Biomarkers in Preschool Children With Wheeze to TArget Therapy wIth inhaLed cORticosteroids (TAILOR): a Feasibility Study".
Conditions: Wheezing
Sponsor: Imperial College London

 
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© Imperial College of Science, Technology and Medicine 
  
 
 
“TAILOR” Study 
 
 
 
 
Biomarkers in preschool children with wheeze to TArget therapy wIth 
inhaLed cORticosteroids (TAILOR): a feasibility study. 
 
 
 
Version 9.0 – 22nd September 2023 
 
 
 
 
MAIN SPONSOR: 
Imperial College London  
FUNDERS: 
Asthma UK Centre for Applied 
Research 
STUDY COORDINATION CENTRE: Oxford University Hospitals NHS 
Foundation Trust 
IRAS Project ID: 
300524 
REC reference: 
21/PR/1195 
 
 
 
 

 
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© Imperial College of Science, Technology and Medicine 
  
Signature Page 
 
The undersigned confirm that the following protocol has been agreed and accepted 
and that the Chief Investigator agrees to conduct the study in compliance with the 
approved protocol and will adhere to the principles outlined in the Declaration of 
Helsinki, the Sponsor’s SOPs, and other regulatory requirement. 
 
I agree to ensure that the confidential information contained in this document will not 
be used for any other purpose other than the evaluation or conduct of the investigation 
without the prior written consent of the Sponsor. 
 
I also confirm that I will make the findings of the study publicly available through 
publication or other dissemination tools without any unnecessary delay and that an 
honest accurate and transparent account of the study will be given; and that any 
discrepancies from the study as planned in this protocol will be explained. 
 
This protocol has been written in accordance with the Sponsor’s guidance for writing 
non-CTIMP protocol. 
 
 
PROTOCOL MODIFICATIONS 
A/A 
Version 
Date 
1. 
1.0 
27 
June 
2021 
2. 
2.0 
23 
August 
2021 
3. 
3.0 
15 September 2021 
4. 
4.0 
01 
February 
2022 
5. 
5.0 
28 
February 
2022 
6. 
6.0 
20 
June 
2022 
7. 
7.0 
05 
May 
2023 
8. 
8.0 
05 
May 
2023 
9. 
9.0 
22 September 2023 
 
 
 
PROTOCOL AUTHORISED BY: 
 
 
 
_________________________        ________________              _______________ 
NAME AND ROLE                            DATE                                    SIGNATURE 
 

 
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© Imperial College of Science, Technology and Medicine 
  
STUDY MANAGEMENT GROUP 
 
Chief Investigator: Professor Andrew Bush 
 
Co-investigators: Mr. Andreas Perikleous, Professor Ian Pavord, Professor 
Christopher Griffiths, Dr. Louise Fleming, Dr. Sarah-Jane Bowen 
 
Statistician: Dr Steff Lewis, AUKCAR 
 
Study Management: Mr. Andreas Perikleous  
 
STUDY COORDINATION CENTRE: Imperial College London 
 
For general queries, supply of study documentation, and collection of data, please 
contact: 
 
Study Coordinator:  
Andreas Perikleous 
Address: 
Exhibition Rd, South Kensington, London SW7 2BX 
E-mail: 
andreas.perikleous18@imperial.ac.uk 
Telephone: 
+44 (0) 7590817023 
Web Address: 
N/A 
Registration: 
N/A 
Fax: 
N/A 
 
 
CLINICAL QUERIES 
Clinical queries should be directed to Professor Andrew Bush   
 
SPONSOR 
Imperial College London is the main research Sponsor for this study.  For further 
information regarding the sponsorship conditions, please contact the Head of 
Regulatory Compliance at: 
 
Research Governance and Integrity Team 
Imperial College London and Imperial College Healthcare NHS Trust 
Room 215, Level 2, Medical School Building 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 9459/ 0207 594 1862 
http://www3.imperial.ac.uk/clinicalresearchgovernanceoffice  
 
FUNDER 

 
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© Imperial College of Science, Technology and Medicine 
  
 
Asthma UK Centre for Applied Research 
 
This protocol describes the “TAILOR” study and provides information about 
procedures for entering child participants.  Every care was taken in its drafting, but 
corrections or amendments may be necessary. These will be circulated to investigators 
in the study.  Problems relating to this study should be referred, in the first instance, to 
the Chief Investigator.  
 
This study will adhere to the principles outlined in the UK Policy Framework for Health 
and Social Care Research. It will be conducted in compliance with the protocol, the 
Data Protection Act and other regulatory requirements as appropriate.  
 
TABLE OF CONTENTS 
 
                       Page Number                 
 
1. 
GLOSSARY OF ABBREVIATIONS .................................................................... 6 
2. 
STUDY SUMMARY .............................................................................................. 6 
3. 
TAILOR STUDY – PROTOCOL FLOWCHART................................................ 11 
4. 
INTRODUCTION ................................................................................................ 13 
4.1. BACKGROUND .................................................................................................. 13 
4.2. RATIONALE FOR CURRENT STUDY .............................................................. 14 
4.3. PRE-CLINICAL/CLINICAL DATA ..................................................................... 14 
5. 
STUDY’S AIM AND OBJECTIVES ................................................................... 15 
5.1. STUDY RISK / BENEFIT ANALYSIS ................................................................ 15 
6. 
STUDY DESIGN ................................................................................................. 17 
6.1. STUDY OUTCOME MEASURES ...................................................................... 20 
7. 
CHILD PARTICIPANT ENTRY .......................................................................... 20 
7.1. PRE-REGISTRATION EVALUATIONS AND RECRUITMENT........................ 20 
7.2. INCLUSION AND EXCLUSION CRITERIA ...................................................... 24 
7.2.1. CHILDREN ........................................................................................................ 24 
7.2.2. HEALTHCARE PROFESSIONALS ................................................................. 24 
7.3. WITHDRAWAL CRITERIA ................................................................................ 24 
8. 
ADVERSE EVENTS ........................................................................................... 25 
8.1. DEFINITIONS ..................................................................................................... 25 
8.2. REPORTING PROCEDURES ............................................................................ 25 
8.2.1. NON SERIOUS AES ......................................................................................... 25 
8.2.2. SERIOUS AES .................................................................................................. 25 

 
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8.3. THE TYPE AND DURATION OF THE FOLLOW-UP OF SUBJECTS AFTER 
AES ...................................................................................................................... 26 
8.4. PREGNANCY ..................................................................................................... 26 
8.5. ANNUAL PROGRESS REPORTS (APRS) ....................................................... 26 
8.6. REPORTING URGENT SAFETY MEASURES ................................................. 26 
8.7. MANAGEMENT OF POTENTIAL STUDY RISKS ............................................ 27 
9. 
ASSESSMENT AND FOLLOW-UP ................................................................... 27 
10. END OF STUDY ................................................................................................. 27 
11. STATISTICS AND DATA ANALYSIS ............................................................... 27 
12. REGULATORY ISSUES .................................................................................... 28 
12.1. ETHICS APPROVAL .......................................................................................... 28 
12.2. CONSENT ........................................................................................................... 28 
12.3. CONFIDENTIALITY ........................................................................................... 29 
12.4. INDEMNITY ........................................................................................................ 29 
12.5. SPONSOR .......................................................................................................... 29 
12.6. FUNDING ............................................................................................................ 29 
12.7. AUDITS ............................................................................................................... 29 
13. DATA MANAGEMENT AND QUALITY ASSURANCE .................................... 29 
13.1. CONFIDENTIALITY ........................................................................................... 29 
13.2. DATA COLLECTION TOOL .............................................................................. 29 
13.3. DATA HANDLING AND ANALYSIS ................................................................. 30 
13.4. ARCHIVING ARRANGEMENTS ....................................................................... 30 
13.5. DIRECT ACCESS TO SOURCE DATA ............................................................ 30 
14. INSURANCE AND INDEMNITY ........................................................................ 30 
15. STUDY MANAGEMENT .................................................................................... 30 
16. PUBLICATION POLICY ..................................................................................... 31 
17. STATEMENT OF COMPLIANCE ...................................................................... 31 
18. REFERENCES ................................................................................................... 32 
19. APPENDICES ..................................................................................................... 34 
19.1. APPENDIX 1:  RECRUITMENT PLAN.............................................................. 34 
19.2. APPENDIX 2:  FOLLOW-UP PLAN .................................................................. 36 
19.3. APPENDIX 
3: 
TRACKTM 
SCORE 
QUESTIONNAIRE 
(TEST 
FOR 
RESPIRATORY AND ASTHMA CONTROL IN KIDS) ..................................... 37 
19.4. APPENDIX 4: MONTHLY QUESTIONNAIRE .................................................. 38 
19.5. APPENDIX 5: EXIT QUESTIONNAIRE ............................................................ 39 
 

 
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© Imperial College of Science, Technology and Medicine 
  
1. GLOSSARY OF ABBREVIATIONS 
 
AE 
Adverse Event 
APR 
Annual Progress Report 
AR 
Adverse Reaction 
CI 
Chief Investigator 
CRF 
Case Report Form 
ED 
Emergency Department 
EVW 
Episodic Viral Wheeze 
FeNO 
Fractional Exhaled Nitric Oxide 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GP 
General Practitioner 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
ICS 
Inhaled Corticosteroids 
ID 
Identification Number 
IL 
Interleukin 
LPLV 
Last Patient Last Visit 
MHRA 
Medicines and Healthcare Products Regulatory Agency 
MTW 
Multiple-Trigger Wheeze 
Non-CTIMP 
Non-Clinical Trial of an Investigational Medicinal Product 
OCS 
Oral Corticosteroids 
PI 
Principal Investigator 
PIS 
Patient Information Sheet 
REC 
Research Ethics Committee 
R&D 
Research and Development 
RGF 
Research Governance Framework 
SAE 
Serious Adverse Event 
SMF 
Study Master File 
SOP 
Standard Operating Procedure 
SPTs 
Skin Prick Tests 
 
 
KEYWORDS: 
Wheezing, preschool, children, atopic sensitisation, atopy, aeroallergens, blood 
eosinophils, eosinophilia, FeNO. 
 
