Nocturnal Scratching and Quality of Sleep in Children with Atopic Dermatitis.

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.

Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand.

BACKGROUND: Cholangiocarcinoma (CCA) is an intractable cancer, and its incidence in northeastern Thailand is the highest worldwide. Infection with the liver fluke Opisthorchis viverrini (OV) has been associated with CCA risk. However, animal experiments have suggested that OV alone does not induce CCA, but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters. Therefore, in humans, other environmental and genetic factors may also be involved. AIM: To examine relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes. METHODS: This hospital-based case-control study enrolled 95 case-control pairs matched by age (± 5 years) and sex. We examined relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes, serum anti-OV, alcohol consumption, and smoking. Polymorphisms of CYP2E1, IL-6 (-174 and -634), IL-10 (-819), and NF-κB (-94) and their co-occurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed. RESULTS: Although CCA risk was not significantly associated with any single polymorphism, persons with the GSTT1 wild-type and CYP2E1 c1/c2 + c2/c2 genotype had an increased risk (OR = 3.33, 95%CI: 1.23-9.00) as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype. The presence of anti-OV in serum was associated with a 7- to 11-fold increased risk, and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms. CONCLUSION: In addition to infection with OV, gene-gene interactions may be considered as one of the risk factors for CCA development.

Efficacy of steroid pulse therapy for miliary tuberculosis complicated by acute respiratory distress syndrome.

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

Necessity and choice of therapy for Henoch-Schönlein purpura nephritis.

BACKGROUND: Henoch-Schönlein purpura nephritis often resolves spontaneously, without treatment, making decisions regarding therapeutic interventions difficult. METHODS: Fifty-four patients who were diagnosed as having Henoch-Schönlein purpura nephritis between April 2004 and March 2018, and developed hematuria and/or proteinuria, were studied retrospectively. The observation period ended at the disappearance of hematuria or proteinuria, or the last observation date before December 2019 for each patient. Twenty-four of the patients received no treatment (Group A), 19 underwent renin-angiotensin-aldosterone system inhibitors only (B), 4 experienced steroid pulse therapy and combination therapy only (C) and the remaining 7 received steroid pulse therapy and combination therapy following renin-angiotensin-aldosterone system inhibitors (C). Clinical characteristics were examined according to the treatment method. Survival analysis for persistent urinary abnormalities was performed according to treatment modality, with multiple treatment records created per subject, if necessary. RESULTS: The highest urine protein/creatinine levels were significantly higher in groups B and C than in group A. The lowest estimated glomerular filtration rate was not significantly different among the three groups. In groups A and B, proteinuria resolved in >90% of patients. Survival analysis showed that steroid pulse therapy and combination therapy was not related to the better resolution of hematuria or proteinuria than renin-angiotensin-aldosterone system inhibitors. CONCLUSIONS: Several patients with Henoch-Schönlein purpura nephritis went into remission either without treatment or with renin-angiotensin-aldosterone system inhibitors alone. The treatment plan for patients with Henoch-Schönlein purpura nephritis needs to be determined carefully.

The association between early formula and reduced risk of cow's milk allergy during the first three year of life: a Japanese cohort study.

