The chitinase-like protein YKL-40: A possible biomarker of inflammation and airway remodeling in severe pediatric asthma

Konradsen, Jon R.; James, Anna; Nordlund, Björn; Reinius, Lovisa E.; Söderhäll, Cilla; Melén, Erik; Wheelock, Åsa M.; Carlsen, Karin C. Lødrup; Lidegran, Marika; Verhoek, Marri; Boot, Rolf G.; Dahlén, Barbro; Dahlén, Sven Erik; Hedlin, Gunilla

doi:10.1016/j.jaci.2013.03.003

Cited by 115 publications

(124 citation statements)

References 34 publications

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“…Serum YKL-40 levels and chitotriosidase activity have not previously been examined in parallel in patients with COPD and patients with asthma. The finding of increased serum YKL-40 in patients with asthma confirms previous observations (7,8,24,25). The higher levels in patients with severe asthma than in patients with mild asthma, along with the correlation between YKL-40 and reduced lung function, strengthen the association of serum YKL-40 with disease severity (7,8).…”

Section: Discussionsupporting

confidence: 88%

“…The finding of increased serum YKL-40 in patients with asthma confirms previous observations (7,8,24,25). The higher levels in patients with severe asthma than in patients with mild asthma, along with the correlation between YKL-40 and reduced lung function, strengthen the association of serum YKL-40 with disease severity (7,8). The exact biological role of YKL-40 remains unclear, but it consistently correlates with airway obstruction in studies of patients with asthma (7,8,24).…”

Section: Discussionsupporting

confidence: 86%

“…The higher levels in patients with severe asthma than in patients with mild asthma, along with the correlation between YKL-40 and reduced lung function, strengthen the association of serum YKL-40 with disease severity (7,8). The exact biological role of YKL-40 remains unclear, but it consistently correlates with airway obstruction in studies of patients with asthma (7,8,24). YKL-40 associates with measures of airway remodeling, such as bronchial wall thickness and subepithelial Figure 2.…”

Section: Discussionmentioning

confidence: 82%

“…Although AMCase has been associated with airway inflammation predominantly in animal models (3), chitotriosidase activity is increased in the airways of smokers and subjects with chronic obstructive pulmonary disease (COPD) compared with healthy control subjects (4,5), as well as in the serum of patients with asthma (6). YKL-40 levels are increased in the serum and lungs of patients with asthma compared with healthy control subjects, and they correlate with markers of disease severity (7,8).…”

mentioning

confidence: 99%

“…YKL-40 levels and chitotriosidase activity are subject to genetic regulation and were therefore also analyzed, taking into account the effect of common polymorphisms in the CHI3L1 and CHIT1 genes, respectively. CHI3L1 rs4950928 (2131C.G) has been associated with features of asthma and increased serum YKL-40 (8,12), and individuals homozygous for a relatively common 24-bp duplication in exon 10 of CHIT1 (rs3831317) display a complete lack of chitotriosidase activity (13). To assess whether acute airway obstruction and inflammation affect chitinase levels in blood or sputum, we also examined the effect of inhaled allergen on YKL-40 levels in two separate subsets of patients with mild atopic asthma following high-dose or repeated lowdose allergen challenge.…”

mentioning

confidence: 99%

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Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease

James

Reinius

Verhoek

et al. 2016

Am J Respir Crit Care Med

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113

102

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Rationale: Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels.Objectives: 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.Methods: 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).Measurements and Main Results: 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.Conclusions: 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.

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