Discovery of the novel and potent histamine H1 receptor antagonists for treatment of allergic diseases.

Desloratadine, a second-generation histamine H1 receptor antagonist, has established itself as a first-line drug for the treatment of allergic diseases. Despite its effectiveness, desloratadine exhibits an antagonistic effect on muscarinic M3 receptor, which can cause side effects such as dry mouth and urinary retention, ultimately limiting its clinical application. Herein, we describe the discovery of compound Ⅲ-4, a novel H1 receptor antagonist with significant H1 receptor antagonistic activity (IC50 = 24.12 nM) and enhanced selectivity towards peripheral H1 receptor. In particular, Ⅲ-4 exhibits reduced M3 receptor inhibitory potency (IC50 > 10,000 nM) and acceptable hERG inhibitory activity (17.6 ± 2.1 µM) compare with desloratadine. Additionally, Ⅲ-4 exhibits favorable pharmacokinetic properties, as well as in vivo efficacy and safety profiles. All of these reveal that Ⅲ-4 has potential to emerge as a novel H1 receptor antagonist for the treatment of allergic diseases. More importantly, the compound Ⅲ-4 (HY-078020) has recently been granted clinical approval.

Desloratadine alleviates ALS-like pathology in hSOD1G93A mice via targeting 5HTR2A on activated spinal astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.

Loratidine is associated with improved prognosis and exerts antineoplastic effects via apoptotic and pyroptotic crosstalk in lung cancer.

BACKGROUND: Tumor-associated inflammation suggests that anti-inflammatory medication could be beneficial in cancer therapy. Loratadine, an antihistamine, has demonstrated improved survival in certain cancers. However, the anticancer mechanisms of loratadine in lung cancer remain unclear. OBJECTIVE: This study investigates the anticancer mechanisms of loratadine in lung cancer. METHODS: A retrospective cohort of 4,522 lung cancer patients from 2006 to 2018 was analyzed to identify noncancer drug exposures associated with prognosis. Cellular experiments, animal models, and RNA-seq data analysis were employed to validate the findings and explore the antitumor effects of loratadine. RESULTS: This retrospective study revealed a positive association between loratadine administration and ameliorated survival outcomes in lung cancer patients, exhibiting dose dependency. Rigorous in vitro and in vivo assays demonstrated that apoptosis induction and epithelial-mesenchymal transition (EMT) reduction were stimulated by moderate loratadine concentrations, whereas pyroptosis was triggered by elevated dosages. Intriguingly, loratadine was found to augment PPARγ levels, which acted as a gasdermin D transcription promoter and caspase-8 activation enhancer. Consequently, loratadine might incite a sophisticated interplay between apoptosis and pyroptosis, facilitated by the pivotal role of caspase-8. CONCLUSION: Loratadine use is linked to enhanced survival in lung cancer patients, potentially due to its role in modulating the interplay between apoptosis and pyroptosis via caspase-8.

Efficacy of different oral H1 antihistamine treatments on allergic rhinitis: a systematic review and network meta-analysis of randomized controlled trials.

INTRODUCTION: Oral H1 antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more effective in improving symptoms of patients. OBJECTIVE: To evaluate the efficacy of different oral H1 antihistamine treatments on patients with allergic rhinitis by performing a network meta-analysis. METHODS: The search was executed in PubMed, Embase, OVID, the Cochrane Library and ClinicalTrials.gov for relevant studies. The network meta-analysis was performed by using Stata 16.0, and the outcome measures of the analysis were symptom score reductions of patients. Relative risks with 95% Confidence Intervals were used in the network meta-analysis to compare the clinical effect of treatments involved, and Surface Under the Cumulative Ranking Curves (SUCRAs) were also calculated to rank the treatments' efficacy. RESULTS: 18 eligible randomized controlled studies, involving a total of 9419 participants, were included in this meta-analysis. All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction. According to the results of SUCRA, rupatadine 20 mg and rupatadine 10 mg were ranked relatively high in reductions of total symptom score (SUCRA: 99.7%, 76.3%), nasal congestion score (SUCRA: 96.4%, 76.4%), rhinorrhea score (SUCRA: 96.6%, 74.6%) and ocular symptom score (SUCRA: 97.2%, 88.8%); rupatadine 20 mg and levocetirizine 5 mg were ranked relatively high in reductions of nasal itching score (SUCRA: 84.8%, 83.4%) and sneezing score (SUCRA: 87.3%, 95.4%); loratadine 10 mg was ranked the lowest in each symptom score reduction besides placebo. CONCLUSION: This study suggests that rupatadine is the most effective in alleviating symptoms of patients with allergic rhinitis among different oral H1 antihistamine treatments involved, and rupatadine 20 mg performs better than rupatadine 10 mg. While loratadine 10 mg has inferior efficacy for patients to the other antihistamine treatments.

