[EFFICACY AND SAFETY OF PEDIATRIC SUBLINGUAL IMMMUNOTHERAPY WITH CEDARCURE® IN CLINICAL PRACTICE FOR JAPANESE CEDAR POLLINOSIS IN THE FIRST FOLLOW-UP SEASON].

BACKGROUND: We studied clinical efficacy and safety of pediatric sublingual immunotherapy of cedar pollinosis in the first follow-up year, compared with adult cases or untreated cases. METHODS: We compared 103 pediatrics under 15 yeas old (age, 10.8±2.6 years; male-to-female ratio, 68;35) and 89 adults (age, 38.9±12.5 years; male-to-female ratio, 34;55) treated with Cidarcure®, and untreated 299 patients (age, 31.3±16.0; male-to-female ratio, 144;155). The clinical efficacy was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire and visual analog scale (VAS) during the peak season of moderate amount of pollen dispersal (3582 grains/cm2/season) in 2020. Adverse events of sublingual immunotherapy were also checked at every visits. RESULTS: All patients in both pediatric and adult group successfully maintained the highest dose of 5000JAU as planned. Pediatrics compared with adults showed slightly better effects in all the assessments, but they were not significant. Both pediatrics and adults of sublingual immunotherapy showed significant better effects in all the assessments compared with untreated group. Percentage of total cases of adverse events in pediatric group was low, but it was not significant. Percentage of pruritus of ear and throat was significantly low in pediatric group. CONCLUSION: Pediatric sublingual immunotherapy for cedar pollinosis was treated in safe, and reduced symptoms as well as the effects of adults.

[CLINICAL EFFICACY OF 69 PATIENTS WITH JAPANESE CEDAR POLLINOSIS TREATED BY SUBLINGUAL IMMUNOTHERAPY WITH CEDARCURE® IN THE FIRST FOLLOW-UP YEAR].

BACKGROUND: Cedarcure® for sublingual immunotherapy of cedar pollinosis was purchased in 2018. We studied clinical efficacy of Cedarcure® in the first year. METHODS: We compared 69 patients treated with Cedarcure® (age, 18.0±13.5 years; male-to-female ratio, 40;29) and a control group of 97 patients treated with Cedartolen® (age, 29.8±16.2 years; male-to-female ratio, 44;53) during the peak season of large amount of pollen dispersal (10933 grains/cm2/season) in 2019. The clinical efficacy was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire and visual analog scale (VAS). RESULTS: All the assessments except nasal congestion were slightly better in Cedarcure® group, but they were not significant. There was no difference of concomitant medication in both groups. Because insurance coverage of Cedartolen® is for patients over 12 years old in Japan, the efficacy in Cedarcure® group enhanced better in all assessments if comparing the patients of over 12 years old. Percentage of adverse events was even in both over and under 12 years old. CONCLUSION: Cedarcure® was treated in safe, and reduced symptoms as well as Cedartolen®.

[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.

Applicability of the cross-culturally modified University of Pennsylvania Smell Identification Test in a Japanese population.

BACKGROUND: The University of Pennsylvania Smell Identification Test (UPSIT) is a popular olfactory function test used throughout the world. In Japan, however, it is not widely used because it is written in English and some of the test odorants are unfamiliar to the Japanese population. Recently, a cross-culturally modified UPSIT was developed. This study was designed to determine if the Japanese version of the UPSIT (UPSIT-J) is effective in Japanese populations. METHODS: We administered the UPSIT-J to 50 normosmic Japanese subjects and 54 Japanese patients with known olfactory dysfunction. Subjects were also administered the Japanese standard olfactory threshold test (T&T olfactometry), the Odor Stick Identification Test for Japanese (OSIT-J) and i.v. olfactometry (the Alinamin test). Test results from the UPSIT-J and subjects' opinions were compared with the standard Japanese tests of olfactory function. RESULTS: Most subjects reported that the UPSIT-J was easy and interesting compared with OSIT-J and easier and more interesting than the T&T olfactometry and Alinamin test. Identification rates for nine of the UPSIT-J odorants were found to be <80% for normal subjects. UPSIT-J scores correlated with subjects' self-reported levels of olfactory function (r(s) = 0.85), OSIT-J score (r(s) = 0.86), recognition threshold of the T&T olfactometry (r(s) = 0.80), and Alinamin test results (r(s) = 0.38 for latency; r(s) = 0.52 for duration time). CONCLUSION: Although a cultural bias was detected for some test odorants, this study indicates that the UPSIT-J is effective for use in the clinic to assess olfactory function in the Japanese population.

