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.

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.

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.

TGF-ß2 promotes RPE cell invasion into a collagen gel by mediating urokinase-type plasminogen activator (uPA) expression.

Transforming growth factor-beta (TGF-ß) is one of the main epithelial-mesenchymal transition (EMT)-inducing factors. In general, TGF-ß-induced EMT promotes cell migration and invasion. TGF-ß also acts as a potent regulator of pericellular proteolysis by regulating the expression and secretion of plasminogen activators. Urokinase-type plasminogen activator (uPA) is a serine protease that binds to its cell surface receptor (uPAR) with high affinity. uPA binding to uPAR stimulates uPAR's interaction with transmembrane proteins, such as integrins, to regulate cytoskeletal reorganization and cell migration, differentiation and proliferation. However, the influence of TGF-ß and the uPA/uPAR system on EMT in retinal pigment epithelial (RPE) cells is still unclear. The purpose of this study was to determine the effect of TGF-ß2, which is the predominant isoform in the retina, and the uPA/uPAR system on RPE cells. In this study, we first examined the effect of TGF-ß2 and/or the inhibitor of uPA (u-PA-STOP(®)) on the proliferation of a human retinal pigment epithelial cell line (ARPE-19 cells). Treatment with TGF-ß2 or u-PA-STOP(®) suppressed cell proliferation. Combination treatment of TGF-ß2 and u-PA-STOP(®) enhanced cell growth suppression. Furthermore, western blot analysis, fibrin zymography and real-time reverse transcription PCR showed that that TGF-ß2 induced EMT in ARPE-19 cells and that the expression of uPA and uPAR expression was up-regulated during EMT. The TGF-ß inhibitor SB431542 suppressed TGF-ß2-stimulated uPA expression and secretion but did not suppress uPAR expression. Furthermore, we seeded ARPE-19 cells onto Transwell chambers and allowed them to invade the collagen matrix in the presence of TGF-ß2 alone or with TGF-ß2 and u-PA-STOP(®). TGF-ß2 treatment induced ARPE-19 cell invasion into the collagen gel. Treatment with a combination of TGF-ß2 and the uPA inhibitor strongly inhibited ARPE-19 cell invasion compared with treatment with TGF-ß2 alone. Furthermore, the interaction between uPA and ARPE-19 cells was analyzed using a surface plasmon biosensor system. The binding of uPA to ARPE-19 cells was observed. In addition, TGF-ß2 significantly promoted the binding activity of uPA to ARPE-19 cells in a time-dependent or cell-number-dependent fashion. These results indicate that TGF-ß-induced EMT-associated phenotype changes in ARPE-19 cells and the invasiveness of ARPE-19 cells into a collagen gel matrix are mediated, at least in part, by uPA.

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.