内皮细胞激活、固有免疫激活和炎症与感染HIV的青少年支气管扩张剂后气流受限及阻塞相关。

Endothelial Activation, Innate Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction Among Adolescents Living With HIV.

作者信息

Attia Engi F, Bhatraju Pavan K, Triplette Matthew, Kosamo Susanna, Maleche-Obimbo Elizabeth, West Timothy Eoin, Richardson Barbra A, Zifodya Jerry S, Eskander Sherry, Njiru Christine D, Warui Danson, Kicska Gregory A, Chung Michael H, Crothers Kristina, Liles Wayne Conrad, Graham Susan M

机构信息

Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA.

International Respiratory and Severe Illness Center, University of Washington, Seattle, WA.

出版信息

J Acquir Immune Defic Syndr. 2020 Mar 1;83(3):267-277. doi: 10.1097/QAI.0000000000002255.

DOI:10.1097/QAI.0000000000002255

PMID:32032277

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7735385/

Abstract

BACKGROUND

Chronic inflammation, innate immune activation, T-cell imbalance and endothelial activation have been linked with lung diseases. We sought to determine whether markers of these pathophysiologic pathways were associated with spirometry and chest computed tomography (CT) abnormalities among adolescents living with HIV (ALWH).

SETTING

Coptic Hope Center for Infectious Diseases in Nairobi, Kenya.

METHODS

We performed a cross-sectional study of ALWH (10-19 years old). Participants underwent chest CT, spirometry, and venipuncture for serum biomarkers. We also collected demographic, anthropometric, T-cell subset, antiretroviral therapy, and exposure data. We compared characteristics and biomarkers by airflow obstruction [postbronchodilator FEV1/FVC z-score (zFEV1/FVC) < -1.64]. We used multivariable linear regression to determine associations of log10-transformed biomarkers and chest CT abnormalities with lower postbronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with postbronchodilator zFEV1/FVC and chest CT abnormalities.

RESULTS

Of 47 participants with acceptable quality spirometry, 21 (45%) were female, median age was 13 years and 96% had perinatally-acquired HIV. Median CD4 was 672 cells/µL. Overall, 28% had airflow obstruction and 78% had a chest CT abnormality; airflow obstruction was associated with mosaic attenuation (P = 0.001). Higher endothelial activation (sVCAM-1, sICAM-1), inflammation and innate immune activation (serum amyloid-A, sTREM-1, sCD163), and T-cell imbalance (lower CD4/CD8) markers were associated with airflow limitation. Factors comprising endothelial and innate immune activation were associated with airflow limitation.

CONCLUSIONS

Endothelial activation, innate immune activation, T-cell imbalance, and chronic inflammation are associated with airflow limitation and obstruction, providing insights into chronic lung disease pathophysiology among ALWH.

摘要

背景

慢性炎症、固有免疫激活、T细胞失衡及内皮激活与肺部疾病相关。我们试图确定这些病理生理途径的标志物是否与感染HIV的青少年（ALWH）的肺功能测定及胸部计算机断层扫描（CT）异常有关。

地点

肯尼亚内罗毕的科普特希望传染病中心。

方法

我们对ALWH（10 - 19岁）进行了一项横断面研究。参与者接受了胸部CT、肺功能测定及静脉穿刺以检测血清生物标志物。我们还收集了人口统计学、人体测量学、T细胞亚群、抗逆转录病毒治疗及暴露数据。我们根据气流受限情况[支气管扩张剂后FEV1/FVC z评分（zFEV1/FVC）< -1.64]比较了特征及生物标志物。我们使用多变量线性回归来确定经log10转换的生物标志物及胸部CT异常与支气管扩张剂后较低的zFEV1/FVC（气流受限）之间的关联。我们对生物标志物进行了探索性主成分分析，并确定了各因素与支气管扩张剂后zFEV1/FVC及胸部CT异常之间的关联。

结果

在47名肺功能测定质量合格的参与者中，21名（45%）为女性，中位年龄为13岁，96%通过母婴传播感染HIV。CD4细胞计数中位数为672个/µL。总体而言，28%存在气流受限，78%有胸部CT异常；气流受限与马赛克样衰减相关（P = 0.001）。较高的内皮激活（可溶性血管细胞黏附分子-1、可溶性细胞间黏附分子-1）、炎症及固有免疫激活（血清淀粉样蛋白A、可溶性髓系细胞触发受体-1、可溶性CD163）以及T细胞失衡（较低的CD4/CD8）标志物与气流受限相关。包括内皮及固有免疫激活的因素与气流受限相关。