Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Dermatology Quality of Life Index scores in Bangladeshi patients with atopic eczema and their families in East London.

BACKGROUND: Atopic eczema (AE) is a chronic relapsing, pruritic disease that greatly affects the child and family's quality of life (QoL). It is usually common and severe among children of Bangladeshi ethnicity. OBJECTIVES: This is a cross-sectional quantitative study in patients with AE of Bangladeshi origin, which aims to analyse different components of the family, children and adult quality-of-life indices and their relationship to patient age, sex, eczema severity and distribution, other allergic associations, parental education and socioeconomic level. METHODS: Children and young adults of Bangladeshi origin aged 0-30 years, clinically diagnosed with AE were recruited as part of the Tower Hamlets Eczema Assessment project, a clinical phenotyping study of AE in the Bangladeshi population living in East London. Questionnaires completed by children/parents included the Family Dermatology Life Quality Index (FDLQI), Infant's Dermatology Quality of Life (IDQOL) and the Children's Dermatology Life Quality Index (CDLQI). Young adults completed the Dermatology Life Quality Index (DLQI). The disease severity was assessed objectively using the Eczema Area Severity Index (EASI). Patients and parents who did not read or speak English were aided by Bengali/Sylheti-speaking research assistants. RESULTS: Overall, 460 Bangladeshi children and 98 adults with AE were recruited. Burden of care, extra housework and emotional distress were the highest affected domains in parental QoL, while itching and sleep were the highest for children. Significant factors influencing FDLQI score were EASI [marginal effect (ME) 1.01, 95% confidence interval (CI) 1.00-1.03; P = 0.004], age (ME 0.98, 95% CI 0.97-0.99; P = 0.004), extensor eczema distribution (ME 1.25, 95% CI 1.03-1.52; P = 0.023), parental English fluency (ME 1.29, 95% CI 1.10-1.52; P = 0.002) and atopic comorbidities (ME 1.10, 95% CI 1.04-1.17; P = 0.001). Parental socioeconomic class was a nonsignificant factor. IDQOL/CDLQI was influenced significantly by the child's age (ME 0.99, 95% CI 0.97-1.00, P = 0.023), 'nonclear' eczema distribution clusters especially the 'severe extensive' cluster (ME 1.46, 95% CI 1.15-1.84; P = 0.002) and nonsignificantly by EASI and parental English literacy and socioeconomic levels. DLQI was affected significantly by nonclear eczema distribution groups especially 'severe extensive' (ME 2.49, 95% 1.76-3.53; P < 0.001) and nonsignificantly by patient age, and female sex. CONCLUSIONS: AE is a chronic disease where many external factors other than disease severity affect QoL of patients and their families, -especially in under-represented minority groups who face different linguistic and cultural barriers.

Investigating the impact of London's ultra low emission zone on children's health: children's health in London and Luton (CHILL) protocol for a prospective parallel cohort study.

BACKGROUND: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. METHODS: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6-9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. DISCUSSION: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. CLINICALTRIALS: GOV: NCT04695093 (05/01/2021).

European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials.

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.

An enhanced care package to improve asthma management in Malawian children: a randomised controlled trial.

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<0.001). Fewer intervention children attended emergency healthcare (7.3% vs 25.4%, p=0.02) and missed school (20.0% vs 62.7%, p<0.001) compared with standard care children. INTERPRETATION: The intervention resulted in decreased asthma symptoms and exacerbations. Wider scale-up could present substantial benefits for asthmatic patients in resource-limited settings. TRIAL REGISTRATION NUMBER: PACTR201807211617031.

Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents.

