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We have previously reported that JC pollen SLIT tablets also suppress allergic symptoms caused by JCY pollen[5]; however, whether the optimal dosage of JC pollen SLIT tablets for the treatment of JC pollinosis is also optimal for JCY allergic rhinitis has not been established. Keywords: cross-reactivity; homologous; Japanese cedar; Japanese cypress; sublingual immunotherapy EN cross-reactivity homologous Japanese cedar Japanese cypress sublingual immunotherapy 563 568 6 01/31/23 20230201 NES 230201 Japanese cedar (JC) pollinosis is the most prevalent and important tree pollen allergy in Japan,[[1]] and about 70% of JC pollinosis patients also have a symptomatic allergy to Japanese cypress (JCY) pollen.[1] Consequently, combined JC/JCY pollinosis sufferers experience severe symptoms during the JC (February to April) and JCY (April to May) pollen dispersal seasons. [Extracted from the article]

There have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment. This was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015–2017) and followed-up for an additional 2 years (2018–2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions. The mean combined total nasal symptom and medication score (range 0–18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity. JC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period. [ABSTRACT FROM AUTHOR]

Background and Objective: Nasal symptoms were reduced following allergen‐specific sublingual immunotherapy (SLIT) for allergic rhinitis. The mechanisms underlying the effectiveness of SLIT for Japanese cedar pollinosis are poorly understood. We studied changes in the numbers of metachromatic cells, eosinophils, and neutrophils following SLIT for Japanese cedar pollinosis. Methods: Nasal swabs were taken in the preseason (n = 32) and in pollinosis season (n = 49) from subjects given sublingual drop immunotherapy for an average duration of 1.5 years. The numbers of metachromatic cells (mast cells and basophils), eosinophils and neutrophils were determined and compared with those from untreated subjects in preseason (n = 65) and in season (n = 54). Results: SLIT subjects had a significantly reduced frequency of moderate to most severe symptoms in comparison to untreated subjects in preseason (P <.001, the Mann‐Whitney U test), and (P <.00001) in season. Metachromatic cell counts in nasal swabs of SLIT subjects in preseason and in season were lower than those of untreated subjects (P =.014, the Mann‐Whitney U test) and (P =.00001) respectively. Eosinophil numbers in SLIT subjects were not significantly different than in untreated subjects in both preseason (P =.29) and in season (P =.09). However, when SLIT subjects in season were divided into those with greater than or equal to 1.5 years, or <1.5 years of SLIT duration, the degree of eosinophilia in those with SLIT greater than or equal to 1.5 years was significantly lower (P =.011) than in untreated patients, but not in those with SLIT less than 1.5 years (P =.9). There were no significant differences in neutrophil numbers in nasal swabs between untreated and SLIT subjects in preseason and in season. Conclusion: One of mechanisms underlying the effectiveness of sublingual drop immunotherapy for Japanese cedar pollinosis is a reduction of the number of metachromatic cells in preseason and in season. Eosinophilia was also reduced in season in those given SLIT for greater than or equal to 1.5 years. [ABSTRACT FROM AUTHOR]

Background and objective: Nasal symptoms of allergic rhinitis can be reduced with allergen‐specific subcutaneous immunotherapy (SCIT). However, the mechanisms underlying the effectiveness of SCIT for Japanese cedar pollinosis are not well understood. We studied changes in the numbers of metachromatic cells, eosinophils and neutrophils in nasal swabs following SCIT for Japanese cedar pollinosis. Methods: Subjects were either untreated or given SCIT for 0.5 to 13 years duration. For the 2019 seasons, nasal swabs were taken in the pollinosis preseason (immunotherapy n = 36; untreated control, n = 62) and in the pollinosis season (immunotherapy n = 45; untreated control n = 46) and the numbers of mast cells, eosinophils and neutrophils assessed by microscopy. Results: There were significant improvements in symptom severities following SCIT in comparison to untreated subjects (P <.0003, the Mann‐Whitney U test) in preseason, and (P <.00001) in season. Metachromatic cell counts from nasal swabs of SCIT subjects in preseason and in the season were lower than those of untreated subjects (P =.0029 and P =.031, respectively). Eosinophil numbers in nasal swabs of subjects given SCIT were lower than in untreated subjects (P =.0031) in season, but not in preseason. There were no significant differences in degrees of neutrophilia between untreated and SCIT subjects in preseason and in season. Conclusion: One mechanism underlying the effectiveness of SCIT for Japanese cedar pollinosis involves a reduction in the number of metachromatic cells in nasal swabs in the preseason and an inhibition of increases in the number of metachromatic cells and eosinophils in season. [ABSTRACT FROM AUTHOR]

