Maximal medical treatment of adenoid hypertrophy: a prospective study of preschool children.

PURPOSE: This study aimed to examine the effectiveness of the combined maximal medical treatment for adenoid hypertrophy in preschool children. METHODS: Sixty-four children underwent one-year combined therapy with intranasal mometasone furoate, oral desloratadine, nasal saline irrigation, and bacteriotherapy. Additionally, decongestion drops were applied during scheduled breaks. RESULTS: Of the 64 treated children, 72% showed clinical improvement in adenoid symptoms while 28% did not improve and underwent surgery. These groups differed significantly in terms of the overall reduction in ailments after treatment (p < 0.001), infection rate (p < 0.001), catarrh severity (p < 0.001) and nasal patency (p < 0.001). Endoscopic examination confirmed that responders experienced, on average, a decrease of 8.4% in the adenoid/choana ratio and an improvement in mucosal coverage of the adenoid. These effects were not observed in the group of children whose parents opted for surgery after nine months of conservative treatment. CONCLUSIONS: The proposed new schema of long-term maximal medical treatment with the use of combined intermittent treatment of intranasal mometasone furoate and decongestion drops, oral desloratadine, nasal saline irrigation, and bacteriotherapy can be attempted in patients with adenoid hypertrophy symptoms, and responders may avoid the need for surgery. The applied treatment breaks resulted in a low number of therapeutic side effects.

Clinical Efficacy of Vitamin D3 Adjuvant Therapy in Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). OBJECTIVE: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. METHODS: Out of 127 patients with potential eligible AR, 60 were randomly assigned into two groups and were finally included in our analysis (n=30 for each intervention). The patients with potential eligible AR were randomly allocated to intervention with desloratadine citrate disodium (DCD, 8.8 mg/day) without and with vitamin D3 nasal drops (1.5х106 IU, once/week) for four weeks. Thirty healthy control subjects were included in our study. We assessed the changes in the serum 25(OH)D, peripheral blood eosinophils, interleukin (IL)-4 levels, and nasal symptoms. Serum 25(OH)D, peripheral blood eosinophils, and IL-4 levels were detected respectively with liquid chromatography-tandem mass spectrometry (LC-MS/MS), a blood detector, and enzyme-linked immunosorbent assay. RESULTS: Our patients who received vitamin D3 adjuvant therapy had a higher serum 25(OH)D level (47.57 ± 2.83 vs. 31.51 ± 2.95 ng/ml, p=0.000) and lower AR symptoms score (2.07 ± 1.89 vs. 3.37 ± 1.50, p=0.005), serum IL-4 (10.38 ± 3.41 vs. 12.79 ± 5.40 pg/ml, p=0.043), and peripheral blood eosinophils (0.34 ± 0.09 vs. 0.41 ± 0.10 109/l, p=0.003) compared with DCD single treatment. The efficacy rates of DCD with and without vitamin D3 in AR were 97% and 84%, respectively. CONCLUSION: Nasal vitamin D3 combined with DCD could improve the clinical symptoms of AR. Vitamin D3 adjunct therapy showed significant effects on inhibiting inflammation in patients with AR. We concluded that vitamin D3 supplementation could be an effective adjuvant therapy in AR patients.

Prediction of Human Disproportionate and Biliary Excreted Metabolites Using Chimeric Mice with Humanized Liver.

