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ObjectiveTaking a qualitative approach, we aimed to understand how London’s Ultra Low Emission Zone (ULEZ) might work to change behaviour and improve health in the context of the school journey.DesignPrimary qualitative study embedded within an existing natural experimental study.SettingA population-level health intervention implemented across London.ParticipantsPurposive sampling was used to recruit children (aged 10–11 years) from ethnically and socioeconomically diverse backgrounds within an existing cohort study, Children’s Health in London and Luton.MethodsIn-person and online interviews were conducted with 21 families and seven teachers from the children’s schools between November 2022 and March 2023. Verbatim transcripts were analysed drawing on Braun and Clarke’s reflexive thematic analysis and guided by realist evaluation principles to identify contexts, mechanisms and outcomes using NVivo.ResultsCommon context, mechanism, outcome (CMO) configurations were identified reflecting congruent narratives across children, parents and teachers, for example, current active travellers (context) reported reductions in pollution (mechanism) leading to improvements in health, including alleviated symptoms of asthma (outcome). These CMOs were broadly captured by two themes: (i) how you travelled before the ULEZ matters: the impact of travel mode on experiences of the ULEZ and (ii) your context matters: the role of socioeconomic position in experiences of the ULEZ. Participants highlighted the potential for the ULEZ to positively impact their choice of travel mode to school, experiences of the journey and their health. However, the impact of the ULEZ differed inequitably by journey length, travel mode before implementation and access to reliable and affordable public transport.ConclusionsThe capacity for the ULEZ to both narrow and exacerbate inequities across different travel contexts suggests when developing such schemes, more emphasis needs to be placed on providing accessible and affordable alternatives to driving.

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 3.51, 95% CI 1.68–7.31). Children in the intervention group were also less likely to switch from active to inactive modes (OR 0.22, 0.12–0.41). Moderator analyses showed that children living further from school were more likely to switch from inactive to active modes (OR 5.20; 1.67–15.21) compared to those living closer (OR 1.54, 0.33-7.21). 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.

Moderator analyses showed that children living further from school were more likely to switch from inactive to active modes (OR 5.20; 1.67–15.21) compared to those living closer (OR 1.54, 0.33–7.21) This value was transformed into a binary variable using a 0.78-km cut-off, This value was transformed into a binary variable using a 0.86-km cut-off, 5 …distance to school (≤ 0.78 km or > 0.78 km), …distance to school (≤ 0.86 km or > 0.86 km), A new paragraph needs to be inserted between the 1 st and 2nd paragraph of Data Analysis, as follows: Sensitivity analyses showed that this exclusion did not significantly affect model fit (likelihood ratio test p = 0.964) and improved AIC and BIC values (Appendix Table 3), indicating a better-fitting, more parsimonious We conducted two sensitivity analyses We conducted additional sensitivity analyses Children who were not included in the analysis at any time point (reasons for exclusion can be found in Fig. 2) from the London cohort (n = 664) were more likely to be male (48.5% vs. 42.4%), from a minority ethnic background (70.1% vs. 66.3%) and lived closer to school (52.7% vs. 48.0%) compared to children living in London who were included in the analyses (Appendix Table 3). Luton children not included in the analyses (n = 768) were more likely to be older (7.9 vs. 7.7 years) at baseline, less likely to have parents in full-time employment (28.9% vs. 34.9%), more likely to live further from (58.9% vs. 51.7%) and lived in areas with higher levels of crime and neighbourhood deprivation than children living in Luton who were included in the analyses 6 There may have been evidence of negative confounding, as the effect size of the fully adjusted model (OR 3.02; 95% CI 1.60–5.70) and the fully adjusted multilevel model (OR 3.64; 95% CI 1.21–10.92) were greater than that of the crude model There may have been evidence of negative confounding, as the effect size of the fully adjusted model (OR 3.47; 95% CI 1.73–7.02) and the fully adjusted multilevel model (OR 3.51; 95% CI 1.68–7.31) were greater than that of the crude model The effect sizes of the fully adjusted (OR 0.14, 95% CI 0.08–0.23) and multilevel model (OR 0.11, 0.05–0.24) were smaller than that of the crude model The effect sizes of the fully adjusted (OR 0.23, 95% CI 0.13–0.40) and multilevel model (OR 0.22, 0.12–0.41) were smaller similar to than that of the crude model Appendix Table 4 and 5 Appendix Table 5 and 6 7 Only distance to school statistically significantly moderated the intervention’s effect on switching from inactive to active modes of transport. Descriptive baseline characteristics of the study population* Covariate London (n = 1000) Luton (n = 982) p-value* Age (mean, SD)  Baseline 7.9 (0.9) 7.7 (0.9)  < 0.001  Follow-up 8.9 (0.9) 8.7 (0.7)  < 0.001 Sex (n, %)  Male 424 (42.4) 490 (49.9) 0.002  Female 576 (57.6) 492 (50.1) Ethnicity (n, %)  BAME 629 (66.3) 572 (59.8)  < 0.001  White 320 (33.7) 384 (40.2) Employment status (n, %)  Full-time 279 (32.2) 317 (34.9) 0.038  Part-time 224 (25.9) 231 (25.4)  Unemployed 126 (14.5) 119 (13.1)  Other 237 (27.4) 241 (26.5) Occupational category (n, %)  Professional/Managerial 368 (56.0) 310 (45.7) 0.007  Skilled 96 (14.6) 112 (16.5)  Unskilled 70 (10.7) 79 (11.7)  Other 123 (18.7) 177 (26.1) Distance to school (n, %)  Near (≤ 0.86 km) 475 (51.3) 351 (48.3) 0.254  Far (> 0.86 km) 451 (48.7) 375 (51.7) Vehicle ownership** (n, %)  Yes 461 (54.1) 798 (89.7)  < 0.001  No 391 (45.9) 92 (10.3) Crime Quintile (n, %)  1 (highest crime) 309 (31.0) 302 (30.9)  < 0.001  2 301 (30.2) 328 (33.6)  3 172 (17.2) 237 (24.3)  4 115 (11.5) 89 (9.1)  5 (lowest crime) 101 (10.1) 21 (2.1) IDACI Quintile (n, %)  1 (highest level of deprivation) 578 (57.9) 190 (19.4)  < 0.001  2 269 (27.0) 368 (37.7)  3 75 (7.5) 282 (28.9)  4 34 (3.4) 114 (11.7)  5 (lowest level of deprivation) 42 (4.2) 23 (2.4) Sums of the number of participants with each characteristic may equal the total number of participants if data is missing N Number, BAME Black, Asian, and Minority Ethnic, SD Standard deviation, km Kilometre, IDACI Index Deprivation Affecting Children Index *p value refers to independent samples t-tests for continuous variables or Pearson's χ2 tests for categorical variables **Vehicle ownership data was only collected at follow-up Table 2.

