Objective detection of wheeze at home by parents through a digital device: usage patterns and relationship with SABA administration.

INTRODUCTION: Wheezing is an important indicator of exacerbated respiratory symptoms in early childhood and must be monitored to regulate pharmacological therapy. However, parents' subjective perception of wheezing in their children is not always precise. We investigated the objective identification of children's wheezing by parents using a digital wheeze detector (WheezeScanTM, OMRON Healthcare Co. Ltd), its longitudinal usage patterns, and its relationship with SABA administration. METHODS: We conducted a secondary nested analysis of data from the intervention arm of a multi-center randomized controlled trial completed in 2021-2022 in Berlin (Germany), London (United Kingdom), and Istanbul (Turkey). Children aged 4 to 84 months with doctor's diagnosed wheezing (GINA step 1 or 2) were included. Using an electronic diary (Wheeze-MonitorTM, TPS), parents monitored and recorded for 120 days at home the presence or absence of their child's wheezing, detected both, with WheezeScanTM ("objective" wheezing), and subjective ("perceived" wheezing). Parents also recorded the child's symptoms, medication intake, and family quality of life. Questionnaires regarding symptom control, quality of life, and parental self-efficacy were answered at baseline and after 90 and 120 days. RESULTS: Eighty-one/87 families completed the intervention arm of the study. WheezeScanTM was on average used 0.7 (SD 0.6) times a day, with each patient reporting a positive, negative, or "error" outcome on average in 57%, 39%, and 5% of measurements, respectively. The use of WheezeScanTM declined slightly during the first 90 days of monitoring and steeply thereafter. Repeated usage of WheezeScanTM in the same day was more frequent after a "wheeze" (HR 1.5, 95% CI 1.37-1.65, p < 0.001) and an "error" (HR 2.01, 95% CI 1.70-2.38, p < 0.001) result, compared to a "no wheeze" outcome. The average per-patient daily agreement between "objective" and "perceived" wheezing/non-wheezing was 75% at the start of the monitoring period and only weakly persisted as time passed (Spearman's rho=0.09). The frequency of short-acting beta-2-agonists (SABA) administration was lower in days with closely interspaced consecutive device uses during which the patient's status was perceived as "never wheeze" (32/455, 7%) than in those perceived as "persistent wheeze" (53/119, 44%; OR 36.6, 95% CI [14.3, 94.1]). CONCLUSION: Daily use of a digital WheezeScanTM at home allows parents to detect their child's unperceived wheezing and discloses to caregivers the longitudinal patterns of a child's wheezing disorder. Digital monitoring of wheezing also highlights poor adherence to guidelines in SABA administration for wheezing children, with under-treatment being much more frequent than over-treatment. This pioneering study opens new perspectives for further investigation of digital wheeze detectors in the early diagnosis and proper self-management of wheezing disorders in childhood.

Asthma symptoms, severity, and control with and without a clinical diagnosis of asthma in early adolescence in sub-Saharan Africa: a multi-country, school-based, cross-sectional study.

