ATOPIC CHILDREN WITH CYSTIC-FIBROSIS HAVE INCREASED URINARY LEUKOTRIENE E(4) CONCENTRATIONS AND MORE SEVERE PULMONARY-DISEASE

Background: We investigated the hypothesis that cysteinyl leukotriene (LT) production is altered in atopic patients with cystic fibrosis (CF). Methods: Urinary LTE4 was measured in two groups of children with CF: atopic ACF group, n = 22) and nonatopic (NACF group, n = 13); and in two groups of unaffected children, those with atopic asthma (AA group, n = II) and nonatopic normal control subjects (NN group, n = 12). Results: Atopic groups excreted significantly more urinary LTE, (geometric means [95% confidence intervals] in picomoles per millimole creatinine), ACF group: 104 (73-147) and AA group: 195 (136-282) compared with NACF group: 19 (9-39) and NN group: 27 (15-48). The ACF group had significantly more airflow obstruction than the NACF group, with forced expiratory volume in 1 second (percent predicted, mean +/- SD) in ACF: 58 +/- 21 versus NACF: 81 +/- 23, and forced vital capacity (percent predicted, mean +/- SD) 72 +/- 17 versus 87 +/- 23, respectively. There were significant correlations between the degree of airflow obstruction, bronchodilator responsiveness, and urinary LTE4 concentration within the entire CF group. We used multiple regression analysis to assess the respective influence of age, atopy, sensitization to Aspergillus fumigatus, and colonization with Pseudomonas aeruginosa on urinary LTE4 concentration. The atopic state was the only significant variable associated with urinary LTE4 production in subjects with CF. Conclusions: The similarities in urinary LTE(4) between ACF and AA groups suggest that the atopic state is the prime determinant of urinary LTE(4) excretion. Enhanced cysteinyl LT production associated with atopy in CF may increase the severity of pulmonary disease.