Children's Health, Respiratory Inflammation and Short-term Air Pollution
Phase: NA
Conditions: Asthma Acute, Respiratory
Sponsor: Queen Mary University of London

 
 
 
 
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Joint Research Management Office (JRMO) Research Protocol 
for Research Studies 
 
 
 
Full Title  
Short-term air pollution exposure and risk of 
airway inflammatory response in children 
 
Short Title 
CHERISH (Children's HEalth, Respiratory 
Inflammation and SHort-term air pollution)  
 
Sponsor 
Queen Mary University of London (Queen Mary) 
 
Contact person: 
 
Dr Mays Jawad 
Research Governance Operations Manager 
Joint Research Management Office 
Dept W, Research Services  
69-89 Mile End Road  
London, E1 4UJ 
 
Phone: 020 7882 7275/6574 
 
Email: 
research.governance@qmul.ac.uk  
 
 
REC Reference 
QME25.1220 
Research Ethics Committee 
 
Chief Investigator (CI) 
            Dr Abigail Whitehouse 
Senior Clinical Lecturer in Children's 
Environmental Health 
Honorary Consultant in Paediatric Respiratory 
Medicine 
Blizard Institute 
The Faculty of Medicine and Dentistry 
Queen Mary University of London 
4 Newark St 
London 
E1 2AT 
a.whitehouse@qmul.ac.uk 
 
Investigator list 
Dr James Scales (Co- CI) 
 
Centre for Primary Care 
Wolfson Institute of Population Health 
Barts and the London School of Medicine and 
Dentistry 
Queen Mary University of London 

 
 
 
 
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Dr Ian Mudway (Co-I)  
 
Environmental Research Group 
Imperial College London 
 
Iq Mead (Co-I) 
 
 
Environmental Research Group 
Imperial College London 
 
Dr Hajar Hajmohammadi (Co-I) 
Centre for Primary Care 
Wolfson Institute of Population Health 
Barts and the London School of Medicine and 
Dentistry 
Queen Mary University of London 
 
Dr Helen Wood (Co-I)  
 
Centre for Primary Care 
Wolfson Institute of Population Health 
Barts and the London School of Medicine and 
Dentistry 
Queen Mary University of London 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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1. Contents 
 
1. 
Contents ............................................................................................................ 3 
2. 
Glossary ............................................................................................................ 5 
3. 
Signature page .................................................................................................. 6 
4. 
Summary and synopsis ..................................................................................... 7 
5. 
Introduction ........................................................................................................ 9 
5.1. 
Background ............................................................................................... 9 
5.2. 
Rationale ................................................................................................... 9 
6. 
Study objectives ................................................................................................ 9 
6.1. 
Primary hypothesis .................................................................................... 9 
6.2. 
Objectives ................................................................................................ 10 
6.3. 
Physiological secondary endpoints: ......................................................... 10 
6.4. 
Immune response primary endpoint ......................................................... 10 
6.5. 
Secondary Immune response endpoint .................................................... 10 
6.6. 
Control variables ...................................................................................... 10 
6.7. 
Biobanking ............................................................................................... 11 
7. 
Study population .............................................................................................. 11 
7.1. 
Inclusion criteria ....................................................................................... 11 
7.2. 
Exclusion criteria ...................................................................................... 11 
8. 
Study design .................................................................................................... 11 
9. 
Study procedures ............................................................................................ 12 
9.1. 
Participant pathway summary .................................................................. 12 
9.2. 
Abstaining from medication. ..................................................................... 13 
9.3. 
Exercise and exposure protocol: .............................................................. 14 
9.4. 
Study Timeline ......................................................................................... 15 
10. 
Statistical considerations ............................................................................. 15 

 
 
 
 
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10.1. 
Randomization ..................................................................................... 15 
10.2. 
Sample size ......................................................................................... 15 
10.3. 
Method of analysis ............................................................................... 16 
10.4. 
Descriptive analysis ............................................................................. 16 
10.5. 
Statistical modelling ............................................................................. 16 
11. 
Ethics........................................................................................................... 17 
11.1. 
Risks / benefits..................................................................................... 17 
11.1.1. 
Risks to participants: Asthma attack or unwell .................................. 17 
11.1.2. 
Risk mitigation: Asthma attack or unwell .......................................... 17 
11.1.3. 
Response to Asthma attack or unwell participants: .......................... 18 
11.2. 
Risks to participants: Accidental personal data release ........................ 19 
11.3. 
Risk Mitigation: Accidental personal data release ................................ 19 
11.1. 
Annual Safety Reporting ...................................................................... 19 
11.2. 
Benefits ................................................................................................ 19 
12. 
Public involvement ....................................................................................... 20 
13. 
Data handling and record keeping ............................................................... 20 
13.1. 
Data management ............................................................................... 20 
13.2. 
Source Data ......................................................................................... 21 
13.3. 
Confidentiality ...................................................................................... 21 
13.4. 
Record retention and archiving ............................................................ 22 
14. 
Laboratories................................................................................................. 22 
14.1. 
Sample preparation and collection ....................................................... 22 
14.2. 
Laboratory procedures ......................................................................... 22 
14.3. 
Sample storage and transfer ................................................................ 23 
15. 
Safety reporting ........................................................................................... 23 
16. 
Monitoring and auditing ............................................................................... 24 
17. 
Study committees ........................................................................................ 24 

 
 
 
 