BACKGROUND: Rapid urbanisation and population growth in sub-Saharan Africa has increased the incidence of asthma in children and adolescents. One major barrier to achieving good asthma control in these adolescents is obtaining a clinical diagnosis. To date, there are scant data on prevalence and severity of asthma in undiagnosed yet symptomatic adolescents. We therefore aimed to assess symptom prevalence and severity, the effect of symptoms on daily life, and objective evidence of asthma in young adolescents from sub-Saharan Africa with and without a clinical diagnosis of asthma by spirometry and fractional exhaled nitric oxide (FeNO). METHODS: We designed a two-phase, multi-country, school-based, cross-sectional study to assess symptom prevalence and severity in sub-Saharan African adolescents. In phase 1 we surveyed young adolescents aged 12-14 years who were attending selected primary and secondary schools in Blantyre in Malawi, Durban in South Africa, Harare in Zimbabwe, Kampala in Uganda, Kumasi in Ghana, and Lagos in Nigeria. The adolescents were screened for asthma symptoms using the International Study of Asthma and Allergies in Children (ISAAC) questionnaire. Then, after opt-in consent, symptomatic adolescents were invited to complete a detailed survey on asthma severity, treatment, and exposure to environmental risk factors for phase 2. Adolescents performed the European Respiratory Society's diagnostic tests for childhood asthma. A positive asthma test was classified as a forced expiratory volume in 1 sec (FEV1) predicted under 80%, a FEV1 under the lower limits of normal, or FEV1 divided by forced vital capacity (FEV1/FVC) under the lower limits of normal; positive bronchodilator responsiveness or reversibility was defined as either an increase in absolute FEV1 of 12% or more, or an increase of 200 mL or more, or both, after 400 µg of salbutamol (shortacting ß2 agonist) administered via a metered-dose inhaler and spacer, or FeNO of 25 parts per billion or higher, or any combination of these. The study was registered with ClinicalTrials.gov (NCT03990402) and is complete. FINDINGS: Between Nov 1, 2018, and Nov 1, 2021, we recruited 149 schools from six regions in six sub-Saharan countries to participate in the study. We administered phase 1 asthma questionnaires from Jan 20, 2019 to Nov 11, 2021, and from 27 407 adolescents who were screened, we obtained data for 27 272 (99·5%). Overall, 14 918 (54·7%) adolescents were female and 12 354 (45·3%) adolescents were male, and the mean age was 13 years (IQR 12-13); nearly all recruited adolescents were of black African ethnicity (26 821 [98·3%] of 27 272). In phase 1, a total of 3236 (11·9% [95% CI 11·5-12·3]) reported wheeze in the past 12 months, and 644 (19·9%) of 3236 had a formal clinical diagnosis of asthma. The prevalence of adolescents with asthma symptoms ranged from 23·8% in Durban, South Africa to 4·2% Blantyre, Malawi. Using ISAAC criteria, severe asthma symptoms were reported by 2146 (66·3%) of 3236 adolescents, the majority of whom (1672 [77·9%] of 2146) had no diagnosis of asthma by a clinician. Between July 16, 2019, and Nov 26, 2021, we administered the phase 2 questionnaire to the 1654 adolescents who had asthma symptoms in phase 1 and consented to proceed to the second phase. In the phase 2 cohort, 959 (58·0%) were female and 695 (42·0%) were male, and the mean age was 13 years (IQR 12-14). One or more diagnostic tests for asthma were obtained in 1546 (93·5%) of 1654 participants. One or more positive asthma tests were found in 374 (48·8%) of 767 undiagnosed adolescents with severe symptoms, and 176 (42·4%) of 415 of undiagnosed adolescents with mild-to-moderate symptoms. Of the 392 adolescents in phase 2 with clinician-diagnosed asthma, 294 (75·0%) reported severe asthma symptoms, with 94 (32·0%) of those with severe symptoms not using any asthma medication. In general, findings in both phases 1 and 2 were consistent across sub-Saharan African countries. INTERPRETATION: A large proportion of adolescents in sub-Saharan Africa with symptoms of severe asthma do not have a formal diagnosis of asthma and are therefore not receiving appropriate asthma therapy. To improve the poor state of asthma control in sub-Saharan Africa, potential solutions such as educational programmes, better diagnosis, and treatment and screening in schools should be considered. FUNDING: UK National Institute for Health and Care Research and UK Medical Research Council.

Children's Health in London and Luton (CHILL) cohort: a 12-month natural experimental study of the effects of the Ultra Low Emission Zone on children's travel to school.