INTRODUCTION: The A allele of rs1042713 (Arg16 amino acid) in the ß2-adrenoreceptor is associated with poor response to long-acting ß2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second-line controller with LABA or a leukotriene receptor antagonist according to Arg16Gly genotype would result in improvements in Pediatric Asthma-Related Quality of Life Questionnaire (PAQLQ). METHODS: We performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12-18 years with asthma taking inhaled corticosteroids. 241 participants (mean±sd age 14.7±1.91 years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 4-week run-in participants were followed for 12 months. The primary outcome measure was change in PAQLQ. Asthma control, asthma exacerbation frequency and healthcare utilisation were secondary outcomes. RESULTS: Genotype-directed prescribing resulted in an improvement in PAQLQ compared to standard care (0.16, 95% CI 0.00-0.31; p=0.049), although this improvement was below the pre-determined clinical threshold of 0.25. The AA genotype was associated with a larger improvement in PAQLQ with personalised versus standard care (0.42, 95% CI 0.02-0.81; p=0.041). CONCLUSION: This is the first RCT demonstrating that genotype-driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care. Adolescents with the AA homozygous genotype benefited most. The potential role of such ß2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.

Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.

BACKGROUND: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). OBJECTIVES: We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. METHODS: We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. RESULTS: We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. CONCLUSION: Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.

Differential association of air pollution exposure with neonatal and postneonatal mortality in England and Wales: A cohort study.

BACKGROUND: Many but not all studies suggest an association between air pollution exposure and infant mortality. We sought to investigate whether pollution exposure is differentially associated with all-cause neonatal or postneonatal mortality, or specific causes of infant mortality. METHODS AND FINDINGS: We separately investigated the associations of exposure to particulate matter with aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and sulphur dioxide (SO2) with all-cause infant, neonatal, and postneonatal mortality, and with specific causes of infant deaths in 7,984,366 live births between 2001 and 2012 in England and Wales. Overall, 51.3% of the live births were male, and there were 36,485 infant deaths (25,110 neonatal deaths and 11,375 postneonatal deaths). We adjusted for the following major confounders: deprivation, birthweight, maternal age, sex, and multiple birth. Adjusted odds ratios (95% CI; p-value) for infant deaths were significantly increased for NO2, PM10, and SO2 (1.066 [1.027, 1.107; p = 0.001], 1.044 [1.007, 1.082; p = 0.017], and 1.190 [1.146, 1.235; p < 0.001], respectively) when highest and lowest pollutant quintiles were compared; however, neonatal mortality was significantly associated with SO2 (1.207 [1.154, 1.262; p < 0.001]) but not significantly associated with NO2 and PM10 (1.044 [0.998, 1.092; p = 0.059] and 1.008 [0.966, 1.052; p = 0.702], respectively). Postneonatal mortality was significantly associated with all pollutants: NO2, 1.108 (1.038, 1.182; p < 0.001); PM10, 1.117 (1.050, 1.188; p < 0.001); and SO2, 1.147 (1.076, 1.224; p < 0.001). Whilst all were similarly associated with endocrine causes of infant deaths (NO2, 2.167 [1.539, 3.052; p < 0.001]; PM10, 1.433 [1.066, 1.926; p = 0.017]; and SO2, 1.558 [1.147, 2.116; p = 0.005]), they were differentially associated with other specific causes: NO2 and PM10 were associated with an increase in infant deaths from congenital malformations of the nervous (NO2, 1.525 [1.179, 1.974; p = 0.001]; PM10, 1.457 [1.150, 1.846; p = 0.002]) and gastrointestinal systems (NO2, 1.214 [1.006, 1.466; p = 0.043]; PM10, 1.312 [1.096, 1.571; p = 0.003]), and NO2 was also associated with deaths from malformations of the respiratory system (1.306 [1.019, 1.675; p = 0.035]). In contrast, SO2 was associated with an increase in infant deaths from perinatal causes (1.214 [1.156, 1.275; p < 0.001]) and from malformations of the circulatory system (1.172 [1.011, 1.358; p = 0.035]). A limitation of this study was that we were not able to study associations of air pollution exposure and infant mortality during the different trimesters of pregnancy. In addition, we were not able to control for all confounding factors such as maternal smoking. CONCLUSIONS: In this study, we found that NO2, PM10, and SO2 were differentially associated with all-cause mortality and with specific causes of infant, neonatal, and postneonatal mortality.

