RT Journal Article
SR Electronic
T1 Characterisation of asthma subgroups associated with circulating YKL-40 levels
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1700800
DO 10.1183/13993003.00800-2017
VO 50
IS 4
A1 Gomez, Jose L.
A1 Yan, Xiting
A1 Holm, Carole T.
A1 Grant, Nicole
A1 Liu, Qing
A1 Cohn, Lauren
A1 Nezgovorova, Vera
A1 Meyers, Deborah A.
A1 Bleecker, Eugene R.
A1 Crisafi, Gina M.
A1 Jarjour, Nizar N.
A1 Rogers, Linda
A1 Reibman, Joan
A1 Chupp, Geoffrey L.
YR 2017
UL http://erj.ersjournals.com/content/50/4/1700800.abstract
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