Chronic obstructive pulmonary disease: patho-physiology, current methods of treatment and the potential for simvastatin in disease management

Background. Chronic obstructive pulmonary disease (COPD) is a debilitating disease, causing severe and irreversible respiratory problems, affecting millions of people worldwide. Consequently, in recent years, research has focused on investigating new therapeutic approaches for the treatment of this pathology. Some drug classes, such as ACE inhibitors, PDE4 inhibitors and statins have demonstrated to have anti-inflammatory properties and an effect in improving COPD. Specifically, simvastatin (SV) has shown to be effective in reducing COPD morbidity and mortality. Methods. For the SV transport study, Calu-3 cell monolayers were grown on a liquid covered culture method using 0.33 cm2 Transwell supports (0.4 µm pore size). 100µM SV solution was placed alternatively in the apical or in the basolateral chamber, and samples were collected in the other compartment every hour for 4 hours. For the effect of SV on mucus inhibition study, Calu-3 cell monolayers were grown using an air interface culture model [3]. Samples for microscope analysis were collected at day 2, 7, 11 and 14, respectively. Each sample was fixed with paraformaldheyde (4%), stained with alcian blue and placed onto a glass slide; photos of the stained cell surface were taken and mucus layer quantified as RGBB ratio. Results: Simvastatin was transported in both the apical to basal (1.78% ± 0.09%) and basal to apical directions (1.00% ± 0.22%) suggesting a rational for delivery to the lung. Analysis of the microscopy images showed that chronic administration of simvastatin for 14 days caused a significant inhibition in mucus production. Conclusion: Simvastatin can penetrate by passive diffusion into Calu-3 monolayer. Also, the administration of simvastatin at chronic doses inhibits mucus production. These preliminary findings suggest that local delivery to simvastatin directly to the lung may have a therapeutic effect on mucus reduction and consequently be used for COPD treatment