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A case is reported describing a complication of an unsuccessful attempt to aspirate the reservoir of a ventriculoperitoneal shunt system with a suspected shunt infection. This arose due to a misunderstanding of the anatomy of the shunt and resulted in an intracerebral haematoma. The complications of cerebrospinal fluid shunting and the difficulty in the diagnosis thereof are outlined. We discuss the role and method of shunt tapping in diagnosing shunt problems before reviewing the literature describing the rationale. The variation in shunt design is emphasized. Guidelines are then proposed not to dissuade physicians from tapping shunts but to ensure that the procedure is performed safely and in collaboration with neurosurgical units.

The open-circuit multiple-breath inert gas washout method is used to measure functional residual capacity and also to quantify ventilation distribution. The technique is readily applicable in preschool children as it requires quiet tidal breathing. Guidelines for data collection and interpretation in this age group will shortly be published by the European Respiratory Society and the American Thoracic Society.

RATIONALE: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants.\ud \ud OBJECTIVE: To assess changes in pulmonary function during the first year of life in CF NBS infants.\ud \ud METHODS: Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV₀.₅) were measured at 3 months and 1 year of age.\ud \ud MAIN RESULTS: Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV₀.₅ improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p

Interstitial lung disease (ILD) in infants is rare. Clinical and radiological features are often non-specific, and overlap with growth disorders and infection. In infants with severe respiratory compromise, lung biopsy is often necessary to guide acute management, but the risk and diagnostic yield of this procedure is incompletely understood.To retrospectively review infants undergoing open lung biopsy for suspected ILD at a large referral center; to determine morbidity and mortality related to the procedure; and to describe subsequent diagnosis and outcome.Lung biopsies performed in infants (aged1 year) between January 1, 2005 and March 31, 2012 were identified and clinical data were collected. Biopsies were reclassified using the ChILD classification for diffuse lung disorders in infants.Twenty-seven infants were identified, with the number of biopsies performed increasing each year over the study period. There was no mortality and negligible morbidity associated with biopsy. Diagnoses seen were similar to those reported by the ChILD network. Histopathological diagnosis was not compatible with life in the absence of lung transplant in 6/27 (22%) of infants. Of the 14 children longitudinally followed up (median 0.5 (0.4 - 5.81) years), only four continued to require supplemental oxygen.Lung biopsy in infants with suspected ILD is safe, and histopathological diagnosis frequently assists treatment decisions, particularly with regard to withdrawal of care.

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.

Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 ( PLCB4 ) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 ( GNAI3 ) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.

Extrapolation of adult-based evidence into pediatric management decisions is often unavoidable owing to a lack of sufficiently powered, suitably designed pediatric studies. Pediatric data are emerging but are challenged by the lower numbers of lung and heart–lung transplants performed annually as compared to adult transplantation. Pediatric data are further diluted by the relatively large number of centers that perform pediatric transplants internationally. This chapter will discuss available pediatric data to illustrate the similarities that exist between pediatric and adult subjects with respect to incidence, risk factors, diagnosis, and management of bronchiolitis obliterans (BO). Although the pediatric lung transplant literature generally supports the use of data that are extrapolated from lung transplantation in adults, specific challenges also exist that are unique to the pediatric age range, and the resultant differences in approach are outlined.

