Very low birth weight survivors have reduced peak bone mass and reduced insulin sensitivity.

CONTEXT: Increasing numbers of very low birth weight (VLBW) infants are surviving into adulthood because of improvements in neonatal intensive care. Adverse events in early life can have long-term effects through reprogramming of metabolic systems. OBJECTIVE: To determine whether young adult VLBW survivors have abnormalities of skeletal development or endocrine function. DESIGN: Cross-sectional, observational, case-control study. PARTICIPANTS: Thirty-seven VLBW subjects and 27 healthy controls at peak bone mass (mean age 23). MEASUREMENTS: Differences between cases and controls in body size, body composition, bone mass and bone geometry [assessed by dual-energy X-ray absorptiometry (DXA), hip structure analysis and peripheral quantitative computed tomography (pQCT)], bone turnover [urine N-terminal telopeptide of type I collagen (NTX), serum C-terminal telopeptide of type I collagen (CTX)], aminoterminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase), hormones (sex steroids, IGF-1, PTH and 25-OH vitamin D) and insulin sensitivity (HOMA-IR and oral glucose tolerance testing). RESULTS: VLBW subjects had lower bone density at the lumbar spine (5.7%) and femoral neck (8.6%), which persisted after correction for bone size by the estimation of volumetric density (bone mineral apparent density). Urine NTX was higher in VLBW subjects than in controls, but there were no significant differences in other bone turnover markers. VLBW survivors had lower insulin sensitivity (mean INS-30 controls = 57.0, VLBW subjects = 94.3, P < 0.01), but there were no differences in whole body fat mass or truncal fat mass between VLBW subjects and controls. CONCLUSIONS: Young adult VLBW survivors have reduced bone density for their bone size and reduced insulin sensitivity, which may have significant implications for their risk of fracture and diabetes in later life.

Use of home oxygen for children in England and Wales.

BACKGROUND: With the introduction of a standardised ordering system in February 2006, the opportunity arose to collect data on children requiring home oxygen in England and Wales. The authors' aim was to determine the incidence and patterns of home oxygen prescribing. METHODS: A paediatric home oxygen clinical network and the Children's Home Oxygen Record Database were established. During a 3-year period (February 2006 to January 2009), prescribers were requested to submit copies of the Home Oxygen Order Forms. In addition, anonymised point prevalence data on all patients currently receiving home oxygen in June 2007 were obtained from the four provider companies. RESULTS: Children's Home Oxygen Record Database--Forms were analysed for 888 children <16 years (58% boys) with a median age of 4.1 months; 656 (74%) were <1 year. 541 (68%) had a diagnosis of chronic neonatal lung disease; 53 (7%), neurodisability; and 49 (6%), cardiac disease. Order forms were often incomplete, and prescribing practice was variable. Provider's cross-sectional survey--There were 3338 children <16 years, representing 4% of all patients on home oxygen. Median age was 3.1 years with a peak at 6 months. The prevalence for paediatric home oxygen use in England and Wales was 0.33 per 1000, with a peak of 1.08 per 1000 for those <1 year. Marked regional variation was noted. CONCLUSIONS: This is the first national dataset available for children prescribed home oxygen in England and Wales. The study emphasises the need for a coordinated approach to home oxygen prescribing and justifies the recent publication of evidence-based guidelines.

Tonsillectomy and adenoidectomy in children with sleep-related breathing disorders: consensus statement of a UK multidisciplinary working party.

