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BACKGROUND: Basic science, epidemiological and interventional research supports a link between vitamin D and tuberculosis (TB) immunity, infection and disease. We evaluated the association between vitamin D levels and TB infection and disease in UK children recruited to the National Institute for Health Research IGRA Kids Study (NIKS).METHODS: Children presenting between 2011 and 2014 were eligible if they had history of exposure to an adult case with sputum smear/culture-positive TB, or were referred and diagnosed with TB disease. Children were assessed at baseline and at 6–8 weeks for immunological evidence of TB infection (interferon-gamma release assay and/or tuberculin skin test) and evidence of TB disease. Some centres routinely measured total 25-hydroxy vitamin D (25-OHD) levels.RESULTS: A total of 166 children were included. The median 25-OHD levels were higher in non-infected children (45.5 nmol/l) than in those with tuberculous infection (36.2 nmol/l) and TB disease (20.0 nmol/l). The difference between TB infection and disease was statistically significant (P < 0.001). By logistic regression, lower vitamin D levels were associated with TB disease among participants with infection or disease, with no evidence of confounding by age, sex, bacille Calmette-Guérin vaccination status, ethnicity, non-contact referral, season or centre.CONCLUSION: Children with TB disease had lower vitamin D levels than children with infection. Implications for prevention and treatment remain to be established.

The Global Lung Function Initiative (GLI) all-age reference equations for carbon monoxide transfer factor were published in 2017 and endorsed by the European Respiratory Society and American Thoracic Society. In order to understand the impact of these new reference equations on the interpretation of results in children referred from haematology and oncology paediatric services, we retrospectively analysed transfer factor results from any paediatric patient referred from haematology/oncology in the period 2010–2018. We examined transfer factor of the lung for carbon monoxide (TLCO), transfer coefficient of the lung for carbon monoxide (KCO) and alveolar volume (VA) from 241 children (age range 7–18 years, 130 male). The predicted values from Rosenthal and GLI were plotted against height. The difference in interpretation of results was analysed by looking at the percentage of patients below the lower limit of normal for each parameter. Overall, the Rosenthal predicted values for TLCO were higher than those predicted by GLI. Predicted KCO using Rosenthal was higher in all observations. In contrast, the Rosenthal predicted VA was generally lower than the GLI value. The GLI predicted values for transfer factor show considerable differences compared with currently used paediatric UK reference values, differences that will have a significant impact on interpretation of results., There will be significant clinical differences in the results of transfer factor when switching to the GLI-2017 from Rosenthal-1993 reference values, strongly recommending implementing the use of GLI-2017 reference equations for paediatrics https://bit.ly/3o0zR4f

Introduction: Cardio-pulmonary Exercise Testing (CPET) is used for diagnosis and monitoring of cardiovascular and respiratory conditions in children. There are several reference values published for CPET. Despite this, the most commonly used in paediatric labs in the UK are from Cooper et al in 1984. Up-to-date values have been published since this which may be more applicable and valid to the current population. Objectives: We aimed to compare 3 sets of reference equations for maximal oxygen uptake (VO22peak) in children to see if there were any clinical differences depending on which equation was used. We hypothesized that there would be significant differences between the reference sets. Methods: We reviewed data from our CPET database to look at predicted values for VO2peak using Cooper 1984 (CO), Bongers 2012 (BO) and Blanchard 2018 (BL). Predicted VO2peak was calculated for each reference equation and the % predicted was compared using Bland Altman analysis. Results: There were 766 subjects - 431 males. Age range was 5 -18 years. Table 1 shows the mean bias with ULOA and LLOA for each of the comparisons of % predicted. A reduced VO2peak was found in 49%, 69% & 70% for CO, BO and BL respetively. Conclusion: The choice of reference values used for CPET in children will significantly affect whether the results are deemed normal. 3 of the commonly used equations show large limits of agreement. The most recent values by Blanchard look promising as they use a corrected bodyweight, height, age and sex and have published Z scores with the data. The main drawback is they only start from 12 years onwards.

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Background: It is known that some people with Pectus Excavatum (PE) have impaired lung and cardiac function. Surgical correction by the Nuss procedure is becoming more common and as well as improving the aesthetics of the chest it may potentially improve any cardio-respiratory impairment. Objectives: We aimed to determine the occurrence of impaired cardio-pulmonary function in adolescents with PE. We aimed to assess for any improvement in physiological function 1 year post Nuss repair in a group of patients who underwent surgery. Methods: We retrospectively analysed pulmonary function and cardiopulmonary exercise testing (CPET) results in patients with PE. We looked for a statistically significant difference 1 year post Nuss in a variety of parameters. Results: 27 adolescents (21 male) with PE had pulmonary function and CPET. 30% had evidence of restrictive lung function. 56% had a reduced aerobic capacity (VO2peak) and 81% had a reduced Oxygen pulse. Only 15% had evidence of ventilatory limitation during CPET. Table 1 shows demographics and summary results. Conclusion: A significant number of adolescents with PE will have impaired cardio-pulmonary function. However ventilatory limitation is not the limiting factor in the majority of patients during CPET. Nuss repair may improve lung volumes and cardiac function 1 year post surgery.

No abstract available.

