Anna J James1,2, Lovisa E Reinius2,3,4, Marri Verhoek5, Anna Gomes1,2, Maciej Kupczyk1,2, Ulf Hammar1, Junya Ono6, Shoichiro Ohta7, Kenji Izuhara8, Elisabeth Bel9, Juha Kere2,3,4, Cilla Söderhäll2,3,4, Barbro Dahlén2,10, Rolf G Boot5, Sven-Erik Dahlén1,2. 1. 1 Institute of Environmental Medicine. 2. 2 Center for Allergy Research. 3. 3 Center for Innovative Medicine, and. 4. 4 Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. 5. 5 Department of Biochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands. 6. 6 Shino-Test Corporation, Sagamihara, Japan. 7. 7 Department of Laboratory Medicine and. 8. 8 Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga University, Saga, Japan. 9. 9 Department of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and. 10. 10 Department of Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Abstract
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.
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.
Authors: Gleb Andryianau; Michal Kowalski; Michal C Piotrowicz; Adam A Rajkiewicz; Barbara Dymek; Piotr L Sklepkiewicz; Elzbieta Pluta; Filip Stefaniak; Wojciech Czestkowski; Sylwia Olejniczak; Marzena Mazur; Piotr Niedziejko; Robert Koralewski; Krzysztof Matyszewski; Mariusz Gruza; Agnieszka Zagozdzon; Magdalena Salamon; Aleksandra Rymaszewska; Mikolaj Welzer; Karolina Dzwonek; Jakub Golab; Jacek Olczak; Agnieszka Bartoszewicz; Adam Golebiowski Journal: ACS Med Chem Lett Date: 2020-04-24 Impact factor: 4.345
Authors: Amal Ahmed Abd El-Fattah; Nermin Abdel Hamid Sadik; Olfat Gamil Shaker; Amal Mohamed Kamal Journal: Mediators Inflamm Date: 2018-10-25 Impact factor: 4.711
Authors: Jose L Gomez; Xiting Yan; Carole T Holm; Nicole Grant; Qing Liu; Lauren Cohn; Vera Nezgovorova; Deborah A Meyers; Eugene R Bleecker; Gina M Crisafi; Nizar N Jarjour; Linda Rogers; Joan Reibman; Geoffrey L Chupp Journal: Eur Respir J Date: 2017-10-12 Impact factor: 16.671