Research on pathophysiology and the establishment of serum biomarkers for cigarette-smoke-associated acute eosinophilic pneumonia

急性嗜酸性肺炎(AEP)的表现与急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)非常相似，包括其特发性急性间质性肺炎(AIP)。AEP急性期通常缺乏外周血嗜酸性粒细胞增多，因此，建立AEP的血清生物标志物将具有临床应用价值。我们检测了17例AEP、13例AIP、12例肺炎合并ALI/ARDS和7例肺泡出血患者血清中胸腺和活化调节趋化因子(TARC/CCL17)、嗜酸性粒细胞趋化因子/CCL11、KL-6和表面活性蛋白-D(SP-D)的水平。通过测量受试者工作特征曲线下面积(AUC)来评价各标志物的诊断能力。AEP患者血清TARC/CCL17水平明显高于其他疾病组。更重要的是，即使在急性期外周嗜酸性粒细胞缺乏的情况下，AEP中也可观察到循环中高水平的TARC/CCL17。TARC/CCL17的AUC最大，以6,259~7,039pg/ml为界点，AEP与其他证型的敏感度和特异度均为100%。大多数AEP患者血清KL-6水平较低，其敏感性为81.6%，特异性为100%。嗜酸性粒细胞趋化因子/CCL11和SP-D的AUC较小，分别为0.73(95%可信区间0.60~0.85)和0.53(95%可信区间0.31~0.64)。提示循环TARC/CCL17和KL-6的检测有助于AEP与其他原因的急性肺损伤的鉴别。

The presentation of acute eosinophilic pneumonia (AEP) closely resembles that of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) including its idiopathic form, acute interstitial pneumonia (AIP). AEP usually lacks peripheral eosinophilia at the acute phase; therefore, the establishment of serum biomarkers for AEP would be clinically useful. We measured the levels of thymus-and activation-regulated chemokine (TARC/CCL17), eotaxin/CCL11, KL-6 and surfactant protein-D (SP-D) in serum for patients with acute parenchymal lung diseases including AEP (n=17), AIP (n=13), pneumonia-associated ALI/ARDS (n=12), and alveolar hemorrhage (n=7). To evaluate the diagnostic ability of each marker was estimated by measuring the area under the receiver operating characteristic curve (AUC). The serum TARC/CCL17 levels of AEP patients were much higher than those of patients in other disease groups. More importantly, high circulating TARC/CCL17 levels were observed in AEP even at acute phase when peripheral eosinophilia was absent. TARC/CCL17 showed the largest AUC, and the TARC/CCL17 levels with cut-off points between 6,259 and 7,039pg/ml discriminated AEP from other syndromes with sensitivity and specificity of 100%. The KL-6 level was low in most patients with AEP, and the sensitivity was 81.6% in cutoff with 100% specificity. The AUC for eotaxin/CCL11 and SP-D was small with the values of 0.73 (95% confidence interval [CI], 0.60 to 0.85) and 0.53 (95% CI, 0.31 to 0.64), respectively. This study indicates that the measurement of circulating TARC/CCL17 and KL-6 is useful for discriminating AEP from other causes of acute lung injury.