While some studies have suggested that statins might be beneficial in the treatment of fibrotic lung disease, others have suggested that they may contribute to the progression of pulmonary fibrosis by enhancing secretion of inflammasome-regulated cytokines, and numerous case reports have suggested that statins may contribute to the development of various types of ILD.
"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 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 at Brigham and Women's Hospital in Boston. "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." Bleomycin has been shown to induce lung inflammation and fibrosis.
The findings were published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
Assessment included pulmonary function testing and CT scanning for radiologic features of ILA. Among 1,184 subjects with no evidence of ILA, 315 (27%) used statins, compared with 66 of 172 (38%) subjects with ILA. After adjustment for a number of covariates, including a history of high cholesterol or coronary artery disease, statin users had a 60 percent increase in the odds of having ILA , compared to subjects not taking statins. 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 both studies. 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. Cigarette smoking by itself may lead to pulmonary inflammation. 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."
About the American Journal of Respiratory Research and Critical Care Medicine:
With an impact factor of 10.191, the AJRRCM is a peer-reviewed journal published by the American Thoracic Society. It aims to publish the most innovative science and the highest quality reviews, practice guidelines and statements in the pulmonary, critical care and sleep-related fields.
Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society's 15,000 members prevent and fight respiratory disease around the globe through research, education, patient care and advocacy.
Nathaniel Dunford | EurekAlert!
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy