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Jonathan Grigg,1 Anjan Nibber,2 James Y Paton,3 Alison Chisholm,2 Theresa W Guilbert,4 Alan Kaplan,5 Steve Turner,6 Nicolas Roche,7 Elizabeth V Hillyer,8 David B Price8,9 On behalf of the Respiratory Effectiveness Group 1Blizard Institute, Queen Mary University of London, London, UK; 2Respiratory Effectiveness Group, Cambridge, UK; 3School of Medicine, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK; 4Pulmonary Division, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; 5Family Physician Airways Group of Canada, University of Toronto, Toronto, ON, Canada; 6Department of Child Health, Royal Aberdeen Children’s Hospital, University of Aberdeen, Aberdeen, UK; 7Respiratory Medicine, Cochin Hospital Group, AP-HP, University of Paris Descartes (EA2511), Paris, France; 8Observational and Pragmatic Research Institute Pte Ltd, Singapore, Singapore; 9Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: An inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) may prevent wheezing/asthma attacks in preschoolers with recurrent wheeze when added to short-acting β-agonist (SABA).Objective: The aim of this historical matched cohort study was to assess the effectiveness of these treatments for preventing wheezing/asthma attacks.Methods: Electronic medical records from the Optimum Patient Care Research Database were used to characterize a UK preschool population (1–5 years old) with two or more episodes of wheezing during 1 baseline year before first prescription (index date) of ICS or LTRA, or repeat prescription of SABA. Children initiating ICS or LTRA on the index date were matched 1:4 to those prescribed only SABA for age, sex, year of index prescription, mean baseline SABA dose, baseline attacks, baseline antibiotic prescriptions, and eczema diagnosis. Wheezing/asthma attacks (defined as asthma-related emergency attendance, hospital admission, or acute oral corticosteroid prescription) during 1 outcome year were compared using conditional logistic regression.Results: Matched ICS and SABA cohorts included 990 and 3,960 children, respectively (61% male; mean [SD] age 3.2 [1.3] years), and matched LTRA and SABA cohorts included 259 and 1,036 children, respectively (65% male; mean [SD] age 2.6 [1.2] years). We observed no significant difference between matched cohorts in the odds of a wheezing/asthma attack: ICS vs SABA, OR (95% CI) 1.01 (0.85–1.19) and LTRA vs SABA, OR (95% CI) 1.28 (0.96–1.72).Conclusion: We found no evidence that initiation of ICS or LTRA therapy is associated with fewer attacks during 1 outcome year than SABA alone for a heterogeneous group of preschool children with recurrent wheeze in the real-life clinical setting. Keywords: electronic medical records, inhaled corticosteroids, leukotriene receptor antagonists, observational study, ICS particle size, short-acting β-agonist

Background: A socioeconomic gradient in childhood obesity is known to be present by the age of school entry in the UK. The origin of this gradient is unclear at present, but must lie in socioeconomic differences in habitual physical activity, sedentary behaviour, or dietary intake.Aims: To test the hypothesis that habitual physical activity and/or sedentary behaviour are associated with socioeconomic status (SES) in young Scottish children.Methods: Observational study of 339 children (mean age 4.2 years, SD 0.3) in which habitual physical activity and sedentary behaviour were measured by accelerometry over six days (study 1). In a second study, 39 pairs of children of distinctly different SES (mean age 5.6 years, SD 0.3) were tested for differences in habitual physical activity and sedentary behaviour by accelerometry over seven days.Results: In study 1, SES was not a significant factor in explaining the amount of time spent in physical activity or sedentary behaviour once gender and month of measurement were taken into account. In study 2, there were no significant differences in time spent in physical activity or sedentary behaviour between affluent and deprived groups.Conclusion: Results do not support the hypothesis that low SES in young Scottish children is associated with lower habitual physical activity or higher engagement in sedentary behaviour. [ABSTRACT FROM AUTHOR]

