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Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air.

Meyer N, Dallinga JW, Nuss SJ, Moonen EJ, van Berkel JJ, Akdis C, van Schooten FJ, Menz G - Respir. Res. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: High Altitude Clinic (Hochgebirgsklinik) Davos, Davos-Wolfgang, Switzerland. norbert.meyer@insel.ch.

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.

Conclusion: This study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.

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Related in: MedlinePlus

VOC concentrations in exhaled air in asthma patients and healthy subjects. VOC in exhaled air were compared between healthy donors and asthma patients. The four VOCs, which have been selected for cluster analyses, are shown in A. VOCs not selected for cluster analyses are shown in B.
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Fig2: VOC concentrations in exhaled air in asthma patients and healthy subjects. VOC in exhaled air were compared between healthy donors and asthma patients. The four VOCs, which have been selected for cluster analyses, are shown in A. VOCs not selected for cluster analyses are shown in B.

Mentions: For the formation of asthma endotype clusters by clinical features, asthma medications and VOCs in exhaled air unsupervised hierarchical two-step cluster analysis was used. The clinical features included forced expiratory volume in one-second (FEV1), its ratio to the inspiratory vital capacity (IVC), FEV1 improvement after 3 weeks in the high altitude clinic and Junipers asthma symptom score assessed at admittance. The therapy features included the fraction of patients using systemic steroids, inhaled steroids or long β2 agonists and the frequency of short β2 agonist usage per day. To have an equal proportion between clinical parameters, asthma therapy features and VOCs in exhaled air for cluster analysis, we selected 4 VOCs for cluster analysis, which were detectable in asthma but not in healthy subjects (Figure 2). In detail, VOCs 141, 424, 470, 478 were selected (Figure 2A).Figure 2


Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air.

Meyer N, Dallinga JW, Nuss SJ, Moonen EJ, van Berkel JJ, Akdis C, van Schooten FJ, Menz G - Respir. Res. (2014)

VOC concentrations in exhaled air in asthma patients and healthy subjects. VOC in exhaled air were compared between healthy donors and asthma patients. The four VOCs, which have been selected for cluster analyses, are shown in A. VOCs not selected for cluster analyses are shown in B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4264530&req=5

Fig2: VOC concentrations in exhaled air in asthma patients and healthy subjects. VOC in exhaled air were compared between healthy donors and asthma patients. The four VOCs, which have been selected for cluster analyses, are shown in A. VOCs not selected for cluster analyses are shown in B.
Mentions: For the formation of asthma endotype clusters by clinical features, asthma medications and VOCs in exhaled air unsupervised hierarchical two-step cluster analysis was used. The clinical features included forced expiratory volume in one-second (FEV1), its ratio to the inspiratory vital capacity (IVC), FEV1 improvement after 3 weeks in the high altitude clinic and Junipers asthma symptom score assessed at admittance. The therapy features included the fraction of patients using systemic steroids, inhaled steroids or long β2 agonists and the frequency of short β2 agonist usage per day. To have an equal proportion between clinical parameters, asthma therapy features and VOCs in exhaled air for cluster analysis, we selected 4 VOCs for cluster analysis, which were detectable in asthma but not in healthy subjects (Figure 2). In detail, VOCs 141, 424, 470, 478 were selected (Figure 2A).Figure 2

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: High Altitude Clinic (Hochgebirgsklinik) Davos, Davos-Wolfgang, Switzerland. norbert.meyer@insel.ch.

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.

Conclusion: This study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.

Show MeSH
Related in: MedlinePlus