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<p>Inhaled nitric oxide (iNO), long used as a selective pulmonary vasodilator, has demonstrated potential antimicrobial and antiviral properties when administered at high concentrations (&gt; 20 parts per million, ppm). While definitive evidence is still lacking, this narrative review synthesizes the emerging clinical and mechanistic properties supporting high-dose iNO as a potential therapeutic strategy for lower respiratory tract infections, including drug-resistant bacterial pneumonias, COVID-19, nontuberculous mycobacteria, and bronchiolitis. We summarize safety data from laboratory studies, Phase I trials, clinical findings from 27 predominantly early-phase studies, and highlight its as both hospital-based and home-based therapy. High-dose iNO acts through multiple pathways, including direct microbial killing, biofilm disruption, immune modulation, and mucociliary enhancement, and holds promise in addressing unmet needs in respiratory infection management. We also propose a roadmap for future research to optimize dosing, delivery, and efficacy endpoints in well-defined patient populations.</p>

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The therapeutic potential of high-dose inhaled nitric oxide for antimicrobial effects: a narrative review and future directions

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月5日

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  • Lorenzo Berra,
  • Nikolay Kamenshchikov,
  • Asher Tal,
  • Bijan Safaee Fakhr,
  • Emanuele Rezoagli,
  • Rachel Thomson,
  • Binglan Yu,
  • Amir Elalem,
  • Huajie Li,
  • Bin Wang,
  • Run Dong,
  • Elisa Mereto,
  • Andrea Bolchini,
  • Matthew Ludwig,
  • Thomas Lambert,
  • Cristina Miett,
  • Stefano Spina,
  • Hatus Wanderley,
  • Ryan Carroll,
  • Giovanni Bruno

摘要

Inhaled nitric oxide (iNO), long used as a selective pulmonary vasodilator, has demonstrated potential antimicrobial and antiviral properties when administered at high concentrations (> 20 parts per million, ppm). While definitive evidence is still lacking, this narrative review synthesizes the emerging clinical and mechanistic properties supporting high-dose iNO as a potential therapeutic strategy for lower respiratory tract infections, including drug-resistant bacterial pneumonias, COVID-19, nontuberculous mycobacteria, and bronchiolitis. We summarize safety data from laboratory studies, Phase I trials, clinical findings from 27 predominantly early-phase studies, and highlight its as both hospital-based and home-based therapy. High-dose iNO acts through multiple pathways, including direct microbial killing, biofilm disruption, immune modulation, and mucociliary enhancement, and holds promise in addressing unmet needs in respiratory infection management. We also propose a roadmap for future research to optimize dosing, delivery, and efficacy endpoints in well-defined patient populations.