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 C F: atopic ACF group, n = 22) and nonatopic (NACF group, n = 13); and i n two groups of unaffected children, those with atopic asthma (AA grou p, n = II) and nonatopic normal control subjects (NN group, n = 12). R esults: Atopic groups excreted significantly more urinary LTE, (geomet ric means [95% confidence intervals] in picomoles per millimole creati nine), ACF group: 104 (73-147) and AA group: 195 (136-282) compared wi th NACF group: 19 (9-39) and NN group: 27 (15-48). The ACF group had s ignificantly 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. The re were significant correlations between the degree of airflow obstruc tion, bronchodilator responsiveness, and urinary LTE4 concentration wi thin the entire CF group. We used multiple regression analysis to asse ss the respective influence of age, atopy, sensitization to Aspergillu s fumigatus, and colonization with Pseudomonas aeruginosa on urinary L TE4 concentration. The atopic state was the only significant variable associated with urinary LTE4 production in subjects with CF. Conclusio ns: The similarities in urinary LTE(4) between ACF and AA groups sugge st that the atopic state is the prime determinant of urinary LTE(4) ex cretion. Enhanced cysteinyl LT production associated with atopy in CF may increase the severity of pulmonary disease.