目的:在ANCA相关性血管炎(AAV)患者中常见肺病变,主要是由于AAV肺部受累或感染,由于临床表现高度相似,难以区分。我们旨在分析AAV患者中AAV受累或感染后肺部病变的临床特征,并进一步确定鉴别诊断的标志物。
方法:将2016年1月至2021年7月武汉大学人民医院收治的140例AAV患者纳入本研究。根据肺部状况的性质,这些患者被分为非肺部病变组,肺部感染组和非肺部感染组,和他们的人口统计,临床症状,成像特征,以及实验室结果进行了比较。绘制受试者工作特征(ROC)曲线,然后评估单一生物标志物和复合生物标志物对肺部感染的诊断效能。
结果:肺部感染组患者年龄明显大于无病变组患者(63.19±14.55vs54.82±15.08,p=0.022)。肺部感染组的患者表现出更频繁的症状和更明显的肺部影像表现。与非肺部感染组患者比较,肺部感染组患者发热症状发生率较高,胸闷,咳嗽和咳痰,咯血(52.94%vs16.00%,61.76%vs40.00%,72.06%比46.00%,27.94%vs8.00%,p分别<0.05),和更多的变化在肺部CT扫描图像的补丁/条纹紧凑的不透明度,肺泡出血,支气管扩张,胸腔积液,以及纵隔淋巴结肿大(89.71%vs52.00%,11.76%vs2.00%,22.06%vs8.00%,50.00%vs20.00%,48.53%对24.00%,p分别<0.05)。此外,肺部感染组患者血清降钙素原(PCT)水平明显升高,C反应蛋白(CRP),淀粉样蛋白A(SAA),血液中性粒细胞与淋巴细胞比率(NLCR),红细胞沉降率(ESR),伯明翰血管炎活动评分(BVAS)优于其他两组患者(p<0.05)。在所有生物标志物中,PCT对肺部感染AAV患者的诊断效能最高(0.928;95CI0.89-0.97),临界值为0.235ng/ml,敏感性为85.3%,特异性为84%。此外,PCT-CRP-NLCR复合生物标志物在区分AAV患者感染性和非感染性肺损伤方面显示出更高的诊断效能(0.979;95%CI0.95-1.00).
结论:AAV合并肺部感染患者临床症状较多,肺部影像学改变明显。PCT和复合生物标志物PCT-CRP-NLCR对AAV患者肺部感染显示出高诊断效能。由感染或AAV受累引起的肺部病变是常见且难以区分的。我们旨在确定可用于AAV患者肺部病变的鉴别诊断的生物标志物。
OBJECTIVE: Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis.
METHODS: 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated.
RESULTS: The patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p < 0.05, respectively), and more changes in pulmonary CT scanning images in terms of patched/striped compact opacity, alveolar hemorrhage, bronchiectasis, pleural effusion, as well as mediastinal lymphadenopathy (89.71% vs 52.00%, 11.76% vs 2.00%, 22.06% vs 8.00%, 50.00% vs 20.00%, 48.53% vs 24.00%, p < 0.05, respectively). In addition, patients in the lung infection group had significantly higher levels of serum pro-calcitonin (PCT), C-reactive protein (CRP), amyloid A (SAA), blood neutrophil-to-lymphocyte ratio (NLCR), erythrocyte sedimentation rate (ESR), as well as Birmingham vasculitis activity score (BVAS) than patients in the other two groups (p < 0.05). Among all biomarkers, PCT exhibited the highest diagnostic efficacy (0.928; 95%CI 0.89-0.97) for pulmonary infected AAV patients at a cut-off score of 0.235 ng/ml with 85.3% sensitivity and 84% specificity. Moreover, the composite biomarker of PCT-CRP-NLCR showed more diagnostic efficacy (0.979; 95% CI 0.95-1.00) in distinguishing the infectious and non-infectious lung injuries in AAV patients.
CONCLUSIONS: AAV patients with lung infection manifested more clinical symptoms and prominent lung image changes. The PCT and composite biomarker PCT-CRP-NLCR showed high diagnostic efficacy for a lung infection in AAV patients. Pulmonary lesion caused by either infection or AAV involvement is commonly seen and difficult to distinguish. We aim to identify the biomarkers that can be applied in the differentiation diagnosis of pulmonary lesions in AAV patients.