Absorption across the nasal airway mucosa in house dust mite perennial allergic rhinitis

House dust mite allergens express protease activity and it has been suggested that this property has pathogenic effects by increasing airway absorption. In accordance, house dust mite allergens may increase mucosal permeability in vitro. The objective of the present study was to examine nasal absorption of desmopressin (1-deamino-8-D-arginine vasopressin) in patients with perennial house dust mite allergic rhinitis and in healthy subjects in vivo. Patients with perennial allergic rhinitis were examined after a 4-week treatment withdrawal period, when symptoms of allergic rhinitis occurred, and healthy subjects were examined together with the patients. Desmopressin (20 microg ml(-1)) was moved into the nasal cavity using a nasal pool-device that contained 15 ml fluid. The fluid was kept in the nasal cavity for 15 min and then recovered. Urine was collected for 24 h after the nasal administration and the urinary excretion of desmopressin was determined as an index of nasal absorption. The urinary excretion of desmopressin was 1148+/-535 pmol 24 h(-1) in patients with perennial house dust mite allergic rhinitis and 1012+/-291 pmol 24 h(-1) in healthy subjects. We conclude that nasal airway absorption of the 1067 Da peptide desmopressin is unaffected in perennial house dust mite allergic rhinitis compared with healthy subjects.     

变应性鼻炎血清总IgE水平测定及临床意义

目的研究血清总IgE在季节性与常年性变应性鼻炎中的变化,并探讨其临床意义。方法采用酶联免疫法检测62例变应性鼻炎患者和20例健康者血清总IgE水平,并进行相关性分析。结果季节性和常年性变应性鼻炎血清总IgE明显高于健康对照组(P<0.01),季节性变应性鼻炎血清总IgE明显高于常年性变应性鼻炎(P<0.01)。季节性变应性鼻炎症状和体征高于常年性,差异有统计学意义(P<0.05)。结论血清总IgE水平与变应性鼻炎的发作强度呈正相关,有助于临床诊断及病情评估。     

Effectiveness and safety of electric heating moxibustion for perennial allergic rhinitis: A pilot,randomized, assessor-blind trial

BackgroundThe prevalence of allergic rhinitis (AR), an inflammatory disease, is gradually increasing. Studies have reported that moxibustion is effective for treating AR. Electric heating moxibustion (EM) was developed to offer adaptable heat stimulation without the generation of smoke.ObjectivesThe objective of this study was to examine the possibility of EM in treating perennial allergic rhinitis (PAR) and to assess the feasibility of using this technique on a larger scale by comparing EM with acupuncture (AC).DesignA randomized pilot study was conducted on 40 patients with PAR. Patients were randomly assigned to one of two treatment groups: EM or AC. The primary outcome measure was the change in the total nasal symptom score (TNSS) between before and after treatment. The secondary outcome measures were the changes in the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal endoscopy index for pattern identification, pattern identification questionnaire for AR, total serum immunoglobulin E (IgE), eosinophil count, and adverse effects (AEs).ResultsThe results showed a statistically significant improvement in mean TNSS and RQLQ scores in both groups (p < 0.05), but no significant difference between the two groups. However, mean changes in itching and sneezing TNSS were significantly higher in the AC group. There was no significant difference in total serum IgE or eosinophil count before versus after treatment, nor was there any significant difference of three pattern subgroups between the two groups in the mean TNSS change. While the AC group reported two treatment-related AEs, there were no treatment-related AEs in the EM group.ConclusionThis trial provides evidence that EM isa safe alternative treatment for patients with PAR.Trial registrationClinicalTrials.gov, NCT03342105. Registered on 14 November 2017.     

When hay fever doesn't quit. Diagnosing seasonal and perennial allergic rhinitis

Seasonal allergic rhinitis is usually easily diagnosed by the seasonal nature of characteristic symptoms combined with evidence of appropriate specific IgE antibodies. Perennial allergic rhinitis, however, may present a diagnostic challenge. The physician may find IgE antibodies to allergens perennially encountered by the patient and should look for other causes of chronic rhinitis. Examination of nasal secretions can be a diagnostic aid, but measurements of eosinophils and total IgE in serum have limited diagnostic value.     

