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Objectives To demonstrate the challenges of interpreting cross-country comparisons of paediatric asthma hospital admission rates as an indicator of primary care quality. Methods We used hospital administrative data from >10 million children aged 6–15 years, resident in Austria, England, Finland, Iceland, Ontario (Canada), Sweden or Victoria (Australia) between 2008 and 2015. Asthma hospital admission and emergency department (ED) attendance rates were compared between countries using Poisson regression models, adjusted for age and sex. Results Hospital admission rates for asthma per 1000 child-years varied eight-fold across jurisdictions. Admission rates were 3.5 times higher when admissions with asthma recorded as any diagnosis were considered, compared with admissions with asthma as the primary diagnosis. Iceland had the lowest asthma admission rates; however, when ED attendance rates were considered, Sweden had the lowest rate of asthma hospital contacts. Conclusions The large variations in childhood hospital admission rates for asthma based on the whole child population reflect differing definitions, admission thresholds and underlying disease prevalence rather than primary care quality. Asthma hospital admissions among children diagnosed with asthma is a more meaningful indicator for inter-country comparisons of primary care quality.

Background/objectiveLimited research exists regarding the association between grandmaternal smoking during pregnancy and the risk for asthma and altered lung function in grandchildren. This study aimed to investigate this association in a three-generation design.Methods37 291 participants (25 747 adults and 11 544 children) were included from the Lifelines study, a prospective longitudinal three generation cohort study in The Netherlands. Spirometry was available in 69.5% and 61.1% of the included adults and children. Logistic and linear regression were used to analyse the association between grandmaternal smoking during pregnancy and (1) asthma, (2) early childhood asthma (ie, onset before 6 years) and (3) lung function level. Maternal and paternal grandmaternal smoking were studied separately and the analyses were stratified by adult/child and by gender. The analyses were adjusted for gender, current smoking, birth variables and socioeconomic status.ResultsIn the adult population, maternal grandmaternal smoking during pregnancy was associated with a higher risk for asthma (OR (95% CI): 1.38 (1.06 to 1.79)), early childhood asthma (1.49 (95% CI 1.06 to 2.11)) and a lower FEV1/FVC% predicted (B (95% CI): −1.04 (−1.91 to −0.16) in men. These findings were not observed in a separate analysis of children that participated in this study. There was also no significant association between paternal grandmaternal smoking and asthma/lung function.ConclusionMaternal grandmaternal smoking during pregnancy is associated with higher asthma risk and lower lung function in male grandchildren and a reverse effect in male grandchildren of subsequent generations. Our study highlights the deep-rooted effects of tobacco smoking across generations.

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO. In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.

Background Asthma, a common childhood condition, often presents with chronic cough. While evaluating for chronic cough, many specialists obtain a baseline chest radiograph (CR) to assess for other causes. Usually read as ‘normal’, sometimes CRs will reveal evidence of airway inflammation in the form of subtle findings, such as ‘increased interstitial markings’ or ‘peribronchial thickening’. There is sparse literature in the outpatient setting correlating findings on baseline CRs with adverse outcomes such as systemic steroid use, emergency department (ED) visit or hospitalisation. Methods This was a retrospective study of patients seen at our institution's Pediatric Pulmonology outpatient clinic. We reviewed the charts of all new patients aged 0–18 years who presented between January 2015 and December 2017. Patients were included if they were diagnosed with asthma, had a CR after the initial visit and were followed up at least twice. Adverse outcomes include systemic steroid use, ED visit or hospitalisation. Results 130 subjects were included. 89 subjects had clear CRs and 41 subjects had CRs with airway inflammation. Overall events were higher in the airway inflammation group (22.5% vs 46.3%, respectively, p Conclusion This study shows a positive correlation between airway inflammation findings on baseline CR and subsequent ED visits in patients with asthma.

BackgroundThere is conflicting research about the association between asthma and poor educational attainment that may be due to asthma definitions. Our study creates seven categories of current chronic and acute asthma to investigate if there is an association for poorer educational attainment at age 6–7 years, and the role of respiratory infections and school absence.MethodsThis study used a population-based electronic cross-sectional birth cohort 1998–2005, in Wales, UK, using health and education administrative datasets. Current asthma or wheeze categories were developed using clinical management guidelines in general practice (GP) data, acute asthma was inpatient hospital admissions and respiratory infections were the count of GP visits, from birth to age 6–7 years. We used multilevel logistic regression grouped by schools to ascertain if asthma or wheeze was associated with not attaining the expected level in teacher assessment at Key Stage 1 (KS1) adjusting for sociodemographics, perinatal, other respiratory illness and school characteristics. We tested if absence from school was a mediator in this relationship using the difference method.ResultsThere were 85 906 children in this population representative cohort with 7-year follow-up. In adjusted multilevel logistic regression, only asthma inpatient hospital admission was associated with increased risk for not attaining the expected level at KS1 (adjusted OR 1.14 95% CI (1.02 to 1.27)). Lower respiratory tract infection (LRTI) GP contacts remained an independent predictor for not attaining the expected level of education. Absence from school was a potential mediator of the association between hospital admission and educational attainment.ConclusionsClinicians and educators need to be aware that children who have inpatient hospital admissions for asthma or wheeze, or repeated LRTI, may require additional educational support for their educational outcomes.

Background Recent advancements in drilling technology led to a rapid increase in natural gas development (NGD). Air pollution may be elevated in these areas and may vary by drilling type (conventional and unconventional), production volume and gas flaring. Impacts of NGD on paediatric asthma are largely unknown. This study quantifies associations between specific NGD activities and paediatric asthma hospitalizations in Texas. Methods We leveraged a database of Texas inpatient hospitalizations between 2000 and 2010 at the zip code level by quarter to examine associations between NGD and paediatric asthma hospitalizations, where our primary outcome is 0 vs ≥1 hospitalization. We used quarterly production reports to assess additional drilling-specific exposures at the zip code-level including drilling type, production and gas flaring. We developed logistic regression models to assess paediatric asthma hospitalizations by zip code-quarter-year observations, thus capturing spatiotemporal exposure patterns. Results We observed increased odds of ≥1 paediatric asthma hospitalization in a zip code per quarter associated with increasing tertiles of NGD exposure and show that spatiotemporal variation impacts results. Conventional drilling, compared with no drilling, is associated with odds ratios up to 1.23 [95% confidence interval (CI): 1.13, 1.34], whereas unconventional drilling is associated with odds ratios up to 1.59 (95% CI: 1.46, 1.73). Increasing production volumes are associated with increased paediatric asthma hospitalizations in an exposure–response relationship, whereas associations with flaring volumes are inconsistent. Conclusions We found evidence of associations between paediatric asthma hospitalizations and NGD, regardless of drilling type. Practices related to production volume may be driving these positive associations.

