Longitudinal Studies of HIV-Associated Lung Infections and Complications

描述（由申请人提供）： 随着艾滋病毒阳性（HIV+）患者的预期寿命延长，接受高度活跃治疗的患者的预期寿命也增加了 在抗逆转录病毒治疗（HAART）的情况下，吸烟引起的慢性并发症是发病率和死亡率的主要原因。我们已经证明，慢性阻塞性肺疾病（OLD）是一个重要的问题，在调整吸烟和其他混杂因素后，与HIV阴性（HIV-）患者相比，HIV+患者更普遍。吸烟也是艾滋病毒感染率增加的其他疾病的危险因素，即肺癌、细菌性肺炎、肺结核和肺孢子虫肺炎。我们假设HIV阳性患者对吸烟后果的易感性增强。那些吸烟和艾滋病毒感染者可能更容易因氧化应激增加而导致肺损伤，已知氧化应激在艾滋病毒感染以及吸烟和老年人中升高。我们的第一个目标是1）比较HIV+和HIV-患者肺部疾病的发病率、危险因素和结局。我们将确定由HIV感染引起的肺部疾病的独立风险，以及肺部并发症的风险与吸烟或伴随的OLD的相关程度。这些分析将在一项正在进行的、大型的、多中心的、前瞻性的观察性研究中进行，该研究针对HIV+和HIV-受试者，即退伍军人老龄化队列研究，该研究最近获得了到2011年的资助。目标2和3的研究将深入关注较小的受试者群体，以了解HIV+和HIV-患者之间OLD的临床和病理生理差异。我们假设，与HIV-吸烟者相比，HIV+吸烟者的OLD进展更快，并且加速进展与氧化应激增加有关。我们将获得基线和系列评估肺功能，外周血，呼出气冷凝物，和支气管肺泡灌洗液标本的HIV+和HIV-当前和以前的吸烟者或有风险的OLD。其他目的是2）比较HIV+和HIV-吸烟者中OLD进展的风险因素，和3）比较HIV+和HIV-吸烟者中OLD的氧化应激和进展的标志物。提出的研究有望增加我们对HIV+患者肺部疾病的理解，并产生可直接用于 改善病人护理。此外，深入了解易患老年痴呆症的原因， OLD的进展可以改善对HIV+和HIV-患者的护理。

DESCRIPTION (provided by applicant): 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 is 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.