Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Allergic diseases affect both children and adults, but generation-specific prevalence rates are unclear. METHODS: An online questionnaire was used from December 2021 to January 2022 to survey the prevalence of allergic diseases among staff and their families of designated allergic disease medical hospitals in Japan. In this study, bronchial asthma (BA), atopic dermatitis (AD), food allergies (FAs), allergic rhinitis (AR), allergic conjunctivitis (AC), metal allergies (MAs), and drug allergies (DAs) were the allergic diseases surveyed. RESULTS: In total, 18,706 individuals were surveyed (median age, 36 years; quartile range, 18-50). Allergic disease was reported in 62.2% of respondents. Across all ages, prevalence rates were as follows: BA (14.7%), AD (15.6%), FAs (15.2%), AR (47.4%), AC (19.5%), MAs (1.9%), and DAs (4.6%). The prevalence of BA and AR was higher in male children, whereas that of FAs and AC was higher in adult females. The prevalence of MAs and DAs peaked during adulthood and predominated among females. CONCLUSIONS: Our results suggest that approximately two-thirds of the Japanese population may have an allergic disease, with AR being the most prevalent.

DOI： 10.31662/jmaj.2022-0218

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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DOI： 10.1111/all.15514

PubMed

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The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today. The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.

DOI： 10.1016/j.alit.2022.11.003

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jacig.2022.10.006

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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.

DOI： 10.1016/j.jphs.2022.10.004

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Language：English  

DOI： 10.1016/j.alit.2021.08.012

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.15036/arerugi.71.926

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.15036/arerugi.71.85

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. JC pollen sublingual immunotherapy (SLIT) tablets are licensed for the treatment of JC pollinosis. OBJECTIVE: To assess the disease-modifying effects of JC pollen SLIT tablets over 5 years (2014-2019), comprising a 3-year treatment period and 2-year follow-up. METHODS: A total of 1042 patients with JC pollinosis (aged 5-64 years) were included in the study. An optimal dose-finding study was performed in the first 15 months, after which 240 patients in the placebo (P) group and 236 patients in the optimal active dose (A) group (5000 Japanese allergy units) were re-randomized to receive P or A for an additional 18 months (designated AA, AP, PA, and PP groups). Clinical efficacy was evaluated by the total nasal symptom and medication score (TNSMS) during the peak symptom period of each JC pollen season over 3 years of treatment and 2 years of observation after treatment cessation. RESULTS: The AA, AP, and PA groups exhibited significantly reduced TNSMS; however, the largest relative reduction was seen in the AA group both during the treatment period (third season, 46.3% vs PP, P < .001) and during the 2-year follow-up period (fourth and fifth seasons, 45.3% and 34.0% vs PP, respectively; P < .001). The most common adverse drug reactions were mild reactions at the administration site. CONCLUSIONS: JC pollen SLIT tablets show sustained clinical efficacy during 3 years of treatment and sustained disease-modifying effects for at least 2 years after treatment cessation.

DOI： 10.1016/j.jaip.2021.06.060

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DOI： 10.1016/j.alit.2021.08.012

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Japanese cedar pollinosis is an endemic disease affecting a large proportion of Japan's population. Five seasons have passed since sublingual immunotherapy (SLIT) for Japanese cedar pollinosis was included in the public insurance coverage in Japan. In this study, we evaluated the clinical effects of long-term SLIT for Japanese cedar pollinosis on upper respiratory symptoms primarily represented by nasal symptoms and inflammation of the respiratory tract in the 2019 season, in which considerable amount of cedar pollen was dispersed. METHODS: This study involved 95 patients who were undergoing SLIT for Japanese cedar pollinosis after the initiation at some point between 2014 and 2018, and this group of patients was compared with a control group comprising 21 patients receiving preseasonal prophylactic treatment (with a second-generation antihistaminic drug). We evaluated the patients' nasal/eye symptoms, total nasal symptom and medication score (TNSMS), and quality of life according to relevant guidelines. In addition, the levels of peripheral blood eosinophils, serum total IgE, Japanese cedar antigen-specific IgE, Cryj1-specific IgG4, and fractional exhaled nitric oxide (FENO) were measured as objective indices. RESULTS: From the fourth season (SLIT4), nasal discharge, sneezing, nasal obstruction symptoms, and TNSMS significantly decreased compared with those in the preseasonal prophylactic treatment and SLIT1 groups. In the patients suspected to have eosinophilic airway inflammation (with a baseline FENO ≥25 ppb), the interannual variability of FENO levels significantly reduced after 5 years of treatment. CONCLUSION: The efficacy of SLIT was noted from the first year of treatment, even in a year when pollen profusely dispersed. Thus, long-term continuous treatment with SLIT may alleviate nasal symptoms as well as eosinophilic airway inflammation.

DOI： 10.1016/j.anl.2021.01.003

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Language：English   Publishing type：Research paper (scientific journal)  

Owing to the successful application of sublingual immunotherapy (SLIT), allergen immunotherapy (AIT) has become one of the leading treatments for allergic diseases. Similar to the case with other AITs, such as subcutaneous and oral immunotherapies, not only the alleviation of allergic symptoms, but also the curing of the diseases can be expected in patients undergoing SLIT. However, how and why such strong efficacy is obtained by SLIT, in which allergens are simply administered under the tongue, is not clearly known. Various potential mechanisms, including the induction of blocking antibodies, T cell tolerance, regulatory B and T cells, CD103-CD11b+ classical dendritic cells, and CD206+ macrophages, and the reduction of innate lymphoid cells, mast cells, and basophils, have been suggested. Recently, through a comparative analysis between high- and non-responder patients of SLIT, we have successfully proposed several novel mechanisms. Here, we introduce our recent findings and summarize the current understanding of the mechanisms underlying the strong efficacy of SLIT.

DOI： 10.3390/pathogens10020147

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

In recent years, the number of patients with allergic rhinitis (AR), including Japanese cedar pollinosis (JCP), has increased. Dr. Baba conducted epidemiological surveys in 1998 and 2008 to investigate the prevalence of AR in Japan, using questionnaires for otolaryngologists and their families. We carried out same questionnaire survey to investigate the changes in the prevalence of JCP, perennial allergic rhinitis (PAR), and pollinosis other than JCP in 2019. The results of our survey revealed a prevalence of AR of 49.2%, and a prevalence of JCP of 38.8%. These rates represented marked increases over the previously recorded results. Furthermore, a marked increase in incidence of JCP was observed in the younger age groups.

DOI： 10.3950/jibiinkoka.123.485

Scopus

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Language：English   Publishing type：Research paper (scientific journal)  

Basophils were reported to be associated with allergy pathogenesis and the efficacy of allergen immunotherapy. Using a purified cedar allergen, we recently studied the effectiveness of sublingual immunotherapy for patients with Japanese cedar pollinosis. Patients were classified as high responders (HR) and nonresponders (NR), and comprehensive microarray analysis was used to examine peripheral basophils in both groups. A total of 153 genes were differentially expressed in HR and NR patients. Most of these differentially expressed genes encoded intracellular molecules, and expression levels were higher in HR patients than in NR patients. mRNA expression of the gene encoding D4, zinc, and double plant homeodomain (PHD) fingers family 2 (DPF2) was significantly correlated with copy number variation (CNV). Genetic variation in the DPF2 gene and its expression in basophils might be associated with the efficacy of sublingual immunotherapy.

DOI： 10.1272/jnms.JNMS.2020_87-104

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BACKGROUND: There have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. METHODS: This was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. RESULTS: The percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. CONCLUSIONS: Dual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses.

DOI： 10.1016/j.alit.2019.07.007

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Language：Japanese   Publisher：日本鼻科学会  

DOI： 10.7248/jjrhi.59.216

CiNii Research

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BACKGROUND: We conducted a randomized, placebo-controlled, double-blind clinical trial to investigate the optimal dose and long-term efficacy and safety of Japanese cedar (JC) pollen tablets for SLIT (JapicCTI-142579). Here, we report details of the effects of the JC pollen SLIT tablet on rhinitis and conjunctivitis symptoms over three pollen dispersal seasons. METHODS: A total of 1042 JC pollinosis patients (aged 5-64 years) were randomized to receive tablets containing placebo (P), 2000, 5000, or 10,000 Japanese allergy units (JAU) of JC pollen for 15 months to identify an optimal dose. Patients receiving P (n = 240) and the optimal dose (5000 JAU; A, n = 236) were then randomized to receive P or A for an additional 18 months (AA, AP, PA, and PP groups, allocation ratio 2:1:1:2). Nasal and ocular symptoms, rescue medication use, and quality of life (QOL) were assessed on quantitative scales. RESULTS: In the second and third seasons, the AA, AP, and PA groups exhibited significantly better improvements in nasal, ocular, and medication scores compared with the PP group in the order AA > AP > PA > PP during the second season and AA > PA > AP > PP during the third season. Rescue medication use and QOL scores were also significantly better in the AA, AP, and PA groups compared with the PP group. CONCLUSIONS: The JC pollen SLIT tablet relieved nasal and ocular symptoms and medication use and improved QOL in a treatment duration-dependent manner. Continuous dosing regimens appear to enhance the efficacy of the drug.

DOI： 10.1016/j.alit.2019.05.002

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DOI： 10.1016/j.alit.2019.03.007

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BACKGROUND: Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. The JC pollen sublingual immunotherapy (SLIT) tablet was developed using the highest concentration of JC pollen extract. OBJECTIVE: This was a randomized, double-blind, placebo-controlled phase II/III trial to investigate the optimal dose of the JC pollen SLIT tablet and examine long-term efficacy and safety for 3 years with the selected dose, and 2-year follow-up. METHODS: A total of 1042 patients with JC pollinosis (aged 5-64 years) were equally randomized into 4 groups and received daily treatment with 2,000, 5,000, or 10,000 Japanese allergy unit (JAU) or placebo. The primary end point was the total nasal symptom and medication score (TNSMS) during the peak symptom period in the first season. Key secondary end points were TNSMS for the JC pollen dispersion season and total nasal and ocular symptom and medication score for the peak symptom period and JC pollen dispersion season. RESULTS: For the primary end point, absolute reductions and relative mean reductions in TNSMS compared with placebo were 1.50 and 21.4%, 2.24 and 32.1%, and 2.18 and 31.2% for 2,000, 5,000, and 10,000 JAU, respectively (P < .001 in all groups). For all key secondary end points, efficacy was confirmed for all doses (P < .001 in all groups). The treatment was well tolerated. Long-term efficacy of 5,000 JAU was shown over the 3 years. CONCLUSIONS: The optimal dose of the JC pollen SLIT tablet was 5,000 JAU, with good efficacy and safety over a 3-year treatment period. This sustained effect was dependent on treatment duration.

DOI： 10.1016/j.jaip.2018.11.044

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.15036/arerugi.68.81

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Language：Japanese   Publishing type：Research paper (scientific journal)  

From the era of subcutaneous immunotherapy (SCIT) in 1960s, allergen immunotherapy (AIT) has been established as a highly effective and curable treatment for allergic diseases. Furthermore, the recent appearance of sublingual immunotherapy (SLIT) in which the complicated administration procedure in SCIT was improved has been causing paradigm shifts in the treatment of allergic rhinitis. During the long history of AIT, the mechanisms by which this therapy leads its strong efficacy have been investigated but not fully clarified yet. The production of blocking antibodies that interrupt allergen-IgE binding, normalization of Th1/Th2 balance, and introduction of regulatory T cells are the major candidate mechanisms, though there are several conflicting reports. In our recent clinical study of SLIT against Japanese cedar pollinosis, we also tried to elucidate its mechanisms. Especially by comparing high-responder and non-responder patients using integrated analysis with multiple data, not by comparing with a placebo control group using individual data, we have successfully identified several target molecules and cascades of SLIT. Herein, we would like to describe the potential mechanisms by which AIT exhibits its strong efficacy with referring our recent novel findings.

DOI： 10.1254/fpj.154.23

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Language：Japanese   Publisher：(公財)東京都福祉保健財団人材養成部職員研修室  

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Sublingual immunotherapy (SLIT) is an effective treatment for allergic diseases. However, the mechanism by which this therapy exhibits its efficacy has not been fully delineated. To elucidate the mechanisms of SLIT in the treatment of cedar pollinosis (CP), we performed a multivariate analysis of microarray data on mRNA expression in CD4⁺ T cells and basophils. Although 2-year treatment with SLIT using cedar extracts was effective in >70% of patients with CP, the remaining patients did not respond to this therapy. The mRNA expression levels in peripheral CD4⁺ T cells and basophils from both high- and non-responder patients before and after undergoing SLIT were comparatively studied using microarray analysis. By processing the data using serial multivariate analysis, an apoptosis pathway was extracted in both CD4⁺ T cells and basophils. Conclusively, the strong treatment effectiveness of SLIT in patients with CP may be caused by the induction of apoptosis in CD4⁺ T cells and basophils in these patients (Trial registry at University Hospital Medical Information Network Clinical Trials Registry Database, UMIN000016532).

