Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children.

BACKGROUND: Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers to take time away from employment. About a third of children experience a wheezing episode before the age of five years. EVW therefore represents a significant public health problem. Many pre-school children only wheeze in association with viral infections and in such cases EVW appears to be a separate entity from atopic asthma. Some trials have explored the effectiveness of leukotriene receptor antagonists (LTRAs) as regular (maintenance) or episodic (intermittent) treatment in this context. OBJECTIVES: To evaluate the evidence for the efficacy and safety of maintenance and intermittent LTRAs in the management of EVW in children aged one to six years. SEARCH METHODS: We searched the Cochrane Airways Group register of trials with pre-specified terms. We performed additional searches by consulting the authors of identified trials, online trial registries of manufacturers' web sites, and reference lists of identified primary papers and reviews. Search results are current to June 2015. SELECTION CRITERIA: We included randomised controlled trials with a parallel-group or cross-over (for intermittent LTRA only) design. Maintenance was considered as treatment for more than two months and intermittent as less than 14 days. EVW was defined as a history of at least one previous episode of wheezing in association with a viral respiratory tract infection in the absence of symptoms between episodes. As far as possible, relevant specific data were obtained from authors of studies that included children of a wider age group or phenotype.   DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion in the review and assessed risk of bias. The primary outcome was number of children with one or more viral-induced episodes requiring one or more treatments with rescue oral corticosteroids. We analysed combined continuous data outcomes with the mean difference and dichotomous data outcomes with an odds ratio (OR). MAIN RESULTS: We identified five studies eligible for inclusion in the review (one investigated maintenance treatment, three intermittent therapy and one had both maintenance and intermittent treatment arms) these included 3741 participants. Each study involved oral montelukast and was of good methodological quality, but differed in choice of outcome measures thus limiting our ability to aggregate data across studies. Only primary outcome and adverse event data are reported in this abstract.For maintenance treatment, specific data obtained from a single study, pertaining to children with only an EVW phenotype, showed no statistically significant group reduction in the number of episodes requiring rescue oral corticosteroids associated with daily montelukast versus placebo (OR 1.20, 95% CI 0.70 to 2.06, moderate quality evidence).For intermittent LTRA, pooled data showed no statistically significant reduction in the number of episodes requiring rescue oral steroids in children treated with LTRA versus placebo (OR 0.77, 95% CI 0.48 to 1.25, moderate quality evidence). Specific data for children with an EVW phenotype obtained from a single study of intermittent montelukast treatment showed a small, but statistically significant reduction in unscheduled medical attendances due to wheeze (RR 0.83, 95% CI 0.71 to 0.98).For maintenance compared to intermittent LTRA treatment no data relating to the primary outcome of the review were identified.There were no other significant group differences identified in other secondary efficacy outcomes for maintenance or intermittent LTRA treatment versus placebo, or maintenance versus intermittent LTRA treatment. We collected descriptive data on adverse events as reported by four of the five included studies, and rates were similar between treatment and placebo groups.Potential heterogeneity in the phenotype of participants within and across trials is a limitation of the evidence. AUTHORS' CONCLUSIONS: In pre-school children with EVW, there is no evidence of benefit associated with maintenance or intermittent LTRA treatment, compared to placebo, for reducing the number of children with one or more viral-induced episodes requiring rescue oral corticosteroids, and little evidence of significant clinical benefit for other secondary outcomes. Therefore until further data are available, LTRA should be used with caution in individual children. When used, we suggest a therapeutic trial is undertaken, during which efficacy should be carefully monitored. It is likely that children with an apparent EVW phenotype are not a homogeneous group and that subgroups may respond to LTRA treatment depending on the exact patho-physiological mechanisms involved.

The evidence for high flow nasal cannula devices in infants.

