Adverse Effects of Inhaled NO

20 ppm NO for 25 hr (Frostell etal., 1993b). Wessel etal. (1994) measured MetHb levels above 5% in four of 123 patients, mostly children, who had inhaled NO at up to 100 ppm for therapy. Methemoglobinemia is not detected with ordinary pulse oximetry devices (Rieder et al., 1989). 

Nakajima et al. (1980) and others (e.g., et al., 1976) exposed mice to 10 ppm NO for 6 months and reported enhanced red blood cell turnover as well as increased spleen weight. Young et al. (1994) exposed healthy adults to doses of NO above 100 ppm. Administering 512 ppm NO in 21 % oxygen, they measured a mean MetHb level rise to 5% in less than 60 min, reversing to below 3% within 1 hr after ceasing NO breathing. Thus, for most adults MetHb formation is usually not a problem at inhaled NO doses below 100 ppm. 

The toxicity of NO2 is often studied since it is a major component of air pollution however, a safe level is difficult to determine. A confounding effect is a certain tolerance to later NO exposure after a preliminary low-level exposure for a brief time (Mustafa and Tierney, 1978). NO2 levels of less than 0.5 ppm have been reported to enhance human airway hyperreactivity (Bylin et al., 1988). Toxic pulmonary effects of breathing NO2 at or below 5 ppm have been reported. These include altered surfactant chemistry and metabolism (Muller et al., 1994), epithelial hyperplasia of the terminal bronchioles, and increased cellularity of the alveoli in rats (Evans et al., 

as well as diffuse inflammation (Muller etal., 1994) and hyperreactivity (Frampton et al., 1991). Exposure to higher inhaled NO2 levels causes pulmonary edema and death (Greenbaum etal., 1967 Clutton-Brock, 1967). The problems of NO2 exposure will remain of great concern when home-assembled delivery devices are used for prolonged administration of NO as therapy without the careful monitoring of NO and NO2 levels. 

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