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FIZZ2 as a Biomarker for Acute Exacerbation of Chronic Obstructive Pulmonary Disease

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Abstract

Purpose

Found in inflammatory zone 2 (FIZZ2) is associated with lung inflammation. The aim of the study was to investigate the expression and utility of FIZZ2 as a marker for chronic obstructive pulmonary disease (COPD).

Methods

Immunohistochemistry was used to detect the expression of FIZZ2 in COPD. The serum concentration of FIZZ2 was measured by enzyme-linked immunosorbent assay and the episodes of acute exacerbations of COPD (AECOPD) in the following year were recorded.

Results

FIZZ2 expression was elevated in bronchial epithelial cells (0.217 ± 0.021 vs 0.099 ± 0.010, p < 0.0001) and negatively correlated with the pulmonary function (FEV1/FVC%) (p = 0.0149) and positively correlated with the smoking index (p = 0.0241). Serum level of FIZZ2 in COPD were significantly higher than that in healthy controls (561.6 ± 70.71 vs 52.24 ± 20.52 pg/ml, p < 0.0001) and increased with the COPD severity. Serum levels of FIZZ2 negatively correlated with the pulmonary function [Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), FEV1%, FEV1/FVC) (r =  − 0.3086, − 0.3529, − 0.3343, and − 0.2676, respectively, p = 0.0003, p < 0.0001, p < 0.0001, p = 0.0014). The expression of human serum FIZZ2 was positively correlated with the smoking index (r = 0.2749, p = 0.0015). There was a positive correlation between the FIZZ2 concentration and the frequency of AECOPD episodes in the following year (r = 0.7291, p < 0.0001).

Conclusion

FIZZ2 expression was elevated in patients with COPD and its serum concentration might be a potential biomarker for AECOPD.

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Data Availability

The datasets analyzed during the current study are available in the GitHub repository at https://github.com/pivadoc/Surfactant/issues/1.

Abbreviations

FIZZ2:

Found in inflammatory zone 2

COPD:

Chronic obstructive pulmonary disease

CSE:

Cigarette smoke extract

16HBEs:

Human bronchial epithelial

AECOPD:

Acute exacerbations of COPD

BECs:

Bronchial epithelial cells

RELMs:

Resistin-like molecules

ELISA:

Enzyme-linked immunosorbent assay

ANOVA:

Analysis of variance

FEV1:

Forced expiratory volume in one second

FVC:

Forced vital capacity

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Acknowledgements

Thanks to Yunhui Wu, Man Jia, Yaqi Meng, and Jiayan Xu for their experimental technical help.

Funding

There is no research funding source.

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Author notes

  1. Ying Zhou and Yingying Qiao have contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Ying Zhou & Xin Yao

  2. Department of Respiratory Medicine, Nanjing Gulou Group Anqing Petrochemical Hospital, 11 Shihua First Road, Anqing, 246002, China

    Ying Zhou

  3. Department of Respiratory Medicine, The Third Affiliated Hospital of Suzhou University, 185 Juqian Street, Changzhou, 213003, China

    Yingying Qiao & Jun Zhou

  4. Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK

    Ian M. Adcock

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  1. Ying Zhou
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Contributions

YZ and XY designed this study; YQ and JZ collected serum samples; YZ conducted experiments, data analysis and interpretation; YZ wrote the manuscript; XY and IMA strictly revised the manuscript. All authors read and approved the final paper.

Corresponding authors

Correspondence to Jun Zhou or Xin Yao.

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Conflict of interest

Ying Zhou, Xin Yao, Yingying Qiao, Jun Zhou, and Ian M. Adcock have nothing to disclose.

Ethical Approval

The protocol was approved by the ethics committee of The First Affiliated Hospital of Nanjing Medical University (2014-SR-150).

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Zhou, Y., Qiao, Y., Adcock, I.M. et al. FIZZ2 as a Biomarker for Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Lung 199, 629–638 (2021). https://doi.org/10.1007/s00408-021-00483-1

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