BackgroundHospitalisation for bronchiolitis is a risk factor for asthma and impaired lung function during childhood, but outcomes in young adults are poorly described. Our primary aim was to study the prevalence of asthma and atopy, and lung function at 17–20 years of age after bronchiolitis in infancy and, secondarily, the impact of viral aetiology (respiratory syncytial virus (RSV) vs non-RSV) and sex on these outcomes.MethodsThis Norwegian cohort study enrolled 225 young adults hospitalised for bronchiolitis in infancy during 1996–2001 and 167 matched control subjects. The follow-up included questionnaires for asthma and examinations of lung function and atopy. Outcomes were analysed by mixed effects regressions.ResultsCurrent asthma was more frequent in the postbronchiolitis group versus the control group: 25.1% (95% CI 19.0% to 31.2%) vs 13.1% (95% CI 7.9% to 18.2%), but not atopy: 44.3% (95% CI 37.1% to 51.5%) vs 48.2% (95% CI 40.5% to 55.8%), adjusted predicted proportions (95% CIs). Asthma prevalence did not differ between the RSV group and the non-RSV group: 24.0% (95% CI 16.1% to 32.0%) vs 23.8% (95% CI 12.8% to 34.7%) nor between sexes. Forced expiratory volume in 1 s (FEV1), the ratio FEV1/forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC, were lower in the postbronchiolitis group.ConclusionYoung adults hospitalised for bronchiolitis had higher prevalence of asthma, but not atopy, and a more obstructive lung function pattern than control subjects. The asthma prevalence was high after both RSV bronchiolitis and non-RSV bronchiolitis, and there was no difference between sexes. Bronchiolitis in infancy is associated with respiratory morbidity persisting into young adulthood.

Background Clinical practice guidelines (CPGs) aim to standardize clinical care. Increasingly, hospitals rely on locally produced guidelines alongside national guidance. This study examines variation between national and local CPGs, using the example of acute paediatric asthma guidance from the United Kingdom and the Netherlands. Methods Fifteen British and Dutch local CPGs were collected with the matching national guidance for the management of acute asthma in children under 18 years old. The drug sequences, routes and methods of administration recommended for patients with severe asthma and the tone of recommendation across both types of CPGs were schematically represented. Deviations from national guidance were measured. Variation in recommended doses of intravenous salbutamol was examined. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II. Results British and Dutch national CPGs differed in the recommended drug choices, sequences, routes and methods of administration for severe asthma. Dutch national guidance was more rigidly defined. Local British CPGs diverged from national guidance for 23% of their recommended interventions compared to 8% for Dutch local CPGs. Five British local guidelines and two Dutch local guidelines differed from national guidance for multiple treatment steps. Variation in second-line recommendations was greater than for first-line recommendations across local CPGs from both countries. Recommended starting doses for salbutamol infusions varied by more than tenfold. The quality of the sampled local CPGs was low across all AGREE II domains. Conclusions Local CPGs for the management of severe acute paediatric asthma featured substantial variation and frequently diverged from national guidance. Although limited to one condition, this study suggests that unmeasured variation across local CPGs may contribute to variation of care more broadly, with possible effects on healthcare quality.

BackgroundNeural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.MethodsThirty-eight asthmatics and 19 non-asthmatics (aged 14–21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs.ResultsNon-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed.ConclusionNEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.

BackgroundThere is a high burden of asthma morbidity and mortality in Latin America. It has been proposed that this relates to limited access to diagnostic tests, asthma medications and specialised doctors. However, little is known of what caregivers of asthmatic children and healthcare professionals (HCPs) perceive as barriers and facilitators to adequate care. We aimed to explore the barriers and facilitators to asthma care access from caregivers’ and HCP’s perspective in an Ecuadorian low-resource setting.MethodsIn 2017, we conducted 5 focus group discussions (FGD) with 20 caregivers of asthmatic children and 12 in-depth interviews with 3 paediatricians, 6 general doctors and 3 respiratory therapists in Esmeraldas city, Ecuador. FGDs and interviews were digitally recorded, transcribed, open-coded in QDA Miner, categorised using an interpretative phenomenological approach and analysed thematically. Barriers and facilitators were classified into availability, accessibility, acceptability and contact of healthcare services, based on Tanahashi model of health service access.ResultsLimited resources, use of alternative medicines, fear of medication side-effects and lack of specific training for doctors and knowledge in families were common barriers for both caregivers and HCPs. Caregivers and HCPs proposed the implementation of public health asthma-focused programmes that would include close community-based follow-up of people with asthma, educational sessions for their families and public engagement activities. HCPs also suggested implementing training programmes on asthma management for general doctors.ConclusionMultiple barriers identified by caregivers and HCPs referred to economic and health service organisational issues, fear of side effects of medication or ineffective self-management. Increasing caregivers and HCPs’ asthma knowledge, as well as HCPs’ communication skills to establish a patient-centred approach with a shared decision-making process could improve asthma care in this setting.