Introduction Lung clearance index (LCI) is a sensitive measure of lung disease in infants, with potential applications in clinical practice and research. However, measuring LCI in infants is technically challenging and there is no simple method of assessing LCI outside of specialist research laboratories in this population. We have previously described an alternative method of measuring LCI, in which expired gas is collected and analysed to derive functional residual capacity (FRC) and LCI without directly measuring flow. This eliminates one of the major technical challenges, whilst also reducing the system’s dead space. This method is highly accurate in vitro, with a mean accuracy of FRC measurement to within 1%, down to FRC of 100ml.1 The method does not require large external gas tanks, and washout is performed breathing room air, making the system fully portable. Aim To assess the performance of this method in vivo. Method Healthy controls and infants with CF are currently being recruited to undergo LCI measurement using this method. Practical applicability of the system is determined by the number of successful tests and within-subject repeatability, defined as coefficient of variation (CV%) of same-visit repeats. Comparison will be made with LCI measurements obtained using a respiratory mass spectrometer, currently considered the gold standard for infant LCI measurement. Results To date, 10 healthy controls (mean age 53 weeks) and 2 infants with CF (mean age 55 weeks) have successfully undergone LCI measurement using this method. Mean LCI in controls was 6.62 (range 5.79–7.91). Mean within-subject CV% was 5.9%. Mean LCI in infants with CF was 7.63 (CV 5%). Conclusion Preliminary data suggest this is a feasible and reproducible method of performing LCI in infants. Results in both infants with CF and controls fall within ranges predicted by the respiratory mass spectrometer2 and within accuracy limits set by international guidelines. This could provide a more accessible alternative to current technologies, enabling this test to be offered in more centres. References Shawcross, et al. Ped Pulmonol 2016;51:491–497. Lum, et al. Eur Respir J 2013;41:1371–7.

Introduction Convection Dependent Inhomogeneity (CDI, a measure of ventilation inequality among larger lung units) quantified by Scond cannot be assessed in subjects with severe ventilation inhomogeneity (VI) as assumptions underlying the calculation are invalid; an alternate index that has been suggested is Scond.1 Aim To compare these two methods of CDI assessment in CF children Methods Children with cystic fibrosis (CF; 67) and healthy controls (61) performed multiple breath washout with sulphur hexaflouride measured using mass spectrometry. Scond was calculated from 1.5 to 6 turnovers and Scond* from breath 2 to 3 turnovers. Results All measures of VI were significantly higher for CF vs control, mean difference: LCI 4.0, Scond 0.054, Scond* 0.081. In CF, LCI correlated better with Scond* than Scond (See figure: correlation coefficient LCI vs. Scond* 0.75; LCI vs. Scond 0.42). If children with moderate-severe VI (LCI > 11) were excluded there was an improved correlation for both relationships (correlation coefficient LCI vs. Scond 0.83; LCI vs. Scond* 0.86). An asymptote for the Scond vs LCI relationship was at Scond 0.07 and Scond* 0.13. Conclusion Scond* quantifies the mechanism of VI in moderate to severe lung disease, but it may reach asymptote in very severe VI. Reference Verbanck. Respiratory Physiology & Neurobiology, 2013.

Background Breathing pattern cannot be controlled in small children, so multiple breath washout SnIII analysis has to exclude inadequate volume breaths. Aim To compare an existing mathematical breath exclusion algorithm with a physiological method. Methods School age children with CF (30) and controls (30) performed SF6MBW with mass spectrometer, with uncontrolled tidal breathing. Two different breath exclusion methods were compared, with exclusion based on: 1) Expired tidal volume (VT) deviating by >25% of the median VT1 2) VT Runs with >33% excluded breaths were removed. Volume corrected Scond was calculated from subjects with 3 valid runs. Results Far fewer subjects were excluded by the physiological Langley method, than by the mathematical method (Table). The mean and SD for Scond was identical by both methods, implying that the mathematical algorithm excludes valid data. Conclusion A physiological approach to data cleaning prior to SnIII analysis allows retention of data that would be inappropriately excluded mathematically. References Bigler A, et al. Paediatric Pulmonol 2015;50(8):805–13. Langley FE, et al. Colloques INSERM 1975;51:209–212.

