INTERMITTENT, HIGH-DOSE NITRIC OXIDE INHALATION THERAPY FOR HOSPITALIZED INFANTS WITH BRONCHIOLITIS: A POTENTIAL TREATMENT FOR VIRAL INFECTIONS

David Greenberg ^1,2 Asher Tal ^1,2 Aviv Goldbart ¹ Shalom Ben-Shimol ¹ Inbal Golan-Tripto ¹ Yael Feinstein ¹ Ron Dagan ¹ Einav Levi ² Rinat Kalaora ² Yossef Av-Gay ^2,3

¹Pediatrics Department, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel
²R&D, AIT Ltd., Rehovot, Israel
³Department of Microbiology, University of British Columbia, Vancouver, British Columbia, Canada

Background: Nitric oxide (NO) has been previously shown to possess in vitro and ex vivo broad spectrum antimicrobial activity. When administered via inhalation, it is safe in animal models as well as healthy adults. The aims of this study were to determine safety, tolerability and efficacy of intermittent high-dose inhaled NO (HD-Inh-NO) for the treatment of hospitalized infants with bronchiolitis.

Methods: This was a double-blind, randomized controlled (HD-Inh-NO vs. oxygen only) study. HD-Inh-NO (160ppm) was given 5 times/day, for 30 min each time, to hospitalized 2-12m old infants with bronchiolitis. Inhaled FiO₂, NO, Met-Hemoglobin (MetHb), NO_2, Oxygen saturation (SaO₂) heart and respiratory rates, and blood pressure were continuously monitored. Efficacy was measured by length of hospitalization (LOS) and time to achieve SaO₂≥92% in room air (if treated for >24h).

Results: 43 infants were enrolled. In both treatment groups, the majority of subjects were positive for RSV (71.4% and 63.6% in the NO and control groups, respectively). 25 were hospitalized for >24h and thus were evaluable for efficacy (HD-Inh-NO – 14; oxygen only -11). Among all 43 patients no differences in adverse and serious adverse events (AE/SAE) were found between the HD-Inh-NO (n =22/5) and the oxygen only group (n = 22/6). No HD-Inh-NO related AE/SAEs were documented. Mean LOS and time to achieve SaO₂≥92% (n=25) were shortened by 28.3±29.4 and 34.8±34.6 hours respectively (p=0.032, both).

Conclusion: Intermittent high-dose (160ppm) nitric-oxide inhalation is safe and tolerated. HD-Inh-NO reduced hospitalization time and the duration of oxygen requirement in young infants with bronchiolitis.