Experts believe a pioneering breakthrough by a Manchester hospital research team could pave the way for doctors to better understand and treat adults with Cystic Fibrosis (CF), helping them live longer and healthier lives.
CF is the commonest inherited genetic disease in Europe and the US affecting tens of thousands of people. Although significant advances in care have improved – with some patients now surviving into their 40′s and 50′s – it remains incurable.
For many years the fungus Aspergillus has been known to damage the lungs of CF patients by infecting them and causing an allergic reaction. This two year study, which was led by Dr Caroline Baxter and colleagues at UHSM (University Hospital of South Manchester), shows that 50 per cent of patients had allergic aspergillosis or Aspergillus bronchitis and an additional 15 per cent were sensitised to this common airborne fungus.
Dr Baxter, who did this work as a Clinical Fellow at the hospital’s Adult Cystic Fibrosis Unit explains: “CF primarily affects the lungs. Lifelong chest infections due to multiple bacteria require repeated course of intravenous antibiotics and frequent hospitalisation. Unfortunately, current diagnostic tests for aspergillus disease in CF patients are notoriously imprecise. As a consequence of this failure, choosing the best therapeutic option for treatment has been very difficult, contributing to a decline in lung function.”
Professor Kevin Webb who leads the Centre says the Aspergillus disease has long been a conundrum for CF physicians. “We face steroid therapy and the risk of diabetes if we treat, or worse lung function if we do not. Aspergillus also impacts on transplant options for patients, curtailing life expectancy. Dr Baxter’s work is pivotal to CF care for the coming decades, as we strive to enable patients to live a normal life for as long as possible.”
Professor David Denning, who is Director of the National Aspergillosis Centre and Professor of Medicine and Medical Mycology at UHSM adds: “This ground breaking research has opened the door to a more informed therapeutic management of Aspergillus disease in CF patients and a greater understanding of its origin and development. As antifungal treatment of these complications tends to be long term, with or without steroids, better studies of the impact of antifungal therapy can now be done.
What causes CF? Cystic fibrosis is caused by a genetic mutation; specifically a mutation in a gene called CFTR. A genetic mutation is when the instructions found in all living cells become scrambled in some way, meaning that one or more of the processes of the body do not work in the way they should.
The CFTR mutation allows too much salt and water into cells. This results in a build-up of thick, sticky mucus in the body’s tubes and passageways. These blockages damage the lungs, digestive system and other organs, resulting in the symptoms of cystic fibrosis.
Who is affected? Cystic fibrosis is most common in white people of northern European descent. It is estimated that 1 in every 2,500 babies born in the UK will be born with cystic fibrosis and there are over 9,000 people living with the condition in this country. The condition is much less common in other ethnic groups.
What is the Outcome for people with CF? In previous years most children with cystic fibrosis would die of related complications before reaching adulthood. The outlook has improved considerably in recent years due to advancements in treatment, although most people with cystic fibrosis will have a shorter than average life expectancy. However, this may well improve in the future.
Dr Caroline Baxter undertook the development of sputum galactomannan (a measure of Aspergillus growth) and real-time Aspergillus PCR, which enables researchers to produce millions of copies of a specific DNA sequence. The new methods were compared to conventional serological and skin testing methods in 146 CF adults (average age 29 years). The new methods were superior to conventional methods and identified three distinct classes of aspergillosis as well as separating out CF patients who were disease free. Respiratory decline over two years was seen in all three patients groups with aspergillosis, whether allergic or infection.
University Hospital of South Manchester NHS Foundation Trust