Every four minutes, someone in the U.S. dies from chronic obstructive pulmonary disease, or COPD --the incurable pulmonary disorder usually caused by smoking. COPD is the third highest cause of death in the U.S. after heart disease and cancer.
But new research conducted at UC Davis and accepted for publication in the European Respiratory Journal shows that cholesterol-busting statins may protect against the severe inflammation that can lead to airway scarring and COPD. This finding is the first to show that statins protect against bronchial, or large airway, injury -- a key route to acute COPD complications.
For the study, UC Davis scientists exposed rats to high concentrations of tobacco smoke for three days - long enough to trigger acute, damaging airway reactions. Some of the animals were pre-treated with statins for 10 days before the smoke exposure.
The pre-treatment protected them from acute inflammation that destroys the lining of airways. This inflammation leads to such symptoms as cough and phlegm production -- and eventually to COPD and persistent breathlessness.
The researchers showed that the 10-day pre-treatment was essential, whereas treatment only during smoke exposure did not have the same protective effect. This suggests that statins may be protective against smoke-induced lung injury and possibly COPD, and that the timing of treatment may be important.
The scientists have launched new studies to determine if statins will protect air passageways from long-term tobacco smoke exposure, which often leads to COPD, physical debilitation and oxygen dependence.
Smoking-induced inflammation leads to cell death and abnormal transformation of epithelial cells that line the airways. Smoking destroys the cells' ability to clear the airways of toxins and other harmful particles.
"Many aspects of COPD are irreversible," said Amir A. Zeki, one of the co-leaders of the research. "Once the mucosal surface of airway passages is damaged by inflammation, it can scar and lose its essential protective function. This can lead to chronic symptoms, shortness of breath, cough and phlegm production.
"But the message here is that there may be hope for some patients with COPD," he said.
The rats received treatment with simvastatin by injection, the effects of which specifically targeted the lungs, said Kent Pinkerton, a collaborator on the research who developed the COPD animal model used in the study. Pinkerton is a professor of pediatrics at UC Davis Health System, professor of anatomy, physiology and cell biology at the UC Davis School of Veterinary Medicine and director of the UC Davis Center for Health and Environment .
The mechanism underlying the statin effect on inflammation is unknown, but the research demonstrates that a 10-day treatment with statins led to a "dramatic reduction" in acute inflammation, Pinkerton said.
"If this strategy holds true for patients, they many not need to take the drugs for an extended period to receive benefits," said Ben Davis, a scientist in the Center for Center for Health and Environment and first author on the research.
The team's discovery stems from a unique research program sponsored by the UC Davis Clinical and Translational Science Center (CTSC). Davis and Zeki participated as scholars in the CTSC Mentored Clinical Research Training Program in 2009. The program brings together basic and clinical researchers to learn from each other, with the aim of encouraging collaborations that advance basic research discoveries into better treatments and cures for patients.
Zeki is a physician-scientist with expertise in severe asthma in the Division of Pulmonary, Critical Care and Sleep Medicine at UC Davis Health System. He also conducts basic research in the Center for Comparative Respiratory Biology and Medicine on the UC Davis campus.
Davis's career has focused on inflammation and its contribution to disease. In the last six years he has studied inflammatory lung disease. Zeki's main research during the past four years has focused on the mechanisms by which statins protect against allergic inflammation in asthma, using both humans and a mouse model.
In the CTSC training program, Zeki and Davis launched a plan to conduct joint research to study the potential of statins to protect against tobacco-induced airway damage. After successful grant funding, they launched the collaboration with Pinkerton, using his lab's COPD animal model. The team also hopes to determine the exact mechanisms by which the statins exhibit their protective effects in lungs.
"We had a very fruitful collaboration," Davis said, "and we are excited about the prospects for working together to further advance this basic finding into clinical research, and ultimately to treating patients with COPD and other pulmonary diseases."
The research study, "Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy, was supported with grants from the CTSC K12 Award (KL2 RR 024144), American Asthma Foundation (09-0269), Tobacco-Related Disease Research Program (18KT-0037and 18XT-0154).
The UC Davis Clinical and Translational Science Center is part of a national consortium, led by the National Center for Advancing Translational Sciences at the National Institutes of Health, that focuses on bringing the next generation of innovative methods and technologies to improve human health. Its goals are to reduce the time it takes for research discoveries to become treatments for patients, as well as to train the next generation of clinical researchers. For more information, visit <a href="http://healthsystem.ucdavis.edu/ctsc">healthsystem.ucdavis.edu/ctsc</a>.