Background: In the past 10 years, medication errors have come to be recognised as an important cause of iatrogenic disease in hospital patients.Aims: To determine the incidence and type of medication errors in a large UK paediatric hospital over a five year period, and to ascertain whether any error prevention programmes had influenced error occurrence.Methods: Retrospective review of medication errors documented in standard reporting forms completed prospectively from April 1994 to August 1999. Main outcome measure was incidence of error reporting, including pre- and post-interventions.Results: Medication errors occurred in 0.15% of admissions (195 errors; one per 662 admissions). While the highest rate occurred in neonatal intensive care (0.98%), most errors occurred in medical wards. Nurses were responsible for most reported errors (59%). Errors involving the intravenous route were commonest (56%), with antibiotics being the most frequent drug involved (44%). Fifteen (8%) involved a tenfold medication error. Although 18 (9.2%) required active patient intervention, 96% of errors were classified as minor at the time of reporting. Forty eight per cent of parents were not told an error had occurred. The introduction of a policy of double checking all drugs dispensed by pharmacy staff led to a reduction in errors from 9.8 to 6 per year. Changing the error reporting form to make it less punitive increased the error reporting rate from 32.7 to 38 per year.Conclusion: The overall medication error rate was low. Despite this there are clear opportunities to make system changes to reduce error rates further. [ABSTRACT FROM AUTHOR]

Background: Time spent in 24-h movement behaviors is important to health and wellbeing in childhood, but levels of these behaviors in children with chronic disease are unknown., Methods: A case-control-study included 80 children with chronic disease; 20 with type 1 diabetes mellitus (T1DM), 20 with juvenile idiopathic arthritis (JIA), 20 with congenital heart disease (CHD), 20 with cystic fibrosis (CF); pair-matched individually for age, sex, and timing of measures with 80 healthy children. Habitual time spent in movement behaviors and step counts were all measured with an activPAL accelerometer over 7 days. Comparisons against recommendations and differences between the groups were made., Results: Time spent in physical activity and step counts/day were significantly lower in T1DM and CHD groups compared to controls. Only 20/80 children with chronic disease and 29/80 controls met step count recommendations. Sedentary time was significantly higher in children with CF compared to controls. Time spent asleep was slightly greater in children with chronic disease, significant only for the JIA group. Sleep disruption was consistently greater in those with chronic disease, reaching significance for T1DM, CHD, and CF groups., Conclusions: For some groups of children with chronic disease, 24-h movement behaviors may differ substantially from recommendations, and slightly but systematically from their healthy peers. Optimizing levels of 24-h movement behaviors should confer a number of benefits for child health, development, and wellbeing.

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 ( T LCO ), transfer coefficient of the lung for carbon monoxide ( K CO ) and alveolar volume ( V A ) 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 T LCO were higher than those predicted by GLI. Predicted K CO using Rosenthal was higher in all observations. In contrast, the Rosenthal predicted V A 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., Competing Interests: Conflict of interest: P.D. Burns has nothing to disclose. Conflict of interest: J.Y. Paton has nothing to disclose., (Copyright ©ERS 2021.)

Globally, asthma is one of the most common chronic conditions that affect individuals of all ages. When poorly controlled, it negatively impacts patient's ability to enjoy life and work. At the population level, effective use of recommended strategies in children and adults can reduce symptom burden, improve quality of life and significantly reduce the risk of exacerbation, decline of lung function and asthma-related death. Inhaled corticosteroid as the initial maintenance therapy, ideally started within 2 years of symptom onset, is highly effective in both children and adults and across various degrees of asthma severity. If asthma is not controlled, the choice of subsequent add-on therapies differs between children and adults. Evidence supporting pharmacological approach to asthma management, especially for those with more severe disease, is more robust in adults compared to children. This is, in part, due to various challenges in the diagnosis of asthma, in the recruitment into clinical trials and in the lack of objective outcomes in children, especially those in the preschool age group. Nevertheless, where evidence is emerging for younger children, it seems to mirror the observations in adults. Clinicians need to develop strategies to implement guideline-based recommendations while taking into consideration individual variations in asthma clinical phenotypes, pathophysiology and treatment responses at different ages.

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).

Context: Moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) are important for child and adolescent health., Objective: 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., Methods: Data sources: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus and CINAHL from 2000-2017. 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., Results: 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., Conclusions: 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.

HERMES: European accreditation of training centres in paediatric respiratory medicine http://ow.ly/ZBmUg.

