pulmicort and azelastine

We performed a systematic review of randomized, controlled trials to determine whether intranasal corticosteroids offered an advantage over topical antihistamines in the treatment of allergic rhinitis.. We searched for studies using MEDLINE, Embase, Cinahi, and Cochrane databases, pharmaceutical companies, and references of included trials.. Criteria for considering trials included: 1) published randomized controlled trials; 2) single- or double-blind studies; and 3) presence of one of the following clinical outcomes: nasal symptoms, eye symptoms, global symptoms evaluation of quality of life and side effects.. Nine studies including 648 subjects (mean age 30.4 years, range 13 to 73) with allergic rhinitis were selected. Intranasal corticosteroids produced significantly greater reduction of total nasal symptoms (standardized mean difference -0.36, 95% confidence interval -0.57 to -0.14), sneezing (-0.41, -0.57 to -0.24), rhinorrhea (-0.47, -0.64 to -0.29), itching (-0.38, -0.56 to -0.19), and nasal blockage (-0.86, -1.07 to -0.64) than did topical antihistamines. There was no significant difference between treatments for ocular symptoms (-0.07, -0.27 to 0.12). The effects on sneezing, rhinorrhea, itching, and ocular symptoms were significantly heterogeneous between studies. Other outcomes (total nasal symptom score and nasal blockage) were homogeneous between studies. Subgroup and sensitivity analysis suggested that most of the heterogeneity of outcomes could be explained on the basis of the methodologic quality of studies.. Intranasal corticosteroids produced greater relief of nasal symptoms than did topical antihistamines (topical H1 receptor antagonists). However, there was no difference in the relief of the ocular symptoms.

Topics: Administration, Intranasal; Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Middle Aged; Phthalazines; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Treatment Outcome

Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes, after intranasal administration of azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement. Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine. Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between azelastine and placebo recipients and preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR).. Twice-daily intranasal azelastine offers an effective and well tolerated alternative to other antihistamine agents currently recommended for the symptomatic relief of mild to severe SAR and PAR in adults and children (aged > or = 12 years in the US; aged > or = 6 years in some European countries including the UK). The rapid onset, confined topical activity and reduced sedation demonstrated by the intranasal formulation of azelastine may offer an advantage over other antihistamine agents, although this has yet to be confirmed.

Topics: Administration, Intranasal; Adult; Beclomethasone; Budesonide; Child; Drug Tolerance; Glucocorticoids; Histamine H1 Antagonists; Humans; Neutrophils; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Allergic Rhinitis (AR) is a prevalent chronic inflammatory nasal condition with significant negative effects on the patients' quality of life. This study aimed to investigate the efficacy of Montelukast and intranasal antihistamine in combination with intranasal corticosteroid (INCS) in moderate to severe allergic rhinitis on the patients' quality of life and AR control.. This double-blind randomized clinical trial study was carried out on 66 moderate to severe AR patients referred to Namazi Hospital, Shiraz, Iran from 2020 to 2021, who were randomly divided into 3 groups. Group one received Montelukast add-on therapy and Budesonide nasal spray. The second group received intranasal antihistamine (Azelastine) add-on therapy and Budesonide nasal spray and the third group as the control group received intranasal Budesonide spray with a placebo tablet.To measure the impact of each medication on the patient's quality of life and AR control, we employed the Sino-Nasal Outcome Test-22 questionnaire (SNOT 22). We evaluated the symptoms and compared them at baseline, one and three months after the start of treatments. Spirometry was performed to investigate the possibility of co-morbid asthma at baseline and end of the study.. The patients' mean age was 30.13 ± 12.7 years. Most patients experienced perennial AR (65.2%). Reduction of mean scores SNOT22 was statistically different between groups (P-value < 0.001). Three months after treatment, the mean decrease of SNOT-22 in the Azelastine group was statistically significant compared to both Montelukast (P-value < 0.001) and control groups (P-value < 0.001). No significant difference was observed between the Montelukast and control groups (P-value = 0.142). 23 of 66 patients were diagnosed with asthma and asthma treatment was initiated. The amount of FEV1 change after AR treatment was not statistically significant between the groups in asthmatic patients (P-value = 0.351).. Based on our findings, we recommend Azelastine in conjunction with an intranasal corticosteroid for the treatment of moderate to severe allergic rhinitis. In moderate to severe AR or even asthma management, Montelukast has no greater impact than INCS.