A Randomized,Multicenter, Double-blind,Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis

Purpose

The aim of this study was to evaluate the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma compared with the efficacy and safety of montelukast alone.

A CLINICAL COMPARISON OF INTRANASAL BUDESONIDE WITH BECLOMETHASONE DIPROPIONATE FOR PERENNIAL NON-ALLERGIC RHINITIS: A 12 MONTH STUDY

SUMMARY To evaluate possible differences in efficacy and safety between budesonide and beclomethasone dipropionate when used intranasally in the treatment of perennial non-allergic rhinitis, a 12-month open study was undertaken in 24 patients suffering from perennial non-allergic rhinitis. Both drugs were applied intranasally from pressurised aerosols at a daily dosage of 400 μg. On entry and at visits after 1, 2, 4, 6, 9 and 12 months, rhinoscopy was performed and the severity of nasal symptoms graded according to a four-point rating scale. All nasal symptoms were reduced from baseline during the treatment period in both groups. Tachyphylaxis was not observed. No clinically significant changes in haematology or blood chemistry parameters were observed in either group, and analysis of plasma cortisol levels revealed no influence of either drug on the hypothalamic-pituitary-adrenal axis. Local adverse reactions were uncommon and mild. Budesonide and beclomethasone dipropionate used intranasally at 400 μg per day were found to be safe, and budesonide was found to have a significantly higher (p<0.05) efficacy than beclomethasone dipropionate in alleviating symptoms of perennial non-allergic rhinitis.     

鼻腔结构矫正结合射频治疗常年性变应性鼻炎

目的：观察鼻内镜手术结合射频治疗伴有鼻腔结构异常的常年性变应性鼻炎的疗效。方法：46例伴有鼻中隔偏曲或下鼻甲肥大的常年性变应性鼻炎患者，在鼻内镜下行鼻中隔黏膜下矫正术或下鼻甲黏膜下部分切除术，同时结合射频热凝下鼻甲、鼻丘、与鼻丘对应的鼻中隔等副交感神经密集部位。结果：术后随访1年以上，术后1个月和术后1年的总有效率分别为97．8％、82．6％。7例复发，其中6例发生在手术6个月以后。结论：对伴有鼻中隔偏曲或下鼻甲肥大的常年性变应性鼻炎患者，鼻内镜手术结合射频治疗是理想的治疗方法，术后复发多在6个月以后。     

A review of the efficacy of desloratadine,fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis

Background: Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion.Objective: This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihista-mines desloratadine, fexofenadine, and levocetirizine.Methods: MEDLINE and EMBASE were searched for nasal challenge studies and clinical trials published in English between January 1, 1991, and January 31, 2009, using the following terms, alone or in combination: antihistamines, second-generation antihistamines, allergic rhinitis, intermittent allergic rhinitis, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis, nasal challenge, nasal blockage, and nasal congestion. Studies that were not active or placebo controlled, that did not evaluate change in nasal congestion scores, or that focused on treatments other than desloratadine, fexofenadine, and levoce-tirizine for nasal congestion associated with AR were excluded.Results: Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetiri-zine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P ≤ 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P ≤ 0.005).Conclusions: In the studies reviewed, desloratadine, fexofenadine, and levocetirizine were effective in relieving the nasal congestion associated with AR compared with placebo. This effect began as early as day 2 and was consistent and progressive throughout treatment. Desloratadine, fexofenadine, and levocetirizine are appropriate options for the treatment of nasal congestion in patients with AR.     

Omalizumab for treatment of allergic rhinitis

Introduction: Immunoglobulin E (IgE) is a key pathogenic factor of allergic rhinitis, a prevalent disease adversely affecting quality of life and productivity.

