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Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants

Delgado-Eckert, Edgar and Fuchs, Oliver and Kumar, Nitin and Pekkanen, Juha and Dalphin, Jean-Charles and Riedler, Josef and Lauener, Roger and Kabesch, Michael and Kupczyk, Maciej and Dahlen, Sven-Eric and Mutius, Erika von and Frey, Urs and Pasture, and Bioair Study groups, . (2017) Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants. Thorax. pp. 107-115.

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Official URL: https://edoc.unibas.ch/64011/

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Abstract

Asthma is characterised by inflammation and reversible airway obstruction. However, these features are not always closely related. Fluctuations of daily lung function contain information on asthma phenotypes, exacerbation risk and response to long-acting β-agonists.; In search of subgroups of asthmatic participants with specific lung functional features, we developed and validated a novel clustering approach to asthma phenotyping, which exploits the information contained within the fluctuating behaviour of twice-daily lung function measurements.; Forced expiratory volume during the first second (FEV1) and peak expiratory flow (PEF) were prospectively measured over 4 weeks in 696 healthy and asthmatic school children (Protection Against Allergy - Study in Rural Environments (PASTURE)/EFRAIM cohort), and over 1 year in 138 asthmatic adults with mild-to-moderate or severe asthma (Pan-European Longitudinal Assessment of Clinical Course and BIOmarkers in Severe Chronic AIRway Disease (BIOAIR) cohort). Using enrichment analysis, we explored whether the method identifies clinically meaningful, distinct clusters of participants with different lung functional fluctuation patterns.; In the PASTURE/EFRAIM dataset, we found four distinct clusters. Two clusters were enriched in children with well-known clinical characteristics of asthma. In cluster 3, children from a farming environment predominated, whereas cluster 4 mainly consisted of healthy controls. About 79% of cluster 3 carried the asthma-risk allele rs7216389 of the 17q21 locus. In the BIOAIR dataset, we found two distinct clusters clearly discriminating between individuals with mild-to-moderate and severe asthma.; Our method identified dynamic functional asthma and healthy phenotypes, partly independent of atopy and inflammation but related to genetic markers on the 17q21 locus. The method can be used for disease phenotyping and possibly endotyping. It may identify participants with specific functional abnormalities, potentially needing a different therapeutic approach.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB)
03 Faculty of Medicine > Departement Biomedical Engineering
UniBasel Contributors:Delgado-Eckert, Edgar
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1468-3296
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:26 Feb 2019 16:30
Deposited On:26 Feb 2019 16:30

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