Age-specific associations of early daycare, older siblings, severe airway infection, and preterm birth with subsequent atopic diseases.

BACKGROUND: The effects of infection and developmental adaptations in infancy on the prevalence of subsequent atopy-related diseases at different ages during childhood are not fully determined. This study aims to examine the similarities and differences in the age-specific association of asthma, allergic rhinitis/conjunctivitis, and atopic dermatitis with early-life infection-related factors (i.e., daycare, older siblings, and severe airway infection) and developmental adaptations (i.e., preterm birth and rapid weight gain) in children. METHODS: In this longitudinal cohort study (n = 47,015), children were followed from 0.5 to 11 years. The potential risks and protective factors, including daycare attendance at 0.5 years, existence of older siblings, history of hospitalization due to cold/bronchitis/bronchiolitis/pneumonia during 0.5-1.5 years, preterm birth, and rapid weight gain in the first 2.5 years, were assessed using multivariable logistic regression with adjustments for potential confounders. RESULTS: A protective association was observed between early-life daycare attendance and asthma at 5.5-9 years, which disappeared after 10 years. A protective association was also noted throughout childhood between early daycare attendance and older siblings with allergic rhinitis/conjunctivitis. However, the association between early daycare and atopic dermatitis was found to be risky during childhood. In contrast, the early-life history of hospitalization owing to cold/bronchitis/bronchiolitis/pneumonia was identified to be a risk factor for developing both asthma and allergic rhinitis/conjunctivitis. Preterm birth was a significant risk factor for childhood asthma. CONCLUSION: Different age-specific patterns were demonstrated in the relationship between early daycare, severe airway infection, preterm birth, and atopy-related diseases in childhood.

Association between early antibiotic treatment and clinical outcomes in children hospitalized for asthma exacerbation.

BACKGROUND: Professional society guidelines recommend against routine early antibiotic use in the treatment of asthma exacerbation without comorbid bacterial infection. However, high antibiotic prescribing rates have been reported in developed countries. OBJECTIVE: We sought to assess the effectiveness of this strategy in the routine care of children. METHODS: Using data on 48,743 children hospitalized for asthma exacerbation with no indication of bacterial infection during the period 2010 to 2018, we conducted a retrospective cohort study to compare clinical outcomes and resource utilization between children who received early antibiotic treatment and those who did not. RESULTS: Overall, 19,866 children (41%) received early antibiotic treatment. According to the propensity score matching analysis, children with early antibiotic treatment had longer hospital stay (mean difference, 0.21 days; 95% CI, 0.18-0.28), higher hospitalization costs (mean difference, $83.5; 95% CI, 62.9-104.0), and higher risk of probiotic use (risk ratio, 2.01; 95% CI, 1.81-2.23) than children who did not receive early antibiotic therapy. Similar results were found from inverse probability of treatment weighting, g-computation, and instrumental variable methods and sensitivity analyses. The risks of mechanical ventilation and 30-day readmission were similar between the groups or slightly higher in the treated group, depending on the statistical models. CONCLUSIONS: Antibiotic therapy may be associated with prolonged hospital stay, elevated hospitalization costs, and high risk of probiotic use without improving treatment failure and readmission. Our findings highlight the need for reducing inappropriate antibiotic use among children hospitalized for asthma.

Recent Practice Patterns and Variations in Children Hospitalized for Asthma Exacerbation in Japan.

