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通过宏基因组学下一代测序诊断的非HIV免疫功能低下肺孢子菌肺炎患者的特征及预后因素

Characteristics and Prognostic Factors of Non-HIV Immunocompromised Patients With Pneumocystis Pneumonia Diagnosed by Metagenomics Next-Generation Sequencing.

作者信息

Duan Jiali, Gao Jing, Liu Qiuhong, Sun Mengfei, Liu Yang, Tan Yingshuai, Xing Lihua

机构信息

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Med (Lausanne). 2022 Mar 3;9:812698. doi: 10.3389/fmed.2022.812698. eCollection 2022.

Abstract

OBJECTIVE

The aim of this study was to evaluate the potential of metagenomic next-generation sequencing (mNGS) for the diagnosis of pneumocystis pneumonia (PCP) in patients with non-human immunodeficiency virus-infection and to discuss the clinical characteristics and identify prognostic factors associated with patients with non-HIV PCP.

METHODS

Forty-six patients with PCP who were admitted in respiratory intensive care unit (ICU) between May 2018 and May 2020 were retrospectively reviewed. The subjects were divided into survivor and non-survivor groups according to the patients' outcome. Conventional methods and mNGS for detecting were analyzed. The patients' demographics, comorbidities, laboratory parameters, and treatments were compared and evaluated in both groups to identify risk factors for mortality by using univariate and multivariate logistic regression.

RESULTS

Metagenomic next-generation sequencing (mNGS) showed a satisfying diagnostic performance of 100% positive of detecting from bronchoalveolar lavage (BAL) specimens in forty-six patients with non-HIV PCP, compared to only 15.2% for Gomori Methenamine silver (GMS) staining and 84.8% for Serum 1,3-beta-D-glucan (BDG). Among them, the mean age was 46.4-year-old (range 18-79-year-old) and mortality rate was 43.5%. The dominant underlying conditions were connective tissue diseases (34.8%), autoimmune kidney diseases (30.4%), followed by hematologic malignancies (10.9%), and solid organ transplantation (6.5%). A total of 38 cases (82.6%) received glucocorticoid and 19 cases (41.3%) used immunosuppressant within 3 months before diagnosed PCP. Multiple infections were very common, over two thirds' cases had mixed infections. Compared with survivors, non-survivors had a higher acute physiology and chronic health evaluation II (APACHE II) score (14.4 ± 4.8 vs. 10 ± 3.4), Procalcitonin (PCT) [ng/ml: 0.737 (0.122-1.6) vs. 0.23 (0.095-0.35)], lactic dehydrogenase (LDH) [U/L: 1372 (825.5-2150) vs. 739 (490.5-956)], and neutrophil-lymphocyte ratio (NLR) [21.6 (15.67-38.2) vs. 11.75 (5.1-15.52)], but had a lower PaO/FiO ratio (mmHg:108.8 ± 42.4 vs. 150.5 ± 47.5), lymphocytes [×10/L: 0.33 (0.135-0.615) vs. 0.69 (0.325-1.07)] and CD4+ T cells [cell/μl: 112 (53.5-264) vs. 255 (145-303.5)], all < 0.05. Furthermore, we found non-survivors' PaO/FiO ratio of day 3 and day 7 had not improved when compared with that of day one, and platelet level and NLR became worse. Multivariate analysis showed that other pathogens' co-infection (OR = 9.011, 95% CI was 1.052-77.161, = 0.045) and NLR (OR = 1.283, 95% CI was 1.046-1.547, = 0.017) were the independent risk factors of poor prognosis.

CONCLUSION

mNGS is a very sensitive diagnostic tool for identifying in patients who are non-HIV immunocompromised. PCP in patients who are non-HIV infected is associated with a high rate of multiple infections and severe condition. Mixed infection and elevation of NLR were the independent risk factors of poor prognosis.

摘要

目的

本研究旨在评估宏基因组下一代测序(mNGS)在非人类免疫缺陷病毒感染患者中诊断肺孢子菌肺炎(PCP)的潜力,并探讨非HIV-PCP患者的临床特征及确定其预后相关因素。

方法

回顾性分析2018年5月至2020年5月间收治于呼吸重症监护病房(ICU)的46例PCP患者。根据患者结局将其分为存活组和非存活组。分析检测的传统方法和mNGS。比较并评估两组患者的人口统计学特征、合并症、实验室参数及治疗情况,采用单因素和多因素逻辑回归分析确定死亡危险因素。

结果

宏基因组下一代测序(mNGS)对46例非HIV-PCP患者支气管肺泡灌洗(BAL)标本检测的诊断性能令人满意,检测阳性率达100%,相比之下,戈莫里甲胺银(GMS)染色仅为15.2%,血清1,3-β-D-葡聚糖(BDG)为84.8%。其中,患者平均年龄为46.4岁(范围18 - 79岁),死亡率为43.5%。主要基础疾病为结缔组织病(34.8%)、自身免疫性肾病(30.4%),其次为血液系统恶性肿瘤(10.9%)和实体器官移植(6.5%)。共有38例(82.6%)患者在诊断PCP前3个月内接受了糖皮质激素治疗,19例(41.3%)使用了免疫抑制剂。多重感染非常常见,超过三分之二的病例存在混合感染。与存活者相比,非存活者的急性生理与慢性健康状况评分II(APACHE II)更高(14.4±4.8 vs. 10±3.4)、降钙素原(PCT)[ng/ml:0.737(0.122 - 1.6)vs. 0.23(0.095 - 0.35)]、乳酸脱氢酶(LDH)[U/L:1372(825.5 - 2150)vs. 739(490.5 - 956)]及中性粒细胞与淋巴细胞比值(NLR)[21.6(15.67 - 38.2)vs. 11.75(5.1 - 15.52)]更高,但动脉血氧分压/吸氧浓度比值(PaO/FiO)更低(mmHg:108.8±42.4 vs. 150.5±47.5)、淋巴细胞[×10⁹/L:0.33(0.135 - 0.615)vs. 0.69(0.325 - 1.07)]及CD4⁺T细胞[cell/μl:112(53.5 - 264)vs. 255(145 - 303.5)]更低,差异均<0.05。此外,我们发现非存活者第3天和第7天的PaO/FiO比值与第1天相比未改善,且血小板水平和NLR变差。多因素分析显示,其他病原体合并感染(OR = 9.011,95%CI为1.052 - 77.161,P = 0.045)和NLR(OR = 1.283,95%CI为1.046 - 1.547,P = 0.017)是预后不良的独立危险因素。

结论

mNGS是用于识别非HIV免疫受损患者中肺孢子菌的非常敏感的诊断工具。非HIV感染患者的PCP与多重感染率高及病情严重有关。混合感染和NLR升高是预后不良的独立危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f24e/8928194/d1ca39d3dba6/fmed-09-812698-g0001.jpg

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