Division of Pulmonary Medicine, Department of Internal Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
Respir Res. 2011 Aug 26;12(1):116. doi: 10.1186/1465-9921-12-116.
Acute lung injury (ALI) is a serious respiratory disorder for which therapy is primarily supportive once infection is excluded. Surgical lung biopsy may rule out other diagnoses, but has not been generally useful for therapy decisions or prognosis in this setting. Importantly, tissue and peripheral blood eosinophilia, the hallmarks of steroid-responsive acute eosinophilic pneumonia, are not commonly linked with ALI. We hypothesized that occult eosinophilic pneumonia may explain better outcomes for some patients with ALI.
Immunohistochemistry using a novel monoclonal antibody recognizing eosinophil peroxidase (EPX-mAb) was used to assess intrapulmonary eosinophil accumulation/degranulation. Lung biopsies from ALI patients (n = 20) were identified following review of a pathology database; 45% of which (i.e., 9/20) displayed classical diffuse alveolar damage (ALI-DAD). Controls were obtained from uninvolved tissue in patients undergoing lobectomy for lung cancer (n = 10). Serial biopsy sections were stained with hematoxylin and eosin (H&E) and subjected to EPX-mAb immunohistochemistry.
EPX-mAb immunohistochemistry provided a >40-fold increased sensitivity to detect eosinophils in the lung relative to H&E stained sections. This increased sensitivity led to the identification of higher numbers of eosinophils in ALI patients compared with controls; differences using H&E staining alone were not significant. Clinical assessments showed that lung infiltrating eosinophil numbers were higher in ALI patients that survived hospitalization compared with non-survivors. A similar conclusion was reached quantifying eosinophil degranulation in each biopsy.
The enhanced sensitivity of EPX-mAb immunohistochemistry uniquely identified eosinophil accumulation/degranulation in patients with ALI relative to controls. More importantly, this method was a prognostic indicator of patient survival. These observations suggest that EPX-mAb immunohistochemistry may represent a diagnostic biomarker identifying a subset of ALI patients with improved clinical outcomes.
急性肺损伤(ALI)是一种严重的呼吸系统疾病,一旦排除感染,治疗主要是支持性的。外科肺活检可以排除其他诊断,但在这种情况下,对治疗决策或预后通常没有帮助。重要的是,组织和外周血嗜酸性粒细胞增多,类固醇反应性急性嗜酸性肺炎的标志,与 ALI 并不常见。我们假设隐匿性嗜酸性肺炎可能解释了一些 ALI 患者更好的预后。
使用一种新的识别过氧化物酶(EPX-mAb)的单克隆抗体进行免疫组织化学染色,以评估肺内嗜酸性粒细胞的聚集/脱颗粒。通过对病理数据库的回顾,确定了来自 ALI 患者(n=20)的肺活检;其中 45%(即 9/20)显示出经典的弥漫性肺泡损伤(ALI-DAD)。对照组取自因肺癌行肺叶切除术的患者未受累组织(n=10)。对苏木精和伊红(H&E)染色和 EPX-mAb 免疫组织化学染色的连续活检切片进行了染色。
与 H&E 染色切片相比,EPX-mAb 免疫组织化学染色对检测肺内嗜酸性粒细胞的敏感性提高了 40 多倍。这种敏感性导致与对照组相比,ALI 患者的肺内嗜酸性粒细胞数量更高;仅使用 H&E 染色,差异无统计学意义。临床评估显示,与非幸存者相比,住院期间存活的 ALI 患者的肺浸润性嗜酸性粒细胞数量更高。通过对每个活检进行定量嗜酸性粒细胞脱颗粒也得出了类似的结论。
与对照组相比,EPX-mAb 免疫组织化学染色的增强敏感性独特地识别了 ALI 患者的嗜酸性粒细胞聚集/脱颗粒。更重要的是,这种方法是患者生存的预后指标。这些观察结果表明,EPX-mAb 免疫组织化学染色可能代表一种诊断生物标志物,可识别具有更好临床结局的 ALI 患者亚群。