The Impact of Malnutrition on the Developing Lung and Long-Term Lung Health: A Narrative Review of Global Literature.

Worldwide, over 2 billion children under the age of 5 experience stunting, wasting, or are underweight. Malnutrition contributes to 45% of all deaths in this age group (approximately 3.1 million deaths) [1]. Poverty, food insecurity, suboptimal feeding practices, climate change, and conflict are all contributing factors. Malnutrition causes significant respiratory problems, including increased risk of respiratory infections, impaired lung function, and increased risk of subsequent adult respiratory disease, including asthma, COPD, and lung cancer. Childhood malnutrition not only has serious consequences for children's health but it also has numerous consequences on wellbeing and educational attainment. Childhood malnutrition is a complex and multifaceted problem. However, by understanding and addressing the underlying causes, and investing in prevention and treatment programs, it is possible to maximize children's health and wellbeing on a global scale. This narrative review will focus on the impact of childhood malnutrition on lung development, the consequent respiratory disease, and what actions can be taken to reduce the burden of malnutrition on lung health.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Best step-up treatments for children with uncontrolled asthma: a systematic review and network meta-analysis of individual participant data.

BACKGROUND: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting ß2-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo. RESULTS: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control. CONCLUSIONS: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

BACKGROUND: Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR variant F508del is the commonest CF-causing variant (found in up to 90% of people with CF (pwCF)). The F508del variant lacks meaningful CFTR function - faulty protein is degraded before reaching the cell membrane, where it needs to be to effect transepithelial salt transport. Corrective therapy could benefit many pwCF. This review evaluates single correctors (monotherapy) and any combination of correctors (most commonly lumacaftor, tezacaftor, elexacaftor, VX-659, VX-440 or VX-152) and a potentiator (e.g. ivacaftor) (dual and triple therapies). OBJECTIVES: To evaluate the effects of CFTR correctors (with or without potentiators) on clinically important benefits and harms in pwCF of any age with class II CFTR mutations (most commonly F508del). SEARCH METHODS: We searched the Cochrane CF Trials Register (28 November 2022), reference lists of relevant articles and online trials registries (3 December 2022). SELECTION CRITERIA: Randomised controlled trials (RCTs) (parallel design) comparing CFTR correctors to control in pwCF with class II mutations. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias and judged evidence certainty (GRADE); we contacted investigators for additional data. MAIN RESULTS: We included 34 RCTs (4781 participants), lasting between 1 day and 48 weeks; an extension of two lumacaftor-ivacaftor studies provided additional 96-week safety data (1029 participants). We assessed eight monotherapy RCTs (344 participants) (4PBA, CPX, lumacaftor, cavosonstat and FDL169), 16 dual-therapy RCTs (2627 participants) (lumacaftor-ivacaftor or tezacaftor-ivacaftor) and 11 triple-therapy RCTs (1804 participants) (elexacaftor-tezacaftor-ivacaftor/deutivacaftor; VX-659-tezacaftor-ivacaftor/deutivacaftor; VX-440-tezacaftor-ivacaftor; VX-152-tezacaftor-ivacaftor). Participants in 21 RCTs had the genotype F508del/F508del, in seven RCTs they had F508del/minimal function (MF), in one RCT F508del/gating genotypes, in one RCT either F508del/F508del genotypes or F508del/residual function genotypes, in one RCT either F508del/gating or F508del/residual function genotypes, and in three RCTs either F508del/F508del genotypes or F508del/MF genotypes. Risk of bias judgements varied across different comparisons. Results from 16 RCTs may not be applicable to all pwCF due to age limits (e.g. adults only) or non-standard designs (converting from monotherapy to combination therapy). Monotherapy Investigators reported no deaths or clinically relevant improvements in quality of life (QoL). There was insufficient evidence to determine effects on lung function. No placebo-controlled monotherapy RCT demonstrated differences in mild, moderate or severe adverse effects (AEs); the clinical relevance of these events is difficult to assess due to their variety and few participants (all F508del/F508del). Dual therapy In a tezacaftor-ivacaftor group there was one death (deemed unrelated to the study drug). QoL scores (respiratory domain) favoured both lumacaftor-ivacaftor and tezacaftor-ivacaftor therapy compared to placebo at all time points (moderate-certainty evidence). At six months, relative change in forced expiratory volume in one second (FEV1) % predicted improved with all dual combination therapies compared to