Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey.

BACKGROUND: Acute asthma exacerbation in children is often caused by respiratory infections. In this study, a coordinated national surveillance system for acute asthma hospitalizations and causative respiratory infections was established. We herein report recent trends in pediatric acute asthma hospitalizations since the COVID-19 pandemic in Japan. METHODS: Thirty-three sentinel hospitals in Japan registered all of their hospitalized pediatric asthma patients and their causal pathogens. The changes in acute asthma hospitalization in children before and after the onset of the COVID-19 pandemic and whether or not COVID-19 caused acute asthma exacerbation were investigated. RESULTS: From fiscal years 2010-2019, the median number of acute asthma hospitalizations per year was 3524 (2462-4570), but in fiscal years 2020, 2021, and 2022, the numbers were 820, 1,001, and 1,026, respectively (the fiscal year in Japan is April to March). This decrease was observed in all age groups with the exception of the 3- to 6-year group. SARS-CoV-2 was evaluated in 2094 patients from fiscal years 2020-2022, but the first positive case was not detected until February 2022. Since then, only 36 of them have been identified with SARS-CoV-2, none of which required mechanical ventilation. Influenza, RS virus, and human metapneumovirus infections also decreased in FY 2020. In contrast, 24% of patients had not been receiving long-term control medications before admission despite the severity of bronchial asthma. CONCLUSION: SARS-CoV-2 was hardly detected in children with acute asthma hospitalization during the COVID-19 pandemic. This result indicated that SARS-CoV-2 did not induce acute asthma exacerbation in children. Rather, infection control measures implemented against the pandemic may have consequently reduced other respiratory virus infections and thus acute asthma hospitalizations during this period. However, the fact that many hospitalized patients have not been receiving appropriate long-term control medications is a major problem that should be addressed.

Changes in clinical features of food-related anaphylaxis in children during 5 years.

Background: Despite being frequently recommended, adrenaline auto-injectors (AAIs) are insufficiently prescribed and used for the prehospital management of anaphylaxis. Objective: This study aimed to investigate recent changes in the clinical features and prehospital management of food-related anaphylaxis in children. Methods: We retrospectively compared the clinical features of children who were hospitalized for food-related anaphylaxis in 2013 and 2018. The patients' medical records were reviewed for causative foods, triggers, location, AAI prescription, and/or use, wheezing on admission, and treatment. Results: Overall, 62 consecutive patients (43 males; median age, 5.6 years) hospitalized in 2018 were compared with 57 patients (37 males; median age, 4.3 years) hospitalized in 2013. There were no significant differences between the cohorts in age, gender, causative foods, or wheezing on admission. Cow's milk, wheat, and egg represented over half of the causative foods in both groups. Compared with 2013, the incidence of anaphylaxis decreased at home but increased at nurseries and schools in 2018. Exercise was a significantly more common trigger for anaphylaxis in 2018. Furthermore, a significant increase was observed in AAI administration by lay helpers or the patients themselves and in ambulance transportation. After admission, intramuscular adrenaline was administered to 26 patients in 2013 and 12 patients in 2018. Patients receiving prehospital adrenaline were significantly less likely to require in-hospital adrenaline injections. Conclusion: Food-related anaphylaxis triggered by exercise and AAI use have increased. Hence, raising awareness and educating caregivers, patients, teachers, and medical professionals are essential for the optimal management of this disorder.

Effect of age on exercise-induced bronchoconstriction in children and adolescents with asthma.

OBJECTIVE: The relationship between exercise-induced bronchoconstriction (EIB) and exertional dyspnea in children and adolescents is yet to be fully established. This study examined whether indicators of fractional exhaled nitric oxide (FeNO), forced expiratory volume in 1 s (FEV1) percent predicted at baseline, and dyspnea are useful for predicting children and adolescents with EIB. METHODS: We enrolled 184 children and adolescents diagnosed with asthma (mean age 11.2 years); participants were divided into two groups according to age (12 years) and were subjected to a 6-min exercise challenge test. Lung function tests and modified Borg scale scores were used to examine perceptions of dyspnea at 0, 5 and 15 min after exercise. RESULTS: Among children, the maximum percentage drop in FEV1 after exercise correlated significantly with FeNO (adjusted ß = 2.3, P < 0.001) and with the perception of dyspnea at 5 min after exercise (adjusted ß = 1.9, P < 0.001). Among adolescents, the maximum percentage drop in FEV1 correlated with FeNO (adjusted ß = 2.7, P = 0.007) and with lung function (FEV1, percent predicted; adjusted ß = -0.28, P = 0.006). Children with EIB had significantly stronger dyspnea after exercise than did children without EIB. Adolescents even without EIB may experience more exertional dyspnea than children without EIB. CONCLUSIONS: Overall, our findings indicated that EIB was associated with FeNO and exertional dyspnea in asthmatic children. By contrast, EIB was associated with FEV1 percent predicted at baseline and FeNO but not with exertional dyspnea in asthmatic adolescents.

Annual changes in the prevalence of asthma may be related to air pollution in Fukuoka: 29†years of observation.