Knowledge of short- and longer-term repeatability of lung function in health and disease is essential to determine bronchodilator reversibility thresholds and to recognise if changes in lung function represent disease progression, therapeutic intervention or normal variability. Multiple-breath washout indices (lung clearance index, conductive ventilation inhomogeneity (Scond)) and specific airway resistance (sRaw) were measured in healthy children and stable wheezers. Measurements were performed at baseline and after 20 min without intervention to assess repeatability and determine bronchodilator reversibility thresholds. Bronchodilator reversibility was assessed by repeating baseline measurements 20 min after inhaled salbutamol. 28 healthy controls, mean±sd age 6.1±0.7 years and 62 wheezers 5.4±0.6 years were tested. Baseline variability in multiple-breath washout indices and sRaw was not significantly different between wheezers and healthy controls. Significant bronchodilator reversibility was only observed in wheezers for Scond (16%), but in both wheezers (37%) and healthy controls (20%) for sRaw. Some wheezers and healthy controls demonstrated increases in multiple-breath washout indices post-bronchodilator. Lung clearance index and sRaw demonstrate low baseline variability in healthy and diseased subjects. Neither multiple-breath washout indices nor sRaw are ideal for assessing bronchodilator reversibility in young children with stable wheeze. These findings will help to interpret the effect of therapeutic interventions in children with respiratory diseases.

Objectives: There are few data examining what impact the potentially disruptive period of transition to adult services has on the health of adolescents with CF. The aim was to compare lung function, growth, co-morbidity and infection status pre and post transition to assess any quantifiable change in clinical status. 51 consecutively transitioning adolescents (59% male, mean age 17.07 years) were Identified. Markers of health were assessed in the 12 months before and after transition. Methods: Z scores were calculated for height, weight and BMI. Lung function, positive microbiology, courses of antibiotics, use of feeding supplements and presence of comorbidities in the 12 months pre and post transition were compared. Results

It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation. We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients. Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0-11.4) Hz versus 7.4 (6.4-9.2) Hz; p

Various functional residual capacity (FRC) repeatability criteria have been proposed for lung clearance index (LCI) measurement by multiple breath washout (MBW). Adult guidelines recommend three technically acceptable tests with FRC values within 10%, whilst preschool guidelines recommend two such tests. Feasibility of and need for recommendations in children is unclear.Retrospective analysis of MBW data was undertaken in healthy control (n = 90) and cystic fibrosis (CF) subjects (n = 108) encompassing infancy, pre-school and school age ranges. Feasibility of FRC repeatability recommendations was investigated in those with three technically acceptable tests. Validity of mean LCI from the first two tests alone (vs. all three) was investigated by comparing mean data and sensitivity to detect abnormal peripheral airway function in CF.LCI coefficient of variation (CoV) was related to FRC CoV (P 0.001) and disease category (P = 0.002). Application of adult repeatability criteria decreased LCI CoV (4.7 vs. 8.5%, P 0.001), but had poor feasibility beyond infancy (62/150, 41%). Preschool recommendations increased feasibility but only to 70% overall. There was no difference in mean LCI (All three minus 1st two tests) in healthy controls [mean (95% CI) difference: 0.02 (-0.01, 0.06; P = 0.15)], this difference being statistically but not clinically significant in CF subjects [0.07 (0.00,0.13; P = 0.04)]. Sensitivity in CF subjects was unaffected.Adult FRC repeatability recommendations improved LCI repeatability in pediatric subjects, but poor feasibility limited utility. In an experienced pediatric MBW center, recent preschool recommendations can be extended to two technically acceptable tests, irrespective of FRC repeatability, without significantly affecting mean LCI or compromising sensitivity.

To the Editors: In preschool children, exposure to traffic-related emissions is associated with increased prevalence of respiratory symptoms [1–3] and, in school-aged children, with reduced lung function growth [4]. However, to date, the association between air pollution and preschool lung function remains unclear. In a cross-sectional study, we investigated the effects of residential proximity to main roads and air pollutants on lung function in healthy preschool children. Spirometric forced vital capacity, forced expiratory volume in 1 s and 0.5 s, lung clearance index (LCI) by multiple breath washout, plethysmographic specific airway resistance (s R aw) and exhaled nitric oxide fraction ( F eNO) were measured in healthy preschool children as part of another study protocol [5 …