At the end of his mandate as Breathe Chief Editor, James Paton reflects on the previous 3 years http://ow.ly/RctU8.

Background: Sitting time and breaks in sitting influence cardio-metabolic health. New monitors (e.g. activPAL™) may be more accurate for measurement of sitting time and breaks in sitting although how to optimize measurement accuracy is not yet clear. One important issue is the minimum sitting/upright period (MSUP) to define a new posture. Using the activPAL™, we investigated the effect of variations in MSUP on total sitting time and breaks in sitting, and also determined the criterion validity of different activPAL™ settings for both constructs., Methods: We varied setting of MSUP in 23 children (mean (SD) age 4.5 y (0.7)) who wore activPAL™ (24 hr/d) for 5-7 d. We first studied activPAL™ using the default setting of 10 s MSUP and then reduced this to 5 s, 2 s and 1 s. In a second study, in a convenience sample of 30 pre-school children (mean age 4.1 y (SD 0.5)) we validated the activPAL™ measures of sitting time and breaks in sitting at different MSUP settings against direct observation., Results: Comparing settings of 10, 5, 2 and 1 s, there were no significant differences in sitting time (6.2 hr (1.0), 6.3 hr (1.0), 6.4 hr (1.0) and 6.3 hr (1.6), respectively) between settings but there were significant increases in the apparent number of breaks - (8(3), 14(2), 21(4) and 28 (6)/h) at 10, 5, 2 and 1 s settings, respectively. In comparison with direct observation, a 2 s setting had the smallest error relative to direct observation (95% limits of agreement: -14 to +17 sitting bouts/hr, mean difference 1.83, p = 0.2)., Conclusion: With activPAL™, breaks in sitting, but not total sitting time, are highly sensitive to the setting of MSUP, with 2 s optimal for young children. The MSUP to define a new posture will need to be empirically determined if accurate measurements of number of breaks in sitting are to be obtained.

Purpose: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g., sedentary time) contributing to positive energy balance in early childhood. For preschool children, single-unit monitors such as the activPAL™ are promising. However, validation is required because activity patterns differ from adults., Methods: Thirty preschool children participated in a validation study. Children undertaking usual nursery activity while wearing an activPAL™ 1 h were recorded using a video camera. Video (criterion method) was analyzed on a second-by-second basis to categorize posture and activity. This was compared with the corresponding activPAL™ output. In a subsequent substudy investigating practical utility and reliability, 20 children wore an activPAL™ for seven consecutive 24-h periods., Results: A total of 97,750 s of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), and walk (16%); with 3% of time in non-sit/lie/upright postures (e.g., crawl/crouch/kneel-up). Sensitivity for the overall total time-matched seconds detected as activPAL™ "sit/lie" was 86.7%, specificity was 97.1%, and positive predictive value was 96.3%. For individual children, the median (interquartile range) sensitivity for activPAL™ sit/lie was 92.8% (76.1%-97.4%), specificity was 97.3% (94.9%-99.2%), and positive predictive value was 97.0% (91.5%-99.1%). The activPAL™ underestimated total time spent sitting (mean difference = -4.4%, P < 0.01) and overestimated time standing (mean difference = 7.1%, P < 0.01). There was no difference in overall percent time categorized as "walk" (P = 0.2). The monitors were well tolerated by children during a 7-d period of free-living activity. In the reliability study, at least 5 d of monitoring was required to obtain an intraclass correlation coefficient of ≥ 0.8 for time spent "sit/lie" according to activPAL™ output., Conclusions: The activPAL™ had acceptable validity, practical utility, and reliability for the measurement of posture and activity during free-living activities in preschool children.