High flow nasal cannula (HFNC) devices deliver an adjustable mixture of heated and humidified oxygen and air at a variable flow rate. Over recent years HFNC devices have become a frequently used method of non-invasive respiratory support in infants and preterm neonates that is generally popular amongst clinicians and nursing staff due to ease of use and being well tolerated by patients. Despite this rapid adoption relatively little is known about the exact mechanisms of action of HFNC however and only recently have data from randomised controlled trials started to become available. We describe the features of a modern HFNC device and discuss current knowledge about the mechanisms of action and results of clinical studies in preterm neonates and infants with bronchiolitis. We also highlight future areas of research that are likely to increase our understanding, inform best clinical practice and strengthen the evidence base for the use of HFNC.

Understanding how facilitators adapt to needs of STEM faculty in online learning communities: a case study.

Background: Faculty Learning Communities (FLCs) and Faculty Online Learning Communities (FOLCs) are ways to support STEM faculty implementing research-based curricula. In these communities, faculty facilitators take on the role of sharing expertise and promoting discussion. However, as members gain more experience, their needs change from addressing logistical to pedagogical issues. Hence, facilitators need to change their practices in response. However, there is little research on the mechanisms of faculty facilitator change. In this article, we provide a case study of a specific STEM FOLC facilitator and demonstrate the usefulness of a teacher change model to investigate facilitator change. Results: Guided by our adaptation of the Interconnected Model of Professional Growth (IMPG), we conducted interviews with FOLC facilitators, and selected a case facilitator who reported changes in facilitation goals and strategies over time. The model helped us identify specific areas of change and potential mechanisms for these changes. Using themes of change identified in the case facilitator interview, we developed coding schemes to analyze his FOLC meetings over a 2-year period. We found empirical evidence from multiple data sources, including FOLC meetings and facilitator reflections, that supported the change themes, including: changing his role as an "expert" by sharing his own expertise less and drawing on others' expertise more frequently, changing his response to members' comments by jumping in to answer less frequently and withholding his own responses more often to encourage member sharing, and a change in group discussions towards less logistical and more pedagogical conversations. Conclusions: Our findings suggest that the IMPG can be fruitfully adapted to study facilitator change. A diagrammatic representation of the IMPG provides a description the types of change the case facilitator experienced and the factors that supported those changes. We discuss how the methodology used to analyze facilitator actions in FOLC group meetings may be useful to study other types of professional growth. Finally, because our analytical model allowed us to identify mechanisms of facilitator change, we describe the implications and provide suggestions to support facilitators in other faculty community groups. Supplementary Information: The online version contains supplementary material available at 10.1186/s40594-022-00371-x.

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.

Case Report: Severe Acute Pulmonary COVID-19 in a Teenager Post Autologous Hematopoietic Stem Cell Transplant.

Pulmonary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally described as mild, and SARS-CoV-2 infection in immunocompromised children are observed as generally mild as well. A small proportion of pediatric patients will become critically ill due to (cardio)respiratory failure and require intensive care treatment. We report the case of a teenager with Hodgkin's lymphoma who acquired SARS-CoV-2 (detected by PCR) on the day of her autologous stem cell transplant and developed acute respiratory distress syndrome, successfully treated with a combination of antivirals, immunomodulation with steroids and biologicals, and ECMO.

British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011.

The British Thoracic Society first published management guidelines for community acquired pneumonia in children in 2002 and covered available evidence to early 2000. These updated guidelines represent a review of new evidence since then and consensus clinical opinion where evidence was not found. This document incorporates material from the 2002 guidelines and supersedes the previous guideline document.

Ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis lung disease.

