title: Factors that influence the volatile organic compound content in human breath.
abstract: BACKGROUND
  Thousands of endogenous and exogenous volatile organic compounds (VOCs) are excreted in each breath. Inflammatory and deviant metabolic processes affect the level of endogeneous VOCs, which can serve as specific biomarkers for clinical diagnosis and disease monitoring. Important issues that still need to be tackled are related to potential confounding factors like gender and age and endogenous and exogenous factors, like f.i. smoking.
  
  
  METHODS
  The aim of this study was to systematically access the effect of endogenous and exogenous factors on VOC composition of exhaled breath. In the current study breath samples from 1417 adult participants from the LifeLines cohort, a general population cohort in the Netherlands, were collected and the total content of VOCs was measured using gas chromatography-time-of-flight-mass spectrometry. Breath samples were collected in Groningen and transferred to carbon tubes immediately. These samples were then shipped to Maastricht and measured in batches. VOCs profiles were correlated to 14 relevant characteristics of all participants including age, BMI, smoking and blood cell counts and metabolic parameters as well as to 16 classes of medications.
  
  
  RESULTS
  VOCs profiles were shown to be significantly influenced by smoking behavior and to a lesser extent by age, BMI and gender. These factors need to be controlled for in breath analysis studies. We found no evidence whatsoever in this 1417 subjects' cohort that white blood cell counts, cholesterol or triglycerides levels have an influence on the VOC profile. Thus they may not have to be controlled for in exhaled breath studies.
  
  
  CONCLUSIONS
  The large cohort of volunteers used here represents a unique opportunity to gauge the factors influencing VOCs profiles in a general population i.e. the most clinically relevant population. Classical clinical parameters and smoking habits clearly influence breath content and should therefore be accounted for in future clinical studies involving breath analysis.
authors.affiliation: Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands. Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, The Netherlands. Thayer school of engineering, Dartmouth College, Hanover, NH, United States of America.
authors.forename: L
authors.initials: L
authors.lastname: Blanchet
authors.forename: A
authors.initials: A
authors.lastname: Smolinska
authors.forename: A
authors.initials: A
authors.lastname: Baranska
authors.forename: E
authors.initials: E
authors.lastname: Tigchelaar
authors.forename: M
authors.initials: M
authors.lastname: Swertz
authors.forename: A
authors.initials: A
authors.lastname: Zhernakova
authors.forename: J W
authors.initials: JW
authors.lastname: Dallinga
authors.forename: C
authors.initials: C
authors.lastname: Wijmenga
authors.forename: F J
authors.initials: FJ
authors.lastname: van Schooten
mesh_terms: D000367:Age Factors; D015415:Biomarkers / Q000032:analysis; D015992:Body Mass Index; D001944:Breath Tests / Q000379:methods*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D015986:Confounding Factors, Epidemiologic; D003267:Contraception; D045853:Exhalation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012907:Smoking; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D015415:Biomarkers; D055549:Volatile Organic Compounds; D002784:Cholesterol