Background: Randomized controlled trials (RCT) are required to test relationships between physical activity and cognition in children, but these must be informed by exploratory studies. This study aimed to inform future RCT by: conducting practical utility and reliability studies to identify appropriate cognitive outcome measures; piloting an RCT of a 10 week physical education (PE) intervention which involved 2 hours per week of aerobically intense PE compared to 2 hours of standard PE (control)., Methods: 64 healthy children (mean age 6.2 yrs SD 0.3; 33 boys) recruited from 6 primary schools. Outcome measures were the Cambridge Neuropsychological Test Battery (CANTAB), the Attention Network Test (ANT), the Cognitive Assessment System (CAS) and the short form of the Connor's Parent Rating Scale (CPRS:S). Physical activity was measured habitually and during PE sessions using the Actigraph accelerometer., Results: Test- retest intraclass correlations from CANTAB Spatial Span (r 0.51) and Spatial Working Memory Errors (0.59) and ANT Reaction Time (0.37) and ANT Accuracy (0.60) were significant, but low. Physical activity was significantly higher during intervention vs. control PE sessions (p < 0.0001). There were no significant differences between intervention and control group changes in CAS scores. Differences between intervention and control groups favoring the intervention were observed for CANTAB Spatial Span, CANTAB Spatial Working Memory Errors, and ANT Accuracy., Conclusions: The present study has identified practical and age-appropriate cognitive and behavioral outcome measures for future RCT, and identified that schools are willing to increase PE time., Trial Registration Number: ISRCTN70853932 (http://www.controlled-trials.com).

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Objective: To assess whether a physical activity intervention reduces body mass index in young children., Design: Cluster randomised controlled single blinded trial over 12 months., Setting: Thirty six nurseries in Glasgow, Scotland., Participants: 545 children in their preschool year, mean age 4.2 years (SD 0.2) at baseline., Intervention: Enhanced physical activity programme in nursery (three 30 minute sessions a week over 24 weeks) plus home based health education aimed at increasing physical activity through play and reducing sedentary behaviour., Main Outcome Measure: Body mass index, expressed as a standard deviation score relative to UK 1990 reference data. Secondary measures were objectively measured physical activity and sedentary behaviour; fundamental movement skills; and evaluation of the process., Results: Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry. Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up (P=0.0027; 95% confidence interval 0.3 to 1.3) after adjustment for sex and baseline performance., Conclusions: Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial., Trial Registration: Current Controlled Trials ISRCTN36363490.

Background: A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress., Methods: Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events., Results: An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69, 95% confidence interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 (95% confidence interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children., Conclusion: The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5-7 weeks later.

Background: Strategies for the prevention and treatment of childhood obesity require a better understanding of the relation between the pattern of free-living physical activity and total energy expenditure (TEE)., Objective: We assessed the relations between TEE and physical activity level (PAL) during engagement in different intensities of physical activity., Design: We used a cross-sectional study of 104 children (median age: 5.4 y) in Scotland. TEE was measured with use of doubly labeled water (DLW), and resting energy expenditure was predicted to determine PAL. Time spent sedentary and in light-intensity activity and in moderate- and vigorous-intensity physical activity (MVPA) was assessed by accelerometry concurrent with DLW measurements. Correlation and regression were used to assess the relations between measures of sedentary behavior, intensities of activity, and PAL as the dependent variable., Results: Time spent sedentary was negatively correlated with PAL (r = -0.33, P < 0.01), and time spent in light-intensity activity was positively correlated with PAL (r = 0.31, P < 0.01). In multiple regression analyses, both time spent sedentary and in light-intensity activities were significantly associated with PAL. Time spent in MVPA was not associated with PAL; engagement in MVPA was limited in this sample (median: 3% of waking hours; range: 0-14%). PAL was significantly higher in boys than in girls., Conclusion: In this sample and setting, PAL was not influenced by engagement in MVPA but was influenced by time spent sedentary and in light-intensity activities. This study suggests that in young children, MVPA could make only a minor contribution to free-living TEE and PAL.

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 <1100 counts/min. In the cross-validation, sensitivity was 83%: 438/528 inactive minutes were correctly classified. Specificity was 82%: 1251/1526 noninactive minutes were correctly classified using this cut-off., Discussion: Sedentary behavior can be quantified objectively in young children using accelerometry. This new technique could be considered for a wide variety of applications in the etiology, prevention, and treatment of childhood obesity.