Areas covered: Binding of inhaled allergens to IgE on the surface of basophils and mast cells, with subsequent cross-linkage of IgE and aggregation of high-affinity receptors for IgE (Fc?RI), triggers the release of inflammatory mediators, followed by the onset of allergic rhinitis symptoms. Current therapeutic strategies include corticosteroids, mast cell stabilizers, leukotriene receptor antagonists, anticholinergics, antihistamines and allergen immunotherapy. Removal of circulating free IgE by the recombinant humanized monoclonal anti-IgE antibody, omalizumab (Xolair), represents a novel therapeutic approach. Omalizumab selectively binds to the C?3 domain of IgE at the site of Fc?R1 binding, thus blocking binding of IgE to effector cells. We review omalizumab's clinical efficacy, administration, use with immunotherapy and safety in allergic rhinitis.

Expert opinion: Omalizumab may provide a new treatment strategy for allergic rhinitis. The high cost of omalizumab precludes its chronic use for allergic rhinitis and it is not FDA approved for this indication; however, its periodic use may be justified in treatment resistant patients, especially those with seasonal disease.     

Previous ear, nose and throat surgery in children presenting with allergic perennial rhinitis

Children with allergic perennial rhinitis had a four-fold greater likelihood of having had an ear, nose and throat (ENT) operation than children with orthopaedic problems. Whilst the patients who had ENT operations had significantly lower serum IgA and IgE levels than the non-operated patients, there was no difference in clinical features of atopy or allergy skin-test responses between the two groups of rhinitic patients. Forty per cent of the perennial rhinitics had an improvement in symptoms following ENT operations, whereas 90% improved on medical therapy. Thus, patients with perennial rhinitis should have allergy investigations and the benefit of medical treatment prior to consideration for surgery.     

Double-blind comparison of cetirizine and loratadine in children ages 2 to 6 years with perennial allergic rhinitis.

Antihistamines are the pharmacologic cornerstone of treatment for allergic rhinitis. The comparative effects of the newer, more specific H (1) -antagonists cetirizine and loratadine among younger patients are not well characterized. The efficacy and safety of cetirizine and loratadine were compared in a prospective, randomized, double-blind, longitudinal, parallel-group study of 80 children, 2 to 6 years of age, with perennial allergic rhinitis caused by house dust mites or plant pollens (verified by a radioallergosorbent or skin test). Patients received cetirizine or loratadine at 0.2 mg/kg once daily in the morning for 28 days. Histamine skin tests and eosinophil counts from nasal smears were performed at baseline and at the end of treatment. Individual rhinitis symptoms were assessed by the investigator at baseline and on day 28 and by parents at baseline and daily in symptom diaries. Global assessments were made by using a visual analog scale at baseline and at the end of treatment. Cetirizine produced significantly greater inhibition of the wheal response compared with loratadine (P <.0001). Eosinophil counts were improved to a comparable degree with both agents. Cetirizine and loratadine produced comparable improvements in symptoms and according to a global evaluation as assessed by the investigator at the end of treatment. Both agents produced substantial symptomatic relief according to patients' daily diary assessments; however, cetirizine was more effective than loratadine in relieving the symptoms of rhinorrhea, sneezing, nasal obstruction, and nasal pruritus (P <. 0001). Both treatments were well tolerated; two patients receiving cetirizine were dropped from the study because of adverse events. Cetirizine and loratadine provided effective, well-tolerated relief of the symptoms of perennial allergic rhinitis in small children. Cetirizine was more effective than loratadine in inhibiting the wheal response to histamine challenge and afforded greater reductions in most individual symptoms assessed daily by the parent.     