BACKGROUND: High antibiotic prescribing rates for adults with an asthma exacerbation have been reported in developed countries, but few studies have assessed the variation of antibiotic and adjunctive treatment in the routine care of children. OBJECTIVE: We evaluated the trends in health resource utilization for children hospitalized for asthma exacerbation, ascertained the variations of practices across hospitals and geographic location, and classified these different patterns at hospital levels. METHODS: Using data on Japanese children hospitalized for asthma exacerbation with no indication of bacterial infection during 2010-2018, we conducted a retrospective observational study to assess the trends in initial treatment patterns and their variations. Mixed-effect generalized linear models were used to investigate the treatment trends. Hierarchical cluster analyses were performed to classify the treatment variations across hospitals. RESULTS: Overall, 54,981 children were eligible for the study. Proportions of antibiotic use decreased from 47.2% in 2010 to 26.9% in 2018. Similarly, utilization of antitussives, antihistamines, and methylxanthine showed decreasing trends over the period, whereas the use of mucolytics and ambroxol increased. These treatment variations were more considerable in hospital levels than in 47 prefecture levels. Hierarchical cluster analyses classified these patterns into 6 groups, mostly based on mediator release inhibitor, ambroxol, and antitussives. CONCLUSIONS: Wide variations in antibiotics and adjunctive treatments were observed across hospital levels. Our findings support the improvement in reducing inappropriate antibiotic use and highlight the need for comparative effectiveness research of the adjunctive treatments among children hospitalized for asthma.

Transepidermal water loss measurement during infancy can predict the subsequent development of atopic dermatitis regardless of filaggrin mutations.

BACKGROUND: Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Few studies have used noninvasive techniques to measure epidermis function in asymptomatic neonates. METHODS: Data of 116 infants from our previous randomized controlled study were analyzed. Skin barrier function was measured through transepidermal water loss (TEWL), stratum corneum hydration (SCH), and pH. The association between skin barrier function and time to AD development was evaluated. Patients were classified with high or low TEWL, and SCH and pH were assessed. The survival function of the time to AD development and hazard ratios were estimated. Allergic sensitization to egg white and ovomucoid at 32 weeks was assessed. RESULTS: Regardless of a filaggrin mutation, TEWL (optimal cutoff, 6.5 g/m(2)/h) of the forehead within the first week of life showed a lower p-value than TEWL of the leg, and the SCH and pH measurements. Baseline TEWL of the forehead was not different between groups, except for the mean gestational age, and it was not affected by humidity. We found a significant difference in the cumulative AD incidence between the high and low TEWL groups for the forehead only (p < 0.05). The probability without AD was lower in the high TEWL group than in the low TEWL group. For only the high TEWL group, AD development decreased significantly with daily emollient use. The high TEWL group exhibited a higher rate of sensitization to ovomucoid (p = 0.07). CONCLUSIONS: TEWL of the forehead during the first week of life is associated with AD development.

Application of moisturizer to neonates prevents development of atopic dermatitis.

BACKGROUND: Recent studies have suggested that epidermal barrier dysfunction contributes to the development of atopic dermatitis (AD) and other allergic diseases. OBJECTIVE: We performed a prospective, randomized controlled trial to investigate whether protecting the skin barrier with a moisturizer during the neonatal period prevents development of AD and allergic sensitization. METHODS: An emulsion-type moisturizer was applied daily during the first 32 weeks of life to 59 of 118 neonates at high risk for AD (based on having a parent or sibling with AD) who were enrolled in this study. The onset of AD (eczematous symptoms lasting >4 weeks) and eczema (lasting >2 weeks) was assessed by a dermatology specialist on the basis of the modified Hanifin and Rajka criteria. The primary outcome was the cumulative incidence of AD plus eczema (AD/eczema) at week 32 of life. A secondary outcome, allergic sensitization, was evaluated based on serum levels of allergen-specific IgE determined by using a high-sensitivity allergen microarray of diamond-like carbon-coated chips. RESULTS: Approximately 32% fewer neonates who received the moisturizer had AD/eczema by week 32 than control subjects (P = .012, log-rank test). We did not show a statistically significant effect of emollient on allergic sensitization based on the level of IgE antibody against egg white at 0.34 kUA/L CAP-FEIA equivalents. However, the sensitization rate was significantly higher in infants who had AD/eczema than in those who did not (odds ratio, 2.86; 95% CI, 1.22-6.73). CONCLUSION: Daily application of moisturizer during the first 32 weeks of life reduces the risk of AD/eczema in infants. Allergic sensitization during this time period is associated with the presence of eczematous skin but not with moisturizer use.

