Smoking cessation and the natural history of HIV-associated emphysema

描述(由申请人提供)： 据估计，艾滋病毒血清阳性人群中吸烟的流行率约为50%，是普通人群的两倍多。此外，艾滋病毒感染者似乎特别容易受到吸烟的不利影响。与这种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生之前，艾滋病毒血清阳性者患加速肺气肿的风险增加。这种风险似乎与吸烟易感性增加有关。鉴于艾滋病毒血清阳性人群的老龄化、吸烟在这一群体中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)可能很快就会在疾病负担方面使其他与艾滋病毒相关的肺部并发症相形见绌。在此背景下，当前提案的总体目标不仅是研究HAART时代艾滋病毒相关肺气肿的自然历史，而且调查这一自然历史是否可以改变。事实上，虽然许多研究人员强调了在艾滋病毒血清阳性者中戒烟的重要性，但令人惊讶的是，对这一领域的研究很少。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，我们将致力于实现以下具体目标： 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。 具体目的2：研究戒烟对HIV血清阳性人群肺功能下降、呼吸道症状发生率和肺气肿发生/发展的影响。 目的3：探讨戒烟对HIV血清阳性者肺泡巨噬细胞生物学特性的影响。 这项建议意义重大。首先，它将深入了解肺气肿在非常敏感的人群中的自然历史，促进我们对艾滋病毒相关肺部并发症和肺气肿过程的总体理解。更重要的是，该提案将开始解决戒烟方案在吸烟率极高的患者群体中的有效性。因此，本文获得的结果将具有重要和直接的临床意义。

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.