Topics: Acetates; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Cyclopropanes; Double-Blind Method; Histamine Antagonists; Histamine H1 Antagonists; Humans; Nasal Sprays; Phthalazines; Quality of Life; Quinolines; Rhinitis, Allergic; Sulfides; Treatment Outcome; Young Adult

Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known.. To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients.. A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period.. Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events.. A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine nasal spray.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Budesonide; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Perennial

We studied the activity of a topical form of a corticosteroid (budesonide) and an antihistamine (azelastine) in the treatment of seasonal allergic rhinitis by including an assessment of mediator concentrations and the percentage of eosinophils in the nasal secretions before and after the treatment. Nasal allergen challenge (NAC) during the season was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction. The study compared in a randomized way (2 parallel groups) the effect of budesonide (Rhinocort Aqua) and azelastine (Allergodil nasal spray) in a group of 14 patients during the pollen season. The study showed that azelastine significantly reduced sneezing, total nasal resistance and increased nasal airflow even when significant increases in histamine, tryptase and leukotriene C4 (LTC4) concentrations in nasal secretions were evidenced immediately after NAC. Budesonide showed a strong (p<0.05) decrease in infiltration and activation of eosinophils, and on tryptase and LTC4 release after NAC. These effects (not for LTC4) lasted at least for 1 week after therapy. Azelastine is a powerful topical antihistamine, while budesonide appears to be a potent long-acting anti-inflammatory agent.

Topics: Adolescent; Adult; Allergens; Budesonide; Eosinophils; Female; Humans; Hypersensitivity, Immediate; Inflammation Mediators; Leukocyte Count; Male; Middle Aged; Nose; Phthalazines; Pollen; Rhinitis, Allergic, Seasonal; Seasons

Two experiments were performed during the pollen season to study the activity of different antiallergic drugs in the treatment of seasonal allergic rhinitis. Nasal allergen challenge (NAC) was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction during the season. The first study assessed the effect of H1 (Cetirizine 10 mg a day) and of a combination of H1 (Cetirizine 10 mg) plus H2 (Cimetidine 800 mg a day) antagonists on nasal symptoms, mediator release and eosinophil count in a group of 16 patients with seasonal allergic rhinitis. During the same season a second study compared in a randomized way (2 parallel groups) the effect of Budesonide (Rhinocort Aqua) and Azelastine (Allergodil nasal spray) in a group of 14 patients. Results showed that both antihistamines, applied topically of dosed orally, reduced sneezing even when significant increases of histamine concentration in nasal secretions were evidenced immediately after NAC. When a combination of Cetirizine and Cimetidine was administered, a significant (p < 0.01) reduction of nasal airway resistance and increase of nasal airflow after NAC were demonstrated as well. In addition, topical application of Budesonide showed a strong (p < 0.01) effect on the infiltration and activation of eosinophils during the season, and on tryptase release after NAC. These effects lasted at least for one week after therapy.

Topics: Adult; Airway Resistance; Anti-Allergic Agents; Bronchodilator Agents; Budesonide; Cimetidine; Female; Histamine H2 Antagonists; Humans; Male; Middle Aged; Mucus; Nasal Provocation Tests; Phthalazines; Pregnenediones; Rhinitis, Allergic, Seasonal