DOI： 10.4168/aair.2018.10.5.562

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BACKGROUND: We have recently demonstrated that T cell-mediated nasal hyperresponsiveness (NHR) is a representative pathophysiological feature of allergic rhinitis (AR). Although several anti-allergic drugs are used for the treatment of AR, the efficacy of these drugs on T cell-mediated NHR have not been elucidated. In these studies we investigated the effects of dexamethasone (Dex), montelukast (Mk), and chlorpheniramine (Chl) on NHR in antigen-immunized and antigen-specific Th2 cell-transferred mice. METHODS: OVA-immunized BALB/c mice were treated with Dex, Mk, or Chl and challenged intranasally with OVA. We then assessed NHR, the number of inflammatory cells in the nasal lavage fluid (NALF), mRNA expression of Th2 cytokines in the nasal tissue, the population of CD3+CD4+ cells in the nasal lymphoid tissue (NALT), and antigen-specific serum IgE and IgG levels. Antigen-induced NHR and changes in antigen-specific T cells in the NALT were investigated in OVA-specific Th2 cell-transferred mice. RESULTS: Dex significantly suppressed antigen-induced NHR, inflammatory cell infiltration, and IL-4, IL-5, IL-6, and IL-13 expression in immunized mice. Chl was completely ineffective, and only IL-13 expression was suppressed by Mk. None of these drugs affected IgE and IgG production. Antigen-induced NHR and the increase in antigen-specific T cells in the NALT of Th2 cell-transferred mice were inhibited by Dex, but not by Mk or Chl. CONCLUSIONS: Steroids are effective for the reduction of NHR in AR by suppressing the accumulation of inflammatory cells, especially antigen-specific T cells.

DOI： 10.1016/j.alit.2018.05.002

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DOI： 10.1016/j.alit.2018.02.003

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BACKGROUND: Sublingual immunotherapy (SLIT) can improve the symptoms of allergic rhinitis and modify its natural history; however, its efficacy varies among patients. This study aimed to determine which factors modify the effect of SLIT through post hoc analysis of a previous phase 3 trial of standardized Japanese cedar (JC) pollen extract (CEDARTOLEN®). METHODS: The study included 482 patients who had previously completed a phase 3 trial during two seasons. The SLIT and placebo groups each contained 241 subjects. Because pollen dispersal differed in the two seasons, we identified good and poor responders from the SLIT group in the 2nd season. We compared patient baseline characteristics, changes in serum immunoglobulin, and severity of symptoms in the 1st season between good and poor responders, as well as between SLIT and placebo groups. RESULTS: When we compared the baseline characteristics of good and poor responders, a significant difference was observed in body mass index (BMI) such that the patients with BMI ≥25 presented with lower treatment efficacy. No significant difference was observed in correlation with any other factors or treatment-induced alterations of serum immunoglobulin levels. We found that 75.3% of the patients with moderate symptoms and 50.9% of the patients with severe or very severe symptoms in the 1st season met our criteria for good responders in the 2nd season. CONCLUSIONS: BMI might modify the effect of SLIT; however, other factors were not related clearly. The severity of symptoms in the 1st season of treatment does not predict that in the 2nd season.

DOI： 10.1016/j.alit.2017.07.005

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OBJECTIVE: This study aimed to investigate whether interactions between multiple serum cytokines may be implicated in the mechanism of action (MOA) of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. METHODS: A Tokyo Metropolitan Bureau of Social Welfare and Public Health-initiated clinical study of active SLIT involving 202 patients with Japanese cedar pollinosis was jointly conducted by Tokyo Metropolitan Institute of Medical Science and Nippon Medical School between 2006 and 2008. Fifty target cytokines were quantified in serum samples collected at 6 times from baseline to the end of the study, for 300 cytokine measurements in total, using Bio-Plex Pro Human Cytokine Group I/II Panels. Therapeutic outcome was assessed based on nasal symptom scores and quality-of-life questionnaire results. RESULTS: Fifty-five percent of patients were free of symptoms or reported symptomatic improvements by 2 grades or greater after 2 years of SLIT treatment, while 27% showed no improvement or worsening of symptoms. Thirty-eight patients who benefited the most from treatment (responders) as well as 37 patients who benefited the least from treatment (non-responders) were identified and their serum cytokine profiles were compared. Cluster analysis of the 300 cytokine measurements identified 6 cytokine clusters that were strongly correlated with a positive response to treatment, and this correlation was consistent throughout the treatment. CONCLUSION: Certain cytokine clusters are strongly correlated with a positive therapeutic outcome, suggesting they have a role in the MOA of immunotherapy.

DOI： 10.1272/jnms.JNMS.2018_85-40

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.15036/arerugi.67.914

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Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND/OBJECTIVE: As few reports are available on treatment goal for Japanese cedar pollinosis treated with allergen immunotherapy, therapeutic effect has to be assessed based on subjective symptoms in clinical practice. This research was conducted to investigate the informative treatment goal in clinical practice by using the results of TO-194SL phase III clinical trial. METHODS: In this investigation, correlation between total nasal symptom medication score (TNSMS), which was predefined as the primary endpoint, and secondary endpoints evaluated by severe symptom day, quality of life (QOL) score, and overall evaluation by subject, was firstly investigated. Based on the results, stratified analyses of the secondary endpoints to confirm relationships on the stratified results, TNSMS, and cedar season were performed. RESULTS: Correlation between TNSMS and evaluations which were severe symptom day, QOL score, and overall evaluation by subject was reasonably observed. TNSMS generally showed 3 or below (classified as mild) throughout the entire pollen season when these evaluations reached each threshold. CONCLUSIONS: The results of this investigation suggest that a few evaluation items would help patients to realize the therapeutic effects of allergen immunotherapy if they could be the treatment goal in clinical practice.

DOI： 10.15036/arerugi.67.938

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Sublingual immunotherapy (SLIT) is effective against allergic rhinitis, although a substantial proportion of individuals is refractory. Herein, we describe a predictive modality to reliably identify SLIT non-responders (NRs). We conducted a 2-year clinical study in 193 adult patients with Japanese cedar pollinosis, with biweekly administration of 2000 Japanese allergy units of cedar pollen extract as the maintenance dose. After identifying high-responder (HR) patients with improved severity scores and NR patients with unchanged or exacerbated symptoms, differences in 33 HR and 34 NR patients were evaluated in terms of peripheral blood cellular profiles by flow cytometry and serum factors by ELISA and cytokine bead array, both pre- and post-SLIT. Improved clinical responses were seen in 72% of the treated patients. Pre-therapy IL-12p70 and post-therapy IgG1 serum levels were significantly different between HR and NR patients, although these parameters alone failed to distinguish NR from HR patients. However, the analysis of serum parameters in the pre-therapy samples with the Adaptive Boosting (AdaBoost) algorithm distinguished NR patients with high probability within the training data set. Cluster analysis revealed a positive correlation between serum Th1/Th2 cytokines and other cytokines/chemokines in HR patients after SLIT. Thus, processing of pre-therapy serum parameters with AdaBoost and cluster analysis can be reliably used to develop a prediction method for HR/NR patients.

DOI： 10.1093/intimm/dxx034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

OBJECTIVE: Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR). METHODS: Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements. RESULTS: Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR. CONCLUSION: Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622).

DOI： 10.1016/j.anl.2016.07.021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOCIETY ALLERGOLOGY  

BACKGROUND: Bilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). METHODS: This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13). RESULTS: A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated. CONCLUSIONS: After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.

DOI： 10.1016/j.alit.2016.05.014

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Language：Japanese   Publisher：The Oto-Rhino-Laryngological Society of Japan, Inc.  

DOI： 10.3950/jibiinkoka.120.1381

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.15036/arerugi.66.788

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DOI： 10.15036/arerugi.66.960

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Objective: Sublingual immunotherapy (SLIT) appears to offer practical advantages for the treatment of allergic rhinitis (AR). Based on a review of the scientific literature, we present recommendations as guiding principles to administer SLIT safely.
Methods: Clinical questions concerning SLIT were prepared. Literature published between January 2003 and December 2012 was searched from PubMed, the Cochrane Library, and Japana Centra Revuo Medicina. Qualified studies were analyzed and the results were evaluated, consolidated, and codified. We answered 17 clinical questions and, based on this, presented evidence-based recommendations.
Results: Sublingual immunotherapy improved symptoms (e.g., quality of life [QOL]) and reduced medication scores in seasonal AR and perennial AR. Most SLIT-induced adverse effects were local oral reactions, although systemic adverse effects such as gastrointestinal symptoms, urticaria, and asthma are occasionally reported. There have been no reports of lethal anaphylactic reactions by SLIT. When SLIT is continued for 3-4 years, its effect persists long after discontinuation.
Conclusion: A correct diagnosis of AR and sufficient informed consent from patients are required before initiating SLIT. Sublingual immunotherapy should be continued for 3 years or longer. The initial administration of SLIT during the uptitration of an allergen vaccine and the general condition of patients are critical for the safe performance of SLIT. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2015.08.015

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1254/fpj.146.259

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background: Japanese cedar (JC) pollinosis is the most common seasonal allergic rhinitis in Japan. Standardized JC pollen extract is available for subcutaneous immunotherapy, but this treatment is limited by potentially serious side effects. The aim of this double-blind, randomized comparative study was to evaluate the efficacy and safety of standardized JC pollen extract in a new oral formulation (CEDARTOLEN (R), Torii Pharmaceutical Co., Ltd., Tokyo, Japan) for sublingual immunotherapy (SLIT) for JC pollinosis. Methods: A total of 531 subjects with JC pollinosis were randomized into 2 groups at a ratio of 1: 1 to receive daily sublingual administration of standardized JC pollen extract with a maintenance dose of 2,000 Japanese allergy units (JAU) or placebo for 2 consecutive pollen seasons. The efficacy was evaluated using the total nasal symptom and medication score (TNSMS) as the primary end point. Secondary end points included the total ocular symptom and medication score (TOSMS) and scores for individual symptoms and medication. Results: The TNSMS was significantly lower (p &lt; 0.0001) in the SLIT group than in the placebo group in the peak symptom period by 18 and 30% in the first and second seasons, respectively. All secondary end points were also significantly lower in the SLIT group in both seasons. No systemic anaphylaxis occurred. Conclusions: SLIT with daily administration of standardized JC pollen extract was effective for improving nasal and ocular symptoms of JC pollinosis and reducing the use of relief medication. The JC pollen extract was well tolerated with only local adverse events. (C) 2015 S. Karger AG, Basel

DOI： 10.1159/000381059

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.64.1136

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Objective: In anticipation of the development of guidelines for antigen-specific subcutaneous immunotherapy (SCIT), we present recommendations that can serve as guiding principles based on a review of the scientific literature.
Methods: Clinical questions (CQs) concerning SCIT were prepared. Literature searches for publications between January 1990 and February 2011 were performed in PubMed, the Cochrane Library, and Japana Centra Revuo Medicina Web version 4. Qualified studies were analyzed and the results were evaluated, consolidated, and codified.
Results: We present answers for 13 CQs on the indications, methods, effectiveness and mechanisms of SCIT, with evidence-based recommendations.
Conclusion: The guiding principles are intended to be applied to children (&lt;= 15 years old) and adults (&gt;= 16 years old) with allergic rhinitis (AR). These principles can be used by otorhinolaryngologists for diagnosis of AR, evaluation of severity and rhinoscopic findings, performance of antigen challenge tests, and management of systemic anaphylactic reactions associated with SCIT. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2013.06.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS  

Strenuous exercise reduces immune cell function and increases the risk of respiratory and gastrointestinal infections. In addition, it affects mood state and causes physical fatigue. Athletes require both mental and physical conditioning to execute good performance. In this study, we conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the immunopotentiation and fatigue-alleviation effects of Lactobacillus gasseri OLL2809 (LG2809) and alpha-lactalbumin (alpha LA) in university-student athletes after strenuous exercise. A total of 44 university students who performed strenuous exercise daily were separated into 3 groups to receive a 4-week course of placebo, 100 mg LG2809, or 100 mg LG2809 in combination with 900 mg alpha LA, respectively. Before and after each dietary treatment, the subjects performed strenuous cycle ergometer exercise for 1 h. Before and after each exercise session, blood samples and visual analogue scale scores for fatigue were obtained. In addition, the mood of each subject before and after the dietary treatment was evaluated using the Profile of Mood States (POMS) questionnaire. LG2809 ingestion was effective in preventing reduced natural killer cell activity due to strenuous exercise and elevating mood from a depressed state. In addition, LG2809 + alpha LA was found to alleviate minor resting fatigue, which was supported objectively by the significant reduction in the serum reactive oxygen metabolites and transforming growth factor beta 1 levels. These effects could be helpful for athletes to maintain mental and physical condition.

DOI： 10.1139/apnm-2012-0490

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOCIETY ALLERGOLOGY  

Background: Statistically significant results of medical intervention trials are not always clinically meaningful. We sought to estimate the minimal clinically important difference (MCID) (the smallest change in a given end-point that is meaningful to a patient) during seasonal alteration of Japanese cedar/cypress pollinosis (JCCP).
Methods: Results of a double-blinded, placebo-controlled trial of JCCP patients conducted between 2008 and 2010 were analyzed using an anchor-based method in which a face scale for Japanese rhinoconjunctivitis quality-of-life questionnaire (JRQLQ) was set as an anchor. MICDs were calculated as changes of average scores, including those for naso-ocular symptoms with 5 items in diary cards (T5SS), naso-ocular symptoms with 6 items (T6SS) and QOL with 17 items on the JRQLQ when face scale scores either improved or deteriorated by one point.
Results: In 2009 and 2010, 3,698 and 374, respectively, grains/cm(2) of pollens were dispersed. The MCIDs for T5SS in 2009 and 2010 were 1.426 (0.285 per item) and 1.441 (0.288), respectively. The MCIDs for T6SS were 4.115 (0.686) and 3.183 (0.531) in 2009 and 2010, respectively. The MCIDs for QOL were 10.469 (0.616) and 6.026 (0.354) in 2009 and 2010, respectively.
Conclusions: For T5SS in the diary, T6SS and QOL in JRQLQ, unit differences of 1.5 (0.3 per item), 3.6 (0.6) and 8.2 (0.5), respectively, were considered clinically meaningful by JCCP patients. The MCID for symptoms recorded in the diary was stable irrespective of the dispersed pollen level.

