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Abstract Background Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown. Objective To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population. Methods We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1st stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2nd stage), 541 independent patients, and 744 controls (3rd stage). Results SNPs located in the 5' region of PEX19 (rs2820421) were significantly associated with P < 0.05 through the 1st to the 3rd stage analyses; however, the P values did not reach statistically significant levels (combined, P = 3.8 × 10-5; statistically significant levels with Bonferroni correction, P = 6.57 × 10-7). SNPs on HPCAL1 (rs3771140) and on IL18R1 (rs3213733) were associated with asthma in the 1st and 2nd stage analyses, but the associations were not observed in the 3rd stage analysis. Conclusion No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.

Background: Atopic dermatitis (AD) is a chronic, inflammatory skin condition affecting up to one-quarter of children. Uncontrolled pruritus associated with childhood AD, and the accompanying scratching, negatively impacts quality of life (QoL), sleep and development. The humanized monoclonal antibody nemolizumab, used concomitantly with topical agents, was shown to reduce pruritus and improve QoL in patients with AD aged ≥ 13 years. However, data relating to its efficacy and safety in younger children (aged < 13 years) have been lacking., Objectives: To evaluate the efficacy and safety of nemolizumab, administered concomitantly with topical agents, in Japanese paediatric patients (aged 6-12 years) with AD and inadequately controlled moderate-to-severe pruritus., Methods: This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre, 16-week, phase III study. Patients aged ≥ 6 and < 13 years, with confirmed AD, and an inadequate pruritic response despite treatment with topical agents and oral antihistamines were randomly assigned (1 : 1) to receive nemolizumab 30 mg or placebo every 4 weeks (Q4W). The primary efficacy endpoint was the change in the weekly mean 5-level itch score from baseline to week 16; secondary efficacy endpoints were related to pruritus, indicators for AD and QoL. Safety was assessed via adverse events (AEs) and laboratory test results., Results: In total, 89 patients were enrolled, received either nemolizumab 30 mg (n = 45) or placebo (n = 44) Q4W, and completed the study. The mean patient age was 9.1 (SD 1.9) years, and mean duration of AD was 8.5 (2.7) years. The change in 5-level itch score from baseline to week 16 showed a statistically significant difference in the nemolizumab treatment group (-1.3) compared with placebo (-0.5; least-squares mean difference -0.8, 95% confidence interval -1.1 to -0.5; P < 0.0001). Improvements with nemolizumab were observed from the second day of administration. Secondary endpoints were in favour of nemolizumab. No AEs resulted in discontinuation, and the overall safety profile in patients aged 6-12 years was comparable with that in older patients (aged ≥ 13 years) with AD., Conclusions: Nemolizumab is a potential new treatment option for paediatric patients with AD whose pruritus has not been sufficiently improved with topical treatments and antihistamines., Competing Interests: Conflicts of interest A.I. reports receiving grants and honoraria from Maruho Co. Ltd; and honoraria from AbbVie, Eli Lilly Japan, Japan Tobacco Inc., LEO Pharma, Novartis, Sanofi and Torii Pharmaceutical Co. Ltd. T.K. reports receiving grants and honoraria from Maruho Co. Ltd; grants from Grafa Laboratories; and honoraria from AbbVie, AstraZeneca, Kyorin Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma, Sanofi, Taiho Pharma, Teijin and Torii Pharmaceutical