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Late Breaking Abstract - Increased serum levels of YKL-40 in male smoking chronic obstructive pulmonary disease patients associated with altered miRNA levels in alveolar macrophages

Benedikt Zöhrer, Anna James, Nabil Souihi, Bettina Brundin, Reza Karimi, David J. Erle, Sven-Eric Dahlén, C. Magnus Sköld, Åsa M. Wheelock
European Respiratory Journal 2020 56: 4714; DOI: 10.1183/13993003.congress-2020.4714
Benedikt Zöhrer
1Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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  • For correspondence: benedikt.zohrer@ki.se
Anna James
2The Institute of Environmental Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
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Nabil Souihi
3Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, The Institute of Environmental Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
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Bettina Brundin
1Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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Reza Karimi
1Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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David J. Erle
4Division of Pulmonary and Critical Care, Department of Medicine and Cardiovascular Research Institute and Lung Biology Center, University of California–San Francisco, San Francisco, United States of America
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Sven-Eric Dahlén
2The Institute of Environmental Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
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C. Magnus Sköld
1Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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Åsa M. Wheelock
1Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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Abstract

Background: The protein YKL-40 (CHI3L1) is associated with smoking and chronic obstructive pulmonary disease (COPD). Smoking is a major risk factor for COPD, and the importance of gender on molecular COPD sub-phenotypes is emerging.

Aims and Objectives: To investigate the influence of gender and smoking on YKL-40 levels, and putative regulatory mechanisms of YKL-40 expression in the lung.

Methods: YKL-40 was quantified by ELISA in serum and bronchoalveolar lavage (BAL) fluid in never-smokers (n=40), smokers with normal lung function (n=40), as well as smokers (n=27) and ex-smokers (n=11) with mild to moderate COPD. CHI3L1 mRNA and associated miRNA were quantified in BAL cells and bronchial epithelial cells (BEC) using microarray.

Results: Serum YKL-40 was significantly elevated in the male smoking COPD patients compared to male smokers without COPD (p<0.05) and male healthy never-smokers (p<0.01). Furthermore, serum YKL-40 levels correlated with goblet cell abundance (r=0.71) and mean corpuscular hemoglobin (r=0.75) in male smoking COPD patients. In BAL fluid, no significant differences in YKL-40 levels were observed. CHI3L1 mRNA levels in BAL cells were altered in a similar fashion to serum YKL-40 levels, with no alterations observed in BEC. A subset of 10 miRNA known to target CHI3L1 were decreased in BAL cells of male COPD-smokers versus male smokers.

Conclusions: Alveolar macrophages, which make up >85% of BAL cells, could account for the higher YKL-40 serum levels observed in smoking men with COPD, possibly via specific miRNA. This could point towards a male-dominated COPD sub-phenotype associated with chitinase alterations.

  • Biomarkers
  • COPD
  • Smoking

Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4714.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Late Breaking Abstract - Increased serum levels of YKL-40 in male smoking chronic obstructive pulmonary disease patients associated with altered miRNA levels in alveolar macrophages
Benedikt Zöhrer, Anna James, Nabil Souihi, Bettina Brundin, Reza Karimi, David J. Erle, Sven-Eric Dahlén, C. Magnus Sköld, Åsa M. Wheelock
European Respiratory Journal Sep 2020, 56 (suppl 64) 4714; DOI: 10.1183/13993003.congress-2020.4714

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Late Breaking Abstract - Increased serum levels of YKL-40 in male smoking chronic obstructive pulmonary disease patients associated with altered miRNA levels in alveolar macrophages
Benedikt Zöhrer, Anna James, Nabil Souihi, Bettina Brundin, Reza Karimi, David J. Erle, Sven-Eric Dahlén, C. Magnus Sköld, Åsa M. Wheelock
European Respiratory Journal Sep 2020, 56 (suppl 64) 4714; DOI: 10.1183/13993003.congress-2020.4714
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