What if asthma attacks are not only an inflammatory response to allergens, like pet dander, but are exacerbated by a powerful nervous system response that sends signals for airways to narrow?
That’s the question underlying an intriguing hypothesis being tested by Nicholas Jendzjowsky, PhD, a postdoctoral scholar in the Cumming School of Medicine’s Department of Physiology and Pharmacology. If proven, it could lead to therapies which block that nervous system response and are effective whatever the initial asthma trigger, from allergens to exercise to air quality.
Asthma affects three million Canadians including 13 per cent of children, and accounts for 500 deaths in this country every year. Jendzjowsky’s asthma research has recently earned him an Alberta Innovates postdoctoral fellowship, adding to several other prestigious postdoctoral awards he has received while working at the University of Calgary.
The 'little brain' of chemoreceptors regulates breathing
At the centre of Jendzjowsky’s research — and at the proposed intersection of inflammatory and nervous system responses during an asthma attack — is a cluster of chemoreceptor cells in the neck called the carotid body. Known by Jendzjowsky and colleagues as the "little brain," the carotid body detects chemicals in the blood, including oxygen and carbon dioxide, and it responds by signalling an adjustment in the rate and depth of breathing.
“Asthmatics appear to have an altered carotid body response, which may affect their ability to breathe,” Jendzjowsky says. “The carotid body pathway has been largely overlooked as an important part of the pathophysiology attributed to asthma; proving this new pathway would be a big step in respiratory research.
“The novel aspect of our work is the discovery that inflammatory mediators released during asthma may stimulate these neuronal centres to regulate airway diameter.”
What does that mean? It means Jendzjowsky and his fellow researchers have discovered that a chemical released as part of the inflammatory response during an asthma attack may cause the nervous system to react — though not helpfully — by closing up airways.
Connecting an inflammatory response to the nervous system
As with all science, it isn’t a straight line from hypothesis to discovery, but rather a puzzle of connect the dots.
For one, there was the question of the chemical released during an asthma attack. It is not a new molecule — it was already understood to be associated with lung disease — but its presence during an asthma attack is a recent revelation.
The link from that chemical, an "inflammatory marker," to the carotid body is also new. In fact, it was discovered by Jendzjowsky’s supervisor, Richard Wilson, PhD, a professor in the Cumming School of Medicine’s Department of Physiology and Pharmacology and a member of the Hotchkiss Brain Institute (HBI) and Alberta Children’s Hospital Research Institute, and his research associate Arijit Roy, PhD.
“We’d been working on a specific receptor in the carotid body, and the idea came to me while listening to a talk on inflammation at a conference,” Wilson says. “I texted Arijit immediately to see if one particular inflammatory mediator activates the carotid body, and within a week, Arijit had demonstrated the connection!”
With the understanding that this molecule is elevated during an asthma attack, and the knowledge that it stimulates the chemoreceptors of the carotid body (which regulates breathing), it remained for Jendzjowsky to uncover exactly what the carotid body does in reaction to the high levels of this molecule in asthmatics.
“I plan to test whether this inflammatory molecule stimulates the carotid body to increase lung resistance and airway constriction, demonstrating a new link from the carotid body to the parasympathetic or "wine-dine-and-recline" nervous system. Such a demonstration would be a major breakthrough,” Jendzjowsky says.
“If this new molecule is exacerbating an asthmatic attack, then by blocking its receptors in the carotid body, we can reduce the severity of asthmatic attacks.”
Transformative research leading to novel potential therapies
“Nick’s work has the potential to be transformative,” Wilson says. “Very few people are looking at the neuronal control of asthma, and although we’re still in the early stages this is very promising research.”
Wilson says Jendzjowsky brings a unique mix of skills to the lab, in particular his experience working with both animal and human models, which is an unusual combination. His work also bridges two of the University of Calgary’s strategic research themes: Brain and Mental Health led by HBI, and Infection, Inflammation and Chronic Diseases, led by the Snyder Institute for Chronic Diseases.
“Trainees including graduate students and postgrads like Nick are really the future of science for Alberta,” Wilson says. “Alberta Innovate grants are important because they help us recruit and support some of the world’s best and brightest. It’s pushing us forward, and we are making real headway on challenging and complex health issues like asthma.”
Nick Jendzjowsky has also received a Canadian Society of Allergy and Clinical Immunology (CAAIF) postdoctoral fellowship, a T. Chen Fong postdoctoral fellowship, a Canadian Lung Association (CLA-CTS) fellowship, and Campus Alberta Neuroscience (CAN) and ACHRI fellowship support.