Department of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel.
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Pediatr Pulmonol. 2018 Jan;53(1):95-102. doi: 10.1002/ppul.23905. Epub 2017 Nov 27.
The aims of this pilot study were to determine safety, tolerability (primary outcome) and efficacy (secondary outcome) of high-dose inhaled nitric oxide for the treatment of infants with moderately severe bronchiolitis.
This was a pilot, double-blinded, randomized controlled study (phase IIa). Intermittent inhalations of nitric oxide 160 ppm for 30 min or oxygen/air (control) were given 5 times/day to hospitalized infants (2-11 months) with acute bronchiolitis. Oxygen saturation, methemoglobin, and nitric dioxide (NO ) levels and vital signs were monitored.
Forty-three infants were enrolled. Baseline characteristics were comparable in both study groups. Mean clinical score, comprised of four components: respiratory rate, use of accessory muscles, wheezes and crackles, and % room-air oxygen saturation, was 7.86 (±1.1) and 8.09 (±1.2) in the NO and control groups, respectively, consistent with moderate severity. The overall frequency of adverse events was similar between the groups. Repeated nitric oxide inhalations did not result in increased inhaled NO levels or cumulative effect on methemoglobin levels. Secondary outcomes of efficacy were measured by length of hospitalization (LOS) in hours: LOS did not differ between groups. However, in a post-hoc analysis of a subgroup of infants hospitalized for >24 h (n = 24), the median LOS was shorter in the nitric oxide (41.9 h) than in the control group (62.5 h) (P = 0.014).
Our study was unable to detect a difference in side effects using intermittent high-dose nitric-oxide inhalation or supportive treatment alone, in infants with moderate bronchiolitis. Preliminary efficacy outcomes are encouraging.
本研究旨在确定高剂量吸入一氧化氮治疗中度毛细支气管炎婴儿的安全性、耐受性（主要结局）和疗效（次要结局）。
这是一项试点、双盲、随机对照研究（IIa 期）。对患有急性毛细支气管炎的住院婴儿（2-11 个月），间歇性给予 160ppm 一氧化氮吸入治疗 30 分钟或氧气/空气（对照组），每日 5 次。监测氧饱和度、高铁血红蛋白和二氧化氮（NO ）水平及生命体征。
共纳入 43 例婴儿。两组的基线特征相似。由四个部分组成的平均临床评分（呼吸频率、辅助肌肉使用、喘鸣和爆裂音、以及%室内空气氧饱和度）分别为 NO 组 7.86（±1.1）和对照组 8.09（±1.2），表明为中度严重程度。两组的总体不良事件频率相似。重复吸入一氧化氮不会导致吸入 NO 水平增加或高铁血红蛋白水平的累积效应。疗效的次要结局通过住院时间（小时）进行测量：两组之间的 LOS 没有差异。然而，在住院时间>24 小时的婴儿亚组的事后分析中（n=24），NO 组的中位 LOS 短于对照组（41.9 小时与 62.5 小时）（P=0.014）。
我们的研究未能检测到间歇性高剂量一氧化氮吸入或单独支持治疗在中度毛细支气管炎婴儿中使用的副作用差异。初步疗效结果令人鼓舞。