Co. Ltd. T.M. and H.K. are employees of Maruho Co. Ltd., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Objective: Detailed quantitative studies on olfaction remain inadequate in patients with paediatric allergic rhinitis (AR). This study examined olfactory dysfunction in children with AR., Methods: From July 2016 to November 2018, children aged 6-9 years were recruited and grouped as AR (n = 30) or without AR (control group, n = 10). Odour identification was evaluated by the Universal Sniff (U-Sniff) test and the Open Essence (OE). The results were compared between the AR and control groups. Intranasal mucosa findings, nasal smear eosinophil counts, blood eosinophil counts, total immunoglobulin E (IgE) levels, Japanese cedar-specific IgE and Dermatophagoides pteronyssinus-specific IgE were evaluated in all participants. Additionally, the presence of sinusitis and adenoid hypertrophy in patients with AR was also evaluated by sinus X-ray examinations., Results: The median U-Sniff test scores were not significantly different between the AR and control groups (9.0 vs. 10.0, respectively; p = 0.107). The OE score was significantly lower in the AR group than in the control group (4.0 vs. 8.0; p = 0.007, respectively), especially in the moderate-to-severe AR group versus the control group (4.0 vs. 8.0; p = 0.004). Furthermore, in the OE, the correct answer rates for 'wood', 'cooking gas' and 'sweaty socks' were significantly lower in the AR group than in the control group., Conclusions: Paediatric AR patients can reduce olfactory identification ability, and the degree may be associated with the severity of AR in nasal mucosal findings. Furthermore, olfactory dysfunction may slow down the response to 'emergency situations', such as gas leak., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Cow's milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low-level CM exposure, as well as the reproducibility of reaction thresholds., Objective: We undertook an individual participant data (IPD) meta-analysis of studies reporting double-blind, placebo-controlled food challenges in CM to determine the rate of anaphylaxis to low-level exposures and the reproducibility of reaction thresholds., Methods: We performed a systematic review and IPD meta-analysis of studies reporting relevant data. Authors were contacted to provide additional data and/or clarification as needed. Risk of bias was assessed using the National Institute for Clinical Excellence methodologic checklists., Results: Thirty-four studies were included, representing data from over 1000 participants. The cumulative ED 01 and ED 05 (cumulative doses causing objective symptoms in 1% and 5% of the at-risk allergic population) were 0.3 (95% confidence interval [CI], 0.2-0.5) and 2.9 (95% CI, 1.6-5.4) mg, respectively. At meta-analysis, 4.8% (95% CI, 2.0-10.9) and 4.8% (95% CI, 0.7-27.1) of individuals reacting to ≤5 mg and ≤0.5 mg of CM protein had anaphylaxis (minimal heterogeneity, I 2  = 0%). Then 110 individuals underwent repeat double-blind, placebo-controlled food challenges; the intraindividual variation in reaction threshold was limited to a ½-log change in 80% (95% CI, 65-89) of participants. Two individuals initially tolerated 5 mg CM protein but then reacted to this dose at a subsequent challenge, although neither had anaphylaxis., Conclusions: About 5% of CM-allergic individuals reacting to ED 01 or ED 05 exposure might have anaphylaxis to that dose. This equates to 5 and 24 anaphylaxis events per 10,000 patients exposed to an ED 01 or ED 05 dose, respectively, in the broader CM-allergic population. Most of these anaphylactic reactions would be mild and respond to a single dose of epinephrine., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (© 2022 Japanese Dermatological Association.)

