Ebastine in the treatment of seasonal allergic rhinitis

AIM: To test the efficiency and tolerance of the second generation antihistamine drug ebastin (kestine) in patients with seasonal allergic rhinitis (SAR). MATERIALS AND METHODS: Kestin was given for 3 weeks in doses 10 and 20 mg/day to 226 patients with SAR running for 6.8 +/- 6.1 years. SAR symptoms relief, subjective effects, side effects were studied. RESULTS: The total index of rhinitis symptoms diminished from 11.6 to 1.2 scores. Subjective response was registered in 82% of the patients, objective in 77%. Neither treatment aggravations nor serious side effects occurred. 2 patients had drowsiness, head aches, dizziness and discontinued treatment. CONCLUSION: Kestin is effective in SAR, had no serious side effects, is well tolerated.     

Effect of fexofenadine on eosinophil-induced changes in epithelial permeability and cytokine release from nasal epithelial cells of patients with seasonal allergic rhinitis

Recent studies have suggested that antihistamines, widely used in the treatment of symptoms of patients with allergic rhinitis, may also possess antiinflammatory properties. The mechanisms underlying this property, however, are not clearly understood. We have cultured epithelial cells from nasal biopsy specimens from patients with seasonal allergic rhinitis outside the pollen season and studied the effect of 0 to 10(-3) mol/L fexofenadine, the main active metabolite of terfenadine, on eosinophil-induced changes in electrical resistance (measure of permeability) and release of proinflammatory mediators from these cells. Additionally, we have studied the effect of this drug on eosinophil chemotaxis and adherence to endothelial cells induced by conditioned medium from these human nasal epithelial cell (HNEC) cultures. Incubation of HNEC in the presence of eosinophils treated with opsonized latex beads significantly decreased the electrical resistance of these cultures, an effect that was abrogated by treatment of the cultures with 10(-9) to 10(-3) mol/L fexofenadine. Similarly, incubation of HNEC in the presence of eosinophils treated with latex beads also significantly increased the basal release of the chemokine "regulated upon activation, normal T cell expressed and secreted" (RANTES) (from 96.0 to 613.0 fg/microg cellular protein; p < 0.05), IL-8 (from 42.0 to 198.5 pg/microg cellular protein; p < 0.05), granulocyte-macrophage colony-stimulating factor (GM-CSF) (from 0.54 to 3.4 pg/microg cellular protein; p < 0.05), and soluble intercellular adhesion molecule-1 (sICAM-1) (from 7.8 to 18.4 pg/microg cellular protein; p < 0.05) from HNEC. The eosinophil-induced release of IL-8, GM-CSF, and sICAM-1 from the HNEC was significantly attenuated by treatment with fexofenadine. Analysis of the effects of conditioned medium from HNEC demonstrated that this significantly increased both eosinophil chemotaxis and adherence to endothelial cells. Addition of 10(-6) to 10(-3) mol/L fexofenadine to the conditioned medium significantly attenuated eosinophil chemotaxis and adherence to endothelial cells. These results suggest that fexofenadine may reduce nasal inflammation by modulating the release of proinflammatory mediators and adhesion molecules from HNEC.     

Intranasal fluticasone propionate is more effective than terfenadine tablets for seasonal allergic rhinitis

