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.

[OBJECTIVE EVALUATION OF SUBLINGUAL IMMUNOTHERAPY FOR PEDIATRIC ALLERGIC RHINITIS RESPOND TO SQ HOUSE DUST MITE].

BACKGROUND: Sublingual immunotherapy (SLIT) has become applicable to insurance for children in Japan in 2018. However, as for the efficacy of SLIT for children, objective evaluation methods have not been sufficiently investigated. SUBJECTS AND METHODS: We investigated the efficacy of SLIT as both subjective and objective evaluation in 44 children with allergic rhinitis sensitized to house dust mite who started the treatment in the summer of 2018 in our hospital. The children and their patients wrote the allergy diary every day, and in winter/spring/summer vacations, they answered Japanese allergic rhinitis quality of life standard questionnaire and were evaluated with nasal provocation test, blood test, rhinomanometry for 3 years. RESULTS: 29 (66%) of the 44 children continued SLIT for 3 years. Symptom scores, QOL scores, symptom medication scores halved in a year and the effect lasted in the second and third year. Nasal provocation test and rhinomanometry showed significant improvement. Specific IgE increased transiently and then decreased. Specific IgG4 increased annually. CONCLUSION: The present study showed a decrease in scores not only for subjective assessments but also for objective evaluation methods, the house dust nasal provocation test and the nasal airway resistance.

Efficacy and safety of low- and high-dose slow oral egg immunotherapy for hen's egg allergy: Single-center non-inferiority randomized trial.

BACKGROUND: Low-dose oral immunotherapy (OIT) is a safe treatment for hen's egg allergy; however, comparison of its therapeutic effects with those of high-dose OIT has not been reported. OBJECTIVE: To compare the efficacy of low- and high-dose boiled egg-white (EW) OIT for hen's egg allergy. METHODS: Patients with hen's egg allergy were randomly assigned to two groups: OIT using hard-boiled EW with a maximum maintenance dose of 2 and 20 g in the low-dose (L-D) and high-dose (H-D) groups, respectively. The intake dose was ingested twice a week, increased by approximately 20% per week until reaching the target maintenance dose (2 or 20 g hard-boiled EW), and maintained thereafter according to the schedule. The threshold was confirmed via oral food challenge (OFC) after 6 months, and the difference in the proportion of subjects passing the exit OFC between groups was evaluated. RESULTS: Fifty-two patients (L-D, n = 23; H-D, n = 29) were enrolled. Thirty-three patients (L-D, n = 17; H-D, n = 16) completed the 6-month OIT and underwent an exit OFC. In total, three (L-D, 3/17; H-D, 3/16) patients in each group tested negative for an exit OFC with a 20-g reactive dose (p = 1.000). EW-specific IgE levels in both groups decreased significantly after OIT (L-D, p < 0.001; H-D, p = 0.002). CONCLUSIONS: A threshold-elevating effect was observed in the L-D group, not inferior to that in the H-D group. Low-dose OIT may be appropriate to treat hen's egg allergy for the first 6 months.

[LUNG FUNCTION IN EARLY-PERIOD SCHOOL-AGED ASTHMATIC CHILDREN MAY BE A PREDICTOR OF TREATMENT LEVEL AT ADOLESCENCE].

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. FEV1.0% 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 FEV1.0% 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.

Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy.

INTRODUCTION: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. OBJECTIVES: We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy. METHODS: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. RESULTS: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). CONCLUSIONS: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

Effectiveness and Safety of Double-Blind, Placebo-Controlled, Low-Dose Oral Immunotherapy with Low Allergen Egg-Containing Cookies for Severe Hen's Egg Allergy: A Single-Center Analysis.

INTRODUCTION: The usefulness of low-dose oral immunotherapy (OIT) for the treatment of egg allergy has been unclear. OBJECTIVE: To evaluate the efficacy and safety of OIT with low allergen cookies (LACs) containing a low dose of hen's egg. METHOD: Thirty-three patients with severe hen's egg allergy were randomly administered either OIT with LACs (n = 21) or placebo (n = 12). Two patients in the LACs group withdrew before completing OIT. The primary endpoint was the number of good responders (G-R), patients with negative results in the oral food challenge (OFC) with a final dose of 2 g hard-boiled egg whites after 4 months of OIT, in each group. Total OFC Aichi score for anaphylaxis/cumulative protein dose (TS/Pro) as the marker of severity of food allergy was also compared. Adverse events during OIT were evaluated using patients' diaries. RESULTS: The proportion of G-R in the LACs group was higher than in the placebo group (7/19 [37%] vs. 1/12 [8%], χ2 test; p = 0.077). The TS/Pro after OIT in the LACs group was lower than in the placebo group (median score, 44.2 vs. 104.1, p = 0.059; Mann-Whitney U test). The threshold and TS/Pro before and after OIT significantly improved in the LACs group (p = 0.015, p = 0.027, respectively; Wilcoxon signed-rank test). There were 99 recorded incidences of symptoms of 1,938 intake events in the LACs group during OIT. Of these, 90 were mild; no severe symptoms occurred. CONCLUSIONS: OIT with LACs potentially increases the OFC threshold and decreases allergy severity and is a relatively safe treatment modality.