2. STUDY SUMMARY 
 

 
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TITLE: 
Biomarkers in preschool children with wheeze to TArget therapy wIth 
inhaLed cORticosteroids (TAILOR): a feasibility study”. 
AIM: 
 
 
 
 
 
 
OBJECTIVES: 
 
To obtain pilot data to test the hypothesis that aeroallergen sensitisation 
(confirmed by a wheal formation with a diameter ≥ 3 mm after a skin prick 
test is performed), FeNO (offline method) ≥ 10 ppb and a peripheral blood 
eosinophil count  300/μl, alone or in combination, can predict future 
wheezing exacerbations in preschool children as well as response to 
treatment with inhaled corticosteroids, as a preliminary to a large, 
randomised controlled trial. Also, that these tests are acceptable to 
families.   
 
• To recruit 100 preschool children with a history of wheeze, aged one to 
five years old, and determine atopic status, peripheral blood eosinophil 
count (point of care test) and FeNO (offline method). 
• To evaluate the feasibility and acceptability of these tests 
• To categorize the children according to the biomarkers tested and 
assess whether any or all, alone or in combination, predict future 
wheezing exacerbations as well as determine the clinical outcome over 
one year  
• To obtain parents’ and doctors’ insights into whether the biomarkers 
mentioned above could be used in a future intervention study. 
OUTCOME 
MEASURES: 
Primary outcome: 
• Acute attacks of wheeze defined as requiring an unscheduled health 
care visit 
 
Secondary outcomes: 
• Carer days off work  
• Children unable to attend childcare facility  
• Use of oral corticosteroids 
• Use of inhaled β-2 agonist (rescue therapy) 
• Assessment if children’s respiratory or wheezing condition is under 
control by using the TRACKTM score questionnaire (Test for 
Respiratory and Asthma Control in Kids) (Appendix 3). 
POPULATION: Children aged one to five years old presenting either to primary care with 
wheezing episodes or to emergency departments with an acute attack of 
wheeze or to secondary care (e.g., outpatients) or children identified from 
primary care records and have been diagnosed with wheezing by their GP 
or paediatrician. 

 
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ELIGIBILITY: 
(children) 
Inclusion criteria: 
1. Patients aged one to five years old presenting either to primary care or 
to the emergency department or to secondary care (e.g., outpatients) or 
identified from primary care records and have been diagnosed with 
wheezing by their GP or paediatrician who has decided to prescribe any 
bronchodilator, ICS or montelukast on clinical grounds 
2. Parents/Carers able to understand and familiarize themselves with the 
study and are willing to provide informed consent 
 
Exclusion criteria: 
1. Inability to understand and cooperate with study procedures 
2. Significant co-morbidity (respiratory or otherwise), for example cystic 
fibrosis (excluding atopic disorders such as eczema, allergic rhinitis and 
food allergy) 
3. Withholding or withdrawal of informed consent 
4. Severe procedural anxiety (needle phobia)  
5. Child is already enrolled in another study involving investigational 
medicinal product (CTIMP) 
6. History of anaphylaxis or near-fatal asthma that resulted in intubation / 
assisted ventilation. 
 
ELIGIBILITY: 
(Healthcare 
professionals) 
Inclusion Criteria: 
1. Doctors and nurses working in GP practices. 
 
Exclusion Criteria: 
1. Inability to understand and cooperate with study procedures. 
 
DESIGN: 
This is a pragmatic, observational study in children with pre-school wheeze. 
After recruitment and at the first study visit, biomarkers (allergic 
sensitisation, exhaled nitric oxide and peripheral blood eosinophil count) 
will be measured. The children will be followed for a year, with monthly 
electronic questionnaires and study visits every 3 months. All treatment and 
routine monitoring decisions will be at the discretion of the children’s 
general practitioner (GP) or paediatrician (as per usual clinical practice), 
blinded to the study measurements. There will be a second optional 
biomarker measurement 3 months after the first one, in their second study 
visit. Parents/Carers of preschool children presenting either to primary care 
or to the Emergency Department (ED) or to secondary care (e.g., 
outpatients) as well as of those identified from primary care records and 
have been diagnosed by their GP or paediatrician with wheezing, will be 
identified by collaborating doctors and nurses who will ask the parents if 
they are willing to have their child participate in the study (the list of 
recruitment sites is given in Appendix 1 – Recruitment Plan). A patient 
information sheet will be given, containing all the information regarding the 

 
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project and the contact details of the research team, for further questions. 
They will be asked for their willingness to give the study team permission 
to contact them and discuss recruitment. After clinical consultation and 
following submission of the electronic informed consent, the parent/carer 
will be asked to give the contact details of the child’s GP or paediatrician, 
who will be informed about child’s participation in this study through a letter 
sent to his/her email along with the patient information sheet. In addition, 
we will ask them to provide some of the child’s personal data. The parent 
carer will be then shown a standard video questionnaire and will be asked 
to identify what respiratory sounds their children have been making. The 
child will be booked for the above biomarker tests at a single visit and at a 
time of clinical stability. If the child has been prescribed OCS, biomarker 
testing will be delayed by 2 weeks. Firstly, a sample of the child’s exhaled 
tidal breath will be collected in a suitable bag for offline measurement of 
FeNO. Skin prick tests will be performed to (a) house dust mite, (b) grass 
pollen, (c) tree pollen, (d) cat hair € dog hair, as well as negative and 
positive controls and these will be applied on either the child’s back, leg or 
arm. If the child has been prescribed antihistamines, we will ask for these 
to be withheld for 72 hours prior to skin prick testing. Finally, the peripheral 
blood eosinophil count will be measured from a finger prick blood sample, 
using the Haemocue machine, giving a result in approximately 2 minutes. 
All tests will normally take no more than one hour. 
 
Follow-up: We will arrange for a short monthly electronic questionnaire to 
be sent by email to the parents/carers, to record on a monthly basis, the 
days their child was out of childcare, days the carer missed from work, 
unscheduled health care visits and use of rescue therapy or oral 
corticosteroids (including dosage) (Appendix 4: Monthly Questionnaire). 
We will record the children’s TRACKTM score (Test for Respiratory and 
Asthma Control in Kids) (Appendix 3: TRACKTM score questionnaire) every 
3 months to assess wheeze control. In addition, review visits will occur 
every 3 months, but if not feasible, video calls will be arranged through 
Microsoft Teams. Correct inhaler use will be ensured by parental 
education. If a child has had their ICS treatment discontinued, we will 
record whether this was because the treatment was ineffective (treatment 
failure) or if the child was so well that the family or GP did not wish to 
continue (treatment success or spontaneous improvement). If an additional 
medication is prescribed, or the child is referred to secondary care, this will 
be considered as treatment failure. When the study ends, parents/carers 
will be given the opportunity to join a focus group and give their insights 
into the investigations and the conduct of the study and inform the design 
of the future intervention study. In addition, we will ask them to fill in a very 
short questionnaire after the study is finished, to check their perspective 

 
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and acceptability on these biomarkers being used in clinical settings to 
guide children’s therapy in the future (Appendix 5: Exit Questionnaire). 
Finally, a focus group for doctors and nurses will also be conducted to 
check the feasibility of the 3 biomarker tests being used in clinical practice. 
DURATION: 
36 months total study duration, with 1-year follow-up for each child 
participant included. Study’s start date will be 01.09.2021 and end date will 
be 31.12.2023. 

 
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3. TAILOR STUDY – PROTOCOL FLOWCHART 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes 
Start of 
the study 
Patients identified from primary care, 
ED, UCC and primary care records. 
Parents informed about the study and 
given the patient information sheet and 
all the time to consider participation. 
Patient meets 
eligibility criteria. 
Patient is 
recruited. 
Patient is not 
recruited. 
No 
Parent gives 
informed consent. 
No 
Yes 
Participant’s GP or 
paediatrician is informed of 
his/her participation. 
Parents identify 
their child’s 
respiratory sounds. 
Participant is on 
OCS therapy. 
Yes 
Biomarker testing is 
performed 2 weeks 
after treatment stops. 
No 
Participant is on 
antihistamine 
therapy. 
Yes 
Biomarker testing is 
performed 72 hours 
after treatment stops. 
No 
Biomarker testing: 
1) Blood eosinophil count 
2) Atopic sensitization 
3) FeNO (offline method) 
Participant follow-up 
period (12 months) 
Parents complete the monthly electronic 
questionnaires as well as the TRACKTM score 
electronic questionnaire every 3 months. 
* 

 
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Parents and their child 
have follow-up visits in 
primary care every 3 
months. 
No 
Virtual meeting through NHS 
Attend anywhere, WhatsApp 
or Viber 
Yes 
Child’s progress is 
assessed in person. 
Evaluation of biomarkers’ ability to 
predict future wheezing 
exacerbations and response to ICS. 
Parents complete the exit 
questionnaire. 
Parents join focus group. 
End of 
study 
Evaluation of biomarkers’ ability to 
predict future wheezing 
exacerbations and response to ICS. 
Second biomarker testing  
(3 months after the first one) 
Parent agrees for a 
second testing to be
performed. 
Yes 
Second biomarker testing  
is performed. 
No 
The second biomarker testing  
is not performed. 
* 
Doctors and nurses join 
focus group. 

