NASAL MUCOSAL ENDORGAN HYPERRESPONSIVENESS

Nonspecific hyperresponsiveness of the upper and lower airways is a we ll-known characteristic of different inflammatory airway diseases but the underlying mechanisms have not yet been satisfactorily explained I n attempts to elucidate the relation of hyperresponsiveness to disease pathophysiology we have particularly examined the possibility that di fferent airway endorgans may alter their function in allergic airway d isease. 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, epit helium, glands, and sensory nerves. Techniques may be applied further in the nose to determine selectively the responses/function of these e ndorgans. Topical challenge with methacholine will induce a glandular secretory response, and topical capsaicin activates sensory c-fibers a nd induces nasal smart. Topical histamine induces extravasation of pla sma from the subepithelial microvessels. The plasma exudate first floo ds the lamina propria and then moves up between epithelial cells into the airway lumen. This occurs without any changes in the ultrastructur e or barrier function of the epithelium. We have therefore forwarded t he 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. Usi ng 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, alpha(2)-macr oglobulin) in the returned lavage fluids. A secretory hyperresponsiven ess occurs in both experimental and seasonal allergic rhinitis. This t ype of nasal hyperreactivity may develop already 30 minutes after alle rgen challenge. It is attenuated by topical steroids and oral antihist amines. We have demonstrated that exudative hyperresponsiveness develo ps in both seasonal allergic rhinitis and common cold, indicating sign ificant changes of this important microvascular response in these dise ases. An attractive hypothesis to explain airway hyperresponsiveness h as been increased mucosal absorption permeability due to epithelial da mage, possibly secondary to the release of eosinophil products. Howeve r, neither nonspecific nor specific endorgan hyperresponsiveness in al lergic airways may be explained by epithelial fragility or damage sinc e nasal absorption permeability (measured with Cr-51-EDTA and dDAVP) w as decreased or unchanged in our studies of allergic and virus-induced rhinitis, respectively. Thus the absorption barrier of the airway muc osa may become functionally tighter in chronic eosinophilic inflammati on.