DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.
“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.
Dr. Asher Tal
In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.
At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.
“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.
Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).
Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.
The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.
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*This article was added to on 6/25/15.