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Sleep-related breathing disorders are a common problem in infancy and childhood. The most common type of sleep-related breathing disorder in this age group is obstructive sleep apnea syndrome (OSAS), generally caused by factors affecting airway patency, such as tonsillar hypertrophy or obesity. However, in adults OSAS can also be caused by processes affecting the brainstem, such as central nervous system tumors. This report describes a 2-year-old girl who presented with symptoms of snoring, restless sleep, repeated night-time waking, and apneic events while asleep. She had no comorbidities, and examination revealed normal-sized tonsils. A sleep study demonstrated severe OSAS with an obstructive apnea/hypopnea index of 34. Her OSAS completely resolved on excision of the tumor. The case highlights the importance of neurological examination as part of evaluation of OSAS, especially in cases where tonsils are not enlarged and there are no other risk factors for OSAS. CITATION: Buller F, Kamal MA, Brown SK, et al. Obstructive sleep apnea syndrome as a rare presentation in a young girl with a central nervous system tumor. J Clin Sleep Med. 2022;18(4):1211–1214.

The COVID-19 pandemic has resulted in unprecedent changes to clinical practice, and as the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the United Kingdom was unknown, this was characterised via a national survey.An electronic survey was distributed to healthcare professionals involved in the exercise management of CF via established professional networks.In total, 31 CF centres participated. Findings included significant reductions in exercise testing and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue using virtual methods of engaging patients in future practice.These findings highlight adaptation to the COVID-19 pandemic and the need to develop sustainable and standardised telehealth services to manage patients moving forwards.

ObjectiveThe impact on executive function performance of sleep-related disorders in asthmatic children has been scarcely studied in community settings. The aims of the present study were to assess the prevalence of sleep-related breathing disorders (SRBD) in children with intermittent or mild persistent asthma in primary care settings, and to examine the possible correlations with measures of executive function.MethodsWe performed a case–control study including 76 children with asthma (intermittent or mild persistent) and 85 healthy controls. The parents of both patients and controls completed the Paediatric Seep Questionnaire (PSQ) and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire.ResultsWe did not find any statistically significant differences regarding the scales of PSQ. Additionally, there were no statistical differences between asthmatic children and controls regarding the scales of the BRIEF questionnaire. In both asthmatic children and controls the score of the scale of obstructive sleep-related breathing disorder was significantly correlated with the T scores of the two composite scales (BRI and MI) and the Global Executive Composite.ConclusionIn children with intermittent or mild persistent asthma under the care of private general paediatricians there were no statistically significant differences regarding subjective SBD compared to the healthy controls. Also there were no statistical differences between asthmatic children and controls regarding behavioural correlates of executive function during everyday life.

Rationale: The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives: To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods: In a parallel arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged ≥12 years were randomly assigned (1:1 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, while the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted forced expiratory volume in 1s (ΔFEV1) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, and stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results: 117 patients (40% of target sample size) were randomized to an intervention (n=60) or control group (n=57). After 6 months, ΔFEV1 was significantly higher in the control group compared to the intervention group (2.70% predicted, 95% CI 0.13 to 5.26; p=0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions: ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV1 in the control group. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01744561.

Rationale: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. Objectives: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (VO 2 peak) following rigorous adjustment for other predictors. Methods: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. Measurements and Main Results: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that VO 2 peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. Conclusions: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.

BACKGROUND A 25-hydroxyvitamin D (25OHD) may exert immunomodulatory effects on respiratory health, which may translate to improvements in exercise physiology. Thus, we aimed to investigate whether plasma 25OHD is associated with lung function and aerobic fitness in people with cystic fibrosis (pwCF). METHODS A multicentre retrospective review of pwCF (> 9 years old) attending the Royal Hospital for Sick Children (Edinburgh) or Wessex CF-Unit (Southampton) was performed between July 2017 and October 2019. Demographic and clinical data were collected. Plasma 25OHD measured closest in time to clinical cardiopulmonary exercise testing and/or spirometry [forced expiratory volume (FEV1 )% predicted] was recorded. Pancreatic insufficiency was diagnosed based on faecal elastase of

