The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients

Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammation pathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthma with rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88 healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcal superantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameters were retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%, and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, and TSST-1 were also significantly higher in group I (0.300±1.533 kU/L, 0.663±2.933 kU/L, and 0.581±1.931 kU/L) and group II (0.502±2.011 kU/L, 0.695±3.337 kU/L, and 1.067±4.688 kU/L) compared to those in group III (0.03±0.133 kU/L, 0.03±0.14 kU/L, and 0.028±0.112 kU/L). The prevalence of serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higher in patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE to TSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR and AR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation.     

Seasonal Variation of Asthma and Allergic Rhinitis

The seasonal variation of consultations on account of asthma and allergic rhinitis, and the relationship with air concentrations of pollen, spores, and lead, cadmium, dust, soot and sulfur dioxide was investigated in Danish general practice during a 1-year period 1977-78. A population of about 500,000 was studied. Among about 3000 asthmatics there were less consultations during spring than the rest of the year, but the seasonal variation of consultations with symptoms was rather small. The highest rate of consultations was in week 24, which is close to the peak of the grass pollen period. No relationship was found between asthma symptoms and concentrations of pollution indicators. Among about 5000 patients with allergic rhinitis the rate of consultations with symptoms increased at the start of the tree pollen season, still more at the start of the birch pollen season, and was very high during weeks 21-26 in the grass pollen season. Two thirds of all consultations for symptomatic allergic rhinitis took place within 10 weeks (Nos. 18-27). During the grass pollen season there was a relative preponderance of young patients, while during the birch pollen season older patients dominated. No connection was seen between rhinitis symptoms and pollution indicators. The different seasonal variation of asthma and allergic rhinitis indicates that the two patient categories differ as regards symptom-provoking factors. Allergic rhinitis is mainly precipitated by grass and birch pollen. The precipitating factors of asthma were not disclosed in this study, with the exception perhaps of some influence from pollen, and - among 0-4-year-old children - respiratory infections.     

Methodology for development of the Allergic Rhinitis and its Impact on Asthma guideline 2008 update

Background:  We describe the methodology for the 2008 update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The methodology differs from the 2001 edition in several respects. The most prominent change is the application of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to compiling evidence, assessing the quality of evidence and grading of recommendations.
Methods and results:  Representatives of the GRADE working group joined the ARIA guideline panel to achieve these tasks. While most recommendations result from existing systematic reviews, systematic reviews were not always available and the panel compiled the best available evidence in evidence profiles without conducting actual reviews. The panel conducted two meetings and used the GRADE criteria to assess the quality of evidence (four categories of high, moderate, low and very low) and the strength of recommendation (strong and weak) based on weighing up the desirable and undesirable effects of management strategies, considering values and preferences influencing recommendations, and resource implications. The guideline panel has chosen the words 'we recommend'– for strong recommendations and 'we suggest'– for weak recommendations. Both categories indicate the best course of action for a given patient population, but their implementation, requires different considerations as we describe subsequently in this article.
Conclusions:  The 2008 update of the ARIA guidelines has become more evidence-based. Future iterations of the guidelines will further be improved by following the described processes even closer, such as ensuring availability of updated high quality systematic reviews for each question.     

Lymphocyte Subpopulations in Patients with Allergic Rhinitis

The lymphocyte subpopulations were classified using monoclonal antibodies specific for B lymphocytes (B1 antibodies), T lymphocytes (T11 and OKT3 antibodies), helper/inducer T cells (T4 antibodies) and suppressor/cytotoxic T cells (T8 antibodies). Three groups of subjects were studied: 20 normal controls, 29 patients with allergic rhinitis and a subgroup of nine patients who had received immunotherapy. The proportion of B lymphocytes, total T cells and T4 positive (helper/inducer) cells were not significantly different between the groups, but allergic patients were found to have a decreased proportion of suppressor T8 positive (suppressor/cytotoxic) cells and hence a high helper/suppressor cell ratio. These abnormal parameters were found to be normal in the group of allergic patients who had received immunotherapy. These results imply that a suppressor cell deficiency may be an underlying mechanism of allergic disease, and that immunotherapy could correct the suppressor cell deficiency.     