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18. 
Finance and funding .................................................................................... 25 
19. 
Insurance and indemnity .............................................................................. 25 
20. 
Dissemination of research findings .............................................................. 25 
21. 
References .................................................................................................. 27 
 
 
 
 
 
 
 
 
 
2. Glossary 
 
ARTP: Association for Respiratory Technology + Physiology 
ATS: American Thoracic Society 
BMI: Body Mass Index 
CARRii: Centre for Applied Respiratory Research Innovation and Impact 
CC16: Clara cell protein 16 
CI: Chief Investigator  
CHERISH: Children's HEalth, Respiratory Inflammation and SHort-term air pollution  
CHILL: Children’s Health in London and Luton 
CRF: Case Report Form 
DEFRA: Department for Environment, Food & Rural Affairs 
DNA: Deoxyribonucleic acid 
ERS: European Respiratory Society 
EUPATI: European Patients' Academy on Therapeutic Innovation 
FeNO: Fractional exhaled Nitric Oxide 
GDPR: General Data Protection Regulation 
HRA: Health Research Authority 
HTA: Health Technology Assessment 
ICC: Interclass correlations 
ICL: Imperial College London 
IL-6: Interleukin-6 
IL-8: Interleukin-8 
MPO: Myeloperoxidase 
MRC: Medical Research Council 
NO2: Nitrogen Dioxide 
PE: Physical Education 
PI: Principal Investigator 
PPI: Patient and Public Involvement 
PMG: Project Management Group 
QMREC: Queen Mary University of London Research Ethics Committee 
QMUL: Queen Mary University of London 
SAB: Scientific Advisory Board 
SOP: Standard Operating Procedure 

 
 
 
 
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STEM: Science, Technology, Engineering, and Mathematics 
WIPH: Wolfson Institute of Population Health  
3. Signature page 
 
 
 
CI Agreement 
 
The study, as detailed within this Research Protocol, will be conducted in accordance 
with the principles of GCP, the UK Policy Framework for Health and Social Care 
Research, and the Declaration of Helsinki and any other applicable regulations. I 
delegate responsibility for the statistical analysis and oversight to a qualified 
statistician (see declaration below). 
 
 
CI Name: 
Abigail Whitehouse 
 
Signature: 
 
 
Date: 
14/10/25 
 
Statistician’s Agreement 
 
The study as detailed within this research protocol will be conducted in accordance 
with the current UK Policy Framework for Health and Social Care Research,, the World 
Medical Association Declaration of Helsinki (1996), Principles of ICH E6-GCP, ICH E9 
- Statistical principles for Clinical Trials and ICH E10 - Choice of Control Groups. 
 
I take responsibility for the statistical work in this protocol is accurate and take 
responsibility for statistical analysis and oversight in this study.  
 
Statistician’s name: 
_________________ 
 
Signature: 
_________________ 
 
Date: 
_________________ 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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4. Summary and synopsis 
 
Short title 
CHERISH (Children's HEalth, Respiratory Inflammation 
and SHort-term air pollution)  
Methodology 
Randomised mixed factorial design with one within-
subject factor (exposure condition: active vs. rest) and 
air pollution as a continuous variable.  
Objectives / aims 
Objective 1: Provision of an air pollutant database 
covering all exposure days and one week prior to 
exposure days at participating school sites and 
children’s home addresses. 
Objective 2: Assess and compare the acute health 
effects (changes in lung function and airway 
inflammation) of primary school-aged children 
exercising in school playgrounds selected to have a mix 
of air quality characteristics. 
Objective 3: Examine the relationship between 
variations in daily air quality and the physiologic and 
immunologic responses observed.  
Objective 4: Provision of a free outreach and 
engagement workshop for all schools, using Breathe 
London real-time, user-friendly air quality data to 
empower schools to monitor their own air quality. 
 
Number of 
participants 
330 
Inclusion and 
exclusion criteria 
Inclusion 
• 
Girls and boys  
• 
Aged 8 to 11  
• 
Attending schools in Central and East London 
that have been recruited to the study  
Exclusion 
• 
Not able to engage with PE lessons on safety 
grounds, reported by their parents.  
• 
Children with learning or physical disabilities 
sufficient for them to be unable to give informed 
assent to the study, or to carry out study 
procedures. 
 

 
 
 
 
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Statistical 
methodology and 
analysis (if 
applicable) 
Mixed effects models, considering repeated 
measurements within participants and variances 
between groups. 
Study duration 
 
24 months 
1st June 2025 – 31st May 2027 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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5. Introduction 
 
5.1. Background 
 
The global burden of disease survey estimated air pollution contributed to one in 
eight deaths in 2019 (1). Urban areas such as London are a heterogeneous 
patchwork of different air pollutants, which all have different impacts on human 
health. Air pollution disproportionally impacts children due to their growing lungs. 
Understanding how different air quality environments affect children is vital to 
improving health guidance we provide to them and their families.  
 
5.2. Rationale 
 
Air pollution in one in four London school playgrounds exceeds the UK legal limit for 
NO2 (2) with playgrounds in deprived areas exposed to 8% more NO2 than the least 
deprived areas. Research has shown that air pollution stunts lung growth in primary 
school-aged children (3). The UK Government’s Committee on the Medical Effects of 
Air Pollutants is currently reviewing the Air Quality Information System for public 
alerts and the issue of whether or when to ask public organisations such as schools 
to restrict exercise. Despite this, no research has explored the health impacts of 
exposure to air pollution in London’s school playgrounds. The committee is calling for 
studies, such as CHERISH, to investigate the health effects of exercise in polluted 
school playgrounds to guide this critical government policy.  
 