Background: The Global Lung Function Initiative (GLI) all age reference equations for the carbon monoxide transfer factor were published in 2017 and endorsed by the ERS/ATS. Before switching to these new equations we wanted to understand the impact that this would have on the interpretation of results in a population of patients referred from haematology and oncology paediatric services. Objectives: We aimed to determine the impact of the switch from the currently used UK paediatric reference equations for transfer factor (Rosenthal, M et al. thorax 1993;48:803-8) to the GLI and how this affected the interpretation of results in these patients. We hypothesised that there would be clinically significant differences between the 2 sets. Methods: We retrospectively analysed transfer factor results from any paediatric patient referred from haematology or oncology. We looked at DLCO, KCO and VA. The predicted values from Rosenthal and GLI were plotted against height. The difference in interpretation of results was analysed by looking at the % of patients Results: We analysed 245 results. Overall, the Rosenthal predicted values for TLCO were higher than GLI. The predicted KCO from Rosenthal was higher in all observations. In contrast, the predicted VA was generally lower than the GLI value. Table 1 shows the impact on interpretation of results. Conclusions: The GLI predicted values for transfer factor show considerable differences to that of currently used paediatric UK reference values which has a significant impact on interpretation of results.

Rationale and Objective: In order to identify infected contacts of tuberculosis (TB) cases, the UK National Institute for Health and Care Excellence (NICE) recommended the addition of interferon-gamma release assays (IGRA) to the tuberculin skin test (TST) in its 2006 TB guidelines. Treatment for TB infection was no longer recommended for children screened TST-positive but IGRA-negative. We carried out a cohort study to evaluate the risk of TB disease in this group. Methods: Children exposed to an infectious case of TB in their household were recruited from 11 paediatric TB clinics. TST and IGRA were carried out at baseline, IGRA repeated at 8 weeks and TST repeated if initially negative. Children were treated according to 2006 NICE guidelines and followed for 24 months. Measurements and Main Results: Of 431 recruited children 392 completed the study. We diagnosed 48 (12.2%) cases of prevalent TB disease, 105 (26.8%) with TB infection and 239 (60.9%) without TB infection or disease. 18 children aged two years and above had a positive TST but persistently negative IGRA. None received TB infection treatment and none developed TB disease. 90 (26.1%) children qualified for TB infection treatment according to 2006 NICE guidelines. In contrast, 147 (42.7%) children would have qualified under revised NICE guidance, issued in 2016. Conclusions: In this low prevalence setting we saw no incident cases of TB disease in children who were TST-positive but IGRA-negative and did not receive treatment for TB infection. Following the latest NICE guidance, significantly more children will require medication.

Background Obesity has been hypothesized to be associated with reduced moderate-to-vigorous physical activity (MVPA) and increased sedentary time (ST). It is important to assess whether, and the extent to which, levels of MVPA and ST are suboptimal among children and adolescents with obesity. The primary objective of this study was to examine accelerometer-measured time spent in MVPA and ST of children and adolescents with obesity, compared with MVPA recommendations, and with non-obese peers. Methods An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus, and CINAHL, from 2000 to 2015. Study selection and appraisal: studies with accelerometer-measured MVPA and/or ST (at least 3 days and 6 h/day) in free-living obese children and adolescents (0 to 19 years) were included. Study quality was assessed formally. Meta-analyses were planned for all outcomes but were precluded due to the high levels of heterogeneity across studies. Therefore, narrative syntheses were employed for all the outcomes. Results Out of 1503 records, 26 studies were eligible (n = 14,739 participants; n = 3523 with obesity); 6/26 studies involved children aged 0 to 9 years and 18/26 involved adolescents aged 10.1 to19 years. In the participants with obesity, the time spent in MVPA was consistently below the recommended 60 min/day and ST was generally high regardless of the participant’s age and gender. Comparison with controls suggested that the time spent in MVPA was significantly lower in children and adolescents with obesity, though differences were relatively small. Levels of MVPA in the obese and non-obese were consistently below recommendations. There were no marked differences in ST between obese and non-obese peers. Conclusions MVPA in children and adolescents with obesity tends to be well below international recommendations. Substantial effort is likely to be required to achieve the recommended levels of MVPA among obese individuals in obesity treatment interventions. This systematic review has been registered on PROSPERO (International Database of Prospective Register Systematic Reviews; registration number CRD42015026882). Electronic supplementary material The online version of this article (10.1186/s12887-018-1031-0) contains supplementary material, which is available to authorized users.

