A team of British scientists has found a new cause behind much of the damage caused by asthma, offering a faint glimmer of hope for future sufferers of this potentially deadly condition.
Cells lining the airways are squeezed to destruction during an attack, and
medication to prevent this, rather than manage its aftermath, might break the cycle of harm, the King’s College London researchers told the journal Science.
The airways of people with asthma are sensitive to triggers like pollen, pets and exercise, becoming inflamed or swollen, and causing symptoms including coughing, wheezing and breathlessness.
While existing drugs or inhalers can reduce this inflammation and help keep the airways open, repeated attacks can cause permanent scarring and narrowing of the airways.
During an attack, the smooth muscle surrounding the airways starts to squeeze and tighten, known as bronchoconstriction.
The King’s College London team studied this process in detail, using mice and human lung-tissue samples.
Lead researcher Professor Jody Rosenblatt said bronchoconstriction damaged the airway lining, resulting in long-term inflammation, wound healing and infections that cause more attacks.
But until now, this lining damage had been overlooked, she told BBC News.
“This epithelial lining is the body’s first line of defence against things like infections and yet it’s getting damaged during asthma attacks. There’s this constant wounding going on – a vicious cycle.
“If we can block the damage, we are hoping that might stop attacks from happening at all.”
‘Desperately needed’
One possible preventive treatment being explored by the researchers is an element called gadolinium, which appears to help – at least in mice.
But much more work is needed to see if it might be safe and effective enough to try in people, and that will take years.
Asthma and Lung UK research and innovation director Dr Samantha Walker said: “This discovery opens important new doors to explore possible new treatment options desperately needed for people with asthma.”
Study details
Bronchoconstriction damages airway epithelia by crowding-induced excess cell extrusion
Dustin Bagley, Tobias Russell, Jody Rosenblatt et al.
Published in Science on 4 April 2024
Abstract
Asthma is deemed an inflammatory disease, yet the defining diagnostic feature is mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial cell death when cells become too crowded. In this work, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion in both mice and humans. Although relaxing the airways with the rescue treatment albuterol did not affect these responses, inhibiting live cell extrusion signalling during bronchoconstriction prevented all these features. Our findings show that bronchoconstriction causes epithelial damage and inflammation by excess crowding-induced cell extrusion and suggest that blocking epithelial extrusion, instead of the ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.
BBC article – Asthma: Scientists find new cause of lung damage (Open access)
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