病毒性肺炎合并侵袭性肺真菌病的危险因素分析

doi:10.19982/j.issn.1000-6621.20240145

摘要/Abstract

摘要：

目的: 探讨病毒性肺炎合并侵袭性肺真菌病(invasive pulmonary mycosis,IPM)发病的相关危险因素。方法: 采用回顾性研究方法,选取2021年1月至2023年10月在山东第一医科大学附属中心医院住院的105例诊断为病毒性肺炎合并IPM的患者作为观察组;同时,按照1∶1比例选取同时期未合并IPM的病毒性肺炎患者105例作为对照组。收集并分析两组患者的社会人口学特征、临床表现、影像学表现及实验室检查结果等资料,采用logistic回归分析病毒性肺炎患者发生IPM的影响因素。结果: 观察组合并糖尿病、有恶性肿瘤病史、有胸腔积液、合并细菌感染,以及血清G试验阳性者分别占51.4%(54/105)、25.7%(27/105)、43.8%(46/105)、36.2%(38/105)、23.8%(25/105),对照组分别占35.2%(37/105)、6.7%(7/105)、19.0%(20/105)、13.3%(14/105)、2.9%(3/105),差异均有统计学意义(χ²=5.604,P=0.018;χ²=14.037,P<0.001;χ²=14.937,P<0.001;χ²=14.722,P<0.001;χ²=19.945,P<0.001)。多因素logistic回归分析显示,合并糖尿病[OR(95%CI):2.452(1.164~5.163)]、有恶性肿瘤病史[OR(95%CI):11.688(3.707~36.847)]、有胸腔积液[OR(95%CI):2.484(1.123~5.494)]、合并细菌感染[OR(95%CI):3.341(1.410~7.920)],以及血清G试验阳性[OR(95%CI):13.649(3.267~57.029)]是病毒性肺炎患者并发IPM的独立危险因素。结论: 对于确诊为病毒性肺炎的患者,应警惕其中合并糖尿病、有恶性肿瘤病史、有胸腔积液、合并细菌感染、血清G试验阳性者并发IPM的风险。

关键词: 肺炎,病毒性, 肺疾病,真菌性, 共病现象, 因素分析,统计学

Abstract:

Objective: To explore the related risk factors for the development of viral pneumonia combined with invasive pulmonary mycosis (IPM). Methods: Using a retrospective study method, 105 patients diagnosed with viral pneumonia combined with IPM who were hospitalized at the Affiliated Central Hospital of Shandong First Medical University from January 2021 to October 2023 were selected as the observation group; meanwhile, 105 patients with viral pneumonia who did not have IPM during the same period were selected as the control group in a 1∶1 ratio. The sociodemographic characteristics, clinical manifestations, imaging findings, and laboratory test results of the two groups were collected and analyzed. Logistic regression was used to analyze the influencing factors of IPM in patients with viral pneumonia. Results: In the observation group, 51.4% (54/105), 25.7% (27/105), 43.8% (46/105), 36.2% (38/105) and 23.8% (25/105) of the patients had diabetes, a history of malignant tumor, pleural effusion, bacterial infection, and a positive serum G test, respectively; In the control group, the corresponding figures were 35.2% (37/105), 6.7% (7/105), 19.0% (20/105), 13.3% (14/105), and 2.9% (3/105) respectively, and the differences were statistically significant (χ²=5.604, P=0.018; χ²=14.037, P<0.001; χ²=14.937, P<0.001; χ²=14.722, P<0.001; χ²=19.945, P<0.001). Multivariate logistic regression analysis showed that diabetes (OR(95%CI): 2.452 (1.164-5.163)), history of malignancy (OR(95%CI): 11.688 (3.707-36.847)), pleural effusion (OR(95%CI): 2.484 (1.123-5.494)), bacterial infection (OR(95%CI): 3.341 (1.410-7.920)), and positive serum G test (OR(95%CI): 13.649 (3.267-57.029)) were independent risk factors for the occurrence of IPM in patients with viral pneumonia. Conclusion: For patients diagnosed with viral pneumonia, attention should be paid to the risk of IPM in those with diabetes, a history of malignant tumor, pleural effusion, bacterial infection and a positive serum G test.

Key words: Pneumonia, viral, Lung Diseases, fungal, Comorbidity, Factor analysis, statistical

中图分类号:

R563

柴冬雨, 秦淑一, 张荣花, 邹楠楠, 王欣. 病毒性肺炎合并侵袭性肺真菌病的危险因素分析[J]. 中国防痨杂志, 2024, 46(7): 750-755. doi: 10.19982/j.issn.1000-6621.20240145

Chai Dongyu, Qin Shuyi, Zhang Ronghua, Zou Nannan, Wang Xin. Analysis of risk factors for viral pneumonia combined with invasive pulmonary mycosis[J]. Chinese Journal of Antituberculosis, 2024, 46(7): 750-755. doi: 10.19982/j.issn.1000-6621.20240145

