Abstract 1110 Poster Session I, Saturday, 5/1 (poster 79)

Background. Neonatal chronic lung disease (CLD) manifests significant increases in pulmonary vascular resistance and airway flow resistance, and ventilation-perfusion mismatching occurs. Nitric oxide (NO) is a potent vasodilator and may have possible bronchodilatory effects as well. Because of its effects on vascular and airway smooth muscle, and the subsequent possible effects on pulmonary gas exchange, it may prove helpful in the treatment of CLD, by improving blood flow and ventilation. We have conducted a phase II clinical trial of iNO in the treatment of CLD, assessing for possible efficacy and safety. Subjects are infants of ≥10 days of age, with clinical and radiographic evidence of developing or established CLD. All patients require mechanical ventilation and an FiO2 of ≥ 0.40. Patients are excluded on the basis of the following criteria: sepsis diagnosed within the preceding 48 hr., initiation of corticosteroids or beta-agonist therapy within the preceding 48 hr., Grade 4 IVH, obviously lethal congenital anomalies, complex congenital heart disease, and thrombocytopenia (< 100K platelets). Forty trials have been conducted in 31 patients. Demographic factors include gestational age of 26.2 ± 3.3 wk (mean ± SD), birth weight 897 ± 627 g (range 468-3560 g), and age at entry of 10-443 days (median = 20). The trial intervention consists of administration of 20 ppm iNO via the ventilator circuit. The dose was reduced to 10 ppm at 24-36 hr., and then to the lowest effective dose for up to a maximum treatment period of 7 days. No other intervention was made. In order to assess lung inflammation, tracheal aspirate samples obtained as a part of routine care just before, at 48-72 hr. of iNO, and after therapy, were analyzed by ELISA for levels of IL-1β, IL-8, 8-epi-PGF2α, laminin, and, in order to normalize samples for dilution, soluble secretory component of IgA. Results. There was a significant reduction in FiO2 at 3 hr. and 72 hr. compared with baseline (p<0.05). Mean FiO2 decreased by 0.10 at 3 hr. (from 0.70 to 0.60) and by 0.18 at 72 hr. (0.70 to 0.52), while oxyhemoglobin saturation by pulse oximetry rose slightly (p<0.05) (90.4%, 91.9%, and 92.9% at baseline, 3, and 72 hr, respectively), and mean airway pressure was insignificantly lower at both time points. Tracheal aspirate levels of IL-1β, IL-8, 8-epi-PGF2α, and laminin showed no change, in comparison with baseline values, upon exposure to iNO. There have been no cases of new IVH, nor extension of existing IVH. Infection has developed in five patients during treatment. Four patients have died, three subsequent to trial of iNO, and one while receiving treatment. We conclude that iNO appears to improve oxygenation in patients with early or established chronic lung disease, and that preliminary data suggest that such treatment may be safe. Further trials are warranted.