The PXB-mouse is potentially a useful in vivo model to predict human hepatic metabolism and clearance. Four model compounds, [14C]desloratadine, [3H]mianserin, cyproheptadine, and [3H]carbazeran, all reported with disproportionate human metabolites, were orally administered to PXB- or control SCID mice to elucidate the biotransformation of each of them. For [14C]desloratadine in PXB-mice, O-glucuronide of 3-hydroxydesloratadine was observed as the predominant metabolite in both the plasma and urine. Both 3-hydroxydesloratadine and its O-glucuronide were detected as major drug-related materials in the bile, whereas only 3-hydroxydesloratadine was detected in the feces, suggesting that a fraction of 3-hydroxydesloratadine in feces was derived from deconjugation of its O-glucuronide by gut microflora. This information can help understand the biliary clearance mechanism of a drug and may fill the gap in a human absorption, distribution, metabolism, and excretion study, in which the bile samples are typically not available. The metabolic profiles in PXB-mice were qualitatively similar to those reported in humans in a clinical study in which 3-hydroxydesloratadine and its O-glucuronide were major and disproportionate metabolites compared with rat, mouse, and monkey. In the control SCID mice, neither of the metabolites was detected in any matrix. Similarly, for the other three compounds, all human specific or disproportionate metabolites were detected at a high level in PXB-mice, but they were either minimally observed or not observed in the control mice. Data from these four compounds indicate that studies in PXB-mice can help predict the potential for the presence of human disproportionate metabolites (relative to preclinical species) prior to conducting clinical studies and understand the biliary clearance mechanism of a drug. SIGNIFICANCE STATEMENT: Studies in PXB-mice have successfully predicted the human major and disproportionate metabolites compared with preclinical safety species for desloratadine, mianserin, cyproheptadine, and carbazeran. In addition, biliary excretion data from PXB-mice can help illustrate the human biliary clearance mechanism of a drug.

Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study.

BACKGROUND: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. OBJECTIVE: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. METHODS: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. RESULTS: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. CONCLUSION: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID: UMIN000029653.

[Meta-analysis of efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine in treatment of chronic urticarial].

To analyze the efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine as well as desloratadine alone in the treatment of chronic urticaria by Meta-analysis,in order to provide evidence-based reference for clinical treatment.PubMed,CBM,Wan Fang,VIP database and CNKI database were retrieved to collect randomized controlled trials( RCT) about Tripterygium Glycosides Tablets combined with desloratadine( test group) as well as desloratadine alone( control group) in the treatment of chronic urticaria. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation( a total of 15 RCTs were included,involving 1 411 patients). Meta-analysis showed that the total effective rate( RR = 1. 28,95%CI[1. 22,1. 35],P<0. 000 01) and the quality of life improvement rate( RR = 1. 49,95% CI[1. 33,1. 66],P< 0. 000 01) of the test group were better than those of the control group,and the recurrence rate( RR = 0. 29,95%CI[0. 21,0. 40],P<0. 000 01) was significantly lower than that of the control group,with statistically significant differences; there was no statistically significant difference in the incidence of adverse reactions( RR = 1. 02,95%CI[0. 68,1. 53],P = 0. 92) compared with the control group. Based on the included RCTs,the efficacy of Tripterygium Glycosides Tablets combined with desloratadine in the treatment of chronic urticaria were superior to those of desloratadine alone,with similarity in safety. However,due to the low quality of RCTs and the lack of large-scale multi-center studies,the results shall not be further verified by clinical trials.

Real-life experience in the treatment of solar urticaria: retrospective cohort study.

BACKGROUND: Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life (QoL), and treatment is often challenging. AIM: To analyse clinical experience with a tailored stepwise therapeutic approach. METHODS: A retrospective cohort design was used. Patients with suspected SU underwent laboratory investigations and photoprovocation. Those with a high minimal urticaria dose (MUD) were treated with a single antihistamine (protocol 1), and those with a lower MUD received three types of antihistamines (protocol 2); both protocols included a leucotriene receptor antagonist (LRA). In cases of failure, treatment was switched to omalizumab at doses of < 300 mg/month with incremental dosage increases as necessary (monthly dose range, 150-600 mg/month). Symptom relief and photoprovocation under treatment were evaluated. RESULTS: In total, 30 patients (10 men, 20 women) were enrolled. Most (87%) were sensitive to visible light (1-70 J/cm2 ) with or without extension to ultraviolet A. Of the 30 patients, 23 opted for our stepwise approach: 22 achieved complete remission on protocols 1 or 2 (n = 17) or after switching to omalizumab (n = 5), and another patient achieved partial remission under omalizumab. There were no treatment-related severe adverse effects. CONCLUSIONS: Symptoms of SU can be well controlled by treatment with antihistamines and an LRA tailored to the degree of photosensitivity, followed by omalizumab in refractory cases. This has important implications for patient QoL.