BACKGROUND: The Ultra-Low Emission Zone (ULEZ), introduced in Central London in April 2019, aims to enhance air quality and improve public health. The Children's Health in London and Luton (CHILL) study evaluates the impact of the ULEZ on children's health. This analysis focuses on the one-year impacts on the shift towards active travel to school. METHODS: CHILL is a prospective parallel cohort study of ethnically diverse children, aged 6-9 years attending 84 primary schools within or with catchment areas encompassing London's ULEZ (intervention) and Luton (non-intervention area). Baseline (2018/19) and one-year follow-up (2019/20) data were collected at school visits from 1992 (58%) children who reported their mode of travel to school 'today' (day of assessment). Multilevel logistic regressions were performed to analyse associations between the introduction of the ULEZ and the likelihood of switching from inactive to active travel modes, and vice-versa. Interactions between intervention group status and pre-specified effect modifiers were also explored. RESULTS: Among children who took inactive modes at baseline, 42% of children in London and 20% of children in Luton switched to active modes. For children taking active modes at baseline, 5% of children in London and 21% of children in Luton switched to inactive modes. Relative to the children in Luton, children in London were more likely to have switched from inactive to active modes (OR 3.64, 95% CI 1.21-10.92). Children in the intervention group were also less likely to switch from active to inactive modes (OR 0.11, 0.05-0.24). Moderator analyses showed that children living further from school were more likely to switch from inactive to active modes (OR 6.06,1.87-19.68) compared to those living closer (OR 1.43, 0.27-7.54). CONCLUSIONS: Implementation of clean air zones can increase uptake of active travel to school and was particularly associated with more sustainable and active travel in children living further from school.

Deep multiomic profiling reveals molecular signatures that underpin preschool wheeze and asthma.

BACKGROUND: Wheezing in childhood is prevalent, with over one-half of all children experiencing at least 1 episode by age 6. The pathophysiology of wheeze, especially why some children develop asthma while others do not, remains unclear. OBJECTIVES: This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling. METHODS: Unsupervised, group-agnostic integrative multiomic factor analysis was performed using host/bacterial (meta)transcriptomic and bacterial shotgun metagenomic datasets from bronchial brush samples paired with metabolomic/lipidomic data from bronchoalveolar lavage samples acquired from children 1-17 years old. RESULTS: Two multiomic factors were identified: one characterizing preschool-aged recurrent wheeze and another capturing an inferred trajectory from health to wheeze and school-aged asthma. Recurrent wheeze was driven by type 1-immune signatures, coupled with upregulation of immune-related and neutrophil-associated lipids and metabolites. Comparatively, progression toward asthma from ages 1 to 18 was dominated by changes related to airway epithelial cell gene expression, type 2-immune responses, and constituents of the airway microbiome, such as increased Haemophilus influenzae. CONCLUSIONS: These factors highlighted distinctions between an inflammation-related phenotype in preschool wheeze, and the predominance of airway epithelial-related changes linked with the inferred trajectory toward asthma. These findings provide insights into the differential mechanisms driving the progression from wheeze to asthma and may inform targeted therapeutic strategies.

Efficacy of oral corticosteroids for acute preschool wheeze: a systematic review and individual participant data meta-analysis of randomised clinical trials.

