Statins Linked To Lung Disease Progression In Smokers

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Main Category: Statins
Also Included In: Respiratory / Asthma;  Smoking / Quit Smoking
Article Date: 10 Jan 2012 - 10:00 PST

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Statin use appears to be associated with susceptibility or the progression of interstitial lung disease (ILD) in current and former smokers, according to a study published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Although some investigations have indicated that statins may be beneficial in treating fibrotic lung disease, other studies have indicated that statins might contribute to the progression of pulmonary fibrosis, by improving excretion of inflammasome-regulated cytokines. In addition, several case reports have revealed that statins may contribute to various types of interstitial lung disease developing.

George R. Washko, M.D., MmsC, and Gary M. Hunninghake, M.D., MPD, of the Division of Pulmonary and Critical Care at Brigham and Women's Hospital in Boston, explained:

"Based on earlier case reports of statin-associated ILD and data suggesting that smoking is associated with the interstitial lung abnormalities (ILA) which underlie ILD, we hypothesized that statins would increase the risk of ILA in a population of smokers.

Accordingly, we evaluated the association between statin use and ILA in a large cohort of current and former smokers from the COPD Gene 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."

Bleomycin has been demonstrated to activate lung inflammation and fibrosis.

CT scanning for radiologic features of ILA and pulmonary function testing was included in the researchers evaluation. Statins were used by 315 (27%) of the 1,184 participants without ILA, in comparison with 66 of the 172 (38%) of those with ILA.

After the team adjusted for numerous covariates, including a history of coronary artery disease or high cholesterol, they found that participants who used statins had a 60% increased risk of developing ILA than those not taking statins.

The researchers did not identify any other positive links between cardiovascular drugs or disorders and ILA. The connection between ILA and statin use was greatest with statins with higher hydrophilicity (readily absorbed or dissolved in water), such as pravastatin, as well as in older participants.

Furthermore, the researchers analyzed the effects of statins on lung injury and fibrogenesis in an investigation in rodents, which were pretreated with pravastatin before administration of intratracheal bleomycin.

The researchers discovered that statin use worsened bleomycin-induced lung fibrosis. In an additional in vitro investigation, statin pretreatment was shown to improve Nlrp3-inflammasone activation through mitochondrial reactive oxygen species generation in macrophages.

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, explained: "These results implicate activation of the NLRP3 inflammasome in fibrotic lung disease."

Limitations in both investigations included:

• All study participants were current or former smokers, which might have limited the applicability of the results to others.
• Discoveries in the mouse model were not mirrored in human trials.
• Duration and dosage of statin treatment was not available for most of the participants.
• Cigarette smoking by itself may lead to pulmonary inflammation.

Dr. Hunninghake concluded:

"While statin use was associated with ILA in our study, caution should be used when extrapolating these findings to the care of patients.

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."

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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