Cystic fibrosis breakthrough reveals why females fare worse than males

The paper was published May 24 in the New England Journal of Medicine.

The research found that estrogen promoted the presence of a 'mucoid' form of the bacterium Pseudomonas aeruginosa in the lungs of women with cystic fibrosis. These mucoid type of Pseudomonas aeruginosa bacteria are coated in a slimy layer which makes them more difficult to treat with antibiotics and more difficult to clear with the body's own natural defenses which leads to significant lung inflammation, explaining, at least in part, why females with cystic fibrosis often have a worse outcome.

Professor Gerry McElvaney, Director of the Respiratory Research Laboratory RCSI/Beaumont Hospital and joint senior author on the paper commented: "This study opens the way to a new understanding and potentially new therapies in the treatment of cystic fibrosis, a condition in which Ireland has the highest incidence in the world. This research study is among the first examples which shows the effects of gender hormones on infections and therefore has major implications for conditions beyond cystic fibrosis including other respiratory diseases such as asthma."

Dr. Sanjay Chotirmall, a Molecular Medicine Ireland (MMI) Clinician-Scientist fellow is the first author on the paper and Dr. Catherine Greene is the joint senior author.

The clinical research was carried out in the Cystic Fibrosis Unit, Beaumont Hospital and also utilised data from the National Cystic Fibrosis Registry of Ireland.

Cystic fibrosis is a life threatening inherited disease which primarily affects the lungs and the digestive system. A build up of mucus can make it difficult to clear bacteria and leads to cycles of lung infections and inflammation, which can eventually lead to damage of the lungs.

Ireland has both the highest incidence of CF in the world at 2.98 per 10,000 and the highest carrier rate in the world with 1 in 19 individuals classed as carriers. The incidence of cystic fibrosis in this country is almost two and a half times the average rate in other EU countries and the USA ⁽¹⁾. At present, there are approximately 1,200 people with cystic fibrosis living in Ireland ⁽²⁾.

The cystic fibrosis research in the Respiratory Research Division exemplified by this paper is funded by the Health Research Board, Medical Charities Research group, Science Foundation Ireland, Molecular Medicine Ireland (MMI), CF Hopesource, Irish CF research trust along with individual donors such as Fergal Somerville who recently swam the English Channel in support of CF research in Beaumont Hospital.

This paper is an excellent example of the translational research presently underway in RCSI and illustrates interdepartmental and inter-institutional links as co-authors on the paper include colleagues from the Departments of Medicine (Dr. Sonya Cosgrove), General Practice (Dr. Borislav Dimitrov) and Molecular Medicine (Professor Brian Harvey), RCSI; Beaumont Hospital/RCSI (Dr. Cedric Gunaratnam, Professor Shane O'Neill); and the School of Medicine (Dr. Stephen Smith), Trinity College, Dublin.

The study's results are being presented by Dr. Greene at the American Thoracic Society meeting in San Francisco this month and by Dr. Chotirmall at the European Respiratory Society meeting in Vienna later this year

(1) Farrell PM. The prevalence of cystic fibrosis in the European Union. Journal of Cystic Fibrosis 2008 Sep;7(5):450-3.

(2) The Cystic Fibrosis Registry of Ireland