May 09

Disease of the month – Cystic Fibrosis by Dr. Denis Hadjiliadis

Cystic fibrosis is a genetic inherited disease. It is the most common genetic disease in people of European (white) descent that leads to reduced lifespan. There are approximately 30000 patients with the disease living in the United States and approximately 800-1000 in Greece. Parents of affected individuals are healthy “carriers” of the abnormal gene. Patients have two genes affected (one from each parent) therefore they develop the disease. Approximately 1 in 25 people are carriers of the disease both in the United States and Greece.

The disease is caused by abnormalities in a channel called CFTR (cystic fibrosis transmembrane regulator), which leads to abnormal salt transport across the cells. There are more than 2000 CFTR mutations (ways that the channel can be affected), but more than 80% are due to one mutation, DF508. As a result, water cannot move easily in and out of the cell and secretions in many parts of the body are affected and become very thick. The main organs that are affected include the following: 1) pancreas, which does not work at birth or shortly after it, for most patients; as a result they have to take special digestive pills, in order to be able to digest and absorb the food they eat. In addition, patients are at risk for developing bowel blockage at birth and might need surgery to fix, or similar blockage later in life. Malnutrition is very common because of these problems. Some patients have milder disease and their pancreas is working, but they are at risk of inflammation of the pancreas, called pancreatitis due to thick secretions and their pancreas can stop working later; 2) lung disease which leads to thick secretions that retain many bacteria that lead to chronic cough with thick sputum. The bacteria many times lead to bad infections called exacerbations that require antibiotics for treatment; as a result lungs become slowly more damaged with a type of condition called bronchiectasis (lungs look like they have “holes” in them); in addition, patients have trouble breathing air out due to damage in their airway pipes. Bacteria that commonly affect them include Pseudomonas, Staphylococcus aureus and MRSA; lung disease is the most common reason patients with cystic fibrosis die and many of them require a lung transplant to remain alive; 3) diabetes becomes more common later in life for up to two-thirds of patients and leads to worse nutrition and earlier death; 4) liver disease, from thick bile, which leads to cirrhosis in only a small percentage of patients. These patients develop worse nutrition, fluid in their abdomen, bleeding from their gut and many times require liver transplant; 6) frequent sinusitis with nasal polyps; 7) infertility for men; males have absence of an organ called the vas deferens and as a result they have no sperm.

All these severe problems lead reduced lifespan, but when the disease was first described in the 1940s, infants rarely survived beyond preschool age. By the 1980s patients were living until their early adulthood and now the average life expectancy is their early 40s. Many medications that treat the thick mucous, the digestion, the infections and chronic exercises to clear the mucous are used by the patients. Their use as well as care in specialized and accredited centers by a multidisciplinary team that includes physicians, nurses, nutritionists, physical therapists, respiratory therapists and social workers led to the improvement in lifespan. Patients frequently have to do many hours of treatment every day and frequently become disabled because of their condition. Most recently medications that can fix the underlying problem of CFTR have become available for approximately 40-45% of patients and have opened new horizons for treatment. More are in the way for all patients.

Early diagnosis is important in treating the condition, so now all babies born in the United States are tested and all pregnant women are offered testing (and if they are carriers they can seek testing for their male partners). Testing before conception can also help identify couples who are carriers and potentially avoid having children with CF by using in vitro fertilization. This approach will hopefully will lead to further improvement in their quality of life and life expectancy.

About the author

Dr Hadjiliadis completed medical school at the University of Toronto and subsequently pursued Internal Medicine training at the Mayo Clinic in Rochester, MN. He then completed his fellowship in Pulmonary and Critical Care Medicine at Duke University in Durham, NC. He also completed his Master’s of Health Sciences while at Duke University. After that he returned to Toronto for further training in lung transplantation and cystic fibrosis. After joining the faculty there he came to the University of Pennsylvania in 2005, where he has remained ever since.

Dr Hadjiliadis is board certified in Internal Medicine, Pulmonary and Critical Care by the American Board of Internal Medicine, in Internal Medicine and Respirology by the Royal College of Physicians and Surgeons of Canada and in Pulmonology by the Greek Ministry of Health. He has authored multiple publications in his areas of interest and has been the lead investigator in both single center and multicenter trials.

Dr Hadjiliadis is currently the Paul F Harron Jr Associate Professor of Medicine at the University of Pennsylvania. He is the Director of the Adult Cystic Fibrosis Program, a member of the Lung Transplant Program and the Physician Lead of the Advanced Lung Disease Research Group. He sees patients with cystic fibrosis, lung transplantation and bronchiectasis at the Harron Penn Lung Center.