The efficacy and safety of a new antiallergic drug, intranasal azelastine (CAS 58581-89-8), in the treatment of seasonal allergic rhinitis was investigated in a 16 patient double-blind comparison with placebo and another 36 patient open comparison with budesonide (CAS 51333-22-3). Efficacy was assessed in terms of 13 signs and symptoms of allergic rhinitis and tolerability on the basis of spontaneously reported adverse events. In the first study, compared to placebo a one week's treatment with azelastine resulted in substantial relief of sneezing (p = 0.009), nasal itching (p = 0.009), swelling of the nasal mucosa (p = 0.067) and rhinorrhoea (p = 0.262) in patients having the above symptoms at baseline of at least moderate to severe intensity. According to the judgement of the supervising physician, 7/8 azelastine-treated patients but none receiving placebo responded well to therapy (p = 0.001). In the second study a two weeks' treatment with intranasal azelastine was found not to differ significantly from budesonide 67% of patients showed improvement in principal signs of rhinitis after one week's therapy irrespective of treatment. Nasal symptoms, including nasal obstruction, were most markedly improved by both treatments. Azelastine, but not budesonide, also relieved ocular symptoms associated with rhinitis. Adverse events did not occur more frequently under azelastine than under placebo treatment and were often of uncertain relationship to treatment.

Topics: Administration, Intranasal; Adult; Aerosols; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Phthalazines; Pregnenediones; Rhinitis, Allergic, Seasonal

The efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.d.) and budesonide (CAS 51333-22-3) nasal aerosol (0.05 mg/nostril b.i.d.) were compared in a 6-week, multicentre, parallel group study of 193 patients suffering from perennial allergic rhinitis. Total rhinitis symptoms complex (TSC) scores derived from 10 rhinitis symptoms improved during treatment by a mean of 11.4 +/- 6.8 with azelastine and 10.8 +/- 6.4 with budesonide. Response rates, defined as a decrease in TSC of at least 50% at the end of therapy, was 79% with azelastine and 73% with budesonide. There were no significant differences between the treatment groups with respect to either target variable. Objective measurements of nasal flow rate showed a return to normal values during the 6-week therapy. Signs of rhinitis identified by rhinoscopic examination improved in parallel to symptoms. Both medications were well tolerated. The incidence of adverse events of possibly causal relationship to therapy was low. The most frequent event in azelastine treated patients was the experience of an "unpleasant" taste or smell. Occasional epistaxis occurred in both treatment groups but more frequently with budesonide. Results indicate that with the dose used azelastine nasal spray is an effective treatment for perennial allergic rhinitis comparable to that of budesonide nasal aerosol.

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Aged; Bronchodilator Agents; Budesonide; Female; Humans; Male; Middle Aged; Phthalazines; Pregnenediones; Rhinitis, Allergic, Perennial

Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

Topics: Biomarkers; Blotting, Western; Budesonide; Cells, Cultured; Epithelial Cells; Glucocorticoids; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Immunohistochemistry; Nasal Mucosa; Phthalazines; Signal Transduction; Up-Regulation

Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1β and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro. The expression of intercellular adhesion molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) was examined using qPCR and ELISA, respectively. Moreover, the additive effects of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal symptom scores were evaluated in six uncontrolled severe AR patients by budesonide nasal spray alone. We found azelastine significantly inhibited cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing. Azelastine and budesonide additively increased MKP-1 expression and inhibited ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine is able to additively enhance the anti-inflammatory effect of budesonide by modulating MKP-1 expression, which may implicate in the treatment of uncontrolled severe AR.

Topics: Adult; Anti-Inflammatory Agents; Bronchi; Budesonide; Cells, Cultured; Drug Synergism; Dual Specificity Phosphatase 1; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-17; Interleukin-1beta; Male; Middle Aged; Nasal Mucosa; Nasal Sprays; Phthalazines; Rhinitis, Allergic; Severity of Illness Index; Treatment Outcome; Up-Regulation

