Clinical and molecular characterization of the R751L-CFTR mutation.

Cystic fibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressive and life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe the clinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individuals harboring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made in primary human bronchial epithelial cultures (HBEs) and Xenopus oocytes. Molecular properties of R751L-CFTR were investigated in the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotype associated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared with non-CF HBEs and associated with a reduction in sodium absorption by the epithelial sodium channel (ENaC). However, R751L-CFTR function in Xenopus oocytes, together with folding and cell surface transport of R751L-CFTR, was not different from wild-type CFTR. Overall, R751L-CFTR was associated with reduced sodium chloride absorption but had functional properties similar to wild-type CFTR. This is the first report of R751L-CFTR that combines clinical phenotype with characterization of functional and biological properties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and, importantly, inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to alternative non-CFTR factors, which require further investigation.

Diagnosis and management of asthma in children.

Asthma is the the most common chronic respiratory condition of childhood worldwide, with around 14% of children and young people affected. Despite the high prevalence, paediatric asthma outcomes are inadequate, and there are several avoidable deaths each year. Characteristic asthma features include wheeze, shortness of breath and cough, which are typically triggered by a number of possible stimuli. There are several diagnostic challenges, and as a result, both overdiagnosis and underdiagnosis of paediatric asthma remain problematic.Effective asthma management involves a holistic approach addressing both pharmacological and non-pharmacological management, as well as education and self-management aspects. Working in partnership with children and families is key in promoting good outcomes. Education on how to take treatment effectively, trigger avoidance, modifiable risk factors and actions to take during acute attacks via personalised asthma action plans is essential.This review aimed to provide an overview of good clinical practice in the diagnosis and management of paediatric asthma. We discuss the current diagnostic challenges and predictors of life-threatening attacks. Additionally, we outline the similarities and differences in global paediatric asthma guidelines and highlight potential future developments in care. It is hoped that this review will be useful for healthcare providers working in a range of child health settings.

BReATHE interventions (Beating Regional Asthma Through Health Education)-an innovative approach to children's asthma care in the North East and North Cumbria, UK: an interventional study.

To objective of this project was to reduce unplanned hospital admission rates in children related to asthma to the Newcastle upon Tyne Hospitals National Health Service Trust (NUTH).Multiple educational interventions were introduced both locally and regionally including: a collection of educational materials aimed at young people and families, schools, primary care and secondary care on the website www.beatasthma.co.uk; regional training days; a nurse-led one-stop clinic; a new pathway following an acute attendance to hospital with an asthma attack; a local asthma service and cascade training for schools.The primary outcome measure was reduction in unplanned hospital admission rates in children due to asthma to the NUTH.Results showed that admission rates had been increasing at a sustained rate of approximately 30% each year in the 3 years prior to our intervention. After the Beating Regional Asthma Through Health Education interventions, unplanned admissions to NUTH reduced by 29% and this reduction has been sustained for the last 3 years. This compares with a regional increase of 10% over the same time period.In conclusion, simple but effective educational interventions resulted in a significant and sustained reduction in unplanned asthma admissions to NUTH. Further work is underway to extend the reach of these interventions into primary care and schools.

Comparison of new generation motion-resistant pulse oximeters.

AIM: To compare the performance of pulse oximeters during movement and brachial artery occlusion. METHODS: Three machines (MasimoSET, using MasimoSET LNOP Pdt paediatric sensor, Mars 2001 using Novametrix paediatric sensor no. 6455 and Nellcor 595 using Nellcor 595 Oximax-P paediatric sensor and Nellcor 595 MAX-FAST adhesive forehead reflectance sensor) were used simultaneously on the left hand and forehead. The subjects were 18 healthy children aged 6-10 years. Interventions were 20 sequential 90 degrees body turns from mimicking normal movements while asleep followed by step increases in brachial artery occlusion. Mean heart rate (HR) from the four machines was compared with ECG HR. Haemoglobin O(2) saturation was compared with a baseline saturation and the proportion of epochs with false (low) saturation values. RESULTS: The mean difference from ECG HR was not clinically significantly different for any machine but the limits of agreement were such that the Mars Model 2001 and Nellcor 595 (forehead) could have clinically important differences from ECG-derived HR (-20.04-15.00 and -14.95-14.04, respectively). Only the Nellcor 595 with finger probe had limits of agreement within the a priori set value of 4%. The prevalence of epochs with an haemoglobin O2 saturation of greater than 4% below baseline values was lowest for the Nellcor 595 finger probe (1.59%) and highest for the Nellcor forehead probe (20.45%). During brachial artery occlusion, all machines performed well up to within 20 mmHg of total occlusion. CONCLUSION: Current motion-resistant pulse oximeters performed well but only the Nellcor 595 with finger probe achieved our a priori set standards.