Assessing airways deposition, physiology and pharmacokinetics of monodisperse aerosols in obstructive lung 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.Open Acces

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

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.</p

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.

Acknowledgements: On behalf of the CHILL Study Investigators. CHILL (PHR 16/139/01) and MRC PHICAZ (MR/T03226X/1) form a pair of studies led by QMUL and Imperial College respectively, evaluating the impacts of the London ULEZ on health.Funder: National Institute for Health Research Public Health Applied Research Collaboration North ThamesFunder: Barts Charity; doi: http://dx.doi.org/10.13039/100015652Funder: Mayor of LondonFunder: Cambridge Trust; doi: http://dx.doi.org/10.13039/501100003343Funder: Asthma UK Centre for Applied Research; doi: http://dx.doi.org/10.13039/501100014335BACKGROUND: 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

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

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

Acknowledgements: We are grateful to all participating schools, parents and children for their enthusiasm and support. The views expressed in this paper are those of the authors and should not be taken to reflect the official position of the funder. This report contains independent research supported by the National Institute for Health and Care Research ARC North Thames. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care.Abstract 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). </jats:sec

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

Abstract 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)