placebo (high- to moderate-certainty evidence). More pwCF reported early transient breathlessness with lumacaftor-ivacaftor (odds ratio (OR) 2.05, 99% confidence interval (CI) 1.10 to 3.83; I2 = 0%; 2 studies, 739 participants; high-certainty evidence). Over 120 weeks (initial study period and follow-up), systolic blood pressure rose by 5.1 mmHg and diastolic blood pressure by 4.1 mmHg with twice-daily 400 mg lumacaftor-ivacaftor (80 participants). The tezacaftor-ivacaftor RCTs did not report these adverse effects. Pulmonary exacerbation rates decreased in pwCF receiving additional therapies to ivacaftor compared to placebo (all moderate-certainty evidence): lumacaftor 600 mg (hazard ratio (HR) 0.70, 95% CI 0.57 to 0.87; I2 = 0%; 2 studies, 739 participants); lumacaftor 400 mg (HR 0.61, 95% CI 0.49 to 0.76; I2 = 0%; 2 studies, 740 participants); and tezacaftor (HR 0.64, 95% CI 0.46 to 0.89; 1 study, 506 participants). Triple therapy No study reported any deaths (high-certainty evidence). All other evidence was low- to moderate-certainty. QoL respiratory domain scores probably improved with triple therapy compared to control at six months (six studies). There was probably a greater relative and absolute change in FEV1 % predicted with triple therapy (four studies each across all combinations). The absolute change in FEV1 % predicted was probably greater for F508del/MF participants taking elexacaftor-tezacaftor-ivacaftor compared to placebo (mean difference 14.30, 95% CI 12.76 to 15.84; 1 study, 403 participants; moderate-certainty evidence), with similar results for other drug combinations and genotypes. There was little or no difference in adverse events between triple therapy and control (10 studies). No study reported time to next pulmonary exacerbation, but fewer F508del/F508del participants experienced a pulmonary exacerbation with elexacaftor-tezacaftor-ivacaftor at four weeks (OR 0.17, 99% CI 0.06 to 0.45; 1 study, 175 participants) and 24 weeks (OR 0.29, 95% CI 0.14 to 0.60; 1 study, 405 participants); similar results were seen across other triple therapy and genotype combinations. AUTHORS' CONCLUSIONS: There is insufficient evidence of clinically important effects from corrector monotherapy in pwCF with F508del/F508del. Additional data in this review reduced the evidence for efficacy of dual therapy; these agents can no longer be considered as standard therapy. Their use may be appropriate in exceptional circumstances (e.g. if triple therapy is not tolerated or due to age). Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar small improvements in QoL and respiratory function with lower pulmonary exacerbation rates. While the effect sizes for QoL and FEV1 still favour treatment, they have reduced compared to our previous findings. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population, lumacaftor-ivacaftor had an important impact on respiratory function with no apparent immediate safety concerns, but this should be balanced against the blood pressure increase and shortness of breath seen in longer-term adult data when considering lumacaftor-ivacaftor. Data from triple therapy trials demonstrate improvements in several key outcomes, including FEV1 and QoL. There is probably little or no difference in adverse events for triple therapy (elexacaftor-tezacaftor-ivacaftor/deutivacaftor; VX-659-tezacaftor-ivacaftor/deutivacaftor; VX-440-tezacaftor-ivacaftor; VX-152-tezacaftor-ivacaftor) in pwCF with one or two F508del variants aged 12 years or older (moderate-certainty evidence). Further RCTs are required in children under 12 years and those with more severe lung disease.

The impact of poor housing and indoor air quality on respiratory health in children.

It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor. Educational aims: The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study.

BACKGROUND: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds). METHODS: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of preschool wheeze or asthma. RESULTS: Annual asthma incidence rates decreased by 51% from 1403.4 (95% CI 1383.7 to 1423.2) in 2008 to 688.0 (95% CI 676.3 to 699.9) per 105 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year olds (decreasing by 65%, from 2556.9 (95% CI 2509.8 to 2604.7) to 892.3 (95% CI 866.9 to 918.3) per 105 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 (95% CI 1110.6 to 1169.7) to 739.9 (95% CI 720.5 to 759.8)) and 20% (572.3 (95% CI 550.4 to 594.9) to 459.5 (95% CI 442.9 to 476.4)) per 105 PYs, respectively. The incidence of preschool wheeze decreased over time and was slightly more pronounced in the 1‒3 year-olds than in the 4-year-olds. Prevalence of asthma and preschool wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (95% CI 1.31 to 1.35) per 10 PYs in 2008 to 1.81 (95% CI 1.78 to 1.83) per 10 PYs in 2018. CONCLUSION: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1-5-year-olds; this was accompanied by a decline in asthma prevalence. Preschool wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing.

