title: Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects.
abstract: BACKGROUND
  Sputum 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.
  
  
  OBJECTIVE
  We 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.
  
  
  METHODS
  Subjects 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.
  
  
  RESULTS
  Despite 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.
  
  
  CONCLUSIONS
  Despite 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.
authors.affiliation: Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. ahastie@wakehealth.edu
authors.forename: Annette T
authors.initials: AT
authors.lastname: Hastie
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Huashi
authors.initials: H
authors.lastname: Li
authors.forename: Brian M
authors.initials: BM
authors.lastname: Rector
authors.forename: Victor E
authors.initials: VE
authors.lastname: Ortega
authors.forename: Rodolfo M
authors.initials: RM
authors.lastname: Pascual
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D015415:Biomarkers; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D012372:ROC Curve; D013183:Sputum / Q000166:cytology*
chemical_list: D015415:Biomarkers; D007073:Immunoglobulin E