RATIONALE: Ceramide accumulates in the airway epithelium of mice deficient in cystic fibrosis transmembrane conductance regulator, resulting in susceptibility to Pseudomonas aeruginosa infection and inflammation. OBJECTIVES: To investigate quantitatively ceramide levels in the lower airway of people with cystic fibrosis compared with pulmonary hypertension, emphysema, and lung donors. METHODS: Immunohistochemistry was performed on the lower airway epithelium of explanted lungs (eight cystic fibrosis, emphysema, and pulmonary hypertension, respectively) and eight donor lungs using ceramide, neutrophil elastase, and myeloperoxidase antibodies. High-performance liquid chromatography-mass spectrometry was performed on tissue from five lungs with cystic fibrosis and five with pulmonary hypertension. MEASUREMENTS AND MAIN RESULTS: Staining for ceramide was significantly increased in the lower airway epithelium of people with cystic fibrosis (median, 14.11%) compared with pulmonary hypertension (3.03%; P = 0.0009); unused lung donors (3.44%; P = 0.0009); and emphysema (5.06%; P = 0.01). Ceramide staining was increased in emphysematous lungs compared with pulmonary hypertension (P = 0.0135) and unused donors (P = 0.0009). The number of neutrophil elastase- and myeloperoxidase-positive cells in the airway was positively correlated with the percentage of epithelium staining for ceramide (P = 0.001). Ceramide staining was significantly increased in lungs colonized with Pseudomonas aeruginosa (10.1%) compared with those not colonized (3.14%; P = 0.0106). Significantly raised levels of ceramides C16:0, C18:0, and C20:0 were detected by mass spectrometry in lungs with cystic fibrosis compared with pulmonary hypertension. Differences in C22:0 were not significant. CONCLUSIONS: Immunoreactive ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis. Detected by mass-spectrometry ceramide species C16:0, C18:0, and C20:0 but not C22:0 are increased.

Primary bronchial epithelial cell culture from explanted cystic fibrosis lungs.

Lung disease is responsible for more than 95% of morbidity and mortality in cystic fibrosis. The exact pathogenesis of cystic fibrosis lung disease remains poorly understood. Experimental models are therefore vital for use in research. Animal models and immortalized cell lines both have inherent limitations. Explanted lungs removed from people with cystic fibrosis at the time of transplantation represent a potentially valuable but technically and logistically challenging source of primary cystic fibrosis bronchial epithelial cells. In this study, pieces of segmental bronchus from explanted lungs were treated with patient-specific antimicrobials prior to isolation of bronchial epithelial cells. Cultured cells were characterized by their morphology under light microscopy, cytokeratin and hematoxylin-eosin staining, and electrophysiological profile. Primary bronchial epithelial cells were successfully cultured from 15 of 22 patients attempted. The cells exhibited typical epithelial morphology, staining for cytokeratin, lack of responsiveness to forskolin treatment, and remained viable after storage in liquid nitrogen. Seven unsuccessful cultures failed due to early infection with bacteria known to colonize the airways pretransplant. The results show that primary bronchial epithelial cell culture is possible from explanted cystic fibrosis lungs. This provides an important cellular model to elucidate the pathogenic mechanisms in cystic fibrosis lung disease and to investigate potential therapeutic targets.

Pediatric tracheostomy: A large single-center experience.

OBJECTIVES: To describe the epidemiology, specifically the indications, complications, and outcomes, of pediatric tracheostomies performed in one tertiary referral unit. METHODS: Single-center retrospective cohort study of pediatric patients undergoing tracheostomy between May 2010 and May 2018 at the Newcastle upon Tyne Hospitals, United Kingdom. RESULTS: One hundred seventy-two pediatric tracheostomies were performed during the study period with a median age of 141 (interquartile range [IQR] 51-484) days. The most common primary indication was long-term ventilation (38.4%, 66 of 172), followed by weaning from ventilation in cardiac patients (22.1%, 38 of 172). Only 5.2% (9 of 172) of our cohort underwent tracheostomy for subglottic stenosis. The vast majority of tracheostomies were performed electively, with just 6.4% (11 of 172) performed as an emergency procedure. Early and late complication rates were 9.8% (15 of 153) and 40.0% (61 of 153), respectively. Tracheostomy decannulation was successful in 44.4% of children (68 of 153). The median duration the tracheostomy was in situ was 397 (IQR 106-708) days. All-cause mortality was 22.1% (38 of 172), with tracheostomy-related mortality at 1.2% (2 of 172). CONCLUSION: We report one of the largest contemporary case series of pediatric tracheostomies. Present-day pediatric tracheostomy is primarily performed as an elective procedure in ventilated children under the age of 1 year. Pediatric tracheostomy should be considered as a long-term intervention in many children. Nevertheless, a large proportion of children are ultimately decannulated. It is important to acknowledge the significant morbidity associated with this intervention and the small-but-present risk of tracheostomy-related mortality. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E375-E380, 2020.

