Guido Musch Laboratory
Our research focuses on the pathophysiology of Acute Lung Injury (ALI) and aims at understanding how the basic alterations of pulmonary perfusion and ventilation affect clinical manifestations of ALI, as well as the mechanisms that underlie response, or lack of response, to therapeutic interventions.
Rapidly progressive respiratory failure with impairment of gas exchange and diffuse alveolar damage characterizes ALI and its most severe form, the Acute Respiratory Distress Syndrome (ARDS). The mortality rate of ARDS/ALI has been recently reported at 38.5%, and 74,500 persons are estimated to dye from it each year in the United States.
Impairment of gas exchange is due to a mismatch between blood and air flows in the lung: In ALI, large portions of the lung become compressed (i.e., atelectatic) or filled with fluid, thus losing their airflow. If these regions remain perfused, their blood flow can not exchange oxygen and carbon dioxide. Consequently, arterial oxygenation decreases and carbon dioxide increases. The extent of these gas exchange alterations depends on the distribution of the loss of aeration relative to that of perfusion. One aim of our research is to study the relationship between the spatial distribution of these variables in the lung and the ensuing impairment of gas exchange, with the goal of clarifying why ALI patients with similar loss of lung aeration can have starkly different degrees of gas exchange impairment and vice versa.
Mechanical ventilation is used to support the increased work of breathing and improve gas exchange in patients with ALI. Positive end-expiratory pressure (PEEP), large "sighs" (recruitment maneuvers, RMs), and prone positioning have all been used to improve oxygenation in these patients. All these interventions, however, are effective only in a fraction of patients. A second aim of our research is to dissect the pathophysiologic basis of the intersubject variability in the clinical response to these interventions.
In addition to their effect on gas exchange, PEEP, RMs and prone positioning have been hypothesized to modulate the pulmonary inflammatory response associated with ALI and mechanical ventilation (Ventilator-Induced Lung Injury, VILI). The third aim of our research is to dissect the mechanisms by which these interventions can affect the activity of inflammatory cells in the acutely injured lung.