title: External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.
abstract: BACKGROUND
  Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation.
  
  
  OBJECTIVE
  Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma.
  
  
  METHODS
  The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC).
  
  
  RESULTS
  In the external validation cohort, ROC AUC for blood eosinophils was 89% (p<0.001) and for FE(NO) level 78% (p<0.001) to detect sputum eosinophilia ≥3%. Serum periostin was not able to distinguish eosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, p<0.001).
  
  
  CONCLUSIONS
  In patients with mild to moderate asthma, as well as patients with more severe asthma, blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma.
  
  
  BACKGROUND
  NTR1846 and NTR2364.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Wagener
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors.forename: S B
authors.initials: SB
authors.lastname: de Nijs
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, The Netherlands Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Respiratory Therapy Unit, GlaxoSmithKline, London, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Sousa
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Weersink
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Bel
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001249:Asthma / Q000097:blood* / Q000150:complications; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D015815:Cell Adhesion Molecules / Q000097:blood*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004802:Eosinophilia / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D004804:Eosinophils; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D012372:ROC Curve; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology*
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D009569:Nitric Oxide
keywords: Asthma; Eosinophil Biology