Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma.

Item does not contain fulltextRATIONALE: For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids, evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids. OBJECTIVE: To evaluate whether salmeterol/fluticasone propionate (SFP), 50/100 mug twice a day, is noninferior regarding symptom control compared with fluticasone propionate (FP), 200 mug twice a day Diskus in children with symptomatic asthma. METHODS: A multicenter, randomized, parallel-group, double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function. MEASUREMENTS AND MAIN RESULTS: A total of 158 children, 6-16 years old, still symptomatic on FP, 100 mug twice a day, during a 4-week run-in period, were included. Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference [FP minus SFP] 2.6%; 95% confidence interval, -8.1 to 13.4). Both groups showed substantial improvements of about 25 percent points in symptom-free days (both P < 0.001 from baseline). Lung function measurements (FEV(1), FVC, PEF rate, and maximal expiratory flow) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week. No differences were found between FP and SFP regarding exacerbation rates, adverse events, or growth. CONCLUSIONS: In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid

Comparing Global Initiative for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT)

Item does not contain fulltextSeveral tools are useful in detecting uncontrolled asthma in children. The aim of this study was to compare Global Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines, asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children. The area under the curve in the receiver operating characteristic curves for C-ACT and ACT versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with uncontrolled asthma as defined by GINA

Fractional Exhaled Nitric Oxide Monitoring Does Not Improve Asthma Management in Children with Concordant and Discordant Asthma Phenotypes

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乳癌組織中EGF-R與TGF-α之偵測

Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate (EBC) acidity, nitrite, nitrate, hydrogen peroxide (H(2)O(2)), 8-isoprostane, Th1/Th2 cytokines] to indicate (exacerbations of) CF; and (ii) the ability of these non-invasive IM to indicate CF disease severity. In 98 children (48 CF/50 controls), exhaled nitric oxide was measured using the NIOX, and condensate was collected using a glass condenser. In CF interferon (IFN-gamma) and nitrite concentrations were significantly higher, whereas exhaled nitric oxide levels were significantly lower compared with controls (3.3 +/- 0.3 pg/ml, 2.2 +/- 0.2 microM, 10.0 +/- 1.2 p.p.b. vs. 2.6 +/- 0.2 pg/ml, 1.4 +/- 0.1 microM, 15.4 +/- 1.4 p.p.b. respectively). Using multivariate logistic regression models, the presence of CF was best indicated by 8-isoprostane, nitrite and IFN-gamma [sensitivity 78%, specificity 83%; area under receiver operating characteristic curve (AUC) 0.906, p < 0.001]. An exacerbation of CF was best indicated by 8-isoprostane and nitrite (sensitivity 40%, specificity 97%, AUC curve 0.838, p = 0.009). Most indicative biomarkers of CF severity were exhaled nitric oxide, and condensate acidity (sensitivity 96%, specificity 67%; AUC curve 0.751, p = 0.008). In this cross-sectional study, the combination of different exhaled IM could indicate (exacerbations of) CF, and severity of the disease in children. Longitudinal data are necessary to further confirm the role of these markers for the management of CF in children

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development.

Item does not contain fulltextA de novo 4.1-megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array-based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 (SLC2A1 or GLUT1) gene. The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777). GLUT1 deficiency syndrome is characterized by therapy-resistant infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low concentration of glucose in the CSF. It is known that a ketogenic diet can lead to better control of seizures. This case study shows that identifying a microdeletion as the cause of learning disability is not only important for genetic counselling but might also lead to therapeutic intervention

