José G. Venegas, PhD
Associate Professor, Harvard Medical School
Fresh insights that will help our understanding of ARDS, COPD and asthma are being gained from studies applying a newly developed single-isotope ventilation/perfusion scan using PET for quantitative assessment of topographical distributions of inflammation, ventilation, perfusion, intrapulmonary shunts and gas trapping. The method has been used to investigate gas transport physiology in models of ARDS demonstrating the topographic location and magnitude of intrapulmonary shunt. Specifically, a recent study provides a mechanistic explanation for the positive effects of the prone position in ARDS. Recently, the method was refined for use in human subjects. Studies exploiting this technique have now demonstrated that the heterogeneity of ventilation in broncho-constricted asthmatic subjects is prominent at large length scales corresponding to lobar and sub-lobar structures. Remarkably, this behavior is not the result of severe constriction of central airways feeding those structures but to the clustering of severely constricted peripheral airways as predicted by a theoretical model the bronchial tree, including interactions between airway smooth muscle and surrounding parenchyma during tidal breathing. These new insights are suggesting the feasibility for developing new strategies for the treatment of these diseases.
Recently, we have been developing biomarkers of inflammation and function COPD. Using noninvasive Positron Emission Tomography (PET) techniques, we are exploring the usefulness of local neutrophil activity as measured from the uptake of 18F-labeled fluoro-2-deoxy-D-glucose (18F-FDG) by activated neutrophils and local pulmonary trafficking of 18F-FDG-labeled circulating neutrophils in conjunction with measures of local pulmonary ventilation (V&A) and perfusion (Q&), measured from the kinetics of IV injected 13NN in saline solution. The combined use of functional imaging and imaging of neutrophil activity is being used to explore the pathogenesis, progression, diagnosis and treatment of COPD. This investigation is expected to generate new insights into the pathophysiology of COPD that may promote the formulation and evaluation of new approaches to the management of the disease.
Department of Anesthesia, Critical Care and Pain Medicine
55 Fruit Street
Boston, MA 02114