Preventing Aspergillus-induced inflammation in cystic fibrosis
Research type
Research Study
Full title
Preventing Aspergillus-induced inflammation in cystic fibrosis to reduce airway disease.
IRAS ID
253443
Contact name
Adilia Warris
Contact email
Sponsor organisation
University of Aberdeen
Duration of Study in the UK
2 years, 9 months, 1 days
Research summary
Research Summary
Cystic fibrosis is the most common inherited life-limiting disease in North European people affecting over 10,000 people in the UK. Progressive lung damage caused by infection and inflammation is the major determinant of survival with a median age of death of 29 years. Approximately 60% of people with CF are infected with A. fumigatus and its presence is associated with reduced lung function and increased hospitalisation. Aspergillus disease in people with CF ranges from allergic inflammation to Aspergillus bronchitis. Major knowledge gaps exists how to treat Aspergillus disease in people with CF. Based on our earlier observations that A. fumigatus induces an excessive inflammation in CF immune cells, we hypothesize that dampening this inflammation is key in the treatment to prevent Aspergillus-induced lung damage. Our study will asses a number of agents with anti-inflammatory properties including those being developed for the general treatment of CF-related airway disease in pre-clinical models of infections. Better understanding of how they impact on both Aspergillus-induced inflammation as whether there is an effect on fungal killing is crucial. Our overall aim is to identify promising immunotherapeutic interventions with a potential to improve the outcome of Aspergillus disease in people with CF.
Summary of Results
We previously showed that Aspergillus fumigatus, an environmental fungus, which often infects the airways of people with Cystic Fibrosis (CF), is causing hyperinflammation. When stimulating CF immune cells, we noticed an exaggerated production of reactive oxygen species, inflammatory molecules, which do kill pathogens, but also damage healthy tissues, such as the airways. In this study we investigated a number of treatments to modulate the hyperinflammation induced by A. fumigatus. And what we were able to show is that the new CF treatments including ivacaftor and lumacaftor, decrease the hyperinflammation caused by Aspergillus fumigatus. This shows that these new CF treatments not only improve the epithelial cell function, but also the immune cell function in people with CF.
REC name
East of Scotland Research Ethics Service REC 2
REC reference
18/ES/0154
Date of REC Opinion
11 Feb 2019
REC opinion
Further Information Favourable Opinion