DOI： 10.2332/allergolint.13-OA-0570

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Language：Japanese   Publishing type：Research paper (scientific journal)  

We introduce evidence for the efficacy of allergen immunotherapy, including sub-cutaneous immunotherapy (SCIT) and sub-lingual immunotherapy (SLIT), which are used internationally now. There is not the exact methodology established methodology, but a lot of succesful case reports, so SCIT is still used in Japan. The effect is large enough by the proper SCIT method form its evidence including the meta-analysis data. However, judging from the care setting in Japan, various problems still need to be resolved. Therefore, the SLIT approach, which appears to be the more easy-to-adopt approach, has received much attention inotherco-untries. Comparison of these two currently used routes for immunotherapy is still much debated. There are a large number of patients and doctors that are willing to the safer SLIT in Japan. Practical use of SLIT for pollinosis caused by Japanese cedar pollen is expected to be introduced in 2014.

DOI： 10.5631/jibirin.106.769

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOCIETY ALLERGOLOGY  

Background: This study intended to assess the severity of Japanese cedar pollinosis using the Practical Guideline for the Management of Allergic Rhinitis in Japan (PG-MARJ) and the Allergic Rhinitis and its Impact on Asthma (ARIA) Guideline.
Methods: An Internet questionnaire survey of patients with pollinosis was conducted in mid-May 2011 and responses were obtained from 3382 individuals who had potential symptoms of Japanese cedar pollinosis from February to early May 2011 and who had experienced such symptoms for at least two pollen seasons.
Results: According to PG-MARJ, 23.5% of the respondents had severest rhinitis, 29.4% severe rhinitis, 31.3% moderate rhinitis, 13.8% mild rhinitis and 2.0% asymptomatic rhinitis. According to ARIA, 67.2% of them had moderate/severe persistent rhinitis, 23.8% moderate/severe intermittent rhinitis, 4.4% mild persistent rhinitis and 4.6% mild intermittent rhinitis.
Conclusions: Moderate to severe rhinitis was diagnosed in more than 80% of the respondents according to PG-MARJ, while moderate/severe rhinitis was diagnosed in more than 90% of the respondents according to ARIA. Most of the respondents suffered relatively severe pollinosis. More than 80% of the respondents had all the three major symptoms (i.e., sneezing, rhinorrhea and nasal blockage). Disagreement in the severity assessment between the two guidelines was noted in approximately 20% of the respondents.

DOI： 10.2332/allergolint.12-OA-0498

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR.
Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials. (C) 2012 Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.anl.2011.12.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OCEAN SIDE PUBLICATIONS INC  

Pranlukast (PLK) is a cysteinyl leukotriene receptor 1 antagonist approved for the treatment of bronchial asthma and allergic rhinitis in Japan. We previously reported that PLK dry syrup (DS) improved the total nasal symptom score, as well as sneezing, nasal discharge, and nasal obstruction scores over placebo. We investigated the efficacy of PLK DS with a noninvasive method in 10- to 15-year-old children with Japanese cedar (JC) pollinosis challenged with pollen allergen using an artificial exposure chamber (OHIO Chamber). Levels of eosinophil cationic protein (ECP) in nasal secretions, nasal obstruction score, and the relationship with nasal obstruction scores were analyzed. The estimated difference of means in ECP levels (PLK DS - placebo) was -22.9 micrograms (95% CI, -45.2 to -0.5), suggesting PLK DS reduced ECP significantly when compared with placebo (p = 0.0454). The difference in the least square means for nasal obstruction between the PLK DS and placebo was -0.25 (95% CI, -0.36 to -0.14) with a value of p &lt; 0.0001. In addition, a statistically significant, although weak, positive correlation between the nasal obstruction score and nasal ECP levels was observed with placebo treatment (correlation coefficient = 0.2394; p = 0.0428). Moreover, the inhibition rate of nasal ECP with PLK DS relative to placebo was statistically significant, although weak, positively correlated with the inhibition rate of nasal obstruction (correlation coefficient = 0.3373; p = 0.0219). PLK DS significantly decreases nasal ECP levels and nasal obstruction score compared with placebo in children with JC pollinosis challenged with pollen allergen. Suppression of mucosal eosinophilic inflammation is one of the pathways by which PLK DS improves pollinosis-induced nasal obstruction. (Allergy Asthma Proc 33:459-466, 2012; doi: 10.2500/aap.2012.33.3615)

DOI： 10.2500/aap.2012.33.3615

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OCEAN SIDE PUBLICATIONS INC  

Pranlukast (PLK) is a leukotriene receptor antagonist (LTRA) that has been approved for treatment of asthma in patients of all ages and allergic rhinitis (AR) in adults but not for AR in children in Japan. This randomized, double-blind, placebo-controlled, crossover study used an artificial exposure chamber (OHIO Chamber) to investigate the efficacy and safety of PLK in children from 10 to 15 years old with seasonal AR (SAR) due to Japanese cedar (JC) pollen. Eighty-four subjects were enrolled and randomized to the treatment arm and 74 were included in the per protocol set. Subjects received either PLK dry syrup (DS) or placebo for 1 week. They were challenged with JC pollen in the OHIO Chamber for 3 hours. Total nasal symptom scores (TNSSs) were recorded every 30 minutes during the exposure. PLK DS treatment suppressed the TNSS changes from baseline significantly when compared with placebo. The difference in the least square means in TNSS between the PLK DS treated group and placebo group was -0.37 (95% CI, -0.54, -0.20) with a value of p &lt; 0.0001, showing that PLK DS significantly suppressed the nasal symptoms. Regarding specific nasal symptoms, PLK DS significantly suppressed sneezing, nasal discharge, and nasal obstruction. The effect of PLK DS on nasal obstruction was most prominent, with significant improvement relative to placebo beginning 60 minutes after the start of exposure. No serious adverse events were reported during the study. In this study, PLK DS is effective and safe for treatment in children with SAR. (Allergy Asthma Proc 33:102-109, 2012; doi: 10.2500/aap.2012.33.3517)

DOI： 10.2500/aap.2012.33.3517

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OBJECTIVE: The study objective was to investigate the prophylactic efficacy of montelukast (MLK) 10 mg in suppressing seasonal allergic rhinitis (SAR) symptoms induced by Japanese cedar (JC) pollen and to determine how many days before exposure to JC in the artificial exposure chamber (OHIO chamber) would be optimal to start administration. METHODS: This was a single-institution, double-blind, randomized placebo-controlled four-group parallel inter-group comparison study. Adult volunteers with JC pollinosis were divided into four groups: an MLK 7-day administration group (n = 27), an MLK 3-day administration group (n = 27), an MLK 1-day administration group (n = 26), and a placebo group (n = 26). The mean change in total nasal symptom scores (nasal obstruction, nasal discharge and sneezing) (TNSS) and each of the nasal symptom scores during exposure of JC pollen in the OHIO chamber were investigated. RESULTS: The mean change in TNSS was significantly lower in the MLK treatment group, regardless of the number of days of administration, than in the placebo group (p = 0.0192). The results for the individual nasal symptoms showed that nasal obstruction was significantly suppressed in the 1-day administration group as compared with placebo (p = 0.0076), but no differences were found in sneezing score between any of the groups. For nasal discharge, we found a trend towards the effect clearing up after 3 days of administration. No serious adverse events were observed during the study. CONCLUSION: Although this study was acute and this artificial exposure model was conducted out of the pollen season, nasal symptoms that developed in the pollen exposure chamber, especially nasal obstruction, were significantly suppressed by starting oral administration of MLK 10 mg at least 1 day before exposure. These results suggest that prophylactic administration of MLK is effective and safe in the treatment of SAR.

DOI： 10.3109/21556660.2012.728547

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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OBJECTIVE: In practical guidelines for management of allergic rhinitis in Japan, pranlukast is a leukotriene receptor antagonist recommended for the treatment of pollinosis. However, the effect of pranlukast on nasal symptoms for cedar pollinosis has not been thoroughly investigated. The aim of this study is to examine this effect in a double-blind controlled crossover study using a pollen challenge chamber (the OHIO Chamber) developed in Japan. RESEARCH DESIGN AND METHODS: A total of 39 patients with cedar pollinosis were targeted. The subjects were exposed to a specific amount of cedar pollen (8000/m(3)) in the OHIO Chamber during the non-cedar pollen season. Efficacy of pranlukast for the treatment of artificially induced nasal symptoms was compared with that of a placebo using the crossover method. Pranlukast was administered orally for 3 days, after dinner on the day before cedar pollen exposure, after breakfast and after dinner on the day of cedar pollen exposure, and after breakfast on the following day. Pollen testing was carried out twice, with a 1-week wash-out interval. CLINICAL TRIAL REGISTRATION: The University Hospital Medical Information Network in Japan (UMIN), number UMIN000001282. MAIN OUTCOME MEASURES: The effect of pranlukast was evaluated using self-rating of nasal symptoms by the subjects. RESULTS: All 39 subjects demonstrated a positive skin reaction to cedar pollen by a positive CAP-RAST score (class 2 or higher) within the last 3 years, and experienced aggravated congestion during the cedar pollen season for more than 2 years. Nasal congestion was inhibited significantly in the pranlukast group compared to the placebo group during cedar pollen exposure. Furthermore, pranlukast significantly inhibited nasal congestion compared to the placebo on the day after exposure and on the following day. CONCLUSIONS: The effect of pranlukast on cedar pollinosis indicates immediate action, and such an effect could take place continuously after cedar pollen exposure. These results demonstrate that pranlukast is effective for the relief of congestion due to pollinosis.

DOI： 10.3109/21556660.2012.703630

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Among the gramineae species, orchard grass is a typical causative pollen that provokes seasonal rhinitis. The purpose of this study was to examine the protective efficacy of epinastine hydrochloride for signs and symptoms caused by repeated nasal provocation with discs containing orchard grass pollen. Methods: A single-dose, placebo-controlled, double-blind, crossover clinical study was conducted in subjects with orchard grass pollinosis. The pollen challenge was conducted with the use of provocation discs containing orchard grass pollen. Results: Epinastine hydrochloride suppressed nasal symptoms caused by nasal provocation tests using orchard grass pollen discs. Among the nasal symptoms, the number of sneezing was significantly inhibited 30 minutes and 60 minutes after the administration of epinastine hydrochloride, as compared with placebo. There were no adverse reactions to the study drugs. Conclusions: Our results suggest that nasal provocation tests with discs containing orchard grass pollen is a useful method for evaluating the onset of action of antiallergic drugs. As compared with placebo, epinastine hydrochloride decreased early-phase sneezing and the total nasal symptom score after repeated nasal provocations with orchard grass pollen discs. © 2011 Japanese Society of Allergology.

DOI： 10.2332/allergolint.10-OA-0219

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Leukotriene receptor antagonists (LTRAs) are effective for prophylactic treatment of pollinosis based on studies showing that administration of LTRAs prior to or at the start of the pollen season reduces symptoms and QOL disturbance at the peak of pollen dispersal. Two goals of prophylactic treatment of pollinosis are use of fewer types of drugs and delay of onset of symptoms and impairement of QOL. Therefore, this study was performed to determine if pranlukast, a LTRA, met these goals in treatment of pollinosis. Methods: Pranlukast or placebo was administered to patients who visited our hospital immediately before the start of Japanese cedar pollen dispersal. The study was performed for 4 weeks as a double blind randomized trial. Subsequently, all patients were given pranlukast for a further 4 weeks from the peak until the end of pollen dispersal. The incidence of symptoms and use of concomitant drugs were investigated from daily nasal allergy records kept by patients. QOL was evaluated using the JRQLQ questionnaire. Results: In the double blind period of the study, the percentage of patients who used concomitant drugs for nasal symptoms was significantly lower in the pranlukast group compared to the placebo group. Development of nasal symptoms (sneezing, runny nose and nasal congestion) and disturbance of daily activities were significantly delayed in the pranlukast group. No serious adverse reactions occurred in the pranlukast group and no patient withdrew from treatment with pranlukast. Conclusions: Pranlukast is effective for prophylactic treatment of pollinosis. © 2011 Japanese Society of Allergology.

DOI： 10.2332/allergolint.10-OA-0285

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Background: Dexamethasone cipecilate is a corticosteroid nasal spray whose local efficacy durability has been improved by introduction of a liposoluble functional group to its chemical structure. This study was conducted to evaluate the efficacy of once-daily treatment with this drug in patients with perennial allergic rhinitis by a challenge test with house dust antigen (Phase I clinical pharmacology study).
Methods: This study was designed as a randomised placebo-controlled double-blind study in 28 patients with perennial allergic rhinitis. Either 200 mu g dexamethasone cipecilate or placebo was administered once daily for 7 days, and the antigen challenge test conducted 23 h after the dose on each day. We evaluated the efficacy primarily through assessment of suppression of immediate nasal symptoms.
Results: When efficacy durability was evaluated by physicians based on a general assessment of the effects of suppression of nasal symptoms, the percentage of patients with efficacy lasting for 24 h differed significantly between the dexamethasone cipecilate group (69.2%, 9 out of 13) and the placebo group (15.4%, 2 out of 13) (p = 0.015).
Conclusions: Dexamethasone cipecilate was shown to be a corticosteroid having sustainable local efficacy. The results suggest that once-daily administration of dexamethasone cipecilate is effective in patients with allergic rhinitis, and that its efficacy lasts for 24 h.

