title: Prediction of asthma exacerbations in children by innovative exhaled inflammatory markers: results of a longitudinal study.
abstract: BACKGROUND
  In asthma management guidelines the primary goal of treatment is asthma control. To date, asthma control, guided by symptoms and lung function, is not optimal in many children and adults. Direct monitoring of airway inflammation in exhaled breath may improve asthma control and reduce the number of exacerbations.
  
  
  OBJECTIVE
  1) To study the use of fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC), in the prediction of asthma exacerbations in a pediatric population. 2) To study the predictive power of these exhaled inflammatory markers combined with clinical parameters.
  
  
  METHODS
  96 asthmatic children were included in this one-year prospective observational study, with clinical visits every 2 months. Between visits, daily symptom scores and lung function were recorded using a home monitor. During clinical visits, asthma control and FeNO were assessed. Furthermore, lung function measurements were performed and EBC was collected. Statistical analysis was performed using a test dataset and validation dataset for 1) conditionally specified models, receiver operating characteristic-curves (ROC-curves); 2) k-nearest neighbors algorithm.
  
  
  RESULTS
  Three conditionally specified predictive models were constructed. Model 1 included inflammatory markers in EBC alone, model 2 included FeNO plus clinical characteristics and the ACQ score, and model 3 included all the predictors used in model 1 and 2. The area under the ROC-curves was estimated as 47%, 54% and 59% for models 1, 2 and 3 respectively. The k-nearest neighbors predictive algorithm, using the information of all the variables in model 3, produced correct predictions for 52% of the exacerbations in the validation dataset.
  
  
  CONCLUSIONS
  The predictive power of FeNO and inflammatory markers in EBC for prediction of an asthma exacerbation was low, even when combined with clinical characteristics and symptoms. Qualitative improvement of the chemical analysis of EBC may lead to a better non-invasive prediction of asthma exacerbations.
authors: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+),Maastricht, The Netherlands.
authors: Dillys
authors: D
authors: van Vliet
authors: Department of Methodology and Statistics, CAPHRI, MUMC+, Maastricht, The Netherlands.
authors: Ariel
authors: A
authors: Alonso
authors: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Ger
authors: G
authors: Rijkers
authors: Department of Pediatrics, Orbis Medical Center, Sittard, The Netherlands.
authors: Jan
authors: J
authors: Heynens
authors: Department of Pediatrics, Orbis Medical Center, Sittard, The Netherlands.
authors: Philippe
authors: P
authors: Rosias
authors: Department of Family Medicine, CAPHRI, MUMC+, Maastricht, The Netherlands.
authors: Jean
authors: J
authors: Muris
authors: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+),Maastricht, The Netherlands.
authors: Quirijn
authors: Q
authors: Jöbsis
authors: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+),Maastricht, The Netherlands.
authors: Edward
authors: E
authors: Dompeling
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods; D002648:Child; D045853:Exhalation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D008137:Longitudinal Studies; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D009569:Nitric Oxide