Short-acting ß2-agonists and exacerbations in children with asthma in England: SABINA Junior.

Background: Prescription of three or more short-acting ß2-agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited. Methods: This study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or more versus fewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders. Results: Overall 48 560, 110 091 and 111 891 paediatric patients with asthma were aged 1‒5, 6‒11 and 12‒17 years, respectively. During the baseline period, 22 423 (46.2%), 42 137 (38.3%) and 40 288 (36.0%) in these three age cohorts, respectively, were prescribed three or more SABA canisters per year. Across all age ranges, the rate of future asthma exacerbations in those prescribed three or more versus fewer than three SABA canisters per year was at least two-fold higher. >30% of patients across all age cohorts were not prescribed inhaled corticosteroids (ICS), and the median proportion of days covered was only 33%, suggesting inadequate prescribing of ICS. Conclusion: In children, higher SABA prescriptions at baseline were associated with increased future exacerbation rates. These findings highlight the need for monitoring prescription of three or more SABA canisters per year to identify children with asthma at risk of exacerbations.

Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a common, life-shortening, genetic disorder in populations of Northern European descent caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces, and the mutation most notably affects the airways. In the lungs of people with CF, the defective protein compromises mucociliary clearance and makes the airway prone to chronic infection and inflammation, damaging the structure of the airways and eventually leading to respiratory failure. In addition, abnormalities in the truncated CFTR protein lead to other systemic complications, including malnutrition, diabetes and subfertility. Five classes of mutation have been described, depending on the impact of the mutation on the processing of the CFTR protein in the cell. In class I mutations, premature termination codons prevent the production of any functional protein, resulting in severe CF. Therapies targeting class I mutations aim to enable the normal cellular mechanism to read through the mutation, potentially restoring the production of the CFTR protein. This could, in turn, normalise salt transport in the cells and decrease the chronic infection and inflammation that characterises lung disease in people with CF. This is an update of a previously published review. OBJECTIVES: To evaluate the benefits and harms of ataluren and similar compounds on clinically important outcomes in people with CF with class I mutations (premature termination codons). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles. The last search of the Cochrane Cystic Fibrosis Trials Register was conducted on 7 March 2022. We searched clinical trial registries maintained by the European Medicines Agency, the US National Institutes of Health and the World Health Organization. The last search of the clinical trials registries was conducted on 4 October 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) of parallel design comparing ataluren and similar compounds (specific therapies for class I mutations) with placebo in people with CF who have at least one class I mutation. DATA COLLECTION AND ANALYSIS: For the included trials, the review authors independently extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE; trial authors were contacted for additional data. MAIN RESULTS: Our searches identified 56 references to 20 trials; of these, 18 trials were excluded. Both the included parallel RCTs compared ataluren to placebo for 48 weeks in 517 participants (males and females; age range six to 53 years) with CF who had at least one nonsense mutation (a type of class I mutation). The certainty of evidence and risk of bias assessments for the trials were moderate overall. Random sequence generation, allocation concealment and blinding of trial personnel were well documented; participant blinding was less clear. Some participant data were excluded from the analysis in one trial that also had a high risk of bias for selective outcome reporting. PTC Therapeutics Incorporated sponsored both trials with grant support from the Cystic Fibrosis Foundation, the US Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health. The trials reported no difference between treatment groups in terms of quality of life, and no improvement in respiratory function measures. Ataluren was associated with a higher rate of episodes of renal impairment (risk ratio 12.81, 95% confidence interval 2.46 to 66.65; P = 0.002; I2 = 0%; 2 trials, 517 participants). The trials reported no treatment effect for ataluren for the review's secondary outcomes of pulmonary exacerbation, computed tomography score, weight, body mass index and sweat chloride. No deaths were reported in the trials. The earlier trial performed a post hoc subgroup analysis of participants not receiving concomitant chronic inhaled tobramycin (n = 146). This analysis demonstrated favourable results for ataluren (n = 72) for the relative change in forced expiratory volume in one second (FEV1) per cent (%) predicted and pulmonary exacerbation rate. The later trial aimed to prospectively assess the efficacy of ataluren in participants not concomitantly receiving inhaled aminoglycosides, and found no difference between ataluren and placebo in FEV1 % predicted and pulmonary exacerbation rate.  AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effect of ataluren as a therapy for people with CF with class I mutations. One trial reported favourable results for ataluren in a post hoc subgroup analysis of participants not receiving chronic inhaled aminoglycosides, but these were not reproduced in the later trial, suggesting that the earlier results may have occurred by chance. Future trials should carefully assess for adverse events, notably renal impairment, and consider the possibility of drug interactions. Cross-over trials should be avoided, given the potential for the treatment to change the natural history of CF.

Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis.

Cystic fibrosis (CF) has entered the era of variant-specific therapy, tailored to the genetic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators, the first variant-specific therapy available, have transformed the management of CF. The latest standards of care from the European CF Society (2018) did not include guidance on variant-specific therapy, as CFTR modulators were becoming established as a novel therapy. We have produced interim standards to guide healthcare professionals in the provision of variant-specific therapy for people with CF. Here we provide evidence-based guidance covering the spectrum of care, established using evidence from systematic reviews and expert opinion. Statements were reviewed by key stakeholders using Delphi methodology, with agreement (≥80%) achieved for all statements after one round of consultation. Issues around accessibility are discussed and there is clear consensus that all eligible people with CF should have access to variant-specific therapy.

Child poverty and health inequalities in the UK: a guide for paediatricians.

One in three children in the UK lives in relative poverty. There are clear and consistent links between child poverty and paediatric morbidity and mortality. In this review, we discuss drivers for family poverty in the UK, and how this leads to poor child health outcomes. We present a framework for healthcare professionals and institutions to consider interventions and strategies relating to socioeconomic health inequalities. We will focus on approaches to mitigate the effects of child poverty on children using our services at a local level and outline the importance of healthcare workers advocating for structural and high-level policy change to address the deep-rooted societal problems that cause child poverty.

Comparison of UK paediatric SARS-CoV-2 admissions across the first and second pandemic waves.

BACKGROUND: We hypothesised that the clinical characteristics of hospitalised children and young people (CYP) with SARS-CoV-2 in the UK second wave (W2) would differ from the first wave (W1) due to the alpha variant (B.1.1.7), school reopening and relaxation of shielding. METHODS: Prospective multicentre observational cohort study of patients <19 years hospitalised in the UK with SARS-CoV-2 between 17/01/20 and 31/01/21. Clinical characteristics were compared between W1 and W2 (W1 = 17/01/20-31/07/20,W2 = 01/08/20-31/01/21). RESULTS: 2044 CYP < 19 years from 187 hospitals. 427/2044 (20.6%) with asymptomatic/incidental SARS-CoV-2 were excluded from main analysis. 16.0% (248/1548) of symptomatic CYP were admitted to critical care and 0.8% (12/1504) died. 5.6% (91/1617) of symptomatic CYP had Multisystem Inflammatory Syndrome in Children (MIS-C). After excluding CYP with MIS-C, patients in W2 had lower Paediatric Early Warning Scores (PEWS, composite vital sign score), lower antibiotic use and less respiratory and cardiovascular support than W1. The proportion of CYP admitted to critical care was unchanged. 58.0% (938/1617) of symptomatic CYP had no reported comorbidity. Patients without co-morbidities were younger (42.4%, 398/938, <1 year), had lower PEWS, shorter length of stay and less respiratory support. CONCLUSIONS: We found no evidence of increased disease severity in W2 vs W1. A large proportion of hospitalised CYP had no comorbidity. IMPACT: No evidence of increased severity of COVID-19 admissions amongst children and young people (CYP) in the second vs first wave in the UK, despite changes in variant, relaxation of shielding and return to face-to-face schooling. CYP with no comorbidities made up a significant proportion of those admitted. However, they had shorter length of stays and lower treatment requirements than CYP with comorbidities once those with MIS-C were excluded. At least 20% of CYP admitted in this cohort had asymptomatic/incidental SARS-CoV-2 infection. This paper was presented to SAGE to inform CYP vaccination policy in the UK.

Impact of indoor environment on children's pulmonary health.

INTRODUCTION: A child's living environment has a significant impact on their respiratory health, with exposure to poor indoor air quality (IAQ) contributing to potentially lifelong respiratory morbidity. These effects occur throughout childhood, from the antenatal period through to adolescence. Children are particularly susceptible to the effects of environmental insults, and children living in socioeconomic deprivation globally are more likely to breathe air both indoors and outdoors, which poses an acute and long-term risk to their health. Adult respiratory health is, at least in part, determined by exposures and respiratory system development in childhood, starting in utero. AREAS COVERED: This narrative review will discuss, from a global perspective, what contributes to poor IAQ in the child's home and school environment and the impact that indoor air pollution exposure has on respiratory health throughout the different stages of childhood. EXPERT OPINION: All children have the right to a living and educational environment without the threat of pollution affecting their health. Action is needed at multiple levels to address this pressing issue to improve lifelong respiratory health. Such action should incorporate a child's rights-based approach, empowering children, and their families, to have access to clean air to breathe in their living environment.