DOI： 10.1517/13543784.2010.531258

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Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the 2 forms of desensitization for allergic diseases which are used internationally. Despite the lack of sufficient evidence of the mechanism, SCIT has been used in Japan. When SCIT is performed appropriately, it is effective for allergic rhinitis, as supported by high-level evidence, including the results of meta-analysis. However, its use in Japan has not become widespread due to various problems, including the risk of anaphylaxis. Therefore, attention is being focused on SLIT because it is easier to perform but may be similarly effective and has been extensively discussed and evaluated internationally. Comparison of SCIT and SLIT can only be done with some allergen, which has also been discussed extenesively. Many patients and physicians would welcome the use of SLIT in Japan, and its first use against pollinosis due to Japanese cedar pollen is planned for 2014.

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Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.61.206

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A randomized, double-blind, placebo-controlled clinical trial was conducted to determine whether oral administration of heat-killed Lactobacillus gasseri OLL2809 would affect the immune response and reduce the symptoms of Japanese cedar pollinosis (JCP) in subjects with JCP. Following a 1-week pre-observation period, the subjects were randomly divided into two groups and were orally administered a placebo or tablets containing 100 mg of L. gasseri OLL2809 per d for 8 weeks during the pollen season in 2007. The results showed no obvious differences between the groups. Supplementary subgroup analysis revealed that the OLL2809 subgroups with CAP-RAST scores of 4 or 5 exhibited improvement in nasal symptoms scores and serum allergy-related items, including Japanese cedar pollen-specific IgE levels. L. gasseri OLL2809 was found to be effective in reducing symptoms in subjects with a high predisposition to allergies by modulating systemic immune systems.

DOI： 10.1271/bbb.90144

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Objective: To investigate the efficacy and safety of bepotastine, we conducted a randomized, investigator-blind, placebo-controlled and parallel study to evaluate the allergic symptoms and the cognitive function of the subjects with Japanese cedar (JC) pollinosis in response to JC pollen exposure in an artificial exposure chamber. Methods: Twenty-four volunteers with JC pollinosis were enrolled in this study. The subjects were randomly divided into two groups: a bepotastine group and a placebo group (12 subjects each). Subjects received either a 10-mg bepotastine OD (orally disintegrating) tablet or a placebo 10 min before entering the chamber for a 3-h exposure. The nasal and ocular symptoms were evaluated by each patient at regular intervals. The amount of nasal discharge was measured and the number of sneezes recorded. To evaluate the cognitive function, a digit cancellation test (D-CAT), in which the subjects have to eliminate certain numbers within a fixed time, was conducted. Results: Twelve subjects in the placebo group developed nasal and/or ocular symptoms, whereas six subjects in the bepotastine group showed none of the symptoms during exposure. Mean secretion weights and number of sneezes were significantly lower in the bepotastine group than in the placebo group. In D-CAT, no deterioration of work performance was observed in the bepotastine group. No adverse effects were observed in either group. Conclusion: Bepotastine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to JC pollen in an exposure chamber.

DOI： 10.1517/14656560902758368

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Background: An artificial exposure chamber (OHIO Chamber), which allows dispersal of a fixed concentration of Japanese cedar (JC) pollen under stable conditions, was constructed. This study was conducted to identify the exposure conditions assuring validity of the clinical tests conducted using this chamber. Methods: Twenty-four adult patients with JC pollinosis were exposed to different concentrations of JC pollen: 0 (only during the summer period), 4,000, 8,000 and 12,000 grains/m(3), and the nasal and ocular symptoms were self-assessed during a 4-hour period of exposure. The amount of nasal discharge was measured and the sneezing frequency was recorded. This study was conducted twice during the summer and winter periods, i.e. non-pollen seasons. The reproducibility of the symptoms between the two seasons was assessed. Results: None of the subjects developed any symptom at the pollen concentration of 0 grains/m(3). No significant differences in the time to the onset of symptoms were found between the summer and winter study, regardless of the pollen concentration. There were no significant differences between the summer and winter study in the total symptom score and total nasal symptom score at any pollen concentration, suggesting the very favorable reproducibility of symptoms. Conclusions: Efficient and reproducible results are obtained in patients exposed to JC pollen in the OHIO Chamber. The results suggest the conditions of JC pollen exposure have scientific validity and the OHIO Chamber has the potential to contribute significantly to basic and clinical studies of JC pollinosis. Copyright (C) 2009 S. Karger AG, Basel

DOI： 10.1159/000189197

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Language：English   Publisher：Japanese Society of Allergology  

The prevalence of pollinosis caused by cedar pollen has increased by 10% these ten years of 26.5% in the investigation of 2008 in Japan. The pharmacotherapy is a main treatment tool for pollinosis, and the surgical treatment is not acknowledged to the treatment of pollinosis internationally. Moreover, allergen immunotherapy enters a special treatment method, and is an important therapeutic procedure. The allergen immunotherapy is unique for having possibility of curing allergen specific allergic diseases. However the side effect of allergen subcutaneous immunotherapy (SCIT), such as anaphylaxis is kept at a distance in a medical situation in Japan. Then, a sublingual immunotherapy (SLIT) that was safer than it, developed in Europe for pollinosis induced by grass or ragweed, but not in Japan. As a result, the effect of SLIT was proven in the cedar pollinosis in Japan as high level evidence. A whole body immunity induction is thought in the appearance of the effect, and, in addition, it is necessary to be going to be cleared the accurate mechanism of the effect in the future. Moreover, the development of a special SLIT and the import of an overseas product are needed in Japan. © 2009 Japanese Society of Allergology.

DOI： 10.2332/allergolint.08-RAI-0072

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Background: In recent years, many countries have experienced an increase in the prevalence of allergic rhinitis. No effective approach is currently available to prevent the onset of symptoms in allergic individuals. Pranlukast, a leukotriene receptor antagonist with a good safety and efficacy record for the management of allergic inflammation, may be appropriate for early intervention in the management of pollinosis. Objective: To investigate the efficacy of pranlukast as an early intervention in the control of cedar pollinosis. Methods: In a double-blind comparative study, pranlukast (n=102) or placebo (n=91) was administered to cedar pollinosis patients immediately before the start of the dispersion season and continued for 4 weeks. Subsequently, pranlukast was administered to all patients for 2 weeks until the end of the cedar pollen dispersion season (mid-March). All patients were carefully monitored for severity of nasal symptoms, symptom scores, medication scores, symptom-medication scores, and quality of life (QOL). Results: Compared with placebo, therapy with pranlukast before and during the dispersion of cedar pollen in these patients significantly improved nasal symptoms (paroxysmal sneezing, rhinorrhea, and nasal congestion), symptom scores, and symptom-medication scores. The drug also significantly reduced deterioration of QOL, and improved nasal symptoms and QOL throughout the dispersion period. Conclusion: Administering pranlukast immediately before the beginning of cedar pollen dispersion is effective in reducing symptoms of allergic rhinitis throughout the dispersion period. © 2009 Esmon Publicidad.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Lactobacillus gasseri OLL2809 strongly stimulates the production of interleukin (IL)-12 (p70) by innate immune cells. Thus, it is expected to ameliorate allergic diseases. We investigated whether the oral administration of heat-killed L. gasseri OLL2809 suppressed eosinophilia in cedar pollen antigen-challenged mice. Methods: BALB/c mice sensitized with Japanese cedar pollen extract were intraperitoneally challenged with the same extract. The mice were orally given heat-killed L. gasseri OLL2809 at doses of 0.5, 1, or 2 mg/day throughout the experimental period (21 d). After 24 hours of the challenge, the eosinophil number and cytokine levels in the peritoneal lavage fluid and the serum antigen-specific IgG levels were determined. Results: On administering varying amounts of heat-killed L. gasseri OLL2809, the number of eosinophils among the total number of cells was significantly reduced in all groups. In addition, the eosinophil number significantly decreased, and the eosinophil-suppression rate significantly increased by 44% in the 2-mg group. Although the serum immunoglobulin (Ig) G2a and IgG1 levels were not affected, the IgG2a/ lgG1 ratio increased significantly in the 2-mg group compared with that of the control group. Furthermore, the administration of heat-killed L. gasseri OLL2809 resulted in the induction of IL-2 and reduction in granulocyte-macrophage colony-stimulating factor levels in peritoneal lavage fluid. Conclusions: We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis. © 2008 Japanese Society of Allergology.

DOI： 10.2332/allergolint.O-08-541

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollen is a substantial problem in Japan. Sublingual immuno-therapy (SLIT) is safer than conventional antigen-specific immunotherapy, the only treatment modality by which complete cure of the disease can be expected. We investigated the safety and efficacy of SLIT in the treatment of cedar pollinosis patients compared to placebo. Methods: A randomized, placebo-controlled, double-blind study was conducted in 61 cedar pollinosis patients. Increasing doses of standardized Japanese cedar extract or placebo were administered sublingually in intervals ranging from daily to once a week after six weeks. The primary efficacy variable was the mean of the daily total symptom scores (TSS) during the pollen dispersing period. Secondary efficacy variables included the QOL scores and related variables. Results: Primary efficacy variable scores were significantly lower for some days in the SLIT group than in the placebo group (P &lt
.01 or P &lt
.05). Secondary efficacy for the QOL score in SLIT group was almost of half of placebo group. There was no significant difference in the overall incidence of side effects between the SLIT group and the placebo group. Conclusions: SLIT was effective and safe in the treatment of cedar pollinosis. © 2008 Japanese Society of Allergology.

DOI： 10.2332/allergolint.O-07-514

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: A pollen exposure chamber (OHIO Chamber) was built in central Tokyo, Japan, in order to study seasonal allergic rhinitis (SAR). Since satisfactory outcomes were obtained from the controlled pollen exposure at the chamber, we conducted preliminary studies in volunteers with SAR. Methods: Ten volunteers with SAR sensitive to Japanese cedar (JC) pollen were enrolled in this study. In order to investigate the intranasal and intraocular pollen number, volunteers were initially exposed to a low concentration of JC (2500 grains/m3) for at most 1 hour in this chamber. Before and after the exposure, nasal cavities and eyes were washed with 100 ml and 25 ml of saline, respectively. Nasal and eye washing solutions were collected and the number of JC pollen was counted. After 3 hours the volunteers were subsequently exposed to a moderate concentration of JC (4500 grains/m3) for 2 hours. Subjective nasal and ocular symptoms were recorded and the amount of nasal secretion was measured during the allergen exposure periods. Results: During the initial exposure, all volunteers except one stayed in the chamber for 1 hour without any nasal or ocular symptoms. The number of pollen in the nose and eyes was 249.2 ± 120.9 and 13.6 ± 13.6 grains, respectively. During the subsequent 2-hour exposure to JC pollen, nasal and ocular symptoms developed gradually in a time dependent manner in all the volunteers except one. Conclusions: This is the first clinical study using Japanese cedar pollen under well-controlled conditions in the OHIO chamber in which the induction of allergic symptoms was observed. The OHIO chamber will be useful for studying allergic rhinitis in Japan. ©2007 Japanese Society of Allergology.

DOI： 10.2332/allergolint.O-06-453

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We report the case of a 59-year-old man with meningeal carcinomatosis (MC) who presented with peripheral facial palsy and progressive sensorineural deafness. The patient had been operated on for gastric cancer 1 year previously, and no metastases had been detected in the retroperitoneum or thorax at follow-up examination 1 year later. However, he developed headache, deafness, and peripheral facial palsy and was referred to us for further evaluation, as magnetic resonance of the head had shown no abnormalities. Ramsay Hunt syndrome was suspected, but no increase in the cerebrospinal fluid cell count was detected. On the other hand, the balance test suggested a central disorder. In addition, the plasma level of carcinoembryonic antigen suddenly increased, suggesting MC. The cerebrospinal fluid was examined several times
in the end malignant cells and an increase in the cell count were detected, and the diagnosis of MC was established.

DOI： 10.1272/jnms.73.240

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Epinastine hydrochloride and fexofenadine hydrochloride, the second-generation antihistamines, are largely used in the indication of allergic rhinitis in Japan. The purpose of this study was to compare the protective efficacy of epinastine hydrochloride or fexofenadine hydrochloride using a nasal provocation test with Japanese cedar pollen allergen. Methods: A single-dose, placebo-controlled, single-blind crossover clinical study was conducted in patients with Japanese cedar pollinosis. The pollen exposure was done by the antigen provocation by disc method and involved repeated provocation five times per day. Results: Among the active agents studied-epinastine hydrochloride and fexofenadine hydrochloride-epinastine hydrochloride significantly decreased the number of sneezing attacks and the quantity of nasal discharge for 3 hours after drug administration compared with placebo, a finding supported by the quantity of nasal discharge in the nasal findings. In this study, fexofenadine hydrochloride showed no significant difference compared with placebo. Conclusions: This study demonstrates better protection with epinastine hydrochloride than with fexofenadine hydrochloride or placebo in a nasal provocation test with Japanese cedar pollen allergen. ©2006 Japanese Society of Allergology.