Effectiveness of school-based self-management interventions for asthma among children and adolescents: findings from a Cochrane systematic review and meta-analysis.

INTRODUCTION: The evidence that teaching self-management techniques to children and young people with asthma in schools is effective has not, to date, been the subject of systematic review. METHODS: We conducted a systematic review of intervention studies. Studies were eligible if they employed a randomised parallel-group design and were published in English from 1995 onwards. Participants included children with asthma aged 5-18 years who participated within their own school environment. Searches were conducted on the Cochrane Airways Group Specialised Register. Quantitative data were combined using random-effects meta-analyses. RESULTS: Thirty-three outcome evaluation studies were included. School-based interventions were effective in reducing the frequency of emergency department visits (OR 0.70, 95% CI 0.53 to 0.92; studies=13), and moderately effective in reducing levels of hospitalisations (standardised mean differences [SMD] -0.19, 95% CI -0.35 to -0.04; studies=6). A meta-analysis of three studies suggest that the intervention approach could reduce the number of days of restricted activity (SMD -0.30, 95% CI -0.41 to -0.18; studies=3). However, there was uncertainty as to whether school-based self-management interventions impacted on reducing absences from school. CONCLUSIONS: Self-management interventions for children with asthma delivered in schools reduce the number of acute episodes of healthcare usage. We conclude that the school environment is an important space for delivering interventions to improve children's health.

Lung health and exposure to air pollution in Malawian children (CAPS): a cross-sectional study.

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.

School-based self-management interventions for asthma in children and adolescents: a mixed methods systematic review.