Effects of Desloratadine Citrate Disodium on Serum Immune Function Indices, Inflammatory Factors and Chemokines in Patients with Chronic Urticaria.

OBJECTIVE: To determine the effects of desloratadine citrate disodium on serum immunological function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) in patients with chronic urticaria. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Dermatology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China, from January 2017 to January 2018. METHODOLOGY: A total of 128 patients with chronic urticaria were randomly divided into a control group and an observation group, with 64 patients in each group. The patients in the control group were treated with loratadine and those in the observation group were treated with desloratadine citrate disodium. After 4 weeks of treatment, the serum levels of immune function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) were determined. RESULTS: After 4 weeks of treatment, the levels of serum IgE, IL-4, IL-17, IL-33, MCP-1, RANTES and Eotaxin in the observation group were lower than those in the control group (all p<0.001). The levels of serum C3 and C4 in the observation group were higher than those in the control group (both p<0.001). CONCLUSION: Desloratadine citrate disodium can effectively reduce the severity of chronic urticaria, and its therapeutic mechanism may be related to balancing Th1/Th2 cell function, regulating inflammatory mediators and inhibiting the action of chemokines.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (ß) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

Treatment of solar urticaria using antihistamine and leukotriene receptor antagonist combinations tailored to disease severity.

BACKGROUND: Solar urticarial (SU) is characterized by erythema, whealing, and/or pruritus occurring minutes after sun exposure. Treatment is difficult and often unsatisfactory. OBJECTIVES: To determine the action spectra and minimal urticaria dose (MUD) and to tailor a treatment regimen graded according to disease severity in a series of patients with SU. PATIENTS AND METHODS: Eleven patients (seven females, four males, age range: 5-60 years) with a clinical history suggestive of SU, verified by photo-provocation tests to ultraviolet A (UVA), visible light, and/or UVB, were treated with various combinations of antihistamines and leukotriene receptor antagonist. RESULTS: All patients were sensitive to visible light (median MUD 50 J/cm(2)). Three patients were sensitive to UVA (median MUD 3.75 J/cm(2)), and one patient was sensitive to UVB (MUD of 0.03 J/cm(2)). Two patients experienced a spontaneous remission without treatment. One patient declined treatment. The remaining eight patients were managed by a combination of antihistamines (desloratidine, fexofenadine, cetirizine HCl) and a leukotriene receptor antagonist (montelukast). Seven of the 8 patients experienced a sustained remission of symptoms and signs following treatment. CONCLUSIONS: Photoprovocation for SU with determination of action spectra and MUD enables specifically tailored treatment regimens consisting of combinations of antihistamines and leukotriene receptor antagonist.

Tap water nasal irrigation in adults with seasonal allergic rhinitis: a randomized double-blind study.

Saline nasal irrigation is effective in the treatment of seasonal allergic rhinitis, and sodium chloride itself has no antiallergic effects. The mechanism of saline nasal irrigation depends mainly on washing away allergens and inflammatory mediators induced by allergic reactions. Tap water has the same washing effects as saline. In this study, it was investigated if tap water nasal irrigation was effective in the treatment of seasonal allergic rhinitis. Sixty-four patients diagnosed with seasonal allergic rhinitis were enrolled. Patients were randomized to tap water nasal irrigation group and non-tap water nasal irrigation group for treatment. Patients of both groups were treated with desloratadine. Treatment outcomes were measured using allergic rhinitis Quality of Life (QoL) survey was completed at baseline and after 3 weeks of therapy. There were statistically significant differences in QoL scores between tap water nasal irrigation group and non-tap water nasal irrigation group. The tap water nasal irrigation group had better QoL scores than the non-tap water nasal irrigation group. Tap water nasal irrigation can be a valuable adjuvant therapy for patients with seasonal allergic rhinitis.