The Combination Sorafenib-raloxifene-loratadine as a Novel Potential Therapeutic Approach Against Human Liver Cancer.

BACKGROUND/AIM: Liver cancer is one of the malignancies with the highest mortality-to-incidence ratio worldwide. Therefore, novel therapeutic approaches are urgently needed. Combination therapy and drug repurposing can improve the response of the patients to therapy in several cancers. The aim of the present study was to merge these two strategies and evaluate whether the two-drug- or three-drug- combination of sorafenib, raloxifene, and loratadine improves the antineoplastic effect on human liver cancer cells in comparison to the single-drug effect. MATERIALS AND METHODS: The human liver cancer cell lines HepG2 and HuH7 were studied. The effect of sorafenib, raloxifene, and loratadine on the metabolic activity was determined using the MTT assay. The inhibitory concentrations (IC20 and IC50) were calculated from these results and used in the drug-combination experiments. Apoptosis and cell survival were studied by flow cytometry and using the colony formation assay, respectively. RESULTS: In both cell lines, sorafenib, raloxifene, and loratadine in two-drug and three-drug combinations significantly reduced metabolic activity and significantly increased the percentage of apoptotic cells compared to the single-drug effect. In addition, all the combinations significantly reduced the colony-forming capacity in the HepG2 cell line. Surprisingly, the effect of raloxifene on apoptosis was similar to that observed using the combinations. CONCLUSION: The triple combination sorafenib-raloxifene-loratadine may be a novel promising approach in the treatment of liver cancer patients.

The rising cost of rhinologic medications.

BACKGROUND: The high prescription drug cost in the United States may negatively affect patient prognosis and treatment compliance. OBJECTIVE: To fill the knowledge gap and inform clinicians regarding rhinology medications price changes by evaluating trends in price changes of highly used nasal sprays and allergy medications. METHODS: The 2014-2020 Medicaid National Average Drug Acquisition Cost database was queried for drug pricing information for the following classes of medications: intranasal corticosteroids, oral antihistamines, antileukotrienes, intranasal antihistamines, and intranasal anticholinergics. Individual medications were identified by Food and Drug Administration-assigned National Drug Codes. Per unit, drug prices were analyzed for average annual prices, average annual percentage price changes, and inflation-adjusted annual and composite percentage price changes. RESULTS: Beclometasone (Beconase AQ, 56.7%, QNASL, 77.5%), flunisolide (Nasalide, -14.6%), budesonide (Rhinocort Aqua, -1.2%), fluticasone (Flonase, -6.8%, Xhance, 11.7%), mometasone (Nasonex, 38.2%), ciclesonide (Omnaris, 73.8%), combination azelastine and fluticasone (Dymista, 27.3%), loratadine (Claritin, -20.5%), montelukast (Singulair, 14.5%), azelastine (Astepro, 21.9%), olopatadine (Patanase, 27.3%), and ipratropium bromide (Atrovent, 56.6%) had an overall change in inflation-adjusted per unit cost between 2014 and 2020 (% change). Of 14 drugs evaluated, 10 had an increase in inflation-adjusted prices, for an average increase of 42.06% ± 22.27%; 4 of 14 drugs had a decrease in inflation-adjusted prices, for an average decrease of 10.78% ± 7.36%. CONCLUSION: The rising cost of highly used medications contributes to increased patient acquisition costs and may pose barriers of drug adherence to particularly vulnerable populations.