Background Ethnic differences in lung function in school-aged children and adults are well recognized, but little is known about such differences in preschool children. We investigated whether differences exist in fraction of exhaled nitric oxide (F eno ), multiple-breath washout (MBW) indices, specific airways resistance (sRaw), and spirometry indices between healthy preschool children of South Asian and white European origin. Methods F eno , MBW indices (lung clearance index, functional residual capacity, conductive airways inhomogeneity, and acinar airways inhomogeneity), sRaw, and spirometry were measured in healthy South Asian and white children aged 4 to 6 years, and comparisons were made between the two groups. Statistical analyses were by multiple linear regression and t tests. Results Thirty-seven white (mean age 5.8 ± 0.7 years, 49% boys) and 31 South Asian children (mean age 5.4 ± 0.8 years, 52% boys) were recruited. F eno was, on average, 36% higher ( P 1 and fractions thereof (FEV 0.75 and FEV 0.5 ) z -scores were significantly lower in South Asian compared with white children by 0.69 ( P = .01), 0.76 ( P = .004), 0.76 ( P = .009), and 0.85 ( P = .002) z -scores, respectively, but there were no significant differences in FEV 1 /FVC, FEF 25-75 , sRaw, or MBW indices. Conclusions Differences in F eno and forced expiratory lung volumes between South Asian and white children exist from a very young age. Ethnic differences should be taken into account when interpreting lung function results in preschool children for effective management of respiratory conditions.

The aim of this update is to describe the paediatric highlights from the 2010 European Respiratory Society Annual Congress in Barcelona, Spain. Abstracts from the seven groups of the Paediatric Assembly (Respiratory physiology, Asthma and allergy, Cystic fibrosis, Respiratory infection and immunology, Neonatology and paediatric intensive care, Respiratory epidemiology and Bronchology) are presented in the context of the current literature.

This Fourteenth Pediatric Lung and Heart-Lung Transplantation Report covers the pediatric lung transplantation and heart-lung transplantation experience from January 1986 through June 2010. During this period, 1,664 pediatric lung transplant procedures and 653 pediatric heart-lung transplant procedures were reported to the International Society for Heart and Lung Transplantation (ISHLT) Registry. It is important to note that recent figures include pediatric lung and heart-lung transplant procedures dating back to 1987 that were previously not reported to the ISHLT Registry but were retrospectively entered in 2010. In 2009, the last complete year included in this year’s ISHLT Registry report, 127 pediatric lung transplant procedures were reported, which is an increase of 43% compared with 2004. These figures, however, include only the pediatric lung transplant procedures that were reported to the ISHLT Registry and do not necessarily reflect the trend in numbers of pediatric lung procedures performed worldwide. This pediatric lung and heart-lung transplantation report includes a summary of the data analyses performed by the Registry this year and is supplemented by further analyses and additional figures that are available on the ISHLT Registry Web site (www.ishlt.org/registries). This report does not include detailed analyses and figures for pediatric heartlung transplantation because this information has been presented in previous reports and the number of pediatric

Assessment of ventilation inhomogeneity using the multiple breath washout (MBW) technique has been shown to be more sensitive than spirometry in detecting early cystic fibrosis lung disease throughout childhood. The current “gold standard” interface for school age children and adults is a mouthpiece. Although masks are better tolerated by infants and younger children, their use increases equipment deadspace-which could influence measured values and hence interpretation of results. The aim of this study was to examine the effect of using a mask vs mouthpiece on values of functional residual capacity (FRC) and the lung clearance index (LCI) derived from MBW. Method Comparisons were performed in healthy adults. The study design incorporated repeated measures as well as interface comparison. The mask was selected to mimic measurement conditions in infants, the deadspace of 85 mL being approximately 1–2 ml/kg in adults. Mouthpiece (MP) deadspace was ~5 ml. Subjects were randomly allocated to group A (Mask-Mouthpiece-Mouthpiece) or group B (Mouthpiece-Mouthpiece-Mask) protocols. Each subject performed a total of 9 MBW runs, in 3 sets, each consisting of 3 runs, with a 5-minute break between each set. MBW was performed using a mass spectrometer as described previously (Aurora 2005 AJRCCM). Paired t-tests with 95% limits of agreement were used to establish repeatability (MP1 vs. MP2) and any differences between Mask vs. Mouthpiece. This study was approved by the local research ethics committee and written consent obtained from subjects. Results Technically satisfactory comparative data were obtained on 15 occasions in 14 adults (36% males; age: 22–56 years). Respiratory rate and tidal volume were similar using either approach. Repeatability: Both FRC and LCI were repeatable using the mouthpiece [(Mean (95% CI) diff: FRC: 0.012L (-0.05;0.07); LCI: -0.1(-0.3; 0.1)]; Figure 1A and B. Mask vs. Mouthpiece: FRC and LCI were both significantly higher when assessments were made using a mask compared with a mouthpiece: FRC: 0.101L (0; 0.202); LCI: 0.4 (0.2;0.7); Figure 1C and D. Conclusion The increase in LCI when using a facemask exceeded normal within test variability in adults and could influence interpretation of results especially if different patient interfaces are used when collecting data in younger children.