Combination treatment of mice with CRx-153 (nortriptyline and desloratadine) decreases the severity of experimental autoimmune encephalomyelitis.

Pro-inflammatory CD4(+) T cell-mediated autoimmune diseases, such as multiple sclerosis, are hypothesized to be initiated and maintained by self-reactive interferon-gamma (IFN-γ) and interleukin-17 (IL-17) producing CD4(+) T cells. Previous studies have shown moderate to significant alterations in inflammatory T cell responses and potentially treatment of autoimmune disease by administration of antihistamine or tricyclic antidepressants alone. The goal of the present study was to determine if treatment of PLP(139-151)-induced relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) in SJL/J mice with a combination of two FDA approved drugs for other indications could decrease R-EAE disease. The findings show that combination treatment with desloratadine and nortriptyline decreases the mean clinical score, disease relapse frequency, and number of CD4(+) T cells infiltrating into the CNS. In addition, combination treatment of PLP(139-151) primed mice decreases the level of IFN-γ and IL-17 secreted via a decrease in both the number of cells secreting and the amount of cytokine secreted per cell following PLP(139-151) reactivation ex vivo. This is in contrast to an increase in the level of IL-4 produced and the number of IL-4 secreting cells. The data also show that combination treatment with desloratadine and nortriptyline inhibits the production of IFN-γ and IL-17 produced by naive CD4(+) T cells activated in the presence of Th1 cell- and Th17 cell-promoting conditions, while increasing the level of IL-4 produced by naive CD4(+) T cells activated in the presence of Th2 cell-promoting conditions. The present findings suggest a novel method for the development of a putative autoimmune therapy.

Petasol butenoate complex (Ze 339) relieves allergic rhinitis-induced nasal obstruction more effectively than desloratadine.

BACKGROUND: Allergic rhinitis symptoms of itching, sneezing, rhinorrhea, and nasal obstruction significantly decrease patients' quality of life. Compared with histamine and leukotriene receptor antagonists, the petasol butenoate complex Ze 339 displays pharmacologically distinct properties. In vitro it inhibits the biosynthesis of leukotrienes and mediator release from activated eosinophils. OBJECTIVE: This study aimed to assess the efficacy and mode of action of Ze 339, desloratadine, and placebo on allergic rhinitis symptoms, nasal airflow, and local mediator levels after unilateral nasal allergen provocation. METHODS: In this double-blind, randomized, crossover study 18 subjects with allergic rhinitis to grass pollen received Ze 339, desloratadine, and placebo for 5 days before nasal allergen challenge with grass pollen extract. Rhinomanometry, symptom assessment, and local inflammatory mediator measurement were performed during the 24 hours after allergen challenge. RESULTS: With Ze 339, the patient's time to recovery (5.4 ± 1.6 hours) from nasal obstruction after allergen challenge (time for return to 90% of baseline value ± SEM) was significantly shorter than with placebo (9.1 ± 2.3 hours, P = .035) and desloratadine (10.7 ± 2.5 hours, P = .022). Likewise, Ze 339's standardized symptom assessment for nasal obstruction (3.2 ± 1.3 hours) showed significantly faster relief (time for return to baseline value ± SEM compared with placebo, 8.3 ± 2.4 hours; P = .027) and desloratadine (4.5 ± 1.2 hours, P = .030). One interesting finding was that Ze 339 significantly reduced IL-8 and leukotriene B(4) levels in nasal secretions before challenge. CONCLUSION: When compared with desloratadine and placebo, Ze 339 shows better efficacy in relieving nasal obstruction symptoms and inhibiting critical components of the chemokine network and as such represents a novel symptomatic and possible prophylactic treatment for allergic rhinitis.

