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Lung transplantation is a recognised therapy for end stage respiratory failure in children and young people. It is only available in selected countries, and is limited by access to suitable organs. Data on disparities in access and outcomes for children undergoing lung transplantation are limited. It is clear that data from studies in adults, and from studies in other solid organ transplants in children, that systemic iniquities exist in this field. While data relating specifically to paediatric lung transplantation are relatively sparse, professionals should be aware of the risk that health care systems may result in disparities in access and outcomes following lung transplantation in children.

Summary Background Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a new, rare, post-infectious complication of SARS-CoV-2 infection in children. We aimed to describe the 6-month outcomes of PIMS-TS. Methods This retrospective cohort study comprised children (aged Findings 46 children were included in this study. The median age at presentation was 10·2 years (IQR 8·8–13·3), 30 (65%) patients were male and 16 (35%) were female, 37 (80%) were from minority ethnic groups, and eight (17%) had pre-existing comorbidities. All patients had elevated markers of systemic inflammation at baseline. None of the patients died. By 6 months, systemic inflammation was resolved in all but one patient. 38 (90%) of 42 patients who had positive SARS-CoV-2 IgG antibodies within 6 weeks of admission remained seropositive at 6 months. Echocardiograms were normal in 44 (96%) of 46 patients by 6 months, and gastrointestinal symptoms that were reported in 45 (98%) of 46 patients at onset were present in six (13%) of 46 patients at 6 months. Renal, haematological, and otolaryngological findings largely resolved by 6 months. Although minor abnormalities were identified on neurological examination in 24 (52%) of 46 patients at 6 weeks and in 18 (39%) of 46 at 6 months, we found minimal functional impairment at 6 months (median Expanded Disability Status Scale score 0 [IQR 0–1]). Median manual muscle test-8 scores improved from 53 (IQR 43–64) during hospital admission to 80 (IQR 68–80) at 6 months, but 18 (45%) of 40 patients showed 6-min walk test results below the third centile for their age or sex at 6 months. PedsQL responses revealed severe emotional difficulties at 6 months (seven [18%] of 38 by parental report and eight [22%] of 38 by self report). 45 (98%) of 46 patients were back in full-time education (virtually or face to face) by 6 months. Interpretation Despite initial severe illness, few organ-specific sequelae were observed at 6 months. Ongoing concerns requiring physical re-conditioning and mental health support remained, and physiotherapy assessments revealed persisting poor exercise tolerance. Longer-term follow-up will help define the extended natural history of PIMS-TS. Funding None.

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with increased morbidity in CF. Variability in physiological systems is associated with dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker of CFRD or "pre-diabetes". METHODS: Using a machine learning approach, we compared glucose IQR to current diagnostic criteria in a review of continuous glucose monitoring data. RESULTS: Analysis was performed on 248 studies from 142 children. Calculated IQR (cIQR) was increased between children with CFRD, normal glucose homeostasis and indeterminate status (p

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 μg/m3, n = 138), middle (25.6 to 26.8 μg/m3, n = 126), and upper (26.8 to 31.0 μg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p

Outdoor air pollution is increasingly identified as a contributor to respiratory and cardiovascular disease. Pro-inflammatory particles and gases are inhaled deep into the lungs, and are associated with impaired lung growth and exacerbations of chronic respiratory diseases. The magnitude of these effects are of interest to patients and families, and have been assessed in studies specific to CF. Using systematic review methodology, we sought to collate these studies in order to summarise the known effects of air pollution in cystic fibrosis, and to present information on decreasing personal air pollution exposures.

Environmental Mycobacteria share genes and evolve to become pathogens

A 6-year-old previously healthy boy presented with a 5-day history of fever, malaise and pharyngitis. His parents brought him to the emergency department due to a new onset of cough and difficulty in breathing. He was fully immunised with no recent travel history or infectious contacts. At

Aim:Epidemiological studies of deoxyribonucleic acid (DNA) methylation in airway disease have largely been conducted using blood or buccal samples. However, given tissue specificity of DNA methylation, these surrogate tissues may not allow reliable inferences about methylation in the lung. We sought to compare the pattern of DNA methylation in blood, buccal and nasal epithelial cells to that in airway epithelial cells from children.Methods:Samples of blood, and buccal, nasal and airway epithelium were obtained from six children undergoing elective anaesthesia for adenotonsillectomy. DNA methylation was assessed at 450 000 5′-C—phosphate—G-3′ (CpG) sites using the Illumina HumanMethylation450 array.Results:Eighteen samples from all sites were suitable for analysis. Hierarchical clustering demonstrated that the methylation profile in nasal epithelium was most representative of that in airway epithelium; the profile in buccal cells was moderately similar and that in blood was least similar.Conclusion:DNA methylation in blood poorly reflects methylation in airway epithelium. Future epidemiological studies of DNA methylation and airway diseases should consider measurement of methylation either in buccal cells or, preferably, in nasal epithelial cells.

