Relationship Between Exhaled Nitric Oxide and Hyperoxic Stress

Background Recent evidence indicates that expired nitric oxide (NOexp) may provide a useful noninvasive measure of lung oxidative stress resulting from exposure to hyperoxic gas mixtures (UHM 38:430, 2011). Thus the objective of this study was to collate the available data from four related human studies conducted at NSMRL over the past six years in which NOexp was measured immediately prior to and following a variety of hyperoxic exposures to ascertain the relationship between NOexp and hyperoxic stress. Methods NOexp was measured in accordance with American Thoracic Society guidelines using a Sievers NOA 280i Nitric Oxide Analyzer. The hyperoxic exposures (n=89) ranged from one hour normobaric exposures breathing 100% oxygen to eight hour exposures breathing 2 ATA of oxygen in a hyperbaric chamber. All the exposures were conducted in the dry with the subjects at rest. Hyperoxic stress for each exposure was quantified using the formula: Hyperoxic dose = (PiO 2 in ATA x time of exposure in min) – (0.21 x time of exposure). The relationship between hyperoxic dose and the relative change in NOexp was fit to an exponential fall with an asymptote. The best fit model parameters for the asymptote and the PiO 2 dose response constant, b, and goodness of fit (r 2 ) for the equation were derived using least squares linear regression in log space by simultaneously varying b and the asymptote until the sums of squares was minimized. Results The best fit equation was: NOexp % change + 76.9 = 76.9 e (‐O 2 dose/499) (r 2 =0.77, p<0.0001). Conclusions The change in NOexp following dry resting hyperoxic exposures follows an exponential decline that is tightly related to the hyperoxic dose. Acknowledgements Funded by ONR (work unit # N0001413WX20689) through the In‐house Laboratory Independent Research program.