BACKGROUND: Our recent observational study showed that regular consumption of cow's milk (CM) formula during early infancy (3-6 months old) was associated with a reduced risk of CM allergy (CMA) at 12 months old. However, the long-term association is unclear. The present study was aimed to examine how long this inverse association persists after 12 months old. METHODS: This study used the dataset of an ongoing nationwide prospective cohort, the Japan Environment and Children's Study, in which participants were registered between January 2011 and March 2014. We analyzed 65,568 children followed-up until 36 months old. The exposure factors were the consumption statuses of formula milk from 0-3, 3-6, and 6-12 months old. The primary outcome was the prevalence of CMA at 6, 12, 18, 24 and 36 months old. CMA was defined as an allergic reaction and sensitization to CM protein in an individual with no or limited intake of this protein at the evaluation time, combined with physician-diagnosed food allergy. Multivariable regression models were used to estimate the association between the periods of formula consumption and the prevalence of CMA. RESULTS: The prevalence of CMA increased with a peak of 1.51% at 18 months old and then declined to 0.79% at 36 months old. Formula milk from 3-6 months old was associated with a reduced risk of CMA throughout the first 3 years of life, although the extent of the reduction was mitigated with age (adjusted relative risk: [95% confidence interval]: 0.19 [0.10-0.34] at 12 months old, 0.23 [0.16-0.33] at 18 months old, 0.41 [0.26-0.64] at 24 months old, and 0.47 [0.26-0.80] at 36 months old). The association between early formula and CMA were observed in both children with and without eczema, but more prominent and long-lasting in the former than the latter. CONCLUSIONS: Regular exposure to CM protein during infancy was associated with a reduced prevalence of CMA during early childhood. At present, however, this observational study does not necessarily encourage formula feeding, and randomized controlled trials are warranted to confirm the findings and their significance.

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.

Physical growth and neurodevelopment during the first year of life: a cohort study of the Japan Environment and Children's Study.

BACKGROUND: The association between a slower physical growth and poorer neurodevelopment has been established in infants born preterm or small for gestational age. However, this association is inconsistent in term-born infants, and detailed investigations in infancy, when intervention is most beneficial for improving outcomes, are lacking. We therefore examined this association separately by sex during the first year of life in term-born infants. METHODS: Using data collected until children reached 12 months old in an ongoing prospective cohort of the Japan Environment and Children's Study, we analyzed 44,264 boys and 42,541 girls with singleton term-birth. The exposure variables were conditional variables that disentangle linear growth from weight gain relative to linear growth, calculated from the length and weight at birth and 4, 7 and 10 months old. Neurodevelopmental delay was identified using the Japanese-translated version of Ages & Stages Questionnaires, third edition. RESULTS: A reduced risk of neurodevelopmental delay at 6 months old was observed in children with a higher birth weight (adjusted relative risks [aRRs]: 0.91 and 0.93, 95 % confidence intervals [95 % CIs]: 0.87-0.96 and 0.88-0.98 in boys and girls, respectively) and increased linear growth between 0 and 4 months old (aRRs: 0.85 and 0.87, 95 % CIs: 0.82-0.88 and 0.83-0.91 in boys and girls, respectively). A reduced risk at 12 months was found in children with an increased linear growth between 0 and 4 months (aRRs: 0.92 and 0.90, 95 % CIs: 0.87-0.98 and 0.84-0.96 in boys and girls, respectively), boys with an increased relative weight gain between 0 and 4 months (aRR: 0.90, 95 % CI: 0.84-0.97), and girls with a higher birth weight (aRR: 0.89, 95 % CI: 0.83-0.96). CONCLUSIONS: These results suggest that a slow physical growth by four months old may be a predictor of neurodevelopmental delay during infancy.

Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan.

Background: Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment. Method: To characterize KD-related arthritis, 14 patients who required arthritis treatment within 30 days after the diagnosis of KD were recruited from the 23rd KD survey in Japan. Twenty-six additional patients were included from our tertiary center and literature review cohorts. Results: The estimated prevalence of KD-related arthritis in Japan was 48 per 100,000 KD patients. Patients with KD-related arthritis had an older age at onset (52 vs. 28 months, P = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, P < 0.001). Among 40 patients, 18 had arthritis in the acute phase KD (continued fever-onset type) and 22 did in the convalescent phase (interval fever-onset type). Both showed a similar rate of complete KD or IVIG response. Interval-type patients required biologics for arthritis control less frequently (5 vs. 39%, P = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, P = 0.009) than continued-type ones. Interval-types showed lower serum ferritin and interleukin-18 levels than continued-types. When continued-types were grouped according to whether or not they required biologics (n = 7 and n = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels (P = 0.01 and 0.02, respectively). A canonical discriminant analysis differentiated interval-type from continued-type with the combination of age, time to arthritis, and the ferritin and matrix metalloproteinase-3 levels. Conclusion: Arthritis requiring treatment is a rare complication of KD. KD-associated arthritis includes interval-type (KD-reactive) and continued-type (true systemic-onset juvenile idiopathic arthritis [JIA] requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.