BACKGROUND: Oral corticosteroids are commonly used for acute preschool wheeze, although there is conflicting evidence of their benefit. We assessed the clinical efficacy of oral corticosteroids by means of a systematic review and individual participant data (IPD) meta-analysis. METHODS: In this systematic review with IPD meta-analysis, we systematically searched eight databases (PubMed, Ovid Embase, CINAHLplus, CENTRAL, ClinicalTrials.gov, EudraCT, EU Clinical Trials Register, WHO Clinical Trials Registry) for randomised clinical trials published from Jan 1, 1994, to June 30, 2020, comparing oral corticosteroids with placebo in children aged 12 to 71 months with acute preschool wheeze in any setting based on the Population, Intervention, Comparison, Outcomes framework. We contacted principal investigators of eligible studies to obtain deidentified individual patient data. The primary outcome was change in wheezing severity score (WSS). A key secondary outcome length of hospital stay. We also calculated a pooled estimate of six commonly reported adverse events in the follow-up period of IPD datasets. One-stage and two-stage meta-analyses employing a random-effects model were used. This study is registered with PROSPERO, CRD42020193958. FINDINGS: We identified 16 102 studies published between Jan 1, 1994, and June 30, 2020, from which there were 12 eligible trials after deduplication and screening. We obtained individual data from seven trials comprising 2172 children, with 1728 children in the eligible IPD age range; 853 (49·4%) received oral corticosteroids (544 [63·8%] male and 309 [36·2%] female) and 875 (50·6%) received placebo (583 [66·6%] male and 292 [33·4%] female). Compared with placebo, a greater change in WSS at 4 h was seen in the oral corticosteroids group (mean difference -0·31 [95% CI -0·38 to -0·24]; p=0·011) but not 12 h (-0·02 [-0·17 to 0·14]; p=0·68), with low heterogeneity between studies (I2=0%; τ2<0·001). Length of hospital stay was significantly reduced in the oral corticosteroids group (-3·18 h [-4·43 to -1·93]; p=0·0021; I2=0%; τ2<0·001). Subgroup analyses showed that this reduction was greatest in those with a history of wheezing or asthma (-4·54 h [-5·57 to -3·52]; pinteraction=0·0007). Adverse events were infrequently reported (four of seven datasets), but oral corticosteroids were associated with an increased risk of vomiting (odds ratio 2·27 [95% CI 0·87 to 5·88]; τ2<0·001). Most datasets (six of seven) had a low risk of bias. INTERPRETATION: Oral corticosteroids reduce WSS at 4 h and length of hospital stay in children with acute preschool wheeze. In those with a history of previous wheeze or asthma, oral corticosteroids provide a potentially clinically relevant effect on length of hospital stay. FUNDING: Asthma UK Centre for Applied Research.

Outdoor air pollution and near-fatal/fatal asthma attacks in children: A systematic review.

BACKGROUND: Globally, observational studies have demonstrated an association between high levels of air pollution and asthma attacks in children. It remains unclear whether and to what extent exposure may be associated with increased near-fatal/fatal attacks. OBJECTIVE: To systematically review the evidence for an association between ambient outdoor air pollution and fatal and/or near-fatal asthma (NFA). METHODS: Following Cochrane methodology, we searched MEDLINE, EMBASE, Web of Science, Scopus, and Open Grey electronic databases for studies reporting the association of fatal/NFA and air pollution (particulate matter [PM], sulfur dioxide, nitrogen dioxide, black carbon and ozone [O3]) in children. NFA was defined as requiring intensive care unit (ICU) management. RESULTS: Two reviewers independently screened 1358 papers. A total of 276 studies identified asthma attacks related to air pollution, 272 did not meet inclusion criteria after full-text review. Four observational studies described fatal/NFA, of which three addressed NFA. PM2.5 (per 12.5 µg/m3 increase) and O3 (per 22 ppb increase) were associated with NFA in one study (PM2.5, relative risk: 1.26, confidence interval [CI] [1.10-1.44]), O3 (1.19 [1.01-1.40]). PM10 was associated with ICU admission in the context of thunderstorm asthma. Elemental carbon was associated equally with NFA that did not require an ICU admission (p = 0.67). Studies of fatal asthma including children did not demarcate age within the analysis. CONCLUSIONS: Ozone and PM2.5 have been associated with NFA in children but synthesis is limited by the paucity of studies and methodological heterogeneity. Poor reporting of severities of asthma attacks hinders the assessment of whether outdoor air pollution is associated with an increased number of NFA/fatal attacks in children.

Clinical efficacy and satisfaction of a digital wheeze detector in a multicentre randomised controlled trial: the WheezeScan study.

Introduction: Wheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting. Methods: A multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4-84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2). Results: A total of 167 children, with a mean±sd age of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI -2.3-9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful. Conclusion: In the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support.

A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study.

