Effects of Traffic Pollution on Lung Immunity and Pneumonia in Persons with HIV

描述(申请人提供)：世界卫生组织(WHO)估计，目前全球有3400万人感染艾滋病毒，北美有130万人感染。(1)肺炎仍然是艾滋病毒感染者发病和死亡的主要原因，众所周知，艾滋病毒感染会增加一些细菌、分枝杆菌、真菌和病毒肺部感染的易感性。(2-5)吸入污染物，如与交通有关的空气污染，可能会增加这些已经受到免疫抑制的人肺部感染的风险。因此，我们建议研究空气污染物对HIV感染者肺免疫功能和肺部感染易感性的影响。我们的总体假设是，与交通相关的空气污染(TRP)与风险增加有关 对于艾滋病毒感染者的肺部感染，这些吸入的污染物会降低肺泡巨噬细胞的吞噬功能。为了验证这一假设，我们将进行一项嵌套病例对照研究，以评估Trp暴露作为艾滋病毒感染者肺炎的预测因素(特定目标1)。与第二组健康的HIV阳性和阴性参与者一起，我们将进行一项横断面研究，以评估Trp对肺泡巨噬细胞吞噬功能的影响。我们将通过支气管镜和支气管肺泡灌洗(BAL)从每个参与者获得肺泡巨噬细胞(特定目标2)。更好地了解吸入污染物对肺部免疫和肺炎易感性的有害影响，对于预防免疫抑制患者的肺炎，以及通过更有效地管理有害空气污染物来更好地保护我们的弱势群体的政策制定，可能具有巨大的影响。

DESCRIPTION (provided by applicant): The World Health Organization (WHO) estimates that there are currently 34 million people infected with HIV worldwide and 1.3 million in North America.(1) Pneumonia remains a leading cause of morbidity and mortality in HIV-infected individuals, and it is well recognized that HIV infection increases susceptibility to a number of bacterial, mycobacterial, fungal and viral pulmonary infections.(2-5) Inhaled pollutants such as traffic-related air pollution may augment the risk of pulmonary infection in these already susceptible immunosuppressed individuals. Therefore we propose to study the effects of air pollutants on lung immunity and susceptibility to pulmonary infection in those with HIV. Our overall hypothesis is that traffic-related air pollution (TRP) is associated with an increased risk for pulmonary infections in HIV-infected individuals, and that these inhaled pollutants decrease alveolar macrophage phagocytosis. To test this hypothesis, we will perform a nested case-control study to evaluate TRP exposure as a predictor of pneumonia in HIV-infected persons (Specific Aim 1). With a second cohort of healthy HIV-positive and negative participants, we will perform a cross-sectional study to evaluate the effects of TRP on alveolar macrophage phagocytosis. We will obtain alveolar macrophages from each participant using bronchoscopy with bronchoalveolar lavage (BAL) (Specific Aim 2). A better understanding of the detrimental effects of inhaled pollutants on lung immunity and susceptibility to pneumonia could have immense implications in the prevention of pneumonia in immunosuppressed patients, and in policymaking to better protect our vulnerable populations with more effective regulation of harmful airborne pollutants.