The airway circulation has many potential roles in asthma. The vasculature has a major influence on upper airway patency in nasal infection and atopic responses. Given its responsiveness to provocative stimuli in asthma and vasoconstrictive and antiproliferative response to corticosteroids, the bronchial circulation is likely to be a future target for novel asthma therapies.
Introduction Increased vascularity of the bronchial wall is now recognized as a key feature of the tissue remodeling that is characteristic of asthma. Originally described in the era of Leonardo da Vinci, the bronchial circulation has until recently been considered to be primarily a source of oxygenation and tissue nutrients for the airway wall, as well as thermoregulation and humidification of inspired gas. It is also recognized as a primary pathway for elimination of asthma medication drugs.
The bronchial vessel circulation has specific functions of relevance to asthma through regulation of fluid shift into the sub mucosa, by attracting and controlling the migration of inflammatory response cells into the airway wall, as well as being a source of micro-environmental factors for the regulation of tissue remodeling. It is reactive to multiple stimuli and is able to increase blood flow dramatically to provide effective thermoregulation in response to heat stress.
Its responsiveness to chemical mediators of inflammation, capacity to participate in immunologic responses and ability to remodel in response to trophic stimuli make the airway circulatory bed both an important determinant of airway wall thickness and the acute inflammatory reactions changes in airflow characteristic of asthma.
Role Airway Vascularity in Asthmatic Responses
The classical early asthmatic response to allergen is associated with the release of numerous preformed and newly generated inflammatory mediators capable of causing vasodilatation and capillary leakage. Edema formation is an important component of this response, and may be life-threatening when critical upper airway structures are involved. The nasal allergen obstruction seen in susceptible individuals after aeroallergen exposure is a manifestation of highly reactive airway vessels responding with dilation and leakage, though difficult to detect in the stable state between episodes. In addition, the airway vascular response accompanying viral infection may be significantly up regulated by vascular endothelial growth factor (VEGF) released by fibroblasts.
The cellular infiltration that is characteristic of the late asthmatic response is a complex process that involves mobilization of cells from bone marrow and vessel margination sites, adhesion to vessels in the local inflammatory environment, cell rolling and transmigration between endothelial cells. The cell infiltrate includes eosinophils, mast cells and activated Th2 lymphocytes.
The central role of the eosinophil in the pathogenesis of asthma is well described. Regulation of eosinophil numbers in the airway may be achieved through a number of therapeutic strategies including antagonism of the trophic factor interleukin (IL)-5, the use of corticosteroids acting through multiple pathways, as well as via effective inhibition of adhesion glycoproteins in the bronchial circulation. Vessels in asthma are therefore capable of acting through a range of mechanisms to promote the inflammatory response and airway remodeling typical of asthma.
