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A3855 - Redox States of Cysteine/Cystine and Glutathione/Glutathione Disulfide in Plasma and Bronchoalveolar Lavage Fluid in HIV-Infected Patients with COPD
Author Block: J. Ritzenthaler1, W. H. Watson1, P. Peyrani1, T. Wiemken1, T. J. Burke1, Y. Zheng1, J. A. Ramirez2, J. Roman1; 1Medicine, University of Louisville, Louisville, KY, United States, 2Div of Infectious Diseases, Univ of Louisville, Louisville, KY, United States.
Rationale: Lung diseases are major causes of morbidity and mortality in patients infected with HIV. In this age of effective antiretroviral therapy, non-infectious lung diseases such as chronic obstructive pulmonary disease (COPD) are emerging as important causes of illness, but the mechanisms responsible for this occurrence remain unclear. Oxidative stress has been implicated in the pathogenesis of HIV, and it can activate tissue remodeling in the lung. Since, oxidation of the cysteine/cystine (Cys/CySS) redox potential (Eh) stimulates lung fibroblasts to produce an altered extracellular matrix, we hypothesized that this type of oxidative stress might provide a mechanistic link between HIV infection and development/progression of COPD. The purpose of this study was to determine whether HIV infection is associated with oxidation of Eh Cys/CySS, and if this correlates with COPD severity. Methods: Subjects were recruited from the HIV Clinic and other university-operated clinics of the University of Louisville in the following groups: (1) HIV-infected (n=36), (2) COPD (n=32), (3) HIV and COPD (n=28), and (4) uninfected controls with normal lung function (n=34). Pulmonary function was determined by spirometry, and plasma and bronchoalveolar lavage (BAL) fluid were collected for measurement of Cys, CySS, glutathione (GSH) and GSH disulfide (GSSG) by high performance liquid chromatography followed by estimation of redox potentials (Eh) using the Nernst equation. Results: As expected, smoking was inversely correlated with decreased lung function, and the redox state of BAL Eh GSH/GSSG was progressively more oxidized as the number of pack years smoked increased. Overall, we found no significant differences in plasma or BAL redox states among the 4 groups. However, decreased lung function (lower FEV1/FVC ratio) correlated with oxidation of plasma Eh Cys/CySS and BAL Eh GSH/GSSG when compared across all 4 groups. There was no difference in CD4 counts between the HIV and the HIV and COPD groups, but lower CD4 counts were associated with more oxidized plasma Eh Cys/CySS in HIV-infected patients. Conclusions: HIV and COPD patients did not show more oxidation of Eh Cys/CySS when compared to controls. However, lung function declined in parallel with oxidation of plasma Eh Cys/CySS and BAL Eh GSH/GSSG, independent of HIV infection status. In addition, CD4 counts declined in parallel with oxidation of plasma Eh Cys/CySS, independent of COPD status. Altogether, these studies point to an association between oxidative stress and worse lung function and CD4 levels.