Background: Biologics are an important treatment option for patients with severe asthma. Four biologics are available in Japan, and an overlapping eligibility has been observed. The eligibility and availability of drugs depend on the local regulations of different countries. However, there is no precise information about the eligibility for biologics, including dupilumab, in Japan. The aim of the study was to investigate the overlapping eligibility and to analyze the phenotypes of patients with multiple eligibility.

Methods: In this observational study, a retrospective chart review of patients was performed. The eligibility criteria for omalizumab were IgE 30-1500IU/mL and positive IgE for perennial aeroallergen. The eligibility criteria for IL-5-targeted biologics (mepolizumab and benralizumab) were eosinophil counts (Eos) > 150μL, while those for dupilumab were Eos > 150μL or fraction of exhaled nitric oxide (FeNO) > 150ppb or IgE > 167IU/mL. Severe asthma was defined by the severity criteria under treatment based on Japanese guidelines for adult asthma.

Results: One hundred patients with severe asthma were identified. The eligibility for omalizumab, IL-5-targeted therapies, and dupilumab was 43%, 69%, and 82%, respectively. Thirty percent of the patients were eligible for all the four biologics and showed the lowest FEV1, frequent exacerbation history, and the highest levels of Eos, FeNO, and serum periostin. Only 11% of the patients were not indicated for any biologics.

Conclusion: A considerable portion of patients was eligible for all the biologics. Asthma control was poor, and type 2 inflammation was prominent in such patients.

Background: Lung function in early-period school-aged children with asthma influences remission in adolescence. However, there are no reports of this in Japan.

Objective: This study investigated the influence of lung function in early-period school-aged asthmatic children on medication during adolescence.

Subjects and Methods: Forty-nine subjects who had visited our hospital at age 6 years or younger were evaluated on March 31, 2018, at the ages of 16 to 18, to determine their asthma treatment step (step 1 to 4). The patients were divided into four groups, and lung function at six years old.

Results: The groups for steps 1, 2, 3 and 4 had 11, 13, 6, and 8 participants, respectively. FEV_1.0% at six years old for step 1, 2, 3 and 4 had 88.4%, 89.1%, 86.9%, 80.9%, and %V₅₀ had 111.5%, 107.9%, 108.2% and 69.9%, respectively. There were significant differences between the groups of step 4 and 1, 2 regarding FEV_1.0% and %V₅₀.

Conclusion: As for the patient of treatment step 4 of adolescence, lung function decreased at 6 years old in comparison with step 1, 2 patients. Lung function in early-period school-aged asthmatic children may predict the treatment level at adolescence.

Background: The epidemiology of drug-induced anaphylaxis (AN) using the Japanese nationwide database has not been reported, even though drugs are a common trigger of AN.

Objective: This study aimed to describe the epidemiological profile of drug-induced AN, including fatal cases, using the Japanese Adverse Drug Event Report database (JADER).

Methods: We extracted data regarding drug-induced adverse events between April 2004 and February 2018 published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification.

Results: There were 16916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced AN and fatal cases was 1.03 cases/year per 100000 population and 0.03 cases/year, respectively. The most frequent causes of AN were diagnostic agents including X-ray contrast media (20.3%) and biological agents including human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotics (23.9%) were the most frequent causes.

Conclusions: The frequency of drug-induced AN and fatalities in Japan remained unchanged over the 12-year period analyzed in this study. Diagnostic and biological agents were the most frequent causes of AN. Contrarily, fatalities were most frequently caused by diagnostic and antibiotic agents.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of ANCA-related vasculitis. Asthma and sinusitis occur first in the course of EGPA, followed by vasculitis symptoms such as fever, weight loss, and peripheral neuropathy. Otitis media with effusion and sensorineural hearing loss occur occasionally in EGPA patients. Here we report a case of a 39-years-old female patient with asthma that developed at age 37 and sinusitis. The patient was diagnosed with EGPA and treatment was started with oral corticosteroids. During the course of treatment, otitis media with effusion and sensorineural hearing loss developed. Benralizumab was administered for severe asthma. After treatment with benralizumab, the symptoms of asthma, otitis media with effusion and sinusitis dramatically improved. This is the first reported case in which benralizumab was used for treating otitis media and sinusitis associated with EGPA. The findings suggest that benralizumab may be effective for otitis media and sinusitis associated with EGPA.

Background: Long-acting muscarinic antagonists (LAMA) are used for long-term treatment of bronchial asthma in adults. Its use in the management of pediatric bronchial asthma, however, is currently not approved in Japan. Nonetheless, there have been a few reports of its use in children, particularly in cases of severe bronchial asthma or those without atopic disease that are refractory to existing treatment protocols. We report the progress of LAMA in infantile asthma patients.

Cases: Three out of four patients had LAMA introduced at 3 to 5 years of age after being diagnosed with asthma at 1 to 3 years old. Three patients had non-IgE-related asthma and an underlying disease, such as Apert and Noonan syndrome, while one patient had severe IgE-related asthma without a pre-existing disease. In all cases, conventional long-term medications such as medium to high-dose inhaled corticosteroids and long-acting beta-agonists, were given. However, severe bronchial asthma persisted, with some patients having uncontrolled secretions. Since uncontrolled severe-persistent bronchial asthma results in repeated hospitalization and intensive care unit admission, we introduced LAMA, specifically 2.5μg/day of tiotropium (Tio). After the introducing Tio, none of the patients had an acute exacerbation that required hospitalization and the frequency of wheezing was reduced. LAMA was administered for up to 19 months, with no adverse events.

Conclusion: The results of this series suggest that LAMA is an effective and safe option for uncontrolled infantile asthma.