Re-evaluation of over-the-counter histamine H1-receptor antagonists based on their effects on murine models of allergen-induced nasal hyperresponsiveness.

T cells play an essential role in the development of allergen-induced nasal hyperresponsiveness (NHR), a pathophysiological response in allergic rhinitis. The effects of histamine H1-receptor antagonists (antihistamines) on murine NHR models were investigated. Intragastric epinastine, fexofenadine, and loratadine administration suppressed allergen-induced immediate nasal response but not NHR in immunized mice. Regardless of the alleviation of stimulation-induced Th2 cytokine expression by loratadine and desloratadine in vitro, allergen-induced NHR and nasal eosinophil infiltration in Th2 cell-transferred mice were unaffected by loratadine in vivo. This influence on T cell-mediated NHR was excluded from the pharmacological effects of antihistamines.

The Effects of Combined Therapeutic Protocol on Allergic Rhinitis Symptoms and Molecular Determinants.

Current medications to treat allergic rhinitis (AR) include antihistamines, corticosteroids, and anti-leukotrienes. In the present study, we investigated the effects of combination therapy; using these drugs, and evaluates the AR-related markers and parameters in an animal model. After inducing BALB/c mice AR models, the animals were treated with either pranlukast, loratadine, fluticasone, loratadine + fluticasone, loratadine + pranlukast, fluticasone + pranlukast, or loratadine + fluticasone + pranlukast. Clinical symptoms, Immunoglobulin (Ig)G1, ovalbumin (OVA)-specific and total IgE, leukotriene (LT)B4, LTC4, histamine, thymic stromal lymphopoietin (TSLP) serum levels, and interleukin 4 level in the nasal lavage fluid were determined. The expressions of HRH1, CysLT1R, NLR3, Caspase-1, and MUC5a were studied. Allergic symptoms (nasal rubbing and sneezing), serum Igs (IgG1, total and OVA-specific IgE), eicosanoids (LTB4 and LTC4), histamine, TSLP, and IL-4 as well as gene expressions of MUC5a, Caspase-1, NLR3, HRH1, and CysLT1R were reduced in the animals receiving each of the therapeutic regimens; however, more pronounced effects were seen in the group treated with the triple combined protocol (loratadine + fluticasone + pranlukast). The combination of the loratadine, fluticasone, and pranlukast can effectively control the symptoms of AR probably via modulating several related mechanisms at early and late phases of allergic responses.

Loratadine.

Loratadine, 4-(8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylic acid ethyl ester, is an antihistamine drug with long-acting effects and has limited selectivity for peripheral H1 receptors. It is widely used for the prevention of allergic diseases such as rhinitis chronic urticaria, and asthma. This chapter discusses, by a critical extensive review of the literature, the description of loratadine in terms of its names, formulae, elemental composition, appearance, methods of preparation. The profile contains physicochemical properties of Loratadine, including pKa value, solubility and X-ray powder diffraction. In addition, it involves Fourier transform infrared spectrometry, nuclear magnetic resonance spectroscopy and mass spectroscopy for functional groups and structural confirmation of. The chapter also includes methods of analysis of the drug such as compendial, titrimetric, electrochemical, spectroscopic, chromatographic and capillary electrophoretic methods. The chapter also covers clinical applications of the drug such as its uses, doses, ADME profiles and mechanism of action.

Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway.

Loratadine is an anti-histamine routinely used for treating allergies. However, recent findings have shown that Loratadine may also have anti-inflammatory functions, while their exact mechanisms have not yet been fully uncovered. In this paper, we investigated whether Loratadine can be utilized as an anti-inflammatory drug through a series of in vitro and in vivo experiments using a murine macrophage cell line and an acute gastritis mouse model. Loratadine was found to dramatically reduce the expression of pro-inflammatory genes, including MMP1, MMP3, and MMP9, and inhibit AP-1 transcriptional activation, as demonstrated by the luciferase assay. Therefore, we decided to further explore its role in the AP-1 signaling pathway. The expression of c-Jun and c-Fos, AP-1 subunits, was repressed by Loratadine and, correspondingly, the expression of p-JNK, p-MKK7, and p-TAK1 was also inhibited. In addition, Loratadine was able to reduce gastric bleeding in acute gastritis-induced mice; Western blotting using the stomach samples showed reduced p-c-Fos protein levels. Loratadine was shown to effectively suppress inflammation by specifically targeting TAK1 and suppressing consequent AP-1 signaling pathway activation and inflammatory cytokine production.