The British Thoracic Society (BTS) first produced a guideline on asthma and its management in 1990. The first collaborative guideline with the Scottish Intercollegiate Guideline Network (SIGN) using evidence-based medicine methodology was published in 2003.1 It has since become a mainstay of asthma management across the UK and beyond with updates published regularly every 18–24 months. The latest BTS/SIGN guideline for the management of asthma was published in 2016.2 Both BTS and SIGN are committed to continuing updates with the next update planned for publication in 2019. Following publication of National Institute for Health and Care Excellence (NICE) guidelines for diagnosis and monitoring, and for management of chronic asthma,3–5 there are now two if not three national guidelines, for England at least, with some (apparently) striking differences. This statement considers the similarities and differences to assist clinical colleagues in the care of people with asthma. The evidence base considered by the BTS/SIGN and NICE guideline development groups is broadly the same for each guideline, but the methodology used to produce recommendations is significantly different: These different processes have resulted in some discrepancies in recommendations made by BTS/SIGN and NICE. This article seeks to provide some context to these differences in key areas: The BTS/SIGN guideline also provides recommendations …

Introduction and Objectives Asthma is the commonest long-term condition in children with attacks impacting on both school attendance and quality of life. Identifying the child at increased risk of future asthma attacks could inform clinical management and targeting of care. We aimed to systematically review the literature to identify and weight factors associated with increased risk of attacks in children with asthma aged 5–12 years. Methods Using Cochrane methodology, we systematically searched six databases and undertook forward and backward citation searches, with no date/language restrictions. Two reviewers independently selected studies for inclusion, assessed methodological quality, and extracted data. An expert panel of four clinicians independently assessed each factor for both magnitude of risk and degree of confidence in that assessment, based on study quality, effect sizes, biological plausibility, and consistency of Results Consensus was achieved by discussion and agreed at a multidisciplinary workshop. Results From 16 109 records, we included 69 papers (29 cohort, 4 case-control, 36 cross-sectional studies) providing data on 32 potential factors associated with an increased risk of asthma attacks. The panel had high confidence that previous asthma attacks were associated with greatly increased risk of future attacks. Poor access to care and persistent symptoms were associated with moderately/greatly increased risk. A moderately increased risk of attack was associated with sub-optimal drug regimen (low controller/total therapy ratio), comorbid atopic/allergic disease, African-American ethnicity (US studies), poverty, and vitamin D deficiency. Environmental tobacco smoke (ETS) exposure, younger age, and obesity were associated with slightly increased risk. Gender, urban residence, and Hispanic ethnicity (US studies) were not associated with risk. The evidence for other factors was inconclusive. Conclusions Assessment of clinical and demographic features (especially persistent symptoms, previous attacks, and sub-optimal drug regimen) may help clinicians to ‘spot the child’ at increased risk of asthma attacks and focus appropriate management. Population level factors (poverty, poor access to care) may be used by health service planners and policymakers to target healthcare initiatives.

Introduction Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. 1 The Scottish Medicines Commission has accepted it for restricted use in adults as an add-on treatment for severe refractory eosinophilic asthma. Here we describe the use of Mepolizumab as an unlicensed medicine with local approval for use in adolescents with severe asthma. Methods Mepolizumab was offered to adolescents with severe eosinophilic asthma not eligible for Omalizumab because of previous allergic reaction (n=2) or failure to respond (n=1) to Omalizumab, or excessively high IgE (n=4). Eosinophilic asthma was confirmed: blood eosinophil count ≥300 cells/µL or exhaled nitric oxide concentration (FeNO) ≥50 ppb in the previous year. All received high-dose ICS +LABA and had low ACT scores (mean 10.4±2.88). Four were on daily oral steroids. Mean exacerbations requiring oral steroids in the previous year were 4.9±1.68. Prior to commencing and before each monthly injection, pulmonary function (FeNO and forced expiratory volume in 1 s (FEV 1 )), blood eosinophil count, Asthma Control Test (ACT) and Paediatric Asthma Quality of Life Questionnaire (PAQLQ) were measured. Long-term medications not adjusted. Data from clinical case notes. Results Seven adolescents (mean age 13.9±1.9, range 11–17 years; 5 males, 2 females) each received 4 Mepolizumab doses (100 mg sc) at monthly intervals with no serious adverse reactions. Blood eosinophil count decreased in all (mean pre-treatment 0.8±0.62 × 10 9 cells/L,0.1±0.06 × 10 9 cells/L after 4 doses). ACT score improved in 6/7 patients (86%) (mean pre-treatment 10.4±2.88, 13.6±5.16 after 4 doses). PAQLQ improved in 4/7 patients (57%) (mean pre-treatment 3.8±1.30, 4.4±1.41). We did not demonstrate improvement in FEV 1 . Mean FeNO was −15±29 ppb (figure 1). During treatment, none required hospitalisation for asthma attacks, 2/7 patients (29%) were attack free, 5/7 patients (71%) had reduced attack frequency. Conclusion In adolescents with refractory eosinophilic asthma not eligible for Omalizumab, these data suggest that Mepolizumab is well tolerated, reduces risk of exacerbations, may improve asthma control and quality of life but does not improve lung function. Reference Pavord ID, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet2012;380(9842):651–9.