 
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4. 
INTRODUCTION  
 
4.1. BACKGROUND 
Wheezing in preschool children is a common and troublesome problem, leading to 
impaired quality of life and repeated admissions to hospital (1). Management hitherto 
has been largely on the basis of history, rather than biomarker driven, and bedevilled 
by meaningless questions such as ‘At what age can you diagnose asthma?’(2,3). 
There is some merit in dividing these children into episodic viral wheeze (EVW, children 
who only wheeze with a usually clinically diagnosed viral respiratory tract infection) and 
multiple trigger wheeze (MTW, children who wheeze both with respiratory viral 
infections and with triggers such as exercise and allergen exposure between colds) 
(4), but such a distinction relies on accurate parental perception of symptoms (5). This 
is notoriously inaccurate, and for, example, when compared with a video questionnaire, 
it is clear that many sounds which are not the result of intrathoracic airway narrowing 
are described as wheeze by parents/carers.  
 
The Lancet Asthma Commission has highlighted that ‘asthma’ is an umbrella term for 
a clinical syndrome comprising wheeze, chest tightness, breathlessness and 
sometimes increased cough (2). The focus has moved to defining so-called ‘treatable 
traits’, such as whether there is eosinophil airway inflammation, usually driven by the 
signature Type 2 cytokines Interleukin (IL) -4, -5, and -13, which are responsive to 
inhaled corticosteroids (ICS) (6,7). Nowhere is this concept of treatable traits more 
important than in preschool wheeze, wherein only a few children who wheeze have 
any evidence of allergic sensitisation or Type 2 inflammation. At age one year, even 
children with such severe symptoms as to merit bronchoscopy in a tertiary referral 
children’s hospital had no evidence of any inflammation or airway remodelling (8). By 
30 months of age, in another cross-sectional study, some but by no means all had 
evidence of eosinophil airway inflammation, reticular basement membrane thickening 
and airway smooth muscle hypertrophy and hyperplasia (9). Clinical experience 
reflects this diversity, and although atopic preschool wheezers are more likely to 
respond to ICS, as we have shown, many atopic wheezers do not have an eosinophil 
airway phenotype (10), and are thus unlikely to be ICS responsive. We have recently 
confirmed that there is a good correlation between bronchoalveolar lavage and 
peripheral blood eosinophil concentrations (11).  
 
Another biomarker for eosinophil airway inflammation is exhaled nitric oxide (FeNO). 
In older children and adults, titrating ICS dose using FeNO has been shown to reduce 
asthma attacks and improve outcomes (12). The use of FeNO to guide management 
not been studied in pre-school children. Young children usually cannot perform the 
standard slow exhalation, but we have experience in measuring FeNO off-line by 
collecting tidally exhaled air, which is the technique we propose to use.  
 

 
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Allergic sensitisation as determined by skin prick tests, is another association of airway 
Type 2 inflammation in children, which has been used to predict response to ICS (13). 
Any biomarker which is of practical use in the management of preschool wheeze has 
to be able to provide an answer quickly and be available in primary care where most 
of these children are treated. A portable point of care measurement of peripheral blood 
eosinophil count from a finger prick blood sample will be carried out in a network of 
primary health care centres in and around Oxford (a finger prick being the sort of test 
done repeatedly at home for diabetic children to monitor insulin requirements) and 
exhaled nitric oxide measurements, meaning that both tests are practical by the above 
criteria. 
 
Finally, it should be noted that atopy is not an ‘all-or-nothing’ phenomenon (14). We 
propose to perform exploratory, hypothesis generating analyses quantifying atopy by 
the sum of skin prick test wheals, to see if the predictive power of this test can be 
further improved.  
 
4.2. RATIONALE FOR CURRENT STUDY 
Inhaled corticosteroids are effective treatment at all ages for patients with eosinophil 
airway disease, but have side-effects, including growth suppression, adrenal failure 
and increased susceptibility to respiratory infection. Only some children with preschool 
wheeze have airway eosinophilia, and thus benefit from inhaled corticosteroids, but 
these cannot be distinguished from the non-eosinophil phenotypes clinically.  By using 
three simple point of care tests (blood eosinophil count, skin prick test to aeroallergens 
and FeNO) we aim to select out the subgroup of responders who will benefit, while 
avoiding exposing non-responders to potential side-effects. 
 
4.3. PRE-CLINICAL/CLINICAL DATA 
This highly variable pathophysiology of pre-school wheeze is reflected in the response 
to treatment, making the determination of phenotype much more than a matter of 
academic importance. In the first serious attempt to apply personalised medicine to 
this group of patients, the INFANT study investigators used a three way crossover 
design to compare the differential response to therapy with intermittent ICS, regular 
ICS and montelukast in 300 children (15). Sixty improved spontaneously over the 
duration of the study. Atopic sensitisation predicted a good response to ICS, shown by 
reduced numbers of attacks of wheeze and better control of chronic symptoms. In a 
retrospective analysis, an elevated blood eosinophil count and even better, a 
combination of positive SPTs and peripheral blood eosinophils >300/μl were the best 
predictors of a good response to regular ICS. Leukotriene receptor antagonists were 
not beneficial in any group. Those with no positive SPTs or elevated eosinophil count 
rarely had acute attacks of wheeze. These findings, especially the predictive power of 
blood eosinophil count, need to be tested prospectively in primary care, the setting in 
which most of these children are treated, in a large prospective randomised controlled 
trial. Prior to this, pilot data to inform power calculations, and the feasibility and 

 
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acceptability of this approach needs to be determined. Additionally, although FeNO in 
preschool children is not well standardized there is one study which proposed FeNO 
values  10 ppb to be predictive of eosinophil inflammation in preschool children (16). 
 
5. 
STUDY’S AIM AND OBJECTIVES 
 
AIM: 
To obtain pilot data to test the hypothesis that aeroallergen 
sensitisation (confirmed by a wheal formation with a diameter ≥ 3 
mm after a skin prick test is performed), FeNO (offline method) ≥ 10 
ppb and a peripheral blood eosinophil count  300/μl, alone or in 
combination, can predict future wheezing exacerbations in 
preschool children as well as response to treatment with inhaled 
corticosteroids, as a preliminary to a large, randomised controlled 
trial. Also, that these tests are acceptable to families.   
 
OBJECTIVES: 
 
• To recruit 100 preschool children with a history of wheeze, aged 
one to five years old, and determine atopic status, peripheral 
blood eosinophil count (point of care test) and FeNO (offline 
method). 
• To evaluate the feasibility and acceptability of these tests 
• To categorize the children according to the biomarkers tested and 
assess whether any or all, alone or in combination, predict future 
wheezing exacerbations as well as determine the clinical 
outcome over one year  
• To obtain parents’ and doctors’ insights into whether the 
biomarkers mentioned above could be used in a future 
intervention study. 
 
5.1. STUDY RISK / BENEFIT ANALYSIS 
Benefits:  The only tests of clinical significance to the child are the skin prick tests, 
which might for example inform a decision about the purchase of a pet. The family will 
be informed about these results. The other tests won't be of clinical significance. The 
ultimate benefit will be in the future if we can show with a large intervention trial that 
measuring one or more of these biomarkers helps predict future wheezing 
exacerbations as well as guide treatment more efficiently, thus children stop receiving 
unnecessary medications. The benefit generated by this trial is to show that these 
markers can be measured in practice, and they are acceptable to the families.   
 
Risk analysis: Child participants’ routine clinical management is not changed in this 
observational study. Clinicians have no access to study data. Risks relate to study 
procedures: all procedures [blood sampling through finger prick test, skin prick tests 
and FeNO collection (offline method)] will be performed by trained research personnel. 

 
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© Imperial College of Science, Technology and Medicine 
  
Skin prick tests are safe and used clinically for many years, but adrenaline and 
antihistamines will be available while the study procedures are being performed, in the 
highly unlikely event of an allergic reaction (Figure 1). All research staff will be trained 
in management of acute reactions / anaphylaxis. The finger prick test is the same as 
used by diabetic patients to monitor blood glucose. Collecting breath into a bag is 
devoid of risk. 
 