BACKGROUND: Asthma is a common respiratory condition in children that is characterised by symptoms including wheeze, shortness of breath, chest tightness, and cough. Children with asthma may be able to manage their condition more effectively by improving inhaler technique, and by recognising and responding to symptoms. Schools offer a potentially supportive environment for delivering interventions aimed at improving self-management skills among children. The educational ethos aligns with skill and knowledge acquisition and makes it easier to reach children with asthma who do not regularly engage with primary care. Given the multi-faceted nature of self-management interventions, there is a need to understand the combination of intervention features that are associated with successful delivery of asthma self-management programmes. OBJECTIVES: This review has two primary objectives.• To identify the intervention features that are aligned with successful intervention implementation.• To assess effectiveness of school-based interventions provided to improve asthma self-management among children.We addressed the first objective by performing qualitative comparative analysis (QCA), a synthesis method described in depth later, of process evaluation studies to identify the combination of intervention components and processes that are aligned with successful intervention implementation.We pursued the second objective by undertaking meta-analyses of outcomes reported by outcome evaluation studies. We explored the link between how well an intervention is implemented and its effectiveness by using separate models, as well as by undertaking additional subgroup analyses. SEARCH METHODS: We searched the Cochrane Airways Trials Register for randomised studies. To identify eligible process evaluation studies, we searched MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Cochrane Database of Systematic Reviews (CDSR), Web of Knowledge, the Database of Promoting Health Effectiveness Reviews (DoPHER), the Database of Abstracts of Reviews of Effects (DARE), the International Biography of Social Science (IBSS), Bibliomap, Health Technology Assessment (HTA), Applied Social Sciences Index and Abstracts (ASSIA), and Sociological Abstracts (SocAbs). We conducted the latest search on 28 August 2017. SELECTION CRITERIA: Participants were school-aged children with asthma who received the intervention in school. Interventions were eligible if their purpose was to help children improve management of their asthma by increasing knowledge, enhancing skills, or changing behaviour. Studies relevant to our first objective could be based on an experimental or quasi-experimental design and could use qualitative or quantitative methods of data collection. For the second objective we included randomised controlled trials (RCTs) where children were allocated individually or in clusters (e.g. classrooms or schools) to self-management interventions or no intervention control. DATA COLLECTION AND ANALYSIS: We used qualitative comparative analysis (QCA) to identify intervention features that lead to successful implementation of asthma self-management interventions. We measured implementation success by reviewing reports of attrition, intervention dosage, and treatment adherence, irrespective of effects of the interventions.To measure the effects of interventions, we combined data from eligible studies for our primary outcomes: admission to hospital, emergency department (ED) visits, absence from school, and days of restricted activity due to asthma symptoms. Secondary outcomes included unplanned visits to healthcare providers, daytime and night-time symptoms, use of reliever therapies, and health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ). MAIN RESULTS: We included 55 studies in the review. Thirty-three studies in 14,174 children provided information for the QCA, and 33 RCTs in 12,623 children measured the effects of interventions. Eleven studies contributed to both the QCA and the analysis of effectiveness. Most studies were conducted in North America in socially disadvantaged populations. High school students were better represented among studies contributing to the QCA than in studies contributing to effectiveness evaluations, which more commonly included younger elementary and junior high school students. The interventions all attempted to improve knowledge of asthma, its triggers, and stressed the importance of regular practitioner review, although there was variation in how they were delivered.QCA results highlighted the importance of an intervention being theory driven, along with the importance of factors such as parent involvement, child satisfaction, and running the intervention outside the child's own time as drivers of successful implementation.Compared with no intervention, school-based self-management interventions probably reduce mean hospitalisations by an average of about 0.16 admissions per child over 12 months (SMD -0.19, 95% CI -0.35 to -0.04; 1873 participants; 6 studies, moderate certainty evidence). They may reduce the number of children who visit EDs from 7.5% to 5.4% over 12 months (OR 0.70, 95% CI 0.53 to 0.92; 3883 participants; 13 studies, low certainty evidence), and probably reduce unplanned visits to hospitals or primary care from 26% to 21% at 6 to 9 months (OR 0.74, 95% CI 0.60 to 0.90; 3490 participants; 5 studies, moderate certainty evidence). Self-management interventions probably reduce the number of days of restricted activity by just under half a day over a two-week period (MD 0.38 days 95% CI -0.41 to -0.18; 1852 participants; 3 studies, moderate certainty evidence). Effects of interventions on school absence are uncertain due to the variation between the results of the studies (MD 0.4 fewer school days missed per year with self-management (-1.25 to 0.45; 4609 participants; 10 studies, low certainty evidence). Evidence is insufficient to show whether the requirement for reliever medications is affected by these interventions (OR 0.52, 95% CI 0.15 to 1.81; 437 participants; 2 studies; very low-certainty evidence). Self-management interventions probably improve children's asthma-related quality of life by a small amount (MD 0.36 units higher on the Paediatric AQLQ(95% CI 0.06 to 0.64; 2587 participants; 7 studies, moderate certainty evidence). AUTHORS' CONCLUSIONS: School-based asthma self-management interventions probably reduce hospital admission and may slightly reduce ED attendance, although their impact on school attendance could not be measured reliably. They may also reduce the number of days where children experience asthma symptoms, and probably lead to small improvements in asthma-related quality of life. Many of the studies tested the intervention in younger children from socially disadvantaged populations. Interventions that had a theoretical framework, engaged parents and were run outside of children's free time were associated with successful implementation.

A cleaner burning biomass-fuelled cookstove intervention to prevent pneumonia in children under 5 years old in rural Malawi (the Cooking and Pneumonia Study): a cluster randomised controlled trial.