BackgroundSevere disease directly associated with SARS-CoV-2 infection in children is rare. However, the indirect consequences of the COVID-19 pandemic on paediatric health have not been fully quantified. We examined paediatric health-care utilisation, incidence of severe disease, and mortality during the lockdown period in Scotland.MethodsThis national retrospective cohort study examined national data for emergency childhood primary and secondary care utilisation following national lockdown on March 23, 2020. To determine whether social distancing measures and caregiver behavioural changes were associated with delayed care-seeking and increased disease severity on presentation, unplanned, emergency admissions requiring invasive mechanical ventilation for the two national Paediatric Intensive Care Units (PICUs) were analysed. PICU admissions were grouped by diagnostic category, and disease severity on presentation calculated. National statutory death records were consulted to establish childhood mortality rates and causes of death. For all observations, the lockdown period was compared to equivalent dates in 2016-2019.FindingsWe identified 273,455 unscheduled primary care attendances; 462,437 emergency department attendances; 54,076 emergency hospital admissions; 413 PICU emergency admissions; and 415 deaths during the lockdown study period and equivalent dates in previous years. The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell, with an odds ratio of 0·52 for chance of admission during lockdown (95% CI 0·37-0·73, p < 0·001). Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared to 2016-2019.InterpretationNational lockdown led a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.FundingNoneResearch in contextEvidence before this studyData on the indirect effects of the COVID-19 pandemic on children at a population level are limited. We searched PubMed and medRxiv on October 13, 2020, for studies published from Jan 1, 2020 examining the indirect effects of non-pharmaceutical interventions (NPIs), and associated changes in caregiver health-care seeking behaviour, on the risk of severe paediatric disease and death. We used the search terms COVID-19, SARS-CoV-2, non-pharmaceutical interventions, indirect, and children, as well as manually searching references in other relevant papers. Terms were searched individually and in combination as necessary, with no language restrictions. We identified one study that modelled the indirect effects of the COVID-19 pandemic on child deaths in low- and middle-income countries. Other studies analysed in isolation the effects of NPIs and other behavioural changes on emergency department attendances, hospital admission rates, paediatric intensive care unit (PICU) admission rates, or the incidence of specific presentations, such as asthma exacerbations. Some case series described delayed care-seeking for children with non-SARS-CoV-2 disease. We did not identify any national studies examining the indirect effects of the COVID-19 pandemic on the incidence of severe paediatric disease and mortality.Added value of this studyThis national study quantified the changes following national lockdown in Scotland on March 23, 2020. We examined data for unscheduled primary care and emergency department attendances, emergency hospital admissions, emergency paediatric intensive care unit (PICU) admissions requiring invasive mechanical ventilation, and paediatric mortality. Rates were compared with previous years. We found a reduction in paediatric emergency care utilisation rates associated with national lockdown. This reduction is likely to be due to a combination of changes in health care seeking behavior, and a fall in overall burden of paediatric infectious disease. These measures did not appear to have been associated with evidence of severe harm to children in Scotland, as evidenced by severity scores on presentation to PICU or mortality.Implications of all the available evidenceThis is the first comprehensive population-based assessment at a national level of the indirect effects of the COVID-19 pandemic on severe paediatric morbidity and mortality. Despite a significant reduction in health-care utilisation rates, we did not find associated evidence of severe harm. This study will assist policy makers, health-care providers and the public in evaluating the effects of lockdown on the risk of severe paediatric disease at a population level.

Citation:Urquhart DS, Hill EA, Hill LE, et al. Adults with epilepsy appear to differ from children in regard to daytime sleepiness. J Clin Sleep Med. 2020;16(8):1393–1394.

The impact of lumacaftor/ivacaftor on exercise tolerance in people with cystic fibrosis (CF) has not been thoroughly studied.We conducted a multisite Phase 4 trial comparing the impact of lumacaftor/ivacaftor on exercise tolerance with that of placebo in participants ≥ 12 years of age with CF homozygous for F508del-CFTR. The primary endpoint was relative change from baseline in maximum oxygen consumption (VOSeventy participants were randomized to receive lumacaftor/ivacaftor (n = 34) or placebo (n = 36). The least-squares mean difference for lumacaftor/ivacaftor versus placebo in relative change in VODefinitive conclusions regarding the impact of lumacaftor/ivacaftor on exercise tolerance cannot be drawn from these results; however, multicenter studies using CPETs can be reliably performed with multiple time points and conventional methods, provided that calibration can be achieved. Future studies of exercise tolerance may benefit from lessons learned from this study. NCT02875366.

Annual review exercise testing is recommended by the Cystic Fibrosis (CF) Trust. Testing to date has focused on evaluating aerobic fitness, a key prognostic indicator. Tests available range from simple field tests, to comprehensive evaluations of aerobic exercise (dys)function – cardiopulmonary exercise testing (CPET).‘Field tests’, although easy to perform are limited in the information they provide. Whereas CPET, the ‘gold standard’ measure of aerobic fitness, is recommended as the first choice exercise test by the European CF Society Exercise Working Group. CPET offers a precise cardiovascular, respiratory and metabolic evaluation of exercise capacity, including assessment of mechanism(s) of exercise limitation.