 
 
Figure 1. Anaphylaxis case reports after skin prick test. (A) Clinical study in 
Cambridge, UK involving 31,000 participants (17), (B) Retrospective analysis from 4 
allergy centres in Italy (Verona, Genoa and Naples) involving 55,105 participants (18). 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 17 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
6. 
STUDY DESIGN 
This is a pragmatic, observational study involving preschool children with wheeze 
aged one to five years old. All treatment and routine monitoring decisions will be at 
the discretion of their treating general practitioner (GP) or paediatrician (as per usual 
clinical practice), blinded to the study measurements. After clinical consultation and 
following submission of the electronic informed consent through the Qualtrics® 
platform (offered by Imperial College London), the parent/carer will be asked to give 
the contact details of the child’s GP or paediatrician, who will be informed about child’s 
participation in this study through a letter sent to his/her email along with the patient 
information sheet. The parent carer will be then shown a standard video questionnaire 
and will be asked to identify what respiratory sounds their children have been making. 
The child will be booked for the three biomarker tests [atopic sensitisation, blood 
eosinophil count and FeNO (off-line method)]. The tests will be carried out once and 
at a time of clinical stability. In this visit, a sample of the child’s exhaled tidal breath 
will be collected in a suitable bag in duplicate for offline measurement of FeNO later 
on with chemiluminescence. Skin prick tests will be performed to: (a) house dust mite, 
(b) grass pollen, (c) tree pollen, (d) cat hai€(e) dog hair, as well as normal saline and 
histamine and these will be applied on either the child’s back, leg or arm. If the child 
has been prescribed antihistamines, we will ask for these to be withheld for 72 hours 
prior to skin prick testing. FeNO values (offline method) ≥ 10 ppb will indicate Type 2 
inflammation and wheal diameter, measured with a specialised skin prick test ruler, ≥ 
3mm will indicate sensitisation to the applied aeroallergen. In addition, skin prick tests 
will allow the assessment of which aeroallergen is the most useful predictor of 
outcomes in preschool children. Finally, the peripheral blood eosinophil count will be 
measured from a finger prick blood sample, using the Haemocue machine, allowing a 
result in approximately 2 minutes. Values ≥ 300 cells/μl indicate Type 2 inflammation. 
All tests will normally take no more than one hour. 
 
The recruitment period will approximately last 9 months, and all preschool wheezers 
can join the study at any point (Appendix 1: Recruitment Plan). Parents/Carers of 
preschool children presenting to primary care or to the Emergency Department (ED) 
or to secondary care (e.g., outpatients) as well as those identified from primary care 
records and who have been diagnosed by a GP or paediatrician with wheezing, will 
be approached by collaborating doctors and nurses who will ask their parents if they 
are willing to have their child participate in the study (Appendix 1: Recruitment Plan). 
A patient information sheet will be given, containing all the information regarding the 
project and the contact details of the research team, for further questions. They will 
be asked for their willingness to give the study team permission to contact them and 
discuss recruitment, and if so, they will submit their contact details in an electronic 
form made with Qualtrics® questionnaire platform (offered by Imperial College 
London), which allows gathering data according to the GCP guidelines and as used 
for years in the Breathing Together study (19). This form will be available online in the 
Asthma UK Centre for Applied Research’s (AUKCAR) website. The initial introduction 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 18 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
will be made either by the clinical team (above) with the study team contacting them 
at a later date to give more information or by Mr. Andreas Perikleous if he is there in 
person.  
 
Additionally, the Emergency Department of Oxford Universities Hospital (OUH) Trust 
will identify patients who have previously presented and diagnosed with wheezing in 
the Emergency Department. A regular search of the OUH databases will be performed 
by the clinical care team to identify patients who meet the eligibility criteria and have 
attended the Emergency Department. Parents/carers of eligible participants will be 
informed about the study by phone by a member of their clinical care team and asked 
whether they agree to be contacted by the study team to give them more information 
and send them the participant information sheet. Their contact details will be then 
submitted in the TAILOR study contact details form. 
 
If the child has been prescribed OCS, testing will be delayed by 2 weeks for biomarker 
testing as soon as the electronic informed consent is submitted. Finally, parents will 
be informed through the patient information sheet as well as, in person, that a second 
optional testing will take place 3 months after the first one, in their second study visit. 
This will allow assessing the reproducibility of the obtained biomarker results, thus 
additionally assess their stability. 
 
Patient recruitment at a site will only commence once the study team has ensured the 
following: 
 
• HRA approval 
• Completed Local Site Delegation of Duties and Signature Log 
• Confirmation of Capacity and Capability  
 
All recruitment procedures will be in accord with the GCP, and parents/carers will be 
given detailed information regarding the study as well as all the time they need to 
understand it. Parents/guardians have at least 24 hours to consider participation. 
Recruitment will only commence after parents/carers have fully understood the project 
and given informed consent online through the Qualtrics® platform (offered by Imperial 
College London). 
 
Child participants entering the study upon their parents’ wish, will be fully screened by 
the Principal Investigator (PI) or someone else from the research team who is suitably 
qualified and delegated to do so, with the latter taking informed consent as well. After 
the electronic informed consent sheet is submitted, parents will be asked to provide 
the contact details of their child’s GP or paediatrician, to inform him/her about the 
child’s participation in this study through a letter sent by email along with this patient 
information sheet. In addition, we will ask them to provide some of the child’s personal 
data (Appendix 1: Recruitment Plan, Table 3: The personal data that will be obtained 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 19 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
by each individual participant). Children’s full name, date of birth, gender, ethnicity as 
well as, their parent’s full name, telephone number and email address will be added in 
the child’s patient card. All other data obtained from the study will be added in the Case 
Report Form (CRF).  
 
Follow-up: We will arrange for a short monthly electronic questionnaire to be sent by 
email to the parents/carers, in order to record on a monthly basis, the days their child 
was out of childcare, days the carer missed from work, unscheduled health care visits 
and use of rescue therapy or oral corticosteroids (including dosage) (Appendix 4: 
Monthly Questionnaire). In addition, we will record the children’s TRACKTM score (Test 
for Respiratory and Asthma Control in Kids) (Appendix 3: TRACKTM score 
questionnaire) every 3 months, to assess wheeze control. The questionnaires will be 
made and sent through the Qualtrics® questionnaire platform (offered by Imperial 
College London). There will be review visits every 3 months, to evaluate their 
progression in person, but if not feasible, video calls will be arranged through Microsoft 
Teams. Correct use of spacers will be ensured after guiding parents on how to use 
them and will be done by their GP or paediatrician as well as from Mr. Andreas 
Perikleous who is a registered pharmacist in the UK.  
 
In the event that a child has had their ICS treatment discontinued, we will record 
whether this was because the treatment was ineffective (treatment failure) or if the 
child was so well that the family or GP did not wish to continue (treatment success or 
spontaneous improvement). If an additional medication is prescribed, or the child is 
referred to secondary care, this will be considered as treatment failure. When the 
study ends, participants’ parents/carers will be invited to a face-to-face focus group 
interview, or a one-to-one interviews, or remotely through Microsoft Teams, 
depending on their availability at the end of the study period. The focus group and one 
to one interviews will utilise a semi structured questionnaire, to provide qualitative 
feedback on the acceptability of the 3 biomarker tests. In addition, a separate focus 
group for doctors and nurses will be conducted to assess the feasibility of the 3 
biomarker tests being used in clinical practice. They will be given all the information 
regarding the study as well as the study’s patient information sheet. Those agreeing 
to take part, will sign a consent form. They will be attending either a face-to-face focus 
group interview, or a one-to-one interview, or remotely through Microsoft Teams, 
depending on their availability. A semi structured questionnaire will be utilised. Where 
possible a second independent researcher will sit in the focus groups discussion and 
interviews to ensure there is no bias. The conversations from the focus group and one 
to one interviews will be transcribed and coded into themes. We will utilise an external 
company 
for 
transcribing 
the 
conversations 
called 
1st 
Class. 
https://www.1stclass.uk.com/ 
 
The focus group and one to one interviews will be audio recorded, transcribed and put 
into themes to conduct an inductive thematic analysis. 25% of the transcripts will be 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 20 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
double coded by an independent researcher, experienced in qualitative research to 
ensure that the correct themes have been used and to ensure that there is no bias. 
The focus group and one to one interviews will be used to assess the acceptability 
and feasibility of measuring biomarkers in primary care and using them to help 
determine management of preschool wheeze. 
 
In addition, we will ask them to fill in a very short electronic questionnaire after the 
study is finished, to check their perspective and acceptability on these biomarkers 
being used to guide children’s therapy in the future (Appendix 5: Exit Questionnaire). 
    
The whole duration of this study is expected to be 20-21 months, with 1-year follow-up 
for each patient included. 
 
6.1. 
STUDY OUTCOME MEASURES 
Primary outcome: 
Acute attacks of wheeze defined as requiring an unscheduled health care visit 
 
Secondary outcomes: 
• Carer days off work 
• Days the child unable to attend childcare facility  
• Use of oral corticosteroids 
• Use of inhaled β-2 agonist (rescue therapy) 
• Assessment if children’s respiratory or wheezing condition is under control by 
using the TRACKTM score questionnaire (Test for Respiratory and Asthma Control 
in Kids) (Appendix 3). 
 