6. Study objectives 
 
6.1. Primary hypothesis 
 
Primary hypothesis: Exposure to air pollution in school playgrounds is associated 
with acute decrements in lung function following physical activity as measured by 
oscillometry resistance at R5. 
Secondary hypothesis (ii): Exposure to air pollution during physical activity is 
associated with the induction of inflammation in children compared to rest.  
 
 
 
 
 
 

 
 
 
 
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6.2. Objectives 
 
Objective 1: Provision of an air pollutant database covering all exposure days and 
one week prior to exposure days at participating school sites and children’s home 
addresses. 
Objective 2: Assess and compare the acute health effects (changes in lung function 
and airway inflammation) in primary school-aged children of exercising in school 
playgrounds selected to have a mix of air quality characteristics.  
Objective 3: Examine the relationship between variations in daily air quality and the 
physiologic and immunologic responses observed  
Objective 4: Provision of a free outreach and engagement workshop for all schools, 
using Breathe London real-time, user-friendly air quality data to empower schools to 
monitor their own air quality.  
 
Primary endpoint 
Airways resistance as measured by oscillometry R5 
6.3. Physiological secondary endpoints:  
• 
R5-R20.  
• 
X5 
• 
X5-X20 
6.4. Immune response primary endpoint 
• 
IL6 
6.5. Secondary Immune response endpoint 
• 
Th1/Cellular Immunity: Granzyme A, Granzyme B 
• 
Acute/Innate Inflammation: IL-1b, IL-8, TNFa, MPO 
• 
Th2/Type 2 Immunity: IL-4, IL-5 
• 
Factors That Promote the Th2 Response (Alarmins): TSLP and IL-33 
• 
Dual or Regulatory Role Mediators: IL-10 
• 
TH17-Associated: IL-23 
• 
Vascular/Endothelial Markers: VEGF, E-selectin 
• 
Oxidative stress: Glutathione, LOPs 
6.6. Control variables 
• 
Physical activity measured by accelerometery 
• 
Prior exposure to air quality measured as: PM10 and PM2.5, nitrogen 
dioxide (NO2). 

 
 
 
 
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• 
Temperature, wind direction (if required)  
• 
Prior exposure from Breathe network. 
6.7. Biobanking 
• 
Any nasal mucus samples not used in the analysis will be biobanked for 
secondary analysis.  
• 
We shall target Child Action for a follow-on grant to analyse biobanked 
samples.  
 
 
7. Study population 
 
School Selection 
We shall purposely recruit schools from the CHILL and Breathe networks (Central 
and East London) to ensure a gradient in NO2 between the two groups of five 
schools. Breathe London have provided historical data which shows that we are able 
to provide the required air quality contrasts by working with schools already within 
their network.  
 
Participant Selection 
Children will be recruited via a school bag approach where information sheets and 
consent forms are sent home via school SMS systems and in children’s school bags. 
Additional information/opportunity to ask questions will be provided via playground 
information sessions, talks at parent’s evenings, school newsletters, and class talks.  
 
7.1. Inclusion criteria 
• 
Girls and boys  
• 
Aged 8 to 11  
• 
Attending Central and East London schools recruited to the study  
 
7.2. Exclusion criteria 
• 
Not able to engage with PE lessons on safety grounds reported by their 
parents.  
• 
Children with learning or physical disabilities sufficient for them to be unable 
to give informed assent to the study, or to carry out study procedures. 
 
 
8. Study design 
 
Randomised mixed factorial design with one between-subjects factor with a within-
subjects factor (exposure condition: active vs. rest) and air pollution as a continuous 
variable. 

 
 
 
 
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9. Study procedures 
9.1. Participant pathway summary 
 
Students will be recruited via a school bag approach - where study documents are 
sent to parents in children's school bags. To ensure informed consent, further 
support will be provided in the form of playground information sessions, parent talks, 
school assemblies, school newsletters, and class talks - informing children and 
parents about the study and providing opportunity to ask questions. 
Parents and participants will provide informed consent/assent after they have time to 
consider their involvement (minimum 24 hours) and ask any questions. Following 
provision of written informed consent, participants’ parents/guardians will complete a 
short baseline and demographic questionnaire and provide their address to support 
air pollution exposure estimates.   
 
Following provision of written informed consent, the CHERISH study team will visit 
the schools on two occasions, separated by a minimum washout period of two 
weeks. The study team will set up in a spare classroom. Tables will be wiped down 
and individual stations with bottles of sterile saline solution will be set out along with 
oscillometers and FeNO devices. When consented children enter the room, they will 
be asked initial assent questions (SOP 1). Once they have provided their assent, 
they will have their height and weight measured (SOP 2) and will then undergo the 
nasal sampling and lung function assessment (SOP 4 and SOP 8, respectively). All 
children will perform a FeNO test (SOP 3). They will also be provided with activity 
monitors. 
The children will then take part in either the 90-minute PE lesson led by West Ham 
United Foundation or the science workshop led by Centre of the Cell. The sessions 
will be designed to keep children at either sedentary or moderate levels of physical 
activity. Schools will be randomised in terms of the order in the which the two 
sessions are delivered (i.e., PE followed by science workshop or science workshop 
followed by PE). All children will take part in both sessions. 
At the end of the session children will undergo a second round of lung function 
testing and will hand back their activity monitors.  
The next day the study team will attend the school again and they shall perform the 
assent questions, lung function assessment, and the sample collection in an identical 
way to the pre-exposure assessment.  
Screening, Recruitment & Informed Consent 
 
Central and East London schools will be selected from the Breathe London Network 
or CHILL study as this ensures they already possess the required air quality 
monitoring infrastructure to report air pollution. 10 schools will be recruited with 

 
 
 
 
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varied air pollution concentrations (as determined by historic air quality data from 
Breathe London). 
An average of 33 participants will be recruited at each school according to the criteria 
in section 7.1. 
 
