Two vital cellular mechanisms within the body are impaired in a group of severe asthmatics - meaning they don’t respond well, or at all, to vital medication that can prevent possibly life-threatening asthma attacks, according to new research.
The researchers told delegates at the British Thoracic Society’s Winter Meeting on 7 December 2017, that the results are at an ‘early stage’ - but could pave the way for developing drugs that might help increase the expression and functioning of these vital proteins meaning this group of severe asthmatics could benefit more from a crucial asthma treatment.
The majority of asthmatics can control their asthma very effectively using two treatments that tackle long term airway inflammation - inhaled corticosteroids (ICS) and long-acting beta-agonists. However approximately 5% have a severe form of the disease that can prove difficult to treat.
The underlying problem in many of these people is insensitivity to corticosteroids. This can mean that the drugs don’t work as well, or at all, in these individuals. The molecular mechanisms and processes within the body that underly this issue are not fully known.
The research team investigated whether the reduced expression and functioning of:
- a key receptor that binds to medication within the body & helps activate it (gluco-corticoid receptor or GR)
- a protein that helps transport the medication into the nucleus of cells (Importin 7) - could be related to insensitivity to the medication.
In the study, using the U-BIOPRED database, researchers analysed blood, urine and sputum samples of 611 subjects to compare the gene expression of GR and Importin 7 in severe asthmatics, mild/moderate asthmatics and people without asthma - and then employed additional testing to find out whether reduced expression was linked with inflammation and poor lung function.
The findings showed that asthmatics who had reduced levels of Importin 7 also had lower lung function scores, higher levels of inflammation and greater oral corticosteroid use (indicative of severe asthma).
Dr Pankaj Bhavsar, member of the British Thoracic Society, and lead researcher from Imperial College, London said:
“Our study has shown that molecular mechanisms that help in transporting, and enabling our bodies to respond to, this key asthma medication aren’t working properly in some severe asthmatics.
"This is exciting but early scientific work – but it could lead in the future to targeted drugs which will enable severe asthmatics, who are currently insensitive to corticosteroids, to be able to benefit far more from the treatment.
"The mechanisms we analysed may also play a key role in the body’s insensitivity to similar medications for health problems such as psoriasis, arthritis and neurological problems. So we hope that our findings will inform new studies that could help a wide group of people with chronic conditions.”
Mr Ranga Mullegama is the winner of the BTS medical student research prize for this work. This is awarded to the very best basic, translational or clinical research performed in the UK respiratory community by medical students.
For more information visit the British Thoracic Society.