[Increased throat symptoms in Japanese cypress pollinosis].

BACKGROUND: Seasonal allergic rhinitis caused by Japanese cypress pollen is highly associated with that by Japanese cedar pollen, due to the similar antigen of the two pollens. Clinically, patients with cypress pollinosis complain of strong throat symptoms. METHOD: Weekly nasal and throat symptoms during the pollen season in patients with Japanese cedar-cypress pollinosis were measured using a visual analog scale (VAS). Symptoms other than rhinoconjuctivitis by Japanese rhinitis quality of life questionnaire No2 were compared in two different pollen scattering-seasons. RESULT: VAS showed that nasal symptoms appeared parallel with pollen scattering, and that they were severe in the cedar season more than in the cypress season. On the other hand, throat disco,fort and cough were worse in the cypress season, even though this study took place of during a year when there was only a small amount of cypress-pollen scattering. The severity of symptoms other than rhinoconjunctivitis in cedar pollinosis depended on the total amount of pollen, however, cypress pollinosis showed severe throat symptoms in both a small and a mass scattering year. CONCLUSION: Although cypress and cedar pollinosis is considered as the same disease, cypress pollinosis showed more severe symptoms other than rhinoconjunctivitis. Throat symptoms in particular are more severe in cypress pollinosis, even in the year of a small amount of scattering.

SLIT improves cedar pollinosis by restoring IL-10 production from Tr1 and Monocytes∼IL-10 productivity is critical for becoming allergic∼.

BACKGROUND: Allergen-specific immunotherapy (SIT) is currently used for several allergic disorders and IL-10-producing regulatory T cells (Tr1) induced by SIT suppress allergic reactions. We investigated the relation between IL-10 production and acquiring allergy. METHODS: A prospective study was undertaken to evaluate the effect of SIT on IL-10 production in T cells and other cell fractions in children with pollinosis. In addition, blood samples were collected from non-allergic healthy controls and patients with pollinosis to compare the levels of IL-10 production. PBMC were cultured with pollen peptides or control allergens, and the IL-10 production from monocyte and CD4 T cell was analyzed. RESULTS: Monocytes and CD4 T cells from SIT group of patients produced high levels of IL-10, suggesting that the induction of IL-10 is essential for inducing T cell tolerance. IL-10 production from monocytes and T cells was significantly increased in non-allergic controls compared to patients with pollinosis. This high IL-10 production was observed even when PBMC were stimulated with antigens other than pollen peptides. CONCLUSIONS: IL-10 is critical for induction of specific T cell tolerance, and increased production of IL-10 by monocytes and T cells during inflammatory responses or after SIT may influence effector cells in allergy. Present data implicates that the low productivity of IL-10 by monocytes and T cells is closely related with sensitivity to multiple allergens, and resistance to allergic diseases. Augmentation of constitutive IL-10 production from immune system is a potential therapeutic approach for allergic disorders.

[The enhanced clinical efficacy by treated years and the sustained efficacy after treatment of sublingual immunotherapy for Japanese cedar pollinosis].

BACKGROUND: Although sublingual immunotherapy (SLIT) is hopeful therapy for seasonal allergic rhinitis by Japanese cedar pollen, there are many issues to study. We studied the adding effects on clinical efficacy by the treated years and sustained efficacy 1 year after a 3-year period of SLIT. METHODS: Clinical efficacy of SLIT in patients with Japanese cedar pollinosis treated for different years of 1 year (n=7), 2 years (n=18) or 4 years (n=5) were compared in 2009. Patients, who finished SLIT after a 3-year period and did not received SLIT at the fourth year (n=12), was also compared with those who received SLIT at the fourth year (n=5). RESULTS: By adding treated year, clinical efficacy of sneezing, rhinorrhea and congestion became better, and symptom-medication score (SMS) was significantly better in the fourth year of SLIT. Patients with the fourth year of SLIT showed better SMS compared with those who finished at the third year. CONCLUSION: Consecutive treatment of SLIT showed better efficacy. Although it was recommended to continue SLIT therapy at least four years, it needed further study because of small number of patients.

[Clinical usefulness of smell identification test card: Open Essence].