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Image 1 [ABSTRACT FROM AUTHOR]

Background: The concept of local allergic rhinitis (LAR) has been advocated recently. Allergic rhinitis in Japan is characterized by house dust mites (HDMs) and Japanese cedar pollen (JCP). To investigate LAR in Japan, total IgE and antigen-specific IgE (sIgE) were measured in inferior turbinate mucosa and their relationships with skin test (ST) and nasal allergen provocation test (NAPT) and as well as serum IgE levels were examined. Methods: Subjects were 50 rhinosinusitis patients for surgery. ST was performed and serum total IgE and sIgE levels were measured preoperatively. Patients with class-0 serum anti-HDM or anti-JCP sIgE levels were subjected to NAPT with HDM or JCP, respectively, or both. In all patients, inferior turbinate mucosa was weighed and mashed, and total IgE and sIgE levels were then measured as local mucosal date per gram and per milligram. Because there is no clinical consensus how to evaluate nasal sIgE yet, both positive NAPT and detectable sIgE in obtained nasal mucosa were adopted as the diagnostic criteria of LAR in order to strictly elucidate the possibility of presence of LAR in Japan. Results: JCP LAR was definitely diagnosed in 2 of 14 patients (14.3%) and HDM LAR in 5 of 21 (23.8%) in cases with rhinosinusitis symptoms in the absence of positive ST nor serum sIgE. Conclusion: The present results positively support LAR by HDM or JCP being present in Japan. [ABSTRACT FROM AUTHOR]

Objective: Long-term safety and efficacy of 10- and 20-mg rupatadine in Japanese patients with perennial allergic rhinitis (PAR) were investigated in a 52-week open-label study (JapicCTI-152952, clinicaltrials.jp). Methods: The rupatadine dose was fixed to 10 mg once daily for the first 2 weeks. Thereafter, the study investigator was allowed to increase the dosage to 20 mg if the response was insufficient. Safety was evaluated on the basis of treatment-emergent adverse events, laboratory findings, and vital sign measurements. The primary efficacy endpoint was changed from baseline to Week 2 in the total 4 nasal symptom score. Secondary efficacy endpoints included changes over time in ocular symptoms, patient and physician clinical overall impression, and patient quality-of-life. Results: Seventy-two immunoglobulin E positive patients (mean age = 32.1 years), consisting of 58 adults (age ≥ 18 years) and 14 adolescents (12–17 years), were enrolled. Ninety-four treatment-emergent adverse events were reported in 48 patients (66.7%), including nine adverse drug reactions in nine patients (12.5%). The most frequently reported adverse drug reaction was somnolence (9.7%). The primary and secondary efficacy endpoints demonstrated a statistically significant clinical benefit with rupatadine. The rupatadine dose was increased from 10 to 20 mg in 36 patients (50.0%), which resulted in better symptom management. Conclusions: Rupatadine 10- and 20-mg once-daily doses were well tolerated in long-term use. Updosing to 20 mg is a reasonable option in PAR patients whose symptoms cannot be controlled effectively by the 10-mg dose. [ABSTRACT FROM AUTHOR]

