Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS One. 2013;8(2):e56249. doi: 10.1371/journal.pone.0056249. Epub 2013 Feb 15.
Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.
We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls.
Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm(3). Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively).
In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.
尽管在 HIV 治疗方面取得了进展,但细菌性肺炎仍在导致 HIV 感染患者出现相当大的发病率和死亡率。目前尚无研究探讨生物标志物与接受治疗的 HIV 感染患者发生细菌性肺炎风险之间的关联。
我们在管理抗逆转录病毒治疗策略试验中进行了一项嵌套、匹配、病例对照研究,该试验将参与者随机分配至持续联合抗逆转录病毒治疗(cART)组。发生细菌性肺炎(病例)和未发生细菌性肺炎(对照)的患者按照临床中心、吸烟状况、年龄和基线 cART 使用情况进行 1:1 匹配。比较病例和对照者之间的血清 16 型克拉细胞蛋白(CC16)、表面活性蛋白 D(SP-D)、C 反应蛋白(hsCRP)、白细胞介素-6(IL-6)和 D-二聚体的基线水平。
病例(n=72)和对照(n=72)患者的性别比例分别为 25.7%为女性,51.4%为黑人,65.3%为当前吸烟者,9.7%为糖尿病患者,36.1%为乙型/丙型肝炎合并感染,75.0%在基线时接受 cART 治疗。中位(IQR)年龄为 45(41,51)岁,CD4+计数为 553(436,690)个细胞/mm3。病例和对照者之间的基线 CC16 和 SP-D 无显著差异,但病例者的 hsCRP 显著高于对照者(2.94µg/mL 比 1.93µg/mL;p=0.02)。与对照者相比,病例者的 IL-6 和 D-二聚体水平也更高,尽管差异无统计学意义(p 值分别为 0.06 和 0.10)。
在接受 cART 治疗的 HIV 感染患者中,较高水平的全身性炎症标志物与细菌性肺炎风险增加相关,而两种肺特异性炎症生物标志物 CC16 和 SP-D 与细菌性肺炎风险无关。