The studies proposed in the present grant application have the long-term objective of exploring the relative importance of the bronchial circulation, vascular engorgement, and airway wall edema in the production of acute airway obstruction form multiple causes, as well as its role in producing heightened reactivity. Although techniques are not yet available to directly measure in vivo bronchial blood flow in humans, previous work from our laboratory has shown that by using a specially designed thermal probe to measure changes in intra-thoracic airstream temperature, a reflection of flux in the blood supply to the airways may be obtained. Using this technique, we have demonstrated that the rate and magnitude of airway rewarming following exercise is significantly greater in asthmatics as compared to normals, implicating that an enhanced bronchial blood flow may be etiologic in EIA. The proposed studies will explore the contribution of the bronchial vasculature to the production of obstruction from two perspectives. First, bronchial vascular volume and tone will be enhanced or decreased via fluid infusions of saline or dextran, diuretic administration, and alpha agonist inhalation to assess the effects of altered blood flow and capillary permeability upon bronchial reactivity and intra-airway thermal profiles. The second group of investigations will explore the role of the bronchial circulation in the heightened airway responsivity which is seen following antigen exposure. Intraairway thermal profiles during exercise challenges will be measured before and after antigen inhalation to determine if airway hyperactivity is possibly linked to bronchial blood flow. These proposed protocols are designed to provide further confirmatory evidence for the importance of the bronchial circulation in the production of asthma from multiple stimuli and to separate out the mechanical effects produced by vascular engorgement alone from those engendered by airway wall edema due to capillary leakiness. In this manner, new insights into the pathophysiology of acute airway obstruction will be gained and serve to direct further research and therapeutic endeavors towards the vasculature and its interaction with airway smooth muscle.
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| Gilbert, I A; Regnard, J; Lenner, K A et al. (1991) Intrathoracic airstream temperatures during acute expansions of thoracic blood volume. Clin Sci (Lond) 81:655-61 |