Breast feeding and infant development in a cohort with sibling pair analysis: the Japan Environment and Children's Study.

OBJECTIVES: To investigate the association between breast feeding and infant development during the first year of life using sibling comparison. DESIGN: Nationwide prospective birth cohort study with sibling pair analysis. SETTING: 15 regional centres that participated in the Japan Environment and Children's Study. PARTICIPANTS: This study included 77 119 children (singleton, term birth and no malformation/severe diseases) whose mothers were registered between January 2011 and March 2014, including 3521 duos or trios of siblings. PRIMARY OUTCOME MEASURES: The primary outcome was developmental delay at 6 and 12 months of age, assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Multivariable regression analyses adjusted for confounders were performed to estimate the risk ratios of delay associated with any or exclusive breast feeding. Pairs of siblings discordant for statuses were selected, and conditional regression analyses were conducted with a matched cohort design. RESULTS: Developmental delay was identified in 6162 (8.4%) and 10 442 (14.6%) children at 6 and 12 months of age, respectively. Any breast feeding continued until 6 months or 12 months old was associated with reduced developmental delay at 12 months of age (adjusted risk ratio (95% CI): 0.81 (0.77 to 0.85) and 0.81 (0.78 to 0.84), respectively). Furthermore, exclusive breast feeding until 3 months was associated with reduced developmental delay at 12 months of age (adjusted risk ratio, 0.86 (95% CI 0.83 to 0.90)). In sibling pair analysis, the association between any breast feeding until 12 months and reduced developmental delay at 12 months of age persisted (adjusted risk ratio, 0.64 (95% CI 0.43 to 0.93)). CONCLUSIONS: The present study demonstrated the association of continuous breast feeding with reduced developmental delay at 1 year of age using sibling pair analysis, in which unmeasured confounding factors are still present but less included. This may provide an argument to promote breastfeeding continuation.

Possible association between early formula and reduced risk of cow's milk allergy: The Japan Environment and Children's Study.

BACKGROUND: Despite evidence for the protective effects of early regular exposure to peanut and egg proteins against allergies, the optimal timing of cow's milk (CM) protein exposure is unknown. OBJECTIVE: We aimed to determine when during the first year of life CM-based formula consumption becomes associated with lower CM allergy (CMA) risk. METHODS: We used the data set of the Japan Environment and Children's Study (JECS), a nationwide birth cohort involving over 100 000 mother-child pairs. CMA was defined as an allergic reaction to a CM product in an individual not consuming CM products at the time of evaluation, combined with physician-diagnosed food allergy. For each exposure, we identified when formula milk was commenced, and its consumption status during 0-3, 3-6 and 6-12 months old. RESULTS: The prevalence of CMA was 0.23% and 1.03% at 6 and 12 months old, respectively. Multivariable regression analyses revealed that introducing regular consumption of formula within the first 3 months of age was associated with lower risk of CMA at 12 months. Regular consumption at 3-6 months was strongly associated with a reduction in 12-month CMA (adjusted relative risks [95% confidence intervals]: 0.22 [0.12-0.35]), whereas no association was observed at 0-3 months (1.07 [0.90-1.27]). CONCLUSION AND CLINICAL RELEVANCE: Regular exposure to formula milk at age 3 months or older is associated with lower CMA at 12 months old, suggesting that the effect of very early CM exposure on CMA may disappear if the exposure is brief. At present, however, the results of this observational study should not be used for formula recommendation and randomized controlled trials are required to confirm this association.

