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Background: Ciclesonide exhibits clinical efficacy at 160 microg (ex-actuator) once daily but the anti-inflammatory effects at this dose are not known. We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 microg once daily in the morning exhibited significant anti-inflammatory effects., Methods: Seventeen patients with mild persistent asthma (FEV(1) 3.35 l) were recruited into a double-blind placebo-controlled randomized crossover study. Measurements were made after ciclesonide and placebo treatment as well as after run-in and washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup)., Results: The mean (SEM) AMP bronchial challenge PC(20) following ciclesonide (140 (63) mg/ml) was significantly (P < 0.001) increased compared with placebo (17 (8) mg/ml), run-in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to an eightfold (CI: 5.3-12.0) for ciclesonide vs placebo. Likewise, there were significant improvements in exhaled NO levels and a significant reduction in induced sputum eosinophil cell counts., Conclusion: We have shown that inhaled ciclesonide given at 160 microg once daily in the morning exhibits significant anti-inflammatory effects that are in keeping with the previously described clinical effects.

Background: The aim of this clinical trial was to investigate whether repeated inhalation of the new inhaled steroid ciclesonide reduces the early-phase (EAR) and late-phase (LAR) reactions after allergen challenge in patients with mild allergic asthma. Also, this study provides further data on safety and tolerance of ciclesonide., Methods: The study was designed as a double-blind placebo-controlled randomized crossover trial. Following a baseline period, patients were randomized to either of two treatment sequences (ciclesonide/placebo, placebo/ciclesonide) each of which lasted for one week and were separated by 3-5 weeks from the alternate treatment sequence. Patients received 800 micro g ciclesonide twice daily by means of a Cyclohaler. At the end of each treatment patients were subjected to an allergen challenge., Results: Thirteen asthmatic patients (mean FEV1 of 91% predicted) who experienced an EAR and LAR after allergen challenge participated in the study. The time-average FEV1 decreases 0-2 h (2-12 h) after allergen challenge as measure of the EAR (LAR) were significantly reduced (P < 0.05, one-sided) from 0.426 L to 0.233 L (EAR) and from 0.443 L to 0.213 L (LAR), respectively. Thus, the study results suggest that ciclesonide significantly lowered the extent of EAR and LAR compared to placebo. Ciclesonide was well tolerated and no drug-related adverse events were reported. Cortisol excretion in 24-h urine showed no significant difference between ciclesonide and placebo., Conclusions: The study supports the efficacy and safety of ciclesonide.

The study investigated the effect of the oral H1-blocker terfenadine on allergen challenge in subjects with nasal allergy in comparison with the topical steroid, budesonide. A randomized, placebo-controlled, double-blind, crossover study with 3 experimental days was performed outside the pollen season. Seventeen nonsmokers with hay fever (symptoms, positive skin prick test, and RAST against timothy) were treated for 14 days before each experimental day, where the response to nasal challenge with four different concentrations of timothy was measured every 15 min for 6 h. The nasal cavity dimensions were measured by acoustic rhinometry and the olfactory function as the threshold for the sense of smell of butanol. Nasal symptoms were determined by questionnaires. Both terfenadine and budesonide dry powder had an effect on the hay fever symptoms during nasal pollen challenge. Terfenadine was more efficient than budesonide against histamine-mediated symptoms such as sneezing and itching. Budesonide increased nasal airway dimensions better than terfenadine (P < 0.01). A marked effect of budesonide was seen 1-2 h after challenge, suggesting an effect on "early late phase" reaction in the nose. In 7/17 subjects, a significant (P < 0.05) improvement of olfactory function after budesonide treatment was seen. In conclusion, topical steroid (budesonide) is superior to antihistamine (terfenadine) in treatment of nasal congestion in hay fever, especially for the postchallenge reaction, and may, in some cases, relieve the decreased sense of smell during pollen challenge.

The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma-derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double-blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 micrograms per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa.

Anti-IgE-induced histamine release from human leukocytes is inhibited when the cells before challenge are cultured overnight in the presence of glucocorticoids (GCSs). The present report suggests that the GCSs might exert their effect by at least a dual mechanism of action. Histamine release was induced by a suboptimum concentration of anti-IgE. When the release recorded in the presence of the steroid is plotted against the release recorded in its absence, the data points of several experiments fit a regression line characterized by two parameters: its slope and its intercept with the abscissa. Structure-activity examination with selected GCSs indicates that the orders of potency for affecting these two parameters are not identical. Furthermore, pulse experiments suggest that the cells require different times of contact with the steroid to express inhibition according to the two parameters. The removal of adherent cells or platelets did not markedly affect the degree of leukocyte histamine release or its inhibition by a given GCS, suggesting that the steroid interacts directly with the basophil. Finally, steroid-induced inhibition was not affected by the putative phospholipase A2-inhibitor p-bromophenacylbromide (BPB) or the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA).

