Redistribution of pulmonary perfusion during bronchoconstriction in asthma

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DESCRIPTION (provided by applicant): Asthma affects over 17 million people in the United States and the incidence is rising. Research in asthma has focused on the airways, however, little is known about how regional pulmonary perfusion changes during an asthma attack. Recent studies from our lab using positron emission tomography (PET) functional imaging have shown for the first time that dramatic perfusion redistribution, away from patchy areas of low ventilation, take place in spontaneously breathing human subjects with asthma during methacholine-induced bronchoconstriction. The long-term objective of this research is to understand the mechanisms of, and factors that modify, the regional perfusion redistribution during bronchoconstriction in asthma. The main hypotheses to be tested in this project are 1) The redistribution of perfusion away from ventilation defects is primarily caused by hypoxic pulmonary vasoconstriction and is not solely an artifact of methacholine-induced bronchoconstriction and 2) For a given degree of constrictive stimulus, the redistribution of perfusion away from poorly ventilated areas will be less effective in the supine than in the prone position because gravitational forces would tend to oppose the effectiveness of hypoxic vasoconstriction. These hypotheses will be tested using state-of-the-art PET-CT functional imaging of regional perfusion and ventilation with the following specific aims: 1) Assess whether elimination of the hypoxic stimulus by breathing a high oxygen concentration blunts the redistribution of perfusion during methacholine-induced bronchoconstriction (SA-1A). 2) Assess whether a similar perfusion redistribution occurs during bronchoconstriction induced by other bronchoconstrictive stimuli and, if so, evaluate the extent to which hypoxic pulmonary vasoconstriction is involved in that redistribution (SA-1B). 3) Compare the magnitude of redistribution of perfusion away from poorly ventilated regions in the prone and supine positions breathing with and without a high oxygen concentration (SA-2). This research is designed to improve our understanding of the mechanisms that match blood flow and airflow in the lungs during an asthma attack and how these change during recovery from an asthma attack. Knowledge of this important lung function may lead to improved asthma therapy and possibly reduce asthma-related deaths. Asthma affects one out of every twenty Americans. During an asthma attack, the lung tries to match airflow and blood flow in order to maintain oxygen delivery to vital organs. One of the causes of asthma deaths may be impairment in the ability of the lung to perform this important function. This research will study the mechanisms for matching airflow and blood flow during an asthma attack so that better treatments can be developed to prevent asthma deaths.