The inflammatory component of allergic rhinitis was studied by measuring the concentration and content of eosinophil cationic protein (ECP, specific for eosinophils) and myeloperoxidase (MPO, specific for neutrophils) in samples of nasal secretion from 20 pollen-allergic subjects. All secretion samples contained measurable concentrations of both proteins. The mean ECP concentrations on two occasions without pollen exposure were 950 and 1170 micrograms/l. The ECP concentration during the pollen season without any therapy (mean 1160 micrograms/l) did not differ significantly from the baseline values, but intranasal corticosteroid therapy resulted in a significant decrease (mean 530 micrograms/l). The concentration of MPO was about 10 times higher than that of ECP, but the changes in MPO were nonsignificant throughout the observation period. An inverse correlation was found between the threshold dose in histamine challenges and the ECP level expressed either as concentration or as content. Furthermore, the ECP concentration and content 1 day after a positive allergen challenge were both significantly correlated with the strength of the challenge reaction. Measurements of ECP in nasal secretions are useful for studying the presence and activity of eosinophils in the nasal mucosa, and may prove of value in clinical investigations on patients with allergic rhinitis.
14 adult patients with allergic rhinitis due to timothy pollen were observed for 13 weeks during the grass pollen season. IgE, IgA and timothy-specific IgE antibodies could be quantified in all serum and secretion samples. Total IgE and specific IgE antibodies in both serum and secretion reached significantly higher levels in samples taken during and after the pollen season than before the season. These seasonal changes proved to be significantly more pronounced in nasal secretion than in serum. An indication of local production in the nasal mucosa of IgE, IgA and specific IgE antibodies was also found.
Different ways of collecting relatively large volumes of nasal secretion with as physiological a composition as possible were studied. Nasal secretion was collected by the so-called nasal spray washing method from 5 patients with allergic rhinitis due to pollen and 5 healthy persons during a pollen-free season. The collection was performed without any provocation and following nasal provocation with histamine or allergen solution. With the radioimmunosorbent test, in which the lower limit of measurement was 0.1 units/ml, IgE could be quantified in 52 of 60 analysed secretions. IgA, IgG and albumin were demonstrated in all secretions. In the allergic patients, following histamine and allergen provocation, a relative increase in the concentration of IgE and albumin and a significant decrease of the IgA/albumin ratio in nasal secretion was found. In the healthy subjects, such changes in the secretion were observed only after histamine provocation. Calculations also suggested some local production of IgE, but not at all of the same order of magnitude as of IgA.
Summary Eighteen adult patients with allergic rhinitis due to Timothy pollen were observed for 36 weeks before, during and after the grass pollen season. Eight patients were treated by parenteral hyposensitization with grass pollen extract, and ten patients who were given no immunotherapy served as controls. Timothy‐specific IgE, IgG and IgA antibodies in samples of serum and nasal secretion were quantified by radioimmunological technique. In comparison with the control group, the serum concentration of Timothy‐specific IgE antibodies increased significantly (P <0.05) during the preseasonal hyposensitization treatment and then decreased significantly (P <0.05) during and after the pollen season while this therapy was being continued. In the hyposensitized patients the serum concentration of both IgG and IgA antibodies increased highly significantly (P <0.01 and P <0.001, respectively) during immunotherapy. In nasal secretion quantitative changes of the three types of antibodies were usually less pronounced or not detectable at all. The concentration of IgG antibodies, however, showed some increase in the nasal secretion during hyposensitization. These minor increases in allergen‐specific IgG and IgA antibodies in nasal secretion might explain why parenteral hyposensitization in allergic rhinitis often does not give complete relief from symptoms.
The use of lithium as an exogenous marker to determine the dilution of nasal spray washing samples was investigated in vitro and in vivo. The correlation coefficient between the true and calculated dilution determined in vitro, using pooled secretions, was 0.99 (p less than 0.001). Thirteen washings from healthy subjects contained 5-22% secretion, while five washings from asymptomatic allergic patients contained 21-39%. The described application of exogenous lithium as a marker of dilution of nasal secretion seems a promising tool for use when a washing method is employed to take samples for biochemical investigations.
Summary Nasal secretions from eighteen patients with allergic rhinitis with a positive case history, intradermal test and nasal provocation test, but with negative or only weakly positive RAST (radioallergosorbent test) on the serum against a total of thirty‐five allergens, were studied. In the RAST an immunosorbent‐purified anti‐IgE with Dɛ2 specificity was used, which raised the detection limit. Nasal secretion was collected by washing the nasal mucosa with 0.9% and 18% NaCl solution respectively, and the latter secretion was also lyophilized and concentrated. In ten cases RAST was slightly positive on the nasal secretion, and in three of the concentrated secretions the RAST value was higher than on the serum. In none of the serum or nasal secretion samples was RAST positive according to the cut off value for a positive result defined by the reference system used in Phadebas RAST®. From these results it is concluded that RAST analyses of nasal secretion from patients with allergic rhinitis is of no appreciable value in routine clinical allergological diagnosis. However, the increased sensitivity of RAST obtained with isotope‐labelled anti‐Dɛ2 may be useful in the serological diagnosis of patients with low grade allergy having low levels of IgE antibodies in serum.
12 patients suffering from grass pollen hay fever were treated for 14 weeks pre- and co-seasonally by intranasal self-administration of an aqueous solution of a glutaraldehyde-treated timothy grass pollen allergen. These patients had a statistically significant decrease in nasal symptom scores during the grass pollen peak period and in nasal challenge end-point titre after the season compared to placebo-treated patients. No significant effect was seen on the eye symptoms. 1 patient withdrew from the trial as a consequence of too strong local nasal reactions during treatment. Most other patients treated with active material reported mild local reactions during the first minutes after administration of the nasal spray. In the actively treated group a significant increase in serum and nasal secretion of grass pollen specific IgE, IgG and IgA antibodies was obtained during the treatment. In contrast, in the placebo group a significant increase in IgE antibody levels in serum and secretion occurred during the pollen season. The reduction in symptoms and increase in antibody production together with the simplicity of the procedure makes this approach to immunotherapy attractive.
Immunotherapy has been used for more than 60 years in patients with allergic rhinitis (21). The mechanism underlying the clinical improvement that is often achieved by such treatment is still unclear. One factor that might contribute to this effect in parenteral hyposensitization is the occurrence of high levels of so-called blocking antibodies (3). These are considered to belong mainly to the immunoglobulin class G (16, 17).A good allergen extract for hyposensitization should stimulate a high production of blocking antibodies without giving any local or general side effects. With a view to obtaining such allergen solutions, depot preparations with delayed absorption of the allergen (5, 8, 15) have been developed. Further efforts have been made, by modifying an allergen with different chemical substances (15,18,20,26), to reduce its allergenicity, i.e. its symptom-evoking properties, while at the same time retaining its immunogenicity, i.e. its ability to initiate an immune response. The term allergoid has been applied to such preparations (18).Treatment of timothy grass pollen extract with glutaraldehyde has been found to give an allergoid with ability to stim-
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