BACKGROUND: We compared the efficacy and tolerability of the intranasal corticosteroid fluticasone propionate with that of the antihistamine terfenadine in patients with seasonal allergic rhinitis. METHODS: Two hundred thirty-two adults and adolescents with seasonal allergic rhinitis received intranasal fluticasone propionate (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 2 weeks in a double-blind, randomized, parallel-group study. Main outcome measures were clinician- and patient-rated individual and total nasal symptom scores (based on ratings of nasal obstruction, sneezing, nasal itching, and rhinorrhea); clinician-rated overall response to therapy; changes in nasal inflammatory cell counts; adverse events; and morning plasma cortisol concentrations. RESULTS: Both clinician- and patient-rated total and individual nasal symptom scores were significantly lower in the fluticasone group than in either the terfenadine group or the placebo group at nearly every measured time point throughout the treatment period. After 2 weeks of therapy, clinician-rated total nasal symptom scores decreased by 49% in the fluticasone group compared with 27% in the terfenadine group and 19% in the placebo group. In general, therapy with terfenadine was not statistically distinguishable from that with placebo based on patient-rated total or individual nasal symptom scores. According to clinician ratings, 64% of fluticasone-treated patients compared with 49% and 44% of patients treated with terfenadine and placebo, respectively, experienced significant or moderate improvement. A greater percentage of fluticasone-treated patients compared with either terfenadine- or placebo-treated patients experienced reductions in intranasal eosinophil and basophil counts after 2 weeks of therapy. No unusual or serious drug-related adverse events were reported. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone aqueous nasal spray, a well-tolerated corticosteroid preparation that can be administered once daily, is more effective than terfenadine tablets or placebo in controlling symptoms of seasonal allergic rhinitis.     

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis

INTRODUCTION: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. INTERVENTIONS: Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. MEASUREMENTS AND RESULTS: Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups. CONCLUSION: In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.     

Nedocromil sodium is rapidly effective in the therapy of seasonal allergic rhinitis

BACKGROUND: Nedocromil sodium has proven to be efficacious in prophylactic and long-term therapy for the treatment of seasonal allergic rhinitis. We examined the speed of onset of intranasal nedocromil sodium (1%) for relief of symptoms due to ragweed allergic rhinitis. METHODS: In a double-blind, placebo-controlled trial, 104 patients received either nedocromil sodium or placebo four times daily. Patients spent 10 hours per day for 2 consecutive days in Iowa City Park during the peak of ragweed season. Only patients who had significant symptoms during 3 hourly baseline assessments received drug. Symptom scores for stuffy nose, runny nose, itchy nose, and sneezing and global symptom summary scores were recorded at 19 hourly time points during the 2 days. In the evening patients recorded symptom scores for the postexposure period. RESULTS: In comparison with placebo, nedocromil significantly improved rhinitis symptoms as evidenced by lower symptom summary scores within 2 hours (p = 0.016). Further, this reduction in rhinitis symptoms was maintained throughout the 2-day pollen exposure period. After patients left the study site, postexposure symptom summary scores were also significantly lower in patients treated with nedocromil compared with those treated with placebo (p < 0.007). CONCLUSIONS: Nedocromil significantly relieved preexisting seasonal allergic rhinitis symptoms during peak pollen exposures within 2 hours of the first dose, and the therapeutic benefits were maintained on a dosing regimen of four times a day.     

Diagnostic problems before specific immunotherapy in patients with late-summer seasonal allergic rhinitis

Skin prick tests were performed on 245 patients with late summer seasonal allergic rhinitis, and of these patients, 135 specific serum IgE test were performed. On the basis of skin prick test results, 94% of the patients were found to be sensitive to Ragweed: 18% of these patients had monosensitisation to Ragweed, and 56% were sensitive not only to Ragweed but also to Mugwort. The correlation between results of skin prick tests and specific serum IgE tests was found to be very good (95%) with Ragweed antigen experiencing no problem in the diagnostic process before immunotherapy. However, in 48% of patients with positive skin prick tests to Mugwort the specific serum IgE was found to be negative. Before immunotherapy, a specific nasal provocation test was performed on 12 of these patients with Mugwort to examine the real sensitivity of the shock-organ. This careful allergen research will demonstrate which components of allergen extract should be used for immunotherapy in late summer seasonal allergic rhinitis patients.     