Background and Objective: We reported neutrophil-associated tissue damage in cedar pollinosis subjects with refractory nasal symptoms prior to pollinosis season. Because the leukotriene receptor antagonist, montelukast, can inhibit neutrophil recruitment and activation, we investigated its effects on symptom relief and nasal neutrophilia in pollinosis subjects in the preseason. Methods: In the pollinosis preseason, symptomatic (PreSyP, n = 149) and asymptomatic subjects (PreAsP, n = 145) were prophylactically treated, and in season symptomatic subjects (InSyP, n = 134) were treated. Individuals were assigned to 1 of 2 treatment protocols: administration of cetirizine and fluticasone nasal spray (Cet-Flu) or montelukast, fexofenadine, and fluticasone nasal spray (Mo-Fex-Flu). Differences in symptom relief and inflammatory cell infiltration in nasal swabs were investigated. Results: In pollen season, 59% of PreSyP subjects given Cet-Flu and 88% of those treated with Mo-Fex-Flu had none or mild symptoms (P <.00001). In PreAsP subjects in season, 71% of Cet-Flu and 98% of Mo-Fex-Flu recipients had none to mild symptoms (P <.0000001). The proportions of subjects in the PreSyP group with nasal swabs with neutrophils 1+ to 3+ before and after treatment by Mo-Fex-Flu were 59% and 18%, respectively (P <.0001), and in PreAsyP, subjects with neutrophils 2+ to 3+ were 17% and 5%, respectively (P =.034). In PreSyP, a significant reduction in the percentage of subjects with mast cells >1+ was seen following both Cet-Flu (P =.027) and Mo-Fex-Flu (P =.0014) treatments. Conclusion: In PreSyP and PreAsP subjects, treatments with Mo-Fex-Flu were more effective than Cet-Flu to reduce nasal symptom scores. These effects were associated with reduction in the number of neutrophils and mast cells in nasal swabs. [ABSTRACT FROM AUTHOR]

Abstract Background Rupatadine is a novel non-sedating second-generation H 1 -antihistamine with antiplatelet-activating factor activity, first marketed in Spain in 2003. It is used for treating allergic rhinitis in more than 80 countries. This study investigated its efficacy and safety in Japanese patients with seasonal allergic rhinitis (SAR). Methods This was a randomized, placebo-controlled, double-blind study conducted at 4 medical institutions in Japan (JapicCTI-152785). Adolescent and adult SAR outpatients aged 12–64 years entered a 1-week placebo run-in period. After eligibility was confirmed, patients orally received placebo, rupatadine 10 mg, or 20 mg once daily for 2 weeks. The primary endpoint was a change from baseline to second week of treatment in total 4 nasal symptom score (T4NSS). Results Nine hundred patients were randomly assigned to placebo, rupatadine 10 mg, or rupatadine 20 mg (302, 298, and 300 patients, respectively). The least squares mean difference in the primary endpoint between rupatadine and placebo was −1.085 for 10 mg, and −1.415 for 20 mg (analysis of covariance, both P < 0.001). The rates of adverse events were 6.6%, 14.1%, and 15.0% for placebo, rupatadine 10 mg, and rupatadine 20 mg, respectively. Somnolence was most frequently reported: 7.0% for rupatadine 10 mg and 7.3% for rupatadine 20 mg. No serious adverse drug reactions were observed, and no adverse events resulted in premature discontinuation. Conclusions Rupatadine 10 and 20 mg were significantly superior to placebo in improving nasal and ocular symptoms of SAR, and were well tolerated. [ABSTRACT FROM AUTHOR]

Background The emedastine patch was developed in Japan as the first transdermal drug delivery system of emedastine difumarate for allergic rhinitis. Methods A multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison was conducted in patients with seasonal allergic rhinitis. Patients were administered Emedastine patches (4 or 8 mg), placebo, or levocetirizine hydrochloride (5 mg tablet) once daily for 2 weeks (double-dummy technique). The primary objective was superiority to placebo by the change of the total nasal symptom score (sneezing, rhinorrhea, and nasal congestion) in Week 2. Levocetirizine was a reference drug and not a comparator in this study. Results A total of 1276 patients were randomized to receive the 4 mg emedastine patch (n = 384), 8 mg emedastine patch (n = 382), placebo (n = 384), or levocetirizine (n = 126). The least squares mean (LSM) of the change from baseline of the total nasal symptom score (TNSS) in Week 2 was significantly larger in both emedastine patch groups than in the placebo group (adjusted p < 0.0001). In secondary analysis, LSM of the change in the TNSS was −1.20, −1.49, −0.44, and −1.32 in the 4 mg emedastine patch, 8 mg patch, placebo, and levocetirizine, respectively. Reductions in the number of episodes and scores of individual nasal symptoms were all significantly larger throughout the day in the emedastine patch groups than the placebo group (all p < 0.05). No clinically significant safety problems occurred. Conclusions The emedastine patch (4 and 8 mg) effectively and safely controlled symptoms of seasonal allergic rhinitis with sustained action throughout the day. Study registration: JapicCTI-153092. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline. [ABSTRACT FROM AUTHOR]

