“Based on earlier case reports of statin-associated ILD and data suggesting that smoking is associated with interstitial lung abnormalities (ILA), we hypothesized that statins would increase the risk for ILA in a population of smokers,” said George R. Washko MD, MMsC, and Gary M. Hunninghake MD, MPH, of the Division of Pulmonary and Critical Care. “Accordingly, we evaluated the association between statin use and ILA in a large cohort of current and former smokers from the COPDGene study. In addition to the association between statin use and ILA we found in humans, we also demonstrated that statin administration aggravated lung injury and fibrosis in bleomycin-treated mice.”
The study is published in the January 6, 2012 online issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
A total of 2,115 subjects were included. Assessment included pulmonary function testing and CT scanning for radiologic features of ILA. Compared to subjects not taking statins, statin users had a 60 percent increase in the odds of having ILA after adjustment for a number of covariates including a history of high cholesterol or coronary artery disease. No other positive associations between ILA and cardiovascular medications or disorders were detected. The association between statin use and ILA was greatest with statins with higher hydrophilicity (readily absorbed or dissolved in water), such as pravastatin, and in higher age groups.
The effects of statins on lung injury and fibrogenesis were also examined in a study in mice, which were pretreated with pravastatin prior to intratracheal bleomycin administration. Statin use was found to exacerbate bleomycin-induced lung fibrosis. In a further in vitro study, statin pretreatment was shown to enhance Nlrp3-inflammasome activation through mitochondrial reactive oxygen species generation in macrophages.
“These results implicate activation of the NLRP3 inflammasome in fibrotic lung disease,” said Jin-Fu Xu MD, and Augustine M. K. Choi, MD, of the Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, in Shanghai, China and the Division of Pulmonary and Critical Care at Brigham and Women’s Hospital in Boston, respectively.
There were some limitations to the study. Findings in the mouse model were not replicated in human samples. All study subjects were current or former smokers, perhaps limiting the applicability of the results to others. Finally, the duration and dosage of statin therapy was not available for the majority of patients.
“While statin use was associated with ILA in our study, caution should be used when extrapolating these findings to the care of patients,” concluded Dr. Hunninghake. “The significant benefits of statin therapy in patients with cardiovascular disease probably outweigh the risk of developing ILA, and statin use may benefit some patients with respiratory disease. Clinicians should be aware, though, that radiological evidence of ILD can develop in some patients treated with statins.”
This research was supported by the National Institutes of Health, National Nature Science Foundation of China, Parker B. Francis Foundation and the National Library of Medicine. The COPDGene project was supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis and Sunovion.
This press release was provided by the American Thoracic Society.
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