Onset of action of aqueous beclomethasone dipropionate nasal spray in seasonal allergic rhinitis

Beclomethasone dipropionate nasal spray is widely used in the treatment of seasonal allergic rhinitis; however, the time of onset of action has not been determined. This study assessed the onset of action, level of relief, and efficacy of beclomethasone nasal spray in patients with seasonal allergic rhinitis. In a double-blind, randomized, placebo-controlled, parallel-group, multicenter, 7-day study, symptomatic patients were administered two inhalations of beclomethasone dipropionate (n = 80) or placebo (n = 81) into each nostril twice daily. Patients assessed the onset of action and level of relief at 6, 24, and 48 hours and at days 3 and 7. Investigators evaluated symptoms at days 0, 3, and 7 and response to therapy at days 3 and 7. The difference in the cumulative number of patients reporting relief of symptoms was statistically significant in favor of beclomethasone dipropionate by hour 24 (P = 0.05). Patients in the beclomethasone dipropionate group experienced a greater level of relief than patients receiving placebo at hour 24, and improvement increased over the 7-day study compared with a decrease in relief in the placebo group. Beclomethasone dipropionate was significantly more effective than placebo in reducing symptoms (P < or = 0.02), and patients in the beclomethasone dipropionate group showed a more favorable response to treatment than did patients in the placebo group (P < 0.01). Adverse events were minor in both groups. Beclomethasone dipropionate nasal spray produced significant onset of relief of symptoms the first day of treatment; improvement was sustained and increased over the course of the study.     

Cost-effective pharmacotherapy for allergic rhinitis

This article provides guidelines for pharmacotherapy to maximize symptom relief from allergic rhinitis. Consideration of frequency, severity, and site of symptoms is important in directing pharmacotherapy efficacy and maximizing cost-effectiveness. The agents available include antihistamines, decongestants, steroids, mast cell stabilizers, anticholinergic agents, and mucolytics. Appropriate indications for each and combinations of various agents are discussed within the context of drug efficacy, side effects, affordability, and ease of compliance. The direct and indirect costs of allergic rhinitis are not well delineated but are explored to put the costs of therapy in perspective.     

Double-strength beclomethasone dipropionate (84 micrograms/spray) aqueous nasal spray in the treatment of seasonal allergic rhinitis

Determination of microgram quantities of protein in the Bradford Coomassie brilliant blue assay is accomplished by measurement of absorbance at 590 nm. However, as intrinsic nonlinearity compromises the sensitivity and accuracy of this method. It is shown that under standard assay conditions, the ratio of the absorbances, 590 nm over 450 nm, is strictly linear with protein concentration. This simple procedure increases the accuracy and improves the sensitivity of the assay about 10-fold, permitting quantitation down to 50 ng of bovine serum albumin. Furthermore, protein assay in presence of up to 35-fold weight excess of sodium dodecyl sulfate (detergent) over bovine serum albumin (protein) can be performed. A linear equation that perfectly fits the experimental data is provided on the basis of mass action and Beer's law.     

The best therapy for allergic rhinitis

Ankle fractures are common and good results are expected. Insulin dependent diabetes mellitus is also common, and long-standing disease is associated with peripheral neuropathy. A trauma unit will inevitably receive patients with both problems. We describe two salutary lessons and suggest how our experience with diabetic neuroarthropathy might be avoided.     

Management of allergic rhinitis

Allergic rhinitis constitutes one of the commonest causes for visits to a general practitioner. An increased understanding of the pathophysiology of the condition has led to a more rational use of the pharmacological agents available to treat this troublesome condition. Identification of the offending allergens is essential if rational approaches to management are to be employed.     

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis

The aim of this study was to evaluate the improvement in patient comfort and field positional accuracy provided by a new pelvic stabilization system when delivering multiple field radiotherapy to the pelvis. The Pelvic Cradle (BEHTS Manufacturing, Brisbane, Qld, Australia) is a stabilization device that provides reproducible patient positioning and levelling. Ninety patients were randomized into three groups. The first group was treated using the Pelvic Cradle, the second group was treated using current stabilization practices, and the third group was treated using the Pron Pillo (Chattanooga Pharmacal Company, USA) and current stabilization practices. Port films were assessed for field displacement in the lateral and cranio-caudal directions. A patient survey was used to evaluate the patient's perception of comfort while receiving treatment. When compared to the control group, the pelvic cradle group demonstrated a 48% improvement in the mean lateral deviation from 3.8 mm to 2.0 mm (P < 0.001) and a 36% improvement in the mean cranio-caudal deviation from 3.9 mm to 2.5 mm (P < 0.001). The Pelvic Cradle was found to provide an improved level of field positional accuracy while maintaining patient comfort.     

