TY - JOUR
T1 - Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease
AU - James, Anna J.
AU - Reinius, Lovisa E.
AU - Verhoek, Marri
AU - Gomes, Anna
AU - Kupczyk, Maciej
AU - Hammar, Ulf
AU - Ono, Junya
AU - Ohta, Shoichiro
AU - Izuhara, Kenji
AU - Bel, Elisabeth
AU - Kere, Juha
AU - Söderhäll, Cilla
AU - Dahlén, Barbro
AU - Boot, Rolf G.
AU - Dahlén, Sven-Erik
AU - AUTHOR GROUP
AU - Gaga, Mina
AU - Siafakas, Nikos M.
AU - Papi, Alberto
AU - Fabbri, Leonardo M.
AU - Joos, Guy
AU - Brusselle, Guy
AU - Rabe, Klaus F.
AU - Kanniess, Frank
AU - Hiemstra, Pieter
AU - Johnston, Sebastian L.
AU - Chanez, Pascal
AU - Vachier, Isabelle
AU - Gjomarkaj, Mark
AU - Sterk, Peter J.
AU - Howarth, Peter H.
AU - Nizankowska-Mogilnicka, Ewa
AU - Middelveld, Roelinde
AU - Holgate, Stephen T.
AU - Wilson, Susan
PY - 2016
Y1 - 2016
N2 - Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure. Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16). Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels. YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes
AB - Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure. Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16). Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels. YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes
U2 - https://doi.org/10.1164/rccm.201504-0760OC
DO - https://doi.org/10.1164/rccm.201504-0760OC
M3 - Article
C2 - 26372680
SN - 1073-449X
VL - 193
SP - 131
EP - 142
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2
ER -