Clinical trials and outcome reporting in congenital diaphragmatic hernia overlook long-term health and functional outcomes-A plea for core outcomes.

AIM: To review the selection, measurement and reporting of outcomes in studies of interventions in Congenital Diaphragmatic Hernia (CDH). METHODS: We searched the Cochrane Central Register of Controlled Trials from 2000-2020 for randomised trials and observational studies. Outcomes reported were classified into seven key domains modelled on the patient journey. RESULTS: Our search yielded 118 papers; 27 were eligible. The most frequent domains measured were 'short-term markers of disease activity' (17/27), whereas long-term outcomes (3/27) and outcomes relating to functional health status (8/27) were reported infrequently. There was heterogeneity in the methods and timing of outcome reporting. Primary outcomes were varied and not always clearly stated. CONCLUSION: Long-term health and functional outcomes involving interventional studies in CDH are infrequently reported, which hinders the process of shared decision-making and evidence-based healthcare. A CDH core outcome set is needed to standardise outcome reporting that is relevant to both families and healthcare teams.

Long term outcomes in CDH: Cardiopulmonary outcomes and health related quality of life.

BACKGROUND: With improvements in clinical management and an increase in CDH survivorship there is a crucial need for better understanding of long-term health outcomes in CDH. AIM: To investigate the prevalence of cardiopulmonary health morbidity and health related quality of life (HRQoL) in CDH survivors. METHODS: We included all studies (n = 65) investigating long-term cardiopulmonary outcomes in CDH patients more than 2 years published in the last 30 years. The Newcastle-Ottawa Scale and the CASP checklist for cohort studies were utilized to assess study quality. Results were reported descriptively and collated by age group where possible. RESULTS: The incidence of pulmonary hypertension was highly variable (4.5-38%), though rates (%) appeared to diminish after 5 years of age. Lung function indices and radiological outcomes were frequently abnormal, and Health Related Quality of Life (HRQoL) reduced also. Long term diseases notably emphysema and COPD are not yet fully described in the contemporary literature. CONCLUSION: This study underscores cardiopulmonary health morbidity and a reduced HRQoL among CDH survivors. Where not already available dedicated multidisciplinary follow-up clinics should be established to support these vulnerable patients transition safely into adulthood. Future research is therefore needed to investigate the risk factors for cardiopulmonary ill health and morbidity in CDH survivors. TYPE OF STUDY: Systematic review of case control and cohort studies.

Allergen Management in Children with Type 2-High Asthma.

Children exposed to various indoor and outdoor allergens are placed at an increased risk of developing asthma in later life, with sensitization in these individuals being a strong predictor of disease morbidity. In addition, aeroallergen exposure influences asthma outcomes through an interplay with adverse determinants of health. The goal of this review is to provide an introductory overview of factors related to aeroallergen exposure in type 2-high childhood asthma. These include the relevance of exposure in asthma exacerbations and severity, and the evidence-base for avoidance and treatment for sensitization to these allergens. This review will focus on both indoor aeroallergens (house dust mite, pet, cockroach, mold, and rodent) and outdoor aeroallergens (pollens and molds). Treatment of aeroallergen sensitization in children with asthma includes avoidance and removal measures, although there is limited evidence of clinical benefit especially with single-strategy approaches. We will also address the interplay of aeroallergens and climate change, adverse social determinants, and the current COVID-19 pandemic, when we have seen a dramatic reduction in asthma exacerbations and emergency department visits among children. While there are many factors that are hypothesized to contribute to this reduction, among them is a reduced exposure to outdoor seasonal aeroallergens.

Deprescribing montelukast in children with asthma: a systematic review.

BACKGROUND: National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP). OBJECTIVE: To systematically review evidence regarding deprescribing montelukast in CYP with established asthma. DESIGN: Systematic review. DATA SOURCES: Embase, Medline, PubMed and CINAHL were searched up to October 2020. STUDY SELECTION: Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included. RESULTS: The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased. CONCLUSION: Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP. PROSPERO REGISTRATION NUMBER: CRD42020213971.