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Breakthrough in Understanding CF Gender Gap

Tuesday August 10, 2010

Ireland has the highest incidence of Cystic Fibrosis (CF) in the world. At 2.98 per 10,000 population, it is almost four times higher than in the US or elsewhere in the EU. It has long been known that female CF patients have poorer survival rates, poorer lung function and are more susceptible to lung infections than their male counterparts.  Now research undertaken in Beaumont Hospital has shed new light on why this is and will hopefully point the way towards new therapies.

Normally a protective layer of fluid defends the lungs from infections. However, in CF sufferers this layer is unusually thin and becomes even thinner in females at times in their menstrual cycle when their levels of oestrogen are high. This makes them even more prone to pick up infections than they are already. The new research undertaken at Beaumont has found that in addition to increasing female CF patients susceptability to infection, increased levels of oestrogen also interfere with their defence mechanisms. Oestrogen inhibits the release of the chemical signal IL-8, which in turn is needed to trigger the influx of white blood cells into the lungs to fight infection when cells are attacked by bacteria.

Joint lead author of the paper, Dr Sanjay Chotirmall, Specialist Registrar in Respiratory Medicine in the Respiratory Research Division of the Royal College of Surgeons, Beaumont Hospital, explains "This reduced response to infection, combined with a greater likelihood of acquiring an infection in the first place, which are both caused by high oestrogen levels, goes a long way towards explaining why females with cystic fibrosis have more aggressive disease, particularly with the onset of puberty".

Dr Chotirmall hopes the research will contribute to narrowing the gender gap in cystic fibrosis outcomes by identifying new potential targets for treatment, such as stabilisation of oestrogen levels or more aggressive use of infection prevention strategies at the times when oestrogen levels are at their highest.

The research team from the Respiratory Research Division, Department of Medicine, RCSI Beaumont Hospital and RCSI Department of Molecular Medicine, also included Dr Catherine Greene (joint lead author), Ms Irene Oglesby, Dr Warren Thomas, Prof Shane O'Neill, Prof Brian Harvey and Prof Gerry McElvaney. The research was supported by the Higher Education Authority PRTLI Cycle 4 through a Molecular Medicine Ireland Clinician-Scientist Fellowship Programme and the findings were recently published in the American Journal of Respiratory and Critical Care Medicine.