Every child and young person has the right to breathe clean air, with healthy lungs. Preconception, in utero and early life exposures, affect children’s lungs, their lung growth and their long-term health. Government, societal and individual action to address this is needed, including the provision and distribution of the necessary resources, both to protect children now and to prevent future ill health, disability and premature death.1–5 Government, charities, professional bodies and other organisations must consider impacts on child health in all their policies and ensure that children, as well as their families and carers, have appropriate protection and support. To address this, the Asthma UK and British Lung Foundation Partnership Children’s Charter for Lung Health, endorsed by The British Paediatric Respiratory Society and the British Thoracic Society as well as the Association of Chartered Physiotherapists in Respiratory Care and the Association of Respiratory Nurse Specialistshere sets out 10 principles in three groups to guide policy development and action (figure 1). Figure 1 The Asthma UK and British Lung Foundation Partnership Children’s Charter for Lung Health. ### Giving lungs the best start—parental health and health in pregnancy Healthy lung growth and development starts before birth. Healthy babies require healthy parents. Addressing inequality, social deprivation, structural racism and the corporate determinants of health6 is fundamental to this, so that preconception and pregnancy risk factors like poverty, poor housing, smoking, dietary factors, obesity and stress can be reduced or avoided. Parents must have the capabilities to live in as healthy a way as possible, in all aspects of daily life, in the home and at work. ### Growing lungs need to breathe clean air Exposure to particulate and other forms of pollution harms lung growth, increases the risk of developing lung disease and causes acute attacks in children who …

We examined 4388 children from the 2003 to 2006 National Health and Nutrition Examination Survey and used survey-design-adjusted multivariable logistic regression to evaluate associations between dietary advanced glycation end product (AGE) and meat consumption frequencies and respiratory symptoms. Higher AGE intake was significantly associated with increased odds of wheezing (adjusted OR 1.18; 95% CI 1.02 to 1.36), wheeze-disrupted sleep (1.26; 95% CI 1.05 to 1.51) and exercise (1.34; 95% CI 1.08 to 1.67) and wheezing requiring prescription medication (1.35; 95% CI 1.13 to 1.63). Higher intake of non-seafood meats was associated with wheeze-disrupted sleep (2.32; 95% CI 1.11 to 4.82) and wheezing requiring prescription medication (2.23; 95% CI 1.10 to 4.54).

WOS: 000471695200014, PubMed ID: 31006357, Background To investigate the behaviour of the inflammatory marker neutrophil-to-lymphocyte ratio (NLR) in the presence of peripheral blood eosinophilia (PBE) in paediatric asthma patients with lower respiratory tract (LRT) infections. Methods This retrospective study enrolled consecutive patients aged >= 5 years who were diagnosed with asthma and whose haemogram values were available. The patients were further subdivided based on the presence or absence of LRT infections and allergies. NLR and C-reactive protein (CRP) were evaluated in relation to the presence or absence of PBE (>= 4% eosinophils). Results A total of 991 patients were enrolled in the study. Patients with LRT infections had significantly higher leucocyte and neutrophil counts, a greater NLR and a higher level of CRP compared with patients without LRT infections. Overall, patients with PBE had significantly lower NLRs and CRP regardless of the presence or absence of an LRT infection. The PBE percentage showed moderate inverse correlations with NLR (r = -0.34) and CRP (r = -0.20). Conclusion The presence of PBE was significantly associated with lower NLR and CRP regardless of the presence or absence of an infectious condition.

BACKGROUND: Non-pharmaceutical interventions (NPI) mitigation measures implemented to mitigate COVID-19 has brought unprecedented global impact. Changes in daily living routines, reduction in physical activities, and changes in environmental indicators were suggested to positively impact paediatric asthma indicators in western cultures. Little is known about such impact in developing countries. This study investigated the potential impact of COVID-19 NPI measures on paediatric asthma exacerbation admissions in Northern Jordan. METHODS: Aggregate data from a paediatric hospital, Princess Rahma Pediatric Teaching Hospital, and King Abdulla University Teaching Hospital were utilised from 2018 to 2020. The number of paediatric asthma exacerbation admissions was calculated by week and compared by year, lockdown status, and weeks for lockdown (weeks 13-19). The stringency index was correlated with the number of weekly paediatric asthma exacerbation admissions for 2020. RESULTS: A total of 1,207 paediatric asthma exacerbation admissions were reported; 40.3%, 35.2%, and 24.5% in 2018, 2019 and 2020, respectively. The number of weekly admissions ranged from 1 to 13 paediatric asthma cases (mean (SD) = 7.6 (2.7)). In 2018 and 2019, respectively, mean weekly admissions were 9.2 (1.9) and 8.0 (2.0) paediatric asthma cases, while in 2020 the mean was 5.6 (2.7) cases. Significant differences in mean weekly paediatric asthma exacerbation admissions were detected by year, with mean weekly admissions for 2020 being significantly lower than that for 2018 and 2019. During the lockdown (22 March to 1 May 2020), mean weekly admissions (2.6 (1.4)) was significantly lower than that before the lockdown (8.6 (2.0)) and after the lockdown (5.2 (2.0)). For the lockdown weeks only, the mean admissions for the year 2020 was significantly lower than that for years 2019 and 2018. The stringency index negatively correlated with the number of weekly admissions. CONCLUSION: NPI measures in Jordan seem to have positively impacted paediatric asthma exacerbation admissions. Further studies are needed to draw public health policies and fine-tune environmental and community policies.

The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma.

Purpose of review Asthma is a chronic inflammatory airway disorder that can involve the entire bronchial tree. Increasing evidence shows that ventilation heterogeneity and small airway dysfunction are relevant factors in the pathogenesis of asthma and represent a hallmark in adults with persistent asthma. Little is known about the contribution of peripheral airway impairment in paediatric asthma, mainly due to the inaccessibility to evaluation by noninvasive techniques, which have only been widely available in recent years. Recent findings Emerging evidence suggests that small airways are affected from the early stages of the disease in childhood-onset asthma. Conventional lung function measurement, using spirometry, is unable to sensitively evaluate small airway function and may become abnormal only once there is a significant burden of disease. Recent studies suggest that chronic inflammation and dysfunction in the small airways, as detected with new advanced techniques, are risk factors for asthma persistence, asthma severity, worse asthma control and loss of pulmonary function with age, both in adults and children. Knowing the extent of central and peripheral airway involvement is clinically relevant to achieve asthma control, reduce bronchial hyper-responsiveness and monitor response to asthma treatment. Summary This review outlines the recent evidence on the role of small airway dysfunction in paediatric asthma development and control, and addresses how the use of new diagnostic techniques available in outpatient clinical settings, namely impulse oscillometry and multiple breath washout, could help in the early detection of small airway impairment in children with preschool wheezing and school-age asthma and potentially guide asthma treatment.