Monitoring strategies in children with asthma: a randomised controlled trial

Item does not contain fulltextBACKGROUND: Asthma guidelines recommend monitoring of asthma control. However, in a substantial proportion of children, asthma is poorly controlled and the best monitoring strategy is not known. OBJECTIVES: We studied two monitoring strategies for their ability to improve asthma outcomes in comparison with standard care (SC): web-based monthly monitoring with the (Childhood) Asthma Control Test (ACT or C-ACT) and 4-monthly monitoring of FENO. METHODS: In this randomised controlled, partly blinded, parallel group multicentre trial with a 1-year follow-up, children aged 4-18 years with a doctor's diagnosis of asthma treated in seven hospitals were randomised to one of the three groups. In the web group, treatment was adapted according to ACT obtained via a website at 1-month intervals; in the FENO group according to ACT and FENO, and in the SC group according to the ACT at 4-monthly visits. The primary endpoint was the change from baseline in the proportion of symptom-free days (SFD). RESULTS: Two-hundred and eighty children (mean age 10.4 years, 66% boys) were included; 268 completed the study. Mean changes from baseline in SFD were similar between the groups: -2.1% (web group, n=90), +8.9% (FENO group, n=91) versus 0.15% (SC, n=87), p=0.15 and p=0.78. Daily dose of inhaled corticosteroids (ICS) decreased more in the web-based group compared with both other groups (-200 mug/day, p<0.01), while ACT and SFD remained similar. CONCLUSIONS: The change from baseline in SFD did not differ between monitoring strategies. With web-based ACT monitoring, ICS could be reduced substantially while control was maintained. TRIAL REGISTRATION NUMBER: NTR 1995

Monitoring childhood asthma: Web-based diaries and the asthma control test

BACKGROUND: Data from asthma diaries are frequently used as an end point in asthma studies; however, data on the validity of Web-based diaries are scarce. OBJECTIVES: First, we examined the validity of a Web-based diary in assessing asthma control. Second, we determined the cutoff points for well-controlled asthma of the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT), and calculated the minimal important difference for both tests. METHODS: Children with asthma, ages 4-18 years (n = 228) completed a 4-week Web-based diary, C-ACT, ACT, and an asthma-related quality-of-life questionnaire at baseline and after 1-year follow-up. RESULTS: The completion rate of the Web-based diaries was 89%. The diary scores correlated strongly with C-ACT and ACT scores (r = -0.73, P /= 22 and ACT >/= 23. The minimal important differences were 1.9 (95% CI, 1.3-2.5) for ACT and 1.6 (95% CI, 1.1-2.1) for C-ACT, and -0.7 points/d (95% CI, -1.1 to -0.4) for the Web-based diary. CONCLUSIONS: Our Web-based diary was valid for recording asthma symptoms. Cutoff points of >/=22 (C-ACT) and >/=23 (ACT) define well-controlled asthma. We recommend a 2 C-ACT and ACT points difference as minimally important

Cost-effectiveness of FENO-based and web-based monitoring in paediatric asthma management: a randomised controlled trial

BACKGROUND: In children with asthma, web-based monitoring and inflammation-driven therapy may lead to improved asthma control and reduction in medications. However, the cost-effectiveness of these monitoring strategies is yet unknown. OBJECTIVE: We assessed the cost-effectiveness of web-based monthly monitoring and of 4-monthly monitoring of FENO as compared with standard care. METHODS: An economic evaluation was performed alongside a randomised controlled multicentre trial with a 1-year follow-up. Two hundred and seventy-two children with asthma, aged 4-18 years, were randomised to one of three strategies. In standard care, treatment was adapted according to Asthma Control Test (ACT) at 4-monthly visits, in the web-based strategy also according to web-ACT at 1 month intervals, and in the FENO-based strategy according to ACT and FENO at 4-monthly visits. Outcome measures were patient utilities, healthcare costs, societal costs and incremental cost per quality-adjusted life year (QALY) gained. RESULTS: No statistically significant differences were found in QALYs and costs between the three strategies. The web-based strategy had 77% chance of being most cost-effective from a healthcare perspective at a willingness to pay a generally accepted euro40 000/QALY. The FENO-based strategy had 83% chance of being most cost-effective at euro40 000/QALY from a societal perspective. CONCLUSIONS: Economically, web-based monitoring was preferred from a healthcare perspective, while the FENO-based strategy was preferred from a societal perspective, although in QALYs and costs no statistically significant changes were found as compared with standard care. As clinical outcomes also favoured the web-based and FENO-based strategies, these strategies may be useful additions to standard care. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR1995)