Context: \ud \ud Moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) are important for child and adolescent health.\ud \ud Objective: \ud \ud To examine habitual levels of accelerometer measured MVPA and ST in children and adolescents with chronic disease, and how these levels compare with healthy peers.\ud \ud Methods: \ud \ud Data sources: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus and CINAHL from 2000–2017.\ud \ud Study selection: Studies with accelerometer-measured MVPA and/or ST (at least 3 days and 6 hours/day to provide estimates of habitual levels) in children 0–19 years of age with chronic diseases but without co-morbidities that would present major impediments to physical activity. In all cases patients were studied while well and clinically stable.\ud \ud Results: \ud \ud Out of 1592 records, 25 studies were eligible, in four chronic disease categories: cardiovascular disease (7 studies), respiratory disease (7 studies), diabetes (8 studies), and malignancy (3 studies). Patient MVPA was generally below the recommended 60 min/day and ST generally high regardless of the disease condition. Comparison with healthy controls suggested no marked differences in MVPA between controls and patients with cardiovascular disease (1 study, n = 42) and type 1 diabetes (5 studies, n = 400; SMD -0.70, 95% CI -1.89 to 0.48, p = 0.25). In patients with respiratory disease, MVPA was lower in patients than controls (4 studies, n = 470; SMD -0.39, 95% CI -0.80, 0.02, p = 0.06). Meta-analysis indicated significantly lower MVPA in patients with malignancies than in the controls (2 studies, n = 90; SMD -2.2, 95% CI -4.08 to -0.26, p = 0.03). Time spent sedentary was significantly higher in patients in 4/10 studies compared with healthy control groups, significantly lower in 1 study, while 5 studies showed no significant group difference.\ud \ud Conclusions: \ud \ud MVPA in children/adolescents with chronic disease appear to be well below guideline recommendations, although comparable with activity levels of their healthy peers except for children with malignancies. Tailored and disease appropriate intervention strategies may be needed to increase MVPA and reduce ST in children and adolescents with chronic disease.

Background: While exercise testing is increasingly used as a prognostic indicator in cystic fibrosis (CF), it is reported to be underused in UK CF centres, particularly in children. Here, we evaluated the cardiopulmonary exercise testing (CPET) results in children and young people with CF at CF annual review and its possible clinical value.\ud \ud Method: An observational study comparing CPET results using a cycle ergometer ramp test (peak oxygen uptake (Vo2peak)) and pulmonary function (forced expiratory volume in 1 s (FEV1)) was performed with body mass index (BMI) used as a disease severity marker. Data were identified from clinical case notes and our CF database.\ud \ud Results: Thirty-eight children and young people (mean age 11±2.4, range 7–14 years; 17 males and 21 females) completed at least one CPET with 95% achieving technically satisfactory tests allowing measurement of Vo2peak. Mean Vo2peak was 107 ±17.6% predicted, range 74%–150% predicted, with 8% having a reduced Vo2peak of

The parents of a 3-year old boy are anxious about their son who has recurring episodes of wheezing. They are frustrated that no one seems to be able to give them answers to their questions and would like a referral to a specialist. Does their son have asthma and what is the prognosis; how can the recurrent wheezing be managed and can the risk of asthma be reduced; are there lifestyle changes that could improve the environment and avoid triggers? Communication and support from the family practice team were essential. Listening to the parents’ concerns, explaining the diagnostic uncertainty, being realistic about what drug treatments could achieve, and providing practical advice on inhaler use and trigger avoidance reassured the parents that there was a strategy for managing their son’s wheeze. The specialist referral was postponed. The parents of a 3-year old boy are anxious about their son who has recurring episodes of wheezing. They are frustrated that no one seems to be able to give them answers to their questions and would like a referral to a specialist. Does their son have asthma and what is the prognosis; how can the recurrent wheezing be managed and can the risk of asthma be reduced; are there lifestyle changes that could improve the environment and avoid triggers? Communication and support from the family practice team were essential. Listening to the parents’ concerns, explaining the diagnostic uncertainty, being realistic about what drug treatments could achieve, and providing practical advice on inhaler use and trigger avoidance reassured the parents that there was a strategy for managing their son’s wheeze. The specialist referral was postponed.

Background: Following exposure to TB, contacts are screened to target preventive treatment at those at high risk of developing TB. The UK has recently revised its recommendations for screening and now advises a 5 mm tuberculin skin test (TST) cut-off irrespective of age or BCG status. We sought to evaluate the impact of BCG on TST responses in UK children exposed to TB and the performance of different TST cut-offs to predict interferon γ release assay (IGRA) positivity.\ud \ud Methods: Children

Recent evidence suggests that between-individual variation in posture and posture transitions may have important health consequences in adults. The early life development of between-individual variation in posture and posture transitions has not been studied, and the physiological consequences of such variations in childhood are unknown, largely because of the absence of objective methods for measuring posture and posture transitions in young children. This study aimed to examine the objective measurement of posture transitions in pre-school children with the activPAL™ monitor (PAL Technologies, Glasgow). Single-unit activity monitors such as the activPAL™ have a limited output, with data categorized as 'sit/lie', 'stand' or 'walk' and the consequences of this for measurement of posture transitions in young children are unknown. Thirty children (mean age 4.1 years) were videoed for 1 h in nursery while wearing an activPAL™. Video was analysed on a second-by-second basis, with all postures categorized. From direct observation, time spent was sit/lie 46%; stand 35%; walk/run 16%; 3% was spent in heterogeneous non-sit/lie/upright postures (crawl, crouch, and kneel up). Despite these 'non-standard' postures being responsible for a low proportion of time, posture transitions involving them contributed to 34% of total transitions. There was a significant rank-order correlation (r = 0.79, p < 0.0001) between the number of posture transitions measured by activPAL™ and by direct observation. 'Non-standard' postures in young children are probably not a problem if the aim is to measure total time sedentary or active, and the activPAL™ may measure between-individual variation in transitions adequately in young children. However, non-standard postures may present problems for the detailed characterization of posture transitions in early childhood.