Background Shortages of clinical staff make chronic asthma care challenging in low-income countries. We evaluated an outpatient asthma care package for children, including task-shifting of asthma management roles. Methods We conducted a non-blinded individually randomised controlled trial at a tertiary-level government hospital in Blantyre, Malawi. Children aged 6–15 years diagnosed with asthma were recruited from outpatient clinic, stratified by Childhood Asthma Control Test (cACT) score and allocated 1:1 from a concealed file, accessed during electronic questionnaire completion. The intervention, delivered by non-physicians, comprised clinical assessment, optimisation of inhaled treatment, individualised asthma education. The control group received standard care from outpatient physicians. Primary outcome for intention-to-treat analysis was change in cACT score at 3 months. Secondary outcomes included asthma exacerbations requiring emergency healthcare and school absence. Findings Between September 2018 and December 2019, 120 children (59 intervention; 61 control) were recruited; 65.8% males, with mean (SD) age 9.8 (2.8) years, mean (SD) baseline cACT 20.3 (2.6). At 3 months, intervention children (n=56) had a greater mean (SD) change in cACT score from baseline (2.7 (2.8) vs 0.6 (2.8)) compared with standard care participants (n=59); a difference of 2.1 points (95% CI: 1.1 to 3.1, p

Background: Several childhood asthma risk loci that relate to immune function have been identified by genome-wide association studies (GWAS), but the underlying mechanisms remain unknown. Objective: Here, we examined whether perturbed innate immune responses mediate the association between known genetic risk variants and development of childhood asthma. Methods: Peripheral blood mononuclear cells from 336 six-month-old infants from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) cohort were stimulated in vitro with six different innate ligands (LPS, CpG, poly(I:C), R848, HDMAPP and aluminium hydroxide together with low levels of LPS) followed by quantification of 18 released cytokines and chemokines 40 h after the stimulations. The innate immune response profiles were decomposed by principal component (PC) analysis, and PC1-5 were used in mediation analyses of the effect of 25 known genetic risk variants on childhood asthma until age 7. Results: The effects of two variants from the 17q21 locus (rs7216389, rs2305480) on asthma and exacerbation risk were significantly mediated by immune parameters induced in response to ligands mimicking intracellular colonization; bacterial DNA (CpG) and double-stranded viral RNA (poly(I:C)). The Th17 and innate lymphoid cell type 3-amplifying cytokine IL-23 was the most prominent cytokine involved. Conclusion: The 17q21 effect on childhood asthma and exacerbations was partly mediated by deregulation of IL-23 in response to intracellular microbial ligands, which may suggest ineffective clearance of intracellular pathogens in the lungs.

IntroductionClinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbersCRD42020132990, CRD42020171624.

IntroductionUncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta2-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations.Methods and analysisThe Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4–11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.Ethics and disseminationThe study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.Trial registrationNCT03769090.

BackgroundGlobal Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally.ObjectiveTo survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico.MethodsGAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016–2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6–7-year-old primary school pupils (school children) and by 13–14-year-old adolescents.ResultsA total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres’ sea level altitude higher than 1500 m above mean sea level (pConclusionsThe most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.

BackgroundThe urbanisation process has been associated with increases in asthma prevalence, an observation supported largely by studies comparing urban with rural populations. The nature of this association remains poorly understood, likely because of the limitations of the urban–rural approach to understand what a multidimensional process is.ObjectiveThis study explored the relationship between the urbanisation process and asthma prevalence using a multidimensional and quantitative measure of urbanicity.MethodsA cross-sectional analysis was conducted in 1843 children living in areas with diverse levels of urbanisation in the district of Quinindé, Ecuador in 2013–2015. Categorical principal components analysis was used to generate an urbanicity score derived from 18 indicators measured at census ward level based on data from the national census in 2010. Indicators represent demographic, socioeconomic, built environment and geographical dimensions of the urbanisation process. Geographical information system analysis was used to allocate observations and urban characteristics to census wards. Logistic random effects regression models were used to identify associations between urbanicity score, urban indicators and three widely used definitions for asthma.ResultsThe prevalence of wheeze ever, current wheeze and doctor diagnosis of asthma was 33.3%, 13% and 6.9%, respectively. The urbanicity score ranged 0–10. Positive significant associations were observed between the urbanicity score and wheeze ever (adjusted OR=1.033, 95% CI 1.01 to 1.07, p=0.05) and doctor diagnosis (adjusted OR=1.06, 95% CI 1.02 to 1.1, p=0.001). For each point of increase in urbanicity score, the prevalence of wheeze ever and doctor diagnosis of asthma increased by 3.3% and 6%, respectively. Variables related to socioeconomic and geographical dimensions of the urbanisation process were associated with greater prevalence of wheeze/asthma outcomes.ConclusionsEven small increases in urbanicity are associated with a higher prevalence of asthma in an area undergoing the urban transition. The use of a multidimensional urbanicity indicator has greater explanatory power than the widely used urban–rural dichotomy to improve our understanding of how the process of urbanisation affects the risk of asthma.