BACKGROUND: Robin sequence (RS) is a congenital disorder characterized by cleft palate, micrognathia, and glossoptosis which can result in clinically significant upper airway obstruction (UAO). Historically, incidence of RS in the UK has been estimated as 1 in 8500 live births. Our study describes birth prevalence, clinical characteristics, and management of RS in the East of Scotland (EoS) region.METHODS: Retrospective case note review of infants born in EoS from 2004 to 2013 with a clinical diagnosis of RS. Cases were identified by searching the regional cleft service patient database and review of Hospital Activity Statistics data. Regional live birth rate provided the denominator for incidence calculations.RESULTS: A total of 105 cases of RS were identified, giving a birth prevalence of 1:2685 live births. No trends in annual incidence were observed over the 10-year period. Intrauterine exposure to potentially teratogenic agents was identified in 17% cases, including Methadone in 8% cases. Signs of UAO were present in 93% of infants, 63% of whom required active airway management. Nasopharyngeal airway (NPA) was the most commonly used intervention (53% cases), whilst only 7% required surgical management. Infants with an underlying syndrome or additional anomalies (RS+) were significantly more likely to be admitted to a tertiary center and require surgical airway or feeding support compared to those with isolated RS.CONCLUSIONS: RS incidence in EoS is substantially higher than that reported within other populations, and than previously reported in the UK. A possible association with intrauterine Methadone exposure warrants further investigation.

The measurement of exercise capacity in persons with cystic fibrosis by Cardiopulmonary Exercise Testing (CPET) offers a functional assessment of lung performance and efficiency in a dynamic setting. Exercise performance can measured against predicted values and the mechanism by which exercise limitation occurs can be identified. In healthy subjects, exercise is limited by cardiac output, such that a significant breathing reserve exists at the end of exercise. However, other mechanisms of exercise limitation which may be identified in CF subjects include ventilatory limitation, and/or limitation due to physical deconditioning. A detailed understanding of exercise capacity and the mechanism for exercise limitation may enable health professionals to tailor an individualised exercise programme for each CF patient.

A high proportion of children and adolescents who have "difficult" or therapy-resistant asthma, are found to have poor adherence to maintenance therapies. Such individuals are thus difficult asthmatics (for reasons of poor adherence) rather than being young people with true difficult asthma. In our centers, once daily ICS/ULABA (Relvar™) is considered if there is an increase in reported interval symptoms, asthma attacks requiring hospital attendance or rescue oral prednisolone, or persistently low lung function despite reported regular use of a twice daily ICS/LABA preparation. In the majority of these young people, a clinical history of overt non-adherence or a clinical suspicion of covert non-adherence will be noted.The aim of our retrospective cohort study was to assess the clinical effectiveness of Relvar™ in a selected adolescent asthma population.In a pre-selected group of adolescents with likely poor prior adherence to inhaled therapies, a change to Relvar™ (once daily combined ICS/ULABA) led to improvements in asthma control, as assessed by ED attendances and oral steroid burden.A prospective study to verify these findings and also explore the effects on quality of life, asthma control, and adherence is warranted.

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data. Funding was received from the European Respiratory Society, grant number TF-2016-12. The research of Jana De Brandt is financially supported by FWO (grant #11B4718N) and the research of Chris Burtin is partially sponsored by Limburg Kankerfonds. Funding information for this article has been deposited with the Crossref Funder Registry. Hebestreit, H (reprint author), Univ Kinderklin, ERN LUNG, Josef Schneider Str 2, D-97080 Wurzburg, Germany. hebestreit@uni-wuerzburg.de

Aim To estimate symptoms of obstructive sleep apnoea (OSA) and excessive daytime sleepiness (EDS) in children with epilepsy (CWE) compared with those in a typically developing comparison group. CWE are known to have poor sleep, with increased rates of OSA suggested. Method The Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (PSQ-SRBD) was used to estimate OSA symptoms, with scores ≤0.33 known to be highly sensitive and specific for OSA. The Epworth Sleepiness Scale (ESS) was used to assess EDS, with scores of 10 or above considered abnormal. Results Thirty-three CWE (21 males, 12 females) were studied (median age [interquartile range {IQR}] 9y [5–12]), along with 42 comparison children (20 males, 22 females; median age [IQR] 6y [4–8.5]). Fifty-five per cent of CWE scored 0.33 or higher on the PSQ-SRBD compared with 7% in the comparison group (p

Background The aim of this position statement was to inform the choice of physical activity tools for use within CF research and clinical settings. Methods A systematic review of physical activity tools to explore evidence for reliability, validity, and responsiveness. Narrative answers to "four key questions" on motion sensors, questionnaires and diaries were drafted by the core writing team and then discussed at the Exercise Working Group in ECFS Lisbon 2013. Results and summary Our current position is that activity monitors such as SenseWear or ActiGraph offer informed choices to facilitate a comprehensive assessment of physical activity, and should as a minimum report on dimensions of physical activity including energy expenditure, step count and time spent in different intensities and sedentary time. The DigiWalker pedometer offers an informed choice of a comparatively inexpensive method of obtaining some measurement of physical activity. The HAES represents an informed choice of questionnaire to assess physical activity. There is insufficient data to recommend the use of one diary over another. Future research should focus on providing additional evidence of clinimetric properties of these and new physical activity assessment tools, as well as further exploring the added value of physical activity assessment in CF.