Oral Immunotherapy With Extensively Hydrolyzed Milk for a 12-Year-Old Child With Persistent, Severe Cow's Milk Allergy.

A 12-year-old girl with severe cow's milk allergy (CMA) was able to safely consume 300 mL of unhydrolyzed cow's milk after three and a half years of oral immunotherapy (OIT) with extensively hydrolyzed milk. The treatment consisted of gradually increasing the intake of hydrolyzed and partially hydrolyzed milk and reintroducing cow's milk. Despite some allergic reactions during treatment, the patient was able to consume more than 200 ml of milk consistently for more than six months without recurrence of symptoms. This case suggests the possibility of an alternative treatment for persistent CMA: not only OIT with cow's milk alone but also a safer introduction to treatment with extensively hydrolyzed formulas.

Differences in Characteristics Between Patients Who Met or Partly Met the Diagnostic Criteria for Food Protein-Induced Enterocolitis Syndrome (FPIES).

BACKGROUND: Some patients with food protein-induced enterocolitis (FPIES)-like allergy do not completely fulfill the diagnostic criteria of the international consensus guideline for FPIES. However, it is unclear whether such FPIES-like patients represent a completely different population from FPIES. OBJECTIVE: This study aimed to clarify differences in characteristics between patients with FPIES who fully met diagnostic criteria and those who partly met them. METHODS: This was a cross-sectional study using data at the time of registration in multicenter, prospective studies of patients with FPIES in Japan. Children who had delayed emesis within 1 to 4 hours and/or diarrhea within 5 to 10 hours after ingestion of food were recruited between March 2020 and February 2022. We examined their compatibility with the diagnostic criteria of the international consensus guideline and their detailed clinical characteristics, including trigger foods, the serving size that elicited symptoms, and antigen-specific IgE antibody titers. RESULTS: Of the 225 patients with FPIES, 140 fully met the diagnostic criteria whereas 79 patients did not fully meet them but demonstrated reproducible symptoms. The frequencies of pallor, lethargy, and diarrhea were significantly higher in those who met the criteria fully, whereas the age at onset, trigger foods, comorbidity, and perinatal information were comparable. Analysis of patients with FPIES to hen's egg revealed significantly higher levels of egg white- and egg yolk-specific IgE in patients who partly met criteria, whereas the serving size eliciting symptoms was comparable. CONCLUSIONS: Patients who partly met the diagnostic criteria may have a milder phenotype of FPIES, but this needs to be validated in further studies using biomarkers reflecting the pathophysiology.

Low-Dose Oral Challenge Test in Pediatric Patients With Peanut Allergy: Tolerance Assessment of a Trace 5 mg Peanut Test After Symptom Induction With a 500 mg Test.

Introduction Peanut allergy (PA) represents a significant public health concern, particularly prevalent in Western countries. Children at high risk for PA may undergo a low-dose oral food challenge (OFC). However, if the result is positive, complete elimination of peanuts from the diet is recommended, and further trace OFC is typically not performed.  Material and methods This cross-sectional study retrospectively examined the rate of positive peanut OFC with a total peanut load of 5 mg in children who tested positive with a total peanut load of 500 mg. Patient information was gathered from medical records. The primary endpoint was the rate at which children who tested positive in the OFC with 500 mg of peanut butter also tested positive with 5 mg of peanut butter equivalent.  Results Among 32 children who underwent an OFC with a total peanut load of 500 mg, two were excluded for not meeting the criteria. Among the remaining 30 children, 14 (46.7%) had a positive 500 mg peanut OFC test, and three (10%) experienced an anaphylactic reaction. Those who tested positive for the OFC had higher peanut-specific and Ara h2-specific immunoglobulin E (IgE) antibodies. An OFC with 5 mg of peanuts performed on 10 of the 14 patients who tested positive for 500 mg of peanuts showed no positive results. Conclusion The results of this study suggest that children with severe PA who exhibit positive symptoms to a total peanut load of 500 mg can tolerate a 5 mg dose of peanuts and should be considered for an OFC.

