title: Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Willetts
authors.forename: Kimberly
authors.initials: K
authors.lastname: Parker
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Wesselius
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Protheroe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jaben
authors.forename: P
authors.initials: P
authors.lastname: Graziano
authors.forename: Redwan
authors.initials: R
authors.lastname: Moqbel
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Leslie
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D055371:Acute Lung Injury / Q000175:diagnosis* / Q000201:enzymology / Q000401:mortality*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D001130:Arizona; D001706:Biopsy; D016022:Case-Control Studies; D047209:Eosinophil Peroxidase / Q000032:analysis* / Q000276:immunology; D004804:Eosinophils / Q000201:enzymology*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011657:Pulmonary Eosinophilia / Q000175:diagnosis* / Q000201:enzymology / Q000401:mortality*; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D047209:Eosinophil Peroxidase