口服白三烯受体拮抗剂与吸入糖皮质激素治疗小儿咳嗽变异型哮喘合并变应性鼻炎的对比研究

目的对比研究口服白三烯受体拮抗剂（LTRA）与吸入糖皮质激素（ICS）对dxJL咳嗽变异型哮喘合并变应性鼻炎的防治效果。方法54例2-5岁患儿随机分为LTRA组（27例）和ICS组（27例）。LTRA组口服孟鲁司特钠，每次4mg，睡前服用1次；ICS组患儿规律吸入布地奈德气雾剂，每日200-400μg，采用储雾罐辅助吸入。药物治疗3个月后继续随访观察15个月。结果LTRA组与ICS组比较．控制症状所需的平均天数为（8．31±3．69）d和（7．20±2．78）d；症状缓解率为92．6％和96．3％，差异无统计学意义（P〉0．05）。在病程的18个月LTRA组复发率（36．0％）显著高于ICM组（15．4％）。转化为典型哮喘者。LTRA组7例（28．0％），ICS组2例（7．7％），差异有统计学意义（P〈0．05）。结论口服LTRA控制小儿咳嗽变异型哮喘合并变应性鼻炎的近期疗效与ICS相当。可作为一线药物使用。但接受LTRA治疗的患儿远期复发率或者转化为典型哮喘的比率高于ICS治疗的患儿。     

The Quality of Health Information on Allergic Rhinitis,Rhinitis, and Sinusitis Available on the Internet

PurposeThe internet has become one of the most important media outlets used to obtain health information. Therefore, the quality of health information available on the internet is very important. We evaluated the quality of internet-derived health information on allergic rhinitis, rhinitis and sinusitis and compared these results to those of previous studies performed five years ago.MethodsThe terms "allergic rhinitis (AR)", "rhinitis" and "sinusitis" were searched among the four most commonly used search engines in South Korea. These websites were evaluated according to the author, the Journal of the American Medical Association (JAMA) benchmarks, the DISCERN questionnaire and the Allergic rhinitis and its Impact on Asthma (ARIA) 2008 Update.ResultsA total of 120 websites were obtained and analyzed. For all diseases, "Oriental physician" had the largest portion (almost half of all websites), followed by "Western physician". Based on analyses using the JAMA benchmark, "Attribution" and "Disclosure" were ignored in almost all surveyed websites. According to the scores of the DISCERN question, the majority of websites did not supply appropriate references for their health information, and information on the negative aspects of treatment such as risks and uncertainty was not provided in several websites. In an analysis based on the ARIA 2008 Update concepts, 65% of websites pertaining to health information on AR contained unreliable information.ConclusionsThe quality of health information on the internet was not acceptable. Thus, governmental regulation or control to improve the quality of health information is required.     

A Comparison of Intranasal and Oral Flunisolide in the Therapy of Allergic Rhinitis

Intranasal flunisolide is an effective treatment for allergic rhinitis. Flunisolide has high bioavailability when administered to normal subjects (50% of an intranasal dose reaches the systemic circulation) with minimal systemic effects. Bioavailability in patients with active rhinitis averages 62.4 +/- 15.7%. The oral dose bioequivalent to 100 micrograms intranasally is 500 micrograms. To define the comparative trial and systemic effects of intranasal flunisolide in patients with active allergic rhinitis, a multicenter, randomized, double-blind, placebo-controlled study was conducted during the 1983 ragweed hayfever season. Ninety-nine patients with ragweed hayfever for greater than or equal to 2 years and positive prick skin tests to ragweed were randomly allocated to one of three treatment groups: 0 = oral flunisolide 500 micrograms b.i.d. and intranasal placebo b.i.d.; N = intranasal flunisolide 50 micrograms per nostril b.i.d. and oral placebo b.i.d.; P = intranasal and oral placebo b.i.d. Treatment continued for 4 weeks. Patients kept daily symptom scores. Patients were evaluated by a blinded observer every 2 weeks and were globally evaluated at the study's end. Data were analyzed for each center and pooled. There were no significant differences in symptom severity of sneezing, nasal congestion, and throat itch in the 0 (oral flunisolide) and P (placebo) groups. N (nasal flunisolide) was significantly more effective than O or P (P less than or equal to 0.005) for each symptom for at least one 2-week period. Global evaluation demonstrated control of overall hayfever severity for N (nasal flunisolide) but not for O (oral flunisolide). We conclude that the therapeutic efficacy of flunisolide is achieved by topical and not by systemic action.     

Comparative Trial of Flunisolide and Beclomethasone Dipropionate Nasal Sprays in Patients with Seasonal Allergic Rhinitis

In order to evaluate the effects of flunisolide and beclomethasone dipropionate nasal sprays on seasonal allergic rhinitis, 45 patients were included in an open parallel comparative trial. The study design was open because of the different dosage schedules for the two preparations. Strict criteria were set up for patient selection, and all patients were carefully examined and assessed before and after the 4-week trial period. Throughout the whole treatment each patient kept a detailed daily record. A substantial or complete control of symptoms was achieved in 18 of the 21 patients on flunisolide and in 20 of the 22 on beclomethasone dipropionate. No serious side effects were observed. Thus it can be concluded that both test drugs are effective and well tolerated in the treatment of seasonal allergic rhinitis.     