Desloratadine for the treatment of cypress pollen-induced allergic rhinitis.

BACKGROUND: Few studies have been conducted to assess treatment options for patients with sensitivities to cypress pollens, important triggers of allergic rhinitis (AR) in the Mediterranean region. OBJECTIVE: To evaluate the effect of desloratadine, a second-generation antihistamine, on AR symptoms caused by cypress pollens native to France. METHODS: Adults (N=233) with symptomatic cypress pollen allergies were randomized to receive desloratadine, 5 mg, or placebo daily for 15 days during 2 consecutive cypress pollen seasons. The primary end point was the percentage change from baseline in morning total nasal symptom scores on day 14; secondary assessments included total symptom score, peak nasal inspiratory flow, the Rhinoconjunctivitis Quality of Life Questionnaire, and global response to therapy. RESULTS: On day 14, the desloratadine group had a significantly greater percentage decrease in total nasal symptom score vs the placebo group (-40% vs. -30%; P < .04). Similarly, on day 14, there was a 47% and 37% respective decrease in total symptom score (P = .01). Mean peak nasal inspiratory flow scores showed numeric, albeit not statistically significant, improvements from baseline through day 14 with desloratadine. A significantly greater improvement in Rhinoconjunctivitis Quality of Life Questionnaire scores occurred with desloratadine vs placebo on day 14 (-1.4 vs. -0.9; P = .004). The mean global response to therapy was better with desloratadine vs placebo (3.4 vs. 3.9; P = .004). The adverse event rate was similar in both groups. CONCLUSION: Desloratadine is efficacious and safe for the treatment of AR induced by cypress pollens; it also improved disease-related quality of life.

Behavioral conditioning of antihistamine effects in patients with allergic rhinitis.

BACKGROUND: Allergic symptoms can be induced by behavioral conditioning. However, the conditionability of antiallergic effects has not yet been studied. Thus, we investigated whether the effects of a histamine 1 (H(1)) receptor antagonist are inducible in patients suffering from house-dust mite allergy using a behavioral conditioning procedure. METHODS: During the association phase, 30 patients with allergic house-dust mite rhinitis received a novel-tasting drink once daily, followed by a standard dose of the H(1) receptor antagonist, desloratadine, on 5 consecutive days. After 9 days of drug washout, the evocation trial commenced: 10 patients received water together with an identically looking placebo pill (water group), 11 patients were re-exposed to the novel-tasting drink and received a placebo pill [conditioned stimulus (CS); CS group] and 9 patients received water and desloratadine (drug group). RESULTS: During the association phase, desloratadine treatment decreased the subjective total symptom scores, attenuated the effects of the skin prick test for histamine and reduced basophil activation ex vivo in all groups. During the evocation trial, the water group, in which subjects were not re-exposed to the gustatory stimulus, showed a reduction in subjective total symptom scores and skin prick test results, but no inhibition of basophil activation. In contrast, re-exposure to the novel-tasting drink decreased basophil activation, the skin prick test result and the subjective symptom score in the CS group to a degree that was similar to the effects of desloratadine in the drug group. CONCLUSIONS: These data show that behaviorally conditioned effects are not only able to relieve subjective rhinitis symptoms and allergic skin reactions, but also to induce changes in effector immune functions.

The effect of regular versus on-demand desloratadine treatment in children with allergic rhinitis.