Since the Odor Stick Identification Test for Japanese (OSIT-J) has proved clinically useful in Japan, the Open Essence (OE) smell identification test card has been developed to amend OSIT-J deficits. To determine its clinical effectiveness, we administered the OE to 93 Japanese subjects reporting olfactory dysfunction. They scored their olfactory dysfunction on levels one to five, i.e., normal to anosmic, using the Japan Rhinologic Society Self-Administered Odor Questionnaire (SAOQ) and the visual analog scale (VAS). They also took the Japanese standard olfactory test (T & T olfactometry) and intravenous olfactometry (Alinamin test). Opinions on the OE and OSIT-J were recorded from those previously administered the OSIT-J and testers familiar with OSIT-J administration. The OE took 5.1+/- 1.6 minutes to administer. Scores correlated significantly for the OE, self-reported olfactory function, SAOQ, VAS, T & T olfactometry recognition threshold, and Alinamin latency and duration time. Subjects and testers reported the OE to be easier, shorter, more interesting, and more convenient, indicating its utility in clinical olfactory dysfunction evaluation and its convenience for both subjects and testers.

[Antigen specific sublingual immunotherapy for pediatric Japanese cedar pollinosis].

BACKGROUND: Sublingual immunotherapy (SLIT) for allergic rhinitis is commonly used in Europe, but not in Japan. Although some studies of SLIT for Japanese cedar pollinosis (JCP) were reported, all the subjects were adults. SLIT is an ideal treatment for children rather than for adults, because it overcomes subcutaneous immunotherapy in the complication of painful injections and habitual visits of a hospital. We tried an open pilot study of SLIT for pediatric JCP. METHODS: Ten pediatric patients with JCP (4 boys and 6 girls, mean ages; 8.5+/-2.2 years old) were treated according to a scheduled doses of SLIT with a therapeutic standardized Japanese cedar pollen extract. They were maintained at the doses of 2000JAU of allergen once a week during pollen scattering. Clinical efficacies during the pollen scattering in the first season were evaluated from their diary of symptoms and medications, visual analog scale (VAS) of symptoms, and a questionnaire for SLIT. RESULTS: The mean severity scores of nasal and ocular symptoms were low. VAS was also very short. Three of 10 patients had no symptoms without any drugs during the pollen season. Two patients were medicated within 5 days. CONCLUSIONS: SLIT was effective for pediatric Japanese cedar pollinosis.

Risk factors of postoperative infection in head and neck surgery.

OBJECTIVES: Patients undergoing head and neck oncological surgery are at great risk of developing complications following surgery. It is important to clarify risk factors contributing to operative wound infections. METHODS: Two hundred and nine cases with head and neck tumor (87 female, and 122 male, averaged 58.6 years old) were studied at Mie University Hospital within a 24-month interval, during 2002 and 2003. RESULTS: Twenty-one (10.0%) surgical site infections (SSIs) were recorded. Univariate analysis revealed that the following factors were significantly related to SSI: blood loss, previous chemotherapy, clean-contaminated surgery, tracheotomy, malignant tumor, advanced T-stage, flap reconstruction, and long operative time. Multivariate analysis showed that blood loss, previous chemotherapy, and the type of surgery contributed to SSI. Otherwise, the following factors did not show any significant correlations: age, body mass index, smoking, alcohol intake, diabetes, sex, previous radiotherapy, N-stage or ASA score. CONCLUSIONS: In order to minimize postoperative wound infection, clinicians managing the head and neck tumor patients should have a thorough understanding of the risk factors leading to postoperative infections such as blood loss, previous chemotherapy, and clean-contaminated surgery.

[Influence of the difference in the pollen count on medical costs in an allergen-specific immunotherapy for Japanese cedar pollinosis].

BACKGROUND: We studied medical economic efficacy and influence by the different number of pollen scattering in patients treated with allergen-specific immunotherapy for Japanese cedar pollinosis. METHODS: We calculated medical treatment costs and the medicine expense from medical records in eighteen cedar pollinosis patients treated with allergen-specific immunotherapy (IT-G) and with medications (M-G). We examined with the same patients for three years of different pollen scattering, mass scattering year (2005), moderate scattering year (2003), a few scattering year (2004). Furthermore, satisfaction of treatment and symptom score measured by visual analog scale in both subjects was studied in a mass scattering year. RESULTS: Total medical costs at hospital was cheaper in IT-G than in M-G. The result was depended on prescribed medical costs. In addition, prescribed medicine agents and total medical costs did not increase by the mass scattering year of pollen. Satisfaction of treatment and symptom score in IT-G was better than that in M-G. CONCLUSION: Immunotherapy had a benefit on a medical economy.