The largest-ever genetic study of people with moderate-to-severe asthma has revealed new insights into the underlying causes of the disease which could help improve its diagnosis and treatment.

Between 10 to 15% of individuals with asthma have the severe type of the condition which does not respond to conventional treatment. Symptoms include debilitating breathlessness leading to increased hospital admissions, despite the high use of medicines.

Asthma experts from the University of Nottingham, the University of Leicester and National Institute for Health Research (NIHR) Nottingham and Leicester Biomedical Research Centres (BRCs) led a global team of researchers to examine genetic data from thousands of people with European ancestry who have moderate-to-severe forms of the disease.

The research, published in The Lancet Respiratory Medicine, describes how they carried out a genome-wide association study (GWAS). This involved comparing the genes of around 10,000 people living with asthma to nearly 50,000 people with normal lung health. The work uncovered several new genetic variants associated with moderate-to-severe asthma and also a person's risk of developing the condition.

Gene variants and asthma

For the first time, the study was also able to pinpoint certain genetic variants associated with the risk of developing moderate-severe asthma that controls the production of mucins the main components of mucus.

The discovery of the potential genetic causes of the disease gives new hope for better treatment of this hard-to-manage condition because these genes could be targeted by new therapies.

Professor Christopher Brightling is a respiratory physican at Leicester Hospitals NHS Trust and the senior investigator from the NIHR Leicester BRC and the University of Leicester.

He said: "New treatments for severe asthma are recently available and others are on the horizon. One major challenge will be understanding which treatment is best for which person. This study of the genetics of severe asthma will help in making these decisions and reveals new potential avenues for future therapies."

Professor Louise Wain, British Lung Foundation Chair in Respiratory Research at the University of Leicester and co-author of the study said: "Millions of people in the UK suffer from asthma, yet the disease affects people very differently with some people experiencing more severe symptoms than others.

Understanding the changes in our genes which trigger the development of asthma and contribute to this variability will hopefully lead to more personalized treatments in the future. Our research offers new hope to those who are left breathless by asthma on a daily basis."

Dr. Erika Kennington, Head of Research at Asthma UK, who part-funded the research, said: "Severe asthma is debilitating, causing terrifying life-threatening asthma attacks and frequent trips to A&E. This research is an important stepping stone in understanding more about the underlying causes of different types of asthma, which could pave the way for more treatments that are tailored to someone's genetics in the future.