{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:01:27Z","timestamp":1789761687275,"version":"4.0.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>A reliable asthma diagnosis is difficult in wheezing preschool children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two hundred two preschool recurrent wheezers (aged 2\u20134 yr) were prospectively followed up until 6 years of age. At 6 years of age, 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 6 years of age was determined with a validation set. Biomarkers in exhaled breath condensate, exhaled volatile organic compounds (VOCs), gene expression, and airway resistance were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>At 6 years of age, 198 children were diagnosed (76 with asthma, 122 with transient wheeze). 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 gene expression of toll-like receptor 4, catalase, and tumor necrosis factor-\u03b1 significantly improved asthma prediction (AUC, 75% [increase of 17%]; PPV\/NPV, 76\/73%). This could not be confirmed after validation. Biomarkers in exhaled breath condensate 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%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrial.gov (NCT 00422747).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201408-1537oc","type":"journal-article","created":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T11:47:03Z","timestamp":1417693623000},"page":"201-207","source":"Crossref","is-referenced-by-count":77,"title":["Exhaled Biomarkers and Gene Expression at Preschool Age Improve Asthma Prediction at 6 Years of Age"],"prefix":"10.1093","volume":"191","author":[{"given":"Ester M. M.","family":"Klaassen","sequence":"first","affiliation":[{"name":"Department of Pediatric Pulmonology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim D. G.","family":"van de Kant","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quirijn","family":"J\u00f6bsis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onno C. P.","family":"van Schayck","sequence":"additional","affiliation":[{"name":"Department of Family Medicine Maastricht, School for Public Health and Primary Care, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Smolinska","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands"},{"name":"Top Institute Food and Nutrition, Wageningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan W.","family":"Dallinga","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik J.","family":"van Schooten","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan J. 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