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

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.

Sputum Gene Expression of IL-13 Receptor α2 Chain Correlates with Airflow Obstruction and Helper T-Cell Type 2 Inflammation in Asthma.

Background: BRP-39/YKL-40 is a chitinase-like protein that plays a critical role in IL-13-induced inflammation. It correlates positively with asthma severity and airway remodeling ( 1 ) via binding to IL-13 receptor α2 chain (IL-13Rα2). Because the relationship of IL-13Rα2 to human asthma has never been evaluated previously, we sought to determine the relationship between IL-13Rα2, YKL-40, and asthma.

Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma.

Introduction: It is increasingly recognized that asthma is a heterogeneous disease. Therefore, it is possible that analysis of gene expression in the airway will reveal clinically meaningful transcriptional endotypes of asthma (TEA clusters).

Methods: We measured whole transcriptome gene expression profiles in the sputum and whole blood of 100 individuals with asthma and 12 control subjects using the Affymetrix HuGene ST 1.

Noninvasive analysis of the sputum transcriptome discriminates clinical phenotypes of asthma.

Rationale: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.

Objectives: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.

Methods: Gene expression in the sputum and blood of patients with asthma was measured using Affymetrix microarrays.

Genetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity and airway expression of YKL-40.

Background: Single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) promoter, the gene encoding YKL-40, are associated with circulating YKL-40 levels and asthma prevalence. However, the effects of gene polymorphisms on asthma severity and airway expression of YKL-40 have not been examined.

Objective: We sought to determine the effect of genetic variation in CHI3L1 on asthma severity and YKL-40 expression in subjects from the Yale Center for Asthma and Airways Disease and the Severe Asthma Research Program.

A chitinase-like protein in the lung and circulation of patients with severe asthma.

Background: The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3-like 1), can be readily measured in the serum.

Urinary hexane diamine to assess respiratory exposure to hexamethylene diisocyanate aerosol: a human inhalation study.

The use of urinary hexane diamine (HDA) as a biomarker to assess human respiratory exposure to hexamethylene diisocyanate (HDI) aerosol was evaluated. Twenty-three auto body shop workers were exposed to HDI biuret aerosol for two hours using a closed exposure apparatus. HDI exposures were quantified using both a direct-reading instrument and a treated-filter method.