Relationship between the early, late, and rechallenge reaction to nasal challenge with antigen: Observations on the role of inflammatory mediators and cells

We challenged each of 55 consecutive ragweed (RW)-allergic patients with hay fever and with graded increasing doses of ragweed extract to investigate the frequency and relationship between the early (ER), late (LPR), and rechallenge reactions (RCRs) to nasal challenge. We evaluated the nasal response by measuring the levels of histamine, TAME-esterase activity, and kinins in the nasal lavage fluid and by grading symptoms. Fifty-one subjects (92.7%) had an ER consisting of a dose-dependent, concommitant increase in both mediators and symptoms. The total amount of TAME-esterase activity and kinins generated during ER correlated significantly with specific serum IgE (ssIgE), intradermal skin test (ST) sensitivity, and basophil histamine release (BHR) to antigen E (p<0.01 for each). Twenty-four (47%) subjects developed a late increase in mediators and 23 (45%) subjects in symptoms. None of the four subjects without an ER developed an LPR. The levels of the late-appearing mediators were not predicted by ST, ssIgE, or BHR. There was a significant but weak association between the intesity of ER and LPR, but there was no significant difference in the IgE antibodies, ST, BHR, and intensity or threshold of ER between dual and early only reactors. The number of eosinophils and neutrophils in the LPR lavages increased over the prechallenge baseline, and their numbers correlated (p<0.05) with ER kinins (r=0.46 and 0.37, respectively), ER TAME-esterase activity (r=0.28 and 0.24, respectively), and in the case of eosinophils, ER histamine (r=029). More subjects had an increase in cells than developed an LPR (76% versus 47%), suggesting the need for additional factors to explain the activation of the incoming cells and the development of LPR. The intensity of RCR was significantly predicted (p<0.05) by ssIgE and ST. The RCR histamine, TAME-esterase activity, kinins, and number of sneezes and other symptoms correlated significantly with the corresponding levels in the ER and LPR (p<0.01 for all). On rechallenge, 21 subjects (41%) had mediator levels greater than levels during ER at the same antigen dose, and an additional 10 subjects (19.5%) had an enhanced symptomatic response without a concomitant increase in mediators. A preceding LPR was not significantly linked to an enhanced RCR, as assessed by increased symptoms or mediator levels. Although 44 subjects (80%) had a late cutaneous reaction, the size of which correlated with the size of the early cutaneous reaction (r=0.51 and 0.48; p<0.001 for wheal and erythema, respectively), there was no significant association between the development of a nasal and a cutaneous LPR, nor did cutaneous LPR predict an enhanced nasal RCR.