Multi-center research studies that include pulmonary function as an objective outcome are increasingly important in pediatric respiratory medicine. The need for local controls rather than depending on published normative data for lung function remains debatable. Aims to compare pulmonary function in childhood controls with no respiratory symptoms from three centers in the United Kingdom and ascertain the extent to which current reference equations are appropriate for this population. Spirometry, plethysmographic lung volumes, and specific airways resistance (sRaw) were measured within specialized pediatric laboratories in children from three geographical locations throughout the UK (London, Leicester, and Glasgow), using identical equipment, software and standard operating procedures. Results were compared between centers and in relation to recent or commonly used UK pediatric reference values. Pulmonary function was assessed in 94 healthy children (mean (SD) age: 7.7 (0.6) years; 88% white Caucasians; ∼30 from each center). There were no significant differences in background demographics or spirometric outcomes when compared between centers. By contrast, statistically significant differences in plethysmographic lung volumes and sRaw were observed between-centers. Significant differences in relation to published reference data for white subjects were noted for FEV1 in all three centers and occasionally for other lung function measures but the differences from predicted values were small (within ± 0.5 z-score) and not clinically significant. After appropriate inter-laboratory standardization, spirometric measurements in children can be measured in different centers without evidence of systematic differences. However, even after extensive standardization procedures, plethysmographic measures appear more prone to inter-center differences and cannot, at present, be reliably compared across centers without incorporating controls at each location.

Objectives To identify the number and current location of all children receiving long-term ventilation (LTV) in the UK, and to establish their underlying diagnoses and ventilatory requirements. Design Single time-point census completed by members of the UK LTV working party using an electronic-based questionnaire Subjects All children in the UK at home or in hospital who, when medically stable, continue to need a mechanical aid for breathing following a failure to wean beyond a 3-month period. Results 933 children under the age of 17 years in 30 regional centres were identified as receiving LTV. 88 children (9.5%) required continuous positive pressure ventilation by tracheostomy over 24 h, while 658 received ventilation while asleep only. Most children are ventilated by a non-invasive mask (n=704; 75%) or tracheostomy (n=206; 22%). Underlying conditions included neuromuscular disease (n=402; 43%), chronic respiratory (n=343; 37%) and central nervous system conditions (n=168; 18%). 129 (14%) children were aged 16 or over. 844 (91%) children were cared for at home with only 49 children listed as being in acute hospital units (n=34) or paediatric intensive care units/high dependency units (n=15). Conclusions The last 10 years has seen a very significant increase in the number of children requiring LTV in the UK with an increasing number cared for at home. This reflects both improving technology and increasing clinical expertise in paediatric non-invasive ventilatory support, and a continuing change in attitude towards long-term support, particularly in children with neuromuscular diseases. There are a substantial number of children who soon will require transition to adult services, yet few such services currently exist.

Asthma is amongst the commonest chronic illnesses of childhood yet there is no single objective test that results in a definitive diagnosis. Diagnosis remains clinical, especially in young children. At present, asthma diagnosis in children is best viewed as a process. The initial steps include a clinical assessment focusing on recognising characteristic clinical features from a detailed history and examination combined with a careful review of possible alternative diagnoses. Since there is no gold standard for diagnosis, clinical evaluation can only give a probability that a given child has a diagnosis of asthma. If the probability of asthma is high, the next step is frequently a trial of anti-asthma treatment, usually a low-dose of an inhaled corticosteroid and a bronchodilator. Fairly to respond to a properly taken anti-asthma treatment suggests an alternative diagnosis. If the probability is low, a diagnosis other than asthma may be suspected. Then further investigation and specialist referral may be indicated. In those with an intermediate probability tests of lung function (expiratory airway obstruction, bronchial reversibility and occasionally bronchial hyperreactivity), and tests for atopy may be helpful.

Background The value of interferon-γ release assays (IGRA) to diagnose active tuberculosis (TB) in children is not established, but these assays are being widely used for this purpose. The authors examined the sensitivity of commercially available IGRA to diagnose active TB in children in the UK compared with the tuberculin skin test (TST). Methods The authors established a paediatric tuberculosis network and conducted a retrospective analysis of data from children investigated for active TB at six large UK paediatric centres. All centres had used TST and at least one of the commercially available IGRA (T-Spot.TB or Quantiferon-Gold in Tube) in the diagnostic work-up for active TB. Data were available from 333 children aged 2 months to 16 years. The authors measured the sensitivity of TST and IGRA in definite (culture confirmed) and probable TB in children, agreement between TST and either IGRA, and their combined sensitivity. Results Of 333 children, 49 fulfilled the criteria of definite TB, and 146 had probable TB. Within the definite cohort, TST had a sensitivity of 82%, Quantiferon-Gold in tube (QFT-IT) had a sensitivity of 78% and T-Spot.TB of 66%. Neither IGRA performed significantly better than a TST with a cut-off of 15 mm. Combining the results of TST and IGRA increased the sensitivity to 96% for TST plus T-Spot.TB and 91% for TST plus QFG-IT in the definite TB cohort. Conclusions A negative IGRA does not exclude active TB disease, but a combination of TST and IGRA increases the sensitivity for identifying children with active TB.

