Simvastatin Therapy and Bronchoalveolar Lavage Fluid Biomarkers in Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive disease underlain by airway inflammation. Despite trials with new generations of anti-inflammatory drugs to alleviate the disease burden, the effective curative treatment remains elusive. In this context, the aim of this study was to assess the influence of simvastatin, a leading member of the family of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known to display anti-inflammatory and immunomodulatory activity, on symptoms and lung function, as well as the proportion of inflammatory cells, cytokines, proteolytic enzymes, and surfactant protein D (SP-D) content in bronchoalveolar lavage fluid (BALF) in COPD patients. There were 50 patients with moderate-to-severe airway obstructions included into the study, subdivided into simvastatin-treated (Zocor - MSD; 40 mg daily) and control simvastatin-untreated groups, other treatment being equal. Pulmonary functions tests and bronchofiberoscopy with BALF procedure were performed before and after 3-month-long treatment in both groups. The major finding was that simvastatin treatment caused a distinct increase in the airway content of SP-D. Further effects, albeit smaller in magnitude, consisted of reductions in the proportion of airway neutrophils and in MMP-9 content, all with a benefit of improved score in the disease activity assessment test. There were no appreciable changes noted in lung function or dyspnea perception, which could be ascribed to simvastatin treatment. We conclude that statin's anti-inflammatory and surfactant homeostasis preserving properties may offer promise as an adjunctive treatment in COPD patients. The SP-D content in BALF has a potential to become a marker of COPD inflammatory activity and treatment monitoring.

Keywords: COPD; Cytokines; Fiber-optic bronchoscopy; Matrix Metalloproteinases; Pulmonary function; Statins; Surfactant protein.