Objective: This study aimed to describe levels of physical activity in a representative sample of preschool children and to quantify tracking of activity over 1 year., Research Methods and Procedures: Physical activity (mean accelerometry counts/minute) was assessed over 3 days using the Computer Science and Applications accelerometer in 3- to 4-year-old children (n = 104; 52 boys; mean age, 3.7 +/- 0.4 years). In 60 children (30 boys), measurements were repeated 1 year later., Results: Mean total activity at baseline was 777 +/- 207 counts/minute in boys and 657 +/- 172 counts/minute for girls; this gender difference was significant (p < 0.001). In the cross-sectional analysis, total activity was significantly positively related to age (r = 0.37, p = 0.007). In the sample followed up for 1 year, mean total activity was 849 +/- 252. The longitudinal analysis confirmed that total physical activity increased over the 1-year period (paired Student's t test, p < 0.001). The tracking rank order correlation coefficient of total activity count over 1 year was r = 0.40 (p < 0.001)., Discussion: This study suggests that total activity increases during the preschool period in Scottish children and that gender differences in total activity are present early in life. Tracking of total activity was only modest, but adequate assessment of tracking requires methodological research aimed at elucidating the biological meaning of accelerometer output.

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 x kg(-1) x day(-1)) and controls (339+/-48 kJ x kg(-1) x 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, before versus after 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.

Objectives: To describe prospectively the evolution of liver abnormalities in cystic fibrosis (CF), and to assess their impact on nutritional status., Study Design: 124 children (61 boys) with CF (median age, 5.4 years; range, 0.1-13.9) were followed longitudinally for a median of four years. Annual clinical examination, biochemistry, and ultrasound assessment were performed. Chrispin-Norman score, anthropometry, and bacterial colonisation of airway secretions were measured at each assessment., Results: At initial assessment, 45% of the patients had no liver abnormalities, 42% had biochemical abnormality, 35% ultrasound abnormality, and 6% had clinical abnormality of the liver. In this cross sectional analysis, abnormal biochemistry was present in 40% of children with ultrasound or clinical abnormalities, but when longitudinal follow up data were analysed, abnormal biochemistry preceded or coincided with abnormal ultrasound or clinical hepatosplenomegaly in three quarters of 53 children developing new abnormalities. Eighty four of 124 children (68%) showed ultrasound or clinical evidence of liver abnormality at some point during the four years of follow up. No association was found between liver disease and nutritional status., Conclusions: Hepatic abnormality was common in this group of children with CF, was often predicted by intermittent biochemical abnormalities, and was not associated with deterioration in nutritional status.

Background: Two clinical formulae (CF conference formula and estimation based on 120% of average requirement for energy) have been recommended for the estimation of energy requirements in cystic fibrosis but their accuracy is unknown., Aim: To compare the accuracy of estimates of energy requirement derived from the two formulae., Methods: Energy requirement, defined as total daily energy expenditure, was measured using the doubly labelled water method in 15 patients (six girls, nine boys; mean (SD) age, 10.0 (2.4) years) who were well and clinically stable. The accuracy of the formulae was assessed using calculation of biases and limits of agreement relative to measured energy requirement., Results: Estimates from the CF conference formula were lower than measured values (mean paired difference, 0.52 MJ/day; 95% confidence interval (CI), -1.10 to 0. 10), but this bias was not significant, and was smaller than that from the alternative formula (mean paired difference, 0.77 MJ/day; 95% CI, -0.20 to 1.74). Limits of agreement relative to measured total daily energy expenditure were narrower for the CF conference formula (-2.72 to 1.68 MJ/day) than for that based on 120% of estimated average requirement (-2.75 to 4.29 MJ/day), but with both formulae errors in estimation at the individual level were large., Conclusions: The CF conference formula offers improved prediction of energy requirements, but the accuracy of both formulae at the individual level is not sufficiently good for clinical purposes.