Evaluation and management of allergic rhinitis

The semaphorin/collapsin gene family is a large and diverse family encoding both secreted and transmembrane proteins, some of which are thought to act as repulsive axon guidance molecules. However, the function of most semaphorins is still unknown. We have cloned and characterized several semaphorins in the zebrafish in order to assess their in vivo function. Zebrafish semaZ2 is expressed in a dynamic and restricted pattern during the period of axon outgrowth that indicates potential roles in the guidance of several axon pathways. Analysis of mutant zebrafish with reduced semaZ2 expression reveals axon pathfinding errors that implicate SemaZ2 in normal guidance.     

Clinical efficacy and safety of levocarbastine++ in the therapy in children suffering from seasonal allergic rhinitis and conjunctivitis who are less than 12 year of age

Levocabastine is an antihistaminic agent for topical application. It is without not advisable general side-effects and since many years is widely used for the treatment of pollinosis in adults and children more than 12 years of age. The group of 32 children aged from 5 to 11 years suffering from seasonal allergic rhinitis and conjunctivitis were treated by means of levocabastine applied topically by 20 days during the period of natural exposition to grass pollen. The clinical efficacy and tolerability including potential side-effects, were evaluated on the basis of clinical-laryngological investigations, visual analogs scales and diary cards filed in by parents of examined children. Levocabastine has been demonstrated to have rapid onset of action in children with SAR and the topical application of the drug does not irritate the mucosa of conjunctivas and nasal cavities.     

Reduction of soluble ICAM-1 levels in nasal secretion by H1-blockers in seasonal allergic rhinitis

ICAM-1, a transmembrane glycoprotein promoting adhesion in immunologic and inflammatory reactions, was found to be increased on nasal epithelial cells of patients with allergic rhinitis. Loratadine, an H1-blocker, was found to reduce in vitro the expression of ICAM-1 on nasal epithelial cells. A double-blind, parallel-group study was carried out during the pollen season to compare the effect of two H1-blockers, cetirizine (10 mg OD) and loratadine (10 mg OD), on the release of soluble ICAM-1 in nasal secretions. A group of untreated patients was used as a control group. sICAM-1 was measured by enzyme immunoassay before and after 2 weeks of treatment. Symptoms were significantly decreased in the actively treated groups. sICAM-1 levels were unchanged in the control group but were significantly reduced in the two treated groups (P < 0.015, Wilcoxon's W test). This study shows that two H1-blockers, loratadine and cetirizine, have a similar effect on sICAM-1 released in nasal secretions during the pollen season.     

Safety of antihistamines in the treatment of allergic rhinitis in elderly patients

Elderly patients may be more susceptible than younger persons to the sedating and anticholinergic effects of first-generation antihistamines. Second-generation antihistamines, such as loratadine, astemizole, and terfenadine, cause minimal sedation and little if any impairment in cognitive and psychomotor activity in healthy nonelderly patients. Although less extensively studied in elderly patients, it is probable that second-generation antihistamines are also less likely to induce the adverse central nervous system effects in older patients that are characteristic of the first-generation antihistamines. Toxic effects to the cardiovascular system, an issue of greater concern among elderly patients who may have subclinical heart disease, has not been observed with first-generation antihistamines. Among the second-generation antihistamines, however, astemizole and terfenadine, but not loratadine, can cause serious cardiovascular adverse effects, including death, when taken in high doses or coadministered with ketoconazole, itraconazole, or macrolide antibiotics.     

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001). CONCLUSIONS: Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.     

