In their 2011 Perspective article in the Journal, Churg and colleagues (1) succinctly critique the merits of using animal models for assessing potential disease-modifying therapies in chronic obstructive pulmonary disease (COPD) and highlight the need to focus on small airways disease. We outline recent human data that suggests statin therapy may have remodeling effects on small airways disease relevant to COPD. We published an article reviewing the animal and human data suggesting that the antiinflammatory or immunomodulatory effects of statins may explain their beneficial effects in patients with COPD (2). Specifically, we suggest that statins achieve this through one or more of the following pharmacological effects: inhibition of cytokine production (TNF-a, IL-6, IL-8), inhibition of neutrophil infiltration, inhibition of fibrotic activity, and/ or antioxidant and antiinflammatory effects. Limited evidence from human studies suggest that statins might confer specific effects on small airways disease. Based on computerized tomographic scans of patients with COPD in the large COPDGene study, those with COPD taking statins had significantly larger small airways diameter than those not taking statins (3). In a prospective study of patients with COPD receiving atorvastatin for 3 months, while FEV1 remained unchanged, there was a significant increase in inspiratory capacity and reduction in thoracic gas volume, suggesting improvement in dynamic hyperinflation (4). In the only randomized control trial (RCT), pravastatin was shown to increase exercise endurance and reduce breathlessness by 30 to 50% in patients with moderate COPD while lung function remained unchanged (2). These studies lead us to postulate that statins may improve small airways function, reduce hyperinflation, and thereby improve exercise endurance and breathlessness. Numerous human studies suggest mechanisms by which statins might do this. First, limited data suggest that statins may reduce airways fibrosis and the development of bronchiolitis obliterans in lung transplantation (2). Second, statin therapy has been shown to inhibit cytokine-induced release of matrix metalloproteinases and to inhibit TGF-b1–induced fibronectin expression in human airway fibroblasts (5, 6). Collectively, these studies suggest that statin therapy may improve small airways function through remodeling effects mediated by airway epithelium. Further studies will be required to confirm these findings. In conclusion, data from both animal (1) and human studies (2–6) suggest that statin therapy might improve small airways disease in COPD despite little change in FEV1. This hypothesis requires testing in carefully designed randomized control trials of statin therapy in COPD such as the STATCOPE trial (http:// clinicaltrials.gov).

Statins and small airways disease in COPD.

Les exacerbations de la BPCO : susceptibilité individuelle et caractéristiques des patients à risque

BPCO: le portrait-robot du patient fréquent-exacerbateur est désormais disponible

Peter A. Bercz

Papers

Statin Use In COPDgene Subjects Is Associated With Larger Airways And Fewer Exacerbations

Prediction Of Future Respiratory Exacerbations In Smokers. The COPDGene Cohort

Airway Dimensions By Computed Tomography In COPD Patients With Bronchodilator Reversibility

Clincal Predictors Of Thromboembolic Events In Chronic Obstructive Pulmonary Disease Subjects In The Copdgene Study