A phase I clinical study of inhaled nitric oxide in healthy adults.

BACKGROUND Nitric oxide (NO) is an approved pulmonary vasodilator for neonates and full term infants up to a dose of 80 ppm. At 100 ppm to 200 ppm, NO has potent antimicrobial activities in vitro and in animal studies which suggest its therapeutic use for infectious diseases in humans. However, whether inhaled NO is safe at 160 ppm in healthy human adults is unknown. The aim of the phase I study was to assess the safety of delivery and the physiologic effects of intermittent 160 ppm NO in healthy human adults. METHODS Ten healthy adult volunteers (5 males, 5 females; 20-62 years) were recruited and inhaled 163.3 ppm (SD: 4.0) NO for 30 min, 5 times daily, for 5 consecutive days. Lung function and blood levels of methemoglobin, nitrites/nitrates, prothrombin, pro-inflammatory cytokines and chemokines were determined before and during treatment. RESULTS All individuals tolerated the NO treatment courses well. No significant adverse events occurred and three minor adverse events, not attributable to NO, were reported. Forced expiratory volume in 1 sec % predicted and other lung function parameters, serum nitrites/nitrates, prothrombin, pro-inflammatory cytokine and chemokine levels did not differ between baseline and day 5, while methemoglobin increased significantly during the study period to a level of 0.9% (SD: 0.08) (p<0.001). CONCLUSION These data suggest that inhalation of 160 ppm NO for 30 min, 5 times daily, for 5 consecutive days, is safe and well tolerated in healthy individuals.