S36 Hypoxia induced bronchodilation and hyperoxia induced bronchoconstriction in human airways

Introduction and objectives Oxygen is often used inappropriately in hospital for patients without significant systemic hypoxia. In lung disease correcting hypoxia has become a key treatment target. Here for the first time we explore the effect of oxygen on airway tone in human lung models. Methods Human lung specimens were obtained at resection for cancer. Rings of human bronchi were mounted in 25 ml organ baths for continuous recording of isometric tension. The effect of changing the oxygen tension in the buffer solution on resting tension and active tension to 1 mM methacholine was investigated by changing the oxygen concentration of the aerating gas. Whole human lungs or lobes were perfused and ventilated as previously described.1 Hypoxia was induced by modifying the perfusion/ventilation circuit. Results Exposure to hypoxia caused a robust relaxation of bronchi from resting tension in 95% oxygen of 2.09±0.44 gf to 1.10±0.44 gf (−46±22%) (n=68) and active tension from 3.23±2.00 gf to 1.47±0.45 gf (−116±33% reversal of active tension) (n=94) which was fully reversed on reoxygenation with 95% oxygen. Stepwise reduction in oxygen concentration caused a concentration dependent reduction in resting (n=43) and active tension (n=36). The magnitude of relaxation to hypoxia from active tension was significantly greater than that to 10 µM isoprenaline (113%±28% and 94%±38% reversal of active tension respectively, n=56, figure 1). Exposure of isolated lungs to hypoxia caused a robust and sustained reduction in peak airway pressure (−22±14%) which was reversed on return to ventilation with room air. Conclusions We have shown that hypoxia causes a robust and reversible relaxation of human airways and that hyperoxia causes a significant contraction of human airways. These results have important clinical implications. The use of oxygen in hospital in-patients may have unrecognised deleterious effects on airway patency. Excessive treatment with oxygen in patients with COPD may enhance bronchoconstriction, V: Q mismatch, and could exacerbate CO2 retention. Further studies are underway to determine the mechanism mediating this profound hypoxic bronchodilation which is potentially a significant therapeutic target. Reference Bennett RT, Jones RD, Morice AH, et al. Thorax2004;59:401–407.