We describe a case of chronic mineralizing pulmonary elastosis in a seven-yr-old boy following DD renal transplantation for Wilms tumour. Fourteen months post-transplantation he developed respiratory symptoms with lung biopsy demonstrating chronic mineralizing pulmonary elastosis thought to be secondary to immunosuppression with MMF. Symptomatic resolution occurred following MMF cessation.

Key points Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. Children with TB are markers of recent disease transmission, usually from infectious adults. The 1 million cases of TB in children registered each year is likely to be a gross underestimate. The diagnosis is challenging and often presumed rather than confirmed. Symptoms, if present, are nonspecific. TB infection occurs when a previously uninfected child inhales an infected aerosol droplet. At this stage, the child usually shows no symptoms, the infection passes undetected and the primary focus heals. In most cases the infection is controlled by the body9s immune system and the organisms remain dormant. This is called latent TB. TB disease can develop either then or at a later stage when the organism multiplies, overpowering the host defences. At this stage, symptoms develop and there may be radiological or microbiological evidence of disease. "More bugs require more drugs". In TB infection, the organism load is small and therefore drug-resistant mutations are rare: hence simpler drug regimes are effective. In TB disease, the number of organisms is greater, so a combination of ≥3 drugs is required. Increasing resistance worldwide has led to four drugs being recommended as standard in many areas. Poor adherence to drug therapy is the main barrier to cure. Although directly observed therapy (DOTS) and intermittent therapy may improve the outcome, neither is a panacea. Co-operation and other strategies are required. Bacille Calmette-Guerin (BCG) vaccination remains the most widely used preventative strategy. Its efficacy is uncertain and its use needs to be targeted to neonates in high-risk areas who are most likely to benefit. The development of new vaccines against pulmonary TB is an important global challenge. Educational aims To describe the epidemiology and natural history of TB in children, focusing on pulmonary TB. To explore the challenges of diagnosis and provide an up-to-date overview of the methods available. To outline the management and prevention of pulmonary TB in children. Summary Despite advances in diagnosis, treatment and prevention, tuberculosis (TB) remains a major cause of mortality and morbidity worldwide. Diagnosis and treatment in children present a challenge, particularly in the face of growing drug resistance and coexistent disease such as HIV. New diagnostic methods have not yet been fully validated for use in children. No new drugs have become available in the past 30 years and many of the commercially available preparations are unsuitable for children. In 2006, a number of major documents and strategies were launched aimed at improving the care of children with TB, a previously neglected area.

AIM: To document previously unreported acute effects of adrenal insufficiency. METHODS: We describe two siblings who presented acutely with hyponatraemia and cerebral oedema following prolonged treatment with high dose inhaled fluticasone. RESULTS: A girl aged 5.5 years presented with vomiting, headache, visual impairment and seizures. She was hyponatraemic but not hypoglycaemic. Her conscious level continued to deteriorate and she died, post mortem examination showing small adrenal glands and cerebral oedema. Four weeks later her 7-year-old brother presented with similar symptoms. Assessment showed hyponatraemia with cerebral oedema. His illness responded to intensive care. A diagnosis of adrenal insufficiency was made retrospectively in both cases. The siblings had been receiving Fluticasone propionate (FP) in doses of up to 2000 microg/day for several years. CONCLUSION: We believe that the hyponatraemia and cerebral oedema was related to cortisol deficiency, leading to impaired excretion of water. We emphasize the need for careful cerebral monitoring in acute adrenal insufficiency presenting with impaired consciousness.

Most childhood asthma is mild/moderate and is easily controlled with regular use of inhaled corticosteroids (ICS) and rescue bronchodilators. However, between 5% and 10% of children will have asthma that remains difficult to control despite high doses of appropriate asthma therapies. Children with ‘difficult to control’ asthma are responsible for a substantial proportion of the morbidity and health care costs associated with asthma. The recognition that not all ‘difficult to control’ asthma is ‘severe’ is perhaps the most important message for paediatricians looking after children with such asthma. Before labelling asthma as ‘severe’, factors that might make asthma difficult to control need to be identified and addressed. In the small number with genuinely severe asthma, there are a number of different subgroups or ‘phenotypes’. In the future, clearer definition of phenotypes is likely to lead to better targeting of therapy and to improved asthma control.

Ninety children aged 6 to 13 y and suffering from chronic asthma were included in a prospective follow-up study lasting 18 mo in order to assess whether life events involving substantial positive effects on the child can protect against the increased risk associated with stressful life events. The main outcome measures included positive life events, positive long-term experiences, severely negative life events, chronic psychosocial stress and new asthma exacerbation. The results showed that, provided they occurred in close proximity to severely negative life events, positive life events, generally related to the child's own achievements, afforded protection against the increased risk of a new asthma exacerbation precipitated by severe events in children whose lives were marked by low to medium levels of chronic stress. No such effect was found in children exposed to high chronic stress nor did long-term positive experiences, such as when the child has a rewarding hobby, affect the asthma risk. Conclusion: Life events with a definite positive effect can counteract the increased risk of an asthma exacerbation precipitated by a severely negative life event, provided the chronic stress is only of low to medium level. Because this protective influence does not apply where there is high chronic stress, reducing this condition must be seen as a priority in children suffering from asthma, as these children are also more vulnerable to negative life events precipitating asthma exacerbation.