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 [NO 2 ], particulate matter with a diameter of less than 2.5micrograms [PM 2.5 ], and less than 10 micrograms [PM 10 ]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV 1 ) 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).

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 μg/m3, n = 138), middle (25.6 to 26.8 μg/m3, n = 126), and upper (26.8 to 31.0 μg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of \"mature\" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.

Carrying out health research with schools can be both challenging and highly rewarding. Here we describe lessons learned from a research partnership lasting over 5 years, initially with 84 primary schools in London and Luton, and extended to 35 secondary schools, during our children health cohort study. This period included school closures and societal disruption during the COVID-19 pandemic, creating additional challenges to ongoing school participation. Our study involved annual health assessment visits to schools to test over 3000 participants and parental self-report questionnaires, to assess the potential benefits of air quality improvements arising from London Ultra Low Emission Zone (introduced in April 2019) on children’s lung development and health. Measures included height, weight, pre- and post- bronchodilator spirometry, physical activity monitoring, cognitive assessment, epigenetic markers of disease risk, SARS-CoV-2 IgE and IgM antibody testing, and heavy metals testing. The average annual participant attrition for our study was 11.6%. The acceptable threshold outlined in the initial protocol was 20%. All schools continued to participate in the study for 5 years. Central to the study success have been: shared agreement on the importance of the research topic; early preparatory work with stakeholders, a parallel engaging and innovative air pollution learning and outreach programme, incentivising school/teacher co-operation and parental questionnaire completion to boost response rates and mitigate non-response bias; and continuity of contact with the accessible and flexible research team. These successes form a template for other health research studies planning long-term engagement with schools.

RationaleSmall airways function studies in lung disease have used three promising multiple breath washout (MBW) derived indices: indices of ventilation heterogeneity in the acinar (Sacin) and conductive (Scond) lung zones, and the lung clearance index (LCI). Since peripheral lung structure is known to change with age, ventilation heterogeneity is expected to be affected too. However, the age dependence of the MBW indices of ventilation heterogeneity in the normal lung is unknown.ObjectivesThe authors systematically investigated Sacin, Scond or LCI as a function of age, testing also the robustness of these relationships across two laboratories.MethodsMBW tests were performed by never-smokers (50% men) in the age range 25–65 years, with data gathered across two laboratories (n=120 and n=60). For comparison with the literature, the phase III slopes from classical single breath washout tests were also acquired in one group (n=120).Measurements and main resultsAll three MBW indices consistently increased with age, representing a steady worsening of ventilation heterogeneity in the age range 25–65. Age explained 7–16% of the variability in Sacin and Scond and 36% of the variability in LCI. There was a small but significant gender difference only for Sacin. Classical single breath washout phase III slopes also showed age dependencies, with gender effects depending on the normalisation method used.ConclusionsWith respect to the clinical response, age is a small but consistent effect that needs to be factored in when using the MBW indices for the detection of small airways abnormality in disease.

Inhaled medication is standard therapy in asthma and COPD. However the amount of drug reaching the lung is influenced by several factors including aerosol particle size and upper airway morphology. While smaller sized aerosol particles may be transported to the small airways there is still a need to examine the systemic risk and efficacy associated with small particle aerosols. On one hand small particles can be transported to the lung periphery (small airways) where they can reduce small airways dysfunction. On the other hand small particles can increase plasma concentrations of the drug worsening systemic side effects. Aerosol particle size determines deposition throughout the whole of the respiratory tract including the upper airway and by altering aerosol delivery characteristics it is possible to avoid deposition in the upper airway. This thesis set out to investigate how to improve drug deposition in the lung by controlling aerosol delivery characteristics mainly particle size and flow rate and investigate how the filtering effects of the upper airway can be overcome. The specific aims of this thesis were: To quantify aerosol deposition in the upper airway both in vitro and in vivo with the hope of using in vitro techniques to predict what happens in vivo. Explore how aerosol particle size effects lung deposition and pulmonary bioavailability through pharmacokinetics. Investigate and evaluate novel tests of small and large airways function and see if these can detect physiological improvement following inhalation of small (1.5 μm) particles and large (6 μm) particles. In vitro tests on upper airway models somewhat predicted what happens in vivo. The increasing effect of both particle size and flow rate was shown to increase upper airway deposition. Tests of respiratory function and inflammation demonstrated greater between test variability than routine tests of lung function and warrant further evaluation. Improvements in small and large airway function were not associated with the deposition of small and large aerosol particles following one off dosing of an inhaled corticosteroid fluticasone propionate and a link between these tests and aerosol particle size warrants further investigation.