Adenotonsillectomy for obstructive sleep apnoea in children.

BACKGROUND: Current treatment of sleep apnoea in children consists of largely surgical based treatments. Adenotonsillectomy is the most commonly used intervention to treat sleep apnoea in children. OBJECTIVES: To determine the efficacy of adenotonsillectomy in the treatment of obstructive sleep apnoea in children. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched with pre-specified terms. Searches were current as of August 2008. SELECTION CRITERIA: Randomised trials recruiting children with a diagnosis of obstructive sleep apnoea. DATA COLLECTION AND ANALYSIS: Two reviewers examined the search results and collected data from the studies in terms of their characteristics before deciding which ones would be included in the review. MAIN RESULTS: One study met the review entry criteria. This study addressed the relative merits of two surgical techniques in treating OSA in children (temperature controlled radiofrequency tonsillectomy and adenoidectomy, and complete tonsillectomy and adenoidectomy). No significant difference was apparent for either symptoms or respiratory disturbance index. More children in the TCFR&A group were able to return to normal diet at 7 days compared with complete T&A. No significant complications were observed in the study. AUTHORS' CONCLUSIONS: One small study failed to find a difference between two surgical techniques, although return to normal diet was more frequent in the group treated by temperature controlled radiofrequency tonsillectomy and adenoidectomy. At present there is still debate as to the criteria required to diagnose significant obstructive sleep apnoea in children. Also the natural history of the condition has not been fully delineated. There is an absence of randomised controlled trials investigating the efficacy of treatment of confirmed obstructive sleep apnoea with adenotonsillectomy in children. Research is required before recommendations for the treatment of obstructive sleep apnoea in children can be formulated. The quality of research in this area could be improved with the use of sleep studies at baseline to determine the extent of severity of sleep apnoea in children who are recruited to studies in this area. Long-term follow up is also required in order to explore the effect of adenotonsillectomy on paediatric sleep apnoea.

Interventions for educating children who are at risk of asthma-related emergency department attendance.

BACKGROUND: Asthma is the most common chronic childhood illness and is a leading cause for paediatric admission to hospital. Asthma management for children results in substantial costs. There is evidence to suggest that hospital admissions could be reduced with effective education for parents and children about asthma and its management. OBJECTIVES: To conduct a systematic review of the literature and update the previous review as to whether asthma education leads to improved health outcomes in children who have attended the emergency room for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register, including the MEDLINE, EMBASE and CINAHL databases, and reference lists of trials and review articles (last search May 2008). SELECTION CRITERIA: We included randomised controlled trials of asthma education for children who had attended the emergency department for asthma, with or without hospitalisation, within the previous 12 months. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We pooled dichotomous data with a fixed-effect risk ratio. We used a random-effects risk ratio for sensitivity analysis of heterogenous data. MAIN RESULTS: A total of 38 studies involving 7843 children were included. Following educational intervention delivered to children, their parents or both, there was a significantly reduced risk of subsequent emergency department visits (RR 0.73, 95% CI 0.65 to 0.81, N = 3008) and hospital admissions (RR 0.79, 95% CI 0.69 to 0.92, N = 4019) compared with control. There were also fewer unscheduled doctor visits (RR 0.68, 95% CI 0.57 to 0.81, N = 1009). Very few data were available for other outcomes (FEV1, PEF, rescue medication use, quality of life or symptoms) and there was no statistically significant difference between education and control. AUTHORS' CONCLUSIONS: Asthma education aimed at children and their carers who present to the emergency department for acute exacerbations can result in lower risk of future emergency department presentation and hospital admission. There remains uncertainty as to the long-term effect of education on other markers of asthma morbidity such as quality of life, symptoms and lung function. It remains unclear as to what type, duration and intensity of educational packages are the most effective in reducing acute care utilisation.

Chronic granulomatous disease presenting as fulminant Aspergillus pneumonitis: a lethal combination?