尘螨滴剂舌下免疫治疗儿童变应性鼻炎疗效及安全性的Meta分析

目的系统评价尘螨滴剂舌下免疫治疗儿童变应性鼻炎的疗效及安全性。方法计算机检索Pub Med、EMbase、CBM、Ovid、h e Cochrane Library（2014年第5期）、CNKI、VIP和Wan Fang Data,收集关于尘螨滴剂舌下特异性免疫治疗儿童变应性鼻炎的随机对照试验（RCT）,检索时限均为建库至2014年5月。由2位评价者按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用Rev Man 5.3软件进行Meta分析。结果最终纳入9个RCT,共计663例患者。Meta分析结果显示：在减少药物使用评分[SMD=–0.61,95%CI（–0.94,–0.27）,P=0.000 4]和降低患者血清特异性Ig E抗体水平[随访时间〉22周：SMD=0.71,95%CI（0.31,1.12）,P=0.000 5]方面,试验组均优于对照组;但两组在鼻部症状评分[SMD=0.06,95%CI（–0.13,0.25）,P=0.55]及不良反应发生率[OR=1.3,95%CI（0.89,1.90）,P=0.17]方面无明显差异。结论尘螨滴剂舌下免疫治疗儿童变应性鼻炎可减少抗组胺药、β受体阻滞剂及鼻喷激素的使用频率,不良反应少,安全性好,但不能有效减轻鼻部症状及在较短时间内降低血清特异性Ig E抗体水平。     

Current and emerging biologic therapies for allergic rhinitis and chronic rhinosinusitis

ABSTRACT

Introduction: Allergic rhinitis and chronic rhinosinusitis, with and without nasal polyps, are the most common chronic inflammatory diseases of the upper airways. They both cause relevant respiratory symptoms and a substantial detriment to patients’ quality of life, mainly in uncontrolled and severe patients.

Areas covered: This review aims to present the most recent evidence on current and emerging biologic therapies for allergic rhinitis and chronic rhinosinusitis and discuss their potential implementation in clinical practice. To select relevant literature for inclusion in this review, we conducted a literature search using the PubMed database, using terms ‘biologics OR biological agents’, ‘allergic rhinitis’ and ‘chronic rhinosinusitis’. The literature review was performed for publication years 2009–2019, restricting the articles to humans and English language publications.

Expert opinion: Biological therapies represent a potential step forward in providing individualized care for all patients with uncontrolled severe upper airway diseases. Biologics recently showed promising results for the treatment of severe uncontrolled allergic rhinitis and chronic rhinosinusitis with nasal polyps with or without associated asthma. Endotyping inflammatory pathways and identifying related biomarkers remain the major challenge for positioning biologics in the care pathway of chronic respiratory diseases.     

Immunological parameters in perennial rhinitis.

As part of a study of the effectiveness of beclomethasone dipropionate in perennial rhinitis five immunologically related parameters were measured. These included skin tests, total IgE, specific IgE, nasal and peripheral blood eosinophil counts. In addition, nasal biopsies were obtained in twenty out of sixty patients. It was apparent that patients with perennial rhinitis formed a heterogeneous group who could be divided into three groups based on the extent of immunological abnormality detected. Group 1 consisted of twenty patients who displayed no abnormality in any of the five parameters studied. Group 2 consisted of twenty-six patients in whom specific IgE was not detected but who had varying degrees of abnormal findings in the other laboratory parameters. The remaining fourteen patients formed a third group in whom specific IgE was detected in addition to abnormalities in other parameters. In general, patients with detectable specific IgE had a higher frequency of abnormal parameters, including abnormal histology of their nasal biopsy, than patients in whom no specific IgE was detected. The heterogeneous nature of perennial rhinitis is discussed. Despite the heterogeneous nature of the total patient group, the majority of patients (80%) treated with beclomethasone dipropionate improved compared to 20% improved in the placebo group. There was no difference in the drug effect between the three groups of patients.     

变应性鼻炎舌下免疫治疗对患者生活质量的影响

目的探讨变应性鼻炎舌下免疫（sublingual immunotherapy,SLIT）治疗对患者生活质量的影响。方法将79例变应性鼻炎患者随机分为实验组40例与对照组39例,对照组给予抗组胺药物及鼻局部皮质类固醇药物治疗,实验组在此治疗基础上给予SLIT治疗。治疗后比较两组患者症状评分、药物评分及鼻炎生活质量情况。结果实验组在治疗3个月后症状评分和2个月后药物评分均较对照组明显降低;2年后实验组患者鼻炎生活质量明显优于对照组,组间比较,均P〈0.01,差异具有统计学意义。结论变应性鼻炎采用SLIT治疗,可明显减轻患者鼻部症状,减少用药量,改善患者鼻炎生活质量,是一种安全、有效的治疗方法。     

