Pathogenesis of alveolopleural fistulae following lung resection.

Delayed lung healing following surgical resection leads to development of alveolopleural fistulae that lead to increased morbidity and mortality in patients. The pathogenesis of delayed lung repair following surgery, however, remains unknown. This proposal stems from a novel clinical observation that high carbon dioxide inside the chest cavity impairs lung healing. The experiments outlined here will further determine the relationship between increased carbon dioxide concentration and lung wound healing. We believe that the results from these studies will provide explanations for many clinical associations between conditions leading to hypercarbia and poor outcomes after lung surgery as well as introduce investigative opportunities to study the role of therapies directed towards lowering carbon dioxide or reversing the carbon dioxide-induced alterations in signaling pathways and promote lung repair.