title: Biomarkers in Exhaled Breath Condensate Are Not Predictive for Pulmonary Exacerbations in Children with Cystic Fibrosis: Results of a One-Year Observational Study.
abstract: BACKGROUND
  Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis.
  
  
  OBJECTIVE
  To investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF.
  
  
  METHODS
  In this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured using high sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded during the study and were defined in two ways. The predictive power of inflammatory markers and the other covariates was assessed using conditionally specified models and a receiver operating characteristic curve (SAS version 9.2). In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2).
  
  
  RESULTS
  Sixty-five percent of the children had one or more exacerbations during the study. The conditionally specified models showed an overall correct prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The results obtained with the KNN algorithm were very similar.
  
  
  CONCLUSIONS
  Although there is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers IL-6, IL-8, TNF-α and MIF is low. At present it is not possible to predict pulmonary exacerbations in children with CF with the chosen biomarkers and the method of EBC analysis. The biochemical measurements of EBC markers should be improved and other techniques should be considered.
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: van Horck
authors.affiliation: Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, Belgium.
authors.forename: Ariel
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Department of Pulmonology, CAPHRI, MUMC+, Maastricht, The Netherlands.
authors.forename: Geertjan
authors.initials: G
authors.lastname: Wesseling
authors.affiliation: Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: de Winter-de Groot
authors.affiliation: Department of Pediatric Respiratory Medicine, Emma Children's Hospital, Academic Medical Centre (AMC), Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van Aalderen
authors.affiliation: Department of Pediatrics, Viecuri Medical Centre, Venlo, The Netherlands.
authors.forename: Han
authors.initials: H
authors.lastname: Hendriks
authors.affiliation: Department of Methodology and Statistics, CAPHRI, MUMC+, Maastricht, The Netherlands.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Winkens
authors.affiliation: Laboratory of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.|Department of Sciences, University College Roosevelt, Middelburg, The Netherlands.
authors.forename: Ger
authors.initials: G
authors.lastname: Rijkers
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
authors.forename: Quirijn
authors.initials: Q
authors.lastname: Jöbsis
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
authors.forename: Edward
authors.initials: E
authors.lastname: Dompeling
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis*; D001944:Breath Tests; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D015415:Biomarkers