Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury

Respiratory Research

James J Lee⁵  Nancy A Lee¹  Kevin O Leslie³  Redwan Moqbel⁴  PGraziano³  Elizabeth Jaben³  Cheryl A Protheroe⁵  Lewis J Wesselius⁶  Kimberly Parker⁶  Lian Willetts² 

[1] Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259 USA;Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta Canada T6G 2S2;Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ 85259 USA;Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba Canada R3E 0W3;Division of Pulmonary Medicine, Department of Internal Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259 USA;Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259 USA

关键词: Eosinophil Peroxidase;    Eosinophils;    Acute Respiratory Distress Syndrome;    Acute Lung Injury;   

Others  :  796806
DOI  :  10.1186/1465-9921-12-116

 received in 2011-04-21, accepted in 2011-08-26,  发布年份 2011

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2011 Willetts et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Ashbaugh DG, Bigelow DB, Petty TL, Levine BE: Acute respiratory distress in adults. Lancet 1967, 2:319-323.
• [2]Wheeler AP, Bernard GR: Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet 2007, 369:1553-1564.
• [3]Rubenfeld GD, Herridge MS: Epidemiology and outcomes of acute lung injury. Chest 2007, 131:554-562.
• [4]Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149:818-824.
• [5]Avecillas JF, Freire AX, Arroliga AC: Clinical epidemiology of acute lung injury and acute respiratory distress syndrome: incidence, diagnosis, and outcomes. Clin Chest Med 2006, 27:549-557. abstract vii
• [6]Levitt JE, Matthay MA: The utility of clinical predictors of acute lung injury: towards prevention and earlier recognition. Expert Rev Respir Med 2010, 4:785-797.
• [7]Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med 2005, 353:1685-1693.
• [8]Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342:1301-1308.
• [9]Levitt JE, Bedi H, Calfee CS, Gould MK, Matthay MA: Identification of early acute lung injury at initial evaluation in an acute care setting prior to the onset of respiratory failure. Chest 2009, 135:936-943.
• [10]Matthay MA, Zimmerman GA: Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol 2005, 33:319-327.
• [11]Agarwal R, Nath A, Aggarwal AN, Gupta D: Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis. Respirology 2007, 12:585-590.
• [12]Tang J, Zhou R, Luger D, Zhu W, Silver PB, Grajewski RS, Su SB, Chan CC, Adorini L, Caspi RR: Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response. J Immunol 2009, 182:4624-4632.
• [13]Adhikari N, Burns KE, Meade MO: Pharmacologic treatments for acute respiratory distress syndrome and acute lung injury: systematic review and meta-analysis. Treat Respir Med 2004, 3:307-328.
• [14]Lin Q, Wang GF, Tang XY, Zou SL: Effects of dexamethasone on acute lung injury in rats induced by lipopolysacharide. Beijing Da Xue Xue Bao 2006, 38:393-396.
• [15]Meduri GU, Headley AS, Golden E, Carson SJ, Umberger RA, Kelso T, Tolley EA: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998, 280:159-165.
• [16]Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006, 354:1671-1684.
• [17]Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, Gibson M, Umberger R: Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 2007, 131:954-963.
• [18]Bernard GR, Luce JM, Sprung CL, Rinaldo JE, Tate RM, Sibbald WJ, Kariman K, Higgins S, Bradley R, Metz CA, et al.: High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 1987, 317:1565-1570.
• [19]Bernard GR: Acute respiratory distress syndrome: a historical perspective. Am J Respir Crit Care Med 2005, 172:798-806.
• [20]Suratt BT, Parsons PE: Mechanisms of acute lung injury/acute respiratory distress syndrome. Clin Chest Med 2006, 27:579-589. abstract viii
• [21]Hallgren R, Borg T, Venge P, Modig J: Signs of neutrophil and eosinophil activation in adult respiratory distress syndrome. Crit Care Med 1984, 12:14-18.
• [22]Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000, 342:1334-1349.
• [23]Wittkowski H, Sturrock A, van Zoelen MA, Viemann D, van der Poll T, Hoidal JR, Roth J, Foell D: Neutrophil-derived S100A12 in acute lung injury and respiratory distress syndrome. Crit Care Med 2007, 35:1369-1375.
• [24]Swanson K, Dwyre DM, Krochmal J, Raife TJ: Transfusion-related acute lung injury (TRALI): current clinical and pathophysiologic considerations. Lung 2006, 184:177-185.
• [25]Jernigan TW, Croce MA, Fabian TC: Apoptosis and necrosis in the development of acute lung injury after hemorrhagic shock. Am Surg 2004, 70:1094-1098.
• [26]Lange M, Hamahata A, Traber DL, Esechie A, Jonkam C, Bansal K, Nakano Y, Traber LD, Enkhbaatar P: A murine model of sepsis following smoke inhalation injury. Biochem Biophys Res Commun 2010, 391:1555-1560.
• [27]Hallgren R, Samuelsson T, Venge P, Modig J: Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome. Am Rev Respir Dis 1987, 135:639-642.
• [28]Beasley MB: The pathologist's approach to acute lung injury. Arch Pathol Lab Med 2010, 134:719-727.
• [29]Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al.: Eosinophilic inflammation in asthma [see comments]. N Engl J Med 1990, 323:1033-1039.
• [30]Allen JN, Davis WB: Eosinophilic lung diseases. [Review]. Am J Respir Crit Care Med 1994, 150:1423-1438.
• [31]Modig J, Samuelsson T, Hallgren R: The predictive and discriminative value of biologically active products of eosinophils, neutrophils and complement in bronchoalveolar lavage and blood in patients with adult respiratory distress syndrome. Resuscitation 1986, 14:121-134.
• [32]Doyle RL, Szaflarski N, Modin GW, Wiener-Kronish JP, Matthay MA: Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 1995, 152:1818-1824.
• [33]Katzenstein A-LA, Askin FB, Livolsi VA: Acute Lung Injury Patterns: Diffuse Alveolar Damage and Bronchiolitis Obliterans- Organizing Pneumonia. In Katzenstein and Askin's surgical pathology of non-neoplastic lung disease. Volume x. 3rd edition. Philadelphia: W.B. Saunders; 1997::477.
• [34]Protheroe CA, Woodruff SA, DePetris G, Mukkada V, Ochkur SI, Janarthanan S, Lewis JC, Pasha S, Lunsford T, Harris L, et al.: A novel histological scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis. Clinical Gastroenterology and Hepatology 2009, 7:749-755.
• [35]Identifiable eosinophil infiltration and/or degranulation is defined as >1 intact eosinophil in at least a single 40x high powered field and/or ?10% of any single 40x high powered field displaying evidence of extracellular deposition of EPX without the presence of infiltrating eosinophils
• [36]Shrout PE, Fleiss JL: Intraclass correlations: uses in assessing rater reliability. Psychol Bull 1979, 86:420-428.
• [37]Grigoryev DN, Finigan JH, Hassoun P, Garcia JG: Science review: searching for gene candidates in acute lung injury. Crit Care 2004, 8:440-447. BioMed Central Full Text
• [38]Levitt JE, Gould MK, Ware LB, Matthay MA: The pathogenetic and prognostic value of biologic markers in acute lung injury. J Intensive Care Med 2009, 24:151-167.