Commensal Fungi in the Lung: Innocent Bystanders or Pathogenic Orchestrators of Severe Asthma?

Summary

Understanding the role of the airway microbiome in the development of severe asthma with fungal sensitisation (SAFS) to help develop more targeted treatments.

What are we doing?

Asthma is a chronic respiratory disease which affects 5.4 million people in the UK. It’s a heterogenous condition and clinical presentation depends on a multitude of factors. Fungi are ubiquitous microorganisms in the environment, and we inhale thousands of fungal spores every day. In approximately 10% of asthmatics, these inhaled fungal spores exacerbate airway inflammation and worsen respiratory symptoms. 

However, the way in which airway immune cells respond to inhaled fungal spores isn’t well defined. The influence of bacterial and fungal species residing within the lungs (the airway microbiome) on this interaction is even less well understood. This needs to be defined to help develop targeted treatments for severe asthma with fungal sensitisation (SAFS).

We’ll identify the fungal and bacterial species residing in the lungs of different groups, including mild asthmatics, severe asthmatics and SAFS patients. We’ll then go on to investigate how key species mediate the interaction between airway immune cells and inhaled fungal spores.  

How are we doing it?

We’ll collect bronchoalveolar lavage samples from patients receiving bronchoscopies at the Royal Devon and Exeter Hospital. We’ll extract Microbial DNA from these samples and use  amplicon sequencing to identify the species present. We’ll use Bioinformatic approaches to compare the airway microbiome of the different patient groups and key species will be incorporated into mechanistic experiments. We’ll assess interactions between selected species, airway immune cells and fungal spores using the in vitro lung-on-a-chip modelling system.

What happens next?

If the airway microbiome is found to be important in the development of SAFS, multiple avenues could be explored:  

• Could the airway microbiome be manipulated to reduce airway inflammation in asthma patients?  
• Does the airway microbiome effect the behaviour of all immune cells or specific populations?  
• Could environmental factors such as pollution and house mould be altering the airway microbiome and asthma development? How could this inform and change policy?  

Supervisors

Dr Peter Cook

Dr Chris Scotton

Prof Michael Gibbons