OBJECTIVE: Case reports of two patients with unusually late initial presentation of chronic granulomatous disease with fulminant Aspergillus pneumonia. DATA SOURCES AND EXTRACTION: Medical notes; retrospective study. STUDY SELECTION: Identical pattern of clinical presentation in two patients referred for support with extracorporeal membrane oxygenation (ECMO). Our Institutional Review Board waived the need for consent. DATA SYNTHESIS: Two school-aged boys presented with features of, and were initially treated, for community-acquired pneumonia. However, the disease course was rapidly progressive to fulminant respiratory failure and because both failed conventional intensive care management, they were referred to ECMO support. Although both died of evolving multiorgan failure, ECMO support allowed open lung biopsy leading to diagnosis of invasive Aspergillus pneumonia and chronic granulomatous disease. CONCLUSIONS: Failure of adequate therapy for acute community-acquired pneumonia and rapid progression to respiratory failure should lead to the possibility of fungal etiology. Congenital immunodeficiency may present for the first time late in life, so acute invasive pulmonary aspergillosis in the absence of known risk factors should lead to consideration of chronic granulomatous disease regardless of patient age.

Congenital Lung Agenesis: Incidence and Outcome in the North of England.

BACKGROUND: Unilateral lung agenesis is an uncommon congenital abnormality, with a lack of reported accurate incidence estimates. Prognosis is also uncertain, with older literature reporting poor outcomes. METHODS: The North of England register of congenital anomalies (Northern Congenital Abnormality Survey) records cases of congenital anomalies to mothers' resident in the region. We used the register to identify all patients with congenital lung agenesis born between 2004 and 2013 to calculate an accurate incidence estimate and report clinical outcomes with contemporary management. RESULTS: Four patients with congenital lung agenesis were born during the study period, giving an estimated incidence in the North of England of 1.22 per 100,000 live births (95% confidence interval, 0.33-3.11). Two patients had associated congenital heart disease requiring corrective surgery, and one had musculoskeletal anomalies. All four patients are alive and well without a regular oxygen requirement. CONCLUSION: Contrary to previous reports, the medium term outcomes in our patients have been good, even when lung agenesis is associated with other congenital anomalies. Long-term prognosis with modern management remains unknown, and the potential for the development of pulmonary hypertension remains a concern. Birth Defects Research 109:857-859, 2017. © 2017 Wiley Periodicals, Inc.

The oral corticosteroid-sparing effect of omalizumab in children with severe asthma.

OBJECTIVE: To report the oral corticosteroid-sparing effect of omalizumab in children with severe asthma. DESIGN: 16-week therapeutic trial. SETTING: Tertiary paediatric asthma clinic. PATIENTS: 34 children with severe asthma maintained on oral prednisolone (median age 12 years; 15 children <12 years and 19 children ≥12 years). INTERVENTIONS: Fortnightly or monthly subcutaneous injections of omalizumab; the dose was calculated as per manufacturer's instructions based on body weight and serum immunoglobulin E concentration. MAIN OUTCOME MEASURES: Reduction in prednisolone dose; mini-Asthma Quality of Life Questionnaire (AQLQ); Childhood Asthma Control Test (ACT); forced expiratory volume in 1 s (FEV(1)). RESULTS: Median daily prednisolone dose reduced from 20 mg to 5 mg (n=34, p<0.0001), including seven children who stopped prednisolone completely. Mini-AQLQ score increased from 3.5 to 5.9 (n=24, p<0.0001). Childhood ACT score increased from 12 to 20 (n=23, p=0.0001). FEV(1) increased from 2.10 to 2.25 litres (n=31, non-significant). The reduction in prednisolone dose and improvements in mini-AQLQ and childhood ACT were significant in children both under and over 12 years of age, with no differences in outcome detected between these two groups. CONCLUSIONS: A 16-week therapeutic trial of omalizumab allowed a significant reduction in daily prednisolone dose and was associated with improvements in asthma control and quality of life in 34 children with severe asthma. Similar benefits were seen in children both above and below 12 years of age. These uncontrolled data are very encouraging. There is an urgent requirement for a multicentre randomised placebo-controlled trial of omalizumab in children with severe asthma, with reduction in oral corticosteroid dose as the primary outcome measure.