Acute respiratory exacerbations have been proposed to contribute to the negative energy balance which causes undernutrition in cystic fibrosis. However, no studies have measured their effect on all components of energy balance. The aim of this study was to measure the effect of an acute respiratory exacerbation on energy balance. Fourteen children (six females, eight males, mean+/-SD age 9.9+/-2.4 yrs) were studied when well and during the course of an acute respiratory exacerbation treated with intravenous antimicrobial therapy. The total energy expenditure was measured using the doubly-labelled water method, resting energy expenditure by ventilated hood indirect calorimetry, energy intake by household measures records, and fat malabsorption from measurements of dietary fat intake and faecal fat output. The exacerbation was associated with a significant reduction in energy intake (mean paired difference 47 kJ x kg of body weight(-1) x day(-1), p<0.01). Changes in fat malabsorption and resting energy expenditure were negligible. The absence of significant changes in body weight and composition, together with the trend towards lower total energy expenditure, suggested no marked negative energy balance during the exacerbation. In conclusion, treatment of acute respiratory exacerbation with intravenous antimicrobial therapy represents a relatively minor challenge to energy balance and nutritional status in children with cystic fibrosis.

Infection with respiratory syncytial virus (RSV) is a common cause of respiratory disease in infancy. Surfactant phospholipids have been shown to be reduced in severe RSV infection. Reduction in surfactant proteins might also contribute to the pathogenesis of this disease. We investigated daily levels of surfactant proteins in bronchoalveolar lavage (BAL) fluid from 18 ventilated infants with RSV infection (median age 3.1 mo) and in a control group of 16 ventilated surgical patients (median age 0.4 mo). Surfactant proteins were measured by ELISA, total protein by the Lowry method. Surfactant protein A (SP-A) was reduced in BAL fluid from children with RSV infection (median 5.6 micrograms/ml; range 0.6 to 151.9 micrograms/ml) compared with control samples (median 9.0 micrograms/ml; range 0.5 to 139.6 micrograms/ml, p = 0.0368). Surfactant protein B (SP-B) was lower in the RSV group (median 12.0 ng/ml; range 0 to 60. 8 ng/ml) than in control patients (median 118.1 ng/ml; range 0 to 778.2 ng/ml, p < 0.0000). Surfactant protein D (SP-D) was also reduced in the RSV group (median 130.3 ng/ml; range 0 to 1,486.0 ng/ml) versus median 600.4 ng/ml; range 0 to 1,869.0 ng/ml, p < 0. 0000. Total protein levels were higher in the RSV group (median 0.49 mg/ml; range 0.13 to 2.46 mg/ml versus median 0.36 mg/ml; range 0.07 to 1.65 mg/ml, p = 0.0079). The median value of SP-A was significantly lower in the initial sample (2.3 micrograms/ml) than in the final one (6.0 micrograms/ml). However, no significant correlation was found between surfactant protein concentrations and disease severity measured by arterial alveolar oxygen ratio. We conclude that alterations in surfactant protein concentrations are present in severe RSV infection and speculate that these may contribute to the abnormalities of lung function seen in this condition.

Objectives: To identify the number and current location of children, aged 0 to 16 years, requiring long term ventilation in the United Kingdom, and to establish their underlying diagnoses and ventilatory needs., Design: Postal questionnaires sent to consultant respiratory paediatricians and all lead clinicians of intensive care and special care baby units in the United Kingdom., Subjects: All children in the United Kingdom who, when medically stable, continue to need a mechanical aid for breathing., Results: 141 children requiring long term ventilation were identified from the initial questionnaire. Detailed information was then obtained on 136 children from 30 units. Thirty three children (24%) required continuous positive pressure ventilation by tracheostomy over 24 hours, and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%), tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying conditions included neuromuscular disease (n=62; 46%), congenital central hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25; 18%). 93 children were cared for at home. 43 children remained in hospital because of home circumstances, inadequate funding, or lack of provision of home carers. 96 children were of school age and 43 were attending mainstream school., Conclusions: A significant increase in the number of children requiring long term ventilation in the United Kingdom has occurred over the past decade. Contributing factors include improved technology, developments in paediatric non-invasive ventilatory support, and a change in attitude towards home care. Successful discharge home and return to school is occurring even for severely disabled patients. Funding and home carers are common obstacles to discharge.