BACKGROUND: WHO estimates exposure to air pollution from cooking with solid fuels is associated with over 4 million premature deaths worldwide every year including half a million children under the age of 5 years from pneumonia. We hypothesised that replacing open fires with cleaner burning biomass-fuelled cookstoves would reduce pneumonia incidence in young children. METHODS: We did a community-level open cluster randomised controlled trial to compare the effects of a cleaner burning biomass-fuelled cookstove intervention to continuation of open fire cooking on pneumonia in children living in two rural districts, Chikhwawa and Karonga, of Malawi. Clusters were randomly allocated to intervention and control groups using a computer-generated randomisation schedule with stratification by site, distance from health centre, and size of cluster. Within clusters, households with a child under the age of 4·5 years were eligible. Intervention households received two biomass-fuelled cookstoves and a solar panel. The primary outcome was WHO Integrated Management of Childhood Illness (IMCI)-defined pneumonia episodes in children under 5 years of age. Efficacy and safety analyses were by intention to treat. The trial is registered with ISRCTN, number ISRCTN59448623. FINDINGS: We enrolled 10 750 children from 8626 households across 150 clusters between Dec 9, 2013, and Feb 28, 2016. 10 543 children from 8470 households contributed 15 991 child-years of follow-up data to the intention-to-treat analysis. The IMCI pneumonia incidence rate in the intervention group was 15·76 (95% CI 14·89-16·63) per 100 child-years and in the control group 15·58 (95% CI 14·72-16·45) per 100 child-years, with an intervention versus control incidence rate ratio (IRR) of 1·01 (95% CI 0·91-1·13; p=0·80). Cooking-related serious adverse events (burns) were seen in 19 children; nine in the intervention and ten (one death) in the control group (IRR 0·91 [95% CI 0·37-2·23]; p=0·83). INTERPRETATION: We found no evidence that an intervention comprising cleaner burning biomass-fuelled cookstoves reduced the risk of pneumonia in young children in rural Malawi. Effective strategies to reduce the adverse health effects of household air pollution are needed. FUNDING: Medical Research Council, UK Department for International Development, and Wellcome Trust.

E-cigarette vapour enhances pneumococcal adherence to airway epithelial cells.

E-cigarette vapour contains free radicals with the potential to induce oxidative stress. Since oxidative stress in airway cells increases platelet-activating factor receptor (PAFR) expression, and PAFR is co-opted by pneumococci to adhere to host cells, we hypothesised that E-cigarette vapour increases pneumococcal adhesion to airway cells.Nasal epithelial PAFR was assessed in non-vaping controls, and in adults before and after 5 min of vaping. We determined the effect of vapour on oxidative stress-induced, PAFR-dependent pneumococcal adhesion to airway epithelial cells in vitro, and on pneumococcal colonisation in the mouse nasopharynx. Elemental analysis of vapour was done by mass spectrometry, and oxidative potential of vapour assessed by antioxidant depletion in vitroThere was no difference in baseline nasal epithelial PAFR expression between vapers (n=11) and controls (n=6). Vaping increased nasal PAFR expression. Nicotine-containing and nicotine-free E-cigarette vapour increased pneumococcal adhesion to airway cells in vitro Vapour-stimulated adhesion in vitro was attenuated by the PAFR blocker CV3988. Nicotine-containing E-cigarette vapour increased mouse nasal PAFR expression, and nasopharyngeal pneumococcal colonisation. Vapour contained redox-active metals, had considerable oxidative activity, and adhesion was attenuated by the antioxidant N-acetyl cysteine.This study suggests that E-cigarette vapour has the potential to increase susceptibility to pneumococcal infection.

Preschool wheeze, genes and treatment.

Preschool wheeze is a common but poorly understood cause of respiratory morbidity that is both distinct from and overlaps with infantile bronchiolitis and school age asthma. Attempts at classification by epidemiology, pathophysiology, therapeutic response and clinical phenotype are imperfect and yet fundamental to both treatment choice and research design. The four main therapeutic classes for preschool wheeze, namely beta2 agonists, anticholinergics, corticosteroids and leukotriene modifiers are employed with variable and often scanty evidence base, with evidence for a genetic influence on response variations. The article will discuss the pharmacogenetics of the various options, summarise current treatment recommendations, and explore future research directions.

ERS statement on protracted bacterial bronchitis in children.

This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.

A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework.

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.