Endothelial Activation, Innate Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction Among Adolescents Living With HIV.
Endothelial Activation, Innate Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction Among Adolescents Living With HIV.
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DOI：
10.1097/qai.0000000000002255
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发表时间：
2020-03-01
期刊：
影响因子：
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通讯作者：
Graham SM
中科院分区：
文献类型：
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作者：
Attia EF;Bhatraju PK;Triplette M;Kosamo S;Maleche-Obimbo E;West TE;Richardson BA;Zifodya JS;Eskander S;Njiru CD;Warui D;Kicska GA;Chung MH;Crothers K;Liles WC;Graham SM
慢性炎症、先天免疫激活、T细胞失衡和内皮细胞激活与肺部疾病有关。我们试图确定这些病理生理途径的标志物是否与艾滋病毒感染青少年（ALWH）的肺功能测定和胸部CT异常相关。肯尼亚内罗毕科普特希望传染病中心我们对ALWH（10-19岁）进行了横断面研究。参与者接受胸部CT、肺功能测定和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、抗逆转录病毒治疗和暴露数据。我们比较了气流阻塞的特征和生物标志物（使用支气管扩张剂后FEV 1/FVC z评分[zFEV 1/FVC] <-1.64）。我们使用多变量线性回归来确定log 10转换的生物标志物和胸部CT异常与支气管扩张剂后较低的zFEV 1/FVC（气流限制）的相关性。我们对生物标志物进行了探索性主成分分析，并确定了与支气管扩张剂后zFEV 1/FVC和胸部CT异常相关的因素。在47名肺量测定质量可接受的参与者中，21名（45%）为女性，中位年龄为13岁，96%患有围产期获得性HIV。中位CD 4为672个细胞/μL。总体而言，28%的患者有气流阻塞，78%的患者有胸部CT异常;气流阻塞与马赛克衰减相关（p=0.001）。较高的内皮激活（sVCAM-1，sICAM-1），炎症和先天免疫激活（SAA，斯特雷姆-1，sCD 163），T细胞失衡（较低的CD 4/CD 8）标志物与气流限制相关。包括内皮和先天性免疫激活的因素与气流限制有关。内皮激活、先天免疫激活、T细胞失衡和慢性炎症与气流限制和阻塞相关，为ALWH中慢性肺部疾病病理生理学提供了见解。
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 CT abnormalities among adolescents living with HIV (ALWH). Coptic Hope Center for Infectious Diseases in Nairobi, Kenya 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 (post-bronchodilator 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 post-bronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with post-bronchodilator zFEV1/FVC and chest CT abnormalities. 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 (SAA, 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. 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.