Summary Childhood asthma is a common chronic condition. Approximately five percent of all children in western countries are prescribed treatment with inhaled corticosteroids (ICS) to prevent asthma ...symptoms. Current guidelines advocate titrating ICS dose to symptoms but this approach is not without problem, e.g. how to discern asthmatic from non-asthmatic symptoms? And when to reduce ICS dose? This review describes the strengths and weaknesses of fractional exhaled nitric oxide (FENO ) as an objective index for individualising asthma control in children. Epidemiological and mechanistic evidence suggest that FENO should be a promising biomarker for eosinophilic airway inflammation (a hall mark for asthma) but somewhat surprisingly, clinical trials in children have not consistently found benefit from adding FENO to a symptom-based approach to ICS treatment in children. There are a number of reasons why FENO has apparently failed to translate from promising biomarker to clinically useful tool, and one reason may be a lack of understanding of what merits a significant intrasubject change in FENO . This review describes the rise and apparent fall of FENO as biomarker for asthma and then focuses on more recent evidence which suggest that FENO may prove to have a role in the management of childhood asthma, and in particular preventing exacerbations.
ChEBI is a database and ontology containing information about chemical entities of biological interest. It currently includes over 46,000 entries, each of which is classified within the ontology and ...assigned multiple annotations including (where relevant) a chemical structure, database cross-references, synonyms and literature citations. All content is freely available and can be accessed online at http://www.ebi.ac.uk/chebi. In this update paper, we describe recent improvements and additions to the ChEBI offering. We have substantially extended our collection of endogenous metabolites for several organisms including human, mouse, Escherichia coli and yeast. Our front-end has also been reworked and updated, improving the user experience, removing our dependency on Java applets in favour of embedded JavaScript components and moving from a monthly release update to a 'live' website. Programmatic access has been improved by the introduction of a library, libChEBI, in Java, Python and Matlab. Furthermore, we have added two new tools, namely an analysis tool, BiNChE, and a query tool for the ontology, OntoQuery.
Maternal ambient air pollution exposure is associated with reduced birthweight. Few studies have examined the effect on growth in utero and none have examined the effect of exposure to particulates ...less than 2.5µm (PM2.5) and possible effect modification by smoking status.
Examine the effect of maternal exposure to ambient concentrations of PM10, PM2.5 and nitrogen dioxide (NO2) for in utero fetal growth, size at birth and effect modification by smoking status.
Administratively acquired second and third trimester fetal measurements (bi-parietal diameter, femur length and abdominal circumference), birth outcomes (weight, crown heel length and occipito-frontal circumference) and maternal details were obtained from routine fetal ultrasound scans and maternity records (period 1994–2009). These were modelled against residential annual pollution concentrations (calendar year mean) adjusting for covariates and stratifying by smoking status.
In the whole sample (n=13,775 pregnancies), exposure to PM10, PM2.5 and NO2 was associated with reductions in measurements at birth and biparietal diameter from late second trimester onwards. Among mothers who did not smoke at all during pregnancy (n=11,075), associations between biparietal diameter and pollution exposure remained significant but were insignificant among those who did smoke (n=2700). Femur length and abdominal circumference were not significantly associated with pollution exposure.
Fetal growth is strongly associated with particulates exposure from later in second trimester onwards but the effect appears to be subsumed by smoking. Typical ambient exposures in this study were relatively low compared to other studies and given these results, it may be necessary to consider reducing recommended “safe” ambient air exposures.
•We examined the effect of maternal pollution exposure for fetal growth and size.•Exposure to particulates and NO2 strongly associated with reductions in head growth and size.•Effects were strongest for non-smokers.•Pollution effects were observed despite a relatively low exposure environment.
Summary Background The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO ...recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis. Methods We did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study BIDS). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation SpO2 <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428. Findings Between Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference −1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged hospital stay. In the modified care group, 12 infants were transferred to a high-dependency unit and 12 were readmitted to hospital. Recorded adverse events did not differ significantly. Interpretation Management of infants with bronchiolitis to an oxygen saturation target of 90% or higher is as safe and clinically effective as one of 94% or higher. Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children, particularly in developing nations where resources are scarce. Funding National Institute for Health Research, Health Technology Assessment programme.
Metabolic syndrome has been identified as a condition of childhood relatively recently. The aim in this study was to describe the prevalence of metabolic syndrome in children allowing for differences ...in metabolic syndrome definitions.
This was a systematic review of the OVID, EMBASE, and CINAHL databases, capturing details of overall prevalence and prevalence within groups categorized by obesity, gender, age, and ethnicity.