OBJECTIVE: Desloratadine is a potent antihistamine. Whether regular or on-demand use of desloratadine influences its therapeutic efficacy in allergic rhinitis is unknown. The aim of the study was to compare the clinical efficacy and the anti-inflammatory activity of regularly administered desloratadine to its on-demand use in children with allergic rhinitis due to pollen allergy. METHODS: Thirty-seven patients with allergic rhinitis with or without mild intermittent asthma were enrolled in a prospective parallel group study. Patients were treated with desloratadine regularly or on-demand during pollen season. Rescue medications and symptom scores were recorded on a diary card. Nasal flow rate and inflammatory markers were recorded, and methacholine (Mch) challenge test was administered before and within the pollen season. RESULTS: Though symptoms were lower in the evening than in the morning (p<0.001), there was no difference between the two groups. There was no difference between the groups with respect to medication score except that the salbutamol use was lower in the regular treatment group during the fourth week (p=0.032) in the pollen season. Nasal flow rate and inflammatory markers failed to show any difference between the groups. A significant reduction in PC20 values (provocative concentration of Mch causing a 20% fall in FEV(1)) was observed in regular (p=0.016) and on-demand (p=0.005) treatment groups compared to the pre-season measurements. The number of children with a PC20 below 8 mg/ml increased significantly in the on-demand group. CONCLUSION: Our study demonstrates that on-demand use of desloratadine during the pollen season is clinically as effective as regular treatment. However, regular treatment may provide better control of lower airway symptoms and airway reactivity.

Eosinophil recruiting chemokines are down-regulated in peripheral blood mononuclear cells of allergic patients treated with deflazacort or desloratadine.

Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophils-basophils activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic-asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, I-309 (CCL1), MCP-1 (CCL2), MIP1-alpha (CCL3), MIP1-beta (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-alpha and MIP1-beta with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.

Effect of a Chinese herbal formula, Shi-Bi-Lin, on an experimental model of allergic rhinitis.

BACKGROUND: Jia Wei Cang Er Zi San, a traditional Chinese herbal formula, has been used to treat allergic rhinitis (AR) for several centuries. However, its effect on experimental animal models and its therapeutic mechanism remain unclear. OBJECTIVE: To study the effect of Shu-Bi-Lin, a modified Jia Wei Cang Er Zi San, on an animal model of AR. METHODS: Shu-Bi-Lin was administered to the guinea pig model of AR. Meanwhile, an antihistamine-treated group for the treatment control, an ovalbumin-sensitized and untreated group for the positive control, and a sham-sensitized, sham-challenged group for the sham control were studied in parallel. Symptomatic and some pathophysiologic variables were evaluated. RESULTS: Sneezing and nasal scratching after challenges were significantly ameliorated in the Shu-Bi-Lin-treated group compared with the ovalbumin-sensitized and untreated group, but rhinorrhea volume was not reduced. Shu-Bi-Lin significantly suppressed the production of IgG1 in the passive cutaneous anaphylaxis test. The thromboxane B2 level in nasal lavage fluid was significantly deceased in the Shu-Bi-Lin-treated group; however, the reduction in histamine and peptide leukotriene levels did not reach statistical significance. In addition, eosinophil infiltration and endothelial nitric oxide synthase immunoreactivity in the nasal tissues were reduced in the Shu-Bi-Lin-treated group. CONCLUSIONS: Shu-Bi-Lin could alleviate the nasal symptoms of AR, and its mechanism might be related to its inhibitory effect on type I anaphylaxis reactions and eosinophil infiltration in the nasal tissues, as well as the inhibition of some mediators related to AR.

Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy.

OBJECTIVE: To assess the efficacy and onset of action of azelastine nasal spray and desloratadine tablets in patients with allergen-induced seasonal allergic rhinitis (SAR). RESEARCH DESIGN AND METHODS: 46 adult patients with a history of SAR were exposed to a controlled grass pollen concentration for 6 h in the Vienna Challenge Chamber (VCC) in each treatment period according to a randomised, double-blind (double-dummy), three-period, three-sequence crossover design (wash-out period of 12 days). Single doses of study medication (one puff nasal spray into each nostril of azelastine, 0.2 mg, or placebo before swallowing one encapsulated tablet of desloratadine, 5 mg) were administered 2 h after the start of the allergen challenge. Results of subjective and objective assessments were recorded throughout the challenge. RESULTS: Efficacy of azelastine nasal spray was significantly superior compared to desloratadine tablets (p = 0.005) and placebo (p < 0.001). Desloratadine was significantly better than placebo (p < 0.001). Decrease both in Major Nasal Symptom Score (MNSS) and in Total Nasal Symptom Score (TNSS) was fastest after azelastine treatment. Improvement of nasal symptom severity was most pronounced after azelastine treatment for all nasal symptoms including nasal congestion. Onset of action was 15 min for azelastine compared to 150 min for desloratadine. Both active preparations were safe and well tolerated. CONCLUSIONS: This study confirms the usefulness of azelastine nasal spray for the symptomatic treatment of seasonal allergic rhinitis. Concerning onset of action in particular, the results favour the topical treatment over systemic therapy.

