title: Diagnosing eosinophilic asthma using a multivariate prediction model based on blood granulocyte responsiveness.
abstract: BACKGROUND
  The identification of inflammatory asthma phenotypes, using sputum analysis, has proven its value in diagnosis and disease monitoring. However due to technical limitations of sputum analysis, there is a strong need for fast and noninvasive diagnostics. This study included the activation state of eosinophils and neutrophils in peripheral blood to phenotype and monitor asthma.
  
  
  OBJECTIVE
  To (i) construct a multivariable model using the activation state of blood granulocytes, (ii) compare its diagnostic value with sputum eosinophilia as gold standard and (iii) validate the model in an independent patient cohort.
  
  
  METHODS
  Clinical parameters, activation of blood granulocytes and sputum characteristics were assessed in 115 adult patients with asthma (training cohort/Utrecht) and 34 patients (validation cohort/Oxford).
  
  
  RESULTS
  The combination of blood eosinophil count, fractional exhaled nitric oxide, Asthma Control Questionnaire, medication use, nasal polyposis, aspirin sensitivity and neutrophil/eosinophil responsiveness upon stimulation with formyl-methionyl-leucyl phenylalanine was found to identify sputum eosinophilia with 90.5% sensitivity and 91.5% specificity in the training cohort and with 77% sensitivity and 71% specificity in the validation cohort (relatively high percentage on oral corticosteroids [OCS]).
  
  
  CONCLUSIONS
  The proposed prediction model identifies eosinophilic asthma without the need for sputum induction. The model forms a noninvasive and externally validated test to assess eosinophilic asthma in patients not on OCS.
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Nuffield Department of Medicine, Oxford University, Oxford, UK.
authors.forename: B
authors.identifier: http://orcid.org/0000-0002-7223-0281
authors.initials: B
authors.lastname: Hilvering
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: S J H
authors.initials: SJH
authors.lastname: Vijverberg
authors.affiliation: Institute for Molecules and Materials, Radboud Universiteit Nijmegen, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Jansen
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Houben
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: R C
authors.initials: RC
authors.lastname: Schweizer
authors.affiliation: Nuffield Department of Medicine, Oxford University, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Go
authors.affiliation: Nuffield Department of Medicine, Oxford University, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.affiliation: Nuffield Department of Medicine, Oxford University, Oxford, UK.
authors.forename: I D
authors.initials: ID
authors.lastname: Pavord
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: J-W J
authors.initials: JJ
authors.lastname: Lammers
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D015415:Biomarkers; D004802:Eosinophilia / Q000097:blood*; D004804:Eosinophils; D045853:Exhalation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009569:Nitric Oxide; D010641:Phenotype; D011379:Prognosis; D012372:ROC Curve; D013183:Sputum / Q000166:cytology / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide
keywords: FeNO; aspirin sensitivity; eosinophil; nasal polyps; sputum