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough., Competing Interests: Conflict of Interest Dr. Hiroshi Mukae received honoraria from Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., KYOLIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., MSD K.K., Taisho Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., and AstraZeneca K.K., a research grant from Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Taisho Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., KYORIN Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd.; Dr. Takeshi Kaneko received honoraria from Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., and Meiji Seika Pharma Co., Ltd., and a research grant from Teijin Home Healthcare Ltd., Ono Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd.; Dr. Toshio Katsunuma received honoraria from KYORIN Pharmaceutical Co., Ltd., Maruho Co., Ltd. and Torii Pharmaceutical Co., Ltd.; Dr. Akio Niimi received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., MSD K.K., KYORIN Pharmaceutical Co., Ltd., GlaxoSmithKline K.K. and Novartis Pharma K.K., a research grant from Novartis Pharma K.K., Boston Scientific Corporation, MSD K.K., and Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd., KYORIN Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd.; Dr. Hiroto Matsuse received honoraria from MSD K.K., AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., and Astellas Pharma Inc.; Dr. Kazuhiro Yatera received honoraria from AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer lngelheim Co., Ltd., Astellas Pharma Inc., GlaxoSmithKline K.K., and KYORIN Pharmaceutical Co., Ltd., and subsidies or donations from Kirigaoka Tsuda Hospital, Tochiku Hospital, Hagiwara Central Hospital, Kurate Hospital, Shionogi & Co., Ltd., Teijin Home Healthcare Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Novartis Pharma K.K., and Nippon Boehringer Ingelheim Co., Ltd.; Dr. Arata Azuma received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Dr. Hirokazu Arakawa received subsidies or donations from Novartis Pharma K.K.; Dr. Takashi Iwanaga received honoraria from KYORIN Pharmaceutical Co., Ltd., a research grant from KYORIN Pharmaceutical Co., Ltd., Pearl Therapeutics, Inc., and Meiji Seika Pharma Co., Ltd., and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., Teijin Pharma Ltd., and KYORIN Pharmaceutical Co., Ltd.; Dr. Yasuhiro Gon received honoraria from Novartis Pharma K.K., AstraZeneca K.K., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd., and KYORIN Pharmaceutical Co., Ltd., and a research grant from Novartis Pharma K.K. and AstraZeneca K.K.; Dr. Hirokazu Sakamoto received a research grant from Sanofi K.K. and Novartis Pharma K.K.; Dr. Yoko Shibata received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and GlaxoSmithKlein K.K.; Dr. Tsutomu Tamada serves as a consultant to Novartis Pharma K.K. and AstraZeneca K.K.; Dr. Yasuhiko Nishioka received honoraria from Nippon Boehringer lngelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., and MSD K.K., a research grant from Taiho Pharmaceutical Co., Ltd., Nippon Boehringer lngelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Bonac Corporation, and subsidies or donations from Ono Pharmaceutical Co., Ltd., Nippon Boehringer lngelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Asahi Kasei Pharma Corporation, and Chugai Pharmaceutical Co., Ltd.; Dr. Shigeharu Fujieda received patent royalties and/or licensing fees from KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Taiho Pharmaceutical Co., Ltd., and a research grant from Mitsubishi Tanabe Pharma Corporation, Tsumura Co., Ltd., Maruho Co., Ltd., and Sanofi K.K.; Dr. Naoyuki Miyashita received honoraria from Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Astellas Pharma Inc., Pfizer Japan Inc., and Taisho Toyama Pharmaceutical Co., Ltd.; Dr. Akihito Yokoyama received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., GlaxoSmithKlein K.K., and Sanofi K.K., and a research grant from Astellas Pharma Inc. and Ono Pharmaceutical Co., Ltd. Drs. Yasushi Obase, Masaharu Shinkai, Kiyoshi Takeyama, Jiro Terada, Yoshihiro Yamamoto, Haruhiko Ogawa, Kiyoyasu Kurahashi, Shusaku Haranaga, Hiroyuki Mochizuki, Shigemi Yoshihara, and Jun Tamaoki have no conflict of interest.Drs. Yasushi Obase, Masaharu Shinkai, Kiyoshi Takeyama, Jiro Terada, Yoshihiro Yamamoto, Haruhiko Ogawa, Kiyoyasu Kurahashi, Shusaku Haranaga, Hiroyuki Mochizuki, Shigemi Yoshihara, and Jun Tamaoki have no conflict of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: This study was aimed at evaluating the efficacy and safety of oral immunotherapy (OIT) in children with severe cow's milk allergy., Methods: The subjects comprised 28 children (aged 3-12 years) with allergic symptoms that were induced