title: Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis.
abstract: BACKGROUND
  Eosinophilic airway inflammation is associated with increased corticosteroid responsiveness in asthma, but direct airway sampling methods are invasive or laborious. Minimally invasive markers for airway eosinophilia could present an alternative method, but estimates of their accuracy vary.
  
  
  METHODS
  We did a systematic review and searched Medline, Embase, and PubMed for studies assessing the diagnostic accuracy of markers against a reference standard of induced sputum, bronchoalveolar lavage, or endobronchial biopsy in patients with asthma or suspected asthma (for inception to Aug 1, 2014). Unpublished results were obtained by contacting authors of studies that did not report on diagnostic accuracy, but had data from which estimates could be calculated. We assessed risk of bias with QUADAS-2. We used meta-analysis to produce summary estimates of accuracy.
  
  
  RESULTS
  We included 32 studies: 24 in adults and eight in children. Of these, 26 (81%) showed risk of bias in at least one domain. In adults, three markers had extensively been investigated: fraction of exhaled nitric oxide (FeNO) (17 studies; 3216 patients; summary area under the receiver operator curve [AUC] 0·75 [95% CI 0·72-0·78]); blood eosinophils (14 studies; 2405 patients; 0·78 [0·74-0·82]); total IgE (seven studies; 942 patients; 0·65 [0·61-0·69]). In children, only FeNO (six studies; 349 patients; summary AUC 0·81 [0·72-0·89]) and blood eosinophils (three studies; 192 patients; 0·78 [0·71-0·85]) had been investigated in more than one study. Induced sputum was most frequently used as the reference standard. Summary estimates of sensitivity and specificity in detecting sputum eosinophils of 3% or more in adults were: 0·66 (0·57-0·75) and 0·76 (0·65-0·85) for FeNO; 0·71 (0·65-0·76) and 0·77 (0·70-0·83) for blood eosinophils; and 0·64 (0·42-0·81) and 0·71 (0·42-0·89) for IgE.
  
  
  CONCLUSIONS
  FeNO, blood eosinophils, and IgE have moderate diagnostic accuracy. Their use as a single surrogate marker for airway eosinophilia in patients with asthma will lead to a substantial number of false positives or false negatives.
  
  
  BACKGROUND
  None.
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands. Electronic address: d.a.korevaar@amc.uva.nl.
authors: Daniël A
authors: DA
authors: Korevaar
authors: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
authors: Guus A
authors: GA
authors: Westerhof
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
authors: Junfeng
authors: J
authors: Wang
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands; Inserm U1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Biostatistics Sorbonne Paris Cité (CRESS), Paris, France; Department of Pediatrics, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France.
authors: Jérémie F
authors: JF
authors: Cohen
authors: Medical Library, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
authors: René
authors: R
authors: Spijker
authors: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
authors: Peter J
authors: PJ
authors: Sterk
authors: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
authors: Elisabeth H
authors: EH
authors: Bel
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
authors: Patrick M M
authors: PM
authors: Bossuyt
mesh_terms: D019540:Area Under Curve; D001249:Asthma / Q000097:blood / Q000175:diagnosis*; D001706:Biopsy; D001944:Breath Tests; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004802:Eosinophilia / Q000097:blood / Q000175:diagnosis; D004804:Eosinophils / Q000166:cytology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007958:Leukocyte Count; D009569:Nitric Oxide / Q000032:analysis; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000175:diagnosis*; D013183:Sputum / Q000166:cytology
chemical_list: D009569:Nitric Oxide; D007073:Immunoglobulin E