Respiratory care · 2026
Methemoglobin and Nitrogen Dioxide Levels During Inhaled Nitric Oxide Therapy at 300 Parts per Million in Healthy Volunteers.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Bruno Giovanni, Dong Run, Wanderley Hatus V, Cenci Stefano, Villalobos Regina, Pidò Sara, Spina Stefano, Mietto Cristina M, Safaee Fakhr Bijan, Bittner Edward A, La Vita Carolyn, Carroll Ryan W, Yu Binglan, Berra Lorenzo
Аннотация
BACKGROUND: High-dose inhaled nitric oxide (iNO) at 300 parts per million (iNO300) has shown antimicrobial and anti-inflammatory effects in preclinical models. Defining its safety profile in humans is essential for therapeutic development in respiratory infections. Human data specifically evaluating methemoglobin (MetHb) and nitrogen dioxide (NO2) kinetics during iNO are limited. This study investigated MetHb and NO2 formation in healthy adults exposed to iNO.
METHODS: In this phase 1 trial, 10 healthy adults received iNO for 30 min, 3 times daily over 5 days. To simulate oxygen therapy in pneumonia, NO was delivered at 2 inspired oxygen fractions (FIO2): 0.21 at 50 L/min and 0.80 at 70 L/min. On day 5, subjects exercised on a stationary bike to simulate increased ventilation in critically ill adults. Continuous MetHb monitoring was performed with pulse CO-oximetry (0.5 Hz), and NO2 was measured using an ultrafast laser-induced fluorescence analyzer (15 Hz).
RESULTS: One hundred forty-eight treatments were administered without major adverse effects. At rest, peak MetHb averaged 5.5 ± 1.2% (range 3.3-9.0%), increasing to 9.0 ± 1.1% (6.8-11.3%) during exercise. Six transient and asymptomatic MetHb elevations above 10% occurred in 3 out of 10 subjects, exclusively during exercise sessions, with all returning to baseline before the next dose. No MetHb accumulation was observed at day 7 follow-up. NO2 levels in the inspiratory limb remained <5 ppm during all treatments. Occasional brief NO2 spikes >5 ppm at the Y-piece occurred only at the inspiration-expiration transition or respiratory pause, representing 0.01-0.14% of sampling time.
CONCLUSIONS: Intermittent administration of iNO was safe in healthy adults under real-time monitoring of MetHb and NO2. These findings support further clinical investigations into iNO as a potential inhaled therapy for lower respiratory tract infections.
METHODS: In this phase 1 trial, 10 healthy adults received iNO for 30 min, 3 times daily over 5 days. To simulate oxygen therapy in pneumonia, NO was delivered at 2 inspired oxygen fractions (FIO2): 0.21 at 50 L/min and 0.80 at 70 L/min. On day 5, subjects exercised on a stationary bike to simulate increased ventilation in critically ill adults. Continuous MetHb monitoring was performed with pulse CO-oximetry (0.5 Hz), and NO2 was measured using an ultrafast laser-induced fluorescence analyzer (15 Hz).
RESULTS: One hundred forty-eight treatments were administered without major adverse effects. At rest, peak MetHb averaged 5.5 ± 1.2% (range 3.3-9.0%), increasing to 9.0 ± 1.1% (6.8-11.3%) during exercise. Six transient and asymptomatic MetHb elevations above 10% occurred in 3 out of 10 subjects, exclusively during exercise sessions, with all returning to baseline before the next dose. No MetHb accumulation was observed at day 7 follow-up. NO2 levels in the inspiratory limb remained <5 ppm during all treatments. Occasional brief NO2 spikes >5 ppm at the Y-piece occurred only at the inspiration-expiration transition or respiratory pause, representing 0.01-0.14% of sampling time.
CONCLUSIONS: Intermittent administration of iNO was safe in healthy adults under real-time monitoring of MetHb and NO2. These findings support further clinical investigations into iNO as a potential inhaled therapy for lower respiratory tract infections.