by ≤ 10 mL of cow's milk in an oral food challenge test (OFC). The subjects were randomly allocated to the treatment group (n = 14) and control group (n = 14); the former received rush immunotherapy for 2 weeks, followed by a gradual increase of cow's milk volume to 100 mL for 1 year, and the latter completely eliminated cow's milk for 1 year. Both groups underwent an OFC with 100 mL of cow's milk after 1 year., Results: The treatment group had significantly higher rates of a negative OFC [7/14 (50%) vs. 0/14 (0%), p < 0.01] compared with the control group. The cow's milk-specific IgE level significantly decreased in the treatment group (p < 0.01) but not in the control group (p = 0.63). During the study period, adrenaline was required in 6/14 patients (43%) of the treatment group and in 0/14 patients (0%) of the control group. Long follow-up data were available at the 2-year point after the study for 8 in the treatment group and 7 (87.5%) of these continued to ingest milk (>100 mL)., Conclusions: The effect of immunotherapy was 50%, but the incidence of adverse events was not low. Further studies focusing on safety is necessary to standardize OIT for cow's milk allergy., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Egg allergy is one of the most common food allergies in children. To date, oral immunotherapy (OIT) has been considered as a promising treatment option for egg allergy. However, safety issues remain concerning severe adverse events requiring epinephrine injection. Hence, establishing a safer method to treat egg allergy would be beneficial. We report here two children with egg allergy who were safely treated with sublingual immunotherapy (SLIT) before transitioning to OIT., Case Presentation: Patient 1 was a 7-year-old girl and Patient 2 was a 5-year-old girl. Although OIT for egg had been attempted in both patients, severe anaphylactic symptoms were induced by ingesting only 0.1 g of heated whole egg. Therefore, SLIT was conducted with aqueous suspensions consisting of water and heated whole egg powder. Suspensions were administered sublingually, kept in the mouth for 2 min, and spat out immediately thereafter. SLIT was continued for 7 months for Patient 1 and 8 months for Patient 2 due to the exploratory character of the study. Afterwards, the patients successfully transferred to low-dose OIT with 1 g of heated whole egg (≒170 mg of egg protein) daily, and are continuing the therapy as of June 2020. As for adverse reactions, Patient 1 expressed oral cavity itchiness once at the beginning of SLIT. Patient 2 had no adverse reaction. The levels of antigen-specific IgE decreased in both patients after SLIT, and further decreased after switching to OIT., Conclusions: Few clinical studies have evaluated the efficacy and safety of SLIT for egg allergy. Although the treatment was conducted in only two patients, our results have shown that SLIT is a promising treatment procedure for egg allergy. Further clinical trials will be needed to additionally assess the efficacy and safety of SLIT in children with food allergy.

Background: The combination drug of inhaled corticosteroid (ICS)/long-acting β2 agonist is being used as a long-term control medication for pediatric asthma patients for those who are poorly controlled by ICS alone. Long-term efficacy and safety of Fluticasone propionate/formoterol fumarate hydrate (FP/FM) was evaluated in pediatric patients with bronchial asthma., Methods: Two inhales of FP/FM (50/5μg) at one time, twice daily were administered for 24 weeks to Japanese asthma patients aged 5 to ＜16 years who had asthma symptoms during the observation period while using the same dosage of ICS during a certain period of time. Adverse drug reactions, morning peak flow (mPEF) and asthma symptoms were evaluated 24 weeks after administration., Results: FP/FM was administered to 53 subjects. 52 subjects completed the 24 week administration. The incidence of adverse drug reactions was 9.4% (5 of 53), and all of the adverse drug reactions were mild. The mPEF increased from the starting value and was maintained through the treatment period. The average change from baseline in the mPEF after 24 weeks of treatment was 21.39±2.93L/min (Least squares mean±standard error). Changes in asthma symptoms were similar to that of morning peak flow., Conclusion: It was considered that FP/FM could be useful for long-term control of pediatric asthma.

Background: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial., Methods: Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991., Results: From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group., Conclusions: Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

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., (Production and hosting by Elsevier B.V.)

