Japanese Cedar Pollinosis Research Articles

Retrospective Observational Study on Telemedicine in Sublingual Immunotherapy for Patients with Japanese Cedar Pollinosis and House Dust Mite Allergic Rhinitis.

Introduction: In Japan, telemedicine has gradually expanded due to deregulation in response to the COVID-19 pandemic. However, its current status remains unclear, as it is primarily provided by general practitioners. This study aims to examine the use of telemedicine in sublingual immunotherapy (SLIT) for patients with Japanese cedar pollen allergy and/or house dust mite allergic rhinitis. Methods: We conducted a retrospective analysis of medical record data from seven otorhinolaryngology clinics and performed an exploratory evaluation between a group that combined telemedicine and in-person visits during the initial 6 months of SLIT and another group with only in-person visits. Results: Following propensity score matching, 51 and 82 patients were eligible for the telemedicine and in-person groups, respectively, with 33 cases in both groups. Both groups had similar characteristics after matching. No significant difference was found in the withdrawal rate at 6 months from the start of SLIT (6.1% and 9.1% in each group; p = 1.00), side effects, or treatment efficacy between the two groups. The average copayment for patients tended to be significantly higher in the telemedicine group after one, three, and 6 months following SLIT initiation. Discussion: The situation of patients who receive an appropriate combination of telemedicine and in-person visits is not significantly different from patients who receive in-person visits alone. This study may help indicate the actual status of telemedicine in Japan. Further investigation at more facilities is necessary in the future to dispel concerns in the practice setting.

The impact of adverse reactions on adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy in Japan

Background Allergen immunotherapy is the only treatment that can achieve remission for allergic diseases. Aims/Objectives To investigate the three-year adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy at a clinic in Japan and identify factors that influence adherence and severe adverse reactions. Material and Methods In total, 174 patients aged 12 years or older who started sublingual immunotherapy for Japanese cedar pollinosis (n = 72), house dust mite allergy (n = 55), or both (n = 47) between May 2017 and June 2018. Patient age, sex, type of pharmacotherapy used, adverse reactions, blood test results, and duration of continuous treatment were investigated. Results The three-year treatment continuation rate was 40.8%. Adverse reaction rates were 12.6% for cedar pollinosis and 40.2% for house dust mite allergy. Patients with dose reductions due to severe reactions had lower first-year continuation rates. In the MITICURE® group, patients with severe reactions had significantly higher serum total IgE levels. Severe reactions were more common in MITICURE® patients with seven or more positive antigen types. Conclusions and Significance Severe adverse reactions reduced early adherence.

The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis

The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis

CRISPR/Cas9-mediated disruption of CjACOS5 confers no-pollen formation on sugi trees (Cryptomeria japonica D. Don)

Sugi (Cryptomeria japonica D. Don) is an economically important coniferous tree in Japan. However, abundant sugi pollen grains are dispersed and transported by the wind each spring and cause a severe pollen allergy syndrome (Japanese cedar pollinosis). The use of pollen-free sugi that cannot produce pollen has been thought as a countermeasure to Japanese cedar pollinosis. The sugi CjACOS5 gene is an ortholog of Arabidopsis ACOS5 and rice OsACOS12, which encode an acyl-CoA synthetase that is involved in the synthesis of sporopollenin in pollen walls. To generate pollen-free sugi, we mutated CjACOS5 using the CRISPR/Cas9 system. As a result of sugi transformation mediated by Agrobacterium tumefaciens harboring the CjACOS5-targeted CRISPR/Cas9 vector, 1 bp-deleted homo biallelic mutant lines were obtained. Chimeric mutant lines harboring both mutant and wild-type CjACOS5 genes were also generated. The homo biallelic mutant lines had no-pollen in male strobili, whereas chimeric mutant lines had male strobili with or without pollen grains. Our results suggest that CjACOS5 is essential for the production of pollen in sugi and that its disruption is useful for the generation of pollen-free sugi. In addition to conventional transgenic technology, genome editing technology, including CRISPR/Cas9, can confer new traits on sugi.

Development of allergen immunotherapy Tablet for Japanese cedar pollinosis

Development of allergen immunotherapy Tablet for Japanese cedar pollinosis

Japanese Cedar Pollen Allergens in Japan.

