An innovative strategy for personalised medicine in a CFSPID case that evolved with time.

We present a challenging case that illustrates how the clinical manifestations in children with CFTR mutations of uncertain significance may change over time. This case highlights the evolution of confirming a diagnosis of CF and emphasises the importance of regular review and monitoring of this patient cohort.

Pre-operative respiratory assessment for children with spinal deformity.

Pre-operative respiratory assessment of children with spinal deformity requires an understanding of the deformity, the proposed surgery and most importantly the children themselves. The assessment and the tailoring of investigations will differ according to the age, developmental level and co-morbidities of the child. This review uses a mixture of evidence and case-based practice in order to set out a suggested framework for pre-operative spinal assessment, and suggested recommendations that may be provided to best support children undergoing surgery for spinal deformity.

Exercise testing in cystic fibrosis: Who and why?

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.

Clinical interpretation of cardiopulmonary exercise testing in cystic fibrosis and implications for exercise counselling.

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.

Respiratory Complications in Children with Prader Willi Syndrome.

Prader Willi syndrome, resulting from the partial deletion or lack of expression of a region of genes on the paternal chromosome 15, has a number of phenotypic features which predispose affected patients to ventilatory problems. These include generalised hypotonia, abnormal arousal and ventilatory responses to hypoxia and hypercapnia, scoliosis and frequently, obesity. The spectrum of the resulting respiratory complications thus runs from sleep disordered breathing, to aspiration and respiratory functional impairment. While the use of growth hormone, in conjunction with multidisciplinary clinical management, is currently the cornerstone of clinical care of these patients, concerns have been raised following reports of sudden death shortly after growth hormone initiation. This review summarizes the respiratory complications commonly seen and draws together the published literature on the impact of growth hormone in relation to various respiratory parameters, aiming to provide the reader with the necessary information to manage these patients as safely as possible.

Six-year follow-up study on the effect of combined anterior and posterior spinal fusion on lung function and quality of life in young people with adolescent idiopathic scoliosis.

OBJECTIVES: 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. DESIGN: Prospective cohort study. PATIENTS: Patients with AIS. SETTING: Tertiary paediatric respiratory centre and national spinal service. DESIGN: 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. RESULTS: 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 (p<0.01). Scoliosis corrected from 100 (15)° to 29 (11)° (p<0.001). 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 (p<0.001, 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. CONCLUSIONS: 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.

Central sleep-disordered breathing and the effects of oxygen therapy in infants with Prader-Willi syndrome.

OBJECTIVES: To describe breathing patterns in infants with Prader-Willi Syndrome (PWS), as well as the effects of supplemental oxygen (O2) 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 children's hospital. INTERVENTIONS: Infants with PWS underwent full polysomnography, and in those with frequent desaturations associated with central events, supplemental O2 during sleep was started and followed with regular split-night studies (periods in both air and O2). 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 (SpO2). O2 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 SpO2. 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 O2 therapy. Longitudinal work with this patient group would help to establish the timing of onset of obstructive symptoms.

Fewer colds, less asthma? A hypothesis to explain the fall in childhood asthma in the UK.

UK asthma prevalence fell significantly between 1993 and 2000. In children aged <5 years hospital admissions for asthma fell by 52% and primary care presentations in children under 14 years by over 40%. From 1994 to 2000, primary care consultations for acute respiratory infections in all age groups fell by 36%, and for the common cold by 46%. Isolates for respiratory syncytial virus notified to the Health Protection Agency voluntary reporting scheme fell by 56% between 1993 and 2003. Falls in UK birth rate and improvements in living conditions were reported by the Office of National Statistics over this time. The authors hypothesise that the fall in asthma reflects a fall in respiratory infections, the most important proximal trigger for asthma exacerbations, and that this in turn may be related to a fall in household members to a number too low for effective virus transmission. Future research into the prevalence of asthma must consider the effect of changing respiratory virus burden on populations.

Vitamin K prescribing patterns and bone health surveillance in UK children with cystic fibrosis.

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 <10% of their CF patients receive vitamin K, whilst vitamin K dosage varied from 0.3-0.5 to 10 mg day(-1). Only one centre undertook no bone health surveillance, and vitamin D levels are measured in 89%, calcium intake assessed in 82% and dual-energy X-ray absorptiometry scans performed in 61% centres. DISCUSSION: Heterogeneity in both vitamin K prescribing practices and bone health surveillance in CF across the UK were noted, underlining the need for a national consensus on bone health management, as well as acting as a call for longitudinal research into the clinical effectiveness of vitamin K therapy in CF.

Postmortem brain MRI with selective tissue biopsy as an adjunct to autopsy following neonatal encephalopathy.

Following the death of a neonate it is essential that parents are given full and accurate information about the probable cause of death. Perinatal autopsy often adds new information or may even change the presumed diagnosis [Cartlidge PH, Dawson AT, Stewart JH, Vujanic GM. Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths. Br Med J 1995;310(6973):155-8; Khong TY. Falling neonatal autopsy rates. Br Med J 2002;324(7340):749-50] informing decisions regarding the management of any future pregnancy. Autopsy can be considered the "gold standard" for the identification of antecedent events leading to a neonatal death. However, recent events in the UK have added to an already declining rate in neonatal autopsies [Brodlie M, Laing IA. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. Br Med J 2002;324(7340):761-3]. To try and redress this balance the Chief Medical Officer has recommended that research should be commissioned into the use of non-invasive imaging to provide a similar standard of information [The Chief Medical Officer. The removal, retention and use of human organs and tissues from post mortem examination. London, England: The Stationary Office, Department of Health; 2001]. Previous publications on postmortem MRI have focused largely on investigation of the foetus and of still birth [Griffiths PD, Variend D, Evans M, Jones A, Wilkinson ID, Paley MNJ, et al. Postmortem MR imaging of the fetal and stillborn central nervous system. Am J Neuroradiol 2003;24(1):22-7; Whitby EH, Paley MN, Cohen M, GriffithsPD. Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy? Semin Fetal Neonatal Med 2005;10(5):475-83]. We report our experience on the use of postmortem brain MRI combined with selective tissue biopsy, in six neonatal deaths in the setting of a large district general hospital.