Characterisation of asthma subgroups associated with circulating YKL-40 levels.

Abstract

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.

• Authors: Jose L Gomez, Xiting Yan, Carole T Holm, Nicole Grant, Qing Liu, Lauren Cohn, Vera Nezgovorova, Deborah A Meyers, Eugene R Bleecker, Gina M Crisafi, Nizar N Jarjour, Linda Rogers, Joan Reibman, Geoffrey L Chupp, SARP Investigators
• Journal: The European respiratory journal (Eur Respir J) Vol. 50 Issue 4 (10 2017) ISSN: 1399-3003 [Electronic] England
• PMID: 29025889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright ©ERS 2017.

Chemical References

• CHI3L1 protein, human
• Chitinase-3-Like Protein 1

Topics

• Adolescent
• Adult
• Age of Onset
• Airway Obstruction (immunology)
• Asthma (blood, diagnosis, physiopathology)
• Chitinase-3-Like Protein 1 (analysis, blood)
• Cluster Analysis
• Cross-Sectional Studies
• Disease Progression
• Female
• Gene Expression Profiling
• Humans
• Inflammation (immunology)
• Male
• Middle Aged
• Reproducibility of Results
• Respiratory System (immunology, physiopathology)
• Severity of Illness Index
• Sputum (metabolism)
• Statistics as Topic
• Symptom Flare Up