World AIDS Day: 40 years of an evolving pulmonary landscape.
World AIDS Day: 40 years of an evolving pulmonary landscape.
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世界艾滋病日：40 年来肺部状况的演变。
DOI：
10.1152/ajplung.00457.2021
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Schnapp,LynnM
中科院分区：
文献类型：
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作者：
Crothers,Kristina;Schnapp,LynnM
随着SARS-CoV-2大流行的第二年接近尾声，我们反思另一种病毒感染，自它出现以来，估计已感染7900万人，并导致全世界3600万人死亡，即人类免疫缺陷病毒(艾滋病毒)(1)。在12月1日，我们纪念世界艾滋病日，也就是现在被确认为获得性免疫缺陷综合征(艾滋病)的第一例报告40年后。自艾滋病流行开始以来，肺部一直是终末器官损伤的主要目标，也是发病率和死亡率的主要原因。然而，这些肺部并发症的流行病学和谱系多年来一直在演变。作为肺部重症监护医生，我们共同见证了在抗逆转录病毒前疗法(ART)(2，3)中，旧金山护理艾滋病毒(PWH)患者的肺炎和其他机会性艾滋病相关并发症的早期激增，并在联合抗逆转录病毒治疗(ART)的早期，认识到这一人群中出现了慢性肺部疾病(CLDs)(4)。随着有效且毒性较低的抗逆转录病毒疗法提高了存活率，合并症的患病率有所增加，与未感染艾滋病毒的人群相比，在PWH患者中通常更常见(5)。与吸烟和衰老相关的慢性低密度脂蛋白现在是影响与健康相关的生活质量、功能状态和PWH死亡率的常见并存[6]。与死亡率增加显著相关的两种疾病是肺癌和慢性阻塞性肺疾病(COPD)，在许多独立于年龄、吸烟和肺部感染的研究中，这两种疾病在PWH中发生的频率都增加了(4，7)。慢性阻塞性肺疾病在慢性阻塞性肺疾病中可表现为肺气肿和慢性支气管炎。然而，最近的研究也发现哮喘和间质性肺异常的风险增加(6)。此外，在围产期感染艾滋病毒的青少年(8例)和结核病幸存者(9例)中，慢性肺病日益被认为是与结核病相关的肺部疾病。在这种不断发展的格局中，未来的工作需要更深入地了解如何预防和治疗威斯康星医院的这些慢性低密度脂蛋白。导致PWH中CLD的机制是多因素的，可能包括免疫、凋亡、蛋白分解和氧化应激途径的扰动(10)。在早期的研究中，艾滋病毒疾病的控制已被证明是一个重要的因素，因为发现肺功能损害的患病率和进展在pwh更严重，cd4细胞计数低于100cell/μL，而艾滋病毒病毒载量高于75,000拷贝/毫升(11)。抗逆转录病毒治疗开始前免疫功能受损的严重程度和持续的免疫功能障碍，表现为低的CD4/CD8比率(低于0.4)，也与CLD(12，13)有关。同样，研究表明，较低的CD4计数、较低的CD4/CD8比率和较高的HIV病毒载量与肺癌的发病率有关，这表明免疫抑制和免疫功能障碍有助于肺癌的发生(14)。持续的病毒库也可能影响慢性阻塞性肺疾病的发展。据报道，肺内的几种细胞群，包括T淋巴细胞、肺泡巨噬细胞和肺周细胞，是复制能力强的病毒的储存库，并导致持续的肺损伤(15，16)。随着全世界更多的人获得抗逆转录病毒治疗，并建议开始治疗而不考虑CD_4细胞数量，这些与未受控制的艾滋病毒疾病相关的机制有望得到缓解，尽管包括慢性阻塞性肺疾病在内的许多合并症在PWH中仍然更常见，即使更早地开始抗逆转录病毒治疗(5)。尽管艾滋病毒病毒抑制，艾滋病毒相关的慢性炎症，免疫激活与…
As the second year of the SARS-CoV-2 pandemic nears to a close, we reflect on another viral infection that has infected an estimated 79 million people and caused 36 million deaths worldwide since its advent, namely, human immunodeficiency virus (HIV)(1). On December 1, we commemorate World AIDS Day, 40 years after the first report of cases now recognized as acquired immunodeficiency syndrome (AIDS). From the beginning of the AIDS epidemic, the lungs have been a major target of end-organ injury and a chief cause of morbidity and mortality. However, the epidemiology and spectrum of these pulmonary complications have evolved over the years. As pulmonary critical care physicians, between us, we have witnessed the early surge of Pneumocystis pneumonia and other opportunistic AIDS-related complications caring for people with HIV (PWH) in San Francisco in the preantiretroviral therapy (ART)(2, 3) and recognized the emergence of chronic lung diseases (CLDs) in this population in the early combination ART era (4). As survival has improved with effective and less toxic ART, comorbidities have increased in prevalence and generally occur more commonly among PWH compared with populations without HIV (5). CLDs related to smoking and aging are now common comorbidities impacting healthrelated quality of life, functional status, and mortality of PWH (6). Two conditions that are significantly associated with increased mortality are lung cancer and chronic obstructive pulmonary disease (COPD), both occurring with increased frequency in PWH in many studies independent of age, smoking, and pulmonary infections (4, 7). COPD can present with features of emphysema and chronic bronchitis in PWH. However, recent studies also find increased risks of asthma and interstitial lung abnormalities (6). Additionally, CLD is increasingly recognized in adolescents who were perinatally infected with HIV (8) and in survivors of tuberculosis as post-tuberculosis-related lung disease (9). In this evolving landscape, future work requires a deeper understanding of how to prevent and treat these CLDs in PWH. The mechanisms leading to CLD in PWH are multifactorial and likely include perturbations in immune, apoptotic, proteolytic, and oxidative stress pathways (10). In earlier studies, HIV disease control has been shown to be a significant factor, as the prevalence and progression of lung function impairment were found to be greater in PWH with CD4 cell counts less than 100 cells/μL and HIV viral load above75,000 copies/mL (11). Severity of immunocompromise with lower nadir CD4 cell count before initiation of ART and ongoing immune dysfunction, reflected by a low CD4/CD8 ratio (below 0.4), is also associated with CLD (12, 13). Similarly, studies have shown that lower CD4 count, lower CD4/CD8 ratio, and higher HIV viral load are related to lung cancer incidence, indicating that immunosuppression and immune dysfunction contribute to lung cancer development (14). Persistent viral reservoirs may also impact development of CLD. Several cell populations within the lung, including T-lymphocytes, alveolar macrophages, and lung pericytes, have been reported to be reservoirs of replication-competent virus and contribute to ongoing lung injury (15, 16). With increased access to ART worldwide and recommendations to initiate treatment regardless of CD4 cell count, these mechanisms related to uncontrolled HIV disease will hopefully be mitigated, although many comorbidities including CLD remain more common among PWH even with earlier ART initiation (5).Despite HIV viral suppression, HIV-related chronic inflammation, immune activation …