There is at the current time a significant opportunity for the ERS to leverage its experience and reputation as an international umbrella organisation to promote high-quality, multinational respiratory research with the goal of improving the health of respiratory patients. This editorial proposes a model for the role and structure of an ERS Research Agency. It is based upon research, implicit knowledge and explicit feedback from ERS members and selected external individuals and organisations. As with any new endeavour there are challenges and threats. Building a Research Agency will be a major undertaking that will require significant organisational planning, resources, effort and commitment. Organisations with multiple stakeholders tend to have a status quo inertia that has to be overcome for any significant new endeavour. The ERS Research Agency could be an investment in the future of respiratory research.

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] 2 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.

Background and Aims: The oxygen uptake efficiency slope (OUES) has been shown to be a valid sub-maximal measure of aerobic capacity and ventilatory efficiency in both adults and children. However, in one study in CF children with mild to moderate disease, OUES had limited discriminatory properties (1). Our aim was to re-examine the validity of OUES in 3 groups of children: CF, TOF and unexplained SOBOE. Methods: We reviewed data from cardiopulmonary exercise tests in children with CF (n=45), TOF (n=30) and patients with unexplained SOBOE (n = 30). All patients had lung function and an incremental exercise test. If the child was tall enough, cycle ergometer was used (n=96) with an appropriately selected ramp ranging from 6.5-25 watts.min-1. Otherwise, a treadmill protocol was used. OUES was calculated over the entire exercise duration. Results: Results are shown in Table 1. The OUES % predicted was lower in TOF, compared to the CF and SOBOE groups (p

There is limited evidence on how much and on which days accelerometry monitoring should be performed to obtain a representative measurement of physical activity (PA) in young children. We measured 76 children (40 M and 36 F, mean age 5.6 years ([SD ± 0.4]) on 7 days using Actigraph accelerometers. Mean daily PA was expressed in counts per min (cpm). Reliability increased as the number of days and hours of monitoring increased, but only to 10 hr per day. At 7 days of monitoring for 10 hr per day, reliability was 80% (95% CI [70%, 86%]). The number of days was more important to reliability than the number of hours. The inclusion or exclusion of weekend days made relatively little difference. A monitoring period of 7 days for 10 hr per day produced the highest reliability. Surprisingly short monitoring periods may provide adequate reliability in young children.

To test for relationships between objectively measured habitual physical activity and fundamental movement skills in a relatively large and representative sample of preschool children.Physical activity was measured over 6 d using the Computer Science and Applications (CSA) accelerometer in 394 boys and girls (mean age 4.2, SD 0.5 yr). Children were scored on 15 fundamental movement skills, based on the Movement Assessment Battery, by a single observer.Total physical activity (r=0.10, P0.05) and percent time spent in moderate to vigorous physical activity (MVPA) (r=0.18, P0.001) were significantly correlated with total movement skills score. Time spent in light-intensity physical activity was not significantly correlated with motor skills score (r=0.02, P0.05).In this sample and setting, fundamental movement skills were significantly associated with habitual physical activity, but the association between the two variables was weak. The present study questions whether the widely assumed relationships between motor skills and habitual physical activity actually exist in young children.

This study examined whether there was a significant seasonal variation in objectively measured habitual physical activity and sedentary behavior in young children. Participants were children who attend nursery in Glasgow, Scotland, and measurements were taken using uniaxial accelerometry over 3 to 6 days. There were small but significant seasonal associations with physical activity and sedentary behavior (ANOVA: p < .001 in both cases). Total physical activity (accelerometry cpm) was significantly lower in spring than in summer, fall, and winter. We also found slight but significant seasonal variations in time spent in low-intensity activity and in moderate-to-vigorous-intensity activity. Sedentary time was significantly lower in summer vs. spring and in fall vs. spring. The present study suggests that seasonality plays only a limited role in physical activity and sedentary behavior in young children in our setting. Single measures of these variables should be adequate for research purposes in the absence of marked seasonal variability. In our sample and setting, the limited degree of seasonality precluded identification of major seasonal barriers to and opportunities for physical activity.

The primary aim of this study was to test the validity of two accelerometers, CSA/MTI WAM-7164 and Actiwatch®, against direct observation of physical activity using the Children’s Physical Activity Form (CPAF). CSA/MTI WAM-7164 and Actiwatch accelerometers simultaneously measured activity during structured-play classes in 3- to 4-year olds. Accelerometry output was synchronized to CPAF assessments of physical activity in 78 children. Rank order correlations between accelerometry and direct observation evaluated the ability of the accelerometers to assess total physical activity. Within-child minute-to-minute correlations were calculated between accelerometry output and direct observation. For total physical activity, CSA/MTI output was significantly correlated with CPAF (r = .72, p < .001), but output from the Actiwatch was not (r = .16, p > .05).

