The researchers demonstrated in mice that an inhalable form of pravastatin, currently only approved for oral use, could improve airway health without increasing levels of the drug in other parts of the body or causing toxic effects.
“Effective treatments for severe asthma are limited and do not address the full range of symptoms without risking significant side effects,” said Amir Zeki, assistant professor of internal medicine and lead author of the study. “This study gives us hope that when inhaled directly into the airways, statins can be delivered safely and at doses that appear to protect the cellular health of the lungs.”
Prevastatin is one of a class of drugs known as statins that regulate cholesterol production in the body. They also may modulate immune responses for a number of diseases, according to Zeki. While previous studies have shown that statins could be effective asthma therapies, this new study addresses one of the obstacles in translating the findings into patient use: how best to deliver the drug.
The investigators tested whether inhaled pravastatin, selected for the study because it is water-soluble and easily converted to an aerosol, could alleviate asthma pathology in a mouse model. Using innovative mass-spectrometry methods developed at UC Davis, they were able to measure statin levels in blood and tissues, including the lungs.
The experimental outcomes showed that pravastatin remained mostly in the lungs, with little absorbed into the rest of the body. The medication was not toxic to the lungs or overall health of the mice. In terms of asthma pathology, the treatment lowered airway over-sensitivity that can lead to bronchospasm, had some anti-inflammatory effects and reduced mucus production in the airway lining.
The optimal statin type and dose still need to be determined, the researchers wrote, but “our results indicate that statins should be explored as a novel class of inhaler therapy for airway diseases such as asthma.”
“Our ultimate goal is to reduce the onset of bronchospasms that make asthma dangerous and can lead to hospitalizations and death,” said Zeki, who specializes in treating patients with severe asthma. “While we can’t cure the disease yet, we might be able to improve symptoms and make it much easier to live with.”
The article, titled “Intratracheal Instillation of Pravastatin for the Treatment of Murine Allergic Asthma: A Lung-targeted Approach to Deliver Statins,” is published in the May issue of Physiological Reports and available at http://physreports.physiology.org/content/physreports/3/5/e12352.full.pdf
In addition to Zeki, the UC Davis study team included Jennifer Bratt, Kevin Chang, Lisa Franzi, Sean Ott, Mark Silveria, Oliver Fiehn, Jerold Last and senior author Nicholas Kenyon.
The study was funded by the National Institutes of Health (grant numbers T32 HL07013, NCATS TR000002, KL2 RR 024144, 1K08HL114882-01A1, HL105573 and U24DK097154), an American Thoracic Society Fellows Career Development Award, the U.S. Department of Defense (grant number W81XWH-10-1-0635) and the LUNGevity Foundation.
More information about UC Davis Health System and its Division of Pulmonary, Critical Care and Sleep Medicine is at http://healthsystem.ucdavis.edu.