Working with mice, scientists at Johns Hopkins University have successfully used a commonly prescribed blood pressure medicine, losartan, to prevent almost all of the lung damage caused from two months of exposure to cigarette smoke.
The treatment targeted lung tissue breakdown, airway wall-thickening, inflammation and lung over-expansion.
As a result of the experiments, efforts are under way at Johns Hopkins for a clinical trial of the drug in people with smoking-related chronic obstructive pulmonary disease, known as COPD, the long-term consequence of smoking and for which, until now, there are no known potential treatments to prevent or repair the resulting lung damage.
COPD is the third leading cause of death in the United States, mostly in people with either chronic bronchitis or emphysema, or both; some 12 million Americans have been diagnosed with COPD. Funding of the trial is from the National Heart, Lung and Blood Institute and the drug’s manufacturer, Merck & Co.
“The results of our study in mice suggest that losartan or similar drugs could serve as an effective treatment for smoking-related lung diseases in humans,” said Dr. Enid Neptune, the study’s senior investigator for the animal experiments. “And because these drugs are already approved for use in the United States as safe and effective treatments for hypertension, incorporating them into our treatment regimen for COPD would be quite rapid.”
A report on the study, published in the 3 January edition of the Journal of Clinical Investigation, is considered a breakthrough discovery, researchers said, because it is the first to show that a drug already in clinical use can prevent most of the serious consequences of smoking in an animal-test model, preserving both lung structure and function.
The study is also believed to be one of the first to extend findings from research on other complex genetic conditions, specifically Marfan syndrome, for which losartan therapy is also being clinically tested, to probe how such treatments can be applied to other complex diseases that damage the lungs.
In smoking-related COPD, breathing becomes difficult and progressively worsens, as the small airways and airspaces that conduct oxygen through the lungs and into the bloodstream become damaged. Airway walls thicken and are more readily obstructed by mucus, and the airspaces lose their elasticity.
“It is very exciting that an existing medication has proven capable in an animal model of not only treating the problems of COPD, but also disrupting the biological pathway that precipitated them,” said Dr. Robert A. Wise, a pulmonologist and professor at Johns Hopkins, who is piloting the clinical studies. “If our tests in people prove successful, we could help restore lung health to millions of people who have suffered from tobacco addiction.”
Dr. Wise said existing remedies for smoking-related COPD are few, and mainly consist of providing relief of symptoms, such as shortness of breath, coughing and mucus production. Drugs that lower blood pressure also help, and surgery can be done to remove damaged portions of the lung or transplant new lungs.
Dr. Neptune and Dr. Wise began their investigation of losartan after a colleague at Johns Hopkins, Dr. Harry (Hal) Dietz, discovered the medication could potentially treat Marfan syndrome, which results from a single genetic mutation and weakens arteries, affecting all major organs, including the lungs.
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