Potential Role of Statin Use in Idiopathic Pulmonary Fibrosis

By Santana, Alfredo N C Kairalla, Ronaldo A; Carvalho, Carlos R R

To the Editor: In their article, Dr. Alexeeff and colleagues showed that statins attenuate lung function decline in the elderly (1). In addition, in a letter to the editor from a previous issue, Fadini and colleagues questioned the potential benefit of statins in idiopathic pulmonary fibrosis (IPF) based on their results that showed marked depletion of endothelial progenitor cells (EPC) in IPF patients, which was more severe in the presence of pulmonary arterial hypertension (PAH), in comparison with control subjects (2). Further, it is important to consider a previous study that evaluated statins in IPF (3), which found no survival differences between groups receiving statins versus no statins. However, the authors noted that the work was statistically underpowered to reliably detect a survival benefit of statins (3). Consequently, we believe that it is necessary to reevaluate the potential role of statins in IPF.

There are data to suggest that statins may have use in IPF. First, statins may modify critical determinants of the profibro- genic machinery responsible for the aggressive clinical profile of IPF, including inhibiting connective tissue growth factor (CTGF) gene and protein expression, reducing collagen gel contraction and down-regulating a-smooth muscle actin expression (4). Statins may prevent harmful lung parenchymal remodeling associated with persistent myofibroblast formation (4). Statins may also have a protective effect in IPF by positively modulating EPC (remembering that EPC down-regulation is associated with IPF and with IPF- relatedPAH)(2). Statinsmaybe beneficial in other EPC-related conditions (such as atherosclerosis and PAH), and also have the potential to attenuate lung function decline in the elderly (1, 2). Other drugs commonly used in PAH (such as bosentan, sildenafil, and anticoagulation drugs) may improve quality of life, walk distance, and/or survival in IPF (5). In our recent article, the degree of vascular remodeling was the unique prognostic factor in IPF in the multivariate analysis, surpassing classic factors such as age, sex, and all the pulmonary function parameters. These findings serve to corroborate the important role of the vascular component in IPF and to stimulate research in this area (6). Finally, current IPF treatment using corticosteroids and cytotoxic drugs has little effect, reinforcing the need to test new drugs/therapies.

In summary, statins may have a role in IPF treatment. Thus, this question needs to be addressed by a well-designed, placebo- controlled clinical trial.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

References

1. Alexeeff SE, Litonjua AA, Sparrow D, Vokonas PS, Schwartz J. Statin use reduces decline in lung function: VA Normative Aging Study. Am J Respir Crit Care Med 2007;176:742-747.

2. Fadini GP, Schiavon M, Rea F, Avogaro A, Agostini C. Depletion of endothelial progenitor cells may link pulmonary fibrosis and pulmonary hypertension [letter]. Am J Respir Crit Care Med 2007;176: 725.

3. Nadrous HF, Ryu JH, Douglas WW, Decker PA, Olson EJ. Impact of angiotensin-converting enzyme inhibitors and statins on survival in idiopathic pulmonary fibrosis. Chest 2004;126:438-446.

4. Watts KL, Sampson EM, Schultz GS, Spiteri MA. Simvastatin inhibits growth factor expression and modulates profibrogenic markers in lung fibroblasts. Am J Respir Cell Mol Biol 2005;32:290- 300.

5. King TE Jr, Behr J, Brown KK, du Bois RM, Lancaster L, de Andrade JA, Stahler G, Leconte I, Roux S, Raghu G. A randomized placebo-controlled trial of bosentan in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2008;177:75-81.

6. Parra ER, Kairalla RA, de Carvalho CR, Capelozzi VL. Abnormal deposition of collagen/elastic vascular fibres and prognostic significance in idiopathic interstitial pneumonias. Thorax 2007;62:428-437.

ALFREDO N. C. SANTANA

RONALDO A. KAIRALLA

CARLOS R. R. CARVALHO

Pulmonary Division

University of Sao Paulo Medical School

Sao Paulo, Brazil

Copyright American Thoracic Society May 1, 2008

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