Scientists’ latest discovery raises hope of cure for Asthma patients

Scientists at King’s College London have discovered that blocking the process that normally causes epithelial cell death could prevent the damage, inflammation, and mucus that result from an asthma attack.

Asthma, also known as bronchial asthma, is a condition in which a person’s airways become inflamed, narrow, swell and produce extra mucus, which makes it difficult to breathe. It can be minor, or it can interfere with daily activities and in some cases, it may lead to a life-threatening attack.

One of the scientists who led the research, Prof Jody Rosenblatt, noted that understanding the mechanism that guides asthma attacks would help provide treatment for preventive measures. She said, “Our discovery is the culmination of more than 10 years’ work. As cell biologists who watch processes, we can see that the physical constriction of an asthma attack causes widespread destruction of the airway barrier. Without this barrier, asthma sufferers are far more likely to get long-term inflammation, wound healing, and infections that cause more attacks. By understanding this fundamental mechanism, we are now in a better position to prevent all these events.”

The experts noted that most current asthma treatments stem from the idea that it is an inflammatory disease and yet, the life-threatening feature of asthma is the attack or the constriction of airways, making breathing difficult. Triggers such as pollen or dust can make asthma symptoms worse and can lead to a life-threatening asthma attack.

Despite the disease’s commonality, the causes of asthma are still not understood. Current medications treat the consequences of an asthma attack by opening the airways, calming inflammation, and breaking up the sticky mucus that clogs the airway and helps control asthma but does not prevent it.

According to the researchers, the answer to stopping asthma symptoms may lie in cell extrusion, a process the researchers discovered that drives most epithelial cell death.

For the study, the scientists used mouse lung models and human airway tissue to discover that when the airways contract, known as bronchoconstriction, the epithelial cells that line the airway get squeezed out to later die.

Bronchoconstriction is a tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath therefore causing so many cell extrusions. It damages the airway barrier which causes inflammation and excess mucus.

In previous studies, the scientists found that a chemical compound ‘Gadolinium’ can block extrusion, in this new study, they found it could work in mice to prevent the excess extrusion that causes damage and inflammation after an asthma attack. The authors noted that gadolinium has not been tested in humans and has not been deemed to be safe or efficacious.

Rosenblatt continued that this constriction and destruction of the airways causes post-attack inflammation and excess mucus secretion that makes it difficult for people with asthma to breathe. “Current therapies do not prevent this destruction — an inhaler such as Albuterol opens the airways, which is critical to breathing but, dishearteningly, we found it does not prevent the damage and the symptoms that follow an attack. Fortunately, we found that we can use an inexpensive compound, gadolinium which is frequently used for MRI imaging, to stop the airway damage in mice models as well as the ensuing inflammation and mucus secretion. Preventing this damage could then prevent the build-up of musculature that causes future attacks,” she said.

One of the co-authors of the study from the University of Leicester, Prof Chris Brightling, said: “In the last decade there has been tremendous progress in therapies for asthma particularly directed towards airway inflammation. However, there remain ongoing symptoms and attacks in many people with asthma. This study identifies a new process known as epithelial extrusion whereby damage to the lining of the airway occurs because of mechanical constriction and can drive many of the key features of asthma. A better understanding of this process is likely to lead to new therapies for asthma.”

The Director of Research and Innovation at Asthma + Lung UK, Dr Samantha Walker, explained that the discovery opens important new doors to exploring the possibility of new treatment options desperately needed for people with asthma rather than focusing solely on inflammation.

He said: “Current medications for asthma work by treating the inflammation, but this isn’t effective for everyone. Treatments aim to prevent future asthma attacks and improve asthma control by taking inhalers every day, but we know that 31 per cent of people with asthma don’t have treatment options that work for them, putting them at risk of potentially life-threatening asthma attacks.”

The paper which has been published in Science is in collaboration with the University of Leicester and the experts believe that the discovery of the mechanics behind cell extrusion could underlie other inflammatory diseases that also feature constriction such as cramping of the gut and inflammatory bowel disease.

Said: “In the last decade there has been tremendous progress in therapies for asthma particularly directed towards airway inflammation. However, there remain ongoing symptoms and attacks in many people with asthma. This study identifies a new process known as epithelial extrusion whereby damage to the lining of the airway occurs because of mechanical constriction and can drive many of the key features of asthma. A better understanding of this process is likely to lead to new therapies for asthma.”

He said: “Current medications for asthma work by treating the inflammation, but this isn’t effective for everyone.”

Treatments aim to prevent future asthma attacks and improve asthma control by taking inhalers every day, but we know that 31 per cent of people with asthma don’t have treatment options that work for them, putting them at risk of potentially life-threatening asthma attacks.”