Background Physical activity (PA) and exercise have become an accepted and valued component of cystic fibrosis (CF) care. Regular PA and exercise can positively impact pulmonary function, improve physical fitness, and enhance health-related quality of life (HRQoL). However, motivating people to be more active is challenging. Supervised exercise programs are expensive and labour intensive, and adherence falls off significantly once supervision ends. Unsupervised or partially supervised programs are less costly and more flexible, but compliance can be more problematic. The primary objective of this study is to evaluate the effects of a partially supervised exercise intervention along with regular motivation on forced expiratory volume in 1 s (FEV1) at 6 months in a large international group of CF patients. Secondary endpoints include patient reported HRQoL, as well as levels of anxiety and depression, and control of blood sugar. Methods/design It is planned that a total of 292 patients with CF 12 years and older with a FEV1 ≥ 35% predicted shall be randomised. Following baseline assessments (2 visits) patients are randomised into an intervention and a control group. Thereafter, they will be seen every 3 months for assessments in their centre for one year (4 follow-up visits). Along with individual counselling to increase vigorous PA by at least 3 h per week on each clinic visit, the intervention group documents daily PA and inactivity time and receives a step counter to record their progress within a web-based diary. They also receive monthly phone calls from the study staff during the first 6 months of the study. After 6 months, they continue with the step counter and web-based programme for a further 6 months. The control group receives standard care and keeps their PA level constant during the study period. Thereafter, they receive the intervention as well. Discussion This is the first large, international multi-centre study to investigate the effects of a PA intervention in CF with motivational feedback on several health outcomes using modern technology. Should this relatively simple programme prove successful, it will be made available on a wider scale internationally. Trial registration ClinicalTrials.gov Identifier: NCT01744561; Registration date: December 6, 2012.

Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (V.O2peak), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I–V. The final analysis included 726 patients (45% females; age range, 8–61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V.O2peak, 77.3 ± 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I–III and either V.O2peak (percent predicted) (adjusted β = −0.95; 95% CI, −4.18 to 2.29; P = 0.57) or maximum work rate (Wattmax) (adjusted β = −1.38; 95% CI, −5.04 to 2.27; P = 0.46) compared with classes IV–V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V.O2peak (β = −8.24%; 95% CI, −14.53 to −2.99; P = 0.003) and lower Wattmax (adjusted β = −7.59%; 95% CI, −14.21 to −0.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for relevant confounders, lung function and body mass index were associated with V.O2peak. CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.

Focus Group.To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand.Australia.A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion.A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities.This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

This statement summarizes the information available on specific exercise test protocols and outcome parameters used in patients with cystic fibrosis (CF) and provides expert consensus recommendations for protocol and performance of exercise tests and basic interpretation of results for clinicians. The conclusions were reached employing consensus meetings and a wide-band Delphi process. Although data on utility are currently limited, standardized exercise testing provides detailed information on physiological health, allows screening for exercise-related adverse reactions and enables exercise counselling. The Godfrey Cycle Ergometer Protocol with monitoring of oxygen saturation and ventilatory gas exchange is recommended for exercise testing in people 10 years and older. Cycle ergometry only with pulse oximetry using the Godfrey protocol or treadmill exercise with pulse oximetry - preferably with measurement of gas exchange - are second best options. Peak oxygen uptake, if assessed, and maximal work rate should be reported as the primary measure of exercise capacity. The final statement was reviewed by the European Cystic Fibrosis society and revised based on the comments received. The document was endorsed by the European Respiratory Society.

Background Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. We report efficacy and safety of lumacaftor and ivacaftor in patients with cystic fibrosis aged 6–11 years homozygous for F508del-CFTR. Methods In this phase 3, randomised, double-blind, placebo-controlled, multicentre study, patients were enrolled at 54 hospitals and medical centres in nine countries (the USA, Australia, Belgium, Canada, Denmark, France, Germany, Sweden, and the UK). Eligible patients weighed at least 15 kg, with a confirmed diagnosis of cystic fibrosis, percent predicted forced expiratory volume in 1 s (FEV 1) of 70 or more, and lung clearance index 2·5 (LCI 2·5) of 7·5 or more at screening (values less than these thresholds were permitted at day 1). All patients were tested for CFTR genotype at screening; eligible patients had to have the F508del-CFTR mutation on both alleles. Exclusion criteria included any comorbidity or laboratory abnormality that might confound the study results or pose additional risk to the patient. Patients were stratified by weight (

Congenital central hypoventilation syndrome (CCHS) is a rare disorder associated with dysregulation of the autonomic ventilatory response to hypoxia and hypercarbia usually caused by polyalanine repeat expansion mutations in the PHOX 2B gene. Non-polyalanine repeat mutations (NPARM) represent approximately 10% of cases, and usually require continuous ventilation during sleep, although our knowledge of disease progression is limited. Here we present a case with a novel NPARM CCHS mutation associated with a premature stop codon for the PHOX 2B protein. Despite the type of the mutation, patient management with supplementary oxygen has been sufficient. Experience from our case may help when counseling parents.