Background: Periostin and squamous cell carcinoma antigen (SCCA) are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV) infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated., Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI) had been met: Group I consisted of mAPI (+) and mAPI (-) patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339)., Results: We enrolled 14 subjects in Group I mAPI (+), 22 in Group I mAPI (-), 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+) and mAPI (-)., Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: While Japanese guideline recommends initial control treatment for preschool children with asthma symptoms more than once a month, Western guidelines do not. To determine whether control treatment with montelukast was more effective than as-needed β 2 -agonists in this population, we conducted a randomized controlled trial., Methods: Eligible patients were children aged 1-5 years who had asthma symptoms more than once a month but less than once a week. Patients were randomly assigned in a 1:1 ratio to receive montelukast 4 mg daily for 48 weeks or as-needed β 2 -agonists. The primary endpoint was the number of acute asthma exacerbations before starting step-up treatment with inhaled corticosteroids. This study is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000002219., Results: From September 2009 to November 2012, 93 patients (47 in the montelukast group and 46 in the no-controller group) were enrolled into the study. All patients were included in the analysis. During the study, 13 patients (28%) in the montelukast group and 23 patients (50%) in the no-controller group had acute exacerbations with the mean numbers of 0.9 and 1.9/year, respectively (P = 0.027). In addition, 10 (21%) and 19 (41%) patients received step-up treatment, respectively. Cumulative incidence of step-up treatment was significantly lower in the montelukast group (hazard ratio 0.45, 95% confidence interval 0.21 to 0.92; P = 0.033)., Conclusions: Montelukast is an effective control treatment for preschool children who had asthma symptoms more than once a month but less than once a week., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: There are no reports on the prevalence and social acceptance of food allergies (FAs) and FAinduced symptoms in nursery schools in Japan., Purpose: The purpose of this study is to clarify the current status of FA among children in nurseries., Methods: Investigations were conducted in childcare facilities nationwide through survey request forms found on the Web page or sent via post., Result: We received responses from 15722 out of the 32210 institutions (48.8%) to whom survey request forms were sent.The overall prevalence of FA was 4.0%, with 6.4% at age less than 1 year, 7.1% at age 1, 5.1% at age 2, 3.6% at age 3, 2.8% at age 4, 2.3% at age 5, and 0.8% at age 6. Ninety-three point four percent of the institutions responded that they catered to children with FA, whereas 3.3% of the institutions responded that they did not. The details of the meal service were as follows: 52.4% were meals without causative foods, 39.5% were alternative meals without causative foods, and 3.3% were packed lunches from home. Seven point six percent of infants had at least one FA symptom in the institutions., Conclusion: Several nursery schools were accepting children with FA, and school lunches were also modified by removing causative food and providing alternative meals. On the other hand, several infants experience FA-induced symptoms, and it is necessary for each department to establish a system to reduce accidental ingestion and to ensure proper emergency response.

Background: Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma., Methods: Thirty-eight Japanese children (aged 7-16 years) who completed the 24-week treatment core study were included in an uncontrolled extension study, in which treatment with omalizumab continued until the pediatric indication was approved in Japan (ClinicalTrials.gov number: NCT01328886)., Results: Thirty-five patients (92.1%) completed the extension study. The median exposure throughout the core and extension studies was 116.6 weeks (range, 46.9-151.1 weeks). The most common adverse events were nasopharyngitis, influenza, upper respiratory tract infection, and asthma. Serious adverse events developed in 10 patients (26.3%), but resolved completely with additional treatments. Incidence of adverse events didn't increase with extended exposure with omalizumab. Twenty-nine patients (76.3%) achieved completely- or well-controlled asthma compared with 9 patients (23.7%) at the start of the extension study. QOL scores, the rates (per year) of hospitalizations and ER visits were significantly improved compared with the baseline of the core study [39.0 vs 48.0 (median), p < 0.001 for QOL, 1.33 vs 0.16, p < 0.001 for hospitalization, 0.68 vs 0.15, p = 0.002 for ER visits]. Remarkably, the mean total IgE level showed a decreasing trend while exposure to omalizumab remained at steady-state., Conclusions: Long-term treatment with omalizumab is well-tolerated and effective in children with uncontrolled severe allergic asthma. No new safety findings were identified., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)