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Characterisation of asthma subgroups associated with circulating YKL-40 levels
Jose L Gomez1, Xiting Yan1, Carole T Holm1
1Section of Pulmonary, Critical Care Medicine and Sleep and Dept of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
The European Respiratory Journal
|October 14, 2017
Summary
High serum YKL-40 levels identify distinct severe asthma phenotypes. These chitinase-like protein (YKL-40) clusters may help identify patients with irreversible obstruction or frequent exacerbations.
Area of Science:
- Pulmonary Medicine
- Immunology
- Biochemistry
Background:
- Chitinase-like protein YKL-40 is implicated in airway inflammation and asthma severity.
- Precise definition of asthma phenotypes linked to YKL-40 levels is lacking.
Purpose of the Study:
- To identify and characterize distinct asthma patient subgroups based on serum YKL-40 levels.
- To investigate the molecular pathways associated with these YKL-40-defined asthma phenotypes.
Main Methods:
- Unsupervised cluster analysis of asthma patients (n=156) based on serum YKL-40.
- Cross-validation in independent cohorts (n=167, n=341).
- Sputum transcriptome analysis to identify molecular pathways in YKL-40 subgroups.
Main Results:
- Four YKL-40 clusters (C1-C4) were identified; C3 and C4 showed high serum YKL-40.
- Cluster C3: earlier onset, severe airflow obstruction, near-fatal exacerbations.
- Cluster C4: adult onset, frequent exacerbations, less airflow obstruction.
- Transcriptome analysis revealed non-type 2 inflammatory pathways in C3 and C4.
Conclusions:
- Elevated serum YKL-40 is associated with two distinct severe asthma phenotypes: irreversible airway obstruction and exacerbation-prone asthma.
- YKL-40 clustering may aid in identifying severe or exacerbation-prone asthma patients.
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