Summary Previous volunteer studies of an effect-site controlled patient-maintained sedation system using propofol have demonstrated a risk of oversedation. We have incorporated a reaction time monitor into the handset to add an individualised patient-feedback mechanism. This pilot study assessed if the reaction time-feedback modification would prove safe and effective in 20 healthy patients receiving sedation while undergoing oral surgery. All patients successfully sedated themselves without reaching any unsafe endpoints. All 20 maintained verbal contact throughout. The mean (SD) lowest peripheral blood oxygen saturation was 98.0 (2.1)% breathing room air. No patient required supplementary oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.6 (0.5) μg.ml−1. The present system was found to be safe and effective, allowing oral surgery treatment under conscious sedation, but preventing oversedation.

Objectives To describe breathing patterns in infants with Prader-Willi Syndrome (PWS), as well as the effects of supplemental oxygen (O 2 ) on breathing patterns. Children with PWS commonly have sleep-disordered breathing, including hypersomnolence and obstructive sleep apnoea, as well as central sleep breathing abnormalities that are present from infancy. Design Retrospective cohort study. Patients Infants with a diagnosis of PWS. Setting Tertiary children9s hospital. Interventions Infants with PWS underwent full polysomnography, and in those with frequent desaturations associated with central events, supplemental O 2 during sleep was started and followed with regular split-night studies (periods in both air and O 2 ). Results Thirty split-night studies on 10 infants (8 female) aged 0.06–1.79 (median 0.68, IQR 0.45, 1.07) years were undertaken. At baseline (ie, air), children with PWS had a median (IQR) central apnoea index (CAI) of 4.7 (1.9, 10.6) per hour, with accompanying falls in oxygen saturation (SpO 2 ). O 2 therapy led to statistically significant reductions in CAI to 2.5/hour (p=0.002), as well as a reduced central event index (CEI) and improved SpO 2 . No change in the number of obstructive events was noted. Central events were more prevalent in rapid-eye movement/active sleep. Conclusions It is concluded that infants with PWS may have central sleep-disordered breathing, which, in some children, may cause frequent desaturations. Improvements in CAI and CEI as well as oxygenation were noted with O 2 therapy. Longitudinal work with this patient group would help to establish the timing of onset of obstructive symptoms.

Contemporary Western society emphasizes thinness for women, and the ideal female body size has become progressively smaller over the past half century. Meanwhile, the actual female body size has increased steadily, and rates of aberrant attitudes and behaviours surrounding food and weight have risen and tend to be much more common in overweight individuals. Thus disordered eating and excess body weight may perpetuate each other's development. We have synthesized the literature concerning female body size and disordered eating within a sociocultural context. Eight cognitions and behaviours that occur in women were examined: media exposure, weight stereotypes, body dissatisfaction, dieting, "fat talk," emotional eating, perfectionism, and the "superwoman" ideal. The research literature suggests that these factors may play a role in both disordered eating and obesity. Furthermore, these factors may induce triggers, exacerbated by perfectionism and excess weight, that increase the risk of binge eating. These triggers include interpersonal discrepancies, low interpersonal esteem, depressive affect, and dietary restraint. Comprehensive interventions targeting the indicated sociocultural cognitions and behaviours, combined with healthy living education, may be the most effective strategy for reducing the prevalence of disordered eating and obesity among females.

Cystic fibrosis (CF) is a life{limiting, hereditary,multisystem disease predominantly affecting thelungs and pancreas. Over the last few years, sur-vival of CF patients has increased markedly. Thishas been attributed to earlier diagnosis, improvedpatient care delivered by multidisciplinary teamsand more effective therapeutic options. It has beensuggested that the pathophysiologic basis of CFlies in different gene mutations that encode abnor-malities in the structure of the cystic fibrosis trans-membrane conductance regulator (CFTR) protein,leading to physiologic defects in ion transport.

Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation.DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls.100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean +/- SEM rates of change of %predicted FEV(1)/year (0.9 +/- 2.3 (DD) vs. - 3.9 +/- 2.8 (DG), p = 0.22), %predicted FEV(1) (76 +/- 8 vs. 74 +/- 11), p = 0.91), or z scores for height ( - 0.47 +/- 0.26 vs. - 0.24 +/- 0.19, p = 0.48) and weight ( - 0.01 +/- 0.22 vs. - 0.29 +/- 0.27, p = 0.44). Median +/- SE survival age at first PA isolation was also not significantly different (3.5 +/- 2.1 vs. 6.5 +/- 2.4 years, p = 0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls.Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.

