A new way to treat asthma symptoms and even repair previously irreversible lung damage could be on the horizon following the discovery of a potential new therapeutic target by scientists at the Universities of Aberdeen and Manchester.
Current treatments for asthma largely involve controlling the inflammation of lung tissue using steroid inhalers. However, 4 people die every day in the UK1 from asthma related complications. With funding from the Medical Research Foundation and Asthma UK, a team of researchers from the University of Aberdeen and the University of Manchester have investigated the scarring that occurs in lung tissue as a result of asthma and have been able to reverse these changes in animal models.
The study is published today in Science Immunology
Although still in the early stages of development, this discovery paves the way for a new way to treat not only asthma, but many different diseases in which similar structural changes in tissues occur. Such diseases include conditions like chronic obstructive pulmonary disease (COPD), chronic heart disease and cirrhosis of the liver and account for approximately 40% of deaths worldwide.
Asthma affects more than 7 million people in the UK and severe asthma can have a hugely detrimental impact on an individual's quality of life. Even when treated, asthma can be fatal and the most recent data shows it contributed to 1,465 deaths in the UK in 20221 - this is despite the availability of new treatments which aim to dampen down inflammation in the lungs.
However, as well as inflammation, asthma also results in what has previously been considered to be irreversible structural lung changes. These changes include making the lungs stiffer and more scarred through increases in things like 'extracellular matrix collagens.'
Using animal models that share features of severe asthma in people, the researchers found that preventing inflammation alone is not enough to reverse this tissue scarring. Instead, they found that blocking the action of specific protein molecules strongly associated with inflammation and tissue damage, 'remarkably reversed' scarring in the lungs.
Dr Tara Sutherland, Lecturer of Immunology, who led the research at the University of Aberdeen, alongside collaborators at the University of Manchester, explains: "Drugs that inhibit inflammation in asthma are crucial for managing the disease. However, these drugs may not always be enough to prevent and reverse lung damage found in severe asthma.
"Our findings show that we also need to consider that structural lung changes occur in severe asthma and that these changes may occur independently of inflammatory pathways.
"A better understanding of these structural changes and their consequences for lung health could lead to development of new therapies that benefit people particularly with severe asthma and could potentially be used alongside drugs that stop inflammation.
"Although a first step in a long process, our study suggests avenues for new treatments that may have the potential to prevent disease progression and even reverse tissue scarring in asthma and many other diseases where fibrosis due to disorganised matrix formation is suggested to account for approximately 40% of worldwide mortality."
James Parkinson, Research Associate from the division of Immunology and Immunity to Infection and Respiratory Medicine at the University of Manchester who collaborated on the project added: "This work adds a new layer to our understanding of how asthma develops. It also reinforces the importance of considering all aspects of airway remodelling when evaluating future potential therapies."
Dr Angela Hind, CEO of the Medical Research Foundation, said: "Asthma affects millions of people in the UK, including 1.1 million children, yet despite current treatments, too many people still die from the condition every day. Severe uncontrolled asthma can cause lasting damage to the lungs and drastically reduce quality of life. This research is a crucial step forward - showing how we might not only prevent that damage, but even reverse it, opening the door to treatments that could transform lives.
"By supporting studies like this, the Medical Research Foundation aims to generate the evidence needed to change how asthma is treated and ultimately improve outcomes for people living with the condition."
Dr Ellen Forty, Research Networks and Partnerships Manager at Asthma + Lung UK added:
"Asthma + Lung UK is pleased to have funded this exciting research which has helped to tease apart some of the ways that damage to lung tissue occurs in severe asthma, showing potential that some aspects of the damage could actually be reversed in mice. Now we need to invest in the next stages of this research to better understand this newly discovered process, and whether it works the same way in humans.
"This study offers hope for a new avenue for future treatments for the 7.2 million people in the UK living with asthma, that could supplement existing medicines. It could also have benefits for those with other lung conditions with similar causes of damage. Funding for lung health research is on life support and urgent action is needed to increase investment."
This research was funded by the Medical Research Foundation and the Asthma and Lung UK Fellowship with support from Medical Research Council and Wellcome.