[STUDY OF DIRECT TB-LAMP USING NON-CENTRIFUGAL SPUTUMS ABOUT EFFICIENCY FOR RAPID DIAGNOSIS OF TUBERCULOSIS].

OBJECTIVE: To evaluate the efficiency of the direct tuberculosis-loop-mediated isothermal amplification (TB-LAMP) assay by using non-centrifuged sputum samples. STUDY PERIOD AND METHODS: The study was conducted between June 2013 and February 2014. We collected 111 sputum samples from patients who had been radiographically diagnosed with tuberculosis and had not received any treatments for longer than 5 days. In the direct TB-LAMP assay, a loop-mediated isothermal amplification kit and 60-µL sputum samples were used. A direct smear microscopy test was used as the smear test. Then, the same sputum samples were processed with a CCE pretreatment reagent, and 100 µL of the solution samples were cultured by using the mycobacterial growth indicator tube (MGIT) culture method. RESULTS: Forty-six of the 111 samples were positive in the smear microscopy tests. All the smear-positive samples were positive in both the MGIT and direct TB-LAMP assay (100%). The mean positive detection time with the direct TB-LAMP assay was 13 minutes 55 seconds. Of 56 smear-negative and MGIT positive samples, 44 (78.6%) were judged to be positive using the direct TB-LAMP assay, with a mean positive detection time of 15 minutes 59 seconds. DISCUSSION: The direct TB-LAMP assay using non-centrifuged sputum samples was demonstrated to have a high detection rate and thus may be considered useful for rapid and effective tuberculosis diagnosis.

[Comparative study of the efficacy of the COBAS TaqMan and LAMP assay for the rapid diagnosis of tuberculosis].

UNLABELLED: OBJECTIVE; The COBAS TaqMan real-time polymerase chain reaction (PCR) assay (TaqMan assay) is a well-accepted and widely distributed molecular-based diagnostic test for tuberculosis. In the present study, we evaluated the efficacy of the LAMP assay (loopamp MTBC detection kit) as an alternative molecular-based diagnostic kit for tuberculosis, through comparison with the TaqMan assay. STUDY PERIOD AND METHODS: This study was conducted over a period of approximately 2 months, between May and July 2012. We collected 48 samples (43 sputum, 2 gastric fluid, 2 pleural fluid, and 1 pus fluid samples) from patients who had been diagnosed with tuberculosis through the culture method, but had not received any treatment for more than one week. All samples were processed using the CC-E pre-treatment reagent (Japan BCG) prior to performing the TaqMan and LAMP assay. For the TaqMan assay, 100 microL of supernatant was used after centrifugation at 1,000 rpm for 1 minute, whereas 60 microL of the precipitate in the same sample was used for the LAMP assay. RESULTS: In total, 23 out of 48 samples were identified as positive for tuberculosis according to smear microscopy tests, among which 15, 4, and 4 samples had smear test scores or 1+, 2+, and 3+, respectively. All the samples that tested positive in the smear test, regardless of the score, also tested positive in both the TaqMan and TB-LAMP assays (100%). Of the 25 smear-negative samples, we noted that 16 tested positive by the TaqMan assay (64%), whereas 20 tested positive by the LAMP assay (80%). DISCUSSION: Compared with the TaqMan assay, the LAMP assay showed a higher positive rate among the smear-negative samples. We believe that this is because substances in the samples acted as co-precipitating agents, resulting in the presence of a larger number of bacteria in the precipitates than in the supernatants. Thus, the findings indicate that the application of the LAMP method to precipitates obtained following CC-E pre-treatments may lead to prompt diagnosis of tuberculosis, with a level of sensitivity comparable to that of culture tests.