Background Lung clearance index (LCI) measured by multiple breath washout (MBW) is a sensitive indicator of early lung disease in Cystic Fibrosis (CF). 1 MBW using sulphur hexafluoride (SF 6 ) and mass spectrometry (MS) is currently the gold standard, but equipment is limited to a few centres. Although commercial devices based on SF 6 have been developed, use of SF 6 is expensive and restricted in some countries. Commercial devices using nitrogen (N 2 ), which is cheaper and widely available, have been developed recently to increase accessibility of this test in research and clinical practice but have yet to be validated in children. The aim of this study was to compare values of LCI and Functional Residual Capacity (FRC) in children using the N 2- MBW EasyOne Pro® LAB system (ndd Medical Technologies) and the MS (AMIS 2000, Innovision ApS). Methods School-age children with CF and healthy controls completed MBW in triplicate on both the EasyOne Pro® and MS in random order on the same occasion. Within-subject agreement between devices for LCI and FRC was assessed by Bland-Altman analysis. Results Of the 50 children recruited, all completed testing using MS, while 5 failed quality control on the EasyOne Pro® LAB. Paired results from both devices were obtained in 26 children with CF (mean age [range]) (13.3y[7.8y-17.4y]) and 19 controls (14.8y [12.5y-16.7y]). LCI was significantly higher in those with CF when using both devices (mean difference[95% CI], CF-controls): 2.47[1.4;3.5] for the MS-SF 6 and 2.20[1.2–3.2] for N 2 -MBW. There were no significant group differences between devices for either LCI (mean difference[95% CI]) -0.14[-0.45;0.16] or FRC -0.15L[-0.2;-0.08]. Within-subject variability was proportional to mean values (see Figure) and ranged from 0.4–15.7% for LCI and 0.0–19.6% for FRC. Conclusion Despite some previous reports that N 2- washout results in higher LCI values than MS-SF 6 washout, on average, we found similar values in both healthy school-age children and those with CF. Further work is required to examine causes of within-subject variability and assess validity and sensitivity over a wider age range, including preschool children, before commercial N 2 -MBW devices can be confidently used in multi-centre trials. Reference Aurora et al . Am J Respir Crit Care Med. 2011;183:752–8

Effective management of respiratory diseases in young children requires objective outcome measures that do not rely simply on parental reports of symptoms, which are known to be unreliable [1,2]. A...

