Serum cystatin C as a potential biomarker for the evaluation COPD.

BACKGROUND Imbalance between protease-antiprotease plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cystatin C in circulating blood is a cysteine protease inhibitor and contributes to elastolysis and tissue destruction. OBJECTIVES The aims of the present study were to investigate whether cystatin C was a promising biomarker for the evaluation and follow-up of patients with COPD. METHODS Serum cystatin C level was determined in groups of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (n = 93), stable COPD (SCOPD) (n = 299) and healthy controls (n = 151). The influences of smoking on the level of serum cystatin C and the correlation of cystatin C with lung functional parameters were further analyzed. RESULTS Serum cystatin C level was significantly higher in COPD patients than that of healthy controls. Smoking increased serum cystatin C level in patients with SCOPD but not in AECOPD and control. In SCOPD group, serum cystatin C level was positively correlated with RV%TLC and negatively correlations with FEV1% predicted, FEV1%FVC, MMEF75/25% predicted, MVV% predicted and DLco% predicted. In multiple line analysis, FEV1% predicted and age were found to be independent predictors of serum cystatin C levels, but not smoking statue, sex and BMI. CONCLUSIONS COPD had a higher level of serum cystatin C, smoking only increased cystatin C level in SCOPD. Serum cystatin C level was negatively correlated with FEV1% predicted. These results suggest that cystatin C might be a potential biomarker for lung tissue destruction and severity of COPD.

[1]  X. Ou,et al.  [Exacerbation phenotyping in chronic obstructive pulmonary disease]. , 2014, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[2]  R. Abboud,et al.  Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema , 2013, European Respiratory Journal.

[3]  N. Zhong,et al.  Non‐smoking‐related chronic obstructive pulmonary disease: A neglected entity? , 2012, Respirology.

[4]  Li Li,et al.  Age-associated changes in pulmonary function: a comparison of pulmonary function parameters in healthy young adults and the elderly living in Shanghai. , 2012, Chinese medical journal.

[5]  S. Hurd,et al.  [An overview of Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) (revised 2011)]. , 2012, Zhonghua yi xue za zhi.

[6]  A. Larbi,et al.  The role of elastin peptides in modulating the immune response in aging and age-related diseases. , 2012, Pathologie-biologie.

[7]  S. Agarwal,et al.  Serum Cystatin C and Emphysema: Results from the National Health and Nutrition Examination Survey (NHANES) , 2012, Lung.

[8]  T. Nyman,et al.  Recognition of Cytoplasmic RNA Results in Cathepsin-Dependent Inflammasome Activation and Apoptosis in Human Macrophages , 2011, The Journal of Immunology.

[9]  K. Tsunekawa,et al.  Influence of Thyroid Hormones and Transforming Growth Factor-β1 on Cystatin C Concentrations , 2010, The Journal of international medical research.

[10]  D. Siscovick,et al.  Age and cystatin C in healthy adults: a collaborative study. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  C. Owen Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease , 2008, International journal of chronic obstructive pulmonary disease.

[12]  G. Folkerts,et al.  Cells, mediators and Toll-like receptors in COPD. , 2008, European journal of pharmacology.

[13]  P. Black,et al.  Changes in elastic fibres in the small airways and alveoli in COPD , 2008, European Respiratory Journal.

[14]  R. Abboud,et al.  Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema. , 2008, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[15]  R. Ekart,et al.  Serum Cystatin C as an Endogenous Marker of Renal Function in Patients with Chronic Kidney Disease , 2008, Renal failure.

[16]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[17]  W. Stark,et al.  Interaction between Human Cathepsins K, L, and S and Elastins , 2007, Journal of Biological Chemistry.

[18]  T. Tetley Inflammatory cells and chronic obstructive pulmonary disease. , 2005, Current drug targets. Inflammation and allergy.

[19]  M. Nugent,et al.  Elastase mediates the release of growth factors from lung in vivo. , 2004, American journal of respiratory cell and molecular biology.

[20]  S. Holgate,et al.  Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment. , 2003, American journal of respiratory and critical care medicine.

[21]  T. Betsuyaku,et al.  Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. , 1998, The European respiratory journal.

[22]  J. Kos,et al.  Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). , 1998, Oncology reports.

[23]  A. Warfel,et al.  Cystatin C and Cathepsin B Production by Alveolar Macrophages From Smokers and Nonsmokers , 1991, Journal of leukocyte biology.

[24]  D. Barnes,et al.  Transforming growth factor beta regulates cystatin C in serum-free mouse embryo (SFME) cells. , 1990, Biochemical and biophysical research communications.

[25]  J. Reilly,et al.  Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. , 1990, The American review of respiratory disease.

[26]  A. Barrett,et al.  The place of human γ-trace (cystatin C) amongst the cysteine proteinase inhibitors , 1984 .

[27]  R. Crystal,et al.  Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema. , 1981, Science.

[28]  M. Cleman,et al.  Cystatin C: an emerging biomarker in cardiovascular disease. , 2013, Current topics in medicinal chemistry.

[29]  R. Abboud,et al.  Alveolar macrophage proteinase/antiproteinase expression and lung function/emphysema , 2013 .

[30]  A. Barrett,et al.  The place of human gamma-trace (cystatin C) amongst the cysteine proteinase inhibitors. , 1984, Biochemical and biophysical research communications.

[31]  P. Macklem,et al.  Significance of the relationship between lung recoil and maximum expiratory flow. , 1967, Journal of applied physiology.