7. 
CHILD PARTICIPANT ENTRY 
 
7.1. PRE-REGISTRATION EVALUATIONS AND RECRUITMENT 
This is a pragmatic, observational study involving preschool children with wheeze 
aged one to five years old. All treatment and routine monitoring decisions will be at 
the discretion of their treating general practitioner (GP) or paediatrician (as per usual 
clinical practice), blinded to the study measurements. After clinical consultation and 
following submission of the electronic informed consent through the Qualtrics® 
questionnaire platform (offered by Imperial College London), the parent/carer will be 
asked to give the contact details of the child’s GP or paediatrician, who will be informed 
about child’s participation in this study through a letter sent to his/her email along with 
the patient information sheet. The parent carer will be then shown a standard video 
questionnaire and will be asked to identify what respiratory sounds their children have 
been making. The child will be booked for the three biomarker tests [atopic 
sensitisation, blood eosinophil count and FeNO (off-line method)]. The tests will be 
carried out once and at a time of clinical stability. In this visit, a sample of the child’s 
exhaled tidal breath will be collected in a suitable bag in duplicate for offline 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 21 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
measurement of FeNO later on with chemiluminescence. Skin prick tests will be 
performed to: (a) house dust mite, (b) grass pollen, (c) tree pollen, (d) cat hair, (e) dog 
hair, as well as normal saline and histamine and these will be applied on either the 
child’s back, leg or arm. If the child has been prescribed antihistamines, we will ask 
for these to be withheld for 72 hours prior to skin prick testing. FeNO values (offline 
method) ≥ 10 ppb will indicate Type 2 inflammation and wheal diameter, measured 
with a specialised skin prick test ruler, ≥ 3mm will indicate sensitisation to the applied 
aeroallergen. In addition, skin prick tests will allow the assessment of which 
aeroallergen is the most useful predictor of outcomes in preschool children. Finally, 
the peripheral blood eosinophil count will be measured from a finger prick blood 
sample, using the Haemocue machine, allowing a result in approximately 2 minutes. 
Values ≥ 300 cells/μl indicate Type 2 inflammation. All tests will normally take no more 
than one hour. 
 
The recruitment period will approximately last 9 months, and all preschool wheezers 
can join the study at any point (Appendix 1: Recruitment Plan). Parents/Carers of 
preschool children presenting to primary care or to the Emergency Department (ED) 
or secondary care (e.g., outpatients) as well as those identified from primary care 
records and who have been diagnosed by a GP or paediatrician with wheezing, will 
be approached by collaborating doctors and nurses who will ask their parents if they 
are willing to have their child participate in the study (Appendix 1 – Recruitment Plan). 
A patient information sheet will be given, containing all the information regarding the 
project and the contact details of the research team, for further questions. They will 
be asked for their willingness to give the study team permission to contact them and 
discuss recruitment, and if so, they will submit their contact details in an electronic 
form made with the Qualtrics® questionnaire platform (offered by Imperial College 
London), which allows gathering data according to the GCP guidelines and as used 
for years in the Breathing Together study (19). This form will be available online in the 
Asthma UK Centre for Applied Research’s (AUKCAR) website. The initial introduction 
will be made either by the clinical team (above) with the study team contacting them 
at a later date to give more information or by Mr. Andreas Perikleous if he is there in 
person. If the child has been prescribed OCS, testing will be delayed by 2 weeks for 
biomarker testing as soon as the electronic informed consent is submitted. Finally, 
parents will be informed through the patient information sheet as well as, in person, 
that a second optional testing will take place 3 months after the first one, in their 
second study visit. This will allow assessing the reproducibility of the obtained 
biomarker results, thus additionally assess their stability. 
Patient recruitment at a site will only commence once the study team has ensured the 
following: 
• HRA approval 
• Completed Local Site Delegation of Duties and Signature Log 
• Confirmation of Capacity and Capability  
 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 22 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
All recruitment procedures will be in accord with the GCP, and parents/carers will be 
given detailed information regarding the study as well as all the time they need to 
understand it. Parents/guardians have at least 24 hours to consider participation. 
Recruitment will only commence after parents/carers have fully understood the project 
and submitted the electronic informed consent form through the Qualtrics® platform 
(offered by Imperial College London). 
 
Child participants entering the study upon their parents’ wish, will be fully screened by 
the Principal Investigator (PI) or someone else from the research team who is suitably 
qualified and delegated to do so, with the latter taking informed consent as well. After 
the electronic informed consent sheet is submitted, parents will be asked to provide 
the contact details of their child’s GP or paediatrician, to inform him/her about the 
child’s participation in this study through a letter sent by email along with this patient 
information sheet. In addition, we will ask them to provide some of the child’s personal 
data (Appendix 1: Recruitment Plan, Table 3: The personal data that will be obtained 
by each individual participant). Children’s full name, date of birth, gender, ethnicity as 
well as, their parent’s full name, telephone number and email address will be added in 
the child’s patient card. All other data obtained from the study will be added in the Case 
Report Form (CRF).  
 
Follow-up: We will arrange for a short monthly electronic questionnaire to be sent by 
email to the parents/carers, in order to record on a monthly basis, the days their child 
was out of childcare, days the carer missed from work, unscheduled health care visits 
and use of rescue therapy or oral corticosteroids (including dosage) (Appendix 4: 
Monthly Questionnaire). In addition, we will record the children’s TRACKTM score (Test 
for Respiratory and Asthma Control in Kids) (Appendix 3: TRACKTM score 
questionnaire) every 3 months, to assess wheeze control. The questionnaires will be 
made and sent through the Qualtrics® questionnaire platform (offered by Imperial 
College London). There will be review visits every 3 months, to evaluate their 
progression in person, but if not feasible, video calls will be arranged through Microsoft 
Teams. Correct use of spacers will be ensured after guiding parents on how to use 
them and will be done by their GP or paediatrician as well as from Mr. Andreas 
Perikleous who is a registered pharmacist in the UK.  
 
In the event that a child has had their ICS treatment discontinued, we will record 
whether this was because the treatment was ineffective (treatment failure) or if the 
child was so well that the family or GP did not wish to continue (treatment success or 
spontaneous improvement). If an additional medication is prescribed, or the child is 
referred to secondary care, this will be considered as treatment failure. When the 
study ends, participants’ parents/carers will be invited to a face-to-face focus group 
interview, or a one-to-one interviews, or remotely through Microsoft Teams, 
depending on their availability at the end of the study period. The focus group and one 
to one interviews will utilise a semi structured questionnaire, to provide qualitative 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 23 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
feedback on the acceptability of the 3 biomarker tests. In addition, a separate focus 
group for doctors and nurses will be conducted to assess the feasibility of the 3 
biomarker tests being used in clinical practice. They will be given all the information 
regarding the study as well as the study’s patient information sheet. Those agreeing 
to take part, will sign a consent form. They will be attending either a face-to-face focus 
group interview, or a one-to-one interview, or remotely through Microsoft Teams, 
depending on their availability. A semi structured questionnaire will be utilised. Where 
possible a second independent researcher will sit in the focus groups discussion and 
interviews to ensure there is no bias. The conversations from the focus group and one 
to one interviews will be transcribed and coded into themes. We will utilise an external 
company 
for 
transcribing 
the 
conversations 
called 
1st 
Class. 
https://www.1stclass.uk.com/ 
 
The focus group and one-to-one interviews will be audio recorded, transcribed and 
put into themes to conduct an inductive thematic analysis. 25% of the transcripts will 
be double coded by an independent researcher, experienced in qualitative research 
to ensure that the correct themes have been used and to ensure that there is no bias. 
The focus group and one to one interviews will be used to assess the acceptability 
and feasibility of measuring biomarkers in primary care and using them to help 
determine management of preschool wheeze. 
 
In addition, we will ask them to fill in a very short electronic questionnaire after the 
study is finished, to check their perspective and acceptability on these biomarkers 
being used to guide children’s therapy in the future (Appendix 5: Exit Questionnaire). 
    
The whole duration of this study is expected to be 20-21 months, with 1-year follow-up 
for each patient included. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 24 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
7.2. INCLUSION AND EXCLUSION CRITERIA 
7.2.1. CHILDREN 
 
INCLUSION CRITERIA 
EXCLUSION CRITERIA 
1. Patients aged one to five years old 
presenting to primary care or to the 
emergency 
department 
or 
to 
secondary care (e.g., outpatients) or 
identified from primary care records 
and have been diagnosed with 
wheezing by their GP or paediatrician 
who has decided to prescribe any 
bronchodilator, ICS or montelukast on 
clinical grounds 
 
1. Inability 
to 
understand 
and 
cooperate with study procedures 
2. Significant co-morbidity (respiratory 
or otherwise), for example cystic 
fibrosis (excluding atopic disorders 
such as eczema, allergic rhinitis and 
food allergy) 
3. Withholding 
or 
withdrawal 
of 
informed consent 
2. Parents/Carers able to understand 
and familiarize themselves with the 
study and are willing to provide 
informed consent 
4. Severe procedural anxiety (needle 
phobia)  
5. Child is already enrolled in another 
study 
involving 
investigational 
medicinal product (CTIMP) 
6. History of near-fatal asthma that 
resulted 
in 
intubation 
/ 
assisted 
ventilation. 
 
7.2.2. HEALTHCARE PROFESSIONALS 
 
INCLUSION CRITERIA 
EXCLUSION CRITERIA 
1. Doctors and nurses working in GP 
practices. 
1. Inability 
to 
understand 
and 
cooperate with study procedures. 
 
7.3. WITHDRAWAL CRITERIA 
Parents can withdraw their child at any time without having to justify their decision. 
Upon withdrawal, patients will continue in their usual clinical care. In addition, the 
investigator may withdraw a child participant from the study if it is considered 
necessary to protect their wellbeing or that of others. Child participants’ data will be 
retained and included in the final study analysis, unless the parent/carer specifies 
otherwise. Reasons for withdrawal, where available, and timing of withdrawal will be 
collected and recorded. Attempts to replace child participants whose parents decided 
to withdraw, will be made in line with recruitment procedures outlined in section 4. If 
the child participant is withdrawn due to an adverse event, the research team will 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 25 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
arrange for follow-up visits or telephone calls to monitor the adverse event until it has 
resolved or stabilised.  
 