Nebulized recombinant human deoxyribonuclease (DNase) reduces sputum viscosity and improves lung function in some cystic fibrosis patients, but individual responses are unpredictable. The aim of this study was to investigate how DNase can be targeted to those cystic fibrosis patients who would benefit most. The Scottish Cystic Fibrosis Group agreed on a randomized, double-blind, placebo-controlled n-of-1 assessment protocol. Patients underwent a maximum of three 4-week assessment periods (2 weeks saline, 2 weeks DNase each). Measurements performed at hospital (exercise, oximetry and spirometry) and home (symptom scores) were used to derive a scoring system to discriminate maximally between DNase and placebo effects. The data on 89 4-week assessments in 52 patients were reported. Twenty-four patients have completed the assessment process (12 responders and 12 nonresponders) to date. Forced expiratory volume in one second (FEVI) was the best discriminator of response, rising by >200 mL after DNase in 33 of 89 (37%) assessments compared with 3 of 89 (3%) after saline. N-of-1 trials, while laborious, permitted genuine treatment effects to be quantified within individuals with confidence, permitting appropriate treatment targeting. This provides a model of how other new expensive therapies may be introduced to maximize patient benefit.

Background: Previous studies have shown poor compliance with regular drug therapy in children and adults with asthma. In preschool children the parents supervise and are responsible for drug administration, but little is known of compliance in this group. In addition, there are few data on the patterns of drug use of inhaled prophylactic asthma therapy or of the relation between compliance and symptom control. A study was undertaken to address these issues with the hypothesis that parental supervision would result in good compliance., Methods: The subjects were 29 asthmatic children aged 15 months to five years already established on inhaled prophylactic medication delivered through a large volume spacer. The prescribed drug regimens varied between subjects. This was an observational study using an electronic inhaler timer device to record the date and time of each actuation of the aerosol canister. Diary cards were used for parallel recording of symptoms and parentally reported compliance with a drug regimen., Results: Variable and generally poor compliance was demonstrated with a median of 50% of study days with full compliance (subject range 0-94%) and an overall median of 77% of prescribed doses of therapy taken during the study period. No relation was found between frequency of prescribed regimen and good compliance. Day care was associated with poorer compliance. No relation between good compliance and low symptom scores was found., Conclusion: Compliance with inhaled prophylactic therapy is poor in preschool children with asthma whose medication is administered under parental supervision.

Background: While there are reports on the outcome in adults and teenagers with cystic fibrosis of colonisation with Burkholderia (Pseudomonas) cepacia, there is little information in children., Methods: In December 1991 only one of 115 children with cystic fibrosis attending a paediatric centre was colonised with B cepacia. Over the next 12 months there was a rapid increase with 23 (20%) becoming colonised; eighteen (79%) of these became colonised in hospital at a time that overlapped with the admission of a B cepacia positive child. Three different bacteriocin types were isolated, with one type (S22/PO) being present in 17 (74%) patients. The outcome for children who became colonised with B cepacia was compared with that in 33 children who continued to be colonised with Pseudomonas aeruginosa alone., Results: Children colonised with B cepacia were older and more poorly nourished than those colonised with P aeruginosa, but did not have poorer pulmonary function. After colonisation, the forced expiratory volume in one second (FEV1) deteriorated between consecutive annual tests, with the average deterioration being greater in those with higher initial levels. Five children with B cepacia died from respiratory failure although none showed a fulminant deterioration. Introduction of segregation measures within hospital led to a dramatic decrease in the number of newly colonised patients., Conclusions: This study provides further evidence for person-to-person spread of B cepacia and confirms the effectiveness of simple isolation measures in interrupting spread. Colonisation with B cepacia and P aeruginosa in children is associated with a more rapid decline in lung function and a significantly increased mortality compared with cases colonised with P aeruginosa alone.

Objective: To investigate how parents use bronchodilator treatment for relief of symptoms when treating their asthmatic preschool children., Design: A commercial electromechanical timer device was attached to a large volume spacer to record the time and date of each use of inhaled bronchodilator over two months. The recorded time and dates were compared with symptoms noted in an asthma diary card., Setting: Large paediatric teaching hospital in Glasgow., Subjects: 29 preschool children with moderately severe asthma attending a specialist paediatric asthma clinic., Main Outcome Measures: Inhaler use measured by the timer device; symptoms and inhaler use recorded by parents in a daily asthma diary., Results: Satisfactory data were obtained in 22 of the 29 children; the median number of study days was 53 (range 18-77). Asthmatic symptoms were recorded on a median of 30 (3-77) days. Bronchodilator was used on a median of 19 (2-73) days, or on 63% (7-100%) of days when symptoms occurred. The median number of puffs used in a day was 1 (range 0-100) and was significantly related to symptom severity in only 14 of the 22 children. In only two of the 22 children was bronchodilator given more frequently than four hourly, and only five children ever used more than 12 puffs a day., Conclusions: The frequency of parental administration of bronchodilator treatment was variable and not closely related to the parent's record of symptom severity. Parents often recorded symptoms in their children but did not treat them.

