Nasal Mucosal Endorgan Hyperresponsiveness

Abstract

Nonspecific hyperresponsiveness of the upper and lower airways is a well-known characteristic of different inflammatory airway diseases but the underlying mechanisms have not yet been satisfactorily explained. In attempts to elucidate the relation of hyperresponsiveness to disease pathophysiology we have particularly examined the possibility that different airway endorgans may alter their function in allergic airway disease. The nose, in contrast to the bronchi, is an accessible part of the airways where in vivo studies of airway mucosal processes can be carried out in humans under controlled conditions. Different endorgans can be defined in the airway mucosa: subepithelial microvessels, epithelium, glands, and sensory nerves. Techniques may be applied further in the nose to determine selectively the responses/function of these endorgans. Topical challenge with methacholine will induce a glandular secretory response, and topical capsaicin activates sensory c-fibers and induces nasal smart. Topical histamine induces extravasation of plasma from the subepithelial microvessels. The plasma exudate first floods the lamina propria and then moves up between epithelial cells into the airway lumen. This occurs without any changes in the ultrastructure or barrier function of the epithelium. We have therefore forwarded the view of mucosal exudation of bulk plasma as a physiological airway tissue response with primarily a defense function. Since the exudation is specific to inflammation, we have also suggested mucosal exudation as a major inflammatory response among airway endorgan functions. Using a “nasal pool” device for concomitant provocation with histamine and lavage of the nasal mucosa we have assessed exudative responses by analyzing the levels of plasma proteins (e.g., albumin, α2-macroglobulin) in the returned lavage fluids. A secretory hyperresponsiveness occurs in both experimental and seasonal allergic rhinitis. This type of nasal hyperreactivity may develop already 30 minutes after allergen challenge. It is attenuated by topical steroids and oral antihistamines. We have demonstrated that exudative hyperresponsiveness develops in both seasonal allergic rhinitis and common cold, indicating significant changes of this important microvascular response in these diseases. An attractive hypothesis to explain airway hyperresponsiveness has been increased mucosal absorption permeability due to epithelial damage, possibly secondary to the release of eosinophil products. However, neither nonspecific nor specific endorgan hyperresponsiveness in allergic airways may be explained by epithelial fragility or damage since nasal absorption permeability (measured with 51Cr-EDTA and dDAVP) was decreased or unchanged in our studies of allergic and virus-induced rhinitis, respectively. Thus, the absorption barrier of the airway mucosa may become functionally tighter in chronic eosinophilic inflammation.