Arlene Stecenko, Pulmonology and Cystic Fibrosis

 


Arlene Stecenko wants to halt the progression of two diseases that devastate patients and perplex scientists: Cystic Fibrosis Diabetes and Idiopathic Pulmonary Fibrosis.

Since arriving at Emory in 2002, Stecenko has held numerous titles and responsibilities. She is the Marcus Professor of Pediatric Pulmonology and Director of the Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep in the Department of Pediatrics. She also served as the founding director of the Adult Cystic Fibrosis Program at the Emory University Cystic Fibrosis Center and holds the position of Investigator for the McKelvey Lung Transplantation Center. The challenges of treating chronic, progressive lung diseases require precisely this kind of cross-disciplinary orientation at which Stecenko excels. She has collaborators at the Children's Healthcare of Atlanta, the CDC, the Departments of Medicine and of Pediatrics at Emory University, and the Cystic Fibrosis Center.

Understanding Cystic Fibrosis Diabetes.

Recent advances in the treatment of Cystic Fibrosis (CF), an inflammatory and infectious lung disease, have led to longer life expectancies for patients. With the majority surviving into their thirties and several decades beyond that, 'managing' the disease has become more complicated. Diabetes poses one such complication. "Twenty-five percent of adults with CF develop diabetes," Stecenko says.

CF has been shown to induce metabolic imbalances, which, in turn, create malnourishment in patients. More important to long term health, however, are the devastating effects that CF diabetes can have on the progression of lung disease. Patients with CF diabetes die prematurely of progressive lung disease, not of stroke, heart attacks, or kidney failure as seen in non-CF diabetes patients. Data from studies in adults with type 2 diabetes indicate that the transient elevations of blood glucose levels occurring after a large meal cause oxidative stress and inflammation. This can be toxic to the cells that produce insulin and thus worsen a patient's glucose intolerance.

Stecenko aims to focus on the prediabetic phase in Cystic Fibrosis. She wants to determine whether acute elevations in blood glucose levels trigger acute oxidative stress and inflammation, events which, in turn, could worsen glucose tolerance and ultimately lead to CF diabetes. This vicious cycle may be particularly exaggerated in Cystic Fibrosis patients because their physicians often prescribe high-fat, high-calorie diets to promote weight gain. Stecenko suspects that the same diet which helps CF patients gain much-needed weight may also hasten the development of diabetes. Says Stecenko: "the high-fat diet may actually be pro-inflammatory...and toxic to cells that produce insulin."

CF Diabetes is particularly hard on women. The life expectancy for these women is 17 years less than either males with CF diabetes or women who have Cystic Fibrosis without diabetes. "It's a devastating disease," says Stecenko. Why CF women do so poorly with diabetes is unknown. Stecenko and her colleagues have noted that CF women suffer the worst of both worlds: although remaining severely malnourished, they also can have off-the-charts body fat ratios. They are testing the concept that CF women are thin people with metabolic syndrome - that their bodies, although very thin, are composed of a large proportion of fat cells that produce pro-inflammatory molecules and oxidative stress, two factors that could precipitate the development and severity of diabetes.

Anti-viral therapies for Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF), a chronic, progressive lung disease whose causes are unknown, is characterized by repeated injury to and scarring of the lungs, making it harder and harder to breathe. More than 200,000 people in the United States suffer from IPF, which is "uniformly fatal," says Stecenko - often within three to five years after diagnosis.

Many patients with IPF also test positive for Epstein-Barr virus (EBV), a type of gammaherpesvirus. Stecenko and colleague Dr. Ana Mora lead a research team whose members are working to determine how IPF and EBV are related.In June 2007 they published the results of a groundbreaking animal model study on the effects of anti-viral therapy for IPF progression. The study looked at mice that had been infected with EBV and had developed progressive pulmonary fibrosis. Giving the infected mice an anti-viral medication (cidofovir) prevented production of new viral particles and saw a marked decrease in lung fibrosis. Happily for the mice, they grew normally - and deterioration in lung function was halted.

Though the study has yet to be replicated in a clinical setting, Stecenko is optimistic. "It is possible that anti-viral therapies could help control lung fibrosis in persons who have IPF and associated herpesvirus infections," she says. This fall, she will collaborate with Emory faculty members in Adult Pulmonary Medicine and with CDC scientists to propose an anti-viral therapy study for humans. "The patients are more than ready for it," she says. "It's a horrible disease."

When she's not working in the lab, Stecenko divides her time between caring for adults with CF and mentoring junior researchers. One of the most rewarding parts of her job, she says, is encouraging young clinical scholars to consider a career in research. "Most of them come in thinking they're going to go into private practice," she says. After working with Stecenko, some of them change their minds about that. Her enthusiasm is infectious. So is her commitment to patients whose lives depend on new advances in lung disease research.