June 26, 2015
Inhaled statins can be used to treat asthma and could be included in a new class of inhalational therapy for the respiratory disease that affects 27 million Americans, suggested a new study.
Researchers at the University of California Davis Health System tested the effects of pravastatin in mice sensitized to ovalbumin (OVA) to cause airway inflammation and used mass-spectrometry technology to gauge statins levels in blood and tissues. The drug showed good drug distribution in lung tissue, and was found in high concentrations with low systematic distribution and no severe toxicity, according to the study.
Inhalational administration of pravastatin stopped OVA-induced goblet cell hyperplasia — excess production of mucous in asthmatic airways that normal ciliary movement cannot remove, which has been associated with airway inflammation — by one-third, according to the study. The study also noted that pravastatin levels were nearly 5 times higher in the lung but only 2.86-fold higher in bronchoalveolar lavage fluid (BALF) than in control mice that received filtered air.
The researchers believed targeting the lungs with inhalational therapy would lower the effective dose of statins to generate anti-inflammatory benefit in the lungs without causing mild or serious side effects associated with statin use. In addition, they said achieving minimal systematic absorption is especially important in pediatric patients and in elderly individuals who can’t take statins due to potential side effects.
The researchers targeted pravastatin because systematic administration had been shown to have an anti-inflammatory effect in ovalbumin mice that mimicked simvastatin. But, they said, pravastatin is water-soluble and easily converted to aerosol, making it ideal for inhalation administration without irritating or damaging airway mucosa. They also suggested other statins could offer an even more potent inhalation treatment of the disease, and said further research could lead to the development of new inhalational treatments for asthma.
“Effective treatments for severe asthma are limited, and do not address the full range of symptoms without risking significant side effects,” said study lead author Dr. Amir Zeki, an asthma treatment specialist and assistant professor of internal medicine at UC Davis. “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.”
Dr. Zeki said his research team’s ultimate goal is to reduce the onset of bronchospasms that make asthma dangerous and can lead to hospitalizations and death. He added, “While we can’t cure the disease yet, we might be able to improve symptoms and make it much easier to live with.”
The study was published online in Physiological Reports.
1. Zeki AA, Bratt JM, Chang KY, et al. Intratracheal instillation of pravastatin for the treatment of murine allergic asthma: a lung-targeted approach to deliver statins. Physiol Rep. 2015;3(5):e12352.