Omalizumab,a novel anti-IgE therapy in allergic disorders

The incidence of allergic diseases is increasing to epidemic proportions both in the developed and developing world with increasing medical costs and lost productivity. The discovery of immunoglobulin (Ig) E heralded a new era in pathophysiological understanding of allergic disorders. Twenty-five years later, a humanised, non-anaphylactogenic antibody was developed against IgE that could provide a therapeutic alternative to the existing medications. RhuMAb-E25 (omalizumab, Xolair^®, Genetech, Inc.) is a novel anti-IgE antibody that is directed against the receptor-binding domain of IgE. This binding is specific towards free IgE thereby preventing it from attaching to the mast cell and its subsequent activation. Initial studies demonstrated attenuation of the early and late asthmatic responses when anti-IgE was administered to asthmatic subjects. Later this novel molecule was found to improve symptom scores, rescue medication use, quality of life scores and peak expiratory flows in patients with allergic asthma. Most importantly, omalizumab treatment reduced the corticosteroid use in asthmatic individuals. In patients with seasonal allergic rhinitis, there was a significant reduction in the nasal and ocular symptoms as well as the use of rescue medications. Omalizumab also demonstrated a high level of safety in adults, adolescents and children with a side effect profile no different from the placebo. Its development is an exciting milestone in the treatment of allergic diseases.     

Use of intranasal cromolyn sodium for allergic rhinitis

Allergic rhinitis affects 10% to 20% of Americans. It frequently coexists with other conditions, such as allergic conjunctivitis, sinusitis, and asthma, and is associated with impaired occupational function and performance in school, decreased quality of life, and increased health care costs. An efficacious agent with minimal adverse effects and a lack of drug interactions is needed to help simplify treatment of allergic rhinitis, especially in patients with comorbidities. Controlled studies of intranasal cromolyn sodium therapy for patients with seasonal and perennial allergic rhinitis are reviewed, and appropriate candidates for treatment with this agent are discussed. Cromolyn inhibits the degranulation of sensitized mast cells, thereby blocking the release of inflammatory and allergic mediators. It reduces symptoms of allergic rhinitis, and, when used prophylactically, cromolyn can prevent symptoms from occurring. Controlled studies comparing cromolyn with placebo, intranasal corticosteroids, and antihistamines have shown the efficacy of cromolyn in relieving rhinitis symptoms. In addition, because cromolyn is poorly absorbed systemically, it is well tolerated and not associated with drug interactions. Intranasal cromolyn has an excellent safety record, is available as an over-the-counter medication, and has been proved to be efficacious in patients with allergic rhinitis.     

Potentiation of human immunoglobulin E synthesis by plasma immunoglobulin E binding factors from patients with the hyperimmunoglobulin E syndrome.

Affinity-purified IgE-binding factors from the plasma of patients with the hyper IgE syndrome (HIE) were assessed for their capacity to enhance IgE synthesis by B cells derived from patients with allergic rhinitis or normal nonatopic donors. IgE-binding factors from three of four HIE patients enhanced IgE synthesis by B cells from patients with perennial allergic rhinitis, or with seasonal allergic rhinitis (SAR) and recent pollen exposure, but did not enhance IgE synthesis by B cells from nonatopic donors or from SAR patients with no recent pollen exposure. IgG synthesis was not affected by HIE IgE binding factors. In contrast, IgE binding factors from three of three nonatopic donors failed to enhance IgE or IgG synthesis. Plasma IgE-binding factors from the fourth patient with HIE contained a mixture of IgE-potentiating activity and IgE-suppressive activity. These two activities could be separated on concanavalin A Sepharose or peanut agglutinin agarose columns. Human IgE potentiating factor, but not IgE suppressive factor, had affinity for concanavalin A but not peanut agglutinin and fractionated into two peaks on gel filtration over Sephadex G-75: one peak with a molecular size of approximately 15,000 D and the other with a molecular size of approximately 60,000 D. The isolation of functional IgE binding factors which potentiate IgE synthesis from the plasma of patients with HIE suggests that IgE-binding factors play an important role in the in vivo regulation of IgE synthesis in man.