During 2008, ENT-UK received a number of professional enquiries from colleagues about the management of children with upper airway obstruction and uncomplicated obstructive sleep apnoea (OSA). These children with sleep-related breathing disorders (SRBDs) are usually referred to paediatricians and ENT surgeons. In some district general hospitals, (DGHs) where paediatric intensive care (PICU) facilities to ventilate children were not available, paediatrician and anaesthetist colleagues were expressing concern about children with a clinical diagnosis of OSA having routine tonsillectomy, with or without adenoidectomy. As BAPO President, I was asked by the ENT-UK President, Professor Richard Ramsden, to investigate the issues and rapidly develop a working consensus statement to support safe but local treatment of these children. The Royal Colleges of Anaesthetists and Paediatrics and Child Health and the Association of Paediatric Anaesthetists nominated expert members from both secondary and tertiary care to contribute and develop a consensus statement based on the limited evidence base available. Our terms of reference were to produce a statement that was brief, with a limited number of references, to inform decision-making at the present time. With patient safety as the first priority, the working party wished to support practice that facilitated referral to a tertiary centre of those children who could be expected, on clinical assessment alone, potentially to require PICU facilities. In contrast, the majority of children who could be safely managed in a secondary care setting should be managed closer to home in a DGH. BAPO, ENT-UK, APA, RCS-CSF and RCoA have endorsed the consensus statement; the RCPCH has no mechanism for endorsing consensus statements, but the RCPCH Clinical Effectiveness Committee reviewed the statement, concluding it was a 'concise, accurate and helpful document'. The consensus statement is an interim working tool, based on level-five evidence. It is intended as the starting point to catalyze further development towards a fully structured, evidence-based guideline; to this end, feedback and comment are welcomed. This and the constructive feedback from APA and RCPCH will be incorporated into a future guideline proposal.

Interrupter technique and pressure oscillation analysis during bronchoconstriction in children.

The use of interrupter resistance (R(int)) is a feasible method of measuring bronchodilator responsiveness and bronchial hyperresponsiveness in preschool children. It has been suggested that analysis of recorded oscillations of the mouth pressure may provide additional indices of changes in airway mechanics. The aim of our study was to determine whether amplitude or damping properties of oscillations were more sensitive than R(int) in describing changes during bronchoconstriction. Data from 44 children (24 boys) who completed tripling dose methacholine (Mch) challenge were analysed. The median (range) age of children was 4.9 (3.1-6.1 years). In addition to baseline and maximal R(int) after Mch [mean (SD) were 0.92 (0.19) and 1.44 (0.35) kPa l(-1) s, respectively], obtained from a commercial device we analysed the following parameters: difference between the first maximum and minimum (A(MxMn)), maximum instantaneous amplitude (A(inst)), amplitudes of fitted mathematical model and the dominant frequency, sum of frequency component amplitudes, two damping factors and frequency. All amplitude parameters changed significantly after Mch. For comparison of the decrease in amplitudes and increase in R(int) we additionally used reciprocals of amplitudes. Using the sensitivity index (SI) i.e. the change after intervention divided by the baseline SD, 1/A(inst) and 1/A(MxMn) were the most sensitive indices to describe the change (with median SI of 6.29 and 6.28, respectively). R(int) had a median SI of 5.13. Frequency and damping factors were less sensitive, with median SI values <1. These findings suggest that oscillation amplitude analysis implemented in the software of commercial devices could have further applications in assessing respiratory mechanics.

Methacholine challenge in pre-school children--which outcome measure?

The aim of our study was to evaluate the utility of interrupter resistance (R(int)), transcutaneous oximetry and auscultation as outcome measures for a recently suggested tripling-dose methacholine (Mch) challenge in pre-school children. We studied 57 children aged 3-6 years. R(int) was measured at baseline and after each Mch dose. Oxygen saturation (SaO(2)) and transcutaneous oxygen pressure (tcpO(2)) were monitored during the challenge. Mch concentrations of 0.22, 0.66, 2.0, 6.0 and 18.0 mg/ml were nebulised during tidal breathing. The challenge was terminated if there was wheeze, SaO(2) below 91% or persistent cough; this final Mch dose was considered as PCW. Nine healthy children, 17 with cough and 25 with wheeze performed the study up to the point of PCW or all five Mch inhalations. If a change of 20% of predicted R(int) or termination by wheeze, desaturation or cough is taken as a completed test, then 39 out of 51 children (78%) had adequate R(int) measurements on each occasions from start to completion. The success rate for tcpO(2) measurements was similar: 38 out of 51 (76%) had complete tcpO(2) data until a 15% fall of tcpO(2) or clinical endpoint was reached. Using the above-mentioned cut-off levels significant change in R(int) or tcpO(2) preceded PCW in most of the cases. Both R(int) and tcpO(2) measurements may allow detection of bronchial hyper-responsiveness at lower Mch doses and also provide a less subjective measure, but will not be feasible in all children.