BackgroundCommunity hospitals, which care for most hospitalised children in the USA, may be vulnerable to declines in paediatric care quality when quality improvement (QI) initiatives end. We aimed to evaluate changes in care quality in community hospitals after the end of the Pathways for Improving Paediatric Asthma Care (PIPA) national QI collaborative.MethodsWe conducted a longitudinal cohort study during and after PIPA. PIPA included 45 community hospitals, of which 34 completed the 12-month collaborative and were invited for extended sustainability monitoring (total of 21–24 months from collaborative start). PIPA provided paediatric asthma pathways, educational materials/seminars, QI mentorship, monthly data reports, a mobile application and peer-to-peer learning opportunities. Access to pathways, educational materials and the mobile application remained during sustainability monitoring. Charts were reviewed for children aged 2–17 years old hospitalised with a primary diagnosis of asthma (maximum 20 monthly per hospital). Outcomes included measures of guideline adherence (early bronchodilator administration via metered-dose inhaler (MDI), secondhand smoke screening and referral to smoking cessation resources) and length of stay (LOS). We evaluated outcomes using multilevel regression models adjusted for patient mix, using an interrupted time-series approach.ResultsWe analysed 2159 hospitalisations from 23 hospitals (68% of eligible). Participating hospitals were structurally similar to those that dropped out but had more improvement in guideline adherence during the collaborative (29% vs 15%, p=0.02). The end of the collaborative was associated with a significant initial decrease in early MDI administration (81%–68%) (adjusted OR (aOR) 0.26 (95% CI 0.15 to 0.42)) and decreased rate of referral to smoking cessation resources (2.2% per month increase to 0.3% per month decrease) (aOR 0.86 (95% CI 0.75 to 0.98)) but no significant changes in LOS or secondhand smoke screening.ConclusionsThe end of a paediatric asthma QI collaborative was associated with concerning declines in guideline adherence in community hospitals.

Background and objectiveUp-to-date economic burden of asthma in Singapore is currently unknown.MethodsWe quantify the per capita and total annual costs of asthma for adults and children by level of symptom control (uncontrolled, partly controlled, and well controlled) via a cross-sectional online survey administered to a national web panel. Participants were asked about healthcare utilisation, days missed from work, and reduced productivity due to their symptoms. These values were then monetised and multiplied by prevalence estimates of adult and child asthmatics to generate total costs.ResultsA total of 300 adults and 221 parents of children with asthma were included in analysis. The total annual cost of adult asthma was estimated to be SGD 1.74 billion (US$1.25 billion) with 42% coming from the uncontrolled group, 45% from the partly controlled group, and 13% from the well-controlled group. For children, the total cost is SGD 0.35 billion (US$0.25 billion), with 64%, 26% and 10% coming from each group respectively. Combined, the annual economic burden of asthma in Singapore is SGD 2.09 billion (US$1.50 billion) with 79% due to productivity losses.ConclusionPoorly controlled asthma imposes a significant economic burden. Therefore, better control of disease has the potential to generate not only health improvements, but also medical expenditure savings and productivity gains.

Introduction: National and state-based minimum data sets remain inadequate in providing a complete representation of emergency presentations, especially among paediatric asthma presentations. Thus, the aim of the study was to identify if a deficit exists in current emergency paediatric asthma hospital presentation datasets and how this may inform an understanding of childhood asthma in Victoria Methods: This retrospective cross-sectional study examined emergency hospital presentation data between 1 February 2017 and 31 January 2019. All paediatric (0-14 years) emergency asthma presentation data were collected from nine hospitals in south-western Victoria, Australia, using the Rural Acute Hospital Data Register (RAHDaR), which gathers both Victorian Emergency Minimum Dataset (VEMD) data from larger government hospitals, and non-VEMD data from smaller, more rural institutions. Results: Of the 854 emergency presentations identified for children with asthma aged 0-14 years, 540 (63.2%) were managed initially at larger government-reporting hospitals. A total of 314 (36.8%) emergency presentations were initially managed at emergency facilities, such as urgent care centres. Overall, it was found that a total 278 (32.5%) of all emergency presentations did not appear in current government datasets. Conclusion: The RAHDaR database, a complete register of data, captures all emergency presentations in south-western Victoria and highlights as much as a 33% deficit in the data currently available to inform asthma resource initiatives including policy development, funding allocation, prevention and management initiatives in Victoria. More accurate data from sources such as RAHDaR are essential to fill the now-evident data chasm.

BackgroundStudies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES).MethodsIncluded in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model.ResultsThe adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5–15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83).ConclusionThis study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.

Asthma is the commonest chronic condition in childhood but mortality from asthma during childhood is a rare occurrence. No national review into asthma deaths in children in Ireland has been performed to date. The aim of this study was to review all cases of mortality from asthma in the paediatric population over a 10-year period in Ireland. The objective was to identify risk factors contributing to asthma deaths in children. A retrospective chart review was performed on cases reported to the National Paediatric Mortality Register (NPMR) with asthma as the primary cause of death. Eleven cases were reported. Consent was obtained for six cases. Median age at death was 11.8 years. All patients presented to the Emergency Department (ED) in asystole. Fifty percent of patients had acute symptoms prior to the fatal episode. None of the patients was attending secondary services. Only 60% had a written personalised asthma action plan (PAAP). Our data suggests that most patients present in extremis and have little warning signs of severity of the attack. Better education on recognition of symptoms and initiation of action plans is required.

ObjectiveResearch has linked early adverse childhood experiences (ACEs) with asthma development; however, existing studies have generally relied on parent report of exposure and outcome. We aimed to examine the association of early life ACEs with empirically determined trajectories of childhood asthma risk, using independent register information on both exposures and outcome.MethodsBased on nationwide registries, we established a study cohort of 466 556 children born in Denmark (1997–2004). We obtained information on ACEs during the first 2 years of life (bereavement, parental chronic somatic and/or mental illness) and childhood asthma diagnosis or medication use from birth through age 10 years from the Danish National Patient and Prescription Registries, respectively. We identified asthma phenotypes using group-based trajectory modelling. We then used multinomial logistic regression to examine the association between early ACEs and asthma phenotypes.ResultsWe identified four asthma phenotypes: non-asthmatic, early-onset transient, early-onset persistent and late-onset asthma. Girls with early-onset transient asthma (OR 1.13, 95% CI 1.04 to 1.24), early-onset persistent asthma (1.27, 95% CI 1.08 to 1.48) or late-onset asthma (OR 1.28, 95% CI 1.11 to 1.48) vs no asthma were more likely to have early life ACE exposure compared with girls without ACE exposure. Results were similar for boys who also had experienced early life ACEs with ORs of 1.16 (95% CI 1.08 to 1.25), 1.34 (95% CI 1.20 to 1.51) and 1.11 (95% CI 0.98 to 1.25), respectively.ConclusionIn a nationwide-population study, we identified three childhood onset asthma phenotypes and found that ACEs early in life were associated with increased odds for each of these asthma phenotypes among both girls and boys.