Transepidermal Water Loss and T-helper 2 (Th2)-Associated Inflammatory Markers in Two Pediatric Patients During the First Four Weeks of Treatment With the Oral Janus Kinase Inhibitor Upadacitinib.

Few studies have evaluated the effects of upadacitinib on skin barrier function and T-helper 2 (Th2)-associated inflammatory biomarkers in severe atopic dermatitis (AD). In this study, we followed two pediatric patients with AD who had previously failed to respond to conventional treatment and measured their serum Th2-associated chemokine thymus and activation-regulated chemokine (TARC) and serine protease inhibitor squamous cell carcinoma antigen (SCCA) 2 levels and transepidermal water loss (TEWL) during the first four weeks of upadacitinib treatment. Both patients showed marked clinical improvement and decreased TEWL, blood eosinophil counts, and serum TARC and SCCA2 levels after four weeks of upadacitinib treatment. These findings suggest that upadacitinib attenuates Th2-associated inflammatory markers and promotes skin barrier integrity.

Food Allergens and Essential Oils in Moisturizers Marketed for Children in Japan.

Introduction Personal skincare leave-on products increase the risk of food allergies. Parents must be imparted with an elevated degree of cognizance regarding the allergenic nature of pediatric skincare products. Material and methods We aimed to examine the data inferred from the promotional material on labeling these products about their proclivity to elicit skin sensitization. This study investigated the relationship between food allergens and essential oil ingredients and highlighted marketing terms, product prices, and ratings of moisturizers for children that are sold on Amazon, Japan. We searched and recorded the product labels and website marketing terms, price (per gram or milliliter), the number of reviews, and allergens and investigated the relationship between the percentage of food allergens in those products and marketing terms, price, and the number of Amazon reviews. Results Among the 164 pediatric skincare products we included, 144 (87.8%) that were manufactured in Japan were the most common; 7 (4.3%), 15 (9.1%), 23 (14.0%), 24 (14.6%), and 54 (32.9%) contained the eight regulated food allergens, grain, nut, fruit, and essential oils, respectively. Marketing terms emphasizing "natural/organic" were more likely to contain grain allergens and essential oils and were more expensive with and without "organic" labeling, respectively, whereas those labeled with marketing terms emphasizing "hypoallergenic" were less likely to contain fruit allergens or essential oils. Products with fewer Amazon reviews were more likely to use the marketing term "natural/organic" and had a higher grain allergen content. Conclusion In Japan, 4.3% of children's skincare products sold on Amazon contain eight food allergens that should obligatorily be labeled when included in food products. In addition, more than 10% of these children's skin care products contain ingredients derived from nuts, while more than 30% contain fruit extracts or essential oils.

Corowa-kun: A messenger app chatbot delivers COVID-19 vaccine information, Japan 2021.

BACKGROUND: There is a long history in Japan of public concerns about vaccine adverse events. Few studies have assessed how mobile messenger apps affect COVID-19 vaccine hesitancy. METHODS: Corowa-kun, a free chatbot, was created on February 6, 2021 in LINE, the most popular messenger app in Japan. Corowa-kun provides instant, automated answers to 70 frequently asked COVID-19 vaccine questions. A cross-sectional survey with 21 questions was performed within Corowa-kun during April 5-12, 2021. RESULTS: A total of 59,676 persons used Corowa-kun during February-April 2021. Of them, 10,192 users (17%) participated in the survey. Median age was 55 years (range 16-97), and most were female (74%). COVID-19 vaccine hesitancy reported by survey respondents decreased from 41% to 20% after using Corowa-kun. Of the 20% who remained hesitant, 16% (1,675) were unsure, and 4% (364) did not intend to be vaccinated. Factors associated with vaccine hesitancy were: age 16-34 (odds ratio [OR] = 3.7; 95% confidential interval [CI]: 3.0-4.6, compared to age ≥ 65), female sex (OR = 2.4; Cl: 2.1-2.8), and history of a previous vaccine side-effect (OR = 2.5; Cl: 2.2-2.9). Being a physician (OR = 0.2; Cl: 0.1-0.4) and having received a flu vaccine the prior season (OR = 0.4; Cl: 0.3-0.4) were protective. CONCLUSIONS: A substantial number of people used the chabot in a short period. Mobile messenger apps could be leveraged to provide accurate vaccine information and to investigate vaccine intention and risk factors for vaccine hesitancy.