Background: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1 -specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intra-peritoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). Methods: Mice were injected intraperito-neally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. Results: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion. Conclusions: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo. [ABSTRACT FROM AUTHOR]

Background and Objective: From mid February to the end of March, each year ∼30% of Japanese have Japanese cedar pollinosis. Moreover, 10-50% of patients with this pollinosis exhibit nasal manifestations in the preseason. These patients have a predominance of neutrophils but not eosinophils in nasal swabs and high carriage of Staphylococcus aureus. We hypothesized that S. aureus or other bacteria and associated neutrophilia were involved in preseasonal symptoms. Methods: Cytology and bacterial colony growth were assessed in nasal swabs in the groups of asymptomatic patients in the preseason (PreAsP) (n = 53) and symptomatic patients in the preseason (PreSyP) (n = 60), and in group of symptomatic patients in season (InSyP) (n = 72). Results: In the preseason, high neutrophilia was present in only 20% of the PreAsP group but in 47% of the PreSyP group (p < 0.01). Nasal carriage of S. aureus in the PreAsP and PreSyP groups were 79%, 75%, respectively, whereas, for Moraxella catarrhalis, these were 9% versus 25% (PreAsP versus PreSyP group; p < 0.05). In patients with positive results for S. aureus and M. catarrhalis, the degrees of neutrophilia (-, ±, +, 2+, 3+) in the PreSyP group were larger than in the PreAsP groups (p < 0.01). In the PreSyP group, the magnitude of neutrophilia was greater (p < 0.05) in subgroups with more colonies of S. aureus than in subgroups with fewer colonies. Conclusion: Nasal symptoms in the preseason are associated with neutrophilia and nasal colonization with S. aureus and M. catarrhalis. Patients with symptoms in the preseason had improved symptom scores when given prophylactic treatment early in season but had more-severe symptom scores late in season than asymptomatic patients in the preseason. Neutrophil-associated tissue damage related to bacterial colonization may underlie these associations. [ABSTRACT FROM AUTHOR]

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 < 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. [ABSTRACT FROM AUTHOR]

