Nav: Home

Genetic variant discovery to help asthma sufferers

March 16, 2018

Research from the University of Liverpool, published today in Lancet Respiratory Medicine, identifies a genetic variant that could improve the safety and effectiveness of corticosteroids, drugs that are used to treat a range of common and rare conditions including asthma, and chronic obstructive pulmonary disease (COPD).

Corticosteroids are very effective in the treatment of asthma and COPD, with more than 20 million prescriptions issued in the UK annually. Unfortunately, corticosteroids can also cause side effects, one of which is adrenal suppression, seen in up to 1/3 of people tested. People with this condition do not make enough cortisol. Cortisol helps the body respond to stress, recover from infections and regulate blood pressure and metabolism.

Adrenal suppression can be very difficult to diagnose, as it can present with a spectrum of symptoms from non-specific symptoms such as tiredness, to serious illness and death. The majority of patients do not develop adrenal suppression, and the reasons why some do, and while other don't, despite using similar doses of corticosteroids were not previously understood.

In a world first researchers from the University's Institute of Translational Medicine, led by Professor Sir Munir Pirmohamed, conducted a genome-wide association study (GWAS) to pinpoint the genes responsible for increasing the risk of a person developing adrenal suppression.

This method searches a person's DNA (genome) for small variations, called single nucleotide polymorphisms (SNPs). Each person carries about three million SNPs, but if a particular SNP occurs more frequently in people with a particular condition than in people without the condition, it can pinpoint the underlying reason for the difference.

The researchers identified two groups of children with asthma, and one group of adults with chronic obstructive pulmonary disease (COPD), all of whom used inhaled corticosteroid medications. Each patient's adrenal function was tested. This is the largest published cohort of children ever tested for adrenal suppression (580 children in total).

Individuals who had a particular variation in a specific gene (platelet derived growth factor D; PDGFD) had a markedly increased risk of adrenal suppression, both in the children with asthma and adults with COPD. This risk increased if the patient had two copies of the variation (one from their mother, one from their father). Children with two copies of the high risk variation in PDGFD were nearly six times more likely to develop adrenal suppression than children with no copies.

Dr Dan Hawcutt, Senior Lecturer Paediatric Clinical Pharmacology University of Liverpool and Honorary Consultant Paediatrician Alder Hey Children's Hospital, said: "This is the first pharmacogenomic study investigating the association between a patient's genotype and corticosteroid induced adrenal suppression.

"Our highly novel findings offer the potential to develop personalised approaches therapy. This could involve screening patients to avoid or minimise steroid use if they are at high risk, or if steroids are needed, developing a specific plan to monitor their adrenal function.

"However, it is important to stress that steroids are effective medications, and patients should not stop taking these medicines without medical input. If you are worried about any side effects, please consult your doctor, nurse or pharmacist looking after you."
-end-
This research was funded by the UK Department of Health Chair in Pharmacogenetics.

The full study, entitled 'Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study using data from PASS and PASIC ', can be found at: http://dx.doi.org/10.1016/S2213-2600(18)30058-4

University of Liverpool

Related Asthma Articles:

Insomnia prevalent in patients with asthma
A team of researchers from the University of Pittsburgh has found that insomnia is highly prevalent in adults with asthma and is also associated with worse asthma control, depression and anxiety symptoms and other quality of life and health issues.
Test used to diagnose asthma may not be accurate
A new study urges caution in the use of the mannitol challenge test for asthma in non-clinical settings.
Turning off asthma attacks
Working with human immune cells in the laboratory, Johns Hopkins researchers report they have identified a critical cellular 'off' switch for the inflammatory immune response that contributes to lung-constricting asthma attacks.
Access to asthma meds, plus flu vaccines, keep kids with asthma healthy
Kids need flu shots to prevent asthma flares, and medications available in school to keep 86 percent in class, according to two studies being presented at the American College of Allergy, Asthma and Immunology Annual Scientific Meeting.
Discovery could lead to better asthma treatment
Scientists have made a discovery that could lead to improved treatment for asthma sufferers.
Do asthma and COPD truly exist?
Defining a patient's symptoms using the historical diagnostic labels of asthma and chronic obstructive pulmonary disease (COPD) is an outdated approach to understanding an individual's condition, according to experts writing in the European Respiratory Journal today.
Asthma in many adolescents is not an allergic disease
New research indicates that asthma in many adolescents is not likely to involve inflammation of the airways and therefore should not be considered an allergic disease.
First classification of severe asthma
Severe asthma can have a devastating effect on sufferers, affecting their ability to work or go to school and to lead normal lives.
Exploring 'clinical conundrum' of asthma-COPD overlap in nonsmokers with chronic asthma
Researchers may be closer to finding the mechanism responsible for loss of lung elastic recoil and airflow limitation in nonsmokers with chronic asthma.
Asthma app helps control asthma: Alerts allergists when sufferers need assistance
New study in Annals of Allergy, Asthma and Immunology shows how an app directly connecting an allergist and an asthma sufferer can provide necessary intervention when asthma isn't under control.

Related Asthma Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".