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: { or } and , limited to and limited to or . We searched MEDLINE (1966 - 1998), EMBASE (1974 - 1998) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006). In addition, we hand searched several abstract books of national and international American and European Societies. The search of MEDLINE and of CENTRAL was last updated in March 2006. SELECTION CRITERIA: For the purpose of this analysis, we included trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included need for ventilator support, chronic lung disease, mortality and other important clinical outcomes. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: We identified eight studies that met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. AUTHORS' CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence.More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g., washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Asthma severity and atopy: how clear is the relationship?

BACKGROUND: The relationship between asthma severity and atopy is complex. Many studies have failed to show significant relationships between clinical severity or lung function and markers of atopic sensitisation. AIM: To determine whether increasing asthma severity is related to atopic sensitisation in a population of children with asthma. METHODS: A total of 400 children (7-18 years) with asthma were recruited as part of a multicentre study of the genetics of asthma. Detailed phenotypic data were collected on all participants. Associations between measures of asthma severity and atopic sensitisation were sought using multilevel models allowing variation at the individual and family level. RESULTS: Children recruited to the study had a range of asthma severities, with just over a third having mild persistent asthma. The logarithm of total serum IgE was associated with increased asthma severity score, decreased FEV1, increased airways obstruction, risk of hospital admission, and inhaled steroid use. Increasing skin prick test reactivity to a panel of seven aeroallergens was associated with increased risk of hospital admission, use of an inhaled steroid, and airways obstruction. The results remained highly significant after corrections for age, gender, and birth order. CONCLUSIONS: In children with asthma, increasing atopy is associated with increasing asthma severity. However, the relationships between asthma severity and skin prick tests, and asthma severity and total serum IgE values, appear subtly different.

Feasibility of shortened methacholine challenge in preschool children.

The aim of our study was to assess the feasibility and safety of a recently suggested tripling-dose methacholine (Mch) challenge in preschool children. Fifty-seven children aged 3-6 years were studied. Mch challenge was carried out using a tidal breathing method, with concentrations of 0.22, 0.66, 2.0, 6.0, and 18.0 mg/ml, at 5-min intervals, given by a Pari Turbo Boy compressor and Pari LC Plus nebulizer, for 1 min only. Oxygen saturation (SaO(2)) was monitored during the challenge. The challenge was terminated if there was wheeze, SaO(2) below 91%, or persistent cough. This final Mch dose was considered the provocative concentration inducing audible wheeze (PCW). Nine healthy children, 17 with cough and 25 with wheeze, completed the study. Mean output from nebulizers (SD) in these 51 children was 0.30 (0.05) ml/min. Geometric means for PCW in these groups were 2.88, 2.58, and 1.28 mg/ml Mch, respectively. The wheezing children were significantly more hyperresponsive than the coughing children (P < 0.05). A tripling-dose Mch protocol is safe and practicable in children over 3 years of age. A further reduction in nebulized dose may be needed for a more discriminatory test.

Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families.

RATIONALE: Previous data have suggested that glutathione-S-transferase (GST) genotypes are important in determining the rate of lung function growth in childhood. This effect was most marked in Caucasian children with asthma. OBJECTIVES: We investigated the association of lung function with GSTM1, GSTP1 and GSTT1 genotypes in Caucasian families with asthma. METHODS: Four hundred and eighteen children and 316 parents from 224 Caucasian families were recruited via a child with asthma, the proband. Associations between lung function and GST genotype were determined using multilevel models. RESULTS: There were no observed associations between lung function and GST genotype in parents. However, in the children, the GSTP1 val(105)/val(105) and GSTM1 null genotypes were associated with significantly higher forced expiratory volume in 1 s (FEV(1)) and FVC values as percentage of predicted. This effect was not statistically significant in the probands but was marked in their siblings in whom GSTP1 val(105)/val(105) was associated with 9.4% higher FEV(1) and 10.7% higher FVC (P=0.005 and 0.001, respectively). The GSTM1 null genotype was associated with a 6.7% higher FEV(1) and 4.1% higher FVC (P=0.003 and 0.063, respectively). These effects remained significant after correcting for the confounders of individual atopic status, tobacco smoke exposure and familial aggregation of lung function values. CONCLUSIONS: GSTM1 and GSTP1 genotypes are important determinants of lung function in childhood. The smaller differences seen in probands are predicted by a simple model in which more rapid decline in lung function is seen in these individuals.