The effects of spinal surgery on lung function and quality of life (QoL) are important patient outcomes. Long-term follow-up of lung function and QoL in those undergoing combined anterior and posterior spinal fusion (A/PSF) for adolescent idiopathic scoliosis (AIS) is poorly documented with only one study extending beyond 2 years, though available evidence points to a decrement in lung function. Our study evaluated long-term change in lung function and QoL following A/PSF for AIS.Prospective cohort study.Patients with AIS.Tertiary paediatric respiratory centre and national spinal service.Spirometry was performed along with QoL (Scoliosis Research Society-22 (SRS-22) questionnaire). Paired t test and one-way analysis of variance were used to compare pre-A/PSF and post-A/PSF data.Data were available for 12 patients (9 female) who underwent A/PSF at mean 13.8 (range 11.8-15) years. Mean follow-up was undertaken 5.8 (range 4.1-6.8) years postoperatively. Height increased from mean (SD) 169 (9) cm preoperatively to 175 (5) cm at follow-up (p0.01). Scoliosis corrected from 100 (15)° to 29 (11)° (p0.001). Mean (SD) forced expiratory volume in 1 s was -3.4 (1.4) z scores preoperatively versus -3.3 (1) z scores postoperatively (p=0.85); and forced vital capacity was -3.4 (1.7) ) z scores pre-A/PSF and -3.4 (1.1) z scores post-A/PSF (p=0.83). SRS-22 scores improved mean (SD) of 3.6 (0.3) preoperatively to 4.2 (0.3) at 2 years postoperatively, and 4.4 (0.4) at 6 year follow-up (p0.001, analysis of variance). High patient satisfaction rates (4.8 (0.3)) were recorded. No correlation was noted between changes in forced expiratory volume in 1 s (r=-0.15, p=0.63) or forced vital capacity (r=-0.12, p=0.71) and change in long-term SRS-22 score.Long-term follow-up of patients with AIS suggests no deficit in pulmonary function, while QoL shows incremental improvement and patient satisfaction is high over 6 years after A/PSF.

Introduction Death in childhood from cystic fibrosis (CF) is now an uncommon event in the UK. We wished to assess the circumstances surrounding deaths (and lung transplantation) in the modern era of CF care. Methods A retrospective review was carried out pooling data from two large paediatric specialist CF units in London for the 10-year period 2000–2009 inclusive. Results There were 11 deaths and eight children who had a lung transplant out of 1022 children cared for in this period. Median age of death was 14.2 years and transplant 13.0 years, with a female preponderance (82% deaths and 75% transplants). Apart from one child (forced expiratory volume in 1 s (FEV 1 ) 69%), lung function indicated severe lung disease (median FEV 1 33%, range 12%–69%). Values 5 years prior to death were not predictive (median FEV 1 62%, range 32%–96%), and those 1 year prior were similar to the last recorded levels. Almost all (10/11) died in hospital and 5/11 (45%) were ventilated. Respiratory failure was the commonest mode of death (64%). Only four children (36%) were receiving palliative care, and in six cases (55%) care was withdrawn. Conclusions The number of deaths in children with CF was small but often unpredictable, so active management was continued until late in the majority, reflected by the fact that almost all were in hospital, and more than half were ventilated. If death from respiratory failure is anticipated following a steady decline, palliative care should be instituted well in advance, with attention to appropriate end of life care.

Exercise in CF is associated with improvements in physical and psychological wellbeing. Exercise testing may have an important role in assessing exercise ability and tailoring patient-specific exercise programmes, and exercise-related outcome measures may prove very useful for research intervention studies. Exercise capacity is of known prognostic importance in both adults and children with CF, and the degree of mutual exclusivity that separates fitness from lung function suggests that exercise testing is a vital diagnostic tool for identifying patients at risk of decline. The question of why exercise test in CF seems self-evident, but how to test is less clear-cut. A variety of field tests exist that are low-cost tests requiring minimal equipment. These act as surrogate tests of exercise capacity and can be submaximal in some cases. The gold standard test is CPET, a maximal test that provides precise exercise data. CPET is, however costly, needs highly specialized equipment and also requires technical expertise to supervise and interpret the test. The choice of test depends upon the question one is trying to answer. The chosen exercise test should be one that allows maximal exercise to be achieved, and may also be influenced by equipment and expertise that is held locally. Research outcomes may need the precision of CPET, whereas if one is looking for year on year within patient comparison, selection of a field test or incremental treadmill or ergometer test without metabolic measures may be appropriate. A desire for precise and reproducible data on exercise capacity in CF, however, may demand CPET as the test of choice of the future.