Despite improved medical therapy, transplantation (Tx) represents the only option for end-stage pulmonary vascular disease.Clinical data of children with idiopathic pulmonary arterial hypertension (IPAH) referred for Tx assessment between January 2002 and June 2007 were related to listing decision and outcome.Seven of the 14 children assessed for Tx were listed. Five were transplanted (lung Tx, n = 3; heart-lung Tx, n = 2) and two died on the waiting list. Mean age at diagnosis was 3.7 (0.4-9.5) years. Time from diagnosis to listing was 3.6 years (range 1.4-9.3). Children listed were in a worse functional class (WHO 3.5 vs. 2.5; P = 0.0006), had a lower SpO(2) on exercise (76.5% vs. 89%; P = 0.0001) and a shorter 6-min walk distance (154 m vs. 330 m; P0.01) than those not listed. Right ventricular function was worse in those listed (P = 0.03), as was pulmonary vascular resistance index (PVRI) on vasodilator testing (34 U m(2) vs. 14.6 U m(2); P = 0.03). Age at diagnosis and at assessment, weight, height, mean pulmonary artery pressure, baseline PVRI, B-type natriuretic peptide, spirometry and resting-SO(2) did not differ between the two groups. For the five children transplanted, median waiting time was 81 days. Age at Tx was 5.4 years. After 2.8 years all transplanted children are alive with a good functional outcome. Two patients died on the active waiting list. All children considered too well for listing are still alive and stable on treatment.Outcome after transplantation in children with IPAH has been encouraging. Defining listing criteria for these patients remains a challenge.

The aim of this article is to describe the paediatric highlights from the 2009 European Respiratory Society Annual Congress in Vienna, Austria. The best abstracts from the seven groups of the Paediatric Assembly (asthma and allergy, respiratory epidemiology, cystic fibrosis, respiratory physiology, respiratory infections and immunology, neonatology and paediatric intensive care, and bronchology) are presented alongside findings from the current literature.

This review examines the utility of flexible bronchoscopy (FB) in paediatric lung transplant recipients and other immunosuppressed children, including indications and contraindications, risk-benefits

Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions.

To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post‐transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxon's rank‐sum and χ2 tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P

Summary Background Lung transplantation has been available as therapy for end-stage lung disease since the early 1980s, but survival after transplantation remains poor, with continued controversy as to the survival benefit from the procedure. We examined the effect of lung or heart-lung transplantation on the survival of a cohort of children with cystic fibrosis and severe lung disease. Methods Between May, 1988, and May, 1998, 124 children with cystic fibrosis were accepted for lung transplantation. 47 received transplants, 68 died while they awaited organs, and nine remained on the active waiting list. We constructed a proportional-hazards model that used variables of prognostic significance in this population. By including transplant status as a time-dependent covariate, we were able to calculate a hazard ratio for transplantation. Date of entry into the study was the date when children were added to the list for transplantation, and measurements were taken at this time. Children were accepted for transplantation if they had a life expectancy of 2 years or less, a poor quality of life, and no contraindications to transplantation. Findings After 1 year, 35 (74%) children were still alive; after 5 years 12 (33%) children were alive. The univariate hazard ratio for transplantation was 0·41 (95% CI 0·23–0·74; p=0·003). Transplantation remained significantly associated with survival after correction for differences in age, sex, height-corrected forced expiratory volume in 1 s, minimum oxygen saturation during a 12 min walk, haemoglobin concentration, albumin concentration, and age-corrected resting heart rate (hazard ratio 0·31 [0·13–0·72]; p=0·007). Interpretation If centres follow our criteria for accepting patients for transplantation, and achieve similar survival after transplantation, they could expect a survival benefit for their patients in line with our results.

To update readers on current recommendations for timing of lung transplantation in individuals with end-stage cystic fibrosis lung disease and on the rationale behind listing decisions.Guidelines for the referral and selection of patients suitable for lung transplantation were recently updated by the pulmonary council of the International Society for Heart and Lung Transplantation. However, an analysis published in 2007 has questioned whether lung transplantation extends life in children with cystic fibrosis. There are some concerns regarding this analysis, and these are discussed in detail. Most importantly, the analysis is specific to the United States and predates the introduction of the lung allocation score, which has had a marked impact on how transplant organs are allocated in this country.It is likely that lung transplantation can extend life in both adults and children with cystic fibrosis, provided the procedure is correctly timed. Further development of the lung allocation score has the potential to increase the survival benefit from the procedure in the United States.