IntroductionAdherence monitoring to inhaled corticosteroids is an essential component of asthma management. Electronic monitoring devices (EMD) provide objective data on date, time and number of actuations. However, most give no information on inhalation. Novel EMD (NEMD) platforms have the potential to monitor both activation and inhalation.AimTo assess the feasibility of NEMDs, in terms of usability, acceptability to patients and healthcare professionals and accuracy.MethodsThis was an open-label, prospective, mixed-methods, pragmatic randomised study. Children with asthma attending specialist tertiary care were randomised to one of four NEMD: Remote Directly Observed Therapy (R-DOT), Hailie Smartinhaler, INhaler Compliance Assessment device (INCA) and the Rafi-tone App. Following monitoring, participants were invited to focus groups or one-to-one interviews. Usability and acceptability were evaluated using themes identified from the focus groups and interviews. Adherence accuracy was determined using adherence data from each NEMD.ResultsThirty-five children were recruited; 18 (51%), (11 males, median age 13.5 (7–16) years) completed monitoring, 14 (78%) provided feedback. Participants identified various features such as ease of use and minimal effort as desirable criteria for an NEMD. The Hailie and INCA fulfilled these criteria and were able to record both actuation and inhalation. Negative themes included a ‘Big Brother’ effect and costs.ConclusionThere was no ‘one size fits all’, as participants identified advantages and disadvantages for each NEMD. Devices that can easily calculate adherence to activation and inhalation have the potential to have greatest utility in clinical practice. Each NEMD has different functionality and therefore choice of platform should be determined by the needs of the patient and healthcare professional.

Background and objective: We conducted a comprehensive assessment of guideline adherence in paediatric asthma care, including inpatient and ambulatory services,in Australia.Methods: National and international clinical practice guidelines (CPG) relating to asthma in children were searched and 39 medical record audit indicator questions were developed. Retrospective medical record review was conducted across hospital inpatient admissions,emergency department (ED) presentations, general practice (GP) and paediatrician consultations in three Australian states for children aged ≤15 years receiving care in 2012 and 2013. Eligibility of, and adherence to, indicators was assessed from medical records by nine experienced and purpose-trained paediatric nurses (surveyors). Results: Surveyors conducted 18 453 asthma indicator assessments across 1600 visits for 881 children in129 locations. Overall, the adherence for asthma care across the 39 indicators was 58.1%, with 54.4% adherence at GP (95% CI: 46.0–62.5), 77.7% by paediatricians (95% CI: 40.5–97.0), 79.9% in ED (95% CI: 70.6–87.3)and 85.1% for inpatient care (95% CI: 76.7–91.5). For14 acute asthma indicators, overall adherence was56.3% (95% CI: 47.6–64.7). Lowest adherences were for recording all four types of vital signs in children aged>2 years presenting with asthma attack (15.1%, 95% CI:8.7–23.7), and reviewing patients’ compliance, inhaler technique and triggers prior to commencing a new drug therapy (20.5%, 95% CI: 10.1–34.8). Conclusion: The study demonstrated differences between existing care and CPG recommendations for paediatric asthma care in Australia. Evidence-based interventions to improve adherence to CPG may help to standardize quality of paediatric asthma care and reduce variation of care. Refereed/Peer-reviewed

Aim Paediatric asthma hospitalisation has decreased in Finland, but has remained stable in Sweden. The reasons for these intercountry differences are unclear. The aim of this study was to explore the trend of dispensed asthma medication, including inhaled corticosteroids (ICS), among paediatric populations in the two countries. Methods We explored trends in dispensed asthma medication among paediatric populations aged 0-19 in Finland and Sweden from 2006 to 2017. The Finnish Statistics on Reimbursements for Prescription Medicines and The Swedish Prescribed Drug Register provided data on all dispensed asthma prescriptions. Results During the study period, the prevalence of dispensed ICS in paediatric populations was fairly stable in Finland and Sweden. Among children aged 0-4, ICS were 1.5 times more commonly dispensed in Sweden than in Finland. The prevalence of children dispensed short-acting beta-2 adrenergic receptor agonists (SABA) increased in both countries, but rose more in Finland (51%) than in Sweden (27%). Conclusion Inhaled corticosteroids were more commonly dispensed for children aged 0-4 in Sweden than in Finland during the study period. This study showed an increasing prevalence of children dispensed SABA in Finland and Sweden, particularly in Finland. Differences and trends in asthma medication may effect asthma hospitalisation and asthma deaths.

ObjectiveTo determine the variability of primary and secondary outcomes used in trials of intravenous bronchodilators in children with acute severe paediatric asthma.MethodsSystematic search of MEDLINE, EMBASE, Cochrane CENTRAL and the WHO International Clinical Trials Registry Platform for randomised trials in children (less than18 years) with acute severe paediatric asthma comparing intravenous bronchodilator therapy to another treatment. Initial search was performed on 7 January 2016 with an updated search performed on 6 September 2018. Primary and secondary outcomes were collated.ResultsWe identified 35 published papers and four registered study protocols. 56 primary outcomes were found, the most common being a clinical asthma score (23/56; 41%). Other identified primary outcomes included bedside tests of respiratory function (11/56; 20%) and measures of length of stay (9/56; 16%). There were a total of 60 different secondary outcomes, the most common were various length of stay measures (24/60; 40%) and adverse events (11/60; 18%).ConclusionStudies comparing intravenous treatment modalities for children with acute severe paediatric asthma exhibit great variation in the type, number and timing of outcome measures used. There are no patient or family-specific outcomes reported. There is a need to develop international consensus.Trial registration numberCRD42017055331.