Abstract: Adrenomedullin (AM) is a potent hypotensive and vasodilatory peptide. AM may exert protective actions against the development of many diseases by modulating the blood circulation and body fluid balance. In addition to these functions, it has recently been reported to play important roles in the development of allergy and infections. The purpose of the present study was to demonstrate the existence of AM in the human nasal mucosa and to discuss whether AM might contribute to the pathogenesis of nasal congestion. We measured the total AM concentrations in the nasal discharge. The total AM concentration in the nasal discharge was significantly higher in the non-allergy group (72.1±55.5fmol/ml) than in the allergy group (37.1±44.2fmol/ml). By immunohistochemical examination, we identified AM-containing cells in the nasal mucosa from both subjects with and without nasal allergy, and also in nasal polyps. Moreover, those cells were positive for anti-tryptase antibody which recognizes mast cells. In nasal allergy, vasodilatation and increase in vascular permeability are characteristic features of the immediate phase response. Reduced AM levels in the nasal discharge may be associated with attenuation of both of these factors. On the other hand, immunohistochemical analysis demonstrated AM-immunoreactive cells in the chronic phase of rhinosinusitis. In the late and inflammatory phase, mast cells produce AM, which possibly acts as an inhibitor of inflammatory cell migration. In conclusion, AM may be actively secreted into the nasal discharge. AM in the nasal discharge may have protective and anti-inflammatory effects in the nasal mucosa. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis involves inflammation of the nasal passages. The use of nasal steroids is generally very effective in providing significant symptom relief. However, compliance for their use is sometimes poor. Methods: To examine the efficacy of early intervention (before pollen dispersal) with oral cysteinyl leukotriene receptor antagonists (LTRA) on pollinosis in patients with allergy to cedar and Japanese cypress pollens, groups of subjects were treated with LTRA or a placebo for 4 weeks at the beginning of the cedar pollen dispersal season. Subsequently, all patients received nasal steroid therapy concomitantly with LTRA throughout the remaining period of the pollen dispersal season. The effects of such early treatment with LTRA on pollinosis were investigated using symptom scores from an allergy diary and quality of life (QOL) scores. Results: Sneezing and nasal congestion scores were significantly lower in the LTRA-pretreated subjects than observed in the placebo-pretreated patients between weeks 4 and 6 and weeks 3 and 5, respectively. QOL scores improved significantly in all domains after concomitant therapy with nasal steroids. The percent improvement in the nasal congestion score after the concomitant therapy was significantly higher in the LTRA group (69%) than in the placebo group (41%). Conclusion: Significant differences observed in symptoms and in QOL effects between LTRA- and placebo-pretreated patients and the absence of major adverse effects noted in these studies suggest that early intervention with LTRA is beneficial and safe and should be considered in the management of pollinosis-associated allergic rhinitis. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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/m3, 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/m3. 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 © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Fluticasone furoate nasal spray (FFNS) is a novel, enhanced-affinity glucocorticoid administered in a unique side-actuated device for the treatment of allergic rhinitis. No previous clinical studies have compared the efficacy of FFNS with another intranasal steroid. The purpose of this study was to compare the efficacy and safety of FFNS, 110 μg/day, once daily with fluticasone propionate nasal spray (FPNS), 200 μg/day, twice daily in patients with Japanese cedar pollinosis to support the regulatory filing in Japan. In this multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients (≥16 years old) were randomized to receive 2 weeks of treatment with FFNS (n = 151), FFNS placebo (n = 72), FPNS (n = 148), or FPNS placebo (n = 75). FFNS once daily was noninferior to FPNS twice daily in mean change from baseline in three total nasal symptom scores (3TNSS; sneezing, rhinorrhea, and nasal congestion; -1.23 ± 0.140 and -1.06 ± 0.142, respectively). Compared with placebo, FFNS was superior in reducing 3TNSS (p < 0.001). Both FFNS and FPNS showed similar mean changes from baseline in 4TNSS (3TNSS and nasal itching) and individual nasal symptom scores. The onset of action for FFNS was observed from the 1st day of treatment, whereas in the FPNS group it was observed on the 2nd day. There were similar improvements in rhinoscopy findings, activity of daily life interference, and patient-rated overall evaluation to therapy in the FFNS and FPNS groups. FFNS was well tolerated. Treatment with once-daily FFNS was effective and noninferior to twice-daily FPNS in reducing nasal symptoms. Faster onset of action for FFNS was observed. [ABSTRACT FROM AUTHOR]

Background: During the course of development of montelukast, a cysteinyl leukotriene receptor 1 antagonist, for treatment of seasonal allergic rhinitis, a double-blind, non-inferiority study was carried out to evaluate the efficacy and safety of montelukast 5 mg and 10 mg compared with pranlukast 450 mg, which has a similar mechanism of action. Methods: Montelukast 5 mg, 10 mg or pranlukast 450 mg and the corresponding placebo were orally administered to patients with seasonal allergic rhinitis three times a day for 2 weeks. Non-inferior efficacy of montelukast 5 mg and 10 mg to pranlukast 450 mg was investigated by the change from the baseline in the composite nasal symptoms scores over the 2-week treatment period. Results: Montelukast 5 rag, 10 mg once daily and the pranlukast 450 mg/day showed significant improvements in the change from the baseline in the composite, daytime and nighttime nasal symptom scores, and the improvement lasted for 2 weeks. Montelukast 5 mg and 10 mg were non-inferior to pranlukast 450 mg in the change from the baseline in the composite nasal symptoms scores. The incidence rates of adverse experiences and drug-related adverse experiences were not significantly different among the three treatment groups. Conclusions: The results indicate that administration of montelukast 5 mg and 10 mg once daily are potent alternatives for the treatment of seasonal allergic rhinitis and demonstrated that the efficacy and the safety profiles are comparable with pranlukast 450 mg/day. [ABSTRACT FROM AUTHOR]

