Oxidative Stress and Pulmonary Injury in US Navy Divers

The potential for pulmonary oxygen toxicity is a primary limiting factor in peacetime and wartime US Navy diving operations. An important mission related goal of the operational diving community is to extend the limits of oxygen tolerance by any effective and practical means. A deterrent to achieving this goal is the unavailability of a specific and sensitive method to quantify the degree of oxidative pulmonary injury incurred during submerged oxygen breathing. Availability of a specific and sensitive biologic marker of oxidative stress and its application to the problem of oxygen toxicity would offer a mechanism to define the limits of oxygen exposure, diagnose, quantify and stage oxidative injury, and assess the value of existing and experimental treatment therapies. Recently, the formation of a novel group of oxygen-based free radical generated compounds, the Isofurans, have been found to be highly correlated with increasing environmental oxygen partial pressure in vitro and in vivo. The primary objective of this study is to examine the production of these Isofurans as a product of submerged oxygen breathing in the US Navy diving community. The secondary objective is to correlate production of Isofurans to subjective symptoms and changes in pulmonary function associated with pulmonary oxygen toxicity. Thirty volunteer US Navy divers will inspire 100% oxygen at 1.3 atmospheres for periods of 4 to 6 hours in a temperature controlled test pool. Exhaled breath condensate, blood and urine samples will be collected before, 30 minutes after and 24 hours following the exposure and Isofuran levels in these fluids will be determined using gas chromatography and mass spectrometry. In addition, indices of static and dynamic pulmonary function and physical symptoms indicative of lung insult will be collected before and after the exposure. A repeated measures ANOVA will be used to compare the biologic sample data across the three sampling periods. Changes from baseline in the Isofuran levels will be correlated with changes in pulmonary function and the occurrence and severity of pulmonary symptoms. Identification of a specific and sensitive biologic marker of oxidative stress and correlation to changes in pulmonary function and subjective symptoms would offer a means with which to precisely determine the physiologic limits of occupational exposure to high oxygen partial pressures. Knowledge of these limits will lead to improved short and long term health outcomes for US Navy divers