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Notizen: The concentration of biomarkers from vessels and inflammatory cells in nasal lavage fluid reflects the degree of hyperresponsiveness in patients with allergic rhinitis. The lavage has usually been performed of both nasal cavities together after prewashings and administration of decongestants. To improve the technique, we introduced a modification involving lavage of the nasal cavities separately without any prewashings or decongestants. We challenged 20 rhinitic subjects sensitive to timothy unilaterally with timothy extract. In nasal lavages performed before, immediately after, and 6 h after the challenge, we determined the concentrations of albumin, histamine, bradykinin, TAME (TV-α-tosyl-L-arginine methyl ester)-esterase, and leukotriene C4 (LTC4). In eight subjects, the procedure was repeated 1 and 2 weeks later. After the challenge, albumin, bradykinin, TAME-esterase, and LTC4 in the nasal lavage fluid increased on the ipsilateral side but not on the Contralateral side. Histamine did not increase after antigen challenge. After 6 h, the biomarkers were not increased. The concentrations of biomarkers did not differ between sides before the challenge and not between visits. Thus, the modified nasal lavage technique is reliable and improved compared to previous methods because it involves reproducible determinations of different biomarkers, and it is simple and easy to perform.

Notizen: In recent years, it has been possible to demonstrate mediator release into the nasal secretion after nasal allergen challenge in patients with allergic rhinitis. Using the nasal provocation model, we determined whether the mediator release was altered in immunotherapy-treated patients. Seventeen grass-pollen-allergic patients were examined under controlled, reproducible conditions. Serial challenges with increasing doses of grass pollen produced increasing numbers of clinical symptoms and release of mediators such as kinins, TAME-esterase activity, and histamine. Ten patients received a semidepot perennial grass-pollen extract for 4 years. Seven patients served as controls and did not receive immunotherapy during the observation period. Data from the group of patients receiving immunotherapy over the first year already showed a partially significant decline in the maximal mediator release after nasal allergen challenges compared to the results of pretreated challenges, whereas controls did not show any significant changes. Nasal allergen challenges after termination of 4 years' immunotherapy significantly modified the mediator release compared to pretreatment values (TAME-esterase activity P〈0.05, kinins P〈0.01, and histamine P〈0.01). Decrease of mediator release paralleled the symptom-medication scores and quantitative skin prick test. Finally, we could demonstrate a significant correlation between specific IgG increase and mediator decrease in the treated group.

Notizen: In 57 patients with house dust allergy and 20 controls protease inhibitor concentrations in nasal secretions were measured before and after antigen challenge. A correlation was found between low inhibitor levels and long duration of disease. Furthermore, significant differences of inhibitor concentrations could be demonstrated between patients with strong or moderate reactions to antigen provocation, and between patients with isolated rhinitis or a combination of rhinitis and bronchial asthma. The clinical significance of the results will be discussed with special regard to different biochemical mechanisms in the pathophysiology of seasonal and perennial immediate-type rhinitis.

Notizen: The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P 〈 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.

Notizen: It has been speculated whether the recently developed non-sedating antihistamines may possess other properties than merely being antagonists at the H1-receptors. To investigate this suggestion 12 patients with strictly seasonal allergic rhinitis participated in a double-blind placebo controlled randomized cross-over study outside the pollen season. At steady state levels of 10 mg loratadine, a new non-sedating antihistamine, the patients were challenged with methacholine. This was followed by a nasal challenge with increasing doses of allergen. 24 h later the patients were rechallenged nasally with the same methacholine dose as the day before. The volume of the methacholine-induced nasal secretion was measured and the response to allergen was determined by scoring technique. In returned nasal lavage fluid the levels of histamine and TAME-esterase activity were measured. It was found that loratadine significantly reduced the immediate allergic nasal symptoms compared with placebo (P 〈 0.01). Loratadine also reduced the allergen-induced release of histamine into the nasal cavity after the strongest allergen dose, from 9.6±1.5 (mean ± SEM) to 6.4±1.4 ng/ml (P 〈 0.05). A similar decrease in the TAME-esterase activity after treatment with loratadine was observed. The TAME-esterase activity decreased from 11.6 *103±2.47 *103 to 5.60 *103±1.45 */103 CMP (P 〈 0.05). There were no significant changes between the active and placebo treatments regarding the methacholine-induced secretory response. This was true for the initial methacholine challenge as well as the secretory response 24 h later. This study shows that loratadine is an effective drug in the suppression of immediate allergic nasal symptoms. One of the beneficial effects of this drug could be a reduction in allergen-induced histamine release. A finding which further implicates that antihistamines may possess other effects than just a blocking of the H1-receptor.

