Given the limitations of the ALI study group and our control subjects noted above, we were surprised at the ability of EPX-mAb immunohistochemistry to distinguish ALI patients from control subjects. Specifically, eosinophils are not considered a reliable histopathological marker of ALI (reviewed in [5, 28] ). Yet in a completely patient-blinded fashion that was reproducible among 3-4 independent evaluators who had no knowledge of one another's assessments, our numerical results were able to identify a group of ALI patients relative to control subjects on the a basis of both increased numbers of tissue infiltrating eosinophils and increased levels of eosinophil degranulation. Furthermore, these evaluations allowed us in a completely clinical outcomeblinded fashion to stratify the ALI patients into those surviving their hospitalization relative to the non-surviving patients. It is clear that the design and power of this study precludes us from overly provocative conclusions regarding the role of eosinophils, including their link with specific symptoms or their part in pathways that exacerbate or attenuate disease pathologies. Nonetheless, this study does suggest that EPX-mAb immunohistochemistry may represent a previously unrecognized diagnostic tool providing prognostic information for the management of ALI patients. In addition, given the paucity of available therapeutic options and discriminatory testing modalities, [1, 6, 8, 10, 19] assays detecting the release of eosinophil products (e.g., ELISA based assessment of degranulation from biological fluids such as breath condensate, intratracheal tube secretions, and/or BAL fluid) may also represent rapid and minimally invasive biomarkers of disease to assess this difficult patient population [38] . Indeed, this initial report provides the Figure 3 Acute Lung Injury patients display quantitatively different levels of eosinophil degranulation that may occur even in the absence of intact infiltrating eosinophils. Representative photomicrographs of the five described levels of eosinophil degranulation within biopsies from ALI patients. Level 0: No evidence of eosinophil degranulation. Level 1a: Nominal levels of eosinophil degranulation representing <3 areas of granule protein release that is <10% of the field of view. Level 1b: Slightly elevated level of eosinophil degranulation representing ≥3 areas of granule protein release that again is <10% of the field of view. Level 2a: Significant level of eosinophil degranulation that includes 10-50% of the field of view. Level 2b: Significant level of eosinophil degranulation that includes extracellular release of EPX, enucleated eosinophils (i.e., cytoplasmic fragments), and/or the presence of free granules (i.e., EPX-containing secondary granules not associated with fragmented eosinophils). The extent of degranulation represents >50% of the field's total area. Scale bar = 50 μm.