IntroductionAsthma attacks are responsible for considerable morbidity and may be fatal. We aimed to identify and weight risk factors for asthma attacks in children (5–12 years) in order to inform and prioritise care.MethodsWe systematically searched six databases (May 2016; updated with forward citations January 2017) with no language/date restrictions. Two reviewers independently selected studies for inclusion, assessed study quality and extracted data. Heterogeneity precluded meta-analysis. Weighting was undertaken by an Expert Panel who independently assessed each variable for degree of risk and confidence in the assessment (based on study quality and size, effect sizes, biological plausibility and consistency of results) and then achieved consensus by discussion. Assessments were finally presented, discussed and agreed at a multidisciplinary workshop.ResultsFrom 16 109 records, we included 68 papers (28 cohort; 4 case-control; 36 cross-sectional studies). Previous asthma attacks were associated with greatly increased risk of attack (ORs between 2.0 and 4.1). Persistent symptoms (ORs between 1.4 and 7.8) and poor access to care (ORs between 1.2 and 2.3) were associated with moderately/greatly increased risk. A moderately increased risk was associated with suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity (USA), poverty and vitamin D deficiency. Environmental tobacco smoke exposure, younger age, obesity and low parental education were associated with slightly increased risk.DiscussionAssessment of the clinical and demographic features identified in this review may help clinicians to focus risk reduction management on the high-risk child. Population level factors may be used by health service planners and policymakers to target healthcare initiatives.Trial registration numberCRD42016037464.

Background With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. Methods The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. Results The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference – all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6–11 years and ≥12 years. Conclusions For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Purpose of review: The purpose of this review is to summarize the recent evidence on the distinct atopic phenotypes and their relationship with childhood asthma. We start by considering definitions and phenotypic classification of atopy and then review evidence on its association with asthma in children. Recent findings: It is now well recognised that both asthma and atopy are complex entities encompassing various different sub-groups that also differ in the way they interconnect. The lack of gold standards for diagnostic markers of atopy and asthma further adds to the existing complexity over diagnostic accuracy and definitions. Although recent statistical phenotyping studies contributed significantly to our understanding of these heterogeneous disorders, translating these findings into meaningful information and effective therapies requires further work on understanding underpinning biological mechanisms. Summary: The disaggregation of allergic sensitization may help predict how the allergic disease is likely to progress. One of the important questions is how best to incorporate tests for the assessment of allergic sensitisation into diagnostic algorithms for asthma, both in terms of confirming asthma diagnosis, and the assessment of future risk.

Background: Infant weight gain is associated with lower lung function and a higher risk of childhood asthma. Detailed individual childhood growth patterns might be better predictors of childhood respiratory morbidity than the difference between two weight and height measurements. We assessed the associations of early childhood growth patterns with lung function and asthma at the age of 10 years and whether the child’s current body mass index (BMI) influenced any association. Methods: We derived peak height and weight growth velocity, BMI at adiposity peak, and age at adiposity peak from longitudinally measured weight and height data in the first 3 years of life of 4435 children enrolled in a population-based prospective cohort study. At 10 years of age, spirometry was performed and current asthma was assessed by questionnaire. Spirometry outcomes included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and forced expiratory flow after exhaling 75% of vital capacity (FEF75). Results: Greater peak weight velocity was associated with higher FVC but lower FEV1/FVC and FEF75. Greater BMI at adiposity peak was associated with higher FVC and FEV1 but lower FEV1/FVC and FEF75. Greater age at adiposity peak was associated with higher FVC, FEV1, FEV1/FVC and FEF75, particularly in children with a small size at birth, and lower odds of current asthma in boys. The child’s current BMI only explained the associations of peak weight velocity and BMI at adiposity peak with FVC and FEV1. Peak height velocity was not consistently associated with impaired lung function or asthma. Conclusion: Peak weight velocity and BMI at adiposity peak were associated with reduced airway patency in relation to lung volume, whereas age at adiposity peak was associated with higher lung function parameters and lower risk of asthma at 10 years, particularly in boys. The Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Liesbeth Duijts received additional funding from the European Union’s Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (no. 696295; 2017), ZonMW The Netherlands (no. 529051014; 2017)). The study was supported by the Netherlands Organization for Health Research and Development (VIDI 016.136.361), a European Research Council Consolidator Grant (ERC-2014-CoG-648916), funding from the European Union’s Seventh Framework Programme under grant agreement no. 289346 (EarlyNutrition), and funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements no. 733206 (LifeCycle) and no. 633595 (DynaHEALTH). Dr Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128). The researchers are independent from the funders.

In 2011, we reported that our paediatric asthma clinic (PAC) appeared to significantly reduce the burden of paediatric asthma in our community. Supported by these results, the PAC underwent a gradual threefold expansion while maintaining the same model of care. We now report on the outcome of that expansion and demonstrate that our PAC continues to significantly reduce the burden of paediatric asthma in our community. As previously, newly enrolled PAC patients continue to show a 12-month reduction in asthma-related emergency department (ED) visits and admissions exceeding 60% and 80%, respectively. This consistent short-term benefit, coupled with clinic expansion, has contributed to a significant improvement in our rate of paediatric asthma-related ED visits or hospitalizations when compared to other Ontario hospitals.

Background Non-communicable lung disease and exposure to air pollution are major problems in sub-Saharan Africa. A high burden of chronic respiratory symptoms, spirometric abnormalities and air pollution exposures has been found in Malawian adults; whether the same would be true in children is unknown. Methods This cross-sectional study of children aged 6–8 years, in rural Malawi, included households from communities participating in the Cooking and Pneumonia Study (CAPS), a trial of cleaner-burning biomass-fuelled cookstoves. We assessed; chronic respiratory symptoms, anthropometry, spirometric abnormalities (using Global Lung Initiative equations) and personal carbon monoxide (CO) exposure. Prevalence estimates were calculated, and multivariable analyses were done. Results We recruited 804 children (mean age 7.1 years, 51.9% female), including 476 (260 intervention; 216 control) from CAPS households. Chronic respiratory symptoms (mainly cough (8.0%) and wheeze (7.1%)) were reported by 16.6% of children. Average height-for-age and weight-for-age z-scores were −1.04 and −1.10, respectively. Spirometric abnormalities (7.1% low forced vital capacity (FVC); 6.3% obstruction) were seen in 13.0% of children. Maximum CO exposure and carboxyhaemoglobin levels (COHb) exceeded WHO guidelines in 50.1% and 68.5% of children, respectively. Children from CAPS intervention households had lower COHb (median 3.50% vs 4.85%, p=0.006) and higher FVC z-scores (−0.22 vs −0.44, p=0.05) than controls. Conclusion The substantial burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in children in rural Malawi is concerning; effective prevention and control strategies are needed. Our finding of potential benefit in CAPS intervention households calls for further research into clean-air interventions to maximise healthy lung development in children.