SummaryBackground Airway dendritic cells (DC) are critical mediators of lung inflammation in asthma, but the characteristics of DC in the airways of healthy children, and children with asthma, are currently unknown. Objective We sought to identify changes in DC subset distribution and activation profile in paediatric asthma using flow cytometry to analyse induced sputum samples obtained from healthy and asthmatic children. Methods Lung function and atopic status were determined by spirometry and skin prick testing. Induced sputum samples were analysed using 7-colour flow cytometry to identify airway DC populations (lineage− HLA-DR+ sputum cells expressing either CD11c as conventional DC or CD123 as plasmacytoid DC). Results Sputum samples containing lower airway plugs were obtained from 10 healthy children and 8 children with asthma. Lineage− HLA-DR+ DC were successfully identified in all samples, and DC comprised a significantly higher proportion of sputum cells in children with asthma compared with age-matched healthy controls (1.29% vs. 0.67%, P = 0.02). DC expression of the costimulatory marker CD86 was significantly reduced in asthmatic children (73.4% vs. 59.7%, P = 0.04). Sputum DC also included numerous CD1c+ cells (mean 57% of the total DC population) and low frequencies of cells expressing the subset markers CD141 or CD123, although the proportions of these did not differ between groups. Conclusions Airway DC can be identified and characterized non-invasively using flow cytometry to analyse paediatric sputum samples. Our data reveal that children with steroid-treated asthma exhibit increased frequency of airway DC with reduced expression of the costimulatory marker CD86, suggesting altered trafficking and/or maturation of these cells either due to asthma or steroid therapies.

Exposure to particulate matter (PM) is associated with adverse health effects, including chronic lung diseases, lung cancer and cardiovascular disease. Personal exposure varies depending on the generation of particles locally, background levels, activity patterns and meteorology. Carbon loading in airway macrophages (AM) is a novel marker to assess personal exposure to combustion-derived particles. This review summarizes the published evidence and describes the validity and reliability of this marker with a focus on the technical aspects. Carbon loading in AM is reported in nine published studies assessing personal exposure to particulate air pollution. The carbon content is quantified by image analysis and is suggested to be suited to assess cumulative exposures. While there is some variation in study technique, these studies each indicate that internal AM carbon reflects either external exposure or important health effects. However, some uncertainty remains regarding potentially confounding materials within particles, the time frame of exposures that this technique reflects, and the optimal strategy to accurately quantify AM carbon. These aspects need to be clarified or optimized before applying this technique in larger populations. Keywords: Carbon loading, Airway macrophages, Particulate matter, Air pollution

Purpose The purpose of this paper is to establish the effect of incorporating Centor scoring into antibiotic prescribing in primary care in London, UK, before and after the introduction of an educational package and prescribing software tool. Design/methodology/approach A quality improvement project with analysis of all sore throat presentations in patients aged 3-14 years, in two phases. Phase 1 (retrospective): 1 January-31 December 2013, followed by an intervention (software tool/education package) and Phase 2 (prospective): 1 March 2014-28 February 2015. Findings In the initial analysis, 162 out of 202 (80.2 per cent) patients were prescribed antibiotics. Following the educational/software intervention, 191 out of 231 (82.7 per cent) patients were prescribed antibiotics (p=0.56, χ2 test). The mean Centor score decreased significantly following the education/software intervention (3.1 vs 2.7, pχ2 test). In all, 100 per cent of patients with tonsillar exudate were prescribed antibiotics in both phases. The apparent order of importance for predictive signs/symptoms given by the prescribers in both phases of the study was tonsillar exudate>lymphadenopathy>fever>absence of cough. Originality/value This is the first time a differential importance given by practitioners on individual Centor criteria has been described. With a low probability of bacterial infection, children with exudate or anterior lymphadenopathy almost always received antibiotics. This is interesting, since studies have previously found that the presence of tonsillar exudate had no significant association with culture-confirmed streptococcal tonsillitis.

UK National Institute for Healthcare Research, Efficacy and Mechanisms Evaluation (NIHR-EME) Programme (Reference 08/43/03). Professor Grigg is part funded by the North Thames Collaboration for Leadership in Applied Health Research and Care.

