非移植患者侵袭性肺曲霉病32例临床特征分析

doi:10.3877/cma.j.issn.1674-6902.2023.06.013

目的

分析非移植患者侵袭性肺曲霉病(invasive pulmonary aspergillosis, IPA)的临床特征与治疗。

方法

回顾性分析2015年1月至2021年8月我院住院治疗的32例侵袭性肺曲霉病的临床表现、微生物学检查、胸部影像学、诊治经过及转归等。

结果

经过临床检查，3例确诊，27例临床诊断，2例拟诊。继发性侵袭性肺曲霉病31例，原发性侵袭性肺曲霉病1例，其中基础肺部疾病20例(62.5%)和应用糖皮质激素10例(31.3%)是最常见的基础疾病和危险因素。主要临床表现为咳嗽、咳痰30例(93.8%)、呼吸困难25例(78.1%)、发热16例(50.0%)和肺部啰音23例(71.8%)。胸部CT平扫以斑片影31例(96.8%)、实变影21例(65.6%)、结节影20例(62.5%)及空洞影15例(46.8%)最常见。血清G试验28例，阳性19例(67.9%)和GM试验16例，其中阳性11例(68.7%)，16例(50.0%)痰培养阳性中，以黄曲霉、烟曲霉常见。患者接受伏立康唑、两性霉素B及其脂质复合体、卡泊芬净单药或联合治疗，总疗程约8～12周，住院时间平均为20.5 d，共治愈8例，好转14例，无效4例，死亡6例。

结论

非移植患者侵袭性肺曲霉病病情凶险，临床表现缺乏特异性，临床怀疑时，尽早完善微生物学等检查，及时进行分层诊断和治疗，以改善IPA患者的预后。

关键词: 侵袭性肺曲霉病, 诊断/治疗, 临床特征

Objective

To describe the characteristics and management of non-transplant patients with invasive pulmonary aspergillosis (IPA).

Methods

The clinical manifestation, microbiological examination, chest imaging, diagnosis, treatment and outcomes of 32 non-transplant patients with IPA from Capital Medical University Affiliated Beijing Anzhen Hospital from January 2015 to August 2021 were retrospectively collected and described.

Results

3 cases fulfilled the criteria of proven IPA, 27 of probable an 2 of possible IPA, and among the 32 patients. One case was primary IPA, and 31 cases were secondary IPA, among which chronic pulmonary diseases 20 cases(62.5%) and uses of glucocorticoid 10 cases(31.3%) were the most common basic diseases and risk factors. The main clinical manifestations included cough 30 cases(93.8%), sputum production 30 cases(93.8%), dyspnea 25 cases(78.1%), fever 16 cases(50.0%) and lung rales 23 cases(71.8%). The chest imaging mainly included patchy infiltrates 31 cases(96.8%), consolidation 21 cases(65.6%), nodules 20 cases(62.5%) and cavities 15 cases(46.8%). 28 cases with glucan(G)test, 19 cases positive plasme(67.9%). 16 cases with plasma galactomannan (GM) test, positive 11 cases(68.7%). 16 cases positive sputum cultures(50%), which mainly included Aspergillosis flavus and Aspergillosis fumigatus. All patients received Voriconazole, Amphotericin B, Amphotericin B Liposome and Caspofungin Acetate therapy alone or in combination and the total course of treatment was about 8-12 weeks. The mean length of stay was 20.5 days (2~123 days). 8 cases were cured, 14 cases improved, 4 cases failed and 6 cases died.

Conclusions

IPA in non-transplant patients is usually insidious at onset without specific manifestations. When clinically suspected, microbiological examination should be done as soon as possible, and graded treatment should be given according to hierarchical diagnosis to improve the prognosis.

Key words: Invasive pulmonary aspergillosis, Diagnosis/treatment, Clinical features

表1 32例IPA患者的实验室检查[n(%)]

实验室检查指标	例数(构成比)
白细胞计数>9.5×10⁹/L	12(37.5)
白细胞计数<3.5×10⁹/L	1(3.1)
淋巴细胞计数<1×10⁹/L	13(40.6)
嗜酸粒细胞计数>0.5×10⁹/L	2(6.3)
Hb<110 g/L	11(34.4)
PLT<100×10⁹/L	4(12.5)
ESR>20 mm/H	18(78.3)
CRP>10 mg/L	23(76.7)
PCT>0.5 ng/ml	8(32.0)
IgE>100 IU/ml	8(57.1)
ALB<30 g/L	12(38.7)
CD4^＋细胞<550个/μl	7(70.0)
D-dimer>500 ng/ml	14(48.3)
LDH>250 U/L	10(45.5)
血G试验(＋)	19(67.9)
血GM试验(＋)	11(68.8)

表1 32例IPA患者的实验室检查[n(%)]

实验室检查指标	例数(构成比)
白细胞计数>9.5×10⁹/L	12(37.5)
白细胞计数<3.5×10⁹/L	1(3.1)
淋巴细胞计数<1×10⁹/L	13(40.6)
嗜酸粒细胞计数>0.5×10⁹/L	2(6.3)
Hb<110 g/L	11(34.4)
PLT<100×10⁹/L	4(12.5)
ESR>20 mm/H	18(78.3)
CRP>10 mg/L	23(76.7)
PCT>0.5 ng/ml	8(32.0)
IgE>100 IU/ml	8(57.1)
ALB<30 g/L	12(38.7)
CD4^＋细胞<550个/μl	7(70.0)
D-dimer>500 ng/ml	14(48.3)
LDH>250 U/L	10(45.5)
血G试验(＋)	19(67.9)
血GM试验(＋)	11(68.8)

图1 1例侵袭性肺曲霉病患者胸部CT平扫影像。注：A：右肺上叶后段见大片实变影，其内可见空气新月征(箭头)，左肺下叶可见斑片影；B：抗真菌治疗12周后，右肺上叶实变影及左肺下叶斑片影较前吸收，右上肺呈纤维索条样高密度影

图2 1例侵袭性肺曲霉病患者胸腔镜下右下肺切除送检病理(HE染色400×)：肺间质内可见真菌孢子及菌丝，菌丝有隔膜，成45°双叉状分枝，并可见大量淋巴细胞聚集

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Clinical features and management of non-transplant patients with invasive pulmonary aspergillosis: analysis of 32 cases

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Clinical features and management of non-transplant patients with invasive pulmonary aspergillosis: analysis of 32 cases