Chronic obstructive pulmonary disease: role of matrix metalloproteases and future challenges of drug therapy

Abstract

COPD is a chronic disease of the lung that is characterised by decreased air flow and associated abnormal inflammatory responses of the lungs. A total of 80% of COPD incidences are observed in patients with history of smoking tobacco. The chronic condition of COPD is characterised by airway remodelling, which leads to emphysema and chronic bronchitis. Inflammatory cells of the immune system play a major role in pathophysiology of COPD. High levels of neutrophils, macrophages and CD8⁺ T cells have been found in bronchoalveolar lavage samples of COPD patients. Matrix metalloproteases (MMPs), which are secreted by these inflammatory cells, have the enzymatic capacity to cause morphological changes in the lungs and contribute significantly to the COPD state. Increased concentrations of MMP-1, -2, -9, -12 and so on have been found in bronchoalveolar lavage samples of COPD patients compared with non-COPD individuals. COPD is rated as among the top five diseases with high mortality rates and it is estimated that in the next 20 years, the healthcare cost alone for COPD will be US $800 million worldwide. The present drug therapies are neither very efficacious nor cost effective; hence, there is unmet medical need to discover small-molecule drugs for COPD. In this regard, synthetic MMP inhibitors show a great promise for COPD treatment.

Keywords::

• cigarette smoke
• COPD
• emphysema
• fibrosis
• inflammation
• matrix metalloprotease

Acknowledgement

The authors sincerely acknowledge SR Voleti, Molecular Modelling Division of Ranbaxy for providing the 3D structure of a MMP (Figure 3).