Lung growth in childhood is impaired by air pollution (Gauderman et al, NEJM 2004). When and where urban children are maximally exposed to air pollution remains unclear. We hypothesised that children are exposed to high peaks of pollution when travelling to and from school, and measured personal black carbon (BC) exposures in children in London and Bangalore. BC exposure (ng/m 3 ) was measured in 44 9-11 yr olds (London n=24, Bangalore n=20) during a school day using a portable monitor, divided into home, commute, and school times and compared by one-way ANOVA. Peaks were defined as BC >10000 ng/m 3 . BC exposure/min was greatest during the school commute (p We conclude that children are exposed to a considerable fraction of their daily air pollution exposure during the short time travelling to and from school. Individual behaviours and legislative efforts should address the air quality of home-school routes in order to maximally benefit children9s lung growth.

BackgroundThe clinical effectiveness of intermittent montelukast for wheeze in young children is unclear. Previous work has been equivocal. Variation in copy numbers of the specificity protein 1-binding motif in the arachidonate 5-lipoxygenase (ALOX5) gene promoter; where the wild type has five copies per allele, denoted here as 5/5, but variant genotypes may have 1–8 copies on each allele, denoted as x/x or 5/x, influences montelukast efficacy in asthmatic adults. This polymorphism may identify a responsive subgroup within this population.ObjectivesTo assess the clinical effectiveness of montelukast in preschool wheezing children. To explore the effect of theALOX5promoter genotype on this effect.DesignA multicentre, parallel-group, double-blind, randomised, placebo-controlled trial.SettingTwenty-one primary care sites and 41 secondary care sites in England and Scotland.ParticipantsChildren aged 10 months to 5 years with two or more wheeze episodes, one within the last 3 months, stratified byALOX5promoter genotype, either 5/5 or [5/x + x/x]. Children with other respiratory vulnerabilities were excluded.InterventionParent-initiated 4 mg oral granules of montelukast or identical placebo administered once daily for 10 days from the onset of every cold or wheeze episode over 12 months.Main outcome measureNeed for unscheduled medical attendance for wheezing.RandomisationChildren were stratified byALOX5promoter genotype, either 5/5 or [5/x + x/x], where x ≠ 5. Children in each stratum were independently randomised to receive montelukast or placebo in a 1 : 1 ratio via a permuted block schedule (size 10). Clinical investigators and parents were blinded to treatment group and genotype stratum.MethodsGenotype was identified by analysis of salivary deoxyribonucleic acid. Analysis was by intention to treat. Primary outcome data came from treatment diaries, scheduled telephone calls and caregiver records.ResultsA total of 1358 children were randomised to receive montelukast (n = 669) or placebo (n = 677). Consent was withdrawn for 12 (1%) children. Primary outcome data were available for 1308 (96%) children. There was no difference in unscheduled medical attendances for wheezing episodes between children in the montelukast and placebo groups {mean 2.0 [standard deviation (SD) 2.6] vs. mean 2.3 (SD 2.7) unscheduled medical attendances; incidence rate ratio (IRR) 0.88, 95% confidence interval (CI) 0.77 to 1.01;p = 0.06}. Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum [mean 2.0 (SD 2.7) vs. mean 2.4 (SD 3.0) unscheduled medical attendances; IRR 0.80, 95% CI 0.68 to 0.95;p = 0.01], but not in those in the [5/x + x/x] stratum [mean 2.0 (SD 2.5) vs. mean 2.0 (SD 2.3) unscheduled medical attendances; IRR 1.03, 95% CI 0.83 to 1.29;p = 0.79,p-interaction = 0.08]. We recorded one serious adverse event: a skin reaction in a child allocated to placebo.InterpretationThere is no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5ALOX5promoter genotype might identify a montelukast-responsive subgroup.LimitationsThe study lacks power to confirm the validity of the suggested genotype stratum effect. Additionally, the effect is contrary to that hypothesised and is not supported by urinary data. We could not robustly measure treatment compliance.Future workFuture work should test the stratum effect with a repeat trial in the apparently more responsive (5/5) stratum only.Study registrationClinicalTrials.gov NCT01142505.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

Pseudomonas aeruginosa is the most problematic organism in patients with cystic fibrosis. This article reviews its pathogenic mechanisms, with particular relevance to the pathophysiology of the cystic fibrosis airway, and recent advances in therapeutic approaches.