Deficiencies of the interferon γ (IFN-γ) pathway have become a well-recognized cause of nontuberculous mycobacterial infection. We report here a case of autosomal dominant IFN-γ receptor 1 (IFN-γ-R1) deficiency presenting at the unusually young age of 16 months with a severe clinical course. Mycobacterium avium complex was cultured from bronchial washings of a child who presented with primary endobronchial disease after a 4-month history of rhinorrhea, wheeze, and acute lobar consolidation. A maternal history of multifocal Mycobacterium kansasii osteomyelitis and cutaneous M avium complex led to genetic confirmation of IFN-γ-R1 818del4 deletion (a 4 base pair deletion at nucleotide position 818) in both family members. This case demonstrates the link between mycobacterial disease and IFN-γ pathway deficiency, the diagnosis of which facilitates more accurate therapy and genetic counseling. The case also raises questions about the reported distinct presentation, treatment, and prognosis of autosomal dominant and recessive IFN-γ-R1 phenotypes.

Non-invasive positive pressure ventilation (NIPPV) for respiratory failure in cystic fibrosis (CF) is frequently used in adults and has been shown to be of benefit to patients with advanced disease in terms of stabilisation of lung function,1 reduction in symptoms and increased exercise capacity.2 When used as an adjunct to physiotherapy, NIPPV increases oxygen saturations (Spo2), tidal volume, maximum expiratory muscle strength and ease of sputum clearance.3 4 There are no guidelines for the assessment of gas exchange or timing and mode of NIPPV initiation in patients with CF. The British Thoracic Society guideline states ‘there is insufficient evidence to recommend its routine use in patients with CF’.5 The aim of this study was to establish current …

A 5-month-old infant of Zimbabwean origin presented with cough, fever, night sweats and decreased appetite of 2 weeks’ duration. The Mantoux test was positive (8 mm) and early morning gastric aspirates grew fully sensitive Mycobacterium tuberculosis . Chest x ray showed right upper and middle lobe collapse with consolidation. The family had been living …

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Background Bone disease has become an increasingly recognized complication of cystic fibrosis (CF). Although causes of CF bone disease are multifactorial, there has been recent interest in the role of vitamin K in CF bone disease. Aims and methods A questionnaire survey of all UK paediatric CF centre dietitians and centre directors was carried out to ascertain current practice with regard to vitamin K prescribing and bone health surveillance. Results The survey had a 97% response rate representing 3414 CF children. Twenty-three centre directors and 19 dietitians responded, and at least moderate agreement was noted with kappa scores >0.41 for all but one question assessed. Ninety-three per cent centres report that >90% pancreatic insufficient patients receive vitamins A, D and E, yet only 18% centres routinely supplement vitamin K. The majority (60%) report that

Olfactory ensheathing cells transplanted into the injured spinal cord in animals promote regeneration and remyelination of descending motor pathways through the site of injury and the return of motor functions. In a single-blind, Phase I clinical trial, we aimed to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. Participants were three male paraplegics, 18-55 years of age, with stable, complete thoracic injuries 6-32 months previously, with stable spinal column, no implanted prostheses, and no syrinx. Olfactory ensheathing cells were grown and purified in vitro from nasal biopsies and injected into the region of damaged spinal cord. The trial design includes a matched injury group as a control for the assessors, who are blind to treatment status. Assessments, made before transplantation and at regular intervals subsequently, include MRI, medical, neurological and psychosocial assessments, and standard American Spinal Injury Association and Functional Independence Measure assessments. One year after cell implantation, there were no medical, surgical or other complications to indicate that the procedure is unsafe. There is no evidence of spinal cord damage nor of cyst, syrinx or tumour formation. There was no neuropathic pain reported by the participants, no change in psychosocial status and no evidence of deterioration in neurological status. Participants will be followed for 3 years to confirm long-term safety and to compare neurological, functional and psychosocial outcomes with the control group. We conclude transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to one year post-implantation.

It has been our observation that large nursing style stethoscopes are often used on extremely premature infants, whereas paradoxically a smaller neonatal stethoscope is usually used for the term neonate. Stethoscope heads were weighed using precision scales, and a ratio of stethoscope …

A 25 week gestation infant aged 30 days has a continuous murmur and easily palpable pulses. He has already received a course of indomethacin for a “clinically diagnosed” patent ductus arteriosus (PDA). The baby is ventilator dependent. How good (or bad) is clinical examination at diagnosing a clinically important PDA? In a ventilator dependent neonate of very low birth weight (

A 1993 survey1 found that, on average, only 2 h was devoted to undergraduate teaching of sleep medicine and that 7% of medical schools undertook no sleep medicine teaching whatsoever. Since the time of publication of this survey, numerous articles have highlighted the effects of sleep-disordered breathing on human disease as well as child development. Examples include the reporting of obstructive sleep apnoea (OSA) as an independent risk factor for adult hypertension2 3 as …

