Abstract
BackgroundSeveral 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.MethodsBreath 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.ResultsWe 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.ConclusionThis study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0136-8) contains supplementary material, which is available to authorized users.
Highlights
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
To exclude chronic obstructive pulmonary disease, asthma was defined by a reversibility in forced expiratory volume in 1 s (FEV1) of at least 12% predicted after inhalation of a short acting β2-agonist
Identification of Volatile organic compounds (VOC) implicated in the pathogenesis of asthma To investigate, which VOCs are implicated during asthmatic airway inflammation, VOCs in exhaled air were compared between asthma patients and healthy controls
Summary
Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. We aimed to classify new asthma endotypes by combining inflammatory mechanisms investigated by VOC profiles in exhaled air and clinical information of asthma patients. VOCs are present in ambient air as well as result from metabolic processes in many cells and microorganisms They are mainly released during inflammation from cells in response to oxidative stress as a result of activated leukocytes, which produce reactive oxygen species (ROS) [8]. A recent study demonstrate that VOC profiles in exhaled air could classify clinically relevant disease phenotypes based on sputum inflammatory profile [14] and that VOC profiles might predict steroid responsiveness in mild/moderate asthma patients [15]
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