Background: Secretion of nasal discharge was enhanced and airway-resistance in the nasal cavity was augmented, resulting in nasal congestion, when leukotrienes were administered to the nasal mucosa. These results indicate that leukotrienes play an important role in the pathogenesis of allergic rhinitis. Methods: A double-blind clinical study was carried out to evaluate the efficacy and the safety of montelukast, a cysteinyl leukotriene receptor 1 antagonist, 5 mg, 10 mg or placebo orally administered once daily at bedtime for 2 weeks, to Japanese patients with seasonal allergic rhinitis. The composite nasal symptom scores (average over the 2-week treatment period) were compared among the montelukast 5 mg and 10 mg groups with the placebo group. Results: The composite nasal symptom score significantly improved in the montelukast 5 mg and 10 mg groups compared with the placebo group. The administration of montelukast 5 mg or 10 mg once daily was well tolerated and the safety profiles were similar to those of the placebo. There were no significant differences in the incidences of adverse experience or drug-related adverse experience among the montelukast 5 mg, 10 mg groups and the placebo group. Conclusions: Both montelukast 5 mg and 10 mg doses show clinically meaningful efficacy for the treatment of patients with seasonal allergic rhinitis and the safety profiles of those are comparable to that of the placebo. [ABSTRACT FROM AUTHOR]

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 < .01 or P < .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. [ABSTRACT FROM AUTHOR]

Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a substantial problem in Japan. Omalizumab, a novel humanized monoclonal anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms associated with SAR. To investigate the safety and efficacy of omalizumab in the treatment of patients with Japanese cedar pollen-induced SAR compared to placebo or anti-allergic drug, two randomized, double-blind studies were conducted in Japan. Omalizumab (150, 225, 300, or 375 mg) or placebo was administered subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at baseline. IPD was administered 300 mg per day through the season. Primary and all secondary efficacy variable scores were significantly lower in the omalizumab group than in the placebo group (P < .01) and IPD, Th2 cytokine inhibitor group (P < .01). Omalizumab was effective and safe in the treatment of SAR induced by Japanese cedar pollens. And the methods of increasing effects by combining omalizumab with antibody-specific immunotherapy are being considered. These strategy is more effective than immune-therapy alone. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ≤ 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 © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

There is no consensus on the optimal surgical technique for allergic rhinitis (AR). Furthermore, the appropriateness of surgical intervention in children and older individuals remains debatable. This study aimed to analyze trends and patterns in the surgical management of AR in Japan, focusing on parasympathetic neurectomy. Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we conducted a comprehensive review of procedures performed between April 2014 and March 2022. In addition, a cross-sectional survey targeting otolaryngologists across Japan was conducted to gather insights into surgical preferences and practices. The NDB data showed an increasing trend in neurectomies, with the most frequent age group being 25–29 years; the procedure was also performed in pediatric and older patients. The survey among otolaryngologists indicated that 58.2 % of surgeons preferred peripheral branch neurectomy of the posterior nasal nerve. The findings of this study also indicated a cautious approach toward conducting these procedures in children, with 51.2 % of surgeons considering patients less than 18 years of age unsuitable for the procedure. This study highlighted a shift toward simple and minimally invasive surgical methods, such as peripheral branch neurectomy, in Japan. However, further research is needed to understand the long-term outcomes and refine the surgical techniques. The findings of this study also emphasized the need for age-specific considerations when treating pediatric and older patients with AR. [ABSTRACT FROM AUTHOR]