图/表 6

表1

表2

表3

表4

表5

表6

病毒性肺炎患者合并侵袭性肺真菌病影响因素的多因素logistic回归分析

因素	β值	s $x ˉ$ 值	Wald χ²值	P值	OR(95%CI)值
合并冠心病	0.581	0.413	1.979	0.159	1.789(0.796~4.021)
合并糖尿病	0.897	0.380	5.568	0.018	2.452(1.164~5.163)
恶性肿瘤病史	2.459	0.586	17.611	<0.001	11.688(3.707~36.847)
呼吸困难	0.332	0.399	0.690	0.406	1.393(0.637~3.046)
肺干啰音	0.928	0.501	3.432	0.064	2.529(0.948~6.749)
肺湿啰音	0.418	0.393	1.128	0.288	1.518(0.702~3.282)
磨玻璃影	0.923	0.497	3.454	0.063	2.517(0.951~6.663)
胸腔积液	0.910	0.405	5.046	0.025	2.484(1.123~5.494)
淋巴结增大	-0.495	0.493	1.006	0.316	0.610(0.232~1.603)
合并细菌感染	1.206	0.440	7.505	0.006	3.341(1.410~7.920)
中性粒细胞百分比	0.004	0.048	0.007	0.934	1.004(0.914~1.102)
淋巴细胞百分比	0.016	0.056	0.080	0.777	1.016(0.911~1.133)
D-二聚体	0.065	0.051	1.602	0.206	1.067(0.965~1.180)
血清G试验阳性	2.614	0.730	12.835	<0.001	13.649(3.267~57.029)
常量	-3.681	4.478	0.676	0.411	0.025

表6

参考文献 17

[1]	Ruuskanen O, Lahti E, Jennings LC, et al. Viral pneumonia. Lancet, 2011, 377(9773):1264-1275. doi:10.1016/S0140-6736(10)61459-6. pmid: 21435708
[2]	Schauwvlieghe AFAD, Rijnders BJA, Philips N, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med, 2018, 6(10): 782-792. doi:10.1016/S2213-2600(18)30274-1. pmid: 30076119
[3]	Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med, 2019, 200(7): e45-e67. doi:10.1164/rccm.201908-1581ST.
[4]	中华医学会呼吸病学分会感染学组, 中华结核和呼吸杂志编辑委员会. 肺真菌病诊断和治疗专家共识. 中华结核和呼吸杂志, 2007, 30(11):821-834. doi:10.3760/j.issn:1001-0939.2007.11.008.
[5]	张国良, 瞿介明. 呼吸感染性疾病诊治年度进展2023. 中华结核和呼吸杂志, 2024, 47(2):141-146. doi:10.3760/cma.j.cn112147-20231117-00317.
[6]	Schwartz IS, Friedman DZP, Zapernick L, et al. High Rates of Influenza-Associated Invasive Pulmonary Aspergillosis May Not Be Universal: A Retrospective Cohort Study from Alberta, Canada. Clin Infect Dis, 2020, 71(7):1760-1763. doi:10.1093/cid/ciaa007. pmid: 31905235
[7]	Short KR, Kasper J, van der Aa S, et al. Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions. Eur Respir J, 2016, 47(3):954-966. doi:10.1183/13993003.01282-2015. pmid: 26743480
[8]	Herold S, Becker C, Ridge KM, et al. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J, 2015, 45(5):1463-1478. doi:10.1183/09031936.00186214. pmid: 25792631
[9]	Qin C, Zhou L, Hu Z, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis, 2020, 71(15):762-768. doi:10.1093/cid/ciaa248.
[10]	Feys S, Gonçalves SM, Khan M, et al. Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study. Lancet Respir Med, 2022, 10(12):1147-1159. doi:10.1016/S2213-2600(22)00259-4.
[11]	Ni H, Yu H, Lin Q, et al. Analysis of risk factors of fungal superinfections in viral pneumonia patients: A systematic review and meta-analysis. Immun Inflamm Dis, 2023, 11(1):e760. doi:10.1002/iid3.760.
[12]	Shi C, Shan Q, Xia J, et al. Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta-analysis. Mycoses, 2022, 65(2):152-163. doi:10.1111/myc.13410.
[13]	Lao M, Li C, Li J, et al. Opportunistic invasive fungal disease in patients with type 2 diabetes mellitus from Southern China: Clinical features and associated factors. J Diabetes Investig, 2020, 11(3):731-744. doi:10.1111/jdi.13183.
[14]	Azoulay E, Russell L, Van de Louw A, et al. Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med, 2020, 46(2):298-314. doi:10.1007/s00134-019-05906-5. pmid: 32034433
[15]	Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis, 2021, 21(6):e149-e162. doi:10.1016/S1473-3099(20)30847-1.
[16]	Wei H, Li Y, Han D, et al. The values of (1,3)-β-D-glucan and galactomannan in cases of invasive fungal rhinosinusitis. Am J Otolaryngol, 2021, 42(2):102871. doi:10.1016/j.amjoto.2020.102871.
[17]	Verweij PE, Rijnders BJA, Brüggemann RJM, et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. Intensive Care Med, 2020, 46(8):1524-1535. doi:10.1007/s00134-020-06091-6. pmid: 32572532