Pediatric heart transplantation celebrates its twentyfifth birthday in 2007, and the first recipients are now entering adulthood. This, the Tenth Official Pediatric Report of the Registry of the International Society for Heart and Lung Transplantation (ISHLT), is dedicated to the courageous recipients and their families, and to the generous donor families who have made this possible. This report documents decades-long survival enjoyed by many pediatric heart transplant recipients. We can now look back over the past 25 years and evaluate indications, survival and morbidity by age of the recipient and era of transplantation. Because much has changed over one-quarter century, we can only be reasonably certain that the late outcomes of the earliest pediatric transplants will be reflected accurately in current recipients. However, these data form a standard and a point of reference to predict future outcomes and perhaps compare actual outcomes in the years to come, as new therapies and management protocols are developed and tested. The data stream for the Registry of the ISHLT is global, and geographic differences have emerged. Geographic comparisons for age at transplant and indication for transplantation are presented for the first time in this tenth report. Previous publications have reported on a steadily improving early survival. 1 We now have a more complete knowledge base for late survival and we report, for the first time, morbidity as late as 10 years after transplantation. Re-transplantation as an indication for transplant has been slowly increasing in North America, but is almost non-existent elsewhere in the world. This report documents the recent rise in the number of re-transplant procedures and further evaluates the late outcomes after re-transplantation. Questions remain about the role of re-transplantation for pediatric recipients who become adults. Will adult transplant programs worldwide accept the burden of re-transplantation for pediatric recipients who are now in need of a second heart transplant, or perhaps a kidney transplant, due to calcineurin inhibitor‐induced renal failure? Certainly this challenge will grow and the pediatric transplant community must evaluate potential changes at the point of care in childhood that could reduce the demand for re-transplantation and perhaps increase the likelihood of multi-decade survival with less morbidity. The two main post-transplant morbidities that have steadily increased are coronary artery vasculopathy and renal failure. Malignancy has remained an important but low-frequency event. In this report, we continue to evaluate late outcomes as a function of early events

Risk factors, morbidity and mortality from pulmonary fungal infections (PFIs) within the first year after pediatric lung transplant have not previously been characterized.A retrospective, multicenter study from 1988 to 2005 was conducted with institutional approval from the 12 participating centers in North America and Europe. Data were recorded for the first post-transplant year. The log-rank test assessed for the association between PFI and survival. Associations between time to PFI and risk factors were assessed by Cox proportional hazards models.Of the 555 subjects transplanted, 58 (10.5%) had 62 proven (Candida, Aspergillus or other) or probable (Aspergillus or other) PFIs within the first year post-transplant. The mean age for PFI subjects was 14.0 years vs 11.4 years for non-PFI subjects (p0.01). Candida and Aspergillus species were recovered equally for proven disease. Comparing subjects with PFI (n = 58) vs those without (n = 404), pre-transplant colonization was associated with PFI (hazard ratio [HR] 2.0; 95% CI 0.95 to 4.3, p = 0.067). Cytomegalovirus (CMV) mismatch, tacrolimus-based regimen and age15 years were associated with PFI (p0.05). PFI was associated with any prior rejection higher than Grade A2 (HR 2.1; 95% CI 1.2 to 3.6). Cystic fibrosis, induction therapy, transplant era and type of transplant were not associated with PFI. PFI was independently associated with decreased 12-month survival (HR 3.9, 95% CI 2.2 to 6.8).Risk factors for PFI include Grade A2 rejection, repeated acute rejection, CMV-positive donor, tacrolimus-based regimen and pre-transplant colonization.

In their provocative paper, "Lung transplantation and survival in children with cystic fibrosis," Liou and colleagues state that "Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality of life benefit from lung transplantation." Unfortunately, that conclusion is not supportable. Liou's dataset introduced bias against transplantation by using covariates obtained well before the time of transplant (when predicted survival was good) and having a cohort with lower than expected post-transplant survival than reported elsewhere. The calculated hazard ratios are based on factors that may have changed between listing and transplant, and do not reflect true benefit on a patient by patient basis. The findings of the study are contrary to other studies using similar methods. Finally, recent changes in US lung transplant allocation policy may have made the study findings moot. In contrast to Liou's suggestion to perform an ethically and logistically challenging randomized trial to verify the benefit of lung transplantation, a research agenda is recommended for pediatric lung transplantation for cystic fibrosis that focuses on developing strategies to continually reassess and maximize quality of life and survival benefit.