Study Intervention 
 
  
09:00 
10:30 
11:30 
12:30 
24 hours after 
  
Classroom 
Playground 
Playground 
Classroom 
Classroom 
Assent 
x 
  
  
  
  
Baseline 
Survey  
x 
  
  
  
  
Activity 
monitor 
  
x 
x 
  
  
FeNO 
x 
  
  
  
  
Oscillometry 
x 
  
  
x 
x 
Nasal lavage 
x 
  
  
  
x 
 
 
All physiological measures will be performed to the most recent ATS, ERS and ARTP 
guidelines.  
9.2. Abstaining from medication.  
 
Participants will continue to use all their routine asthma medication (e.g. preventer 
inhalers) during the study. In agreement with ERS spirometry guidance, participants 
will be asked to abstain from using reliever medication for six hours prior to 
performing lung function assessment. If participants need to use their medication in 
the six hours prior to the first spirometry testing of an assessment visit they will take 
part in the study and researchers will record the use of medication.  
If participants need to use their inhaler during the testing protocol a member of the 
research team will immediately seek out the school first aid trained member of staff. 
The use of an inhaler should be marked on the CRF. If the symptoms resolve, the 
school policy will be followed. If the school plan is that the participant rejoins PE (and 
the participant agrees and wishes to rejoin) they can return to the PE lesson 
gradually and under observation. The participant should follow the testing pathway 
unless they opt out and withdraw assent.  
 
If the participant is known to have asthma and haven't brought their inhaler, they can 
only take part if the school policy is that they would be allowed to take part in a 
normal exercise class. 

 
 
 
 
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9.3. Exercise and exposure protocol: 
 
To control for variations in air quality, exposure will occur for 90 minutes between 
10:30am and 13:30pm on weekdays. Between pre- and post- health assessments, 
trained coaches will lead an educational outreach PE session designed to maintain a 
consistent level of exercise intensity, monitored by Actigraph physical activity 
monitors. 
We propose standardising exercise intensity to control physiological variation such as 
cardiovascular and ventilatory drift and to standardise inhaled doses of PM and 
gaseous pollutants over the 2-hour period and reflect a typical PE lesson. Moderate 
intensity is chosen, as prior research by the authors has shown that children spend 
break time performing moderate-to-vigorous levels of physical activity, ensuring a 
safe level of intensity, and reflecting children’s typical exercise levels and therefore 
ensuring maximum relevance of the findings. 
 
Sample Collection and Laboratories 
The nasal lavage samples will be collected at the school sites and subsequently 
biobanked. They will be transferred to Blizard laboratories in cooler boxes (4oC) by a 
member of the research team. Upon arrival, samples will be stored within HTA 
approved facilities at -80oC. All transport, storage and disposal protocols will adhere 
to the College’s SOPs, which can be found on the QMUL Governance site. 
See Laboratories Section 14 for details of laboratory procedures for examining the 
samples. 
 
Participant Withdrawal 
Three options are provided to participants should they wish to withdraw: 
• 
May withdraw from a specific part of the study (e.g. one of the lessons – PE 
or science outreach) but continue with the rest of the study, in which case 
data is retained. 
• 
May withdraw at any point and continue no further, data for before this point is 
retained. 
• 
May withdraw and request all data removed - in which case all data for this 
participant is removed from the study. 
 
The sample size for this study has been chosen to account for up to a 15% dropout 
rate without reducing the power of the statistical analysis below 85%. 
 
End of Study 

 
 
 
 
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We define the end of the study as the final interaction with a sample at the laboratory. 
Therefore, the study ends once all included samples have been examined and 
associated data is recorded. 
9.4. Study Timeline 
 
 
10. 
Statistical considerations 
10.1. 
Randomization 
 We shall randomise to activity or sedentary conditions at the school level. This will 
be done prior to school visits via sealed envelopes containing one of the two 
conditions. The envelopes will be sealed before the start of the study by someone not 
part of the study team.  
10.2. 
Sample size  
A total of ten schools will be recruited to this study. Ten schools will be purposively 
recruited using historical air quality data from Breathe London to get higher and lower 
NO2 pollution schools. This strategy will provide the largest air pollution gradient 
possible between the school playgrounds.  
An average of 33 children will be recruited at each school ensuring 165 children are 
recruited to each group. We expect 10% drop out in each group. 
 
For power calculation, we set significance level= 0.05, mean value = 0.572 and 
standard deviation = 0.14 for respiratory resistance (R5). If we want to see 5% 
change in R5, with total of 330 children (33 per school) and clustered within 10 
schools (active vs rest), we then will have a power of 90.21%. Even if we will have a 
dropout rate of 10 to 15%, we will have a power of 85.28%.  

 
 
 
 
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5% change in R5 was chosen as it is a clinically relevant change in airway restriction. 
This is especially true in the specific context of school playground exposures which 
occur daily in school environments. 
 
10.3. 
Method of analysis  
 
Mixed effects models, considering repeated measurements within participants and 
variances between groups. 
 
