Previous studies have demonstrated symptoms and mediator release occurring as long as 11 h after nasal challenge with antigen in selected allergic subjects. Pretreatment with systemic steroids reduced symptoms and mediators including histamine, TAME-esterase activity, and kinins. The aims of the present study were to characterize the cell influx during the late-phase response to antigen challenge and to determine the effect of pretreatment with systemic steroids on this response. We examined cytospin slides of nasal washings obtained before and hourly for 11 h after nasal antigen challenge in 10 asymptomatic allergic subjects with a history of seasonal rhinitis and 5 normal, nonallergic subjects. Allergic subjects received oral prednisone (20 mg 3 times a day) or placebo in a random, double-blind crossover manner for 2 days before each of 2 challenges 1 month apart. On placebo days, a mixed cell influx occurred in allergic subjects during the late response that was 50-fold greater than the cell influx in the nonallergic control subjects (p less than 0.005). During the first 3 h after antigen challenge, eosinophils (p less than 0.005), but not neutrophils or mononuclear cells, were observed. During the late phase (4 to 11 h), neutrophils, eosinophils, and mononuclear cells were all increased. Oral steroid pretreatment blocked the influx of eosinophils (p less than 0.005), but not that of other cells. These data demonstrate an inflammatory cell influx associated with the nasal late-phase response and suggest an important pathogenetic role for the eosinophil.(ABSTRACT TRUNCATED AT 250 WORDS)

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A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

A 'nasal pool' (NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10-min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration-response study of histamine (80, 400 and 2000 micrograms/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine-induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 micrograms/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine-induced plasma exudation response was studied by exposing the mucosa to histamine (400 micrograms/ml) for 12 min, with the NP renewed every minute. Allergen-provocations were performed in subjects with hay fever and TAME-esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration-dependent increase in albumin levels in the NP fluid; 123.3 +/- 25.6, 213.8 +/- 19.7 and 430.2 +/- 32.0 micrograms/ml (mean +/- s.e.m.), respectively. The time-course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6-10 min. The dwell-time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with allergic rhinitis often have immediate symptoms after antigen challenge (the early-phase response), followed several hours later by a recurrence of symptoms (the late-phase response). Systemic glucocorticosteroids are known to inhibit the late-phase but not the early-phase response. We studied the effect of one week of pretreatment with topical (rather than systemic) glucocorticosteroids on the response to nasal challenge with antigen in a double-blind, randomized, placebo-controlled crossover study of 13 allergic patients who had previously had a dual response to nasal challenge. The patients were challenged with three 10-fold increments of allergen, producing an early response, and were then followed for 11 hours, encompassing the late response, before they were rechallenged with the lowest dose of allergen. We monitored their responses by means of symptom scores and measurements of the levels of histamine, tosyl-L-arginine methyl ester (TAME)-esterase activity, and kinins in nasal lavages. Topical glucocorticosteroids significantly reduced both the symptoms and the levels of histamine, TAME-esterase activity, and kinins in the early, late, and rechallenge allergic reactions. The fact that, in contrast to treatment with systemic glucocorticosteroids, prolonged pretreatment with topical glucocorticosteroids inhibited the early-phase response to antigen suggests that the route and duration of administration affect the mechanisms of action of the steroids. We conclude that inhibition of the early-phase as well as the late-phase response by topical glucocorticosteroids may provide an advantage over treatment with systemic glucocorticosteroids in patients with allergic rhinitis.