Friday , December 14 2018

Researchers Find New Way to Prevent Acute Asthmatic Symptoms

Asthma is one of the most common lung diseases, affecting 241 million people worldwide. This disease is characterized by airflow limitation caused by inflammation, excess mucous secretion, remodeling changes, such as goblet cell metaplasia and increased smooth muscle mass and acute conducting airway constriction in response to stimuli, usually allergens. Most people are able to manage their symptoms and live healthy, active lives. However, for some, current treatments are not effective. University of Calgary’s Professor Richard Wilson and co-authors have discovered another way to help asthmatics breathe more easily by targeting treatment at the nervous system. The study, conducted on rats, shows the carotid bodies — tiny collections of neurons on each side of the neck — may be responsible for causing lung airway narrowing during an allergen-induced asthma attack.

Asthma sufferers have trouble breathing because of the narrowing of the airways in their lungs, an example of which is shown in the upper left. In chronic asthma (lower left), repeated cycles of inflammation, damage, and repair lead to airway remodeling and fibrosis, the buildup of collagen and other materials. A signaling molecule known as NF-κB can significantly reduce chronic asthma (lower right). Image credit: National Institute of Allergy and Infectious Diseases.

Asthma sufferers have trouble breathing because of the narrowing of the airways in their lungs, an example of which is shown in the upper left. In chronic asthma (lower left), repeated cycles of inflammation, damage, and repair lead to airway remodeling and fibrosis, the buildup of collagen and other materials. A signaling molecule known as NF-κB can significantly reduce chronic asthma (lower right). Image credit: National Institute of Allergy and Infectious Diseases.

“This idea is going to come out of left field for some people. It’s a completely new way to think about how the body responds during an asthma attack,” Professor Wilson said.

“We’ve been able to show why the carotid bodies react during an asthma attack, how they make the attack worse and perhaps most importantly, how to block them to prevent an attack.”

The carotid bodies signal the brain for many reasons — the main one is to breathe. Cells in the carotid bodies detect oxygen and tell the brain when the oxygen is too low. In response, breathing increases.

Certain chemicals in the blood can also stimulate the carotid bodies.

During an asthma attack, a naturally occurring chemical called lysophosphatidic acid (LPA) increases in the lungs and in the bloodstream.

Professor Wilson and his colleagues discovered that these higher levels of LPA stimulate the carotid bodies, and in response, the carotid bodies increase lung resistance so that the body cannot breathe as efficiently.

“We didn’t expect this result. It’s counterintuitive,” said study first author Dr. Nick Jendzjowsky, also from the University of Calgary.

“Normally, the carotid bodies increase lung resistance to keep the airways open so that the airways don’t collapse when breathing increases to inhale more oxygen. But asthmatics have compromised airways that are full of inflammation; the increased resistance caused by the carotid bodies makes it harder for asthmatics to breathe.”

The team then decided to block the receptors in the carotid bodies from being able to detect the increased levels of LPA during an asthma attack.

“The results were immediate and dramatic. When we blocked the receptors, the carotid bodies were unable to create resistance in the lungs and the asthma attack was eliminated,” Professor Wilson said.

“This was a Eureka! moment for us. The findings indicate that instead of targeting medications to the airways during an asthma attack, we can stop airway narrowing by blocking LPA activation of the carotid bodies.”

“This could open the door for a new treatment for asthma,” Dr. Jendzjowsky said.

“Instead of inhaling medication into the lungs, medicine could be delivered via a pill or injection. During a severe asthmatic attack for example, we could use a similar approach to how EpiPens are used now in response to insect stings.”

The findings appear in the journal Nature Communications.

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Nicholas G. Jendzjowsky et al. 2018. Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving carotid body lysophosphatidic acid receptors. Nature Communications 9, article number: 4030; doi: 10.1038/s41467-018-06189-y

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