Delayed Development of Coronary Artery Aneurysm in Patients with Kawasaki Disease Who Were Clinically Responsive to Immunoglobulin.

OBJECTIVE: To clarify the frequency and characteristics of discrepant outcomes of intravenous immunoglobulin (IVIG) between fever and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: This study included 325 patients who responded to oral aspirin and IVIG alone. The main outcome was CAA 4 weeks after disease onset. CAA was defined as ≥2.5 of maximum z score (Zmax) representing the highest value of 4 coronary artery branches. Immunoglobulin dosage and sequential changes in Zmax were reviewed to investigate the effects on fever and timing of CAA development. Logistic regression analyses with receiver operating characteristic curves using clinical and laboratory variables including the initial Zmax were performed to identify predictors of CAA at 4 weeks. RESULTS: CAAs were either persistent or appeared de novo 4 weeks after diagnosis in 13 of 325 patients who responded to a single or repeated IVIG. Four single-dose IVIG-responders developed CAA although they had pretreatment Zmax of <2.0. The 2 single-dose IVIG responders with the greatest pretreatment Zmax (>4.5) developed persistent CAA. Receiver operating characteristic analysis demonstrated Zmax of 2.57 as the cut-off for predicting CAA. Multivariable analyses identified >2.5 Zmax (OR 9.08, 95% CI 1.26-65.3, P = .028, 50% sensitivity, 91% specificity) as the sole risk factor for CAA at 4 weeks in single-dose IVIG responders. CONCLUSIONS: Delayed development and persistence of CAA in single-dose IVIG responders indicate that some factors other than those responsible for systemic inflammation may contribute to vasculitis in CAA. Baseline Zmax 2.5 aids in predicting CAAs.

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.

Hyperferritinemia and acute kidney injury in pediatric patients receiving allogeneic hematopoietic cell transplantation.

BACKGROUND: Acute kidney injury (AKI) often occurs in pediatric patients who received allogeneic hematopoietic cell transplantation (HCT). We evaluated the risk and effect of HCT-related AKI in pediatric patients. METHODS: We retrospectively studied the survival and renal outcome of 69 children 100 days and 1-year posttransplant in our institution in 2004-2016. Stage-3 AKI developed in 34 patients (49%) until 100 days posttransplant. RESULTS: The 100-day overall survival (OS) rates of patients with stage-3 AKI were lower than those without it (76.5% vs. 94.3%, P = 0.035). The 1-year OS rates did not differ markedly between 21 post-100-day survivors with stage-3 AKI and 29 without it (80.8% vs. 87.9%, P = 0.444). The causes of 19 deaths included the relapse of underlying disease or graft failure (n = 11), treatment-related events (4), and second HCT-related events (4). Underlying disease of malignancy (crude hazard ratio (HR) 5.7; 95% confidence interval (CI), 2.20 to 14.96), > 1000 ng/mL ferritinemia (crude HR 4.29; 95% CI, 2.11 to 8.71), stem cell source of peripheral (crude HR 2.96; 95% CI, 1.22 to 7.20) or cord blood (crude HR 2.29; 95% CI, 1.03 to 5.06), and myeloablative regimen (crude HR 2.56; 95% CI, 1.24 to 5.26), were identified as risk factors for stage-3 AKI until 100 days posttransplant. Hyperferritinemia alone was significant (adjusted HR 5.52; 95% CI, 2.21 to 13.76) on multivariable analyses. CONCLUSIONS: Hyperferritinemia was associated with stage-3 AKI and early mortality posttransplant. Pretransplant iron control may protect the kidney of pediatric HCT survivors.

[LONG-TERM RESULTS OF AIRBORNE POLLEN SURVEYS IN THE JAPANESE ARCHIPELAGO FROM THE PERSPECTIVE OF POLLEN ANTIGEN].

