炎症和免疫激活标志物与 HIV 感染者多中心队列的肺功能相关。
Markers of inflammation and immune activation are associated with lung function in a multi-center cohort of persons with HIV.
机构信息
Division of HIV, Infectious Diseases and Global Medicine.
Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
出版信息
AIDS. 2021 Jun 1;35(7):1031-1040. doi: 10.1097/QAD.0000000000002846.
OBJECTIVES
Studies have shown that people with HIV (PWH) may be at increased risk for chronic lung diseases and lung function abnormalities, which may be associated with immune activation. We tested the association of a panel of 12 immune activation and inflammation biomarkers with spirometry and single-breath diffusing capacity for carbon monoxide (DLco).
DESIGN
Cross-sectional, observational study.
METHODS
Participants were enrolled from the Inflammation, Aging, Microbes and Obstructive Lung Disease cohort of PWH at two US sites. Biomarkers were examined and standardized spirometry and DLco testing were performed. We tested associations between each biomarker and lung function, examined individually and in combination, using multi-variable linear and logistic regression.
RESULTS
Among 199 participants, median forced expiratory volume in 1 s (FEV1) was normal (90% predicted) and median DLco was abnormal (69% predicted). The most common lung function abnormality (57%) was a normal FEV1 to forced vital capacity ratio with an abnormal DLco of 80% or less predicted (iso↓DLco). Two markers (IL-6, high-sensitivity C-reactive protein) were associated with FEV1% predicted, whereas eight markers (soluble CD14, soluble CD163, inducible protein-10, soluble CD27, IL-6, soluble tumor necrosis factor receptors 1 and 2, D-dimer) were associated with DLco% predicted. Compared with those participants with normal spirometry and DLco, five markers (soluble CD14, soluble CD163, interferon gamma inducible protein-10, soluble tumor necrosis factor receptors 1 and 2) were associated with iso↓DLco.
CONCLUSION
Among PWH, different markers of immune activation and inflammation are associated with FEV1% predicted than with DLco% predicted and with an iso↓DLco, representing possible unique pathways of chronic lung disease. Identifying plausible drivers of these inflammatory pathways may clarify mechanisms underlying impaired lung function in HIV infection and may identify therapeutic avenues.
目的
研究表明，艾滋病毒（HIV）感染者（PWH）可能患慢性肺部疾病和肺功能异常的风险增加，这可能与免疫激活有关。我们检测了一组 12 种免疫激活和炎症生物标志物与肺活量测定和一氧化碳单呼吸弥散量（DLco）之间的关联。
设计
横断面观察性研究。
方法
在两个美国地点的 HIV 感染者炎症、衰老、微生物和阻塞性肺部疾病队列中招募参与者。检查了生物标志物并进行了标准化肺活量测定和 DLco 检测。我们使用多变量线性和逻辑回归分别和联合检测了每个生物标志物与肺功能之间的关系。
结果
在 199 名参与者中，用力呼气量 1 秒（FEV1）中位数正常（预测值的 90%），DLco 中位数异常（预测值的 69%）。最常见的肺功能异常（57%）是正常 FEV1 与用力肺活量比值与预测值 80%或更低的异常 DLco（iso↓DLco）。有两个标志物（IL-6、高敏 C 反应蛋白）与 FEV1%预测值相关，而有八个标志物（可溶性 CD14、可溶性 CD163、诱导蛋白-10、可溶性 CD27、IL-6、可溶性肿瘤坏死因子受体 1 和 2、D-二聚体）与 DLco%预测值相关。与正常肺量计和 DLco 的参与者相比，有五个标志物（可溶性 CD14、可溶性 CD163、干扰素γ诱导蛋白-10、可溶性肿瘤坏死因子受体 1 和 2）与 iso↓DLco 相关。
结论
在 HIV 感染者中，不同的免疫激活和炎症标志物与 FEV1%预测值的相关性大于与 DLco%预测值的相关性，与 iso↓DLco 相关，代表慢性肺部疾病的可能独特途径。确定这些炎症途径的合理驱动因素可能有助于阐明 HIV 感染中肺功能受损的机制，并可能确定治疗途径。
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