A long-term safety study of intranasally administered budesonide, a topical glucocorticoid, has been performed. 104 patients with perennial rhinitis, allergic or non-allergic, participated in a multicentre study in seven ENT-clinics utilising an identical protocol. A budesonide dosage of 400 micrograms/day was used as starting dose, but the patients were at liberty to reduce the daily dose to 200 micrograms. The patients were observed at intervals up to 12 months. At the entry and follow-up visits the following parameters were recorded: rhinoscopic findings, nasal symptom scores, blood chemistry, hematology, urinalysis and determination of plasma cortisol levels before and after stimulation with ACTH (Synacthen). Nasal biopsies taken from 50 of the patients at the beginning and completion of the study were examined in a blinded way by an independent pathologist. The analysis revealed no histopathological changes of the nasal mucosa. At rhinoscopy no signs of atrophy or candida were reported. Lividity of the nasal mucosa was significantly reduced during the trial, which was also the case for nasal congestion and secretion. All nasal symptom parameters assessed by the patients were significantly reduced from baseline during the follow-up period. No clinically significant changes in the hematological and blood chemistry parameters were observed. Plasma cortisol analysis before and after challenge with ACTH revealed no influence on the hypothalamic pituitary adrenal axis. No tachyphylaxis was observed; on the contrary, there was a clear tendency for reduction of the daily dose of budesonide necessary to keep the patients symptom-free.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucocorticoids were previously considered not to affect the immediate allergic reaction. However, in a nasal allergen challenge, an inhibitory effect on the nasal symptoms induced at the challenge has been shown to occur in patients treated with a recently developed glucocorticoid, budesonide, for 1 week prior to the challenge. This treatment was also found to reduce tissue histamine levels in the nasal mucosa. Mast cells in the mucosa were therefore studied with a view to finding out whether this reduction could be due to a reduction of mast cells. A double-blind study was performed in 14 asymptomatic patients. Nasal biopsies were made before and after 1 week's treatment with either budesonide or placebo. The number of mast cells was counted in two Epon sections after the specimens had undergone specific staining with toluidine blue. No quantitative or qualitative morphological changes in the mast cells were found as a result of treatment.

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

The "vasoconstrictor" effect of dermally applicated steroids is a widely used parameter when determining the potency of glucocorticoids. A similar effect on the nasal mucosa has been suggested as providing an explanation for the clinical effect of topically administered glucocorticoids in the treatment of nasal disorders such as allergic and vasomotor rhinitis. The recently described 133Xe wash-out method was used for the purpose of blood flow determination in 11 healthy subjects. In a randomized double-blind cross-over study, the effect of topically administered budesonide, a non-halogenated glucocorticoid, for 1 week was compared with that of placebo. No difference was found to occur in the mucosal blood flow after the administration of budesonide, as compared with placebo. It seems likely that a more complex activity than vasoconstriction is responsible for the clinical effect in the treatment of nasal disorders, and further research is required in order to clarify this issue.

Thirty patients with seasonal allergic rhinitis entered a double blind study comparing budesonide (nasal spray, 400 micrograms/d) and i.m. injection of 80 mg methylprednisolone acetate. Symptoms were assessed over a "run in" period of 3-7 days followed by a treatment period of 3 weeks. Pollen counts were evaluated daily. Both the systemic and topical corticosteroid treatment resulted in a significant improvement of nasal and ocular symptoms and were accompanied by reduced antihistamine intake. A comparison of the two treatments in relation to the pollen count yielded statistically significantly fewer nasal symptoms, such as itching, secretion, and sneezing in the budesonide-treated group. Nasal blockage and ocular symptoms remained unchanged, but the use of eyedrops was significantly reduced in the methylprednisolone-treated group. Side effects of both treatments were mild and the incidence negligible. Methylprednisolone-treated patients had a significantly lower cortisol value after 7 days but still had a normal response to ACTH-stimulation. We conclude that the acute symptoms of allergic rhinitis are at least as well ameliorated by regular topical application of budesonide as by a single injection of methylprednisolone acetate. The accompanying allergic conjunctivitis may require additional treatment.

IgE-receptor dependent, but not A23187-induced, histamine release from passively sensitized chopped human lung tissue, or from a dispersed lung cell population obtained from the tissue after enzymatic digestion, is reduced after incubation overnight of cells/tissue with the glucocorticosteroid budesonide (10(-7) M). Since the inhibitory effect of budesonide is reduced in the continuous presence of diluted reagin-rich serum used for passive sensitization, but not in the presence of heat-inactivated serum, it is suggested that the glucocorticosteroid acts by reducing the binding of IgE-antibody to the target cell(s).

We examined the effects of glucocorticosteroids (GCS) on antigen-induced bronchial anaphylactic reactions (BAR) in SD rats immunized with ovalbumin (OA) and alum. The animals were treated with vehicle, budesonide (BUD), dexamethasone (DEX), or hydrocortisone (HC) at various times before intravenous (i.v.) antigen challenge. The drugs were administered either intraperitoneally (i.p.) or intratracheally (i.t.); the BAR was elicited by a low or by a high challenge dose of antigen. A BAR elicited by a low challenge dose of antigen was reduced in a dose-dependent way by all GCS after i.p. administration; at 1 mg/kg, BUD and DEX significantly reduced BAR and at 50 mg/kg all three of the examined compounds inhibited the BAR by 50% or more. For BUD, maximum effect was recorded when it was given 12 h before test. There was only a slight variation in the inhibitory effects of the GCS with immunization conditions of test animals. I.t. instillation of the drugs did not markedly increase their inhibitory capacity as compared to i.p. administration. BAR elicited by a high antigen dose was at best marginally affected by the GCS when given either i.p. or i.t. Thus, antigen-induced airway reactivity in rats can be reduced by GCS treatment provided that this is performed sufficiently long before the test and that the challenge dose of antigen is not too high.