8. 
ADVERSE EVENTS  
 
8.1. DEFINITIONS  
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study 
subject.   
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or 
effect that: 
• Results in death 
• Is life-threatening – refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event which hypothetically might have 
caused death if it were more severe 
• Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation 
• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly or birth defect 
Medical judgement should be exercised in deciding whether an AE is serious in other 
situations.  Important AEs that are not immediately life-threatening or do not result in 
death or hospitalisation but may jeopardise the subject or may require intervention to 
prevent one of the other outcomes listed in the definition above, should also be 
considered serious. 
 
8.2. REPORTING PROCEDURES  
All adverse events will be recorded in the Case Report Form (CRF). Depending on the 
nature of the event the reporting procedures below should be followed.  Any questions 
concerning adverse event reporting should be directed to the Chief Investigator in the 
first instance.   
 
8.2.1. Non serious AEs 
All such events, whether expected or not, should be recorded- it should be specified if 
only some non-serious AEs will be recorded, any reporting should be consistent with 
the purpose of the trial end points.  
 
8.2.2. 
Serious AEs 
An SAE form should be completed and emailed to the Chief Investigator within 24 
hours. All SAEs should be reported to the <name of REC> where in the opinion of the 
Chief Investigator, the event was: 
• ‘related’, i.e., resulted from the administration of any of the research procedures; and 
• ‘unexpected’, i.e., an event that is not listed in the protocol as an expected 
occurrence 
Reports of related and unexpected SAEs should be submitted within 15 days of the 
Chief Investigator becoming aware of the event, using the NRES SAE form for non-

 
                                Research Governance 
                                  and Integrity Team 
 
 
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© Imperial College of Science, Technology and Medicine 
  
IMP studies.  The Chief Investigator must also notify the Sponsor of all related and 
unexpected SAEs. Local investigators should report any SAEs as required by their 
Local Research Ethics Committee, Sponsor and/or Research & Development Office. 
 
 
 
8.3. THE TYPE AND DURATION OF THE FOLLOW-UP OF SUBJECTS AFTER AES 
No related SAEs are anticipated as a result of this study. Unexpected SAEs will be 
managed according to clinical need. Child participants will continue routine clinical care 
throughout and after the study; routine follow up appointments may be expedited if 
required due to clinical need as a result of SAEs. 
 
8.4. PREGNANCY 
N/A as study involves preschool children 
 
8.5. ANNUAL PROGRESS REPORTS (APRS) 
The Chief Investigator (CI) will prepare the APRs for the study. It will be reviewed by 
the study site Research Office and sent to the REC by the CI within 30 days of the 
anniversary date on which the favourable opinion was given by the REC, and annually 
until the study is declared ended. 
 
8.6. REPORTING URGENT SAFETY MEASURES 
The Sponsor and/or the Investigator may take appropriate urgent safety measures in 
order to protect the subjects of a clinical study against any immediate hazard to their 
health or safety. If safety measures are taken, REC approval is not required before the 
measure is taken. The Investigator will immediately and in any event no later than 3 
days from the date the measures are taken, give written notice to the REC and the 
study Sponsor of the measures taken and the circumstances giving rise to those 
measures. In order to prevent any delays in the reporting timelines the Sponsor has 
delegated this responsibility to the CI. Therefore, the CI must report any urgent safety 
measures to the REC directly, and in parallel to the Sponsor. The REC coordinator will 
acknowledge receipt of urgent safety measures within 30 days.  
 
CONTACT DETAILS FOR REPORTING SAEs 
RGIT@imperial.ac.uk 
CI email (and contact details below) 
Fax: 02073518113, attention Professor Andrew Bush 
Please send SAE forms to: Professor Andrew Bush 
Telephone: 02073528121 (Mon to Fri 09:00 – 17:00) 
 
CI: a.bush@imperial.ac.uk 
Fax: 0044-2073518113 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
Page 27 of 39 
V8.0, 22Sep2023 
 
© Imperial College of Science, Technology and Medicine 
  
8.7. MANAGEMENT OF POTENTIAL STUDY RISKS 
Child participants routine clinical management is not changed in this observational 
study. Clinicians have no access to study data. Risks relate to study procedures. All 
procedures [blood sampling through finger prick test, skin prick tests on either the 
child’s back, leg or arm and FeNO collection (offline method)] will be performed by 
trained research personnel. Skin prick tests are safe and used clinically for many years, 
but adrenaline and antihistamines will be available while the study procedures are 
being performed, in the highly unlikely event of an allergic reaction. All research staff 
will be trained in management of acute reactions / anaphylaxis. The finger prick test is 
the same as used by diabetic patients to monitor blood glucose. Collecting breath into 
a bag is devoid of risk. 
 
9. 
ASSESSMENT AND FOLLOW-UP  
We will arrange for a short monthly electronic questionnaire to be sent by email to the 
parents/carers, in order to record on a monthly basis, the days their child was out of 
childcare, days the carer missed from work, unscheduled health care visits and use of 
rescue therapy or oral corticosteroids (including dosage) (Appendix 4: Monthly 
Questionnaire). In addition, we will record the children’s TRACKTM score (Test for 
Respiratory and Asthma Control in Kids) (Appendix 3: TRACKTM score questionnaire) 
every 3 months, to assess wheeze control. There will be review visits every 3 months, 
to evaluate their progression in person, but if not feasible, video calls will be arranged 
through Microsoft Teams. In the case of any incidental findings, there will be thorough 
evaluation of potential benefits or harms before disclosing the information to the child’s 
parent. As this is an observational study, no interventions can be done in the case of 
incidental findings and parents will be advised to discuss this with their child’s GP or 
paediatrician. 
 
10. END OF STUDY 
The end of the study will be when the last of the 100 participants completes his follow-
up period of 12 months with his/her last study visit. The anticipated finishing date is 
December 2023. 
 
11. STATISTICS AND DATA ANALYSIS 
The statistical analysis of the project will be done by Mr. Andreas Perikleous in 
collaboration with Dr Steff Lewis (University of Edinburgh) and the Asthma UK Centre 
for Applied Research (AUKCAR), the funder of the study. Statistical analyses will use 
the GraphPad PRISM software package. A normality test will be performed to assess 
normal (Gaussian) distribution (e.g., the Shapiro-Wilk test. If there is normal 
distribution, then parametric tests will be used, otherwise non-parametric tests. Level 
of significance is set as a p value <0.05. The tests that are currently planned to be 
used are: 
• Chi-Squared test (x2-test) 

 
                                Research Governance 
                                  and Integrity Team 
 
 
Ref: TAILOR Study 
 
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© Imperial College of Science, Technology and Medicine 
  
This test allows assessing if a variable is similar between two or more groups or to test 
if two or more variables are related/dependent 
 
• Fisher’s Exact test 
This test is used when chi-squared values are <5, usually with a small sample size. 
 
• Student t-test or Mann-Whitney test 
These tests are used for comparison between two study groups. The first is for 
normally distributed quantitative variables and the second for non-normally distributed 
quantitative variables.  
 
Data and all appropriate documentation will be stored for a minimum of 10 years after 
the completion of the study, including the follow-up period.   
 
12. REGULATORY ISSUES 
 
12.1. ETHICS APPROVAL  
The Study Coordination Centre has obtained approval from the Queen Square 
Research Ethics Committee (REC) and Health Regulator Authority (HRA). The study 
must also receive confirmation of capacity and capability from each participating NHS 
Trust before accepting participants into the study or any research activity is carried out. 
The study will be conducted in accordance with the recommendations for physicians 
involved in research on human subjects adopted by the 18th World Medical Assembly, 
Helsinki 1964 and later revisions. 
 
12.2. CONSENT   
The Informed Consent form will be electronic and submitted through the Qualtrics® 
platform (offered by Imperial College London). After submission by the parent/carer, 
an automatic email will be sent to his/her email containing a link to access and save 
their true copy of the informed consent form. All will be performed in line with guidance 
from the HRA and MHRA, taken by a member of the research team who has been 
delegated the duty by the PI as recorded on the Sponsor’s Delegation of 
Responsibilities Log and recorded in writing which will be sent to the researcher via 
email. No hard copies will be retained. Those confirming informed consent will have 
had formal training in informed consent and completed GCP training. Consent to enter 
this study will be obtained after a full account has been provided of its nature, purpose, 
risks, burdens and potential benefits, and the patient has had the opportunity to 
deliberate. The patient will be allowed to specify the time they wish to spend 
deliberating. Patients are encouraged to consider taking part, and discuss the study 
with their physician, family, friends and whoever else they wish before deciding. The 
PI or designee will explain to the parents that their child is under no obligation to enter 
the study and they can withdraw at any time during the study, without having to give a 
reason. Participant’s parent/carer will be given a copy of the most recent approved PIS 

 
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as well. The electronic consent form will be retained at the study site [one filed in the 
medical notes, and one filed in the Study Master File (SMF)].  
 
12.3. CONFIDENTIALITY  
The Chief Investigator will preserve the confidentiality of participants taking part in the 
study and is registered under the Data Protection Act. Data will be anonymised. 
 
12.4. INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance 
policies which apply to this study. 
 
12.5. SPONSOR  
Imperial College London will act as the main Sponsor for this study.  Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.   
 
