ELEVATED URINARY LEUKOTRIENE E(4) IN CHRONIC LUNG-DISEASE OF EXTREME PREMATURITY

We determined if pulmonary peptidoleukotrienes contribute to the patho genesis of chronic lung disease of extreme prematurity (CLD) by measur ing urinary leukotriene E(4) (uLTE(4)). Study patients had a birth wei ght < 1000 g and were about 28 d old when they were classified as norm al control subjects (n = 8) or as having CLD (n = 26, abnormal chest X -ray, supplemental O-2 requirement +/- ventilator). Urinary LTE(4) lev els were significantly elevated in CLD compared with the control group (288 +/- 92 versus 35 +/- 10 pg/mg creatinine, mean +/- SE, p < 0.05) . Ventilator-dependent CLD patients, who required dexamethasone and ha d demonstrated uLTE(4) levels above the normal range, needed significa ntly higher peak inspiratory pressures (20 +/- 1 cm H2O versus 15 +/- 1 cm H2O) than similar patients with uLTE(4) in the normal range, and the former group had a significant reduction in uLTE(4) in the first 5 d of dexamethasone therapy (626 +/- 198 to 451 +/- 176 pg/mg Cr) as v entilatory support was reduced. We conclude that peptidoleukotriene pr oduction is activated in patients with CLD (and no other detectable or gan dysfunction) to pathophysiologic levels described in adults with a cute asthma. Prospective studies focused on infants dependent on high levels of ventilatory support may provide insights into the role of le ukotriene synthesis inhibitors or receptor antagonists in the treatmen t of CLD.