Background: Different clinical trials showed the superior efficacy of rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. Methods: This study is a pooled analysis of data of seven randomized, double-blind, placebo-controlled SAR studies comparing responder proportions upon treatment with rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near-to-complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Results: Data from 1470 patients were analyzed: 332 treated with placebo, 662 with rupatadine 10 mg and 476 with rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in rupatadine groups compared to the placebo group across the visits. Among rupatadine-treated patients, those receiving 20 mg compared favourably for both cut-off responses. The time to achieve a proportion of responders was shorter in the rupatadine 20 mg group than in the rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near-to-complete response for both symptom scores was higher in rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. Conclusions: This responder analysis confirms the superior efficacy of rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose-dependent manner, with faster and higher response rates in the 20 mg group. [ABSTRACT FROM AUTHOR]

Background: Health-related social media data are increasingly used in disease-surveillance studies, which have demonstrated moderately high correlations between the number of social media posts and the number of patients. However, there is a need to understand the causal relationship between the behavior of social media users and the actual number of patients in order to increase the credibility of disease surveillance based on social media data.Objective: This study aimed to clarify the causal relationships among pollen count, the posting behavior of social media users, and the number of patients with seasonal allergic rhinitis in the real world.Methods: This analysis was conducted using datasets of pollen counts, tweet numbers, and numbers of patients with seasonal allergic rhinitis from Kanagawa Prefecture, Japan. We examined daily pollen counts for Japanese cedar (the major cause of seasonal allergic rhinitis in Japan) and hinoki cypress (which commonly complicates seasonal allergic rhinitis) from February 1 to May 31, 2017. The daily numbers of tweets that included the keyword "kafunshō" (or seasonal allergic rhinitis) were calculated between January 1 and May 31, 2017. Daily numbers of patients with seasonal allergic rhinitis from January 1 to May 31, 2017, were obtained from three healthcare institutes that participated in the study. The Granger causality test was used to examine the causal relationships among pollen count, tweet numbers, and the number of patients with seasonal allergic rhinitis from February to May 2017. To determine if time-variant factors affect these causal relationships, we analyzed the main seasonal allergic rhinitis phase (February to April) when Japanese cedar trees actively produce and release pollen.Results: Increases in pollen count were found to increase the number of tweets during the overall study period (P=.04), but not the main seasonal allergic rhinitis phase (P=.05). In contrast, increases in pollen count were found to increase patient numbers in both the study period (P=.04) and the main seasonal allergic rhinitis phase (P=.01). Increases in the number of tweets increased the patient numbers during the main seasonal allergic rhinitis phase (P=.02), but not the overall study period (P=.89). Patient numbers did not affect the number of tweets in both the overall study period (P=.24) and the main seasonal allergic rhinitis phase (P=.47).Conclusions: Understanding the causal relationships among pollen counts, tweet numbers, and numbers of patients with seasonal allergic rhinitis is an important step to increasing the credibility of surveillance systems that use social media data. Further in-depth studies are needed to identify the determinants of social media posts described in this exploratory analysis. [ABSTRACT FROM AUTHOR]

Antihistamines targeting the histamine H1 receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H1 receptor occupancy (H1RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20–50%), and sedating (≥50%) groups based on H1RO. Among the non-sedating group, fexofenadine and bilastine are classified into "non-brain-penetrating antihistamines" based on the H1RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H1 receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet has been approved in 11 European countries and Japan for patients with HDM-induced respiratory allergic disease. Objective This trial was conducted to confirm the efficacy and safety of the SQ HDM SLIT tablet in Japanese patients with moderate-to-severe HDM-induced allergic rhinitis (AR). Methods The trial was a randomized, double-blind, placebo-controlled trial including 946 Japanese adults and adolescents (12-64 years). Subjects were randomly assigned to daily treatment with the SQ HDM SLIT tablet at a dose of 10,000 Japanese allergy units (JAU) or 20,000 JAU or to placebo (1:1:1). The primary end point was the total combined rhinitis score (TCRS), which is composed of AR symptom and medication scores during the efficacy evaluation period. Symptom and medication scores of AR and conjunctivitis, rhinitis quality of life, and symptom-free and symptom-severe days were evaluated as secondary end points. Results Analysis of the primary end point demonstrated statistically significant reductions in TCRSs of 1.15 (22%, P < .001) in the 10,000-JAU group and 0.99 (19%, P < .001) in the 20,000-JAU group compared with the placebo group. The statistically significant treatment effect was evident from 12 weeks of treatment onward. All secondary end points, except AR medication score, were statistically significant in favor of active treatment compared with placebo. Post hoc analysis of TCRSs in adolescents showed the same efficacy as in adults ( P < .05). The treatment was well tolerated by both adults and adolescents. Conclusion The trial confirmed the efficacy and safety profile of the SQ HDM SLIT tablet in Japanese adult and adolescent patients with moderate-to-severe HDM-induced AR. These data support the robust efficacy and safety profile of previously reported European data. [ABSTRACT FROM AUTHOR]