Regional variation of airway hyperresponsiveness in children with asthma.

Families with asthmatic children were recruited to take part in a multi-centre collaborative study into the genetics of asthma. Detailed phenotypic information was collected on all family members including: lung function, anthropomorphic measurements, response to methacholine challenge, skin prick testing, serum IgE measurements and a detailed nurse-administered questionnaire. Families were eligible for entry into the study if they had two children with a doctor-diagnosis of asthma. Bennett/Twin nebulisers were supplied to each centre from a single source and these were calibrated to determine gravimetric nebuliser output prior to use. Asthmatic probands from each centre had similar degrees of asthma severity and atopy. There was no significant difference in the sex ratios or ages of the probands or numbers of parents with a history of smoking in the families recruited at each centre. However, there was a significant difference in the number of children with airway hyperresponsiveness, with 90% of the North Staffordshire group but only 60% of the Sheffield group having a PC20 of <8 mg/ml for methacholine. This difference highlights the difficulty of using families from different centres in genetic and epidemiological studies.

Home oxygen for children: who, how and when?

A review of the specific requirements of home oxygen therapy in children which attempts to offer guidance to clinicians and service providers.

Discharge and aftercare in chronic lung disease of the newborn.

This article deals with the discharge planning and continuing care of babies with chronic lung disease of the newborn (CLD), especially those with a continuing oxygen requirement, with some reference to longer term outcome. The pattern of CLD has changed since early descriptions, and the most useful definition for persisting morbidity in a baby with lung disease is a continuing oxygen requirement beyond 36 weeks post-menstrual age. Long-term oxygen therapy to maintain oxygen saturation at a mean of 95% or more and prevent levels below 90% is the cornerstone of management, and with adequate oxygen therapy the excess mortality previously reported in CLD can largely be avoided. Care must be given to the method of assessing oxygen saturation: overnight monitoring using appropriate recording devices is recommended. Exposure to respiratory viruses should be minimized where possible. Metabolic requirements are increased, but if efforts are made to maintain adequate energy input the long-term outlook for catch-up growth in height is good. Respiratory morbidity is increased in early life, but this improves in later childhood, along with lung function and exercise tolerance. Although respiratory symptoms should be treated as they arise, there is no evidence for long-term benefit from any pharmacological intervention in CLD.

Neonatal lungs: maturational changes in lung resistivity spectra.

The electrical resistivity of lung tissue can be related to the structure and composition of the tissue and also to the air content. Electrical impedance tomographic measurements have been used on 155 normal children over the first three years of life and 25 pre-term infants, to determine the absolute resistivity of lung tissue as a function of frequency. The results show consistent changes with increasing age in both lung tissue resistivity (5.8 ohm m at birth to 20.9 ohm m at 3 years of age) and in the changes of resistivity with frequency (Cole parameter ratio R/S=0.41 at birth and 0.84 at 3 years of age). Comparison with a lung model showed that the measurements are consistent with maturational changes in the number and size of alveoli, the extracapillary blood volume and the size of the extracapillary vessels. However, the results show that the process of maturation is not complete at the age of three years.

Neonatal lungs--can absolute lung resistivity be determined non-invasively?

The electrical resistivity of lung tissue can be related to the structure and composition of the tissue and also to the air content. Conditions such as pulmonary oedema and emphysema have been shown to change lung resistivity. However, direct access to the lungs to enable resistivity to be measured is very difficult. We have developed a new method of using electrical impedance tomographic (EIT) measurements on a group of 142 normal neonates to determine the absolute resistivity of lung tissue. The methodology involves comparing the measured EIT data with that from a finite difference model of the thorax in which lung tissue resistivity can be changed. A mean value of 5.7 +/- 1.7 omega(m) was found over the frequency range 4 kHz to 813 kHz. This value is lower than that usually given for adult lung tissue but consistent with the literature on the composition of the neonatal lung and with structural modelling.