[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH CEDAR POLLEN IN A YEAR OF MASSIVE CEDAR POLLEN DISPERSAL AND ITS EFFECT ON JAPANESE CYPRESS POLLINOSIS].

BACKGROUND: We investigated the effect of sublingual immunotherapy (SLIT) on Japanese cedar and cypress pollinosis in a mass scattering year of cedar pollen (total counts: 12353 grains/cm2, approximately four times the average). METHODS: SLIT patients of 84 in the first year, 107 in the second year and 67 in the third year treated with Cedarcure® were included. During the 2023 cedar and cypress pollen dispersal season, nasal and eye symptoms and general symptoms were examined using a visual analog scale (VAS). RESULTS: The VAS during the cedar season significantly decreased to improve with the number of years of SLIT, but the VAS during the cypress period slightly increased. A questionnaire survey before SLIT revealed that only 0.9% to 3.6% of patients had strong cypress symptoms. However, sneezing (p＜0.01), rhinorrhea, itchy eyes and total symptoms (p＜0.05) in the third year of SLIT were significantly stronger during the cypress period than during the cedar period. The VAS of total symptoms during the Japanese cedar pollen season were not affected by the pollen count, and the cure rate was affected by SLIT in the third year. CONCLUSION: The clinical efficacy of cedar SLIT on cedar pollinosis was high even in a mass scattering year, and the effect increased with the number of years of treatment. On the other hand, it was shown that the clinical efficacy on cypress pollinosis was insufficient.

Immunological effects of sublingual immunotherapy with Japanese cedar pollen extract in patients with combined Japanese cedar and Japanese cypress pollinosis.

Sublingual immunotherapy (SLIT) with Japanese cedar (JCe) pollinosis was expected to be effective for Japanese cypress (JCy) pollinosis. However, only a half of JCy pollinosis patients clinically improved. Therefore, we examined the immunological effect of SLIT for JCy pollinosis. Peripheral blood mononuclear cells (PBMCs) from patients with JCe and JCy pollinosis who did and did not receive SLIT were incubated with Cry j 1, Cha o 1 and Cha o 3 antigens. Basophil activation test (BAT) were performed. Production of IL-5 and IL-17 induced by antigens was inhibited in the SLIT group. Cry j 1-specific production of IL-10 was increased, and serum Cry j 1-specific IgE and -IgG4 were elevated. However, Cha o 1- or Cha o 3-specific production of IL-10 and specific IgG4 was not increased. Antigens-specific BAT did not decrease after SLIT. New SLIT with JCe and JCy is needed for patients with combined JCe and JCy pollinosis.

Safety profile and immunological response of dual sublingual immunotherapy with house dust mite tablet and Japanese cedar pollen tablet.

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

[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN A LARGE AMOUNT OF POLLEN DISPARSAL AND IT'S IMPACT OF TREATMENT YEAR].

BACKGROUND: It past 4 years in 2018 after the first treatment of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. The purpose of this study is to clear the clinical efficacy of SLIT in a large amount of pollen dispersal in 2018 (total 5041 grain). METHODS: The subjects were 270 SLIT (83 forth year of treatment, 72 third year, 48 second year, 67 first year), 320 primary pharmacotherapy that started therapies before pollen dispersal, and 424 untreated. The clinical efficacy was evaluated with symptom scores of Japanese rhinoconjuctivitis quality of life questionnaire No1, medication scores and combined total nasal symptom-medication scores, and visual analog scale of nose, eye and total symptoms. RESULTS: Each SLIT was significantly better than untreated in all assessments, and better than primary pharmacotherapy in assessments of total symptom. SLITs of third and forth year of treatment were also better than primary pharmacotherapy in nasal symptoms. SLIT patients, whose symptom scores of nose and eye were 0 and 1 point without any rescue drugs, accounted for 41.0%, 31.9%, 18.8%, 20.9% in the order from the fourth year to the first year. Of them, patients with score 0 occupied 12.0%, 12.5%, 4.2%, 4.5%, in order. There was no patient who needs treatments for adverse events. CONCLUSION: SLIT was significantly effective compared with primary pharmacotherapy or untreated group in a large amount of pollen dispersal. It was better to treat at least for 4 years.

[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN THE THIRD TREATED YEAR WITH JAPANESE CEDAR POLLINOSIS IN 2017].

It past 3 years in 2017 after the first purchase of the drug for sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). We reported the clinical efficacy of SLIT in the first and the second treated year. PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT in the third treated year by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy. METHODS: We compared the clinical efficacy in 2017, of 112 SLIT in the third treated year with 38 SCIT, 364 primary pharmacotherapy that started therapies before pollen dispersal, 254 pharmacotherapy that started therapies after pollen disposal, or 333 non-treatment. The clinical efficacy was evaluated with symptom scores, total nasal symptom scores and combined total nasal symptom-medication scores (TNSMS), symptoms of nose and eye by visual analog scale (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1). RESULTS: Both SCIT and SLIT showed good clinical efficacy without significant difference in every assessment. Both SCIT and SLIT were significantly better than other pharmacotherapy in most assessment. Patients, whose symptom scores of nose and eye were 0 and 1 point without any rescue drugs, accounted for 9 and 24% of total SLIT, respectively. CONCLUSION: SLIT in the third treated year showed good clinical efficacy in reducing symptoms and TNSMS of JCP, and in improving QOL. SLIT was significantly effective compared with other pharmacotherapies.

Enhanced Clinical Efficacy of Sublingual Immunotherapy for Japanese Cedar Pollinosis in the Second Year of Treatment.