Overview of diagnosis and management of allergic rhinitis

Allergic rhinitis remains an important problem that affects people of all ages. Although allergic rhinitis is considered a trivial disease by the public and medical community alike, the evidence of allergic rhinitis as a risk factor to the development of associated diseases such as asthma, sinusitis, otitis media with effusion, and nasal polyps is better appreciated. Pathophysiology and current therapy of allergic rhinitis is reviewed.     

Levocabastine versus cetirizine for perennial allergic rhinitis in children

OBJECTIVE: To compare the efficacy and safety of levocabastine nasal spray asid cetirizine oral for the treatment of perennial allergic rhinitis in children. MATERIAL AND METHODS: In this randomized, prospective experimental, open clinical trial. We studied 30 children with ages between 6 and 16 years with perennial allergic rhinitis. Group 1, 17 subjects (7 female, 10 male) received cetirizine once daily, 5 mg children weientig less dian 30 k asid 10 mg in children weighing more trw' 30 k during 15 days. Group 2, 13 subjects (7 male, 6 female) received levocabastine 2 puffs BID on each nostril during tbe same time. A nasal symptoms score, nasal peal: flow vid eosinophils in a nasal smear were performed before and after treatment. RESULTS: There were no statistical differences in age, weight, height and arid duration of symptoms. Both groups showed improvement of symptoms via nasal peak flow with no differences between them (intergroup); nasal eosinophils remained unchanged. We for third statistical differences pre vid postreatment in each group (intragroup): Group 1, nasal congestion p = 0.002, ocular itch p = 0.01, sneezing p = 0.007, nasal secretion p = 0.01, nasal itch O = 0.009, total points O = 0.0005. Group 2, nasal congestion O = 0.02, ocular itch p = 0.05, sneezing p = 0.01, nasal secretion p = 0.01, nasal itch p = 0.04, total points p = 0.005. Significant differences were found in nasal peal' flow in Group 1 (p = 0.01) but no differences in eosinophils between file two groups. Side effects: 3 subjects in Group 1 (drowsiness, 1 appetite increase said 1 rhinorrea with epistaxis) vide 1 in Group 2 sensation of facial edema. CONCLUSION: Bofil drugs are effective the clinical relief of symptoms of perennial allergic rhinitis in children vied levocabastine has less side effects.     

Efficacy and onset of action of fluticasone propionate aqueous nasal spray on nasal symptoms, eosinophil count, and mediator release after nasal allergen challenge in patients with seasonal allergic rhinitis

In order to determine if peripheral blood stem cells (PBSC) collected after priming with G-CSF in AML in first complete remission (CR) can be used for autologous transplantation and to evaluate the efficacy of early intensification therapy as in vivo purging, we studied 35 consecutive patients with AML in first CR. After standard induction and consolidation chemotherapy, 24 of them were treated with one (10 patients) or two (14 patients) cycles of high-dose cytarabine plus etoposide prior to PBSC collection. G-CSF was used as the priming agent. Of the 35 patients scheduled for peripheral blood stem cell transplantation (PBSCT), three relapsed before transplantation, and the 32 remaining underwent PBSCT. High-dose therapy consisted of either total body irradiation plus cyclophosphamide or busulphan plus cyclophosphamide. The median number of CD34+ cells infused was 3.24 x 10(6)/kg (range 0.15-14). The median times to reach a PMN count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l were 12 (8-28) and 30 (11-345) days, respectively. There was no transplant-related mortality. Twelve patients relapsed between 2 and 21 months post-PBSCT. With a median follow-up of 28 months, actuarial disease-free survival (DFS) is 52.41 +/- 9% in the intent-to-treat group and 57.4 +/- 9.8% in patients who underwent PBSCT. The probability of DFS is significantly higher for patients who receive early intensification therapy prior to both PBSC collection and PBSCT as compared with patients that do not: 68.8 +/- 10.27% vs 35.5 +/- 12.6%, P = 0.0418. These results indicate the feasibility of PBSCT in AML using G-CSF-mobilized PBSC. The use of intensification treatment as 'purging in vivo' prior both to collection of PBSC and PBSCT significantly reduces the risk of relapse in this group of patients.