DOI： 10.2332/allergolint.55.261

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Language：English   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.55.345_1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT RHINOLOGIC SOC  

The incidence of Japanese cedar pollinosis is estimated to be about 13% of the Japanese population. In Japan it is generic to wear a facemask and eyeglasses to prevent pollen inhalation. We examined the usefulness of a facemask and eyeglasses in cooperation with volunteers. The number of pollen particles in the nasal cavity and on the conjunctiva was unchanged by wearing a facemask and eyeglasses. However, the pollen invasion rate was lower in subjects with a facemask and eyeglasses than in subjects without a facemask and eyeglasses. The decrease in pollen invasion rate in the nasal cavity due to wearing a facemask was statistically significant. This suggested that wearing a facemask has a protective effect on pollen invasion to the nose. The pollen invasion rate in the nasal cavity and on the conjunctiva was increased with increases in the wind speed. It may be difficult to avoid pollen even when wearing a facemask and eyeglasses when the wind speed is high. Further study is required to clarify the relationship between the amount of allergens and clinical symptoms.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Background: Based on subjective symptom, it has been documented that so high as 21 to 62% of patients with Japanese cedar pollinosis has pollinosis symptom before the start of pollen season. Since this is not objectively evidenced, we aimed to clarify whether or not it is true. Method: We quantified intranasal pollen by means of our nasal lavage method in patients with Japanese cedar pollinosis shortly after the onset of symptom during pre-, mid- and post-season from 1997 to 2005. Result: Significant differences in intranasal pollen count were revealed among mid- and pre- and post-season. Intra-nasal pollens, so few as 1 or less, were found in 67.8% of patients having pre-seasonal symptom, while in 12.5% during the mid-season. The majority of patients had not sufficient number of intra-nasal pollen to induce pollinosis. However, the intranasal pollen counts in preseason were related well with total airborne pollen amount in next spring. Pollens other than Japanese cedar pollen were also detected in lavages. Conclusion: Many factors such as method of pollen survey, personal nasal hyper- reactivity and irritation by cold air, or with pollens other than Japanese cedar may cause the pre-seasonal pollinosis symptom. High frequencies of pre-seasonal onset in previous reports may be over- estimated due to inaccurate diagnosis of Japanese cedar pollinosis.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background: Although currently in its infancy, quality of life (QOL) research in Japan is rapidly expanding and is expected to become a standard outcome measure in clinical trials. In Japan, QOL has not previously been assessed in patients with allergic rhinitis (AR); we report the first clinical study applying the recently validated Japanese translations of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) Questionnaire to assess the effects of the oral antihistamine, fexofenadine, on QOL and work productivity due to cedar pollinosis. Patients and Methods: A randomized, double-blind, placebo-controlled, single-site study was conducted during the peak cedar pollinosis season in Japan. After a 7-day run-in period, subjects were randomized to receive fexofenadine HCl 60 mg twice daily (bid) or placebo for 2 weeks. Results: Overall, 206 Japanese subjects with AR were included in the intention-to-treat population (fexofenadine, n = 104, and placebo, n = 102). Fexofenadine statistically significantly improved overall QOL compared with placebo (p = 0.005) and improvements were reported in the RQLQ domains: activities (p = 0.047), practical problems (p = 0.003), nasal symptoms (p = 0.003) and eye symptoms (p less than or equal to 0.001). Clinically significant improvements in practical problems, eye symptoms and activity limitations, exceeding the 0.05 level, were observed with fexofenadine. These improvements in QOL were associated with significant symptom relief (p ! 0.001 vs. placebo). Improvements in impairment at work were also reported with fexofenadine. Conclusion: In Japan, this is the first clinical study to show that fexofenadine HCl (60 mg b.i.d.) improves overall QOL and work productivity in patients with seasonal AR using validated Japanese instruments. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000083322

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Patient satisfaction is recommended as a parameter to evaluate medical care from the aspect of patient. Currently, we developed a new patient satisfaction questionnaire in allergic rhinitis by means of internationally standardized psychometric validation and reliability studies. Using this questionnaire, we evaluated patient satisfaction with Japanese cedar pollinosis in 2004, who visited our own clinic (JAAC) or patients, who were sampled from the list of a health research company (JSR), in addition of literature data. As a result, there were marked differences between ours and others. The purpose of this study is to elucidate whether or not our questionnaire has a good and reliable clinical validity, and, if yes, why there were marked differences in various studies. The satisfaction (very good plus good) was 94.4% in the JAAC group and 41.2% in the JSR group respectively. We compared the mean scores of each item in questionnaire in both groups, and found higher scores in the majority of items in the former group than the latter group in accordance with difference in satisfaction. This suggested a good clinical validity in questionnaire. In nasal treatment modality, the JAAC group was characterized by continuous use of combined topical steroid with per oral anti-allergic compound and immunotherapy during whole pollen season, when compared with the JSR group. A persistent contact with patients in immunotherapy plays an important role in establishing good doctor-patient relation and treatment outcome, resulting in increased patient satisfaction.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

Background: Although subcutaneous immunotherapy may cure allergic diseases, it is not commonly used in Japan because of the pain and risk of anaphylactic shock. Sublingual immunotherapy(SLIT)overcomes these limitations and although it is the most advanced form of local immunotherapy for clinical application, it is not used in Japan nor has it been extensively studied. Methods: After obtaining approval from the Ethics Committee of Nippon Medical School and informed consent from five patients with cedar pollinosis(one man, four women
age range, 38-66 years), administration of a therapeutic extract was started in July 2001 or later(mean treatment period, 13.4 months). The clinical efficacy of SLIT and its influence on the quality of life, as measured by the Japanese Allergic Rhinitis QOL Standard Questionnaire, and the incidence of side effects were evaluated in 2003. Results: Between February and April the mean severity score was 1.44 in the patients undergoing SLIT and 1.86 in the patients undergoing pharmacotherapy, and the respective mean QOL total scores during the season were 3.82 and 10.0. Neither systemic nor local side effects occurred during SLIT. Conclusions: SLIT is safe and effective for Japanese cedar pollinosis. ©2005 Japanese Society of Allergology.

DOI： 10.2332/allergolint.54.167

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Background: Nasal symptoms such as sneezing, stuffy nose and runny nose occur in allergic and non-allergic rhinitis. Normal nose also sometimes has these symptoms. It is necessary to define what is the symptom of normal nose in order to make a proper diagnosis of rhinitis, grading of severity of nasal symptom in rhinitis and criteria of normalization after the treatment of rhinitis. Methods: 235 persons who had no perceptive nasal symptom and history of nasal disease at present and past, and cold at present, were sampled from the registered list of a health care organization, and examined their nasal symptom by mailing a self-administered questionnaire of nasal symptom. In addition, 54 patients, who visited 4 otolarngology clinics due to diseases other than rhinitis and were diagnosed as normal nose, were examined, using the same questionnaire. Results: Response rate from persons mailed was 49.8%. Nasal symptom was infrequent in patients at clinic more than persons sampled from the list. Nasal symptom in 117 responders with normal nose had none or occasional and momentary stuffy nose. Sneezing and/or nose blow was less than 5 times a day, and itchy nose and postnasal drip were 30% and 25% respectively. These symptoms, if appeared, were less than 4 days per week. Conclusion: Grading "minus", normal, is zero in sneezing and runny nose and none in stuffy nose in the grading system of nasal symptom used commonly in Japan. These should be changed to none or occasional, momentary, easily tolerable in stuffy nose, less than once a day or grading "plus one" (1-5 times per day) occasionally in sneezing and nose blow. Normalization after treatment could be defined according to this change.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Objective: To clarify natural airborne Japanese cedar pollen contamination of clothes (cotton made T shirt and cap) and face skin for preventive strategy against pollinosis. Methods: Ten non-pollinosis high school students, wearing T-shirt and cap, stayed after face washing in outdoor (school yard) and in-door (school room) for 2 hours alternatively. Wet clothes of each of three different qualities (cotton, cotton blended polyester and wool) were also left at ten points of the schoolyard. Contaminated pollens were collected using adhesive tape and counted under a microscope. Results: Pollen contaminations were lesser in school room than school yard. Lesser contamination was revealed on the surface of cotton-polyester blended clothes without statistical difference when compared with cotton and wool made clothes. Conclusion: From this study, in going out wearing of cotton-polyester blended coat and cap, and after returning home, face washing and keeping coat and cap on a hanger at entry hall are recommended for pollen prevention.

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Language：English   Publishing type：Research paper (international conference proceedings)  

The prevalence of childhood allergic rhinitis is increasing steadily in Japan. Affected children are sensitized mainly by house dust mites
however, the prevalence of Japanese cedar pollinosis (JCP) in children is also on the rise. To ascertain the prevalence and current status of JCP in Japanese children, a retrospective analysis of a nationwide cross-sectional random sampling study was conducted. The survey, conducted shortly after the peak pollen season, was performed by self-evaluation questionnaire in 2001. Data from children aged under 15 years were collected and analysed. In these subjects, the response rate was 75.1%. The prevalence of JCP was 10.2% in children. Rhinorrhoea was the severest symptom reported
19.5% had severe or moderate interference with daily activities and consulted physicians. Few children used prescribed drugs and some took measures to avoid contact with allergens.

DOI： 10.1111/j.1472-9725.2004.00026.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

Background: The aim of the present survey was to investigate the changes associated with fexofenadine administration in the quality of life (QOL) of Japanese cedar pollinosis patients. Methods: After obtaining informed consent, volunteers suffering from Japanese cedar pollinosis were divided into two groups: (i) the fexofenadine group (2 × 60 mg/day)
and (ii) the placebo group. Changes in QOL were examined after administration for 14 days (randomized, double-blind comparison study). The study period was from 27 February to 13 March 2003. Subjects were recruited from the Tokyo metropolitan area
104 were randomized to the fexofenadine group and 103 were randomized to the placebo group. The QOL was evaluated using the Japanese Allergic Rhinitis Standard QOL Questionnaire (JRQLQ no. 1). The JRQLQ is structured to evaluate six domains of usual daily activities, outdoor activities, social functioning, sleep problems, general physical problems and emotional function, as well as the overall QOL. Results: On the 14th day after the start of fexofenadine or placebo administration, the QOL was improved in all domains of the JRQLQ in the fexofenadine group, whereas it had worsened in all domains, except outdoor activities, in the placebo group. The overall evaluation of QOL was significantly more favorable in the fexofenadine group on the 14th day after the start of administration. Conclusions: The present study showed that fexofenadine administration suppressed the deterioration of overall QOL and alleviated the interference with daily life in patients suffering from Japanese cedar pollinosis.

DOI： 10.1111/j.1440-1592.2004.00341.x

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Japanese cedar pollinosis is a major public health problem in Japan because of its severe symptom and high prevalence. However, patient satisfaction by treatment is poor according to current reports. As the treatments, pre-seasonal medication and single peroral anti-allergic drug on demand are frequently used in Japan. Against conventional methods, we treated 301 patients with Japanese cedar pollinosis by persistent use of combined drugs (topical steroid, peroral anti-allergic drug and eye drop) without pre-seasonal medication in 2003. Immunotherapy was also used in 90 patients treated. As a result, 97% of patients was satisfied in this treatment and immunotherapy contributed to reduction in the amount of drug and high treatment outcome.

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Language：Japanese  

It is approved that ENT doctors are specialist for pollinosis. Is it true from the point of view of patients' medical care-seeking behavior? 214 patients with Japanese cedar pollinosis who had visited medical doctors in 2003 pollen-season were randomly sampled from 603 pollinosis patients registered at a disease survey company and we mailed self-evaluation questionnaire on patients' medical care-seeking behavior on the end of pollen season in 2004. Response rate was 65.3%. Patients visited clinics in approximately 90% more than hospitals. They selected ENT in 43.9% and general physicians in 31.1%. Their selections were based on others than their specialty such as easy access and previous experience of visit, because pollinosis is not serious disease like cancer. ENT doctors treated the patients by combination of two kinds of tablet or topical steroid with tablet, while general physicians did with single kind of tablet. The patient satisfaction, and its related questions including preference, wish to revisit in next year and recommendation to their friend were not different in treatment between ENT and general physician. Doctors' attitude, and communication with patients were the most important factor for patient satisfaction as well as treatment out-come. In conclusion, patients prefer agreeable and convenient treatment. If ENT doctors still want to be specialist for pollinosis, they should take care patients well and develop their own specific treatment methodology to cure this disease.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Recent suggestions emphasizes the importance of assessing medical care outcomes from the point of view of both professional opinion and patient's subject like patient satisfaction as well as quality of life. Self-administered questionnaires are often used as an instrument for this purpose. When compared with quality of life, there is less useful questionnaire for patient satisfaction. Accordingly, we here aimed to develope the questionnaire, which is disease-specific, comprehensive, simple, clinically available and satisfied psychometric validation study. The items were collected from patients and satisfaction-related literature's review, and the total 20 were selected finally from them after excluding inadequate or overlapped items. Then, we conducted validation study in 214 subjects sampled randomly from 603 patients with Japanese cedar pollinosis who had visited clinics in 2003 by mailing self-administered questionnaire in spring, 2004. The response rate was 65.3%. In factor analysis, items were divided into four domains such as doctor-patient relationship, treatment outcome, geniality in hospital and convenience of medical service. The former two domains were the most correlated well with patient satisfaction. The quality of this questionnaire such as responsiveness, reliability, construct validity, convergent/discriminate validity, and clinical validity satisfied international standard. Thus, it was verified that our newly developed questionnaire is a useful and scientific tool for examination of patient satisfaction with medical care in allergic rhinitis.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

Background: In allergic rhinitis, antigen-antibody reactions occur in the nasal mucosa through antigen exposure. A strong reaction occurs following exposure to a large amount of antigen, whereas no reaction occurs in the absence of antigens. In seasonal allergic rhinitis, nasal hypersensitivity increases during the pollen-dispersing season, which is known as the 'priming effect'. The purpose of the present study was to clarify whether repeated nasal challenges bring about increased nasal hypersensitivity in patients with perennial allergic rhinitis. Methods: Fourteen patients with perennial allergic rhinitis to house dust mites were enrolled in the present study. Repeated challenge tests were performed once daily for 8 consecutive days with a fixed amount of antigen. Results: Sneezing and nasal secretion were slightly enhanced by repeated challenges only on the 2nd and 3rd days, whereas nasal resistance remained unchanged. Increased sneezing and nasal secretion was marked in a group of subjects who were not sneezing at the first challenge, whereas changes in nasal reaction following repeated challenge were less obvious in subjects who were sneezing at the first challenge. Conclusions: In contrast with pollinosis, nasal provocation reactions were not clearly enhanced by repeated provocation. To further understand nasal reactions induced by antigen challenge, studies should be performed under specified conditions (i.e. in an experimental room) with a prescribed quantity of antigens administered, as well as within a study environment.