The Pathophysiology, Diagnosis and Treatment of Allergic Rhinitis

Treatment of AR requires a stepwise approach depending on the severity and duration of symptoms. Treatment options for AR consist of allergen avoidance, pharmacotherapy, immunotherapy and surgery. For the mechanisms of AR, anti-IgE antibody and specific antibody to cytokines such as IL-4 or IL-5 that correlate with allergic inflammation have recently emerged. SLIT is currently widely used due to its efficacy, safety and convenience, which replaces subcutaneous immunotherapy. Although allergen avoidance and immunotherapy are theoretically ideal, antihistamines and intranasal corticosteroids will play the main role in the management of AR until an innovative treatment develops. However, patients'' main symptom, the duration and severity of AR, patients'' compliance, safety of medication and cost-effectiveness should be considered when treatment options are chosen. In conclusion, physicians should be aware of etiology, pathophysiology, symptoms, signs and diseases related to AR in order to make a correct diagnosis and choose a proper treatment option for each patient.     

Altered microRNA Expression Profiles of Extracellular Vesicles in Nasal Mucus From Patients With Allergic Rhinitis

Purpose

Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR.

Methods

Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath.

Results

Twenty-one vesicle miRNAs were up-regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients.

Conclusions

This study demonstrated that vesicle miRNA may be a regulator for the development of AR.     

变应性鼻炎特异性免疫治疗患者的依从性及相关因素分析

目的研究变应性鼻炎特异性免疫治疗患者的依从性及其影响因素。方法对过去3年接受特异性免疫治疗的变应性鼻炎患者进行回顾性调查，对未完成基础疗程的患者采取电话方式了解其不依从的原因，率的比较采用χ^2检验进行分析。结果特异性免疫治疗患者的完全依从率为70．1％；儿童的完全依从率为84．6％，高于成人（64．16％，58．46％），有统计学意义（χ^2值分别为8．712，6．441，P〈0．05）；不依从的原因调查表明，效果不明显或无效占29．49％，工作忙或学业紧张占20．86％，症状消失或好转占12．23％。结论变应性鼻炎特异性免疫治疗患者的依从性不甚理想，其中儿童的依从性高于成人。调查结果提示治疗中应有针对性地采取相应的干预措施，以提高患者免疫治疗的依从率，从而提高疗效。     

Analysis of Quality of Life and Mental Health in Patients With Atopic Dermatitis,Asthma and Allergic Rhinitis Using a Nation-wide Database,KNHANES VII

PurposeThis study investigated mental health status and quality of life in allergic disease patients compared with non-allergic controls.MethodsThis study used nationwide, population-based, cross-sectional data from the Korean National Health and Nutrition Examination Survey from 2016 to 2018. The propensity matching score was used to balance age and sex distributions between the allergic disease groups and corresponding controls. Atopic dermatitis (n = 446) and asthma (n = 483) groups were compared with controls in a 1:10 ratio, and the allergic rhinitis (n = 2,357) group was compared with controls in a 1:2 ratio. Multiple logistic regression analyses were used to evaluate the odds ratios (ORs) for mental health status and health-related quality of life (HRQoL) based on the presence of allergic diseases.ResultsThe ORs for severe psychological stress, psychological consultation and diagnosis of depression were more significantly increased in the asthma (OR, 1.41, 1.83, and 2.1, respectively) and allergic rhinitis groups (OR, 1.35, 1.48, and 1.83, respectively) compared with non-allergic controls after adjustment for confounding factors. The rate of severe problems in mobility was more significantly increased in the asthma group compared to controls.ConclusionsThe results show that efforts should be made to manage psychological problems and improve HRQoL in patients with atopic dermatitis, asthma and allergic rhinitis.     

Allergic Rhinitis in Danish General Practice

The prevalence rate of allergic rhinitis and the consultation rate caused by this disease were studied in 131 general practices covering a population of 450,000 persons in Denmark. During a 1-year period starting June 1977 all consultations with or without symptoms were recorded.
Allergic rhinitis was defined as paroxysmal sneezing and rhinorrhoea with or without conjunctivitis, and without signs of infection.
Results are presented from three groups of practices classified by self-estimated completeness of reporting. 11–15 per thousand of the total population contacted a practice during the 1-year period (males: 12–17%, females: 10–13%). The highest prevalence rate occurred at 10–19 years of age, and allergic rhinitis was common from five to 44 years of age. The prevalence rate was higher among males up to the age of 30, after which age it was a little higher among females. About two-thirds of the patients consulting had at least one consultation per year with symptoms present.
The number of contacts came to 4.4 per patient per year and 20–25% of these were with symptoms.     

