Histamine and tryptase in nasal lavage fluid following challenge with methacholine and allergen.

BACKGROUND: The level of histamine in nasal lavage fluid has been used as an index of mast cell/basophil activation in a number of studies. Obviously, such an index can only be valid if changes in the secretory activity of nasal glands do not affect the level of histamine in lavage fluid (i.e. hypersecretion, without a simultaneous activation of mast cells/basophils in the nasal mucosa, must not increase the level of histamine). OBJECTIVES: To asses the effect of nasal hypersecretion on histamine levels in lavage fluid. METHODS: Nasal challenges were performed with methacholine and allergen in grass pollen-allergic patients and non-allergic controls. Nasal lavage fluid was collected before and repeatedly for nine hours after nasal challenge, and the level of histamine was compared with that of a specific mast cell-derived enzyme, tryptase. In addition, the effect of methacholine on basophils was examined in vitro. RESULTS: Allergen challenge of allergic patients produced sneezing and a significant increase in histamine and tryptase levels, whereas challenge of non-allergic subjects produced no such response. Interestingly, challenge with methacholine also induced a significant increase in histamine levels. This increase was seen in both allergic and non-allergic subjects and it was not associated with any sneezing or increase in tryptase levels, indicating that mast cells were not activated. Furthermore, stimulation of basophils with methacholine did not induce any histamine release in vitro. CONCLUSIONS: Apparently, there exists a pool of histamine in the human nose that can be transferred to lavage fluid during glandular hypersecretion. The source of this histamine is yet to be identified. As the level of histamine seems to be affected by the secretory activity of nasal glands, we question the use of this single mediator as an index of mast cell/basophil activation in nasal lavage studies.

Budesonide powder administration for the treatment of grass-pollen-induced allergic rhinitis.

The new dry-powder inhaler system, Turbuhaler, has proved to be equivalent to metered-dose inhalers when used in the nose, and the objective of this study was to investigate the efficacy, dose-response effects, and safety of budesonide powder given in the morning during the grass pollen season to patients with grass-pollen-induced allergic rhinitis. Of 190 randomized patients, 186 were treated and 180 completed this double-blind study, which comprised a 4-week treatment period, preceded by a 1-week run-in period. The patients were randomized to three parallel treatment groups: budesonide 400 micrograms, budesonide 200 micrograms, or placebo once in the morning. Assessment of efficacy, by comparing changes in mean scores of nasal symptoms from run-in to treatment, showed a statistically significant effect for all symptoms with active treatments, as compared with placebo. The mean reduction of symptom severity was more pronounced in the 400-micrograms group than in the 200-micrograms group, and this difference was statistically significant for runny nose (P < 0.02) and combined nasal symptoms (P < 0.02). Nasal peak-inspiratory flow improved significantly in both budesonide-treated groups, as compared with placebo (P < 0.01 and P < 0.01). During the treatment period, patients on active treatment showed, on average, a reduction of all nasal symptoms, whereas the placebo-treated patients, on average, showed an increase of nasal symptoms. Approximately 40% in the high-dose group felt total control of rhinitis symptoms, as compared with 26% in the low-dose group. There was no difference between budesonide- and placebo-treated groups in side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma.

Glucocorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma. This therapy is highly effective, and side effects are few and mild. It was the aim of the present study to evaluate a physiological nasal inhalation technique, which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles. Thirty adults with grass pollen-induced rhinitis and asthma inhaled the steroid molecule budesonide through the nose from a pressurized aerosol attached to a spacer device. Compared with inhalation of placebo, the treatment resulted in a significant reduction of nasal symptoms (P = 0.005), of bronchial symptoms (P = 0.005), but not of eye symptoms. In addition, nasal peak inspiratory flow (P = 0.0003) and oral peak expiratory flow (P = 0.02) increased. There was no difference between budesonide and placebo with regard to local side effects, such as nose bleeding, hoarseness, and irritation in mouth and throat. It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects. This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma, especially when conventional spray therapy is associated with local side effects.

An open comparison of dosage frequencies of beclomethasone dipropionate in seasonal allergic rhinitis.

In an open group-comparative study, 123 adult patients with seasonal allergic rhinitis were allocated at random to one of three treatment groups; each of which received a daily dose of 400 micrograms beclomethasone dipropionate as (1) one puff in each nostril four times daily, (2) two puffs in each nostril twice daily and (3) four puffs in each nostril once per day. The result of treatment was assessed on daily symptom scores and the use of antihistamine tablets. There were no statistically significant differences between the three groups. The results indicate that it is unnecessary to give beclomethasone dipropionate nasal spray four times daily, and treatment in the morning and in the evening is recommended.

Extraction and degradation of timothy pollen allergen during simulated in vivo conditions.

Extraction and degradation of timothy pollen in saline has been compared with extraction in nasal secretion and gastric fluid. By measuring the absolute amount of one important allergenic substance by quantitative immunoelectrophoresis and the total allergenic activity by RAST as a function of time it was shown that the allergens were extracted extremely fast and that both the total allergenic activity and the concentration of one allergen reached maximum after about 20 min. Compared with saline, extraction under the simulated in vivo conditions gave a lower maximum level and a faster degradation of allergens.

Intranasal allergen challenge during corticosteroid treatment.

The effect of a corticosteroid drug on type I reactions in the nose was studied in eighteen hay fever patients. They were treated with a daily dosage of 800 microng beclomethasone dipropionate intranasally for I week, in a double-blind, placebo-controlled cross-over trial. Allergen challenge on the last day of each treatment period showed that steroid treatment diminished sneezing and rhinorrhoea, but the effect was not statistically significant (P = 0-10). Immediate nasal blockage was unaffected. There is a marked discrepancy between the minor protection offered by beclomethasone dipropionate in type I allergy, as suggested in this study and the marked efficacy of the drug in the treatment of hay fever. It is suggested that two factors may account for this discrepancy. First, the significance of "delayed" reactions for hay fever symptoms. Second, the difference between a single allergen provocation and continuous exposure. It is suggested that a slight steroid inhibition of immediate reactions following allergen provocation is potentiated during natural exposure due to inhibition of the priming of the end-organ.