10.4. 
Descriptive analysis 
 
After data quality check, we will prepare data description tables including number of 
observations, mean and standard deviation of variables. We will also use graphical 
methods (e.g. scatterplots) to get insight in the correlation between different 
exposure variables and the associations between specific exposures and health 
endpoints.  
 
10.5. 
Statistical modelling   
 
We will use a mixed effects regression model to estimate the effects of different 
pollutants on changes in health outcomes, defined as the difference in various 
measures (e.g. R5 and R5–R20) between pre-exposure and post-exposure (at 0, 2, 
or 24 hours). For each endpoint, one key post-exposure time point will be selected 
based on the time of maximal effect observed in previous controlled exposure 
studies; for example, for R5 this will be 24 hours post-exposure. 
 
We will provide estimates of the effects of pollution exposure and physical activity 
(within participants). Levels (e.g. integrated average concentration report as 
interquartile ranges) of each pollutant will be included in the model. We shall include 
pollutant as a continuous variable. The effects of different pollutants will be compared 
based on statistical significance and effect sizes calculated for selected exposure 
contrasts.  
Two-pollutant models will also be specified to evaluate which pollutant has the 
strongest association with each health endpoint. In our models, we will account for 
potential confounders that may be present, as the exposure contrast cannot be 
entirely predicted by design. We may therefore include meteorological variables (e.g. 
temperature, relative humidity, and wind direction during the exposure) as well as 
individual characteristics such as age, gender, asthma severity, and allergies. 

 
 
 
 
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To account for repeated measures, random intercepts for participants will be included 
in the models, and random slopes will be explored if model convergence permits. 
Covariates will be included in the model to account for repeated measures (health 
outcome at baseline) and to adjust differences between groups (BMI as a Z-score, 
ethnicity, age, gender, asthma status). 
To account for possible clustering effects (children nested in schools) we shall first 
run null models to evaluate the interclass correlations (ICC) if the ICC effect is large 
at the school level we shall include two hierarchical levels by including school and 
student as random effects in the model.  
All mixed models will be implemented in R (version 4.1.3 or newer; R Development 
Core Team), using functions from the lme4 and nlme packages. 
 
 
11. 
Ethics 
 
The study will be sponsored and managed by QMUL and supported by Imperial 
College London, according to MRC guidance. 
This study has received QMUL REC approval (reference QME25.1220). The study 
will be carried out according to the principles of the Helsinki Agreement 2013.  
11.1. 
Risks / benefits 
11.1.1. 
Risks to participants: Asthma attack or unwell 
 
There are risks associated with exposing children to high air pollution via exercise 
protocols. Such activities may increase the likelihood of accidental events, with 
asthma attacks being the most likely. Between 8 and 15% of children recruited to the 
study are likely to have asthma, based on UK prevalence. 
 
11.1.2. 
Risk mitigation: Asthma attack or unwell 
 
To mitigate potential accident events during the study we will take the following 
precautions (SOP 6): 
 
• 
The study will only proceed after University Research Ethics Committee 
approval and sponsor indemnity. 
• 
Our protocol has been devised with people living with asthma, children, 
parents and respiratory paediatric clinicians. 

 
 
 
 
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• 
Participants will only be recruited if their parents report them fit enough to 
participate in PE lessons. 
• 
Participants will have respiratory health assessments prior to the PE 
lesson. 
• 
Usual medication will be continued (e.g. prescribed preventer inhalers). 
• 
The exercise intensity and locations have been selected to be typical of 
school PE lessons, as such participants will not be exposed to unusually 
high air pollution.  
• 
Basic rescue asthma medication (salbutamol and large volume spacer) 
should always be available at assessment sites. If required, first aid will 
be administered by appropriate school staff 
• 
If participants need to use their inhaler during the testing protocol the 
testing will end immediately. A member of the research team will 
immediately seek out the school first aid trained member of staff . The use 
of an inhaler should be marked on the CRF. If the symptoms resolve, the 
school policy will be followed. If the school plan is that the participant 
rejoins PE (and the participant agrees and wishes to rejoin) ,they can 
return to the PE lesson gradually and under observation. The participant 
should follow the testing pathway unless they opt out and withdraw 
assent.   
• 
We shall remind children who report having rescue inhalers, bring them to 
school on the visit days. If the participant is known to have asthma and 
haven't brought their inhaler, they can only take part if the school policy is 
that they would be allowed to take part in a normal exercise class. 
• 
Participants will be closely monitored during the exercise protocol and will 
be repeatedly encouraged to provide feedback about their physical state 
during the exercise. 
• 
A risk register and an adverse events register will be maintained for the 
duration of the study. 
• 
Accidents will be discussed with the Chief Investigator and reported 
promptly to the Sponsor as per Good Clinical Practice regulations and 
reviewed at study Project Management Group.   
11.1.3. 
Response to Asthma attack or unwell participants: 
 
This section should be read alongside SOP 06 and the field-testing risk assessment. 
If a participant has an asthma attack during the protocol the testing will end 
immediately. a member of the research team will immediately seek out the school 
first aid trained member of staff. The use of an inhaler should be marked on the CRF. 
If the symptoms resolve, the school policy will be followed. If the school plan is that 
the participant rejoins PE (and the participant agrees and wishes to rejoin) they can 
return to the PE lesson gradually and under observation. The participant should 
follow the testing pathway unless they opt out and withdraw assent.   
 

