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

## TL;DR

High-dose inhaled nitric oxide shows promise as a broad-spectrum antimicrobial therapy for respiratory infections, with potential for both hospital and home use.

## Contribution

This review proposes a roadmap for future trials to optimize high-dose inhaled nitric oxide as a therapy for drug-resistant lung infections.

## Key findings

- High-dose inhaled nitric oxide has demonstrated antimicrobial and antiviral properties in early-phase studies.
- It acts through multiple pathways, including direct microbial killing and immune modulation.
- Safety data supports its use in both ICU and outpatient settings.

## Abstract

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.

High-dose inhaled nitric oxide is a potential antimicrobial therapy with broad-spectrum activity against bacteria, viruses, fungi, and parasites, and has been safely administered in diverse clinical contexts from ICU to outpatient care. This review summarizes translational and early clinical data and outlines a roadmap for future trials needed to define safety, efficacy, and optimal use in drug-resistant lung infections and acute respiratory failure.