Improving the treatment of non-cystic fibrosis bronchiectasis in children and adolescents requires high-quality research with outcomes that meet study objectives and are meaningful for patients and their parents and caregivers. In the absence of systematic reviews or agreement on the health outcomes that should be measured in paediatric bronchiectasis, we established an international, multidisciplinary panel of experts to develop a core outcome set (COS) that incorporates patient and parent perspectives. We undertook a systematic review from which a list of 21 outcomes was constructed; these outcomes were used to inform the development of separate surveys for ranking by parents and patients and by health-care professionals. 562 participants (201 parents and patients from 17 countries, 361 health-care professionals from 58 countries) completed the surveys. Following two consensus meetings, agreement was reached on a ten-item COS with five outcomes that were deemed to be essential: quality of life, symptoms, exacerbation frequency, non-scheduled health-care visits, and hospitalisations. Use of this international consensus-based COS will ensure that studies have consistent, patient-focused outcomes, facilitating research worldwide and, in turn, the development of evidence-based guidelines for improved clinical care and outcomes. Further research is needed to develop validated, accessible measurement instruments for several of the outcomes in this COS.

Characterising sources of PM2·5 exposure for school children with asthma: a personal exposure study across six cities in sub-Saharan Africa.

BACKGROUND: Air pollution is the second largest risk to health in Africa, and children with asthma are particularly susceptible to its effects. Yet, there is a scarcity of air pollution exposure data from cities in sub-Saharan Africa. We aimed to identify potential exposure reduction strategies for school children with asthma living in urban areas in sub-Saharan Africa. METHODS: This personal exposure study was part of the Achieving Control of Asthma in Children in Africa (ACACIA) project. Personal exposure to particulate matter (PM) was monitored in school children in six cities in sub-Saharan Africa (Blantyre, Malawi; Durban, South Africa; Harare, Zimbabwe; Kumasi, Ghana; Lagos, Nigeria; and Moshi, Tanzania). Participants were selected if they were aged 12-16 years and had symptoms of asthma. Monitoring was conducted between June 21, and Nov 26, 2021, from Monday morning (approximately 1000 h) to Friday morning (approximately 1000 h), by use of a bespoke backpack with a small air pollution monitoring unit with an inbuilt Global Positioning System (GPS) data logger. Children filled in a questionnaire detailing potential sources of air pollution during monitoring and exposures were tagged into three different microenvironments (school, commute, and home) with GPS coordinates. Mixed-effects models were used to identify the most important determinants of children's PM2·5 (PM <2·5 µm in diameter) exposure. FINDINGS: 330 children were recruited across 43 schools; of these, 297 had valid monitoring data, and 1109 days of valid data were analysed. Only 227 (20%) of 1109 days monitored were lower than the current WHO 24 h PM2·5 exposure health guideline of 15 µg/m3. Children in Blantyre had the highest PM2·5 exposure (median 41·8 µg/m3), whereas children in Durban (16·0 µg/m3) and Kumasi (17·9 µg/m3) recorded the lowest exposures. Children had significantly higher PM2·5 exposures at school than at home in Kumasi (median 19·6 µg/m3vs 14·2 µg/m3), Lagos (32·0 µg/m3vs 18·0 µg/m3), and Moshi (33·1 µg/m3vs 23·6 µg/m3), while children in the other three cities monitored had significantly higher PM2·5 exposures at home and while commuting than at school (median 48·0 µg/m3 and 43·2 µg/m3vs 32·3 µg/m3 in Blantyre, 20·9 µg/m3 and 16·3 µg/m3vs 11·9 µg/m3 in Durban, and 22·7 µg/m3 and 25·4 µg/m3vs 16·4 µg/m3 in Harare). The mixed-effects model highlighted the following determinants for higher PM2·5 exposure: presence of smokers at home (23·0% higher exposure, 95% CI 10·8-36·4), use of coal or wood for cooking (27·1%, 3·9-56·3), and kerosene lamps for lighting (30·2%, 9·1-55·2). By contrast, 37·2% (95% CI 22·9-48·2) lower PM2·5 exposures were found for children who went to schools with paved grounds compared with those whose school grounds were covered with loose dirt. INTERPRETATION: Our study suggests that the most effective changes to reduce PM2·5 exposures in these cities would be to provide paving in school grounds, increase the use of clean fuel for cooking and light in homes, and discourage smoking within homes. The most efficient way to improve air quality in these cities would require tailored interventions to prioritise different exposure-reduction policies in different cities. FUNDING: UK National Institute for Health and Care Research.