Lung transplant candidates and recipients are at high risk of infections from vaccine-preventable diseases. However, well-established guidelines neither exist for pre- and post-transplant vaccination nor do monitoring guidelines for pediatric lung transplant recipients. To ascertain the current vaccination and monitoring practices of pediatric lung transplant centers, a self-administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative in April 2006. Sixteen of 18 centers (89%) surveyed responded. Pretransplant, national vaccination guidelines are followed. Eleven centers reported following standardized vaccination guidelines post-transplant. Vaccines were more commonly provided by the primary-care physician pretransplant (69%) rather than post-transplant (38%). Post-transplant, 50% of the centers recommend live vaccines for household contacts but not for the transplant recipient. Pretransplant monitoring of response to prior vaccination was performed inconsistently except for varicella (88%). Only 44% of the transplant centers measure for response to vaccination post-transplant, mostly hepatitis B. Current vaccination practices of pediatric lung transplant centers are heterogeneous. The lung transplant community would be well served by studies designed to evaluate the efficacy of vaccinations in this population.

v r t t 1 t ince its inception in 1980, the registry of the Internaional Society for Heart and Lung Transplantation ISHLT) has chronicled the evolution of heart, lung and eart–lung transplantation. Annual reports from the egistry were inaugurated in 1984, and information bout heart–lung transplantation has been included n the reports from the onset. As lung transplantation eveloped, it was added to the reports beginning in 989. Through June 30, 2006 the registry had accrued ata on 3,262 heart–lung and 23,716 lung recipients rom centers around the world. This section of the 24th fficial report summarizes the current status of adult ung and heart–lung transplantation. Figures in this eport and additional slides are available from the ISHLT ebsite (http://www.ishlt.org). A new organ allocation system for lung transplantaion was implemented in the USA in May 2005. The eniority system, which was based solely on accrued ime on the waiting list, was replaced with a priority ystem that is designed to balance the risk of death on he waiting list and the likelihood of survival after ransplantation. Although the full impact has not been ealized, the shift to this priority system could affect the fficiency of organ allocation and the number of translantations, the relative distribution of indications for ransplantation, the severity of illness of recipients at he time of transplantation, and post-transplantation utcomes. Data from the first cohort of recipients from his new allocation system are included in the aggregate ata analyzed for this report. Because approximately 0% of lung transplantations in the registry are contribted by U.S. centers, the effects of this priority system

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INSPIRE-CF is an on-going 24-month physiotherapy RCT examining the effects of an individually prescribed and weekly supervised exercise programme for children with CF, in terms of lung function, exercise capacity and quality of life. Objectives This interim review evaluated participation in the exercise intervention group in the first year of the study. Methods 71 children (6–15 years) with a range of lung disease severity (FEV1 89%±16%pred; mean±SD) were randomised into 2 groups. Both received standard specialist care, but the intervention group (n = 37) also received weekly exercise training. Participation and reasons for non-attendance were recorded for 12 months after baseline assessment. Results Interim data from 34/37 children in the exercise group were available. Average attendance was 53.5%±23% (mean±SD) of 52 potential weeks in the first 12 months. Individual attendance ranged between 0% and 92% of sessions, with boys attending more often than girls (58% vs 49%). Major reasons for non-attendance were: no membership with fitness centre in place (6.4%), family (5.8%) or trainer holidays (6.3%) and unexplained non-attendance (4.5%). Minor reasons were recorded as child illness (3%), hospital admissions or clinic appointments (2.8%), public holidays (2.5%), school events (1.9%), family events (1.7%), staff training (2.3%), with other reasons Conclusion This interim analysis demonstrates the challenges of implementing a weekly supervised exercise programme for children with CF. Despite advanced planning with families, many factors including home, school and medical care can impact on attendance.