A cure for many childhood respiratory diseases is not yet possible and treatment usually has to focus on disease control. For families, this frequently involves a series of quite complex tasks. Education helps families develop the necessary knowledge, attitudes, beliefs and skills to manage illness effectively, and is one of the main tasks of the clinical team. Unfortunately, health education interventions often fail to bring about any significant gains in the health or well being of the target population. This article describes how a systematic approach can be applied to the development of health educational interventions to maximise their chance of being effective.

Objective: To test the ability of accelerometry to quantify sedentary behavior in 3- to 4-year-old children. Research Methods and Procedures: We developed a cut-off for accelerometry output (validation study) in 30 healthy 3 to 4 year olds, which provided highest sensitivity and specificity for the detection of sedentary behavior relative to a criterion method of measurement, direct observation using the children's physical activity form. We then cross-validated the cut-off in an independent sample of healthy 3 to 4 year olds (n = 52). Results: In the validation study, optimal sensitivity and specificity for the detection of sedentary behavior were obtained at an accelerometry output cut-off of

SETTING: Large specialist paediatric TB clinics in the UK. OBJECTIVE: To evaluate clinical practice and compare with national and international guidelines. DESIGN: A survey based on an electronic questionnaire on the management of latent tuberculous infection (LTBI) and tuberculosis (TB) disease was conducted in 13 specialist paediatric TB clinics. The consensus and discrepancies were evaluated by descriptive analysis. RESULTS: Practice was reportedly different when choosing age limits for preventive treatment for TB contacts with initially negative tuberculin skin tests (TSTs), interpretation of TST results and use of interferon-gamma release assays (IGRAs) in the context of LTBI. In relation to management of children with TB disease, practices varied for duration of treatment of osteoarticular TB, monitoring for ethambutol ocular toxicity and use of pyridoxine. There was limited experience with multidrug-resistant TB (MDR-TB), and over half of the clinics monitored MDR-TB contacts without giving preventive treatment. CONCLUSIONS: The survey showed heterogeneity in several aspects of clinical care for children with TB. Available paediatric TB guidelines differ substantially, explaining the wide variations in management of childhood TB. Prospective paediatric studies are urgently required to inform and standardise clinical practice, especially in the context of evolving drug resistance.

“ If we are to achieve results never before accomplished, we must expect to employ methods never before attempted ” Sir Francis Bacon 1561–1626. British aviators Alcock and Brown made the first transatlantic flight in 1919 – In 2013, the total number of flights in Europe was 9.5 million. In July 1969, Apollo 11 Commander Neil Armstrong landed on the moon – today you can book your flight to space online with Virgin Galactic. Throughout the 1990s, medical education was transformed as a direct consequence of more complex patient needs and the reorganisation of healthcare delivery. Medical education refers to the educational process required to prepare the medical professional for entry into practice as well as provision of educational activities for lifelong learning. This educational process is aimed at physicians, nurses, technicians, physiotherapists, scientists and other related professions who deliver care to the patient and public. Today’s medical professional is bound by demanding healthcare systems [1–3], internationalisation of localised diseases [4], shorter more intense training periods and dependence on medical technology [5]. Global funds, trade and networks are all examples of initiatives that demonstrate our entry into an international, mobile era. In 1993, the European Council (EU) council directive 93/16 stipulated that those EU nationals holding an EU primary or specialist medical qualification were to be allowed to practice within any EU country [6]. We are aware that many European countries are heavily reliant on foreign-trained medical staff to support their medical systems [7]. Patient tourism has also warranted attention [8], as more and more patients opt to cross international borders in search of treatment. The European Respiratory Society (ERS) International Congress welcomes respiratory health professionals from all over the world. As a provider of continuous …

The use of data to challenge and improve healthcare has a long and distinguished history but has often failed to bring about expected improvements. It has never become fully embedded in clinical practice, probably because data alone are insufficient to drive change. There is now a greater appreciation that changing and improving healthcare requires changing behaviours. Clinical audit remains one of the important tools that can be used to facilitate such change.

Childhood obstructive sleep apnoea syndrome (OSAS) acts as a check on growth and nutritional status. An increase in sleeping energy expenditure has been proposed as a possible mechanism, but to date, no studies have determined whether energy requirements (total energy expenditure; TEE) are raised in OSAS. The aim of this study was to test the hypothesis that OSAS is associated with increased TEE.Eleven children (mean±sd 5.8±2.2 yrs of age) with OSAS confirmed by nocturnal polysomnography were each matched with a pair of healthy controls (n=22) of the same age and sex. TEE was measured using the doubly-labelled water method in all subjects. In 10/11 patients TEE was also measured after adenotonsillectomy and changes in TEE assessed.There was no significant difference in TEE between patients (mean±sd 325±44 kJ·kg−1·day−1) and controls (339±48 kJ·kg−1·day−1), nor between patients and age- and sex-specific literature data on TEE, using the doubly-labelled water method. Differences in TEE within patients, beforeversusafter surgery, were minor and not statistically significant.This study does not support the hypothesis that obstructive sleep apnoea syndrome in childhood is associated with increased energy requirements, and suggests that alternative explanations for the effect of this syndrome on growth and energy balance should be sought.

Lung function testing is an increasingly important tool in the diagnosis and monitoring of lung disease in children. However, not all paediatricians will have had training in lung function testing. Here, a structured approach to the interpretation of lung function results is developed. This should help the clinician understand the results from their lung function laboratory.