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Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia.

ABSTRACT: Sputum eosinophilia has been shown to be a predictor of response to anti-eosinophil therapies in patients with airway diseases. However, quantitative cell counts and differentials of sputum are labor intensive. The objective of this study was to validate a novel ELISA-based assay of eosinophil peroxidase (EPX) in sputum as a rapid and reliable marker of airway eosinophils.The utility of EPX-based ELISA as an eosinophil-specific assay was achieved through comparisons with sputum eosinophil differential counts in freshly prepared and archived patient samples from a variety of clinical settings.EPX levels in sputum correlated with eosinophil percentage (r(s) = 0.84) in asthma patients with varying degrees of airway eosinophilia. Significantly, unlike assays of other eosinophil granule proteins (e.g., ECP and EDN), which often detect the presence of these proteins even in asthma patients with neutrophilic bronchitis, EPX-based ELISA levels are not increased in this subset of asthma patients or in COPD patients lacking evidence of an airway eosinophilia. Moreover, sputum EPX was a surrogate marker of airway eosinophilia in other patient studies (e.g., allergen inhalation and treatment trials the anti-(IL-5) therapeutic Mepolizumab™). Finally, EPX levels in cytocentrifuged prepared sputum supernatants correlated with those from rapidly prepared noncentrifuged filtrates of sputum (r(s) = 0.94).EPX-based ELISA is a valid, reliable, repeatable, and specific surrogate marker of eosinophils and/or eosinophil degranulation in the sputum of respiratory patients. The novel EPX assay is a valid and reproducible eosinophil-specific assay that can potentially be developed into a point-of-care assessment of eosinophil activity in airway secretions.

SUBMITTER: Nair P

PROVIDER: S-EPMC3788081 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia.

Nair P P Ochkur S I SI Protheroe C C Radford K K Efthimiadis A A Lee N A NA Lee J J JJ

Allergy 20130809 9

<h4>Background</h4>Sputum eosinophilia has been shown to be a predictor of response to anti-eosinophil therapies in patients with airway diseases. However, quantitative cell counts and differentials of sputum are labor intensive. The objective of this study was to validate a novel ELISA-based assay of eosinophil peroxidase (EPX) in sputum as a rapid and reliable marker of airway eosinophils.<h4>Methods</h4>The utility of EPX-based ELISA as an eosinophil-specific assay was achieved through compar ...[more]

PMID: 23931643

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Project description:BackgroundSputum eosinophil percentages are a strong predictor of airway inflammation and exacerbations and aid asthma management, whereas sputum neutrophil percentages indicate a different severe asthma phenotype that is potentially less responsive to TH2-targeted therapy. Variables, such as blood eosinophil counts, total IgE levels, fraction of exhaled nitric oxide (Feno) levels, or FEV1 percent predicted, might predict airway eosinophil percentages, whereas age, FEV1 percent predicted, or blood neutrophil counts might predict sputum neutrophil percentages. Availability and ease of measurement are useful characteristics, but accuracy in predicting airway eosinophil and neutrophil percentages either individually or combined is not established.ObjectivesWe sought to determine whether blood eosinophil counts, Feno levels, and IgE levels accurately predict sputum eosinophil percentages and whether age, FEV1 percent predicted, and blood neutrophil counts accurately predict sputum neutrophil percentages.MethodsSubjects in the Wake Forest Severe Asthma Research Program (n = 328) were characterized by blood and sputum cell counts, health care use, lung function, Feno levels, and IgE levels. Multiple analytic techniques were used.ResultsDespite significant association with sputum eosinophil percentages, blood eosinophil counts, Feno levels, and total IgE levels did not accurately predict sputum eosinophil percentages, and combinations of these variables did not improve prediction. Age, FEV1 percent predicted, and blood neutrophil counts were similarly unsatisfactory for the prediction of sputum neutrophil percentages. Factor analysis and stepwise selection found Feno levels, IgE levels, and FEV1 percent predicted, but not blood eosinophil counts, correctly predicted 69% of sputum eosinophil percentages of less than 2% or 2% and greater. Likewise, age, asthma duration, and blood neutrophil counts correctly predicted 64% of sputum neutrophil percentages of less than 40% or 40% and greater. A model to predict both sputum eosinophil and neutrophil percentages accurately assigned only 41% of samples.ConclusionDespite statistically significant associations, Feno levels, IgE levels, blood eosinophil and neutrophil counts, FEV1 percent predicted, and age are poor surrogates, both separately and combined, for accurately predicting sputum eosinophil and neutrophil percentages.

Dataset Information

Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia.

Publications

Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia.

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