Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants. Issue 2 (2nd September 2017)

• Record Type: Journal Article
• Authors: 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
• Other Names: author non-byline.; Bitter Sondhja author non-byline.; Braun-fahrländer Charlotte author non-byline.; Büchele Gisela author non-byline.; Dalphin Marie-laure author non-byline.; Depner Martin author non-byline.; Doekes Gert author non-byline.; Ege Markus J author non-byline.; Frei Remo author non-byline.; Genuneit Jon author non-byline.; Hirvonen Maija-riitta author non-byline.; Hyvärinen Anne author non-byline.; Karvonen Anne M author non-byline.; Kaulek Vincent author non-byline.; Loss Georg author non-byline.; Pfefferle Petra Ina author non-byline.; Remes Sami author non-byline.; Renz Harald author non-byline.; Roduit Caroline author non-byline.; Roponen Marjut author non-byline.; Schaub Bianca author non-byline.; Tiittanen Pekka author non-byline.; Middelveld Juliane Weberroelinde author non-byline.; Dahlén Barbro author non-byline.; Gaga Mina author non-byline.; Siafakas Nikos M author non-byline.; Papi Alberto author non-byline.; Fabbri Leonardo M author non-byline.; Joos Guy author non-byline.; Rabe Klaus F author non-byline.; Johnston Sebastian L author non-byline.; Chanez Pascal author non-byline.; Gjormarkaj Mark author non-byline.; Howarth Peter H author non-byline.; Niżankowska-mogilnicka Ewa author non-byline.;
• Is Part Of: Thorax. Volume 73:Issue 2(2018)
• Page Start: 107
• Page End: 115
• Publication Date: 2017-09-02
• Subjects: asthma -- asthma mechanisms -- lung physiology -- paediatric asthma -- respiratory measurement -- not applicable; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2016-209919
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : 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.