Pharmacological actions of statins: potential utility in COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-kB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-a, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.

A review of the Hispanic paradox: time to spill the beans?

“…However, there is also evidence that systemic inflammation plays a primary role in the development (and possibly progression) of these diseases [15,16]. This conclusion comes from numerous prospective studies showing that markers of systemic inflammation, notably elevated interleukin (IL)-6 or C-reactive protein (CRP), are consistently associated with an increased risk of COPD and lung cancer in both population and cohort studies [17][18][19][20][21][22][23][24].…”

“…Smoking is recognised as a critical initiating insult to the bronchial epithelium, triggering a strong pulmonary innate immune response, in those who develop COPD and lung cancer [14][15][16]. However, there is also evidence that systemic inflammation plays a primary role in the development (and possibly progression) of these diseases [15,16].…”

“…Systemic inflammation, to varying degrees, affects between 50% and 70% of those with COPD and lung cancer [20,22,26]. There are then bidirectional effects between smoking-induced airway inflammation and "inherent" systemic inflammation, where the latter may be responsible for persisting neutrophilic inflammation in the lungs [16]. This, in turn, contributes to the aberrant repair-remodelling processes underlying COPD that result from a protease-antiprotease imbalance, excessive oxidative stress and progressive DNA damage [16].…”

“…This, in turn, contributes to the aberrant repair-remodelling processes underlying COPD that result from a protease-antiprotease imbalance, excessive oxidative stress and progressive DNA damage [16]. In such a microenvironment, rich in metalloproteases and growth factors, both epithelial remodelling (epithelial turnover, and mucous gland hyperplasia and metaplasia) and mesenchymal remodelling (small airway fibrosis, emphysema and epithelial-mesenchymal transition) may contribute to the development or progression of lung cancer [16]. Therefore, we propose that attenuation of systemic inflammation might be one of the critical pathophysiological processes linking diet with smokingrelated lung disease.…”

“…There are then bidirectional effects between smoking-induced airway inflammation and "inherent" systemic inflammation, where the latter may be responsible for persisting neutrophilic inflammation in the lungs [16]. This, in turn, contributes to the aberrant repair-remodelling processes underlying COPD that result from a protease-antiprotease imbalance, excessive oxidative stress and progressive DNA damage [16]. In such a microenvironment, rich in metalloproteases and growth factors, both epithelial remodelling (epithelial turnover, and mucous gland hyperplasia and metaplasia) and mesenchymal remodelling (small airway fibrosis, emphysema and epithelial-mesenchymal transition) may contribute to the development or progression of lung cancer [16].…”