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).

Near-fatal and fatal asthma and air pollution: are we missing an opportunity to ask key questions?

There is an increasing body of evidence supporting the link between asthma attacks and air pollution in children. To our knowledge, there has only been one reported case of a fatal asthma attack in a child associated with air pollution and this was in the UK. This article considers why there is a lack of evidence on fatal/near-fatal asthma and air pollution. We also explore three challenges. First, fatal and near-fatal asthma events are rare and not yet well understood. Second, measuring and interpreting personal exposure to air pollution with sufficient temporal and spatial detail are challenging to interpret in the context of individual fatal or near-fatal asthma attacks. Third, current studies are not designed to answer the question of whether or to what extent air pollution is associated with fatal/near-fatal asthma attacks in children. Conclusive evidence is not yet available and systems of data collection for both air pollution and fatal and near-fatal asthma attacks should be enhanced to ensure risk can be determined and impact minimised.

Curbside particulate matter and susceptibility to SARS-CoV-2 infection.

Background: Biologic plausibility for the association between exposure to particulate matter (PM) less than 10 µm in aerodynamic diameter (PM10) and coronavirus disease 2019 (COVID-19) morbidity in epidemiologic studies has not been determined. The upregulation of angiotensin-converting enzyme 2 (ACE2), the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) entry receptor on host cells, by PM10 is a putative mechanism. Objective: We sought to assess the effect of PM10 on SARS-CoV-2 infection of cells in vitro. Methods: PM10 from the curbside of London's Marylebone Road and from exhaust emissions was collected by cyclone. A549 cells, human primary nasal epithelial cells (HPNEpCs), SARS-CoV-2-susceptible Vero-E6 and Calu3 cells were cultured with PM10. ACE2 expression (as determined by median fluorescent intensity) was assessed by flow cytometry, and ACE2 mRNA transcript level was assessed by PCR. The role of oxidative stress was determined by N-acetyl cysteine. The cytopathic effect of SARS-CoV-2 (percentage of infection enhancement) and expression of SARS-CoV-2 genes' open reading frame (ORF) 1ab, S protein, and N protein (focus-forming units/mL) were assessed in Vero-E6 cells. Data were analyzed by either the Mann-Whitney U test or Kruskal-Wallis test with the Dunn multiple comparisons test. Results: Curbside PM10 at concentrations of 10 µg/mL or more increased ACE2 expression in A549 cells (P = .0021). Both diesel PM10 and curbside PM10 in a concentration of 10 µg/mL increased ACE2 expression in HPNEpCs (P = .0022 and P = .0072, respectively). ACE2 expression simulated by curbside PM10 was attenuated by N-acetyl cysteine in HPNEpCs (P = .0464). Curbside PM10 increased ACE2 expression in Calu3 cells (P = .0256). In Vero-E6 cells, curbside PM10 increased ACE2 expression (P = .0079), ACE2 transcript level (P = .0079), SARS-CoV-2 cytopathic effect (P = .0002), and expression of the SARS-CoV-2 genes' ORF1ab, S protein, and N protein (P = .0079). Conclusions: Curbside PM10 increases susceptibility to SARS-COV-2 infection in vitro.

A cross-country qualitative analysis of teachers' perceptions of asthma care in sub-Saharan Africa.