In all, 378 studies published since 2003 were identified, and of these 85 papers were included in the present review. When all studies were considered, the median prevalence of metabolic syndrome in whole populations was 3.3% (range 0%-19.2%), in overweight children was 11.9% (range 2.8%-29.3%), and in obese populations was 29.2% (range 10%-66%). Within-study analyses confirmed higher prevalence for obese compared to overweight (P=0.012) and obese compared to nonobese, nonoverweight children (P<0.001). Within-study analyses also revealed higher median metabolic syndrome prevalence for boys compared to girls (5.1% versus 3.0%, P<0.001) and also in older compared with younger children (5.6% versus 2.9%, P=0.001). Limited evidence was found to suggest differences between ethnic groups, and there were insufficient studies to determine whether metabolic syndrome prevalence was increasing over time.
This is the first systematic review of all of the relevant literature. It describes the magnitude of associations between metabolic syndrome and obesity, age, and gender. We find evidence that ethnicity and geography may be important to metabolic syndrome prevalence in children and these associations require further study.
ChEBI (http://www.ebi.ac.uk/chebi) is a database and ontology of chemical entities of biological interest. Over the past few years, ChEBI has continued to grow steadily in content, and has added ...several new features. In addition to incorporating all user-requested compounds, our annotation efforts have emphasized immunology, natural products and metabolites in many species. All database entries are now 'is_a' classified within the ontology, meaning that all of the chemicals are available to semantic reasoning tools that harness the classification hierarchy. We have completely aligned the ontology with the Open Biomedical Ontologies (OBO) Foundry-recommended upper level Basic Formal Ontology. Furthermore, we have aligned our chemical classification with the classification of chemical-involving processes in the Gene Ontology (GO), and as a result of this effort, the majority of chemical-involving processes in GO are now defined in terms of the ChEBI entities that participate in them. This effort necessitated incorporating many additional biologically relevant compounds. We have incorporated additional data types including reference citations, and the species and component for metabolites. Finally, our website and web services have had several enhancements, most notably the provision of a dynamic new interactive graph-based ontology visualization.
Asthma is a common condition, which is associated with atopy and allergic conditions including hay fever, eczema, and food allergies. Asthma and atopy are both complex conditions where genetic and ...environmental factors are implicated in causation. Interactions between genetic and environmental factors, likely
epigenetic mechanisms, are widely thought to be important in determining the risk for developing asthma and atopy. The nature of the relationship between asthma and atopy is unclear and the answer to the question "does atopy cause asthma?" remains unknown. This review explores the relationship between asthma and atopy from a gene-environment interaction perspective and tackles the question "are similar gene-environment interactions present for asthma and atopy?" The main finding is that gene-environment interactions are described for asthma and atopy in children but these interactions are seldom sought for both asthma and atopy in the same population. In the few instances where a gene-environment interaction is related to both asthma and atopy, there is no consistent evidence that similar interactions are common to asthma and atopy. Many plausible gene-environment interactions for asthma and atopy are yet to be explored. Overall, from the gene-environment interaction perspective, there is absence of evidence to better understand the complex relationship between asthma and atopy.
Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether ...these extend to adulthood and infancy.
To ascertain trajectories of FEV
, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5-16 years and 1390 participants from 8-24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'
) and childhood (FEV
; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors.
We identified four childhood FEV
trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 5% of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92-1·01; p=0·13) for persistently high, 1·01 (0·99-1·02; p=0·49) for below average, and 1·05 (0·98-1·13; p=0·13) for persistently low. Most children in the low V'
trajectory in infancy did not progress to the low FEV
trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure.
Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood.
None.
Childhood asthma is a common condition in children. This review describes the evidence from seven asthma guidelines for using spirometry in the diagnosis and monitoring of childhood asthma. All ...guidelines recommend spirometry as the primary test to be performed for diagnosing asthma in children aged >5 years. Spirometry is often normal in children with asthma. Guidelines are not consistent with respect to whether forced expiratory volume in 1 s (FEV1) or FEV1/forced vital capacity (FVC) should be measured, or their threshold for "abnormal" spirometry, and we describe the sensitivity and specificity for these different cut-offs. The role of spirometry in monitoring asthma is less clear in the guidelines, and some do not suggest spirometry should be done. There is no consensus on what spirometric measurement should be used, how often it should be measured and what is a minimum clinically important change in spirometry. The role of spirometry in diagnosing asthma is more clearly established when compared to its role in monitoring asthma. The potential of spirometry to aid decision making for asthma diagnosis and monitoring in children remains to be fully evaluated.Educational aimsTo provide knowledge of the commonly used guidelines for asthma diagnosis and management.To give insight into the opportunities and challenges in using spirometry to diagnose and monitor asthma in children.To provide an understanding of the precision of spirometry for diagnosing asthma.
Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing ...associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis.
Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements.
There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) 95% CI 0.01, 0.16) and femur length (0.06 0.01, 0.10) and reduced third trimester head size (0.18 SD 0.13, 0.23), femur length (0.27 SD 0.21, 0.32) and estimated fetal weight (0.18 SD 0.11, 0.24). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD 0, 0.19) and third (0.15 SD 0.03, 0.26) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked.
Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy.
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