Longitudinal Studies of HIV-Associated Lung Infections and Complications

描述(由申请人提供)： 因为那些接受高度活跃治疗的艾滋病毒阳性(HIV+)患者的预期寿命增加了 抗逆转录病毒疗法(HAART)，吸烟引起的慢性并发症极大地增加了发病率和死亡率。我们已经证明，慢性阻塞性肺疾病(OLD)是一个重要的问题，在调整了吸烟和其他混杂因素后，与HIV阴性(HIV-)患者相比，OLD在HIV+患者中更常见。吸烟也是艾滋病毒中增加的其他疾病的风险因素，即肺癌、细菌性肺炎、结核病和肺孢子虫肺炎。我们假设HIV+患者对吸烟后果的易感性增加。吸烟和携带艾滋病毒的人可能更容易受到肺损伤，因为氧化应激增加，众所周知，氧化应激在艾滋病毒感染环境中以及在吸烟和老年人中都会增加。我们的第一个目标是1)比较HIV阳性患者和HIV阳性患者肺部疾病的发生率、危险因素和结局。我们将确定艾滋病毒感染导致肺部疾病的独立风险，以及肺部并发症的风险在多大程度上与吸烟或伴随的年龄有关。这些分析将在对艾滋病毒+和艾滋病毒受试者进行的一项正在进行的大型、多中心、前瞻性观察性研究中进行，该研究名为退伍军人老龄化队列研究，该研究最近获得了延续至2011年的资金。AIMS 2和AIMS 3的研究将深入研究一小部分受试者，以了解HIV+和HIV患者之间的老年临床和病理生理学差异。我们假设，与吸烟者相比，老年性痴呆在HIV+中进展得更快，而且这种加速进展与氧化应激增加有关。我们将获得HIV+和HIV阳性吸烟者以及有老年风险或有老年风险的既往吸烟者的肺功能、外周血、呼出的呼吸冷凝物和支气管肺泡灌洗标本的基线和系列评估。其他目的是2)比较HIV+和HIV吸烟者OLD进展的危险因素，以及3)比较HIV+和HIV吸烟者的氧化应激和OLD进展的标志物。建议的研究有望增加我们对HIV阳性患者肺部疾病的了解，并产生可直接用于 改善患者护理。此外，对易患老龄化和加速的原因的洞察 老年的进展可以改善对艾滋病毒阳性患者和艾滋病毒感染者的护理。

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.