Smoking cessation and the natural history of HIV-associated emphysema

描述（由申请人提供）： 艾滋病毒血清反应阳性人群中吸烟的估计流行率约为50%，是一般人群的两倍多。此外，艾滋病毒感染者似乎特别容易受到吸烟的不利影响。与RFA特别相关的是令人信服的证据，即在艾滋病相关肺部并发症发作之前，HIV血清阳性个体发生加速性肺气肿的风险增加。这种风险似乎与对香烟烟雾的敏感性增加有关。鉴于艾滋病毒血清阳性人群的老龄化，这一群体中吸烟的高流行率，以及吸烟相关肺损伤的风险增加，慢性阻塞性肺疾病（COPD）可能很快就会使其他艾滋病毒相关肺部并发症在疾病负担方面相形见绌。在此背景下，当前提案的总体目标不仅是检查HAART时代HIV相关肺气肿的自然史，而且要调查是否可以改变这种自然史。事实上，虽然许多研究人员强调了戒烟对艾滋病毒血清阳性个体的重要性，但对这一领域的研究却少得惊人。目前的建议将从症状、生理和生物学角度研究戒烟对艾滋病毒相关肺气肿病程的影响。因此，我们将追求以下具体目标： 具体目标1：开发和评估一种专门的戒烟干预措施，用于治疗HIV血清阳性吸烟者的尼古丁依赖。 具体目标二：在一组HIV血清阳性个体中，研究戒烟对肺功能下降过程、呼吸道症状患病率和肺气肿发生/进展的影响。 具体目标3：探讨戒烟对从HIV血清阳性个体获得的肺泡巨噬细胞生物学的影响。 这一建议意义重大。开始，它将揭示肺气肿的自然史在一个非常敏感的人群，推进我们的理解艾滋病毒相关的肺部并发症和肺气肿的过程中的一般。更重要的是，该提案将开始讨论戒烟方案在吸烟率极高的患者人群中的疗效。因此，本文获得的结果将具有重要和直接的临床相关性。

DESCRIPTION (provided by applicant): The estimated prevalence of cigarette smoking in the HIV-seropositive population is ~ 50%, over double that in the general population. Furthermore, persons infected with HIV appear to be especially susceptible to the adverse effects of cigarette smoking. Of particular relevance to this RFA is convincing evidence that prior to the onset of AIDS-related pulmonary complications, HIV-seropositive individuals are at increased risk of developing accelerated emphysema. This risk appears to be related to an increased susceptibility to cigarette smoke. In light of the aging of the HIV-seropositive population, the high prevalence of cigarette smoking in this group, and it's increased risk of smoking related lung damage, it is possible that chronic obstructive pulmonary disease (COPD) will soon dwarf other HIV-related pulmonary complications in terms of disease burden. With this as a background, the overall objective of the current proposal is to not merely examine the natural history of HIV-related emphysema in the HAART era, but to investigate whether that natural history can be altered. Indeed, while numerous investigators have highlighted the importance of smoking cessation in HIV-seropositive individuals, there is strikingly little research into this area. The current proposal will study the effect of smoking cessation on the course of HIV-associated emphysema from the symptomatic, physiologic and biologic perspective. As such, we will pursue the following specific aims: Specific Aim 1: To develop and evaluate a specialized smoking cessation intervention for the treatment of nicotine dependence in HIV-seropositive smokers. Specific Aim 2: To examine the effects of smoking cessation on the course of lung function decline, the prevalence of respiratory symptoms and the occurrence/progression of emphysema in a cohort of HIV- seropositive individuals. Specific Aim 3: To explore the effects of smoking cessation on the biology of alveolar macrophages obtained from HIV-seropositive individuals. This proposal is highly significant. To begin with, it will shed insight into the natural history of emphysema in a very susceptible population, advancing our understanding of HIV-related pulmonary complications and the emphysema process in general. More importantly, the proposal will begin to address the efficacy of a smoking cessation regimen in a patient population with an extremely high smoking prevalence. As such, the results obtained herein will have important and immediate clinical relevance.