In this paper we propose to describe the available evidence from the literature on upper airway microbiome and its association with paediatric asthma and allergy. Recent advances in sequencing the bacterial 16S ribosomal RNA (16S rRNA) gene have enabled research into the complex communities of bacteria, known as the microbiome, that exist outside and inside the human body. Although the upper airways have long been recognised to host a microbiome, the lower airways are now known to contain a rich and diverse microbiome. This review first describes the microbiome of the upper and lower airways and then explores associations between the microbiome in the airways and bowel and asthma in children. The characteristics of the microbiome differ between nose and mouth, and between the mouth and bronchus in terms of burden and diversity of bacteria and in the predominant phyla present. There is a small literature which suggests that there are differences in the airway microbiome in early life between children who later have asthma compared to those who do not develop asthma.Conclusion. At the time of writing it is not clear whether the microbiome may cause childhood asthma, whether the conditions in the asthmatic airway encourage a different microbiome or whether a third factor confounds the relationship between airway microbiome and child- hood asthma.

As a retired GP and grandfather of a 3-year-old asthma sufferer I am troubled and not a little alarmed by the current standard of asthma care being offered today, as described in the article …

The National Review of Asthma Deaths (NRAD) report entitled Why Asthma Still Kills ,1 published on World Asthma Day in May 2014, concluded that only one of the 28 children and young people (CYP) who died had been adequately managed by health professionals. Of the 19 NRAD recommendations only one has been initiated nationally in the UK, namely setting up a National Asthma Audit, which has yet to report after nearly 5 years. Care for children with asthma in the UK is mainly provided in primary care, and is often limited to the few tasks set out in the Quality and Outcomes Framework (QOF)2 to provide data to qualify for payments. Currently the QOF requires a recorded asthma diagnosis confirmed by measures of airflow reversibility, smoking status, and evidence of an asthma review in the preceding 12 months that includes an assessment of asthma control using the Royal College of Physicians’ three questions (RCP 3 Questions); the latter are not validated and nor are they recommended for children aged

A recently published approach to paediatric asthma management neither recommended screening for nor suggested any management of hypothalamic-pituitary-adrenal axis suppression in asthmatic children treated with corticosteroids. The existing literature on this topic was therefore reviewed and the quality of the evidence assessed. Recommendations for diagnosis, screening and management are made utilising the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Asthma, an inflammatory disease of the airways, is a common condition, currently affecting about 9% of adults. Obesity is another disease with high prevalence in adults, and asthma that develops in obese individuals appears to be distinct from other forms of asthma, in being particularly severe and difficult to control even with oral corticosteroids. Moreover, recent studies suggest that obesity may have a causal relationship with asthma. In this review, we discuss possible obesity-driven metabolic and immunological pathways that might lead to asthma that is associated with obesity. Our understanding of the mechanisms that underlie this association will likely lead in the future to improved treatments for this significant unmet medical need.

Background Rapid postnatal weight gain has been associated with wheezing and asthma in children, but it remains unclear whether it acts independently of overweight. We aimed to disentangle the roles of infant9s size and weight gain velocity in the development of wheezing in early childhood using a novel method that allows for mutual adjustment for different aspects of growth. Methods Data were obtained from the NINFEA questionnaires where weight measurements from birth up to 18 months of age were assessed in 4492 term singletons. Wheezing was defined as at least one episode of wheezing/whistling in the chest occurring between 6 and 18 months of age. The SuperImposition by Translation And Rotation model was used to estimate individual weight trajectories defined by three child-specific parameters: size , velocity and tempo , that is age at peak weight velocity. These parameters were standardised and related to wheezing using logistic regression with effects expressed as an increase of one SD. Results A median of five weight measurements per child were obtained. Infant size (OR=1.28; 95% CI 1.12 to 1.46) and weight gain velocity (OR=1.30; 95% CI 1.15 to 1.48) were independently positively associated with wheezing. We found no evidence of an effect of tempo on infant wheezing. The estimates were changed only minimally after adjustment for potential confounders. Conclusions Faster growth and larger size in the first 18 months of life are both independently associated with an increased risk of wheezing. These findings suggest that early growth patterns play a role in shaping the occurrence of wheezing.

IntroductionThe lack of effective, consistent, reproducible and efficient asthma ascertainment methods results in inconsistent asthma cohorts and study results for clinical trials or other studies. We aimed to assess whether application of expert artificial intelligence (AI)-based natural language processing (NLP) algorithms for two existing asthma criteria to electronic health records of a paediatric population systematically identifies childhood asthma and its subgroups with distinctive characteristics.MethodsUsing the 1997–2007 Olmsted County Birth Cohort, we applied validated NLP algorithms for Predetermined Asthma Criteria (NLP-PAC) as well as Asthma Predictive Index (NLP-API). We categorised subjects into four groups (both criteria positive (NLP-PAC+/NLP-API+); PAC positive only (NLP-PAC+ only); API positive only (NLP-API+ only); and both criteria negative (NLP-PAC−/NLP-API−)) and characterised them. Results were replicated in unsupervised cluster analysis for asthmatics and a random sample of 300 children using laboratory and pulmonary function tests (PFTs).ResultsOf the 8196 subjects (51% male, 80% white), we identified 1614 (20%), NLP-PAC+/NLP-API+; 954 (12%), NLP-PAC+ only; 105 (1%), NLP-API+ only; and 5523 (67%), NLP-PAC−/NLP-API−. Asthmatic children classified as NLP-PAC+/NLP-API+ showed earlier onset asthma, more Th2-high profile, poorer lung function, higher asthma exacerbation and higher risk of asthma-associated comorbidities compared with other groups. These results were consistent with those based on unsupervised cluster analysis and lab and PFT data of a random sample of study subjects.ConclusionExpert AI-based NLP algorithms for two asthma criteria systematically identify childhood asthma with distinctive characteristics. This approach may improve precision, reproducibility, consistency and efficiency of large-scale clinical studies for asthma and enable population management.