BACKGROUND: In 1986, the Ministry of Health and Welfare started an airborne pollen survey as part of measures against JC pollinosis. We reported the important tree pollen antigens in 2016. We have now estimated the longitudinal investigated results for successful prevention and treatment for allergic symptoms related to grass and weed pollen in Japan. METHOD: Since July 1986 we have monitored airborne pollen, year- round, using a gravitational pollen sampler (Durham's sampler), at more than 20 locations across Japan. Specimens were mailed to our facility, where they were stained with Calberla solution, counted under an optical microscope, and converted to the number of pollen per square centimeter. For convenience the number of collected pollen were compiled every six months, with the January to June samples classified as spring pollen and the July to December as autumn pollen even same family. RESULT: Total pollen counts at each location were extremely small compared to tree-pollen, averaging 73~650 pollen grains per year. The Sagamihara location had the greatest count. Unlike cedar and cypress there were no significant annual fluctuations, but grass and Ambrosia pollen counts are increasing in some regions. Spring grass pollen gave the largest count, at 30% of the total collected. CONCLUSION: This indicated we need to examine the rinoconjuctivitis and oral allergy syndrome related to herbaceous pollen carefully.The importance of airborne pollen surveys for the treatment of the patients with pollen allergies was suggested.

An independent relation of atopic dermatitis to exercise-induced wheezing in asthmatic children.

BACKGROUND: Atopic dermatitis (AD) and exercise-induced asthma (EIA) are common in asthmatic children, and exercise is the most common trigger other than infection for acute onset asthma attack in children. We examined whether AD is related to exercise-induced wheezing (EIW), some proxy for EIA. METHODS: Japanese version of the International Study of Asthma and Allergies in Childhood questionnaires were used. For 12,405 asthmatic school children, AD was defined as itchy rash coming and going for at least 6 months at any time in the last 12 months with affecting places of flexural parts of body, and severity of AD was rated according to frequency of being kept awake at night with the itch as follows: never in the past 12 months, less than one night per week and one or more nights per week. RESULTS: Adjusted for frequency of asthma attack, odds ratios (OR) of children with current AD as compared to those without AD for having EIW were 1.32 (95% confidence interval = 1.15-1.52), 1.35 (1.14-1.68) and 1.10 (0.92-1.31) for primary school, junior high school and high school children, respectively. EIW was more likely observed in accordance with increasing severity of AD in the primary school children with ORs of 1.12, 1.59 and 1.54 (p for trend < 0.01), and in the junior high school ones with ORs of 1.18, 1.31, 2.03 (<0.01), respectively. CONCLUSIONS: AD may be possibly related to EIW. Further studies investigating effect of AD treatment on EIW may be required.

Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.

BACKGROUND: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. METHODS: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into "progression group" (n = 7) that required any therapy and "spontaneous resolution group" (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-ß1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. RESULTS: Three patients developed leukemia during the study period (median, 1147 days; range, 33-3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = -0.46, p = 0.02). CONCLUSION: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.

A nationwide survey on tracheostomy for very-low-birth-weight infants in Japan.

OBJECTIVES: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan. METHODS: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined. RESULTS: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P < 0.01) and longer hospitalization (229 days vs 83 days, P < 0.01) than non-tracheostomized infants. Tracheostomized patients showed higher comorbidities with hypoxic ischemic encephalopathy (odds ratio [OR] 10.98, P < 0.01), muscular disease (OR 10.95, P < 0.01), severe or moderate BPD (OR 7.79, P < 0.01), chromosomal abnormality (OR 4.43, P < 0.01) or sepsis (OR 1.78, P < 0.05) at hospital discharge than non-tracheostomized patients. CONCLUSION: We demonstrated the non-increasing rate in tracheostomy for VLBWIs and such cases were associated with an excellent survival in Japan. These data provide evidence that more attentive care must be practiced in order to reduce the pulmonary and neuromuscular burdens of VLBWIs at birth.