The relationship between the annual changes of the prevalence of bronchial asthma (BA) and that of concentrations of air pollutants has not been reported. We studied the annual prevalence of BA, remission of BA, and wheeze in children at the same five elementary schools in Fukuoka city, Japan, in October to November from 1988 to 2016 by the same methods using the same questionnaire. Annual changes in the prevalence of asthma among boys were related to changes in the air concentrations of NO (r=0.708), NO2 (r=0.665) suspended particulate matter (SPM) (r=0.803), and smoking rate (r=0.741), but there were no such relationships among girls. Annual changes in the prevalence of wheeze were related to changes of NO, NO2, SPM, and smoking rate among boys and girls (NO: r=0.650, 0.660; NO2: r=0.556, 0.490; SPM: r=0.582, 0.518; smoking rate: r=0.656, 0.593, respectively) (all of the above are significant with p<0.05). There was no relationship between remission of BA and any of the pollutants. Annual changes in the prevalence of boys' BA and boys' and girls' wheeze among first-grade children (age 6 or 7 years) in Fukuoka were correlated with changes in the concentration of air pollutants (SPM, NO, NO2 or smoking rate). Recent decrease of asthma prevalence in this area might be related to the decreasing tendency of air pollutant concentration. The causal relationship between the two will need to be verified in the future.

Pale nasal mucosa affects airflow limitations in upper and lower airways in asthmatic children.

BACKGROUND: Severe asthmatics are thought to have severer rhinitis than mild asthmatics. A pale nasal mucosa is a typical clinical finding in subjects with severe allergic rhinitis. OBJECTIVE: The aim of this study was to investigate whether a pale nasal mucosa affects airflow limitations in the upper and lower airways in asthmatic children. METHODS: Rhinomanometry, nasal scraping, and spirometry were performed in 54 asthmatic children (median age, 10 years). The nasal mucosa was evaluated by an otolaryngologist. Thirty-seven patients were treated with inhaled corticosteroids, and 11 patients were treated with intranasal corticosteroids. RESULTS: Subjects with a pale nasal mucosa (n = 23) exhibited a lower nasal airflow (p < 0.05) and a larger number of nasal eosinophils (p < 0.05) in the upper airway as well as lower pulmonary functional parameters (p < 0.05 for all comparisons), i.e., the forced vital capacity (FVC), the forced expiratory volume in 1 second, and the peak expiratory flow, compared with the subjects who exhibited a normal or pinkish mucosa (n = 31). No significant difference in the forced expiratory flow between 25%-75% of the FVC, regarded as indicating the peripheral airway, was observed between the 2 groups. CONCLUSION: A pale nasal mucosa may be a predictor of eosinophil infiltration of the nasal mucosa and central airway limitations in asthmatic children. When allergists observe a pale nasal mucosa in asthmatic children, they should consider the possibility of airflow limitations in not only the upper airway, but also the lower airway.

Impact of omalizumab on medical cost of childhood asthma in Japan.

Omalizumab is effective in children with severe asthma, but its impact on medical cost in Japan is not clear. We evaluated the impact of omalizumab on medical cost by comparing the pre- vs post-omalizumab-initiation medical costs of 12 children with severe asthma who received omalizumab for 2 years, and calculating incremental cost-effectiveness ratio for omalizumab therapy. Health outcome was measured as hospital-free days (HFD). The median total medical costs and medication fee per patient increased significantly after omalizumab initiation because of the high cost of omalizumab. The median hospitalization fee per patient, however, decreased significantly after omalizumab initiation due to reduction in hospitalization. Omalizumab led to an estimated increase of 40.8 HFD per omalizumab responder patient per 2 years. The cost was JPY 20 868 per additional HFD. Omalizumab can therefore reduce hospitalization cost in children with severe asthma in Japan.

[A case of food-dependent exercise-induced anaphylaxis caused by ingestion of orange].

The patient was a 10-year-old girl who presented with a history of anaphylactic episodes on three occasions, that developed in association with exercise after she ate citrus fruit. She underwent tolerance tests, as food-dependent exercise-induced anaphylaxis (FDEIA) induced by citrus fruit was suspected. The result of the test for the combination of intake of oranges and exercise was negative. The patient presented with swollen eyelid and wheezing following combined intake of orange and aspirin, based on which she was diagnosed as having FDEIA. Many patients developing an allergic reaction to fruit are diagnosed as having oral allergy syndrome (OAS), and only few cases of FDEIA are reported. Immunoblot tests revealed antigens of 9 kDa, 39 kDa and 53 kDa in this patient, and an inhibition study with oranges revealed that the 39 kDa and 53 kDa antigens were probably antigen-specific allergens. Although the studied patient showed a strongly positive result for IgE antibodies specifically directed at cedar pollen, no common antigenicity with cedar pollen could be recognized. The final diagnosis was a type of FDEIA caused by 39 kDa and 53 kDa proteins, which are different from antigens previously identified in patients with citrus fruits allergy. It should be the first report of such a case.

Lung sound analysis in a patient with vocal cord dysfunction and bronchial asthma.