12.6. FUNDING  
Asthma UK Centre for Applied Research (AUKCAR) is funding this study. 
 
12.7. AUDITS   
The study may be subject to audit by Imperial College London under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the UK Policy 
Framework for Health and Social Care Research.  
 
13. DATA MANAGEMENT AND QUALITY ASSURANCE 
 
13.1. CONFIDENTIALITY  
All data will be handled in accordance with the General Data Protection Regulation 
(GDPR) (2018), NHS Caldecott Principles, The UK Policy Framework for Health and 
Social Care Research, and the condition of the REC approval. The Case Report Forms 
(CRFs) will not bear the child participants’ name or other personal identifiable data. 
Identification will be performed through the participants’ Identification Number (ID). No 
data will be shared with any external organisation without appropriate consent and data 
sharing agreement in place, as applicable. 
 
13.2. DATA COLLECTION TOOL  
Case Report Forms (CRF) will be designed by the trial coordinator and PI, and the final 
version will be reviewed and discussed with the study Sponsor. Researchers will 
complete electronic versions of the CRF to reduce errors compared to transcribing 
from paper to an electronic database. It is the Investigator’s responsibility to ensure 
the accuracy of all data entered and recorded in the CRFs. The Delegation of 
Responsibilities Log will identify all study personnel responsible for data collection, 
entry, handling and managing the database. 
 

 
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13.3. DATA HANDLING AND ANALYSIS 
The Informed Consent form will be electronic and submitted through the Qualtrics® 
platform (offered by Imperial College London). After submission by the parent/carer, 
an automatic email will be sent to his/her email containing a link to access their true 
copy of the informed consent form. All data will be stored in the Imperial College 
London Microsoft Office 365 cloud account of Mr. Andreas Perikleous, and all will be 
done in accordance with the Imperial College London’s data policy. Data will be backed 
up in a second Imperial College London Microsoft Office 365 cloud account of Mr. 
Andreas Perikleous and in accordance with the aforementioned policy. The CI will act 
as the Data Custodian for the study. Mr. Andreas Perikleous (study coordinator) will 
be responsible for data entry and quality. He will also be responsible for data analysis, 
with support from the study statistician. Data analysis will be performed on separate 
occasions to data entry.  
 
13.4. ARCHIVING ARRANGEMENTS 
Data will be kept in a secure storage unit at the Sponsor site for 10 years. The study 
documents (including the Study Master File (SMF), Case Report Forms (CRFs), 
Informed Consent Forms along with the study database) will be kept for 10 years. The 
study database will be kept electronically on Imperial College London’s computer 
network, in a password-protected encrypted folder. The PI is responsible for the secure 
archiving of study documents. The approved repository for longer retention of local 
materials for studies that involve Imperial College London patients is Box-It Storage 
UK. The study documentation will be prepared for archiving by the research team in 
line with the Research Office Archiving SOP and the transfer will be arranged by the 
Research Office. After 10 years all data, including audio and video recordings, will be 
destroyed in accordance with Imperial College London’s data policy. 
 
13.5. DIRECT ACCESS TO SOURCE DATA 
The Investigator(s)/institution will permit study-related monitoring, audits, REC review, 
and regulatory inspection(s), providing direct access to source data/documents. 
Parents will be informed of this during the informed consent discussion. Parents will 
be asked to consent to provide access to their medical notes. 
 
14. INSURANCE AND INDEMNITY  
NHS bodies are liable for clinical negligence and other negligent harm to individuals 
covered by their duty of care. NHS Institutions employing researchers are liable for 
negligent harm caused by the design of studies they initiate. The provision of such 
indemnity for negligent harm will be stated to the parent/carer of the child participant.  
 
15. STUDY MANAGEMENT 
The day-to-day management of the study will be co-ordinated by Mr. Andreas 
Perikleous.   
 

 
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16. PUBLICATION POLICY  
Data ownership rights will lie with the institution. 
 
17.  STATEMENT OF COMPLIANCE 
The study will be conducted in compliance with the protocol, Sponsor’s Standard 
Operating Procedures (SOPs), GCP and the applicable regulatory requirement(s).  
 
The study conduct shall comply with all relevant laws of the EU if directly applicable or 
of direct effect and all relevant laws and statutes of the UK country in which the study 
site is located including but not limited to, the Human Rights Act 1998, the General 
Data Protection Regulation (GDPR) (2018), the Medicines Act 1968, and with all 
relevant guidance relating to medicines and clinical studies from time to time in force 
including, but not limited to, the ICH GCP, the World Medical Association Declaration 
of Helsinki entitled 'Ethical Principles for Medical Research Involving Human Subjects' 
(2008 Version), the NHS Research Governance Framework for Health and Social Care 
(Version 2, April 2005).  
 
This study will be conducted in compliance with the protocol approved by HRA and 
according to RGF standards. No deviation from the protocol will be implemented 
without the prior review and approval of the Sponsor and HRA except where it may be 
necessary to eliminate an immediate hazard to a research subject. In such case, the 
deviation will be reported to the Sponsor and the REC as soon as possible. 

 
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18. REFERENCES  
1.  
Kalyva E, Eiser C, Papathanasiou A. Health-Related Quality of Life of Children 
with Asthma: Self and Parental Perceptions. Int J Behav Med [Internet]. 
2016;23(6):730–7. Available from: http://dx.doi.org/10.1007/s12529-016-9558-
7 
2.  
Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, et al. After 
asthma: redefining airways diseases. Lancet [Internet]. 2018;391(10118):350–
400. Available from: http://dx.doi.org/10.1016/S0140-6736(17)30879-6 
3.  
Bush A, Pavord ID. ‘We can’t diagnose asthma until <insert arbitrary age>.’ Arch 
Dis Child [Internet]. 2018 Aug 1;103(8):729 LP – 731. Available from: 
http://adc.bmj.com/content/103/8/729.abstract 
4.  
Brand PLP, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, 
et al. Definition, assessment and treatment of wheezing disorders in preschool 
children: An evidence-based approach. Eur Respir J. 2008;32(4):1096–110.  
5.  
Brand PLP, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, et al. 
Classification and pharmacological treatment of preschool wheezing: Changes 
since 2008. Eur Respir J. 2014;43(4):1172–7.  
6.  
Agusti A, Bel E, Thomas M, Vogelmeier C, Brusselle G, Holgate S, et al. 
Treatable traits: Toward precision medicine of chronic airway diseases. Eur 
Respir 
J 
[Internet]. 
2016;47(2):410–9. 
Available 
from: 
http://dx.doi.org/10.1183/13993003.01359-2015 
7.  
Licari A, Manti S, Castagnoli R, Leonardi S, Marseglia GL. Measuring 
inflammation in paediatric severe asthma: Biomarkers in clinical practice. 
Breathe. 2020;16(1):2–11.  
8.  
Saglani S, Payne DN, Zhu J, Wang Z, Nicholson AG, Bush A, et al. Early 
detection of airway wall remodeling and eosinophilic inflammation in preschool 
wheezers. Am J Respir Crit Care Med. 2007;176(9):858–64.  
9.  
O’Reilly R, Ullmann N, Irving S, Bossley CJ, Sonnappa S, Zhu J, et al. Increased 
airway smooth muscle in preschool wheezers who have asthma at school age. 
J Allergy Clin Immunol [Internet]. 2013;131(4):1024-1032.e16. Available from: 
http://dx.doi.org/10.1016/j.jaci.2012.08.044 
10.  Sonnappa S, Bastardo CM, Wade A, Saglani S, McKenzie SA, Bush A, et al. 
Symptom-pattern phenotype and pulmonary function in preschool wheezers. J 
Allergy Clin Immunol [Internet]. 2010;126(3):519-526.e7. Available from: 
http://dx.doi.org/10.1016/j.jaci.2010.04.018 
11.  Jochmann A, Artusio L, Robson K, Nagakumar P, Collins N, Fleming L, et al. 
Infection and inflammation in induced sputum from preschool children with 
chronic airways diseases. Pediatr Pulmonol. 2016;51(8):778–86.  
12.  Pijnenburg MW. The role of FeNO in predicting asthma. Front Pediatr. 
2019;7(FEB).  
13.  Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants 
and preschoolers with recurrent wheezing and asthma: a systematic review with 
meta-analysis. Pediatrics. 2009 Mar;123(3):519–25.  
14.  Moustaki M, Loukou I, Tsabouri S, Douros K. The role of sensitization to allergen 
in asthma prediction and prevention. Front Pediatr. 2017;5(July):1–8.  
15.  Fitzpatrick AM, Jackson DJ, Mauger DT, Boehmer SJ, Phipatanakul W, Children 
B, et al. Individualized Therapy for Persistent Asthma in Young Children. J 
Allergy Clin Immunol [Internet]. 2017;138(6):1608–18. Available from: 
doi:10.1016/j.jaci.2016.09.028 