DOI： 10.1046/j.1323-8930.2003.00299.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Allergic reaction of the nose comprises of an immediate and a late reaction. To evaluate nasal allergic reactions, many experiments have been performed by investigators. In this study, we performed a new tissue culture technique (adhesive explant culture) to analyze the migration of cells into the culture medium from the cultured allergic nasal mucosa in response to an allergen. Basophilic cells (mast cells and basophils) and eosinophils, which were released into the culture medium after the allergen challenge, were evaluated by the analysis of histamine and eosinophil cationic protein (ECP) content in the culture medium. Histamine and basophilic cells in the culture medium were more abundant in the immediate phase (within 30 min) after challenge than in the late phase (from 30 min to 10 hr). On the other hand, ECP and eosinophils in the culture medium were more abundant in the late phase than in the immediate phase. The increase of histamine content in both phases were not inhibited by pre-treatment of emedastine difumarate (EME), an anti-allergic drug. However, the increase of ECP in the late phase was inhibited by pre-treatment with EME. Moreover, the number of EG2-positive cells was also decreased by pre-treatment with EME. These results suggest that EME might lower the activation of eosinophils in the late phase of the allergic reaction. The present study also indicates that this adhesive explant culture system is useful model for studying the cellular allergic responses to drugs ex vivo.

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

Nasal allergy is the most common type I allergic disease. During allergic reaction, chemical mediators may be released from residual cell, and thus, attract additional inflammatory cells. One mediator implicated in this response is bradykinin (BK), a potent proinflammatory nonapeptide. This study was designed to investigate the effect of BK on nasal mucosa, and to determine the role of angiotensin-converting enzyme (ACE) in BK-induced nasal responses. BK nasal provocation (100μg) was studied in 7 normal volunteers and 7 patients with perennial allergic rhinitis. After provoking of BK response, nasal secretions and saline lavage fluids were collected for analysis of total protein (a protein secretion marker), albumin (a vascular permeability marker), and lysozyme (a serous cell marker). In addition, after administering of Captopril 50mg, a specific ACE inhibitor, the same protocol was performed. In both groups, BK induced plasma exudation and serous gland secretion. Premedication with captopril did not alter BK-induced responses in normal individuals. In allergic patients, captopril enhanced BK-induced vascular permeability, but not glandular secretion. These results indicate that allergic subjects have nasal hyperresponsiveness to BK, and that ACE predominantly modulates the vascular permeability of allergic nasal mucosa. It seems likely that BK may contribute to the expression of nasal allergic symptoms, and that inhibition of ACE may lead to increased nasal responsiveness.

DOI： 10.3950/jibiinkoka.102.218

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Cytokines are potentially active biological peptides that are known to play an important role in several immune responses. Several studies have reported the existence of a variety of cytokines in the nasal mucosa of patients with allergic rhinitis. However, there are few reports on cytokines released into the nasal secretion. In the present study, we investigated the sources, and levels of three key proinflammatory cytokines namely, IL-6, IL- 8, and GM-CSF in the nasal secretion, as well the mechanisms of their release, by ELISA and immunohistochemistry. Firstly, we examined the levels of IL-6, IL-8, and GM-CSF in the nasal secretion after in vivo nasal challenge with methacholine (MC), histamine (HI) and allergen (Ag) in patients with nasal allergy to house dust mite (HDMAR). Next, we examined the levels of IL-6, IL-8, and GM-CSF released, in vitro, after Ag challenge of nasal scrapings from patients with HDMAR. Finally, we examined the sources of these cytokines in the nasal mucosa, by immunohistochemistry. After MC challenge in patients with HDMAR, the concentration of IL-6, but not IL-8, and GM-CSF, was significantly greater on the challenged side than on the contralateral side. Ag and HI provocation induced significantly greater levels of IL-6 and IL-8 secretion in patients with HDMAR, on the challenged side than on the contralateral side. GM-CSF was only detected in the nasal secretion after Ag challenge. Immunoreactivity for IL-6 and IL-8 was very similar in that it was predominantly localised to the apical portion of epithelial cells, the superficial lamina propria, gland cells, and migrating cells. The immunoreactivity for GM-CSF varied slightly from that of IL-6 and IL-8: strong immunoreactivity was detected in the basal part of epithelial cells, basement membrane, glandular ducts, and migrating cells. These results suggest that the levels, sources, and mechanisms of release of IL-6, IL-8, and GM-CSF in the nasal secretion of patients with HDMAR do vary, but are important in the manifestation of the allergic reaction.

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01814&link_issn=&doc_id=20230825070034&doc_link_id=%2Faq9johne%2F2023%2F003909%2F035%2F1005-1008%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9johne%2F2023%2F003909%2F035%2F1005-1008%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00009&link_issn=&doc_id=20230912380004&doc_link_id=%2Fcw4aller%2F2023%2F007208%2F004%2F1007-1010%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2023%2F007208%2F004%2F1007-1010%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児臨床アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児臨床アレルギー学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：日本職業・環境アレルギー学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：日本職業・環境アレルギー学会  

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Language：English   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07551&link_issn=&doc_id=20230405410013&doc_link_id=10.3950%2Fjibiinkotokeibu.126.3_248&url=https%3A%2F%2Fdoi.org%2F10.3950%2Fjibiinkotokeibu.126.3_248&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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Authorship：Lead author   Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞POINT ▼アレルギー性鼻炎はI型アレルギー反応の典型である。▼喘息は気道炎症が病態の中心であり,好酸球浸潤が特徴である。▼アレルゲン特異的なアレルギー反応に加えて,環境因子による自然リンパ球が誘導する炎症反応が関与している。

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

J-GLOBAL

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Authorship：Lead author   Language：Japanese   Publisher：(株)全日本病院出版会  

アレルギー性鼻炎とアレルギー性結膜炎は類縁疾患という概念以上に共通点が多いと考えられる.病態や診断手技,疫学等をみてもそれぞれの臓器に発現しているI型アレルギー疾患であると考えられる.臓器特異性があるため,治療薬や治療法に若干の異なる点はあるものの,根底にあるアレルギー病態を考えると共通する治療法によって症状を制御できるはずである.アレルゲン免疫療法は舌下免疫療法の登場で幅広い年齢層に普及が進んでおり,唯一の根治療法である.抗IgE抗体療法は薬物療法の1つだが,従来の薬剤と異なりIgEを介するアレルギー病態を早いステージから制御する効果が期待できる.どちらの治療法もアレルギー性鼻炎に伴うアレルギー性結膜炎においても有用性が証明されており,眼症状に対する治療法として今一度見直していただければ幸いである.(著者抄録)

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＜文献概要＞Point ●アレルギー性鼻炎・花粉症において,アレルギー性か否かの検査には鼻腔内所見,鼻副鼻腔X線検査,鼻汁好酸球検査がある.原因アレルゲンを同定する検査には皮膚テスト,血清特異的免疫グロブリンE(IgE)検査,鼻誘発試験がある.●口腔アレルギー症候群(OAS)では,被疑食品に対する血清特異的IgE検査や皮膚プリックテスト,候補となる感作花粉に対する血清特異的IgE検査が有用である.●好酸球性副鼻腔炎は血中好酸球数・CT所見および臨床所見を,好酸球性中耳炎は中耳貯留液の好酸球の証明および臨床所見をそれぞれスコア化した診断基準が策定されている.

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Authorship：Last author   Language：Japanese   Publisher：(同)クリニコ出版  

舌下免疫療法(sublingual immunotherapy:SLIT)の開発,普及によって,アレルギー疾患治療は新時代を迎えている。SLITには,(1)アレルゲン溶液や錠剤を舌下に保持するだけの簡単な操作であること,(2)皮下免疫療法(subcutaneous immunotherapy:SCIT)や経口免疫療法(oral immunotherapy:OIT)等,アナフィラキシーを誘発する危険性のある他のアレルゲン免疫療法(allergen immunotherapy:AIT)に比べ,副作用がはるかに少ないこと,(3)そのため,在宅でも患者自身による服薬が可能なこと,(4)各種対症療法と比較しても,副作用の懸念が少ないこと,(5)対症療法とは異なり,症状の軽減だけでなく,アレルギー疾患の根治も期待できること等,多くの有益な特長がある。一方,十分な効果を得るためには長期間の治療が必要であることが欠点であるものの,ほぼ唯一のものと言える。2014年から2018年にかけて,少なくとも4種類のSLITを用いた治療法が,我が国で承認された。しかし,SLITがどのようにしてこのような高い有効性を発揮するのか,現在のところ完全には解明されていない。SLITで投与されるアレルゲン量は,経口投与によって免疫寛容を誘導できる実験的な必要量よりはるかに少量である。また,SCITと異なり,SLITではアレルゲンを全身投与しない。SLITの安全性にも大きく寄与するこれらの特長は,他の経路で投与されるアレルゲンによって誘導される生体応答に基づいて提唱されてきた,AITの有効性に関わるさまざまなメカニズムを再検証する上で,貴重なヒントを提供してくれる。本稿では,現時点でのSLITのメカニズムに関する認識について,他AITにおける報告とも比較整理しつつ,我々が実施した臨床試験から得られた新しい知見とともに紹介してみたい。(著者抄録)

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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本特集号では、アレルゲン免疫療法の臨床・研究領域で活躍される多くのご高名な先生方から、本免疫療法の最新情報や将来展望に関する専門的知見をご供覧いただけているものと思う。後藤からも、舌下免疫療法における作用療法の現状について紹介させていただいたので、是非ご参照願いたい。さらにわれわれは、それらの実臨床活動と並行して、アレルゲン免疫療法の作用機構解明を目指し、さまざまな切り口での臨床的・基礎的研究を進めてきた。特に最近、舌下免疫療法に対する治療効果がみられるスギ花粉症患者と、効果がみられない患者との間での網羅的な比較解析を進めることによって、その治療効果に関わる生体反応カスケードの解明に結びつきうる。有力な手がかりも得られつつある。特にその中で、好塩基球を介したアレルゲン免疫療法の新たな奏功機構に関するトピックについて、本稿ではご紹介してみたい。(著者抄録)

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舌下免疫療法のスギ、ダニのどちらを先に投与しても副反応の発現頻度は変化せず、併用しても重篤な副反応は発生せず、副反応の種類も単独投与と変化しなかった。以上のことから5分以内に併用した場合の安全性を確認でき、臨床的に安心して併用療法が実施できるエビデンスが構築できたものと考えられる。(著者抄録)

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舌下免疫療法を始めるために、まず365日毎日舌下投与できるのか確認することがもっとも重要である。3〜5年治療しなければならないと説明するよりも1シーズン治療を行い、その結果をもとに免疫療法をそのまま継続するかどうか検討するという方法も試す価値はあるだろう。併用療法は、初めの1ヵ月間はダニまたはスギを単独で投与する。2〜3ヵ月目の併用期には5分以内の間隔で2剤目を投与すれば単独と同等の安全性を維持できる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Authorship：Last author   Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞POINT ◆鼻アレルギー検査のうち,アレルギー性か否かを鑑別する検査には鼻腔内所見,鼻副鼻腔X線検査,血液・鼻汁好酸球検査があり,原因アレルゲンを同定する検査には皮膚テスト,血清特異的IgE検査,鼻誘発試験がある.◆発作性反復性のくしゃみ,水様性鼻汁,鼻閉の症状があり,鼻汁好酸球検査,皮膚テストまたは血清特異的IgE抗体検査,鼻誘発試験のうち2つ以上が陽性ならアレルギー性鼻炎と確定診断できる.鑑別すべき鼻過敏症に,好酸球増多性鼻炎,血管運動性鼻炎が挙げられる.◆各検査結果が臨床症状と一致しない場合もあり,最終的には問診を基本に検査結果を参考として総合的に判断する.