A 13 week old boy presented to accident and emergency with fever, breathing difficulties, and reduced feeding. On examination, his respiratory rate was 60 breaths/min, pulse was 180 beats/min, oxygen saturation was 91% in air, and temperature was 37.8oC. He had intercostal and subcostal recession and a tracheal tug. Auscultation of the chest showed widespread wheeze and crackles and heart sounds were normal. A chest radiograph showed an obscured right heart border and generalised hyperinflation. Blood tests showed a white cell count of 22.0×109/l, and a nasopharyngeal aspirate was positive for respiratory syncytial virus on polymerase chain reaction testing. The boy was born at term by normal delivery with a birth weight of 4100 g. The antenatal course was uneventful. He was kept in hospital for two days after delivery because he was “mucousy.” His parents described him as a noisy and “snuffly” breather since birth, with frequent coughing and “choking” episodes. Because of this he had been seen by his general practitioner and in casualty several times, but he had not been admitted to hospital before. He had been breast fed and was thriving well. A few hours after admission he suddenly deteriorated after a feed. His pulse rose to 230 beats/min and respiratory rate to 80 breaths/min. Capillary gas showed pH 7.03, partial pressure of carbon dioxide 12.18 kPa, bicarbonate 17 mmol/l, and base excess −7.4. He was admitted to paediatric intensive care and was intubated and ventilated. He remained intubated for 10 days and two attempts to extubate failed because he developed stridor. Once extubated successfully, we performed further investigations to check for any underlying abnormality. The following radiological image was obtained (fig 1⇓).

A previously well, fully immunised 2 year old boy presented to his general practitioner with a five day history of cough and fever. He was initially prescribed oral amoxicillin, which did not improve his condition. On examination, the patient was febrile, tachycardic, and tachypnoeic; he was also in respiratory distress and had markedly reduced air entry on the right side of the chest with stony dullness on percussion. Cardiovascular and abdominal examinations were unremarkable. Inflammatory markers were raised (white cell count 28×109/l−1 and C reactive protein 340 mg/l−1). A chest radiograph was taken (fig 1).⇓ Chest radiograph (posteroanterior view) ### Short answers

A 4 year old boy presented with a history of recurrent wheeze and chest infections over the previous two years, which had caused him to be admitted to hospital many times. Previous chest radiographs had shown right middle and lower lobe changes. The episodes had been treated with antibiotics with limited effect. Treatment for asthma (a bronchodilator and steroid inhalers) also failed to improve the situation. He was admitted for a 24 hour investigation, a 20 hour epoch of which is displayed below (figure)⇓. Twenty hour trace ### Short answers View this table: Details of episodes of reflux

A previously well 20 month old girl presented to the emergency department with a history of fever and tachypnoea. She was accompanied by non-English speaking grandparents, and the available history was limited. She was tachycardic on arrival, with a heart rate of 168 beats a minute, as well as a raised respiratory rate of 52 breaths a minute. Widespread wheeze was audible, and she was given back to back bronchodilator therapy via a nebuliser. She remained tachypnoeic (respiratory rate 38 breaths a minute), with increased air entry on the right side compared with the left. She was, however, free of wheeze. In view of the differential air entry, we undertook chest radiography (fig 1⇓). Fig 1 Chest radiograph of 20 month old girl with respiratory distress ### Short answers Fig 2 Chest radiograph of 20 …

An 11 month old girl presented to the paediatric department with a lower respiratory tract infection. She also had failure to thrive and mild motor developmental delay. On examination, she had swollen wrists bilaterally. A radiograph of her right arm is shown below (fig 1)⇓. Her blood results were urea 4.3 mmol/l, creatinine 29 μmol/l, corrected calcium 2.47 mmol/l, alkaline phosphatase 3340 U/l, and phosphate 1.88 mmol/l. Fig 1 Wrist radiograph of an 11 month old girl with bilateral wrist swelling Fig 2 Wrist radiograph showing splaying, cupping, and widespread demineralisation Fig 3 Chest radiograph showing prominent costochondral joints (rachitic rosary)

A 4 year old boy with Down’s syndrome has a long history of sleep disturbance. He snores at night, his sleep is very restless, and he sleeps for long periods during the day while at nursery. He was admitted for an overnight sleep study, a six hour epoch of which is displayed below (fig 1)⇓. A treatment intervention improved sleep quality. Fig 1 Overnight sleep study showing transcutaneous carbon dioxide (CO2), oxygen saturation (SaO2), and heart recordings ### Short answers Fig 2 Overnight sleep study showing abnormalities in transcutaneous carbon dioxide (CO2), oxygen saturation (SaO2), and heart recordings

A 2-year-old child became cyanosed and apnoeic while having a febrile convulsion. The child’s mother, who had previously undertaken Basic Life Support (BLS) training, noticed the bluish discolouration of the child’s lips. She was concerned that this had …