 
 
 
 
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In the event of a participant feeling unwell, the research team will:  
• 
Calmly reassure the participant and encourage the participant to make 
themselves suitably comfortable.  
• 
The participant will be observed for any signs of distress or breathing 
difficulty.  
• 
Alert the nearest member of school staff 
• 
Seek first aid trained member of school staff 
• 
If required, first aid will be administered by appropriate school staff  
• 
School first aid/safeguarding protocols will be followed. 
11.2. 
Risks to participants: Accidental personal data release 
As with all human participant research there is a risk of inadvertent release or loss of 
personal data through incorrect storage of electronic or hardcopy data or through 
incorrectly transferring or handling data. 
11.3. 
Risk Mitigation: Accidental personal data release 
To mitigate this, we shall follow best practice guidelines provided in SOPs by our 
Clinical Trials Unit (SOP 7). Paper records will be stored securely in locked filling 
cabinets in password locked rooms in the pass-protected Centre for Primary Care in 
the Wolfson Institute of Population Health. Electronic records will be stored in a 
password-protected study database on a secure server in QMUL.  In the study 
database, personal details (name, address, date of birth) will be kept separate from 
research data, which will be identified by a unique study reference number. In tables 
of data, participants will only be identified by number not by initials or name. Data 
management procedures will be completed in compliance with the GDPR and trial 
regulations. Survey reported data will be stored in the QMUL data safe haven, where 
data will be held in a UK server and access will be facilitated by two factor 
authentication. Survey software with integrated data validation checks and audit trails 
will be used to record study data. Any data transfers between QMUL and Imperial 
College London will be completed via encrypted Secure File Transfer Protocol. All 
data will be backed up weekly to ensure data is safeguarded from accidental loss. 
11.1. 
Annual Safety Reporting  
 
The CI will send an Annual Progress Report to the QMREC and the sponsor using 
the Health Research Authority (HRA) template on the anniversary of the QMREC 
“favourable opinion”. 
11.2. 
Benefits  
 

 
 
 
 
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Participants:  
Participants will receive free respiratory health assessments. They shall also receive 
a free lesson  from West Ham United multisport coaches and a ‘snotty science’ 
STEM science workshop explaining how air pollution impacts their health.  
Society:  
 
This study will give evidence to support policy change when it comes to planning of 
play spaces and provide evidence on the direct impact of where our children play in 
relation to traffic pollution exposure. By having this evidence, we will be able to better 
inform families and the wider public on appropriate actions to take. There is also the 
potential to feed into wider policy on health advice such as that given on high air 
pollution days by DEFRA.  
Academic outputs of the study will be fed directly back into the far-reaching education 
projects that are stemming from the Barts-funded and established Children’s 
Environmental Health Service. 
 
 
12. 
Public involvement 
 
As the study progresses the PPI group will be invited to project management group 
(PMG) meetings. The group will collaborate as advisors and partners in the study 
and are invited to provide unsolicited advice. To ensure the PPI group can provide 
meaningful advice and guidance the CI will regularly keep them informed of study 
developments via email. The meetings will follow the EUPATI (European Patients 
Academy on Therapeutic Innovation) roadmap (https://bit.ly/3bugCMk) discussing 
themes of: Research design and planning, research conduct,operations, 
dissemination and communication. 
 
13. 
Data handling and record keeping 
 
13.1. 
Data management 
 
OneDrive will be used to store electronic case report forms all data will be held on 
GDPR compliant databases with integrated data validation checks and audit trails 
(SOP 7). All collected data will be held on backed up encrypted servers. Any data 
transfers between ICL and QMUL will be performed via Secure File Transfer 
Protocols. Paper records, CRFs and consent forms and recruitment logs will be held 
locally in double locked locations in Yvonne Carter Building 58 Turner St E1 2AB 
(QMUL). 
Data Sharing: we will comply with MRC policy on data sharing. A copy of study data 
will be held on the HDRUK BREATHE secure data hub  

 
 
 
 
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https://www.breathedatahub.com. BREATHE’s mission is ‘Better respiratory health 
through better connected data’. 
 
13.2. 
Source Data 
 
 
 
Figure 1. Representation of data flow 
Quantitative data will be generated from patient surveys, health assessments, 
biological samples, and air quality.  
Participant identifiable data will be held within QMUL secure OneDrive. 
All data will be generated, collected, and stored according to MRC policy and the 
findable, accessible, interoperable, and reusable (FAIR) principles. 
 
 
13.3. 
Confidentiality 
 
We shall follow best practice guidelines provided in SOPs by our Clinical Trials Unit. 
Paper records will be stored securely in locked filling cabinets in password locked 
rooms in the pass-protected Centre for Primary Care (WIPH). Electronic records will 
be stored in a password-protected study database on a secure server, in QMUL. In 
the study database, personal details (name, address, date of birth) will be kept 
separate from research data, which will be identified by a unique study reference 
number. In tables of data, participants will only be identified by number not by initials 
or name. Data management procedures will be completed in compliance with the 
GDPR and trial regulations. Survey reported data will be stored in the QMUL data 

 
 
 
 
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safe haven, where data will be held in a UK server and access will be facilitated by 
two factor authentication. Survey software with integrated data validation checks and 
audit trails will be used to record study data. Any data transfers between QMUL and 
Imperial College London will be completed via encrypted Secure File Transfer 
Protocol. All data will be backed up weekly to ensure data is safeguarded from 
accidental loss. 
 
