title: Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air.
abstract: BACKGROUND
  Several classifications of adult asthma patients using cluster analyses based on clinical and demographic information has resulted in clinical phenotypic clusters that do not address molecular mechanisms. Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. VOC profiles in exhaled air could distinguish between asthma patients and healthy subjects. In this study, we aimed to classify new asthma endotypes by combining inflammatory mechanisms investigated by VOC profiles in exhaled air and clinical information of asthma patients.
  
  
  METHODS
  Breath samples were analyzed for VOC profiles by gas chromatography-mass spectrometry from asthma patients (n = 195) and healthy controls (n = 40). A total of 945 determined compounds were subjected to discriminant analysis to find those that could discriminate healthy from asthmatic subjects. 2-step cluster analysis based on clinical information and VOCs in exhaled air were used to form asthma endotypes.
  
  
  RESULTS
  We identified 16 VOCs, which could distinguish between healthy and asthma subjects with a sensitivity of 100% and a specificity of 91.1%. Cluster analysis based on VOCs in exhaled air and the clinical parameters FEV1, FEV1 change after 3 weeks of hospitalization, allergic sensitization, Junipers symptoms score and asthma medications resulted in the formation of 7 different asthma endotype clusters. We identified asthma clusters with different VOC profiles but similar clinical characteristics and endotypes with similar VOC profiles, but distinct clinical characteristics.
  
  
  CONCLUSIONS
  This study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.
authors.affiliation: High Altitude Clinic (Hochgebirgsklinik) Davos, Davos-Wolfgang, Switzerland. norbert.meyer@insel.ch.|Clinic for Rheumatology, Immunology and Allergology, Divison of Allergology, University Hospital of Bern, Bern, Switzerland. norbert.meyer@insel.ch.
authors.forename: Norbert
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (Nutrim), Maastricht University Medical Center, Maastricht, The Netherlands. j.dallinga@maastrichtuniversity.nl.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Dallinga
authors.affiliation: High Altitude Clinic (Hochgebirgsklinik) Davos, Davos-Wolfgang, Switzerland. sarah.janine.nuss@gmail.com.
authors.forename: Sarah Janine
authors.initials: SJ
authors.lastname: Nuss
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (Nutrim), Maastricht University Medical Center, Maastricht, The Netherlands. e.moonen@maastrichtuniversity.nl.
authors.forename: Edwin J C
authors.initials: EJ
authors.lastname: Moonen
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (Nutrim), Maastricht University Medical Center, Maastricht, The Netherlands. j.vanberkel@maastrichtuniversitiy.nl.
authors.forename: Joep J B N
authors.initials: JJ
authors.lastname: van Berkel
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Christine-Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. akdisac@siaf.uzh.ch.
authors.forename: Cezmi
authors.initials: C
authors.lastname: Akdis
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (Nutrim), Maastricht University Medical Center, Maastricht, The Netherlands. f.vanschooten@maastrichtuniversity.nl.
authors.forename: Frederik Jan
authors.initials: FJ
authors.lastname: van Schooten
authors.affiliation: High Altitude Clinic (Hochgebirgsklinik) Davos, Davos-Wolfgang, Switzerland. guenter.menz@hgk.ch.
authors.forename: Günter
authors.initials: G
authors.lastname: Menz
mesh_terms: D000328:Adult; D001249:Asthma / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D016022:Case-Control Studies; D016000:Cluster Analysis; D016002:Discriminant Analysis; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D015415:Biomarkers; D055549:Volatile Organic Compounds