Elevated Serum Matrix Metalloprotease (MMP-2) as a Candidate Biomarker for Stable COPD

Durga Mahor; Vandana Kumari; Kapil Vashisht; Ruma Galgalekar; Ravindra M. Samarth; Pradyumna K. Mishra; Nalok Banerjee; Rajnikant Dixit; Rohit Saluja; Sajal De; Kailash C. Pandey


BMC Pulm Med. 2020;20(302) 

In This Article


Chronic obstructive pulmonary disease (COPD) is a common, preventable & treatable disease, characterized by the irreversible & progressive airflow obstruction in the lungs, usually due to the exposure to noxious particles or gases. COPD is the most significant chronic respiratory disease with high mortality rates, globally, as well as in India. Approximately, 55.3 million cases of COPD were reported in 2016 from India, with an increase in prevalence from ~ 3.3% (1990) to ~ 4.2% (2016, 1). COPD has been estimated to be responsible for 75.6% disability-adjusted life-years (DALYs) of all the chronic respiratory diseases in the Indian context.[1] Globally, COPD has been projected to be the third leading cause of deaths by 2020 (GOLD report, 2019), with inevitable increase in future due to the aging population and continued exposure to the COPD risk factors (air pollution, tobacco smoke etc.). Tobacco smoke is the most common risk factor for COPD, in addition to the other factors such as indoor air pollution, occupational exposures, host genetic factors, age & sex, lung growth & development and socioeconomic status.[2]

In molecular context, COPD pathogenesis is reminiscent of tissue destruction factors, inflammation, airway remodelling and the accompanying pathways/mediators.[3] The characteristic emphysema in COPD could be attributed to the dysreguatlion of the protease/anti-protease balance.[4,5] Various classes of proteases (serine, cysteine and metallo proteases) have previously been reported in the pathogenesis of COPD.[4] Notably, the serine protease- neutrophil elastase (NE) has been shown to play a crucial role in the destruction of alveolar tissue and development of emphysema.[6] Precise regulation of NE activity is regulated by its inhibitor- A1AT (α-1 antitrypsin)[7] and its genetic deficiency (A1AT) has been reported to predispose an individual to early onset of emphysema.[8] Another serine exopeptidase- dipeptidyl peptidase-IV (DPP-IV) is crucial in regulating the inflammatory responses in the lungs by antagonising various inflammatory cytokines. Hence, a significant decrease in DPP-IV levels in COPD patients has been concluded as a good serological marker of COPD.[9] The role of cysteine proteases in the pathogensis of COPD has been established through destruction of alveolar epithelial and endothelial cells via proteolytic activities of caspases- [3/8/9].[10] Degradation of the extracellular matrix is a characteristic feature of COPD, causing emphysema, which is accomp;lished by various matrix metalloproteinases (MMPs)- [9/12/13].[11–15]

In this preliminary study, we set out to explore various serum proteases involved in the pathogeneis sof COPD. The goal of the study was to evaluate serum protease, as candidate serological biomarkers for stable COPD. We performed qualitative and quantitative measurements of various serum proteases in stable COPD patients and controls. Selected protease with overlapping activities in Asthma were also compared for any distinctive elevation. Further, proteome analysis via mas spectrometry of the sera from stable COPD pateints and control was also attempted.