Notizen: The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P 〈 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.

Notizen: It has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non-specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non-specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME-esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush® prior to the allergen challenge as well as at the 24-hr follow up. The allergen challenge induced a five-fold increase in non-specific nasal reactivity, as measured by the methacholine challenges, at the 2-hr follow up from 0·051 ml ± 0·012 (mean ± s.e.m.) to 0·255 ± 0·062 (P 〈 0·01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting. With a similar timing the allergen challenge also induced an increase in the proportion of eosinophils on the mucosal surface from an initial 0·8 ± 0·4% to 6·2 ± 2·1% of the cells as early as 2 hrs later (P 〈 0·05). A significant correlation was foundbetween the levels ofECP and eosinophils in the lavage fluid (r= 0·64, P 〈 0·001) and between the levels of ECP and TAME esterase (r= 0·43, P 〈 0·01). No correlations were, however, disclosed between the increases in non-specific nasal reactivity and the number of eosinophils (regardless of the cell-harvesting technique) or ECP levels at any of the observed time points. It is therefore suggested that the allergen-induced change in non-specific nasal reactivity is a complex phenomenon rather than just the recruitment and activation of eosinophilic granulocytes in the nasal cavity.

Notizen: The study was carried out to investigate the effect of azelastine on the Substance P (SP) concentration in bronchoalveolar (BAL) and nasal (NAL) lavage obtained from atopic grass pollen asthmatics and non-atopic healthy subjects. In BAL and NAL fluids there was a significant elevation in the baseline concentration of SP between asthmatics and volunteers. Allergen provocation induced a rise of SP in BAL and NAL in asthmatics, but not in volunteers. Azelastine pre-treatment resulted in a significant reduction of SP in baseline concentration of SP in BAL and NAL from asthmatics. An elevation of SP in BAL or NAL fluids after allergen provocation was not seen in asthmatics pretreated with azelastine. Azelastine did not influence the SP concentration in BAL and NAL of volunteers.

Notizen: Background and Objective A subset of IL-4 producing CD8+ T cells was recently identified in HIV patients. Based on these findings we examined whether IL-4 producing CD8+ T cells would also be present in allergic patients and what would be the functional relevance of this T-cell population.Methods We investigated the role of CD8+ T cells in IgE production of allergic diseases by analysing the cytokine profile of individual CD4+ and CD8+ T cells.Results In allergic patients about twice as many CD4+ T cells and six times as many CD8+ T cells produced IL-4 as in non-allergic controls. In contrast the frequency of IFNγ+ T-cell subsets did not significantly differ between the allergic and non-allergic individuals. The frequency of 1L4+CD8+ T cells correlated with the level of serum IgE. Coculture experiments with T cells or purified CD8+ T cells together with autologous B cells indicated that CD8+ T cells enhanced IgE in vitro, but not IgM production, even when they were physically separated from B cells. This effect could be partially blocked by addition of an IL-4 binding protein, a soluble IL-4 receptor indicating that lL-4 is involved in CD8+ T-cell mediated IgE production.Conclusions These data indicate a positive role of IL-4 secreting CD8+ T cells in IgE regulation in allergic patients.