes associated with different types of anti-pseudomonal therapies will inform the development of rational early intervention treatment regimens. Better knowledge about temporal relationships between respiratory signs and symptoms, Pa serology, and CF airway microbiology may lead to improved strategies for early detection of Pa and could have important implications for the timing of interventions aimed at preventing or treating early Pa acquisition. Finally, this study will serve as an important source of Pa and S. aureus isolates, serum samples, and DNA samples that will be used and banked for studies designed to enhance the understanding of the pathogenesis of CF, e.g., microarray investigations of early Pa isolates, investigations to identify proteomic biomarkers of airway inflammation, and investigations to identify genetic factors related to CF disease progression, including early lung disease, and clinical outcomes.