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

鼻アレルギー診療ガイドライン2020年版(改訂第9版)が2020年7月に改訂された。今回の改訂では2019年に実施されたアレルギー性鼻炎有病率調査結果が掲載されたこと、病態メカニズムに自然II型リンパ球の関与が明記されたこと、重症・最重症スギ花粉症に対して抗IgE抗体療法が推奨されたことなどが新しい改訂ポイントである。アレルギー性鼻炎・花粉症の治療の原則は、抗原除去・回避、薬物療法、アレルゲン免疫療法、手術療法の4つがある。近年、薬物療法薬では複数の非鎮静性第2世代抗ヒスタミン薬が新しく上市された。鎮静作用がほとんどなく、安全性が高い薬剤が選択できるようになった。舌下免疫療法ではスギ舌下錠が市販され舌下液よりも高い有効性を示し、スギ舌下錠とダニ舌下錠の併用も安全性の高い治療法であることが臨床研究で確かめられた。低年齢のスギ花粉症有病率が増加しているが、根治的治療であるアレルゲン免疫療法を小児期から積極的に開始することも考慮すべきである。また、2019年12月にはアレルギー性鼻炎領域では、世界初の生物学的製剤が重症以上のスギ花粉症に対して適応追加された。抗ヒスタミン薬などの薬物療法や舌下免疫療法は軽症から最重症までの患者に推奨されているが、抗IgE抗体療法は重症以上のスギ花粉症に対してのみ使用できる。患者の病型や重症度に応じて適切に治療方法を選択すべきである。(著者抄録)

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薬剤性鼻炎の発見は、1946年の報告にさかのぼる。点鼻血管収縮薬による薬剤性鼻炎の頻度が高いが、広義には抗うつ薬や降圧薬などによる副作用も薬剤性鼻炎に含まれる。アレルギー性鼻炎の薬物療法において、点鼻血管収縮薬は限定的に使用すべき薬剤であり、ガイドラインでは通年性アレルギー性鼻炎、花粉症ともに、重症や最重症の鼻閉型または鼻閉を主とする充全型に、2週間以内の使用に留めるよう推奨されている。(著者抄録)

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＜Headline＞1 ビラスチン、デスロラタジン、ルパタジンフマル酸塩、エメダスチンフマル酸塩含有経皮吸収型製剤が近年発売され、鼻アレルギー診療ガイドライン2020年版(改訂第9版)に追加された。2 花粉症の薬物療法には初期療法があり、シーズン前に重症化予防対策ができる。3 非鎮静性抗ヒスタミン薬の使い方が花粉症治療の重要なポイントである。4 症状が悪化した場合には病型、重症度に応じて併用療法を行い、患者満足度の向上を目指す。(著者抄録)

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我が国で舌下免疫療法が実用化されてから6年が経過した。海外では1910年代から、我が国では1960年代から皮下免疫療法が行われており、その有効性のエビデンスは多数蓄積されていたが、アナフィラキシーのリスクがあるため施行できる施設が限られていた。1970〜80年代にはアレルゲン免疫療法の皮下以外の投与経路として経鼻・経口・吸入投与が模索されたが、いずれも実用化には至らなかった。1986年に舌下免疫療法における初の二重盲検比較試験が報告され、1998年のWHO見解書では舌下免疫療法は皮下免疫療法に代わる治療になりうると報告された。我が国では2000年から舌下免疫療法の実用化に向けた臨床研究が始まり、2014年に舌下免疫療法治療薬が発売された。舌下免疫療法の実用化により我が国のアレルギー診療は転機を迎え、根治を目指した治療が普及することとなった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

近年になり、スギ花粉症などのアレルギー性鼻炎の増加が指摘されている。馬場らが中心となって1998年と2008年に全国の耳鼻咽喉科医師ならびにその家族を対象としたアンケートによる鼻アレルギー疫学調査が行われ、有病率の推移が詳細に報告されている。今回われわれは、前回の調査から11年後の2019年に同様の調査を行い、スギ花粉症、通年性アレルギー性鼻炎ならびにスギ以外の花粉症の有病率を同定した。アレルギー性鼻炎全体の有病率は49.2%、スギ花粉症単独の有病率は38.8%と前回調査に比べ大きく増加していた。さらに10歳代でスギ花粉症が著明に増加していることも明らかとなった。(著者抄録)

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(株)新興医学出版社  

＜ポイント＞●アレルゲン免疫療法は長期寛解・治癒を誘導する。●皮下免疫療法に比べ、舌下免疫療法は安全性が高い。●アレルゲン免疫療法により自然経過が修飾される。すなわち、喘息の発症予防や新規抗原感作抑制効果が期待できる。●局所副反応に対応できる技能や知識が必要である。(著者抄録)

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Language：Japanese   Publisher：(株)診断と治療社  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J03252&link_issn=&doc_id=20190708140003&doc_link_id=%2Fae4chilj%2F2019%2F002207%2F005%2F0495-0498%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4chilj%2F2019%2F002207%2F005%2F0495-0498%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese  

From the era of subcutaneous immunotherapy (SCIT) in 1960s, allergen immunotherapy (AIT) has been established as a highly effective and curable treatment for allergic diseases. Furthermore, the recent appearance of sublingual immunotherapy (SLIT) in which the complicated administration procedure in SCIT was improved has been causing paradigm shifts in the treatment of allergic rhinitis. During the long history of AIT, the mechanisms by which this therapy leads its strong efficacy have been investigated but not fully clarified yet. The production of blocking antibodies that interrupt allergen-IgE binding, normalization of Th1/Th2 balance, and introduction of regulatory T cells are the major candidate mechanisms, though there are several conflicting reports. In our recent clinical study of SLIT against Japanese cedar pollinosis, we also tried to elucidate its mechanisms. Especially by comparing high-responder and non-responder patients using integrated analysis with multiple data, not by comparing with a placebo control group using individual data, we have successfully identified several target molecules and cascades of SLIT. Herein, we would like to describe the potential mechanisms by which AIT exhibits its strong efficacy with referring our recent novel findings.

DOI： 10.1254/fpj.154.23

PubMed

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(株)全日本病院出版会  

アレルギー性鼻炎の治療は、患者とのコミュニケーションを重視しながら、抗原除去・回避、薬物療法、手術療法、アレルゲン免疫療法の4つの柱がある。2011年に実施したインターネット調査によれば、花粉症治療を行っている内科、耳鼻咽喉科、小児科の医師において治療の中心になる薬剤は第2世代抗ヒスタミン薬であることがわかった。すべての診療科で96%以上の医師が処方しており、まさにゴールドスタンダードである。診療ガイドラインでは軽症〜最重症までのどの重症度に対しても第2世代抗ヒスタミン薬を推奨している。抗ヒスタミン薬の選び方がアレルギー性鼻炎治療の重要なポイントになるといっても過言ではない。重症例に対しては第2世代抗ヒスタミン薬をベース薬と捉え鼻噴霧用ステロイド薬を併用するのが最も多い処方例である。病型および重症度を評価し、的確な併用療法を行うことが重要である。(著者抄録)

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Language：Japanese   Publisher：(株)全日本病院出版会  

アレルギー性鼻炎の治療は、患者とのコミュニケーションを重視しながら、抗原除去・回避、薬物療法、手術療法、アレルゲン免疫療法の4つの柱がある。2011年に実施したインターネット調査によれば、花粉症治療を行っている内科、耳鼻咽喉科、小児科の医師において治療の中心になる薬剤は第2世代抗ヒスタミン薬であることがわかった。すべての診療科で96%以上の医師が処方しており、まさにゴールドスタンダードである。診療ガイドラインでは軽症～最重症までのどの重症度に対しても第2世代抗ヒスタミン薬を推奨している。抗ヒスタミン薬の選び方がアレルギー性鼻炎治療の重要なポイントになるといっても過言ではない。重症例に対しては第2世代抗ヒスタミン薬をベース薬と捉え鼻噴霧用ステロイド薬を併用するのが最も多い処方例である。病型および重症度を評価し、的確な併用療法を行うことが重要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J00009&link_issn=&doc_id=20190311270001&doc_link_id=1390282763104624640&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282763104624640&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

アレルギー性鼻炎・花粉症の治療は患者とのコミュニケーションを重視しながら、抗原除去・回避、薬物療法、手術療法、アレルゲン免疫療法の4つの柱がある。2011年5月にわれわれが実施した1,000人規模のインターネット調査によれば、花粉症治療を行っている内科、耳鼻科、小児科の医師においては治療の中心になる薬剤は第2世代抗ヒスタミン薬であることが分かった。すべての診療科で96%以上の医師が処方しており、まさにゴールデンスタンダードである。診療ガイドラインでは軽症から最重症までのどの重症度に対しても第2世代抗ヒスタミン薬を推奨している。つまり、I型アレルギー疾患の典型であるアレルギー性鼻炎ではヒスタミンが病態形成に最も重要であるといっても過言ではなく、抗ヒスタミン薬の使い方がアレルギー性鼻炎・花粉症治療の重要なポイントになってくる。スギ花粉症の薬物療法において、特徴的なのは初期療法である。花粉飛散開始のタイミングを考慮して症状が悪化する前から薬物療法を開始する方法で、重症度の高い患者に特に効果がある。現代の第2世代抗ヒスタミン薬は即効性が証明されており、症状が少し出たタイミングで投与開始しても効果が期待できる。花粉飛散ピーク時に症状が悪化した場合には、抗ヒスタミン薬の増量や種類変更を考慮するよりもその時の病型や重症度に応じてほかの治療薬を併用することが効果的である。海外のガイドラインでの推奨順位と異なるが、わが国では第2世代抗ヒスタミン薬をベース薬と捉え鼻噴霧用ステロイド薬を併用するのが最も多い処方例である。初期治療による重症化対策を行いながら、併用療法によって重症度に応じた治療を行うことが、患者満足度の向上を目指した花粉症治療には重要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

アレルギー性鼻炎・花粉症の治療は患者とのコミュニケーションを重視しながら、抗原除去・回避、薬物療法、手術療法、アレルゲン免疫療法の4つの柱がある。2011年5月にわれわれが実施した1,000人規模のインターネット調査によれば、花粉症治療を行っている内科、耳鼻科、小児科の医師においては治療の中心になる薬剤は第2世代抗ヒスタミン薬であることが分かった。すべての診療科で96%以上の医師が処方しており、まさにゴールデンスタンダードである。診療ガイドラインでは軽症から最重症までのどの重症度に対しても第2世代抗ヒスタミン薬を推奨している。つまり、I型アレルギー疾患の典型であるアレルギー性鼻炎ではヒスタミンが病態形成に最も重要であるといっても過言ではなく、抗ヒスタミン薬の使い方がアレルギー性鼻炎・花粉症治療の重要なポイントになってくる。スギ花粉症の薬物療法において、特徴的なのは初期療法である。花粉飛散開始のタイミングを考慮して症状が悪化する前から薬物療法を開始する方法で、重症度の高い患者に特に効果がある。現代の第2世代抗ヒスタミン薬は即効性が証明されており、症状が少し出たタイミングで投与開始しても効果が期待できる。花粉飛散ピーク時に症状が悪化した場合には、抗ヒスタミン薬の増量や種類変更を考慮するよりもその時の病型や重症度に応じてほかの治療薬を併用することが効果的である。海外のガイドラインでの推奨順位と異なるが、わが国では第2世代抗ヒスタミン薬をベース薬と捉え鼻噴霧用ステロイド薬を併用するのが最も多い処方例である。初期治療による重症化対策を行いながら、併用療法によって重症度に応じた治療を行うことが、患者満足度の向上を目指した花粉症治療には重要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01099&link_issn=&doc_id=20190404550002&doc_link_id=%2Fdz0jibik%2F2019%2F012203%2F002%2F0187-0191%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2019%2F012203%2F002%2F0187-0191%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)メディカルレビュー社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J04290&link_issn=&doc_id=20190301280004&doc_link_id=%2Fai1aamdd%2F2019%2F001501%2F007%2F0039-0046%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1aamdd%2F2019%2F001501%2F007%2F0039-0046%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01099&link_issn=&doc_id=20190107570014&doc_link_id=%2Fdz0jibik%2F2018%2F012112%2F014%2F1526-1528%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2018%2F012112%2F014%2F1526-1528%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)医薬ジャーナル社  

＜文献概要＞アレルギー性鼻炎・花粉症においては診断マーカーとして,血清特異的IgE(immunoglobulin E)検査,鼻汁好酸球検査があるが,予後や治療効果を予測できるバイオマーカーは今までのところ確立していない。血清IgE抗体は診断には極めて重要な意義があるが,重症度診断や治療効果判定につながるバイオマーカーに関しては今までのところ未解決であり,解決すべき研究テーマのひとつになっている。

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(公財)東京都福祉保健財団人材養成部職員研修室  

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J00009&link_issn=&doc_id=20180810420003&doc_link_id=1390001288059596800&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001288059596800&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：Japanese   Publisher：(一社)日本アレルギー学会  

【背景・目的】これまでスギ花粉症に対するアレルゲン免疫療法の治療目標に関する報告は少なく、臨床現場では自覚症状によって判断せざるを得なかった。今回、TO-194SL第III相臨床試験成績を用いて、実臨床におけるスギ花粉症の治療目標を検討することを目的とした。【方法】臨床試験の副次評価項目であったSevere symptom day、QOLスコア、被験者による総合評価について、主要評価項目であった総合鼻症状薬物スコア(TNSMS)との相関を検討した。さらに各副次評価項目の結果について複数のグループに分類し、スギ花粉飛散期のTNSMSの推移との関係について検討した。【結果】TNSMSとSevere symptom day 0日やQOLスコア平均値、被験者による総合評価には、一定の相関を認めた。これらの評価項目が一定数値以下の場合には、TNSMSの推移は花粉シーズンを通じて概ね3点以下(軽症)の推移だった。【結語】これらの評価法が治療継続のための目標になれば、患者がアレルゲン免疫療法の治療効果を実感できる指標になり得る可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：技術情報協会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞説明のPOINT ・皮下免疫療法では注射部位の発赤,膨疹などがほとんどの症例で発生する。・増量期にアレルギー反応が起こりやすい。・維持期でも体調によってアレルギー反応が高度になることがある。・注射後数時間で遅発性に皮膚反応が起こった場合は全身性のアレルギー反応には移行しない。・アナフィラキシーが発生した場合には,重症度によって適切な処置を迅速に行う必要がある。