Asthma is the most common chronic respiratory disease among school-going adolescents worldwide. However, the burden of severe asthma is highest in Sub-Saharan Africa. This study aimed to explore teachers' perceptions of asthma care across six African countries. We conducted focus group discussions (FGDs) using a semi-structured interview guide. Interviews were audio-recorded, transcribed verbatim and analysed thematically. FGDs were conducted in Kumasi(Ghana), Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda), and Harare (Zimbabwe) between 01 November 2020 and 30 June 2021. We identified two key themes related to asthma care; barriers to asthma care and suggestions to improve the care of adolescents with asthma. Barriers reported by teachers included a lack of knowledge and skills among themselves, adolescents, and caregivers. In addition, some traditional beliefs of teachers on asthma exacerbated challenges with asthma care in schools. Regarding suggestions, most teachers identified a need for all-inclusive asthma training programmes for teachers, adolescents and caregivers, focusing on acute episodes and mitigating triggers. Utilising teachers with personal experiences with asthma to advocate and support these initiatives was suggested. Further suggestions included the need for annual screening to enable early identification of adolescents with asthma and clarify restrictions on teachers administering asthma medications. Teachers across African schools identify multiple barriers to asthma care. Structured school education programs and annual asthma screening are key to addressing some barriers to care.

Barriers to childhood asthma care in sub-Saharan Africa: a multicountry qualitative study with children and their caregivers.

OBJECTIVES: This study identifies barriers and provides recommendations to improve asthma care in children across sub-Saharan Africa, where qualitative data is lacking despite high rates. DESIGN: One of the aims of our National Institute for Health Research global health research group 'Achieving Control of Asthma in Children in Africa' was to use qualitative thematic analysis of transcribed audio recordings from focus group discussions (FGDs) to describe barriers to achieving good asthma control. SETTING: Schools in Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda) and Harare (Zimbabwe). PARTICIPANTS: Children (n=136), 12-14 years with either asthma symptoms or a diagnosis and their caregivers participated in 39 FGDs. All were recruited using asthma control questions from the Global Asthma Network survey. RESULTS: There were four key themes identified: (1) Poor understanding, (2) difficulties experienced with being diagnosed, (3) challenges with caring for children experiencing an acute asthma episode and (4) suboptimal uptake and use of prescribed medicines. An inadequate understanding of environmental triggers, a hesitancy in using metred dose inhalers and a preference for oral and alternate medications were identified as barriers. In addition, limited access to healthcare with delays in diagnosis and an inability to cope with expected lifestyle changes was reported. Based on these findings, we recommend tailored education to promote access to and acceptance of metred dose inhalers, including advocating for access to a single therapeutic, preventative and treatment option. Furthermore, healthcare systems should have simpler diagnostic pathways and easier emergency access for asthma. CONCLUSIONS: In a continent with rapidly increasing levels of poorly controlled asthma, we identified multiple barriers to achieving good asthma control along the trajectory of care. Exploration of these barriers reveals several generalisable recommendations that should modify asthma care plans and potentially transform asthma care in Africa. TRIAL REGISTRATION NUMBER: 269211.

Confocal microscopy 3D imaging and bioreactivity of La Palma volcanic ash particles.

In September 2021 an eruption began of Cumbre Vieja, La Palma (Spain) that lasted 3 months. Previous studies have shown that volcanic ash particles can be associated with adverse effects on human health however, the reasons for this are unclear. Particle shape has been shown to contribute to cellular uptake in prostate cancer cells. Hence we aimed to study 3D structure, elemental composition and effects on cultured lung cells of particles collected from the La Palma volcanic eruption. 3D imaging of PM10 sized and below particles was performed using a LEXT OLS4100 confocal microscope (Olympus Corporation, Japan). A Zeiss EVO 50 (Carl Zeiss AG, Germany) Scanning Electron Microscope (SEM) was used to assess elemental composition. In addition, volcanic particle concentration dose response for pneumococcal adhesion to A549 human alveolar epithelial cells was investigated. Confocal microscopy showed that some PM10 and below sized particles had sharp or angular 3D appearance. SEM x-ray analysis indicated silicate particles with calcium, aluminium and iron. We observed increased colony forming units indicating increased Pneumococcal adhesion due to exposure of cells to volcanic particles. Thus in addition to the toxic nature of some volcanic particles, we suggest that the observed sharp surface particle features may help to explain adverse health effects associated with volcanic eruptions.

