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

急性嗜酸性粒细胞性肺炎（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，包括其特发性形式急性间质性肺炎（AIP）。急性期AEP通常缺乏外周嗜酸性粒细胞；因此，建立AEP的血清生物标志物具有临床意义。我们测量了急性肺实质疾病患者血清中胸腺和激活调节趋化因子（TARC/CCL17）、eotaxin/CCL11、KL-6和表面活性蛋白- d （SP-D）的水平，包括AEP （n=17）、AIP （n=13）、肺炎相关ALI/ARDS （n=12）和肺泡出血（n=7）。通过测量受试者工作特征曲线下面积（AUC）来评估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失的情况下，AEP患者也观察到高循环TARC/CCL17水平。TARC/CCL17的AUC最大，截断点在6259 ~ 7039 pg/ml之间的TARC/CCL17水平区分AEP与其他综合征的敏感性和特异性为100%。大多数AEP患者KL-6水平较低，截止值敏感性为81.6%，特异性为100%。eotaxin/CCL11和SP-D的AUC较小，分别为0.73（95%可信区间[CI]， 0.60 ~ 0.85）和0.53 （95% CI, 0.31 ~ 0.64）。本研究表明，循环TARC/CCL17和KL-6的测定有助于区分AEP与其他原因的急性肺损伤。

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.