Pollen from members of the Cupressaceae tree family is one of the most important causes of allergic disease in the world. Cryptomeria japonica (Japanese cedar) and Chamaecyparis obtusa (Japanese cypress) are Japan's most common tree species. The pollen dispersal season is mainly from February to May. The major allergens of Japanese cedar and Japanese cypress exhibit high amino acid sequence similarity due to the phylogenetic relationship between the two species. An epidemiological study has shown that the prevalence of Japanese cedar pollinosis is approximately 40%. Younger children (5 to 9 years old) showed a high prevalence of Japanese cedar pollinosis as 30% in 2019, indicating that season pollinosis is getting worse. Pharmacotherapy is the most common treatment for pollinosis induced by Japanese cedar and Japanese cypress. Patients' satisfaction with pharmacotherapy is low due to insufficient experienced effect and daytime somnolence. Unlike pharmacotherapy, allergy immunotherapy (AIT) addresses the basic immunological mechanisms of allergic disease and activates protective allergen-reactive pathways of the immune system. AIT is now recognized as the only treatment option with the potential to provide long-term post-treatment benefits and alter the natural course of the allergic disease, including Japanese cedar pollinosis.

Suppressive Effect of Lactococcus lactis subsp. cremoris YRC3780 on a Murine Model of Japanese Cedar Pollinosis.

Accumulating evidence suggests that Lactococcus lactis subsp. cremoris YRC3780 isolated from kefir has the potential to alleviate allergic responses. Herein, we investigated the effect of YRC3780 on a murine model of Japanese cedar pollinosis (JCP). BALB/c mice immunized with cedar pollen extract (CPE) exhibited an increase in serum immunoglobulin E and developed nasal inflammatory responses including sneezing, nasal hyperresponsiveness, and nasal eosinophil accumulation upon intranasal allergen challenge. These responses were suppressed by the oral administration of YRC3780, although the effects on CPE-induced sneezing response and eosinophil infiltration were not statistically significant. Total fecal microbiota diversity was not affected by allergen immunization and challenge or by YRC3780 administration. However, the abundances of Bifidobacteriales, Veillonellaceae, Lactococcus, and Lactococcus lactis were larger and that of Bacteroides was smaller in YRC3780-treated mice compared with those in CPE-challenged and YRC3780-untreated mice. Our findings suggest the usefulness of YRC3780 for alleviating JCP.

Sublingual Immunotherapy for Japanese Cedar Pollinosis: Current Clinical and Research Status.

The incidence of Japanese cedar pollinosis is increasing significantly in Japan, and a recent survey suggested that about 40% of the population will develop this disease. However, spontaneous remission is rare. The increased incident rate of Japanese cedar pollinosis is a huge issue in Japan. Allergen immunotherapy is the only fundamental treatment that modifies the natural course of allergic rhinitis and provides long-term remission that cannot be induced by general drug therapy. Sublingual immunotherapy for Japanese cedar pollinosis has been developed and has been covered by health insurance since 2014 in Japan. The indication for children was expanded in 2018. Clinical trials of sublingual immunotherapy for Japanese cedar pollinosis have demonstrated its long-term efficacy and safety. It is recommended for patients who wish to undergo fundamental treatment regardless of the severity of the practical guidelines for the management of allergic rhinitis in Japan. For sublingual immunotherapy, a long-term treatment period of 3 years or longer is recommended to obtain stable therapeutic effects. In recent years, evidence based on basic research and clinical trials has demonstrated sublingual immunotherapy-induced immunological changes and efficacy in patients; however, biomarkers that objectively predict and judge these therapeutic effects need to be established.

Complement Factor H Is an Early Predictive Biomarker of the Therapeutic Efficacy of Sublingual Immunotherapy for Japanese Cedar Pollinosis.

Sublingual immunotherapy for Japanese cedar pollinosis can improve the symptoms of allergic rhinitis and modify its natural course. However, sublingual immunotherapy requires a long treatment period and some patients do not respond to treatment. In this study, we aimed to identify biomarkers that could predict the efficacy of sublingual immunotherapy at an early stage. In this study, 40 patients from phase III trials were recruited and divided into good and poor response groups. Using peripheral blood mononuclear cells from before and two months after the start of medication, microarray, discriminant analysis, and real-time polymerase chain reaction were performed to extract candidate genes that could be biomarkers. Furthermore, these genes were validated in 30 patients in general clinical practice. Complement factor H was upregulated in the good response group and downregulated in the poor response group. Complement factor H may be a useful biomarker for predicting the efficacy of sublingual immunotherapy for Japanese cedar pollinosis at early time points after treatment initiation.

Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion

Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood. We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response. Antigen-stimulated culturing after SLIT led to clonal expansion of TH2 and regulatory T cells, and most of these CD4+ T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional TH2 cells but increased the trans-type TH2 cell population that expresses musculin (MSC), TGF-β, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type TH2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment. The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic TH2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis

ObjectiveCombination intranasal drugs with a corticosteroid and antihistamine are available in several countries with better effect than treatments with single agents. However, it remains unclear whether this effect is also seen in Japanese cedar pollinosis (JCP), the most prevalent seasonal allergic rhinitis in Japan. We investigated the effect of an add-on intranasal antihistamine with an intranasal corticosteroid in JCP during the pollen dispersal period. (UMIN000025508) MethodsWe performed a double-blinded, randomized, placebo-controlled trial from March 1 to 14, 2017. Patients (n = 20 per group) received either a mometasone furoate nasal spray (MFNS) plus a levocabastine nasal spray (levocabastine group) or MFNS plus a placebo nasal spray (placebo group). The primary endpoint was the difference in the total nasal symptom score (TNSS) after treatment between the two groups. Differences in the total ocular symptom score, total symptom score, total medication score, total symptom-medication score, and five individual symptoms as well as safety were the secondary endpoints. ResultsThe change in the TNSS from baseline was significantly greater in the levocabastine group than in the placebo group. A significant reduction in the TNSS was observed more than 6 days earlier in the levocabastine group than in the placebo group. Such add-on effects were also seen in the secondary endpoints. Both treatments were well-tolerated. ConclusionThe intranasal antihistamine provided better control of not only nasal symptoms, but also of ocular symptoms, and decreased the need for rescue medications when added to intranasal corticosteroid treatment in JCP patients.

Japanese cedar pollinosis and fruit allergy caused by GRPs

Japanese cedar pollinosis and fruit allergy caused by GRPs

Comparative Survey of Children and Adults with Japanese Cedar Pollinosis Using a Self-written Questionnaire on Sublingual Immunotherapy in Clinical Practice

Comparative Survey of Children and Adults with Japanese Cedar Pollinosis Using a Self-written Questionnaire on Sublingual Immunotherapy in Clinical Practice

Clinical Study of 20 Cases of Severe Japanese Cedar Pollinosis Treated with Omalizumab

Clinical Study of 20 Cases of Severe Japanese Cedar Pollinosis Treated with Omalizumab

Investigation of the sensitization rate for gibberellin-regulated protein in patients with Japanese cedar pollinosis.

Pollen-food allergy syndrome (PFAS) usually manifests as an itching sensation in the mouth and throat immediately after eating fresh fruits and vegetables. However, some patients with PFAS experience systemic symptoms including anaphylaxis. In Europe, cypress gibberellin-regulated protein (GRP) has been noted to cause allergenicity and exhibit cross-reactivity with peach GRP. Japanese cedar (Cryptomeria japonica), classified in the cypress family, is the primary causative substance among all environmental allergens in Japan. However, studies on the prevalence of GRP sensitization in patients with cedar pollinosis are lacking. This study examined the prevalence of GRP sensitization in patients with Japanese cedar pollinosis. We enrolled 52 patients who had requested sublingual immunotherapy treatment with mild-to-severe rhinitis during spring, and had a JCP-specific immunoglobulin E (IgE) levels of >0.7 UA/mL. Peach GRP was purified using affinity chromatography with a monoclonal antibody column. Specific IgE levels to peach GRP were measured using an enzyme-linked immunosorbent assay. Samples exhibiting absorbance at 450 nm of over mean plus three standard deviations of the negative control value were defined as positive. Sera from three patients with severe peach allergy were used as positive controls. Eleven sera from 52 patients with JCP-induced allergic rhinitis were positive for peach GRP. Twenty percent of patients with cedar pollinosis were sensitized to peach GRP. Well-powered studies are needed to clarify whether these patients are at an increased risk for systemic symptoms or whether they primarily demonstrate only localized symptoms.