Important steps towards a big change for lung health: a joint approach by the European Respiratory Society, the European Society of Radiology and their partners to facilitate implementation of the European Union's new recommendations on lung cancer screening.

Enormous progress has been made on the epic journey towards implementation of lung cancer screening in Europe. A breakthrough for lung health has been achieved with the EU proposal for a Council recommendation on cancer screening. https://bit.ly/3J4O0Jb.

Device-Measured Change in Physical Activity in Primary School Children During the UK COVID-19 Pandemic Lockdown: A Longitudinal Study.

BACKGROUND: Lockdown measures, including school closures, due to the COVID-19 pandemic have caused widespread disruption to children's lives. The aim of this study was to explore the impact of a national lockdown on children's physical activity using seasonally matched accelerometry data. METHODS: Using a pre/post observational design, 179 children aged 8 to 11 years provided physical activity data measured using hip-worn triaxial accelerometers worn for 5 consecutive days prepandemic and during the January to March 2021 lockdown. Multilevel regression analyses adjusted for covariates were used to assess the impact of lockdown on time spent in sedentary and moderate to vigorous physical activity. RESULTS: A 10.8-minute reduction in daily time spent in moderate to vigorous physical activity (standard error: 2.3 min/d, P < .001) and a 33.2-minute increase in daily sedentary activity (standard error: 5.5 min/d, P < .001) were observed during lockdown. This reflected a reduction in daily moderate to vigorous physical activity for those unable to attend school (-13.1 [2.3] min/d, P < .001) during lockdown, with no significant change for those who continued to attend school (0.4 [4.0] min/d, P < .925). CONCLUSION: These findings suggest that the loss of in-person schooling was the single largest impact on physical activity in this cohort of primary school children in London, Luton, and Dunstable, United Kingdom.

Defining the in vivo mechanism of air pollutant toxicity using murine stress response biomarkers.

Air pollution can cause a wide range of serious human diseases. For the informed instigation of interventions which prevent these outcomes there is an urgent need to develop robust in vivo biomarkers which provide insights into mechanisms of toxicity and relate pollutants to specific adverse outcomes. We exemplify for a first time the application of in vivo stress response reporters in establishing mechanisms of air pollution toxicity and the application of this knowledge in epidemiological studies. We first demonstrated the utility of reporter mice to understand toxicity mechanisms of air pollutants using diesel exhaust particles compounds. We observed that nitro-PAHs induced Hmox1 and CYP1a1 reporters in a time- and dose-dependent, cell- and tissue-specific manner. Using in vivo genetic and pharmacological approaches we confirmed that the NRF2 pathway mediated this Hmox1-reporter induction stress reporter activity. We then correlated the activation of stress-reporter models (oxidative stress/inflammation, DNA damage and Ah receptor -AhR- activity) with responses in primary human nasal cells exposed to chemicals present in particulate matter (PM; PM2.5-SRM2975, PM10-SRM1648b) or fresh roadside PM10. To exemplify their use in clinical studies, Pneumococcal adhesion was assessed in exposed primary human nasal epithelial cells (HPNEpC). The combined use of HPNEpC and in vivo reporters demonstrated that London roadside PM10 particles induced pneumococcal infection in HPNEpC mediated by oxidative stress responses. The combined use of in vivo reporter models with human data thus provides a robust approach to define the relationship between air pollutant exposure and health risks. Moreover, these models can be used in epidemiological studies to hazard ranking environmental pollutants by considering the complexity of mechanisms of toxicity. These data will facilitate the relationship between toxic potential and the level of pollutant exposure in populations to be established and potentially extremely valuable tools for intervention studies for disease prevention.