With the increased use of oxygen consumption measurements in clinical and sporting studies, measurement variability has become more important to both the paediatric clinician and the sports scientist. In this study we assessed the reproducibility of cardiorespiratory measurements during submaximal and maximal running in children. Ten healthy, physically active boys (mean(s.d.) age 10.7(0.71) years) performed two submaximal and two maximal running tests within a 4 week period. The submaximal protocol consisted of three 6 minute runs at 7.2, 8.0 and 8.8 km/h. Every attempt was made to minimize the sources of non-biological variability at each testing session. During submaximal exercise, oxygen consumption (VO2), heart rate (HR) and fractional utilization appeared to be the most reliable measures accounting for over two-thirds of the total variation (coefficients of reliability (CR) of 68%, 94% and 82% respectively). Ventilation (Ve) and respiratory exchange ratio (RER) proved to be only moderately reliable accounting for less than half of the total variation (CR 50% and 45% respectively). At maximal exercise, VO2, Ve and time to exhaustion were most reliable, accounting for approximately two-thirds of the total variation (CR 65%, 63% and 63% respectively). Within this test environment, a two visit submaximal assessment was capable of estimating VO2 with a standard error of +/- 1.25 ml/kg/min. Similarly, for maximal testing a two visit assessment estimated peak VO2 with a standard error of +/- 2.28 ml/kg/min. On the evidence of these results a two visit assessment for submaximal and maximal exercise testing seems adequate to estimate the stability of submaximal cardiorespiratory measures and peak VO2 in healthy, normally active boys.

Using an electronic inhaler timer device (Nebulizer Chronolog), compliance with the prescribed frequency of inhaled prophylactic medication in 14 asthmatic children was measured. Underuse occurred in 55% of study days while overuse occurred in only 2%. Such devices provide an important new tool for investigating inhaled drug compliance.

The sensitivity and specificity of direct immunofluorescence microscopy performed on Pernasal swab specimens and compared with those of nasopharyngeal aspirates were 93 and 99%, respectively. Posterior nasopharyngeal swabs applied immediately to microscope slides allow a rapid and simple screening procedure for the diagnosis of acute respiratory syncytial virus infections.

During radionuclide scans in 82 infants and children gastro-oesophageal reflux extending to the upper oesophageal/laryngeal level was detected in 636 one minute frames. Only 61 (9.6%) of these frames were associated with vomiting, defined as the appearance of milk at the mouth. Thus the absence of vomiting does not preclude appreciable gastro-oesophageal reflux.

The association between gastro-oesophageal reflux and sleep state in 24 infants with confirmed or suspected gastro-oesophageal reflux was studied by monitoring both the pH in the lower oesophagus and polygraphic tracings made during sleep at night. Gastro-oesophageal reflux during the night was confirmed in 20 infants. Three hundred and sixteen precipitous drops of more than one unit of pH were recorded during the studies, 186 during periods of wakefulness. Of 130 drops in pH during sleep, 62 (48%) began during active sleep and 62 during indeterminate sleep. Of the latter, 56 (90%) were associated with brief gross body movements. Only five of the drops in pH (4%) began during quiet sleep. Gastro-oesophageal reflux stopped during active sleep on 56 occasions (43%), in indeterminate sleep in 62 (47%), and in quiet sleep in 12 (9%). Episodes of gastro-oesophageal reflux starting or ending in quiet sleep were uncommon. The occurrence of gastro-oesophageal reflux during active sleep may partly explain why reflux during sleep is a risk factor for pulmonary disease.