by Simra Ahmad and Georgie Burns
Imagine having to fight just to take a breath. This is the reality for the 7.2 million people in the UK living with asthma. Asthma is an incurable, chronic condition whose symptoms (wheezing, coughing, shortness of breath, chest tightness) can be triggered by everyday activities and devolve into fatal asthma attacks. Tragically, in the UK alone, four people die every day because of these attacks. This reality turns life into a series of daunting challenges for those with asthma, making the need for a cure evident.
So, why don’t we have one? Asthma symptoms are caused by immune cells becoming triggered and infiltrating the lung tissue, resulting in downstream effects and lung inflammation. Therefore, treatments target this inflammation: both attempting to relieve active inflammation (for example, an asthma attack) for temporary, often life-saving relief and to mitigate the chronic inflammation caused, which can help manage the condition long-term. However, these treatments don’t examine the structural changes asthma makes to the lungs, such as scarring in the lung tissue that can prevent the lungs from constricting or relaxing efficiently during breathing.
“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.”
Dr Angela Hind, CEO of the Medical Research Foundation.
Fortunately, change is on the horizon in the form of a team run by Dr Tara Sutherland, Lecturer of Immunology at the University of Aberdeen, who has taken research in this new, exciting direction. Dr Sutherland’s team, composed of both Aberdeen and Manchester University students and researchers, focused on the structural changes which occur in the extracellular matrix (a network of proteins and molecules that surround, support, and provide structure to cells and tissues) during chronic fibrotic disorders, such as asthma/Chronic obstructive pulmonary disease (COPD). Dr Sutherland’s research began with the questions, ‘How are these changes happening?’ and ‘Can we stop them?’, before focusing on inhibiting the production of specific protein molecules, such as chitinase, whose quantity significantly increases during periods of inflammation or injury.
Although Dr Sutherland’s research is still in its early stages, focusing primarily on assays, readouts, and animal models, the results are already more promising than expected. The findings suggest that the structural changes in conditions like asthma, often considered irreversible, can be halted and even reversed by inhibiting chitinase. This potential breakthrough could significantly impact the treatment of asthma, offering a ray of hope for thousands of patients who are suffering from tissue damage and scarring, which could now be reduced in the future.
“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 per cent of worldwide mortality,”
Dr Sutherland.
Dr Sutherland’s groundbreaking research journey began around six years ago at the University of Manchester, before she made the move to our Aberdonian campus. However, work this ambitious always requires a substantial investment of time and resources. Therefore, realistically, she envisions that it could take a decade or more before these new findings lead to medications that can treat asthma and relieve patients of the associated scarring.
The journey to this research becoming a viable treatment option is already underway, with Dr Sutherland’s team beginning to analyse lung biopsies to confirm the mechanisms identified in previous research are consistent in people with severe asthma. However, research on lung tissue, particularly in the case of asthma, presents unique challenges. Collecting lung tissue samples, especially from those already facing complex lung issues, is not a routine procedure, making it a slow process due to the scarcity. To address this, a promising collaboration has been established with Grampian, which is already yielding encouraging results.
“There’s a lot of promising results. It’s just the time it’s going to take to develop and see whether they pan out,”
Dr Sutherland.
Lung biopsies aren’t the only reason Dr Sutherland’s journey to viable treatment is long. Following this, the treatment must undergo human trials, and then it must be determined if the research can be transformed into a drug or another delivery method. Any treatment would then also need to be developed and tested. However, a pharmaceutical treatment for asthma is not the only potential application of Dr Sutherland’s research.
Dr Sutherland’s research could also help patients who suffer from lung scarring due to other conditions like COPD, other chronic fibrosis disorders or severe asthma which doesn’t respond to current treatment options. Most biological processes involved in scarring share the same pathways, no matter the cause, so this new research could also open up a treatment plan for those who cannot use anti-inflammatory drugs.
“I think the study is exciting because it opens up new avenues that could help treat chronic diseases,”
Dr Sutherland.
This new research also provides a foundation for other researchers to build on with their own trials and experiments. It highlights how it’s essential to understand how immune cells interact with tissue structure rather than only focusing on inflammation, and hopefully will inspire others to follow this new, promising research path and revolutionise how asthma, other lung disorders, and even some of the thousands of illnesses that leave behind tissue damage are treated. By targeting the underlying biological processes of tissue damage, this research could help prevent and even reverse structural damage across multiple organs, thereby improving the lives of millions of patients worldwide.
This research was funded by the Medical Research Foundation and the Asthma and Lung UK Fellowship, with support from the Medical Research Council and Wellcome.