The purpose of this study is to determine if there is a relationship between the quantity of leukotriene E4 in urine samples and pulmonary disease status as measured by pulmonary function testing in patients with cystic fibrosis. Leukotrienes, a group of 5-lipoxygenase products of arachidonic acid, are released from resident and circulating inflammatory cells within the lung. LTB4, the main leukotriene released by polymorphonuclear leukocytes, is as chemotactic agent which activates inflammatory cells, potentiates edema formation, and impairs mucociliary clearance. LTC4, LTD4, and LTE4, leukotrienes released by mast cells and eosinophils, induce bronchoconstriction, mucus secretion, and microvascular leak. Because airway inflammation, mucus hypersecretion, and increased bronchial reactivity are key elements of cystic fibrosis lung disease, leukotrienes may be important mediators of pulmonary pathophysiology in cystic fibrosis. While studies to date have indicated an association between leukotriene levels and severity of lung disease in cystic fibrosis, no one has measured leukotriene levels in cystic fibrosis patients over time to see if they vary with the clinical severity of pulmonary disease. Evaluating the role of leukotriene levels as a mediator and marker of disease would be especially meaningful given the recent availability of drugs which decrease leukotriene production, such as Zileuton and eicosapentaenoic acid.
Specific Aims : 1) To determine whether urinary LTE4 levels decrease after treatment for a pulmonary exacerbation in cystic fibrosis patients. 2) To determine whether a correlation exists between urinary LTE4 levels and clinical pulmonary status as it varies in cystic fibrosis patients over a 6 month period. 3) To identify a subgroup of cystic fibrosis patients with high levels of urinary LTE4 for which medical treatment with lipoxygenase inhibitors might be useful.
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