Oxygen concentration in inhaled gas and nitric oxide concentration in exhaled gas. Is nitric oxide concentration in exhaled gas a useful marker for exposure to hyperoxia?
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Background: Exposure to partial pressures of oxygen (PO2) higher than 50 kPa may result in toxic effects on the lungs with reduced vital capacity, maximal expiratory flow rates and diffusion capacity. The risk of developing pulmonary oxygen toxicity is present during diving and hyperbaric oxygen therapy. The traditional lung function tests are not sufficiently sensitive, and new markers of early development of oxygen toxicity are required. Nitric oxide (NO) in exhaled gas is a marker of some inflammatory processes in the lungs and the production of NO is influenced by the PO2. The fraction of NO in exhaled gas (FENO) is reduced by 30% after exposure to hypobaric hypoxia at altitude above 4500meter. NO from the alveolar and bronchial compartments of the lung contribute to FENO. Changes in NO concentration at the alveolar level may have effects on pulmonary blood flow and gas exchange, and thereby contribute to the reduction in diffusion capacity. A reduction in bronchial NO flux is associated with induced bronchoconstriction, while increased alveolar NO concentration is associated with increased alveolar dead space. Aims: The overall aim in the present thesis was to investigate if FENO is a useful marker to predict pulmonary oxygen toxicity. This was investigated through three separated studies that aimed at: 1. To study the dose-response relationship between oxygen exposure and FENO during and after hypoxia and hyperoxia. 2. To investigate the alveolar and bronchial contributions in FENO after exposure to hyperoxia. 3. To investigate the relationship between FENO and lung function. Design: An open randomised crossover design and a non-randomized design. Methods: 73 healthy non-smoking subjects between the ages of 20-40 years and a smaller group of 12 patients between 35-68 years undergoing hyperbaric oxygen therapy were included. FENO was measured before, during and after exposure to hypobaric hypoxia (PO2 = 15 kPa), hyperbaric hyperoxia (PO2 = 240 kPa), normobaric hyperoxia (PO2 = 100 kPa) and when breathing ambient air (PO2 = 21 kPa), all for 90 min. Dynamic and static lung volumes, maximal expiratory flow rates, distribution of ventilation and diffusion capacity (DLCO) were measured before and after exposure to normobaric hyperoxia. Results: The concentration of NO in exhaled gas was reduced by 20-30% after exposure to hyperoxia at PO2 of 100-240 kPa, but no significant change was found after exposure to hypoxia when corrected for altitude effects. The bronchial contribution to NO in exhaled gas was reduced after exposure to hyperoxia, whereas the alveolar NO concentration was unchanged. There was no association between the change in FENO and the changes in lung function after exposure to normobaric hyperoxia. Conclusions: 1. The partial pressure of NO in exhaled gas was unchanged upon arrival at moderate altitude after correcting for gas density effects. There might be a dose-response relationship between PO2 and the change in FENO, where subjects exposed to the highest dose of oxygen showed the greatest reduction in FENO. 2. There was a significant reduction in bronchial contribution to NO in exhaled gas after hyperoxia, but no change in the alveolar NO concentration. 3. The reduction in FENO by 20% after exposure to hyperoxia at PO2 of 100 kPa for 90 min was not associated with the changes in lung function. FENO was not confirmed as a direct marker of pulmonary oxygen toxicity.
Består avPaper I: Exhaled nitric oxide concentration upon acute exposure to moderate altitude. Caspersen C, Stang J, Thorsen E, Stensrud T. Scand J Med Sci Sports 2013; 23:102-107. The article is not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1111/sms.12018
Paper II: Bronchial nitric oxide flux and alveolar nitric oxide concentration after exposure to hyperoxia.Caspersen C, Stensrud T, Thorsen E. Aviat Space Environ Med 2011; 82:946-50. The article is not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.3357/asem.2995.2011
Paper III: Exhaled nitric oxide and lung function after moderate normobaric hyperoxic exposure. Caspersen C, Stensrud T, Storebø M, Thorsen E. Undersea Hyperb Med 2013; 40:7-13. The article is not available in BORA due to publisher restrictions.