The Study of HIV Infection in the Etiology of Lung Disease (SHIELD)

描述(由申请人提供)： 随着高效抗逆转录病毒疗法(HAART)的引入和艾滋病毒感染者存活率的提高，非传染性肺部疾病被认为是致病和死亡的原因。有限的证据表明，艾滋病毒感染者可能更容易患上肺气肿。已经观察到艾滋病毒感染增加了肺癌风险；我们已经证明，在对艾滋病毒感染者中大量使用烟草进行控制后，这种风险仍然存在。艾滋病毒感染被认为是肺动脉高压的独立危险因素；然而，对其流行率和临床表现的准确描述仍然难以捉摸。为了解决这些问题，我们提出了Shield：肺部疾病病因学中艾滋病毒感染的研究，这是一项针对艾滋病毒感染者肺部疾病的合作和系统调查，嵌套在马里兰州巴尔的摩正在进行的三项艾滋病毒队列研究中。我们的具体目标包括：1)确定HIV感染者中慢性阻塞性肺疾病(COPD)的患病率、临床表现和危险因素。前瞻性评估将确定艾滋病毒感染、免疫缺陷、HAART的使用、肺部感染、吸烟和非法药物使用对肺功能衰退率和相关发病率和死亡率的影响；2)确定艾滋病毒感染者中肺癌的发生率、临床表现、危险因素和机制；3)确定艾滋病毒感染者中肺动脉高压(PAH)的患病率、临床表现和危险因素。我们艾滋病毒队列的集体经验跨越了20多年，包括对11,000多名参与者的跟踪调查；对4,000多名艾滋病毒感染者的积极跟踪可纳入COPD、肺癌和PAH的重点研究。Shield代表了一个具有多学科专业知识的研究人员联盟，涉及肺部医学、艾滋病毒和传染病、外科肿瘤学、流行病学和生物统计学、翻译成像技术、免疫学和基础科学。鉴于已建立的合作研究团队、现有的大量资源和基础设施以及我们科学方法的力量，我们预计在确定艾滋病毒感染中的非传染性肺部疾病特征方面取得成功的可能性很高，并有助于更好地了解相关机制。

DESCRIPTION (provided by applicant): Following the introduction of highly active antiretroviral therapy (HAART) and improved survival among HIV-infected persons, non-infectious lung diseases are hypothesized to increase as causes of morbidity and mortality. Limited evidence suggests that HIV-infected persons may be more susceptible to development of emphysema. An increase in lung cancer risk has been observed with HIV infection; we have demonstrated that this risk persists after controlling for heavy tobacco use, among HIV-infected persons. HIV infection is recognized as an independent risk factor for pulmonary hypertension; however accurate characterization of the prevalence and clinical manifestations remains elusive. To address these issues, we propose SHIELD: The Study of HIV Infection in the Etiology of Lung Disease, a collaborative and systematic investigation of lung disease among HIV-infected persons nested within three on-going HIV cohort studies in Baltimore, MD. Our specific aims include: 1) to determine the prevalence, clinical manifestations, and risk factors for chronic obstructive pulmonary disease (COPD) among HIV-infected persons. Prospective evaluation will characterize the effect of HIV infection, immune deficiency, HAART use, pulmonary infections, smoking, and illicit drug use on rates of decline in lung function and on related morbidity and mortality; 2) To determine incidence rates, clinical manifestations, risk factors, and mechanisms for lung cancer among HIV-infected persons, and 3) To determine the prevalence, clinical manifestations, and risk factors for pulmonary arterial hypertension (PAH) among HIV-infected persons. The collective experience of our HIV cohorts spans well over two decades and includes follow-up on more than 11,000 participants; active follow-up of over 4,000 HIV-infected persons are available for inclusion in focused studies of COPD, lung cancer, and PAH. SHIELD represents a consortium of investigators with multidisciplinary expertise in pulmonary medicine, HIV and infectious diseases, surgical oncology, epidemiology and biostatistics, translational imaging techniques, immunology and basic sciences. Given the established collaborative research team, the substantive existing resources and infrastructure, and the strength of our scientific methods, we anticipate a high likelihood of success in characterizing non-infectious lung disease in HIV infection and contributing to an improved understanding of mechanisms involved.