PT  - JOURNAL ARTICLE
AU  - Gomez, Jose L.
AU  - Yan, Xiting
AU  - Holm, Carole T.
AU  - Grant, Nicole
AU  - Liu, Qing
AU  - Cohn, Lauren
AU  - Nezgovorova, Vera
AU  - Meyers, Deborah A.
AU  - Bleecker, Eugene R.
AU  - Crisafi, Gina M.
AU  - Jarjour, Nizar N.
AU  - Rogers, Linda
AU  - Reibman, Joan
AU  - Chupp, Geoffrey L.
TI  - Characterisation of asthma subgroups associated with circulating YKL-40 levels
AID  - 10.1183/13993003.00800-2017
DP  - 2017 Oct 01
TA  - European Respiratory Journal
PG  - 1700800
VI  - 50
IP  - 4
4099  - http://erj.ersjournals.com/content/50/4/1700800.short
4100  - http://erj.ersjournals.com/content/50/4/1700800.full
SO  - Eur Respir J2017 Oct 01; 50
AB  - The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups.Four YKL-40 clusters (C1–C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways.Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.Asthma with high serum YKL-40 levels is associated with severe lung function impairment and severe exacerbations http://ow.ly/wyly30elajo