GJ Quinlan, NJ Lamb, R Tilley, TW Evans and JM Gutteridge
Oxygen Chemistry Laboratory, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.

Acute respiratory distress syndrome in adults (ARDS) carries a high mortality. Patients with ARDS experience severe oxidative stress from neutrophil activation, and from treatment with high inspired oxygen concentrations (F(I)O2). Oxidative stress arises from an increased generation of reactive oxygen species (ROS) which overwhelm existing antioxidant defenses. Patients who do not survive ARDS sustain much greater levels of oxidative molecular damage, suggesting that they are less able to protect themselves against increased oxidative stress. We measured plasma levels of pro-oxidant substrates for xanthine oxidase, namely hypoxanthine and xanthine, and correlated them with the loss of plasma protein thiol groups. All patients with ARDS had higher levels of hypoxanthine (37.48 +/- 3.1 microM in nonsurvivors, 15.24 +/- 2.09 microM in survivors) compared with patients undergoing pulmonary resection (9.22 +/- 1.89 microM), patients in intensive care with sepsis but no lung injury (1.12 +/- 0.69 microM) and normal healthy control subjects (1.43 +/- 0.38 microM). The difference in plasma hypoxanthine levels between survivors and nonsurvivors of ARDS was highly significant (p < 0.001) and showed a negative correlation with loss of protein thiol groups. Xanthine levels were also higher in patients with ARDS but were not significantly different between ARDS survivors and nonsurvivors. Nonsurvivors of ARDS appear to experience higher levels of oxidative stress and damage than do survivors.

This article has been cited by other articles:

				A. Boueiz, M. Damarla, and P. M. Hassoun Xanthine oxidoreductase in respiratory and cardiovascular disorders Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L830 - L840. [Abstract] [Full Text] [PDF]

				R.-E. E. Abdulnour, X. Peng, J. H. Finigan, E. J. Han, E. J. Hasan, K. G. Birukov, S. P. Reddy, J. E. Watkins III, U. S. Kayyali, J. G. N. Garcia, et al. Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent pathways Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L345 - L353. [Abstract] [Full Text] [PDF]

				M. Cepkova and M. A. Matthay Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome. J Intensive Care Med, May 1, 2006; 21(3): 119 - 143. [Abstract] [PDF]

				W. MacNee Treatment of stable COPD: antioxidants Eur. Respir. Rev., September 1, 2005; 14(94): 12 - 22. [Abstract] [Full Text] [PDF]

				E. E. Kelley, A. Trostchansky, H. Rubbo, B. A. Freeman, R. Radi, and M. M. Tarpey Binding of Xanthine Oxidase to Glycosaminoglycans Limits Inhibition by Oxypurinol J. Biol. Chem., September 3, 2004; 279(36): 37231 - 37234. [Abstract] [Full Text] [PDF]

				R. M. Wright, L. A. Ginger, N. Kosila, N. D. Elkins, B. Essary, J. L. McManaman, and J. E. Repine Mononuclear Phagocyte Xanthine Oxidoreductase Contributes to Cytokine-Induced Acute Lung Injury Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 479 - 490. [Abstract] [Full Text] [PDF]

				C.-W. Chow, M. T. Herrera Abreu, T. Suzuki, and G. P. Downey Oxidative Stress and Acute Lung Injury Am. J. Respir. Cell Mol. Biol., October 1, 2003; 29(4): 427 - 431. [Full Text] [PDF]

				R. P. Bowler and J. D. Crapo Oxidative Stress in Airways: Is There a Role for Extracellular Superoxide Dismutase? Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S38 - 43. [Abstract] [Full Text] [PDF]

				J. D. Lang, P. J. McArdle, P. J. O'Reilly, and S. Matalon Oxidant-Antioxidant Balance in Acute Lung Injury Chest, December 1, 2002; 122(6_suppl): 314S - 320S. [Abstract] [Full Text] [PDF]

				R. G. Brower, L. B. Ware, Y. Berthiaume, and M. A. Matthay Treatment of ARDS Chest, October 1, 2001; 120(4): 1347 - 1367. [Abstract] [Full Text] [PDF]

				G. Asimakopoulos, P. L.C. Smith, C. P. Ratnatunga, and K. M. Taylor Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass Ann. Thorac. Surg., September 1, 1999; 68(3): 1107 - 1115. [Abstract] [Full Text] [PDF]

				K. Modelska, M. A. Matthay, L. A. S. Brown, E. Deutch, L. N. Lu, and J. F. Pittet Inhibition of beta -adrenergic-dependent alveolar epithelial clearance by oxidant mechanisms after hemorrhagic shock Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L844 - L857. [Abstract] [Full Text] [PDF]

				M. Houston, A. Estevez, P. Chumley, M. Aslan, S. Marklund, D. A. Parks, and B. A. Freeman Binding of Xanthine Oxidase to Vascular Endothelium. KINETIC CHARACTERIZATION AND OXIDATIVE IMPAIRMENT OF NITRIC OXIDE-DEPENDENT SIGNALING J. Biol. Chem., February 19, 1999; 274(8): 4985 - 4994. [Abstract] [Full Text] [PDF]

				K. A. Skinner, C. R. White, R. Patel, S. Tan, S. Barnes, M. Kirk, V. Darley-Usmar, and D. A. Parks Nitrosation of Uric Acid by Peroxynitrite. FORMATION OF A VASOACTIVE NITRIC OXIDE DONOR J. Biol. Chem., September 18, 1998; 273(38): 24491 - 24497. [Abstract] [Full Text] [PDF]

				P. M. HASSOUN, F.-S. YU, C. G. COTE, J. J. ZULUETA, R. SAWHNEY, K. A. SKINNER, H. B. SKINNER, D. A. PARKS, and J. J. LANZILLO Upregulation of Xanthine Oxidase by Lipopolysaccharide, Interleukin-1, and Hypoxia . Role in Acute Lung Injury Am. J. Respir. Crit. Care Med., July 1, 1998; 158(1): 299 - 305. [Abstract] [Full Text] [PDF]

				W MACNEE and I M WALDEN Lung research funding in the UK: the British Lung Foundation perspective Thorax, April 1, 1998; 53(4): 239 - 240. [Full Text]

				B. M. Hybertson, R. P. Kitlowski, E. K. Jepson, and J. E. Repine Supercritical fluid-aerosolized vitamin E pretreatment decreases leak in isolated oxidant-perfused rat lungs J Appl Physiol, January 1, 1998; 84(1): 263 - 268. [Abstract] [Full Text] [PDF]

				U. S. Kayyali, C. Donaldson, H. Huang, R. Abdelnour, and P. M. Hassoun Phosphorylation of Xanthine Dehydrogenase/Oxidase in Hypoxia J. Biol. Chem., April 20, 2001; 276(17): 14359 - 14365. [Abstract] [Full Text] [PDF]