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

Delgado-Eckert, Edgar; Fuchs, Oliver; Kumar, Nitin; Pekkanen, Juha; Dalphin, Jean-Charles; Riedler, Josef; Lauener, Roger; Kabesch, Michael; Kupczyk, Maciej; Dahlen, Sven-Erik; Mutius, Erika von; Frey, Urs (2018). Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants. Thorax, 73(2), pp. 107-115. BMJ Publishing Group 10.1136/thoraxjnl-2016-209919

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RATIONALE 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. OBJECTIVES 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. METHODS 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. MEASUREMENTS AND MAIN RESULTS 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. CONCLUSIONS 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology

UniBE Contributor:

Fuchs, Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0040-6376

Publisher:

BMJ Publishing Group

Language:

English

Submitter:

Romy Melanie Rodriguez Del Rio

Date Deposited:

09 Apr 2018 15:45

Last Modified:

09 Apr 2018 15:45

Publisher DOI:

10.1136/thoraxjnl-2016-209919

PubMed ID:

28866644

Uncontrolled Keywords:

asthma asthma mechanisms lung physiology not applicable paediatric asthma respiratory measurement

BORIS DOI:

10.7892/boris.109255

URI:

https://boris.unibe.ch/id/eprint/109255

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