Analysis of degradation and pathways of three common antihistamine drugs by NaClO, UV, and UV-NaClO methods.

Antihistamines (ANTs) are medicines to treat allergic diseases. They have been frequently detected in the natural water environment, posing potential threats to the ecological environment and human health. In this study, the degradation of three common antihistamines, loratadine, fexofenadine, and cetirizine, was estimated under different oxidation methods (NaClO, UV, and UV-NaClO). The results showed that UV-NaClO had the highest degree of degradation on the drugs under most conditions: 100% degradation for fexofenadine within 20 s at pH 7 and 10. Under UV irradiation, the degradation efficiencies of the three drugs during 150 s were all above 77% at a pH of 7. The drugs' removal by NaClO was much lower than that of the previous two methods. In addition, this study explored the contribution rates of active oxygen species in the photolysis process. Among them, the contribution of 1O2 to the fexofenadine and cetirizine removal rate reached 70%. Different aqueous matrices (HCO3-, NO3-, and humic acid) had varying degrees of influence on the degradation. Acute toxicity tests and ultraviolet scans of the degradation products showed that the drugs were not completely mineralized, and the toxicities of the intermediates were even higher than those of the parent drugs. There were 9, 8, and 10 chloride oxidation products of loratadine, fexofenadine, and cetirizine, respectively, and 8 photolysis products of cetirizine were identified. For cetirizine, it was found that there were three identical intermediates produced by photodegradation and NaClO oxidation.

Can loratadine help in treating granulocyte-colony stimulating factor-induced bone pain?

ABSTRACT: Febrile neutropenia is an oncologic emergency with serious consequences. Granulocyte colony stimulating factors (G-CSFs), used to stimulate neutrophil production to prevent febrile neutropenia, can cause bone pain in more than 25% of patients. Severe bone pain may not respond to acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, or dose reduction of the G-CSF agent. A study found that patients taking loratadine had fewer treatment-associated adverse reactions and discontinuations than those on naproxen. Although more research is needed, loratadine's tolerability, ease of administration, and potential benefit mean that it should be considered for management of pegfilgrastim-associated bone pain. This article describes a patient whose G-CSF-induced bone pain was completely alleviated by loratadine.

Síndrome DRESS por paracetamol / DRESS syndrome due to acetaminophen

A síndrome DRESS é uma entidade rara e distinta, caracterizada por acometimento cutâneo e envolvimento de órgãos internos, com risco potencial de morte. O diagnóstico e o tratamento pre- coces são de vital importância. Relatos de DRESS por paraceta- mol são raros na literatura, razão pela qual apresentamos este caso. Paciente do sexo masculino, 56 anos, com surgimento de rash maculopapular, febre, linfadenopatia e hipereosinofilia 3 semanas após suspensão de paracetamol, associados ao ante- cedente familiar de reação a fármaco. Evoluiu bem após pulso- terapia com metilprednisolona.

DRESS syndrome is a rare and distinct entity characterized by cutaneous manifestations and internal organs involvement with a potential risk of death. Early diagnosis and treatment are vi- tally important. Reported cases of DRESS syndrome due to ace- taminophen are rare in the literature, and that is the reason for this case report. A 56-year-old male patient with maculopapular rash, fever, lymphadenopathy, and hypereosinophilia three we- eks after suspension of acetaminophen, associated with a family history of drug reaction. It progressed well after pulse therapy with methylprednisolone.

Case Report: Recent Case Reports of Levant Blunt-Nosed Viper Macrovipera lebetina obtusa Snakebites in Iran.

