As life expectancy of HIV-positive (HIV+) patients has increased for those receiving highly active antiretroviral therapy (HAART), chronic complications from smoking contribute substantially to morbidity and mortality. We have demonstrated that chronic obstructive lung disease (OLD) is an important problem and is more prevalent in HIV+ compared to HIV-negative (HIV-) patients, after adjusting for smoking and other confounding factors. Smoking is also a risk factor for other diseases that are increased in HIV, namely lung cancer, bacterial pneumonia, tuberculosis, and Pneumocystis pneumonia. We hypothesize that HIV+ patients have enhanced susceptibility to the consequences of smoking. Those who smoke and have HIV may be more predisposed to lung injury as a result of increased oxidative stress, which is known to be elevated in the setting of HIV,as well as in smoking and OLD.
Our first aim i s to 1) compare the incidence, risk factors, and outcomes for lung disease in HIV+ to HIV- patients. We will determine the independent risk for lung disease conferred by HIV infection, and to what extent the risk of lung complications is related to smoking or to concomitant OLD. These analyseswill be conducted within an ongoing, large, multicenter, prospective observational study of HIV+ and HIV- subjects, the Veterans Aging Cohort Study that has recently had funding renewed through 2011. Studies for Aims 2 and 3 will focus in-depth on a smaller group of subjects to understand clinical and pathophysiologic differences in OLD between HIV+ and HIV-patients. We hypothesize that OLD progresses more rapidly in HIV+ compared to HIV- smokers and that the accelerated progression is related to increased oxidative stress. We will obtain baseline and serial evaluations of pulmonary function, peripheral blood, exhaled breath condensates, and bronchoalveolar lavage specimens in HIV+ and HIV-current and former smokers with or at risk for OLD. Additional aims are to 2) compare risk factors for progression of OLD in HIV+ and HIV- smokers, and 3) compare markers of oxidative stress and progression of OLD in HIV+ and HIV- smokers. The studies proposed are poised to increase our understanding of lung diseases in HIV+ patients and to yield results that can be used directly to improve patient care. Furthermore, insights into reasons for susceptibility to OLD and accelerated progression of OLD can improve care for both HIV+ and HIV-patients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-Z (S1))
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Peavy, Hannah H
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Triplette, Matthew; Attia, Engi; Akgün, Kathleen et al. (2017) The Differential Impact of Emphysema on Respiratory Symptoms and 6-Minute Walk Distance in HIV Infection. J Acquir Immune Defic Syndr 74:e23-e29
Triplette, Matthew; Sigel, Keith M; Morris, Alison et al. (2017) Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening. AIDS 31:1715-1720
Depp, Timothy B; McGinnis, Kathleen A; Kraemer, Kevin et al. (2016) Risk factors associated with acute exacerbation of chronic obstructive pulmonary disease in HIV-infected and uninfected patients. AIDS 30:455-63
Yin, Michael T; Shiau, Stephanie; Rimland, David et al. (2016) Fracture Prediction With Modified-FRAX in Older HIV-Infected and Uninfected Men. J Acquir Immune Defic Syndr 72:513-20
Crothers, Kristina; Petrache, Irina; Wongtrakool, Cherry et al. (2016) Widespread activation of immunity and pro-inflammatory programs in peripheral blood leukocytes of HIV-infected patients with impaired lung gas exchange. Physiol Rep 4:
Rentsch, Christopher; Tate, Janet P; Akgün, Kathleen M et al. (2016) Erratum to: Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United States Veterans from 1997 to 2011. AIDS Behav 20:565
Salinas, Jorge L; Rentsch, Christopher; Marconi, Vincent C et al. (2016) Baseline, Time-Updated, and Cumulative HIV Care Metrics for Predicting Acute Myocardial Infarction and All-Cause Mortality. Clin Infect Dis 63:1423-1430
Leader, Joseph K; Crothers, Kristina; Huang, Laurence et al. (2016) Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort. J Acquir Immune Defic Syndr 71:420-7
Rentsch, Christopher; Tate, Janet P; Akgün, Kathleen M et al. (2016) Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United States Veterans from 1997 to 2011. AIDS Behav 20:555-64
Justice, Amy C; McGinnis, Kathleen A; Tate, Janet P et al. (2016) Risk of mortality and physiologic injury evident with lower alcohol exposure among HIV infected compared with uninfected men. Drug Alcohol Depend 161:95-103

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