A preface to the November 2012 issue of "Clinical & Experimental Allergy Reviews" is presented.

The article offers information on the eighth "Allergy Reviews" forum and discussions on allergic rhinitis which was held in 2010.

A preface for the research studies presented at the Allergic Rhinitis Forum 2009 and discussed within the issue is presented.

A preface for the journal "Clinical and Experimental Allergy Reviews," 9, iv issue is presented.

Introduces a series of articles on research papers about allergic rhinitis presented at the Allergic Rhinitis Forum 2004.

Offers information on the 2003 Allergic Rhinitis Forum held in Japan. Highlights of the event; Prevalence of allergic rhinitis in the country.

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IgE and mast cells play a pivotal role in various allergic diseases, including asthma, allergic rhinitis, and urticaria. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved control of these allergic diseases and introduced a new era for the management of severe allergic conditions. About 10 years of experience with omalizumab treatment for severe allergic asthma confirmed its effectiveness and safety, reducing symptoms, frequency of reliever use, and severe exacerbations in patients with intractable conditions. Omalizumab is particularly useful in childhood asthma, where atopic conditions often determine clinical courses of asthma. Recently, omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) with the fixed dose of 300 mg. Although the mechanisms underlying the actions of omalizumab in CSU are not fully clarified, nearly 90% of patients with CSU showed a complete or a partial response to omalizumab treatment. Furthermore, omalizumab is just approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of an add-on study of omalizumab for inadequately controlled severe pollinosis despite antihistamines and nasal corticosteroids. For proper use of omalizumab to treat severe JC, co-administration of antihistamines is necessary, while patients should meet the criteria including strong sensitization to Japanese cedar pollen (≥class 3) and poor control under standard treatment. In the management of severe allergic diseases using omalizumab, issues including cost and concerns about relapse after its discontinuation should be overcome. At the same time, possibilities for application to other intractable allergic diseases should be considered. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. The Japanese cedar pollen SLIT tablets exhibited treatment duration-dependent efficacy. Image 2 [ABSTRACT FROM AUTHOR]

Background To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial. Methods Japanese patients aged 5–65 years were eligible for the study, if they had HDM-induced allergic rhinitis (AR), allergic bronchial asthma (BA), or both. TO-204 was administered in a dose titration scheme, and the maintenance dose was determined according to the predefined criteria. The treatment period was 52 weeks, and patients who were willing to continue the treatment received TO-204 beyond 52 weeks. This clinical trial is registered at the Japan Pharmaceutical Information Center (Japic CTI-121900). Results Between July 2012 and May 2015, 44 patients (28 with AR and 16 with allergic BA) were enrolled into the study. All patients were included in the analysis. The duration of treatment ranged from 23 to 142 weeks and the median maintenance dose was 200 Japanese allergy units (JAU). Adverse events occurred in 22 patients (50%). The most common adverse event was local reactions related to the injection sites. Four patients experienced anaphylactic reactions when they were treated with the dose of 500 JAU. Two patients experienced anaphylactic shock with the doses of 1000 JAU at onset. These 6 patients could continue the study with dose reduction. Conclusions Safety profile of TO-204 was acceptable in Japanese patients with HDM-induced AR or allergic BA. Higher doses should be administered carefully, because the risk of anaphylaxis increased at doses of 500 or 1000 JAU. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]