 
13.4. 
Record retention and archiving 
 
 
In accordance with the UK Policy Framework for Health and Social Care Research, 
research records will be kept for 20 years after the study has completed while 
personal records will be stored for five years after the study has been completed. At 
the completion of the study data will be moved to a trusted archive centre. At the end 
of the retention period data will be destroyed in accordance best practice guidelines 
at the time of destruction. 
 
 
14. 
Laboratories  
 
14.1. 
Sample preparation and collection 
 
Nasal mucus samples will be collected via nasal lavage (SOP 4). Nasal lavages will 
be performed at two time points, pre and 24-hour post at the school sites. Samples 
will be biobanked in 5 mL aliquots at -80oC at ICL under Human Tissue Act licence 
12521 (local Human Tissue Act lead, Dr Ian Mudway).  
Samples will be collected in disinfected facilities at the field-testing site. Screens will 
be used to ensure participant privacy.   
 
14.2. 
Laboratory procedures 
 
Samples will be assessed using a case-controlled study design. The sample will 
consist of children who report any form of respiratory disease. We shall then 
randomly select a healthy comparator cohort, which is matched for 1) age 2) sex 3) 
Ethnicity 4) air pollution. 
Samples across the interval pre- to 24-hour post will be used to assess neutrophilic 
biology, oxidative stress pathways, and epithelial injury.  
We hypothesise that short-term exposure to ambient air pollution-primarily driven by 
NO₂ and traffic-related co-pollutants induces epithelial stress, leading to neutrophil 

 
 
 
 
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recruitment and activation, and the release of inflammatory mediators and effector 
molecules. 
The inflammatory response will be characterised through measurement of: 
Primary outcome:  
• 
IL6 (key role in Th17 polarisation) 
 
Secondary outcome: 
• 
Th1/Cellular Immunity: Granzyme A, Granzyme B 
• 
Acute/Innate Inflammation: IL-1b, IL-8, TNFa, MPO 
• 
Th2/Type 2 Immunity: IL-4, IL-5 
• 
Factors That Promote the Th2 Response (Alarmins): TSLP and IL-33 
• 
Dual or Regulatory Role Mediators: IL-10 
• 
TH17-Associated: IL-23 
• 
Vascular/Endothelial Markers: VEGF, E-selectin 
• 
Oxidative stress: Glutathione, LOPs 
 
Nasal lavage samples will also be retained as a downstream resource for secondary 
analysis that aligns with ongoing work by JS and AW.  
 
 
14.3. 
Sample storage and transfer 
 
Samples will be transferred from the collection sites in London to QMUL in cooler 
boxes (4oC) using authorized courier services. Upon arrival samples will be stored 
within HTA approved facilities at -80oC. All transport, storage and disposal protocols 
will adhere to the College’s SOPs, which can be found on the QMUL Governance 
site. 
 
 
15. 
Safety reporting 
 
Accident events occurring between visits/questionnaires/sample collections will not 
be recorded or reported as they are not the aim or focus of this study. 
 
The CI’s (Dr James Scales, Dr Abi Whitehouse) may take urgent safety measures to 
ensure the safety and protection of the study subjects from any immediate hazard to 
their health and safety. The measures should be taken immediately. In this instance, 
the approval of the QMREC prior to implementing these safety measures is not 
required. However, it is the responsibility of the CI to inform the sponsor and Main 
Research Ethics Committee (via telephone) of this event immediately.  
The CI has an obligation to inform both the Main QMREC in writing within 3 days, in 
the form of a substantial amendment. The sponsor (Joint Research Management 

 
 
 
 
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Office [JRMO]) must be sent a copy of the correspondence with regards to this 
matter.  
 
16. 
Monitoring and auditing 
 
The Sponsor or delegate retains the right to audit any study, study site, or central 
facility. In addition, any part of the study may be audited by the funders where 
applicable. 
 
For further explanation of monitoring and auditing this section should be read along 
with the documents: 
 
SOP 1) Consent and assent  
 
SOP 2) Height and weight 
 
SOP 3) FeNO 
 
SOP 4) Nasal lavage  
 
SOP 5a) Activity monitoring  
 
SOP 5b) Device preparation  
 
SOP 6) Participant unwell or injured  
 
SOP 7) Data management and quality control 
 
SOP 8) Oscillometry  
Dr Abi Whitehouse and Dr James Scales will be responsible for the data 
management, storage, record keeping, coding, data linkage, and metadata 
generation. All researchers have up to date GCP and Data Governance training. All 
data will be managed according to European Union General Data Protection (GDPR) 
guidelines. 
QMUL studies adhere to the NHS Research Governance, Framework for Health and 
Social Care, the Data Protection Act, and the Human Tissue Act. We follow QA and 
QC protocols are developed by the PCTU. 
We shall hold a trial Master file recording all key study documents and study 
discussions, ethical review board reports, and staff training logs. Detailed meta-data 
will be kept. Methodologies and analyses will be summarised in readme files, 
including information on variables names, missing data labels, definition of acronyms, 
etc. For example, sample tracking records, SOPs, and information on QA/QC 
procedures, stored as pdfs on secure servers with metadata tables linking relevant 
documentation to datasets. For new data acquisitions/ collations data 
dictionary/metadata describing data content will be created embedded in the data or 
stored separately. Methods and analysis techniques will be documented and stored 
in relevant study folders. 
 
