"Bronchoconstriction, deep breaths, and emergent behavior in asthma"
Dr. Tilo Winkler, PhD
Assistant in Biomedical Engineering, Massachusetts General Hospital
Instructor in Anesthesia, Harvard Medical School
August 10, 2009
10:00 - 11:00 am
HSRF, Room 300
Asthma is a disease of rapidly increasing incidence that affects more than 17 million people in the United States alone. Heterogeneous airway constriction, the emergence of large ventilation defects within the lungs, and a lack of improvement or even worsening of constriction following deep breaths, are cardinal features of asthma. The common paradigm in studies of these phenomena is that each airway's behavior is independent from other airways. However, computational results from an integrative model of the airway tree showed that serial and parallel interactions among airways during bronchoconstriction can lead to sudden changes in the behavior of the lungs including catastrophic shifts and self-organized emergence of clustered ventilation defects. Comparing model predictions with experimental results demonstrated that the integrative model could predict not only the emergence of ventilation defects but a series of paradoxical behaviors suggesting that a unifying principle exists and that the serial and parallel interdependencies among airways are an essential mechanism linking the different phenomena. The model showed also that the dynamics of the interdependencies among airways during deep breaths can have dramatic effects on bronchoconstriction. The theoretical and experimental evidence that is now available suggests a paradigm change from independent airway behavior to interdependence among airways. This change may be critical for the understanding of pathological conditions in asthma and for new therapies to help patients.
Dr. Winkler studied biomedical engineering at Dresden University of Technology, Germany, where he also received his PhD in computer science honored with summa cum laude. In 2001, he joined Dr. Venegas' lab at Massachusetts General Hospital in Boston, MA, as research fellow. Since 2003, he has been an instructor at Harvard Medical School and an assistant in biomedical engineering at Massachusetts General Hospital. Dr. Winkler's research in Dresden was focused on the identification of ventilation mechanics and gas exchange during mechanical ventilation. Currently, he works on pulmonary functional imaging using PET and CT, quantitative image analysis, computational modeling, and complex systems behavior in the respiratory system.