支气管哮喘与过敏性鼻炎患者对蟑螂变应原特异性IgE反应的对比研究

为比较支气管哮喘与过敏性鼻炎患者对不同种属蟑螂的过敏反应程度,探讨不同种属蟑螂间可能存在的交叉抗原性及其程度,用ELISA法检测支气管哮喘与过敏性鼻炎患者血清中对三种蟑螂(美洲大蠊、黑胸大蠊和德国小蠊)变应原的特异性IgE抗体(sIgE).结果显示支气管哮喘患者对美洲大蠊、黑胸大蠊和德国小蠊变应原的sIgE阳性率分别为23.5%、16.0%和14.0%,美洲大蠊sIgE阳性率比对德国小蠊为高,有显著性差异(P=0.015),虽然美洲大蠊sIgE阳性率比对黑胸大蠊高、黑胸大蠊sIgE阳性率比对德国小蠊高,但差异均无统计学意义(P=0.060;P=0.575);哮喘患者中美洲大蠊与黑胸大蠊sIgE反应符合率74.0%,美洲大蠊与德国小蠊sIgE反应符合率73.5%,黑胸大蠊与德国小蠊sIgE反应符合率85.0%.过敏性鼻炎患者对美洲大蠊、黑胸大蠊和德国小蠊sIgE阳性率分别为24.8%、17.6%和15.8%,美洲大蠊sIgE阳性率比对德国小蠊高,有显著性差异(P=0.040),虽然美洲大蠊sIgE阳性率比对黑胸大蠊高、黑胸大蠊sIgE阳性率比对德国小蠊高,但差异均无统计学意义(P=0.106,P=0.658);过敏性鼻炎患者对中美洲大蠊与黑胸大蠊sIgE反应符合率为73.9%,对美洲大蠊与德国小蠊sIgE反应符合率为75.2%,对黑胸大蠊与德国小蠊sIgE反应符合率为86.1%.过敏性鼻炎患者对美洲大蠊、黑胸大蠊和德国小蠊sIgE阳性率均比支气管哮喘患者高,但差异均无统计学意义(P=0.764;P=0.688;P=0.638).提示支气管哮喘与过敏性鼻炎患者对三种蟑螂的过敏反应程度基本相当,三种蟑螂间可能存在一定程度的交叉抗原性成分.     

Lung Function Studies in Children with Allergic Rhinitis

Thirty carefully selected children with seasonal allergic rhinitis but without history or signs of lung involvement were examined clinically and by lung function tests during the pollen season as well as in the pollen-free season. During the pollen-free season the children had -if anything - slightly better lung function than a healthy control material. During the pollen season the only change was a slight increase in FRC and a decrease in lung clearance index, directly proportional to the change in FRC. Sixteen of the children performed an exercise test in the pollen-free season. A small increase in the volume of trapped gas (VTG) was noted, indicating a subclinical spasm in small airways. Salbutamol inhalation alter exercise reduced VTG below base-line values, indicating disappearance of subclinical bronchospasm. Hay Fever children thus have a tendency towards bronchospasm after exercise in the pollen-free season, which, owever, is of no clinical importance, as their VTG also after the exercise was less (better) than the predicted normal.     

Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis

PurposeGroup 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens.MethodsFlow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage^- and Lineage⁺ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage^- and Lineage⁺ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit.ResultsThe percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33±IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage^- cells compared to Lineage⁺ cells.ConclusionsAR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.     

Long-term Effects of Specific Allergen Immunotherapy Against House Dust Mites in Polysensitized Patients With Allergic Rhinitis

Purpose

Allergen-specific immunotherapy is the only currently available treatment to modify the natural history of allergic rhinitis (AR). If patients are polysensitized, it is difficult to identify the allergen causing the allergic symptoms. We evaluated the effectiveness of immunotherapy against house dust mites (HDMs) in AR patients polysensitized to both HDMs and seasonal allergens.

Methods

Thirty AR patients polysensitized to both HDMs and seasonal allergens (group A) and 30 patients sensitized to HDMs only (group B) were enrolled in this study. All subjects who received immunotherapy against HDMs for more than 2 years were evaluated by the multiple allergen simultaneous test (MAST) to determine the specific IgE level in luminescence units, total eosinophil counts in peripheral blood, serum total IgE, total nasal symptom scores, and the rhinoconjunctivitis quality of life questionnaire (RQLQ) before and after immunotherapy.

Results

There were no statistical differences in levels of total and specific IgE, or total eosinophil count between the two groups. The total nasal symptom scores, RQLQ and medication scores significantly decreased after immunotherapy in both groups, however no significant differences were noted between the two groups.

Conclusions

We determined that the primary causative allergen of AR in Seoul, Korea is perennial allergens, such as HDMs, rather than seasonal allergens. This study provides a reference for the selection of allergens to use in immunotherapy for polysensitized AR patients living in an urban environment.