Researchers have made a breakthrough in understanding asthma, opening the way for treatments that could help manage this potentially fatal health condition. Present therapies primarily focus on asthma as an inflammatory disease, prompted by attacks of airway constriction, which cause breathing difficulties.
An innovative study using mice has revealed that many elements of an asthma attack – such as inflammation, mucus production and harm to the airway barrier against infection – all emanate from this tense constriction. The study implies that by inhibiting a process that triggers the death of epithelial cells, which protect the interior and exterior body surfaces, the resulting damage, inflammation and mucus associated with an asthma attack could be avoided.
Professor Jody Rosenblatt, from King’s College London, mentioned that this finding is the capstone of over a decade of research. Prof Rosenblatt states that their observation of the physical constriction during an asthma attack causing extensive harm to the airway barrier was a key insight. Without this barrier, asthmatics are much more prone to enduring long-term inflammation, wound healing, and infections, which result in more attacks.
Asthma, with symptoms like wheezing, coughing, breathlessness and chest tightness, can be worsened by triggers such as dust or pollen and can elevate the risk of a perilous asthma attack. The causes of asthma remain enigmatic and the existing medications only address the aftermath of an asthma attack, not its prevention.
The research team suggests that halting asthma symptoms may have to do with cell extrusion, a process they found which leads to most epithelial cell deaths. Researchers at King’s College London utilised rodent lung models and human airway tissue to find that when the airways contract, a condition called bronchoconstriction, the epithelial cells lining the airway are forcibly pushed out, eventually leading to their demise.
Bronchoconstriction leads to numerous cell extrusions, damaging the airway barrier, inciting inflammation and causing surplus mucus. Earlier research indicated that the chemical compound gadolinium can inhibit extrusion.
A recent study revealed that a low-cost compound called gadolinium, often used in MRI imaging, could prevent further airway damage, inflammation, and mucus secretion in mice during an asthma attack. Despite the study’s success in animal trials, researchers have yet to investigate its effectiveness and safety in human subjects.
Professor Rosenblatt, one of the researchers, explained how a persistent build-up of musculature following ongoing damage and inflammation post-asthma attacks can lead to serious breathing difficulties. He pointed out that current therapies such as Albuterol inhalers, although they allow open airway and necessary breathing, sadly do not halt this airway damage or the subsequent symptoms.
The research, conducted in partnerships with the University of Leicester and financially supported by the likes of Wellcome, Howard Hughes Medical Institute and the American Asthma Foundation, holds promise in preventing future asthma attacks by curbing the damage caused by over-extrusion. The findings have been published in the Science journal.