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01099&link_issn=&doc_id=20180508410099&doc_link_id=%2Fdz0jibik%2F2018%2F012104%2F109%2F0492-0492%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2018%2F012104%2F109%2F0492-0492%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本鼻科学会  

モメタゾン点鼻液50μg「TK」56噴霧用(以下、TAC-203)は、ナゾネックスR点鼻液(MSD株式会社)(以下、標準製剤)のジェネリック医薬品として開発した薬剤であり、標準製剤と異なる製剤特性を有する。そこで、TAC-203の有効性及び安全性を適切に評価するため、日本の鼻噴霧用ステロイド薬のジェネリック医薬品開発では初となるプラセボ対照試験(治療学的同等性試験)を実施した。180例(TAC-203:72例、標準製剤:72例、プラセボ:36例)のスギ花粉症患者が登録された。主要評価項目である投与2週時の総合鼻症状スコアのベースラインからの変化量の差[TAC-203-標準製剤]の95%信頼区間は-0.427〜1.112であり、事前に規定した治療学的同等限界(△=±1.13)の範囲内であった。有害事象の発現割合はTAC-203:6/72例(8.3%)、標準製剤:9/72例(12.5%)であった。全身移行性を評価するため初回噴霧後1時間に血漿中モメタゾンフランカルボン酸エステル濃度を測定した結果、標準製剤が過去の臨床試験で設定していた定量下限(50pg/mL)を超える患者はいなかった。以上より、TAC-203と標準製剤の治療学的同等性が確認された。また、TAC-203の忍容性及び安全性は標準製剤と同様であった。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01675&link_issn=&doc_id=20180507330002&doc_link_id=10.7248%2Fjjrhi.57.7&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.57.7&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本鼻科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01675&link_issn=&doc_id=20180507330022&doc_link_id=10.7248%2Fjjrhi.57.90&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.57.90&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：田辺三菱製薬(株)  

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Language：Japanese   Publisher：医薬ジャーナル社  

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

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Language：Japanese   Publisher：(株)日本小児医事出版社  

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Language：Japanese   Publisher：日本小児医事出版社  

CiNii Books

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

新規抗ヒスタミン薬として国内で治験を実施し,2016年に発売されたものが2剤ある。ビラスチンとデスロラタジンである。新規薬剤として共通する特徴は即効性や安全性を重視した薬剤が多いことであり,最近のトレンドといえる。鎮静作用のある第2世代抗ヒスタミン薬が非鎮静性第2世代抗ヒスタミン薬になり,さらにより洗練された製剤に進化したということもできるだろう。(著者抄録)

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本小児耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：鳥居薬品(株)  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：医薬ジャーナル社  

CiNii Books

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

新規抗ヒスタミン薬として現在国内で治験が終了したものや進行中のものがある。Bilastine,Desloratadine,Rupatadineの3剤である。また,新しいドラッグデリバリーとして貼付剤の試験が行われている。新規薬剤として共通する特徴は即効性や安全性を重視した薬剤が多いことであり,最近のトレンドといえる。鎮静作用のある第2世代抗ヒスタミン薬が非鎮静性第2世代抗ヒスタミン薬になり,さらにより洗練された製剤に進化したということもできるだろう。(著者抄録)

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Language：Japanese   Publisher：(株)自然科学社  

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Language：Japanese   Publisher：日本鼻科学会  

DOI： 10.7248/jjrhi.56.279

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：医薬ジャーナル社  

CiNii Books

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

舌下免疫療法を実施するためには,講習会やe-ラーニングを受講しテストに合格する必要がある。また,緊急搬送先医療機関名を登録しなければ,処方可能にはならない。これらのシステムのために混乱が生じているケースもあるが,地域の診療環境にあった方法で準備を整えるべきである。治療薬本来の効果を得るためには,スギ花粉症の正しい診断と毎日の治療継続が重要である。複数のアレルゲンによる症状が明確な患者は皮下免疫療法が適している。治療アドヒアランスをいかに高めるのか,それをいかに維持していくのか,今後の課題も多い。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：日本医師会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(株)全日本病院出版会  

アレルギー性鼻炎の治療は薬物療法による対症療法が中心的に行われてきたが、2014年にスギ舌下免疫療法が実用化されたことによってアレルゲン免疫療法そのものにも注目が集まっている。病態メカニズムを考えれば対症療法よりも根治的治療法で治療することに意義があるが、皮下免疫療法は患者も医師サイドも副作用発生の危険性など、メリットよりもデメリットを懸念し実施率の低い治療法になっていた。舌下免疫療法は安全性が高く、誰もが受け入れやすい治療法に近づいたことによって、より多くの患者が根治療法を受けることが可能になった。舌下免疫療法を実施するためには、講習会やe-ラーニングを受講しテストに合格する必要がある。また、緊急搬送先医療機関名を登録しなければ、処方可能にはならない。処方する医療機関はアナフィラキシーショック発生時に対応できる器械、薬品の準備が必要になる。これらのシステムのために混乱が生じているケースもあるが、地域の診療環境にあった方法で準備を整えるべきである。治療薬本来の効果を得るためには、スギ花粉症の正しい診断と毎日の治療継続が重要である。複数のアレルゲンによる症状が明確な患者は皮下免疫療法が適している。治療アドヒアランスをいかに高めるのか、それをいかに維持していくのか、今後の課題も多い。(著者抄録)

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Language：Japanese   Publisher：金原出版  

DOI： 10.18888/J00639.2016213903

CiNii Books

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：鳥居薬品(株)  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2016126642

Language：Japanese   Publisher：メディカルレビュー社  

CiNii Books

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

アレルギー性鼻炎・花粉症に対する薬物療法では、第二世代抗ヒスタミン薬が中心的な役割を果たしている。2015年中に新しく承認された抗アレルギー薬はないが、現在第III相臨床試験が終了した、あるいは進行中のものが3剤存在している。新規薬剤として共通する特徴は、即効性や安全性を重視した薬剤が多いことであり、最近のトレンドと言える。これらの薬剤の有効性、安全性、比較試験の結果について解説する。(著者抄録)

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Language：Japanese   Publisher：日本鼻科学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(株)医学書院  

＜ポイント＞薬物療法は対症療法であるが,アレルゲン免疫療法は根治的な治療法である.12歳以上のスギ花粉症に対して舌下免疫療法が実用化された.舌下免疫療法は簡便で安全な治療法であるが,副反応の発現に注意する.有効性を高めるために治療アドヒアランスの維持が重要である.(著者抄録)

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本小児医事出版社  

CiNii Books

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Language：Japanese   Publisher：(株)日本小児医事出版社  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本職業・環境アレルギー学会  

スギ花粉症の舌下免疫療法治療薬が2014年に発売された。舌下免疫療法という投与経路は海外ではすでに実用化されているものも複数あるが、本邦では新規の治療法である。従来アレルゲン免疫療法(減感作療法)は、アレルゲンを少量から漸増しながら皮下注射する方法が用いられてきた。舌下免疫療法は疼痛がなく、自宅で投与でき、全身性副反応発生が極めて少ないことから、簡便で安全な免疫療法として主に欧州で普及してきた。舌下免疫療法を開始するにあたって、舌下免疫療法もアレルゲン免疫療法の一方法であることを認識すべきである。具体的には(1)症状を起こしているアレルゲンを確実に診断して治療を開始すること、(2)適応と禁忌を正しく判断すること、(3)副反応に対処できること、の3つに留意して投与開始する必要がある。(著者抄録)

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：医薬ジャーナル社  

CiNii Books

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

アレルギー性鼻炎の臨床試験では、これまで奥田の分類に基づいて患者が自ら症状の変化を鼻アレルギー日記に記入する方法が広く行われてきた。くしゃみ、鼻汁は回数で評価し、鼻閉は自覚症状を基準にし、どのような症状がどの重症度になるか規定している。このような症状スコアだけでなく、併用薬の使用頻度をスコア化した薬物スコア、QOLの変化など複数項目を評価基準することによって薬物療法をより客観的に評価することができる。(著者抄録)

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J-GLOBAL

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Language：Japanese   Publisher：日本鼻科学会  

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Language：Japanese   Publisher：一般社団法人 日本耳鼻咽喉科学会  

DOI： 10.3950/jibiinkoka.118.529

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01675&link_issn=&doc_id=20150601320013&doc_link_id=10.7248%2Fjjrhi.53.579&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.53.579&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：診断と治療社  

CiNii Books

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Language：Japanese   Publisher：(株)診断と治療社  

アレルギー性鼻炎・花粉症に対しては、種々の薬物療法で治療を行う場合が多い。有効性や安全性の高い治療薬が増えてきたという事情もあるが、原因アレルゲンに応じた根治的治療であるアレルゲン免疫療法を選択するケースが少ないのは事実である。本稿ではアレルゲン免疫療法(皮下免疫療法)の意義、方法について解説し、日常診療においてその重要性を再確認できるようにしたい。(著者抄録)

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：医薬ジャーナル社  

CiNii Books

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本職業・環境アレルギー学会  

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

I型アレルギー疾患の根治療法としてアレルゲン免疫療法がある。免疫療法は数年間治療を行うと治療終了後も効果が持続し、長期寛解を誘導できるといわれているが、注射法ではアナフィラキシー反応など副作用の危険性があり本邦では十分に普及していない。舌下免疫療法はそのようなデメリットを改善した方法で、安全に免疫療法を行うことができる。日本ではスギ花粉症に対して舌下免疫療法が医師主導で研究され、2010年秋には国内第III相試験がスタートした。免疫療法はこれまでアレルギー治療の選択肢として軽視されてきたが、舌下免疫療法が実臨床で使用可能になれば、重要な治療オプションになることが期待されている。(著者抄録)

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：医薬ジャーナル社  

CiNii Books

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(株)医学書院  

＜POINT＞病型・重症度によって薬剤の選択を考慮する。重症度が高ければ併用療法を行う。きわめて重症なケースには点鼻血管収縮薬,内服ステロイド薬を1〜2週間程度追加する。第2世代抗ヒスタミン薬配合剤は鼻閉治療の新しい選択肢になる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：医薬ジャーナル社  

DOI： 10.20837/3201401094

CiNii Books

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Language：Japanese   Publisher：医薬ジャーナル社  

DOI： 10.20837/3201401102

CiNii Books

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.545_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.65

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.695

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.469_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.483_2

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

スギ花粉症の舌下免疫療法(sublingual immunotherapy:SLIT)は、その有効性がきわめて高く根治も望める一方で、約3〜4割の患者には数年間に渡る治療を行っても効果が得られない。そこで、治療応答性に関与するバイオマーカーを見出しこの免疫療法に向かない患者を早期に救済する必要がある。本稿では、花粉症病態を反映するバイオマーカーについての研究動向の紹介に加え、アレルゲン免疫療法をはじめとした花粉症治療の効果に関わるバイオマーカーについて、我々の研究成果の一端も紹介しながら解説する。(著者抄録)

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

I型アレルギー疾患の根治療法としてアレルゲン免疫療法がある。免疫療法は数年間治療を行うと治療終了後も効果が持続し、長期寛解を誘導できるといわれているが、注射法ではアナフィラキシー反応など副作用の危険性があり本邦では十分に普及していない。舌下免疫療法はそのようなデメリットを払拭した方法で、安全に免疫療法を行うことができる解決方法である。日本ではスギ花粉症に対して舌下免疫療法が研究され、2010年秋には国内第III相試験がスタートした。免疫療法はこれまでアレルギー治療の選択肢として軽視されてきたが、舌下免疫療法が実臨床で使用可能になれば、重要な治療オプションになることが期待されている。(著者抄録)

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

DOI： 10.15036/arerugi.62.1252_1

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：医薬ジャーナル社  

CiNii Books

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

アレルゲン免疫療法は、長期寛解、治癒を導く根治療法であるが、その反面全身性副反応が発生する危険性を伴っている。近年、アナフィラキシーを起こしにくい免疫療法として舌下免疫療法が注目されている。皮下注射から舌下免疫療法へ移行し、副反応発現は減少するが決してゼロになることはない。舌下免疫療法に注目が集まっている今、正しい診断を行うことができ、起こってしまったアナフィラキシーに対応できる知識と手技を身につけるための講習会制度などが必要である。(著者抄録)

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Language：Japanese  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2013302392

Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：耳鼻と臨床会  

過去2年間に当科アレルギー外来にてアレルゲン免疫療法を開始した134例を対象とし、年齢性別、治療抗原、治療内容、注射回数、副作用、治療効果につき報告した。患者の年齢は30歳から50歳に多く、人数に男女差はみられなかった。治療抗原はスギ単独が54例(40.3%)、スギ+ハウスダストが36例(26.9%)と多かった。各抗原とも2段階、3段階のステップアップを行ったが、開始量、維持量には個人差がみられた。合計3,481回の注射で5回(0.14%)、134例中5例(3.7%)に副作用がみられた。脱落症例は22例(16.4%)であり、うち11例が抗原増量中の脱落であった。スギのアレルゲン免疫療法を行った患者のうち約27.7%が2012年スギシーズン中の薬物療法を必要としなかった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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