The effect of desloratadine on eosinophil/basophil progenitors and other inflammatory markers in seasonal allergic rhinitis: a placebo-controlled randomized study.

BACKGROUND: Eosinophil/basophil (Eo/B) progenitors fluctuate in the peripheral circulation during seasonal allergen exposure in atopic subjects. Several drugs have been shown to modulate Eo/B progenitor levels in the peripheral blood but, to date, the possible effect of antihistamines on Eo/B progenitors has not been explored. Our objective was to evaluate whether the antihistamine desloratadine (DL) can modulate peripheral blood Eo/B progenitors or other markers of allergic inflammation. METHODS: We performed a randomized double-blind placebo-controlled study on the effects of DL on peripheral blood Eo/B progenitors in subjects with symptomatic, seasonal allergic rhinitis during a ragweed pollen season. Forty-five subjects were randomized to treatment for 4 weeks with DL 20 mg daily or placebo. RESULTS: The expected fall in the number of Eo/B progenitors from baseline to 2 weeks of treatment was seen in the placebo group [median drop of 1.0 colony-forming unit (CFU)/10(6) cells], and was greater than in the DL group (median drop of 0.0 CFU/10(6) cells) (p = 0.013). The change in histamine concentration per colony from baseline to 2 weeks of treatment was lower in the DL group (median decrease of 6.1 pg/colony) compared to placebo (median increase of 1.8 pg/colony) (p = 0.01). An increase in the nasal lavage eotaxin concentration from baseline to 4 weeks of treatment was statistically significant in the placebo group but not in the DL group. Eo/B CFU were not affected by varying in vitro concentrations of DL. CONCLUSION: These results suggest that DL can modulate aspects of allergic inflammation in vivo through mechanisms other than simple blockade of H1 histamine receptors.

Desloratadine reduces systemic allergic inflammation following nasal provocation in allergic rhinitis and asthma patients.

BACKGROUND: Preclinical studies have demonstrated that some second-generation antihistamines have anti-inflammatory effects. It is not known whether these effects are also demonstrable in vivo. In this study we investigated the effect of treatment with desloratadine (DL) on systemic inflammation and on nasal and bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects with grass-pollen-allergic rhinitis and asthma. METHODS: Twenty-six subjects with grass-pollen-allergic rhinitis and asthma were randomly allocated to 8 days of treatment with DL (n = 13) or placebo (n = 13) outside the grass pollen season. On day 7 they underwent nasal provocation with grass pollen allergen. Nasal and bronchial biopsies were taken for immunohistochemical evaluation, and blood samples were analysed. Rhinitis and asthma symptoms, peak nasal inspiratory flow and peak expiratory flow, were also measured at specified times. RESULTS: The number of circulating eosinophils decreased during DL treatment, and there was a reduced increase in circulating eosinophils after NP in these subjects. There was also a significant reduction in early bronchial clinical response. There was no significant lessening in the severity of the nasal symptoms. Nasal and bronchial mucosal inflammation parameters did not alter under DL treatment. CONCLUSION: These data suggest that treatment with DL reduces systemic eosinophilia and prevents the increase in circulating eosinophils after NP. DL also significantly reduces the early bronchial clinical response to NP. However, airway mucosal inflammation is not altered by 1 week of treatment.