Envenomation and death resulting from snakebites represent a significant public health problem worldwide, particularly in tropical and subtropical regions. The WHO has defined snakebite as a neglected tropical health concern. Bites from Macrovipera lebetina obtusa usually cause life-threatening systemic hemodynamic disturbances, reduced functionality of the kidneys, and other serious symptoms, including hypotension shock, edema, and tissue necrosis, at the bite site. Herein, we highlight five cases of M. l. obtusa envenomation that presented with wide-ranging manifestations. Many recovered cases were left with long-term musculoskeletal disabilities. In a particular case, a 15-year-old male patient was envenomed in his palm by an 80-cm M. l. obtusa. Within 12 hours, swelling extended to near the shoulder. Fasciotomy was performed on the forearm and part of the upper arm of this patient. Symptoms of severe localized pain and swelling, dizziness, weakness, low blood pressure, and itching around the bite area were documented. The patient remained in the hospital for 13 days.

Desloratadine inhibits heterotopic ossification by suppression of BMP2-Smad1/5/8 signaling.

Heterotopic ossification (HO) is a pathological condition in which ectopic bone forms within soft tissues such as skeletal muscle. Human platelet-derived growth factor receptor α positive (PDGFRα+) cells, which were proved to be the original cells of HO were incubated in osteogenic differentiation medium with Food and Drug Administration-approved compounds. Alkaline phosphatase activity was measured as a screening to inhibit osteogenic differentiation. For the compounds which inhibited osteogenic differentiation of PDGFRα+ cells, we examined dose dependency of its effect using alizarin red S staining and its cell toxicity using WST-8. In addition, regulation of bone morphogenetic proteins (BMP)-Smad signaling which is the major signal of osteogenic differentiation was investigated by Western blotting to elucidate the mechanism of osteogenesis inhibitory effect by the compound. In vivo experiment, complete transverse incision of Achilles tendons in mice was made and mice were fed the compound by mixing with drinking water after operation. Ten weeks after operation, we assessed and quantified HO by micro-computed tomography scan. Intriguingly, we discovered desloratadine inhibited osteogenic differentiation of PDGFRα+ cells using the drug repositioning method. Desloratadine inhibited osteogenic differentiation of the cells dose dependently without cell toxicity. Desloratadine suppressed phosphorylation of Smad1/5/8 induced by BMP2 in PDGFRα+ cells. In Achilles tenotomy mice model, desloratadine treatment significantly inhibited ectopic bone formation compared with control. In conclusion, we discovered desloratadine inhibited osteogenic differentiation using human PDGFRα+ cells and proved its efficacy using Achilles tenotomy ectopic bone formation model in vivo. Our study paved the way to inhibit HO in early clinical use because of its guaranteed safety.

Improvement in Psychological Condition of Patients With Persistent Moderate-Severe Allergic Rhinitis by Drug Therapy Combined With Psychological Intervention.

OBJECTIVE: To investigate the effect of drug treatment combined with psychological intervention on mental disorders in patients with persistent moderate-severe allergic rhinitis. METHODS: Sixty patients with persistent moderate-severe allergic rhinitis who met the criteria were randomly divided into 2 groups: control group and experimental group. The control group was only given medication, whereas the experimental group was given psychological intervention on the basis of the same medication. Cognitive behavioral therapy was used for psychological intervention. After 12 weeks of treatment, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to evaluate the changes in anxiety, depression, and quality of life before and after treatment. RESULTS: The SAS and SDS scores of the control group after treatment were lower than those before treatment, and the difference was statistically significant. Similarly, the SAS and SDS scores of the experimental group after treatment were lower than those before treatment with statistically significant difference. In addition, after treatment, the SAS and SDS scores of the experimental group were statistically lower than those of the control group. The results of RQLQ showed that the scores of each dimension in the control group after treatment were lower than those before treatment, and the difference was statistically significant. Similar results were found in the experimental group. After treatment with these 2 different schemes, the RQLQ scores of sleep, nonnasal/eye symptoms, and emotion in the experimental group were statistically lower than those in the control group. CONCLUSION: Drug therapy or drug therapy combined with psychological intervention can alleviate anxiety and depression of patients with persistent moderate-severe allergic rhinitis and improve their quality of life. Moreover, based on the effect of improving mental disorder and quality of life of patients, drug therapy combined with psychological intervention is better than drug treatment alone.