The impact of omalizumab on paid and unpaid work productivity among severe Japanese cedar pollinosis (JCP) patients

Aims Japanese cedar pollinosis (JCP) is a form of seasonal allergic rhinitis that affects 38.8% of the Japanese population. Particularly severe and most severe symptoms among JCP patients can lead to impairments of paid work productivity and unpaid work activities. Indeed, the current standard of care (SoC) is not always able to relieve these symptoms. Omalizumab, a novel JCP treatment recently approved in Japan, provides an effective add-on therapy to the SoC. This study estimates the effect of omalizumab on paid and unpaid work activities (i.e. its social impact) in patients with severe and most severe JCP symptoms in Japan. Methods The impact of omalizumab was estimated through a one-year static cohort model using the Work Productivity and Activity Impairment Allergy Specific (WPAI-AS) questionnaire derived from a clinical trial on omalizumab enrolling patients with severe and most severe JCP symptoms, which had been conducted in Japan. This effect was quantified using Japanese official statistics on employment and time use. The human capital approach and the proxy good approach were employed to monetize paid and unpaid work activities, respectively. A sensitivity analysis was implemented to account for modeling structural uncertainties. Results Our results show that the use of omalizumab might reduce the paid and unpaid work productivity losses due to severe and most severe JCP by nearly one-third. In the severe symptom period of three weeks, 36.6 million hours of lost paid and unpaid work hours could be avoided, which sums up to a monetized productivity loss of 728.3 million USD. Conclusions Omalizumab could provide substantial benefits in terms of paid and unpaid work activities in patients with severe and most severe JCP. Our results also highlight the importance of considering unpaid work in estimating productivity costs due to poor health.

HLA-DPB1*05:01 genotype is a predictive biomarker of sublingual immunotherapy response for Japanese cedar pollinosis

A predictive biomarker for sublingual immunotherapy (SLIT) efficacy is not available for patients with allergic rhinitis (AR). Amino acid changes in the allergen-binding pocket of HLA-DPB1 were associated with the development of Japanese cedar (JC) pollinosis and sensitization to JC pollen. The aim of this study was to investigate whether the HLA-DPB1 gene is associated with SLIT responsiveness in patients with JC pollinosis.

Post-marketing survey Evaluating the Safety and Efficacy of Japanese cedar pollen sublingual immunotherapy tablet (Stratified analysis by with or without asthma, 2018 to 2020)

The Japanese cedar pollen (JCP) sublingual immunotherapy (SLIT) tablet (5,000 JAU Torii, Japan/ALK, Denmark) has been available for Japanese cedar pollinosis in Japan since 2018. Post-marketing surveillance of the JCP SLIT tablets has been initiated to investigate the safety and efficacy during two seasons.

Effects of sublingual immunotherapy with tablets or drops containing Japanese cedar pollen antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis.

We examined the effects of SLIT with tablets containing JCP antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis during pollen dispersal season. A total of 128 patients with Japanese cedar pollinosis were categorized into four groups:19 one-year SLIT with tablets group, 16 two-year SLIT with drops group, 19 antihistamine group, and 74 untreated group. The scores of nasal symptoms and sleep disturbance were evaluated based on the Japanese guidelines for allergic rhinitis and the Athens Insomnia Scale. The scores of nasal symptoms and sleep disturbance at the peak cedar pollen period in the two-year SLIT with drop group and the one-year SLIT with tablets group were significantly lower than those in untreated group. Additionally, these scores were significantly lower in the one-year SLIT with tablets group than those in the antihistamine group. It is suggested that SLIT with JCP tablets improved both nasal symptoms and sleep disturbances at peak pollen period in patients with Japanese cedar pollinosis. SLIT with JCP tablets for one year was more effective than SLIT with JCP drops for two years and prophylactic treatment with antihistamines. J. Med. Invest. 69 : 97-100, February, 2022.

A Study on Antiallergic Agents Prescribed to Patients with Japanese Cedar Pollinosis at an ENT Clinic in Omura City in Nagasaki Prefecture in 2016 and 2019

I conducted a detailed examination of the prescription rates of antiallergic agents, including oral and nasal preparations, prescribed for patients with Japanese cedar pollinosis in 2016, when there was little cedar pollen in the air, and in 2019, when the atmospheric levels of cedar pollen were much higher.