Exhaled Biomarkers and Gene Expression at Preschool Age Improve Asthma Prediction at 6 Years of Age

E.M.M. Klaassen, K.D.G. van de Kant, Q. Jöbsis, O.C.P. van Schayck, A. Smolinska, J.W. Dallinga, F.J. van Schooten, G.J.M. den Hartog, J.C. de Jongste, G.T. Rijkers, E. Dompeling

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18 Citations (Scopus)

Abstract

Rationale: A reliable asthma diagnosis is difficult in wheezing preschool children. Objectives: To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children. Methods: 202 preschool recurrent wheezers (aged two-four years) were prospectively followed-up until age six years. At age six, a diagnosis (asthma or transient wheeze) was based on symptoms, lung function and asthma medication use. The added predictive value (area under the receiver operating characteristic curve [AUC]) of biomarkers to clinical information (assessed with the Asthma Predictive Index [API]) assessed at preschool age, in diagnosing asthma at age six was determined with a validation set. Biomarkers in exhaled breath condensate [EBC], exhaled volatile organic compounds [VOCs], gene expression, and airway resistance were measured. Measurements and Main Results: At age six, 198 children were diagnosed (76 asthmatics, 122 transient wheezers). Information on exhaled VOCs significantly improved asthma prediction (AUC: 89% (increase of 28%), positive predictive value (PPV)/negative predictive value (NPV) 82/83%) which persisted in the validation set. Information on expression of toll-like receptor 4, catalase and tumor-necrosis-factor alpha significantly improved asthma prediction (AUC: 75% (increase of 17%), PPV/NPV 76/73%). This could not be confirmed after validation. Biomarkers in EBC and airway resistance (pre- and post- bronchodilator) did not improve an asthma prediction. The combined model with VOCs, gene expression and API had an AUC of 95% (PPV/NPV 90/89%). Conclusions: Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children.
Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume191
Issue number2
DOIs
Publication statusPublished - 15 Jan 2015

Keywords

  • children
  • exhaled breath condensate
  • gene expression
  • volatile organic compounds
  • wheeze
  • VOLATILE ORGANIC-COMPOUNDS
  • BREATH CONDENSATE
  • INTERRUPTER RESISTANCE
  • INFLAMMATORY MARKERS
  • PULMONARY-DISEASES
  • CHILDHOOD ASTHMA
  • YOUNG-CHILDREN
  • NITRIC-OXIDE
  • SCHOOL-AGE
  • SYMPTOMS

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