Antiallergic drug desloratadine as a selective antagonist of 5HT2A receptor ameliorates pathology of Alzheimer's disease model mice by improving microglial dysfunction.

Alzheimer's disease (AD) is a progressively neurodegenerative disease characterized by cognitive deficits and alteration of personality and behavior. As yet, there is no efficient treatment for AD. 5HT2A receptor (5HT2A R) is a subtype of 5HT2 receptor belonging to the serotonin receptor family, and its antagonists have been clinically used as antipsychotics to relieve psychopathy. Here, we discovered that clinically first-line antiallergic drug desloratadine (DLT) functioned as a selective antagonist of 5HT2A R and efficiently ameliorated pathology of APP/PS1 mice. The underlying mechanism has been intensively investigated by assay against APP/PS1 mice with selective 5HT2A R knockdown in the brain treated by adeno-associated virus (AAV)-ePHP-si-5HT2A R. DLT reduced amyloid plaque deposition by promoting microglial Aß phagocytosis and degradation, and ameliorated innate immune response by polarizing microglia to an anti-inflammatory phenotype. It stimulated autophagy process and repressed neuroinflammation through 5HT2A R/cAMP/PKA/CREB/Sirt1 pathway, and activated glucocorticoid receptor (GR) nuclear translocation to upregulate the transcriptions of phagocytic receptors TLR2 and TLR4 in response to microglial phagocytosis stimulation. Together, our work has highly supported that 5HT2A R antagonism might be a promising therapeutic strategy for AD and highlighted the potential of DLT in the treatment of this disease.

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.

Effects of oral desloratadine citrate disodium combined with physiological seawater nasal irrigation on IgE levels, IL-4, IL-6, IL-13 and IFN-γ expression and treatment of intermittent allergic rhinitis.

This experiment was performed to explore the effect of oral desloratadine citrate disodium combined with physiological seawater nasal irrigation in the treatment of intermittent allergic rhinitis and its effect on serum inflammatory factors and peripheral blood Th1 and Th2. For this purpose, 100 patients of intermittent allergic rhinitis admitted to our hospital from January 2018 to January 2020. Randomly divided into a control group (n=50) and an observation group (n=50). The control group was given oral desloratadine citrate disodium. The observation group was given physiological seawater nasal irrigation based on the control group. Both groups were treated for one month. Compare the effect of treatment, symptom and sign scores pre and posttreatment, serum immunoglobulin E (IgE) levels, serum interleukin 4 (IL-4), IL-6, IL-13 and interferon-gamma (IFN-γ) levels, peripheral blood helper T cells 1 (Th1) and Th2 and the recurrence rate of patients after 1 year between two groups. Results showed that after one month of continuous treatment, the total effective rate of the observation group was significantly higher than that of the control group (P <0.05). The symptoms and signs scores and serum IgE levels of the two groups pretreatment (before treatment) were not significantly different (P > 0.05). The symptoms and signs scores and serum IgE levels of the two groups decreased significantly posttreatment (after treatment) (P <0.05), and the observation group was significantly lower than the control group (P <0.05). Pretreatment, the levels of serum inflammatory factors (IL-4, IL-6, IL-13, and IFN-γ) and the ratio of peripheral blood Th1 and Th2 to CD4+T cells were not significantly different (P> 0.05). After one month of continuous treatment, the levels of serum IL-4, IL-6, IL-13, and the ratio of peripheral blood CD4+IL-4+/CD4+ in the observation group and the control group were significantly reduced and the ratio of CD4+IFN-γ+/CD4+ was significantly increased (P <0.05). Compared with the control group, those changes were more obvious in the observation group (P <0.05). The one-year recurrence rate of the observation group was 4% (2/50), which was significantly lower than that of the control group, which was 20% (10/50). There was a statistical difference between the two groups (P <0.05). It was concluded that oral desloratadine citrate disodium combined with physiological seawater nasal irrigation can effectively improve the symptoms and signs of intermittent allergic rhinitis and reduce the recurrence rate. This may be related to balancing T cell responses, promoting systemic Th1 responses and inhibiting Th2 responses, and down-regulating inflammatory response.