Healing the airways to breathe better

Dr Thomas Iosifidis is working to develop safe and better treatments for childhood asthma.


Dr Thomas Iosifidis

Despite common misconceptions, asthma remains a substantial global healthcare burden with around 330 million sufferers worldwide. Asthma costs the country $28 billion in healthcare costs, according to a report by Asthma Australia and National Asthma Council Australia.    

Young children are arguably the most disproportionally affected. In fact, asthma is the most common lifelong breathing disorder in children, with one in six Australian children experiencing asthma. In addition, it remains one of the main causes of their hospitalisation. 

The burden of asthma on our community is under-addressed by current treatments. Although asthma symptoms are manageable in most patients, these medications fail to alter lung function decline and may present unwanted side effects. 

Unfortunately, the most vulnerable group of all, children with ongoing asthma, remain at highest risk of having lifelong respiratory diseases such as severe chronic obstructive pulmonary disease. As such, there is a pressing need for new therapies that target the underlying disease processes of asthma in early life and not just treat symptoms.

This is an area of intensive research being undertaken by a team of clinicians and scientists at the Wal-yan Respiratory Research Centre, a partnership between Telethon Kids Institute, Perth Children’s Hospital Foundation and Perth Children’s Hospital. 

The team has focused its research on the epithelium cells lining the airway surface, which form the lung’s first line of defence, a barrier against the outside environment, and are responsible for the initial responses to injury and infection such as viruses – one of the main triggers of asthma flare-ups. 

While studying the triggers of asthma flare-ups may seem intuitive, it is a surprisingly understudied, the reason being that accessing the required tissues from the airways is challenging, particularly in children, due to the invasive nature of airway sampling. 

The team at Wal-yan has pioneered access to these precious samples and shown that the airway lining of children with asthma has abnormal responses to injury, and is inherently ‘leaky’ and inflamed, contributing to ongoing and worsening breathing problems. 

A recent study found experimental and FDA-approved medications used to treat pain in children and adults could enhance repair and reduce inflammation in asthmatic airway epithelial cell cultures. This study has highlighted a potentially new class of drugs that targets a previously unknown disease pathway in asthma. More importantly, the data suggest that this treatment strategy may not only heal damaged airways, but also reduce recurrence and severity of asthma flare-ups in children. 

However, to determine if these treatments are safe and effective to use in a clinical setting, new treatments need to undergo rigorous preclinical testing and human clinical trial assessments. 

The standard drug development pipelines currently cater to adult asthma therapies, which are different to children’s needs. Unfortunately, it is difficult to replicate asthma as seen in children in the lab to test these potential therapies, and so there is a need for the development of patient-specific complex airway models to fast-track identification of new asthma treatments suitable for children. 

The potential solution – organ-on-a-chip technology – has arisen through the collaborative efforts of bioengineering, cell biology and medicine disciplines. A strategic partnership between A/Prof Sean Murphy and his bioengineering team at the Wake Forest Institute for Regenerative Medicine in North Carolina, USA, and our local respiratory medicine research team, funded by WA Health, places the Wal-yan Respiratory Research Centre at the forefront of this field globally.

Combining our access to paediatric-derived airway tissues with the cutting-edge organ-on-a-chip platforms provide an ideal scenario to examine the biological processes underlying early-onset disease in culture models resembling patient-specific tissue environment. 

Additionally, interconnected organ chip models (e.g., lung and liver) on body-on-a-chip platforms are facilitating our drug screening efforts to accurately identify human organ toxicity, not otherwise observed in animal models or conventional cell culture models. 

By using these complex human organ models and technology, we can find the best treatment candidates with strong safety and effectiveness profiles to be progressed into further clinical trials. The conventional drug development pipeline has provided minimal therapeutic options for vulnerable children with asthma, so it is time to upgrade the process and fast-track the delivery of better treatment options. 

ED: Dr Thomas Iosifidis is a postdoctoral researcher with the Wal-yan Respiratory Research Centre.