OBJECTIVE: Vocal cord dysfunction (VCD) is a condition characterized by adduction of the vocal cords, resulting in narrowing or even closure of the glottis during inspiration. This can cause wheezing that originates at the site of narrowing. Some patients have both VCD and asthma. In such cases, an acute episode of VCD can be difficult to differentiate from that of asthma. We tested the usefulness of lung sound analysis (LSA) in such a condition. METHODS: We performed an LSA in a patient with asthma and coexisting VCD diagnosed using laryngoscopy. RESULTS AND CONCLUSION: The LSA during an acute VCD episode revealed monophonic continuous adventitious sounds that were distributed symmetrically over both lung fields. The time domain analysis revealed that the adventitious sounds originated in the neck. These LSA findings clearly indicated that the acute episode was not due to asthma but due to VCD. This case illustrates that the LSA may be a useful tool to differentiate between an acute episode of asthma and that of VCD.

[Relationship between compliance with inhaled corticosteroids and changes in the fraction of exhaled nitric oxide during summer camp for asthmatic children].

BACKGROUND: Recently, the fraction of exhaled nitric oxide (FENO), which can be measured easily and noninvasively even in children, has attracted attention as a method of evaluating airway inflammation. The aim of this study was to investigate the relationship between compliance with inhaled corticosteroids (ICS) before a summer camp for asthmatic children and the changes in the FENO during camp. METHODS: Fifty asthmatic children (26 boys and 24 girls) aged 6-12 years old were recruited from the Fukuoka National Hospital Summer Camp between 2008 and 2010. We measured their FENO on the first and last day of camp. The children were taught appropriate inhalation methods by pediatric pulmonologists and nurses and performed ICS under their supervision every day during the camp. Before the camp, we asked the participants to complete a questionnaire regarding the use of ICS. The participants were classified into four groups according to their adherence to this therapy. The changes in FENO were then examined and compared among the groups. RESULTS: The FENO measured on the last day of camp was significantly lower than that measured on the first day of camp among children who tended to forget to perform ICS. However, no significant difference in the FENO measurements were observed during the camp, when the children were performing ICS every day. CONCLUSION: The FENO decreased significantly after only four days of camp in the poor compliance group. Therefore, teaching children the appropriate method for inhaling ICS is important, especially for children who tend to forget to perform ICS.

Effect of age on relationship between exhaled nitric oxide and airway hyperresponsiveness in asthmatic children.

BACKGROUND: Numerous studies have examined the relationship between the fractional concentration of exhaled nitric oxide (Feno) and airway hyperresponsiveness (AHR). Our objective was to determine the effects of age on the relationship between Feno and AHR in asthmatic children. METHODS: AHR was examined in 267 asthmatic patients (age range, 5 to 20 years). A challenge test was performed using acetylcholine chloride (Ach). We determined the provocative concentration of Ach producing a 20% decrease in FEV(1) from baseline (PC(20)). Feno was examined using the recommended online method before the Ach challenge test. RESULTS: In children < 12 years of age (range, 5 to 11 years), decreasing AHR (PC(20)) was significantly related to higher Feno (r = -0.43; beta = -0.28; p < 0.001). In adolescents >or= 12 years of age (range, 12 to 20 years), decreasing PC(20) was associated with peripheral airway obstruction (FEV(1): r = 0.32; beta = 5.5; p = 0.002; forced expiratory flow at 50% of the FVC: r = 0.24; beta=8.4; p = 0.006; and forced expiratory flow at 25% of FVC: r = 0.28; beta=11.4; p = 0.002). AHR and Feno were weakly related (r = -0.18; beta = -0.14; p = 0.02). CONCLUSIONS: In children with asthma, AHR is associated with airway inflammation. AHR in children with asthma may consist of variable components mainly reflecting airway inflammation. In contrast, in adolescents with asthma, AHR is associated with airway structural changes and weakly with airway inflammation. AHR in adolescents with asthma may consist of chronic components mainly reflecting airway remodeling.

[Efficacy and safety of budesonide inhalation suspension nebulization by mesh nebulizer in Japanese infants and young children with bronchial asthma in 12-week, randomised, open study].

OBJECTIVE: This study evaluated the efficacy and safety of Budesonide Inhalation Suspension (BIS) nebulazation by mesh nebulizer in children ages 6 months to 4 years with moderate to severe persistent asthma. METHOD: This 12-week, randomized, open study involved 30 asthmatic children. They were randomized 3 different nebulizer groups, Pari TurboBoy +LC Plus nebulizer, Pari eMotion and Omron MicroAir NE-22U. BIS administered 0.25 mg once daily (qd). Efficacy was assessed by daily card. Safety was assessed by adverse event, plasma cortisol and growth. RESULT: Baseline concentrations of plasma cortisol were significantly high in the group of Omron MicroAir NE-22U compared to other group. Plasma cortisol were decreased significantly at 4 weeks in Omron MicroAir NE-22U compared with baseline, but those in no subjects decreased under normal range. Asthma symptoms were improved significantly from baseline to 12-week. CONCLUSION: This study demonstrate that usage of mesh nebulizer in BIS 0.25 mg qd is effective and safe in young asthmatic children.