For locally acting drugs, an extended residence time in the nasal cavity is desirable and related to a prolonged effect. We sought to develop a model for comparative determination of intranasal pharmacokinetics. We embedded human respiratory tissue into a solid matrix and coated the surface with artificial nasal fluid. Nasal spray suspensions of fluticasone propionate (FP) and budesonide (Bud) as well as a solution of azelastine hydrochloride (AZ) were applied onto the surface and removed after 30 min to simulate mucociliary clearance. As exemplary anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells. FP and Bud were initially bound to the same extent to the tissue gel while AZ displayed a more 4-fold higher binding than FP or Bud. After equilibrium with plasma, approximately 5-fold higher tissue concentrations of AZ compared to FP and 77-fold higher levels in relation to Bud were determined. This tissue retention revealed an excellent correlation with the volume of distribution of the respective drugs (r=0.9999, p ≤ 0.05). The inhibitory effect of FP on IL-8 release was approximately 5-fold more pronounced compared to AZ. The present model realistically mirrors conditions in vivo where solubility and tissue absorption of intranasally applied drugs compete with mucociliary clearance mechanisms.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Administration, Inhalation; Administration, Intranasal; Aerosols; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Budesonide; Cell Line, Tumor; Delayed-Action Preparations; Epithelial Cells; Fluticasone; Glucocorticoids; Histamine Antagonists; Humans; Interleukin-8; Lung; Lung Neoplasms; Mucociliary Clearance; Nasal Lavage Fluid; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal

A normal ciliary beat frequency of ciliated cells is necessary for the mucociliary clearance of the nose and paranasal sinuses. An in vitro investigation was performed to evaluate the influence of topical corticosteroids and antihistamines on the ciliary beat frequency of human nasal mucosa. The nasal sprays examined contained the corticosteroids budesonide or fluticasone propionate and the topical antihistamines azelastine or levocabastine. All tests were performed on cell cultures of human nasal mucosa during constant conditions. Three of the four nasal sprays tested contained benzalkonium chloride as preservative. An irreversible cessation of ciliary movement was observed in all cells exposed to nasal sprays containing benzalkonium chloride in a 50 per cent solution. The nasal spray containing budesonide was benzalkonium chloride-free and caused minor but fully reversible decreases in ciliary beat frequency after 20 min. As benzalkonium chloride can cause complete standstill of ciliary beat frequency in vitro in human nasal mucosa, we recommend that this preservative should not be used anymore in topical nasal medications.

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Benzalkonium Compounds; Budesonide; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; In Vitro Techniques; Mucociliary Clearance; Nasal Mucosa; Phthalazines; Piperidines; Preservatives, Pharmaceutical

In this paper, the effect of azelastine hydrochloride, a potent inhibitor of leukotrienes (LTs) and H1 receptors for histamine, was assessed as regards modulation of in vitro eosinophilic chemotaxis. In this respect, chemotaxis of eosinophils (EOS), isolated from the peripheral blood of untreated allergic subjects in the acute phase, was significantly diminished after in vitro treatment with azelastine in comparison to values before treatment. When EOS were pre-incubated with serial dilutions of the drug, it was observed that azelastine inhibited chemotaxis in a dose-dependent fashion. Since azelastine acts in vitro as a regulator of the calcium pump, EOS were pre-incubated with different concentrations (0.6 and 3.0 mM) of Ca++. In these experimental conditions azelastine was able to reduce EOS chemotactic activity only in the presence of 0.6 mM Ca++, whereas with higher Ca++ concentrations (3.0 mM) the inhibitory effect of the drug was abrogated. On the other hand, particular attention was paid to inhaled budesonide, a non halogenated glucocorticosteroid derivative, structurally related to 16 alpha-hydroxy prednisolone, which represents a helpful for treatment mild to moderate asthma. Data obtained after in vitro treatment with budesonide of a group of allergic patients demonstrated that EOS chemotactic activity was significantly reduced in these subjects. Conclusively our data show that 1) azelastine acts as a dose-dependent antagonist of chemotaxis; 2) it may exert this action by inhibiting Ca++ flow into cells; 3) inhaled budesonide may induce inhibition of bronchial inflammation by downregulating EOS chemotactic capacity.

Topics: Adolescent; Adult; Anti-Allergic Agents; Budesonide; Calcium; Chemotaxis, Leukocyte; Cyclic AMP; Eosinophils; Humans; Hypersensitivity; Middle Aged; Phthalazines