特征	观察组(105例)	对照组(105例)	统计检验值	P值
性别[例(构成比,%)]			χ²=0.019	0.890
男性	57(54.3)	58(55.2)
女性	48(45.7)	47(44.8)
年龄[岁,M(Q₁,Q₃)]	77(67,85)	72(62,83)	Z=-1.800	0.072
吸烟史[例(构成比,%)]			χ²=0.476	0.490
有	23(21.9)	19(18.1)
无	82(78.1)	86(81.9)
饮酒史[例(构成比,%)]			χ²=1.000	0.317
有	12(11.4)	17(16.2)
无	93(88.6)	88(83.8)

特征	观察组(105例)	对照组(105例)	χ²值	P值
基础疾病
高血压	60(57.1)	57(54.3)	0.174	0.677
冠心病	35(33.3)	22(21.0)	4.069	0.044
糖尿病	54(51.4)	37(35.2)	5.604	0.018
脑血管病	36(34.3)	27(25.7)	1.837	0.175
慢性阻塞性肺疾病	13(12.4)	6(5.7)	2.835	0.092
激素应用史	4(3.8)	2(1.9)	0.686	0.683
恶性肿瘤病史	27(25.7)	7(6.7)	14.037	<0.001
慢性肾脏疾病	5(4.8)	3(2.9)	0.520	0.721
免疫抑制剂应用史	1(1.0)	1(1.0)	0.000	1.000
临床症状
咳嗽/咳痰	99(94.3)	100(95.2)	0.096	0.757
发热	100(95.2)	95(90.5)	1.795	0.180
胸闷/胸痛	20(19.0)	23(21.9)	0.263	0.608
呼吸困难	65(61.9)	42(40.0)	10.080	0.001
咯血	4(3.8)	2(1.9)	0.686	0.683
体征
肺部干啰音	30(28.6)	12(11.4)	9.643	0.002
肺部湿啰音	74(70.5)	45(42.9)	16.309	<0.001

影像特征	观察组(105例)	对照组(105例)	χ²值	P值
结节	30(28.6)	28(26.7)	0.095	0.758
单叶	13(12.4)	14(13.3)	0.043	0.837
多叶	17(16.2)	12(11.4)	1.000	0.317
实变	14(13.3)	15(14.3)	0.040	0.841
单叶	5(4.8)	6(5.7)	0.096	0.757
多叶	9(8.6)	9(8.6)	0.000	1.000
磨玻璃影	93(88.6)	76(72.4)	8.759	0.003
单叶	15(14.3)	12(11.4)	0.383	0.536
多叶	78(74.3)	64(61.0)	4.263	0.039
胸腔积液	46(43.8)	20(19.0)	14.937	<0.001
单侧	8(7.6)	4(3.8)	1.414	0.373
双侧	38(36.2)	16(15.2)	12.066	0.001
淋巴结增大	26(24.8)	13(12.4)	5.322	0.021

指标	观察组(105例)	对照组(105例)	统计检验值	P值
合并细菌感染[例(感染率,%)]	38(36.2)	14(13.3)	χ²=14.722	<0.001
白细胞计数[×10⁹/L,M(Q₁,Q₃)]	7.00(4.33,10.27)	6.69(5.03,9.01)	Z=-0.035	0.972
中性粒细胞百分比[%,M(Q₁,Q₃)]	81.00(72.90,89.15)	76.70(65.35,85.00)	Z=-2.611	0.009
淋巴细胞百分比[%,M(Q₁,Q₃)]	10.70(5.60,18.00)	15.30(8.90,23.95)	Z=-2.774	0.006
C反应蛋白[mg/L,M(Q₁,Q₃)]	47.84(15.30,87.10)	33.45(9.83,68.43)	Z=-1.902	0.057
降钙素原[ng/ml,M(Q₁,Q₃)]	0.11(0.04,0.39)	0.09(0.04,0.21)	Z=-1.063	0.288
D-二聚体[mg/L,M(Q₁,Q₃)]	1.61(1.01,3.10)	1.05(0.59,1.44)	Z=-5.137	<0.001
血清G试验阳性[例(阳性率,%)]	25(23.8)	3(2.9)	χ²=19.945	<0.001

变量	赋值	变量	赋值
合并冠心病	是=1,否=0	胸腔积液	是=1,否=0
合并糖尿病	是=1,否=0	淋巴结增大	是=1,否=0
恶性肿瘤病史	是=1,否=0	合并细菌感染	是=1,否=0
呼吸困难	是=1,否=0	中性粒细胞百分比	原值代入
肺干啰音	是=1,否=0	淋巴细胞百分比	原值代入
肺湿啰音	是=1,否=0	D-二聚体	原值代入
磨玻璃影	是=1,否=0	血清G试验阳性	是=1,否=0