title: Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze.
abstract: Preschool rhinovirus-induced wheeze is associated with an increased risk of asthma. In adult asthma, exhaled volatile organic compounds (VOC) are associated with inflammatory activity. We therefore hypothesised that acute preschool wheeze is accompanied by a differential profile of exhaled VOC, which is maintained after resolution of symptoms in those children with rhinovirus-induced wheeze. We included 178 children (mean±sd age 22±9 months) from the EUROPA cohort comparing asymptomatic and wheezing children during respiratory symptoms and after recovery. Naso- and oropharyngeal swabs were tested for rhinovirus by quantitative PCR. Breath was collected via a spacer and analysed using an electronic nose. Between-group discrimination was assessed by constructing a 1000-fold cross-validated receiver operating characteristic curve. Analyses were stratified by rhinovirus presence/absence. Wheezing children demonstrated a different VOC profile when compared with asymptomatic children (p<0.001), regardless of the presence (area under the curve (AUC) 0.77, 95% CI 0.07) or absence (AUC 0.81, 95% CI 0.05) of rhinovirus. After symptomatic recovery, discriminative accuracy was maintained in children with rhinovirus-induced wheeze (AUC 0.84, 95% CI 0.06), whereas it dropped significantly in infants with non-rhinovirus-induced wheeze (AUC 0.67, 95% CI 0.06). Exhaled molecular profiles differ between preschool children with and without acute respiratory wheeze. This appears to be sustained in children with rhinovirus-induced wheeze after resolution of symptoms. Therefore, exhaled VOC may qualify as candidate biomarkers for early signs of asthma.
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Dept of Pediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Dept of Pediatric Respiratory Medicine, VU Medical Centre, VU University of Amsterdam, Amsterdam, The Netherlands m.p.vanderschee@amc.uva.nl.
authors.forename: Marc P
authors.initials: MP
authors.lastname: van der Schee
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annemarie C
authors.initials: AC
authors.lastname: Schuurman
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Janine S Repelaer
authors.initials: JS
authors.lastname: van Driel
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nora
authors.initials: N
authors.lastname: Adriaens
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Romy M
authors.initials: RM
authors.lastname: van Amelsfoort
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: Snoeren
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Regenboog
authors.affiliation: Dept of Pediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Aline B
authors.initials: AB
authors.lastname: Sprikkelman
authors.affiliation: Dept of Pediatric Respiratory Medicine, VU Medical Centre, VU University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Haarman
authors.affiliation: Dept of Pediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wim M C
authors.initials: WM
authors.lastname: van Aalderen
authors.affiliation: Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D001249:Asthma / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001944:Breath Tests; D002648:Child; D002675:Child, Preschool; D062609:Electronic Nose; D005060:Europe; D045853:Exhalation; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation; D008297:Male; D009930:Organic Chemicals / Q000737:chemistry; D018384:Oxidative Stress; D010850:Picornaviridae Infections / Q000175:diagnosis* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D011446:Prospective Studies; D012372:ROC Curve; D012135:Respiratory Sounds / Q000175:diagnosis; D012229:Rhinovirus / Q000378:metabolism*; D018401:Sample Size
chemical_list: D015415:Biomarkers; D009930:Organic Chemicals