[Pompholyx-like reactions occurring early in treatment of severe atopic dermatitis in children and adolescence].

BACKGROUND: Pompholyx-like reactions may develop for aggressive atopic dermatitis treatments in the incipient phase despite of improvement of other skin symptoms. METHODS: Eighty-nine patients admitted to National Center for Child Health and Development for treatment of atopic dermatitis between April 2007 and March 2009 were recruited. RESULTS: Pompholyx-like reactions were seen in thirteen out of eighty-nine patients between 4 and 32 (mean 16.7±10.4) days following admission. The mean age of patients with these reactions was 6.2±6.1 years (range of 3 months to 23 years). At the time of admission, practical issues of scoring atopic dermatitis: the SCORAD was assessed. The values of SCORAD index with pompholyx were ranging from 16-91 (mean 50.8±17.9), and the index except under one-year old were significantly higher than unaffected patients. These patients were evaluated into their medical record, for evidence of Pompholyx-like lesions: a bilateral vesicular eruption confined to the skin of the palms, soles, or sides of the fingers. Topical corticosteroids are used to treat Pompholyx-like reactions, all them achieved remission between 4 and 50 days (mean 18.5±12.0). In general, pompholyx is more common in summer. However, it seems that there were no significant differences in the pompholyx-like reactions incidence between in summer and in winter. CONCLUSION: The factor for the occurrence of pompholyx-like lesions remains unexplained. Although the original symptoms of eczema were improved, pompholyx-like eczema breakout, therefore, patients often feel uneasy. We should be aware of this clinical condition.

[Factors influencing parental medication adherence in pediatric asthma].

PURPOSE: To identify the factors influencing parental medication control behaviors (inhaling corticosteroids and medication-taking) in pediatric asthma management. METHODS: A specially-designed questionnaire survey was conducted on 942 parents with asthmatic children in hospitals and elementary schools. RESULTS: Factor analysis on inhalation behaviors resulted in five factors: understanding of benefit, mastering on inhalation skills and medication management, family support, anxiety of side effects, and explanation from a doctor (cumulative contribution ratio=51.3%). Factor analysis on medication-taking behavior resulted in five factors: understanding of medication effectiveness and benefit, family support, anxiety of side effects, skills on giving medicines, and family routine (cumulative contribution ratio=50.6%). CONCLUSION: The results indicate the importance of recognizing factors influencing parental medication control behaviors in developing education strategies to maintain and reinforce their asthma management behaviors.

Environmental tobacco smoke and its effect on the symptoms and medication in children with asthma.

Environmental tobacco smoke (ETS) worsens asthmatic symptoms. We analyzed the relationship between levels of ETS and asthmatic symptoms and medication. We asked parents of 282 asthmatic children about the general condition, smoke exposure and medication. Patients were classified into three groups: no-ETS (no smoking), mild-ETS (smoking in the house but not in the same room as patient), and heavy-ETS (smoking in the same room as patient). We classified 116 children in no-ETS group, 124 children in mild-ETS group and 42 children in heavy-ETS group. The symptoms were worst and prevalence of leukotriene receptor antagonist and long-acting beta(2)-agonist use were highest in heavy-ETS group. However, there was no statistical difference between no-ETS and mild-ETS groups in prevalence of anti-asthmatic drug use and symptoms. We conclude that a smoking ban in rooms used by asthmatic children is an easy way to reduce ETS, asthmatic symptoms and the use of anti-asthmatic drugs.

Underrecognition of the severity of asthma and undertreatment of asthma in a rural area of Japan.

BACKGROUND AND AIM: Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics. METHODS: We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics. RESULTS: In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%. CONCLUSION: In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.