Variations in histamine concentration in nasal secretion in patients with allergic rhinitis.

The histamine concentration and content in nasal secretion and the volume of nasal secretion in nasal washing samples were measured under different conditions in 28 patients with allergic rhinitis sensitive to birch pollen. The mean histamine concentration was significantly lower after intranasal birch pollen challenge (2.08 micrograms/ml) than in prechallenge samples (6.96 micrograms/ml), and was also significantly lower in untreated patients during the birch pollen season (2.30 micrograms/ml) than off-season (7.18 micrograms/ml). The same relationship was found between the histamine content of the secretion samples obtained on these occasions. The mean secretion volume was greater after than before challenge, but not significantly higher during the season than off-season. A partial reversion of the changes in histamine concentration and content that occurred during the season was observed during intranasal corticosteroid therapy. The concentration and content of histamine in nasal secretion from symptomatic patients after intranasal histamine challenge did not differ significantly from those in asymptomatic subjects before challenge. It was concluded that although the histamine level in nasal secretion can be used as a marker of changes in the severity of allergic rhinitis, it is not ideal for this purpose.

Eosinophil cationic protein and myeloperoxidase in nasal secretion as markers of inflammation in allergic rhinitis.

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.

Histamine concentrations in nasal secretion and secretory activity in allergic rhinitis.

The prerequisites for using the assayed histamine concentration in nasal secretion as an objective measure of disease activity in allergic rhinitis were investigated. It was demonstrated that in histamine determination procedures the presence of quenching substances in the nasal secretion could lead to underestimation of the histamine concentration. This bias was eliminated in a modified spectrofluorometric assay. Only an insignificant fraction of the histamine in samples collected by nasal spray washing was bound to unfiltrable particles or cells. The mean histamine concentration in nasal secretions from 15 healthy subjects was 11.2 micrograms/ml and in a group of nine patients with allergic rhinitis out of season 3.36 micrograms/ml. The histamine concentration in the latter group decreased during the pollen season and after positive allergen challenge. It is suggested that this decrease is caused by the increase in volume of the secretion during the allergic response. The use of lithium as an exogenous marker permitted quantitation of the increase in the relative amount of nasal secretion recovered by washing in the symptomatic subjects.

Transsphenoidal therapeutic puncture of a cystic pituitary adenoma.

Transsphenoidal diagnostic puncture of skull base tumours has been a routine procedure in Uppsala for a decade. Bromocriptine is the treatment of choice for patients with prolactin secreting pituitary adenomas. Here we report on a patient with a pituitary adenoma who instead developed an increase in tumour size after bromocriptine treatment. Magnetic resonance imaging showed the tumor to be cystic. A transsphenoidal puncture was used therapeutically instead of surgery with excellent result.

A freeze-fracture study of receptor axons and Schwann cells in the human olfactory mucosa.

Electron micrographs of freeze-fracture replicas from the human olfactory mucosa were analysed regarding the structure of the axons of the olfactory receptor cells. In the lamina propria, numerous axons were generally invested with one Schwann cell. The ensheathed axons were often found in close contact with one another. Membrane specializations were not found at these sites, nor were tightening membrane junctions observed in the mesaxons. The Schwann cell plasmalemma exhibited caveolae, whose neck was surrounded by uniformly sized intramembranous particles evenly distributed over the axolemmal fracture planes. There was a marked difference in particle density between the P face (about 850/micron 2) and the E face (about 180/micron 2).

Random distribution of exogenous lithium in nasal secretion and its application in substance determination.

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.

Use of glutaraldehyde-modified timothy grass pollen extract in nasal hyposensitisation treatment of hay fever.

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.

Hyposensitization of patients with allergic rhinitis by intranasal administration of chemically modified grass pollen allergen. A pilot study.

In a pilot study, five adult patients with allergic rhinitis due to grass pollen underwent local intranasal hyposensitization with a chemically modified grass pollen extract--a so-called allergoid. Local hyposensitization during a pre-seasonal period resulted in an increased serum level of timothy-specific IgE antibodies in all patients, indicating that the allergoid had immunogenic properties. In four of the patients the clinical effect during the grass pollen season was judged satisfactory. Pre- and post-seasonal provocation test in these four patients also showed a reduction of the nasal sensitivity during this period. All patients tolerated the treatment well without any marked side effects. These promising preliminary results motivate further investigation into this form of therapy.

Immunoglobulins in serum and nasal secretion. A comparison between patients with aspirin hypersensitivity and allergic rhinitis.

Immunoglobulins A, E and G were studied in serum and nasal secretion from patients with allergic rhinitis, chronic rhinitis and aspirin hypersensitivity, and normal controls. The allergic patients differed from the other groups in having higher IgE values, both in serum and in nasal secretion. The patients with aspirin hypersensitivity did not differ from the control group regarding the IgE values. No difference between the groups was found with respect to IgA and IgG. The results indicate that reaginic antibodies are not involved in causing aspirin hypersensitivity.

Specific IgE antibodies in nasal secretion from patients with allergic rhinitis and with negative or weakly positive RAST on the serum.

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 DE2 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 luophilized 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-DE2 may be useful in the serological diagnosis of patients with low grade allergy having low levels of IgE antibodies in serum.

Nasal polyps treated by beclomethasone nasal aerosol.

A double-blind cross-over study of the effect of insufflation of beclomethasone dipropionate 400 microgram per day for four weeks showed favourable results, as verified statistically, concerning nasal blockage at the end of the treatment period. Rhinomanometry also showed that the nasal patency was significantly improved during the beclomethasone period. There was also a tendency, though not statistically significant, for nasal secretion to react favourable. The polyps did not disappear during the active treatment period and short-term treatment with beclomethasone aerosol can thus only be used as an adjuvant to other models of therapy, whether medical or surgical, in nasal polyps. No clinical side-effects of any importance were observed during the study.

Immunoglobulins in nasal secretion with special reference to IgE. I. Methodological studies.

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.

Immunoglobulins in nasal secretion with special reference to IgE. II. Seasonal studies of Timothy-specific IgE-antibody in 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 secific IgE antibodies was also found.