 
17. 
Study committees 

 
 
 
 
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Study Team Meetings  
The study team will meet weekly chaired by JS to discuss day-to-day delivery of the 
project, and report to the PMG. 
Project Management Group (PMG)  
Monthly project management meetings will be chaired by AW and will consist of the 
co-applicants, collaborators, and research associates. Queen Mary University 
London (QMUL) will lead the health assessment and analysis with HW project 
managing the programme. Breathe London (ICL) will lead the exposure data 
collection and processing and laboratory assessments. Ongoing statistical support 
will be provided by HH. An open invite will be extended to the SAB and a CARRii PPI 
group representative 
Scientific Advisory Board (SAB): 
We present an exceptional team that has worked closely together to successfully 
conduct large scale research programmes. However, in recognition of the early 
career status of the applicant we propose to convene a SAB at least four times a 
year; we propose it be chaired by Professor Chris Griffiths, from QMUL Center for 
primary care. Prof Griffiths currently leads the CHILL study. Other members of the 
board include Prof Klea Katsouyanni, who will provide statistical guidance. In the first 
instance the board's role is to monitor and advise on study conduct and progress on 
behalf of the Sponsor and Barts Charity. However, the board are all known to the 
research team and will meet more frequently than a traditional SAB to provide more 
detailed support and guidance to the study team. 
 
18. 
Finance and funding 
 
This work is funded by Barts Charity under grant code: G-002887 
 
19. 
Insurance and indemnity 
 
The insurance that Queen Mary has in place provides cover for the design and 
management of the study as well as "No Fault Compensation" for participants, which 
provides an indemnity to participants for negligent and non-negligent harm. 
 
20. 
Dissemination of research findings 
 
Dissemination is a standing item on the PMG agenda, ensuring interim study findings 
are rapidly and effectively communicated. Our PPI group will co-write or review all 
study outputs for dissemination via traditional and social media throughout the study.  

 
 
 
 
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The outputs of this study fall into four key areas and in order to fully support all of 
them, we will work not only with PPI groups (Namely, Mums for Lungs and CARRii 
PPI Group) to co-design the dissemination plan, but also to work on ways to ensure 
that the results of the study can be viewed by all in an accessible manner.  
Policy: 
We envisage that the results of this study will be directly relevant to policy makers. 
As AW and ISM sit on the UK governments Committee for Medical effects of Air 
pollutants, we know the UK government is specifically looking for studies which 
describe the health impacts of air pollution on children in school playgrounds to 
inform the UK governments air quality warning system. We shall ensure we present 
our findings to the committee.  
Academic: 
This study will deliver key outcomes on the question of the short-term health impacts 
of traffic derived pollution exposure in our most vulnerable age-group. Previous 
research has looked at this in adults but to date the immediate responses have been 
less well clarified within a paediatric population. This will then feed into the wider 
body of evidence on short-term health effects in children.  
• 
We will deliver a set of high impact publications in primarily environmental 
health journals and present our findings at international conferences.  
• 
We shall make our data available on open access via HDRs BREATHE, a UK 
respiratory health data repository lead by our collaborators. 
• 
We shall explore feasibility of combining our data sets with other comparable 
short exposure studies including IONA (WT-7325450) and the London 
Underground study (MR/S035613/1).  
Clinical: 
While this study will look at all children within the schools, there is likely to be a 
proportion that have underlying health conditions therefore we hope to be able to see 
smaller effects in these children.  
We plan to use the results of this study to support clinician education providing 
specific advice regarding vulnerable children with respiratory illness. This will be 
embedded in the air pollution mitigation advice training that has been recommended 
by multiple parties in relation to reducing the health impacts of air pollution exposure 
in children with wheeze and asthma.   
Public: 
This research proposal and study have been developed due to a recurrent and 
pressing need to fulfil a research gap that has been noticed by parents, schools, and 
the wider public, namely looking at the impact that our play spaces have on children’s 
health. Therefore, a major focus of our communications will focus on disseminating 
the results in an accessible way. 

 
 
 
 
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• 
In the spirit of Breathe London’s open access air quality data we shall provide 
summary data to schools and community groups via the Breathe London 
website. 
• 
We shall provide outreach workshops to schools, led by outreach experts at 
QMUL’s Centre of the Cell.  
• 
We shall prepare press releases to support use in social media platforms and 
public facing websites. 
 We will engage closely with the media teams at QMUL and Barts to support this 
process. 
 
 
21. 
References 
 
1. 
Abbafati C, Abbas KM, Abbasi-Kangevari M, Abd-Allah F, Abdelalim A, 
Abdollahi M, et al. Global burden of 87 risk factors in 204 countries and 
territories, 1990–2019: a systematic analysis for the Global Burden of Disease 
Study 2019. The Lancet [Internet]. 2020 Oct 17 [cited 2025 Sep 
19];396(10258):1223–49. Available from: 
https://www.thelancet.com/action/showFullText?pii=S0140673620307522 
2. 
Sheridan CE, Roscoe CJ, Gulliver J, Fecht D, Preux L de. Inequalities in 
Exposure to Nitrogen Dioxide in Parks and Playgrounds in Greater London. 
International Journal of Environmental Research and Public Health 2019, Vol 
16, Page 3194 [Internet]. 2019 Sep 1 [cited 2025 Sep 19];16(17):3194. 
Available from: https://www.mdpi.com/1660-4601/16/17/3194/htm 
3. 
Mudway IS, Dundas I, Wood HE, Marlin N, Jamaludin JB, Bremner SA, et al. 
Impact of London’s low emission zone on air quality and children’s respiratory 
health: a sequential annual cross-sectional study. Lancet Public Health. 2019 
Jan 1;4(1):e28–40.