Sublingual immunotherapy (SLIT) is thought to have enhanced efficacy in the second year of treatment. We studied treatment efficacy in both the first and the second years of treatment (2015 and 2016, respectively) in patients who began SLIT in 2014. Methods: We compared 132 patients who underwent SLIT (age, 41.8 ± 17.5 years; male-to-female ratio, 75: 57) and a control group of 56 patients who underwent primary pharmacotherapy (age, 44.9 ± 13.5 years; male-to-female ratio, 25: 31). The study was performed during the peak pollen seasons of 2015 and 2016. Pollen dispersal was similar in 2015 and 2016 (2,509 grains/cm2 and 3,505 grains/cm2, respectively). The clinical efficacy of SLIT was evaluated by assessing nasal and eye symptoms and total symptoms with symptom scores and combined symptom-medication scores, visual analog scale scores, and quality of life (QOL) scores according to the Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No. 1). QOL was also evaluated with JRQLQ No. 1. The first endpoint was enhanced efficacy of SLIT in the second year compared with that in the first year. Results: With respect to nasal and eye symptoms, the assessments in the primary pharmacotherapy group were unchanged in the second year; however, most of these assessments in the SLIT group demonstrated significantly enhanced efficacy of SLIT in the second year. In QOL of SLIT, only 2 of 17 showed significantly enhanced efficacy of SLIT in the second year. Conclusion: SLIT shows enhanced efficacy in the second year.

CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN THE SECOND TREATED YEAR FOR 133 PATIENTS WITH JAPANESE CEDAR POLLINOSIS IN 2016.

It past 2 years in 2016 after the first purchase of the drug for sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT in the second treated year by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy. METHODS: We started SLIT at our clinic in October-December, 2014. We compared the clinical efficacy in 2016, of 133 SLIT with 46 SCIT, 351 primary pharmacotherapy that started therapies before pollen dispersal, 221 pharmacotherapy that started therapies after pollen disposal, or 337 non-treatment. The clinical efficacy was evaluated with symptom scores and combined symptom-medication scores (SMS), symptoms of nose and eye by visual analog scale (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1). RESULTS: Fourteen cases by unknown reasons and 3 cases by inevitable reasons were dropped out for 2 years. Both SCIT and SLIT showed good clinical efficacy without significant difference in every assessment. Both SCIT and SLIT were significantly better than other pharmacotherapy in most assessment. Patients, whose symptom scores of nose and eye were 0 or 1 point without any rescue drugs, accounted for 26.3% of total SLIT. CONCLUSION: SLIT in the second treated year showed good clinical efficacy in reducing symptoms and SMS of JCP, and in improving QOL. SLIT was significantly effective compaired with other pharmacotherapies.

Adherence and Clinical Outcome of Sublingual Immunotherapy for Japanese Cedar Pollinosis.

Sublingual immunotherapy (SLIT) for Japanese cedar pollinosis is known to be effective. However, better SLIT adherence is needed to improve its safety and efficacy. 　Purpose: The purpose of this study was to evaluate SLIT adherence and its influence on clinical outcome. 　Methods: We conducted a detailed survey of 132 patients who have been receiving SLIT for 2 years on adherence at each visit using both questionnaires and direct calculation from prescription. Questionnaires on total symptoms using the visual analog scale (VAS), face scale, and total nasal symptom medication score (TNSMS) were obtained at the peak season for Japanese cedar pollinosis. 　Results: Good adherence by prescription for 2 years was observed in 83.1% ± 11.7% of patients. The adherence in the second year (80.8% ± 13.6%) was lower than that in the first year (88.5% ± 9.8%). However, adherence by questionnaire was 13.5% higher than that by prescription. VAS of total symptoms and adherence did not correlate; however, evaluations by VAS, face scale, and TNSMS were significantly improved if the adherence cut-off value was set to 70% or 75%. 　Conclusion: Our results suggest that SLIT adherence for Japanese cedar pollinosis is high and adequate adherence is required for better efficacy.

Purification, characterization, cDNA cloning, and expression of asialofetuin-binding C-type lectin from eggs of shishamo smelt (Osmerus [Spirinchus] lanceolatus).

A novel C-type lectin (OLABL) was isolated from the eggs of shishamo smelt [Osmerus (Spirinchus) lanceolatus] by affinity chromatography on asialofetuin-Sepharose. OLABL had a molecular mass of 29 kDa on SDS-PAGE under nonreducing conditions and two subunits with masses of 15 kDa (OLABL-H) and 14 kDa (OLABL-L) under reducing conditions. Thus, OLABL is a heterodimeric protein. cDNA sequence analysis revealed that the H- and L-subunits of OLABL were composed of 137 and 136 amino acid residues, respectively, and showed almost identical (95%) sequences, with slight differences in the N-terminal and C-terminal regions. Since each subunit contained only the characteristic motif of C-type lectin-like domain (CTLD), EPN-E-WND, OLABL is a member of group VII of the CTLD-containing protein family. Although OLABL had an EPN sequence that is known as a mannose-specific motif found in the collectin family, OLABL agglutinated rabbit erythrocytes without the addition of Ca(2+) ion, and this activity was inhibited by l-rhamnose and d-galactose derivatives, but not by d-mannose and d-glucose. These results indicate that OLABL has similar characteristics to AJL-2, a calcium-independent lactose specific lectin isolated from Japanese eel skin mucus. Recombinant OLABLs (rHisOLABLs), His-tagged homodimers of the H- and L-subunits, were refolded from inclusion bodies expressed by Escherichia coli. rHisOLABL-L was recovered as a soluble form, but rHisOLABL-H was hardly dissolved in a renaturing buffer. The specific activities of rHisOLABL-L, rHisOLABL-H, and native OLABL were 500, 36, and 20, respectively. These findings suggest that the combination of subunits may affect the solubility and activity of these dimeric form lectins.