Rossa Brugha (Junior Doctor): A 3-year-old boy with cystic fibrosis (CF) diagnosed on newborn screening (sweat chloride 90 mmol/L, F508del homozygous) attended routine follow-up in the CF clinic. He had had a wet cough for the previous 3 weeks. In addition to CF, he had previously been diagnosed with gastro-oesophageal reflux (oesophageal pH

Public awareness of the impact of air quality on health is increasing worldwide. Indoor and outdoor air pollutants impair children's growing lungs, and increase the risk of respiratory infections. In many cities, children face indoor air pollution from fuels used for cooking and heating, as well as outdoor pollution from vehicle exhausts. Research identifies at-risk groups and seeks to establish biological plausibility for the associations already observed; and looks towards identifying the harmful pollutants that are responsible for respiratory morbidity and mortality. These findings may then serve to influence public debate and future policy at national and international level to improve air quality in cities, and improve children's health.

Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls.AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (μm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis.AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p0.01) and healthy controls (n=47, p0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p0.05, and rs=-0.44, p0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p0.01 vs control).Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.

Background Measuring inflammation (inflammometry) may assist decisions regarding preventative anti-inflammatory therapies in asthma.1 Prostaglandin metabolites, which reflect airway inflammation, may be measured in urine samples.2 We sought to prospectively assess associations between urine prostaglandins and subsequent asthma exacerbations in children, and to compare these markers to current markers that aim to predict future risk. Methods Children with asthma aged 7–15 underwent spirometry, sputum inductions, completed the childhood asthma control test (C-ACT) and provided urine samples at baseline. Urine was also provided by healthy (non-atopic) controls. Urine PGD, PGE and PGJ metabolites were measured using HPLC-MS. At 3 months, sampling was repeated, data was collected on exacerbations (unscheduled medical attendance or day missed from school due to asthma symptoms) and the receiver operator characteristic was calculated for the baseline assessment. Results 73 children (asthma n = 25, controls n = 48) were included. Urine PGD2, PGE2 and PGJ2 metabolites were increased in asthma in comparison to controls, and 15-dPGJ2 predicted subsequent asthma exacerbation (PPV=75%, NPV=90%, ROC AUC 0.858, p = 0.005). Sputum eosinophils, spirometry and C-ACT did not predict subsequent exacerbations after correction for multiple comparisons, and sputum phenotypes were unstable. Change in C-ACT score was associated with interim control (p = 0.04). Conclusions Urinary prostaglandin metabolites are increased in children with asthma in comparison to controls. Urine 15-dPGJ2 is a biologically plausible, non-invasive marker for inflammometry in childhood asthma, and is superior to assessment of sputum eosinophils, C-ACT, or spirometry. References 1. American journal of respiratory and critical care medicine 2005;171:1077–1082 2. Thorax 2008;63:27–34 ![Abstract S65 Figure 1][1] Abstract S65 Figure 1 (A) Urine 15dPGJ2 at baseline is significantly lower in children who have an asthma exacerbation within 3 months. (B) ROC curve for 15dPGJ2. ROC AUC=0.858, p=0.005. PG:prostaglandin. Bar represents median, comparison by Mann-Whitney test. *p

To the Editor: In the editorial accompanying our article reporting higher alveolar macrophage carbon in adults who cycled to work in London, Ackermann-Liebrich 1 speculated that “very short, high peaks of exposure contribute more to total load of inhaled pollutants and, thus, we ought to control not only the mean pollutant levels but avoid higher peaks.” In our initial analyses, we found no …

This study aimed to compare the use of outpatient ambulatory care versus admission for intravenous antibiotics in the management of preseptal cellulitis.This is a retrospective consecutive cohort study of children younger than 16 years presenting to an Inner London Paediatric Emergency Department with signs and symptoms of preseptal cellulitis.A total of 94 cases were identified during a 17-month period. Of them, 30 children were prescribed oral antibiotics. One child did not receive treatment. Of the 63 children prescribed with intravenous antibiotics, 42 were managed on an ambulatory basis and 21 were admitted. There was no significant difference in duration of treatment in days between those on ambulatory management and those admitted (2.79 ± 0.8 vs 2.76 ± 1.9, P = 0.94) or in the rate of complications. The net cost saving was $205,924 (£131,065;OV0556;147,578) overall, equal to $4900 (£3120;OV0556;3513) per patient.Ambulatory intravenous antibiotics with daily review are a safe and cost-effective alternative to inpatient admission in simple preseptal cellulitis for children in our population who require parenteral antibiotics.