Characterisation of asthma subgroups associated with circulating YKL-40 levels

Eur Respir J. 2017 Oct 12;50(4):1700800. doi: 10.1183/13993003.00800-2017. Print 2017 Oct.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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