 
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16.  Singer F, Luchsinger I, Inci D, Knauer N, Latzin P, Wildhaber JH, et al. Exhaled 
nitric oxide in symptomatic children at preschool age predicts later asthma. 
Allergy Eur J Allergy Clin Immunol. 2013;68(4):531–8.  
17.  Sellaturay P, Nasser S, Ewan P. The incidence and features of systemic 
reactions to skin prick tests. Ann Allergy, Asthma Immunol [Internet]. 
2015;115(3):229–33. 
Available 
from: 
http://dx.doi.org/10.1016/j.anai.2015.07.005 
18.  Liccardi G, Salzillo A, Spadaro G, Senna G, G. Canonica W, D’Amato G, et al. 
Anaphylaxis caused by skin prick testing with aeroallergens: Case report and 
evaluation of the risk in Italian allergy services. J Allergy Clin Immunol [Internet]. 
2003 
Jun 
1;111(6):1410–2. 
Available 
from: 
https://doi.org/10.1067/mai.2003.1521 
19.  Turner S, Custovic A, Ghazal P, Grigg J, Gore M, Henderson J, et al. Pulmonary 
epithelial barrier and immunological functions at birth and in early life-key 
determinants of the development of asthma? A description of the protocol for 
the breathing together study [version 1; referees: 2 approved]. Wellcome Open 
Res. 2018;3(May):1–15.  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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19. APPENDICES 
 
19.1.   APPENDIX 1:  RECRUITMENT PLAN 
The recruitment period will approximately last 9 months, and all preschool wheezers 
can join the study at any point. Parents/Carers of preschool children presenting to 
primary care or to the Emergency Department (ED) or to secondary care (e.g., 
outpatients) as well as those identified from primary care records and who have been 
diagnosed by a GP or paediatrician with wheezing, will be approached by 
collaborating doctors and nurses who will ask their parents if they are willing to have 
their child participate in the study. The list of recruitment sites is given below (Table 
1).  A patient information sheet will be given, containing all the information regarding 
the project and the contact details of the research team, for further questions. They 
will be asked for their willingness to give the study team permission to contact them 
and discuss recruitment, and if so, they will submit their contact details in an electronic 
form made with the Qualtrics® questionnaire platform (offered by Imperial College 
London), which allows gathering data according to the GCP guidelines and as used 
for years in the Breathing Together study (19). Additionally, the questionnaire form 
submission will not collect parents’ IP address or geolocation. This form will be 
available online in the Asthma UK Centre for Applied Research’s (AUKCAR) website. 
The initial introduction will be made either by the clinical team (above) with the study 
team contacting them later to give more information or by Mr. Andreas Perikleous if 
he is there in person. 
 
Name of Participating NHS Organisation 
University of Oxford NHS Hospitals 
 
Location 
Activity 
Oxford University Hospitals NHS Foundation 
Trust  
Participant 
Identification, 
Review 
Visits, 
Biomarker testing (finger prick test, skin prick test, 
collection of FeNO in a bag) 
John Radcliffe Hospital  
 
Oxfordshire Clinical Commissioning Group 
 
Bicester Health Centre 
 
White Horse Medical Practice 
 
Oxfordshire BCSC (Horton Hospital) 
Participant Identification 
Whitchurch Surgery 
 
Norden House Surgery 
 
The Swan Practice 
 
Windrush Surgery 
 
CRN East Midlands 

 
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Table 1. Patient identification and recruitment sites 
Study procedures 
Eligibility assessment 
Before starting the study  
 
Child participant identification 
X 
 
Contact information submission 
X 
 
Telephone/email contact with parents 
X 
 
Inclusion/Exclusion criteria 
 
X 
Patient Information Sheet 
 
X 
Face-to-face project discussion 
 
X 
Electronic Informed Consent 
 
X 
Table 2. Patient recruitment plan 
PERSONAL DATA OBTAINED 
 
a) Child’s Full Name 
e) Medical History 
b) Child’s Date of Birth 
f) Child’s GP contact details 
c) Gender 
g) Parents’ smoking history 
d) Ethnicity 
h) Parent’s telephone and email address 
Table 3. The personal data that will be obtained by each individual participant. 
COLLABORATING HEALTHCARE PROFESSIONALS – PARTICIPANT IDENTIFICATION 
 
 
EMERGENCY DEPARTMENT (ED) 
 
 
 NAME  
DETAILS 
1) Dr. Alex Novak 
• Consultant in Emergency Medicine and Ambulatory Care, 
Oxford University Hospitals NHS FT 
 
• Work Address: Emergency Department, John Radcliffe 
Hospital, Headley way, Oxford OX3 9DU 
2) Dr. Moya Dawson 
• Consultant in Paediatric Emergency Medicine 
 
• Emergency Department, John Radcliffe Hospital, Headley 
way, Oxford OX3 9DU 
 
• Oxford University Hospitals NHS FT 

 
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19.2. APPENDIX 2:  FOLLOW-UP PLAN 
We will arrange for a short monthly electronic questionnaire to be sent by email to the 
parents/carers, in order to record on a monthly basis, the days their child was out of 
childcare, days the carer missed from work, unscheduled health care visits and use 
of rescue therapy or oral corticosteroids (including dosage) (Appendix 4: Monthly 
Questionnaire). In addition, we will record the children’s TRACKTM score (Test for 
Respiratory and Asthma Control in Kids) (Appendix 3: TRACKTM score questionnaire) 
every 3 months, to assess wheeze control. The questionnaires will be made and sent 
through the Qualtrics® questionnaire platform (offered by Imperial College London), 
which allows data gathering data according to the GCP guidelines and as used for 
years in the Breathing Together study (19). Additionally, the questionnaire form 
submission will not collect parents’ IP address or geolocation. There will also be 
review visits every 3 months, to evaluate their progression in person, but if not 
feasible, video calls will be arranged through Microsoft Teams.  
 
 
 
 
 
 
 
 
 
 
 
Table 4. The list of collaborating healthcare professionals in the ED for participant identification. 
 
 
Months 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 
 
 
 
Primary Care Visit 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Video Call (Microsoft Teams)1 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Biomarker Testing2 
 
 
 
X3 
 
 
 
 
 
 
 
 
 
TRACKTM Score Questionnaire4 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Monthly Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Focus Group 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Table 2. The follow-up plan after preschool wheezers’ recruitment. 
1 In case they are not available for primary care visit  
2 Testing the 3 biomarkers, blood eosinophils, atopic sensitisation and FeNO (offline method).  
3 A second testing will be performed 3 months after the first one and will be optional. Parents will be 
informed through the patient information sheet, as well as in person that they have the option to deny 
participation of their child in this second testing. It is written in the informed consent form as well. 
4 The TRACKTM score will be sent to the parents/carers by email or SMS every 3 months and will be 
incorporated to the monthly questionnaire. They will be sent through the Qualtrics® questionnaire 
platform. 

 
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19.3. APPENDIX 
3: 
TRACKTM 
SCORE 
QUESTIONNAIRE 
(TEST 
FOR 
RESPIRATORY AND ASTHMA CONTROL IN KIDS) 
 
1. During the past 4 weeks, how often was your child bothered by breathing problems, such 
as wheezing, coughing or shortness of breath? 
 
Not at all 
Once or twice 
Once every week 
2 or 3 times a week 
4 or more times a week 
 
 20 
 15 
 10 
 5 
 0 
 
2. During the past 4 weeks, how often did your child’s breathing problems (wheezing, 
coughing, shortness of breath) wake him or her up at night? 
 
Not at all 
Once or twice 
Once every week 
2 or 3 times a week 
4 or more times a week 
 
 20 
 15 
 10 
 5 
 0 
 
3. During the past 4 weeks, to what extend did your child’s breathing problems, such as 
wheezing, coughing or shortness of breath, interfere with his or her ability to play, go to 
school or engage in usual activities that a child should be doing at his or her age? 
 
Not at all 
Slightly 
Moderately 
Quite a lot 
Extremely 
 
 20 
 15 
 10 
 5 
 0 
 
4. During the past 3 months, how often did your need to treat your child’s breathing 
problems (wheezing, coughing or shortness of breath) with quick relief medications (e.g., 
albuterol, Ventolin®) 
 
Not at all 
Once or twice 
Once every week 
2 or 3 times a week 
4 or more times a week 
 
 20 
 15 
 10 
 5 
 0 
 
5. During the past 12 months, how often did you child need to take oral corticosteroids (e.g., 
prednisone, prednisolone, Decadron®) 
 
Not at all 
Slightly 
Moderately 
Quite a lot 
Extremely 
 
 20 
 15 
 10 
 5 
 0 
 
 
 
 
 
 
 
 
 
 
 
Total Score 
 
 
 
Figure 1. The TRACKTM Score Questionnaire. TRACK (Test for Respiratory and Asthma 
Control in Kids) is a trademark of AstraZeneca group of companies © 2009. TRACK score 
less than 80 means that the child’s breathing problems are out of control. TRACK score 
above 80 means that the child’s breathing problems seem to be in control.  
 
 
 

 
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19.4.  APPENDIX 4: MONTHLY QUESTIONNAIRE 
 
Introduction: Please take a moment to complete the following questionnaire relating 
to your child’s wheezing condition. The questions will help us identify wheezing 
exacerbations and assess your child’s quality of life. 
 
Question 1: Did your child experience any wheezing symptoms during the last month?  
Not at all 
Once or twice 
Once every week 
2 or 3 times a week 
4 or more times a week 
 
 
 
 
 
 
Question 2: Was the child unable to go to childcare because of breathing problems? 
Yes 
No 
N/A 
 
 
 
If yes, please state how many days: _________(Number) 
 
Question 3: Did you have to take your child for an emergency appointment with your GP, urgent 
care or hospital because of wheezing? 
Not at all 
Once or twice 
Once every week 
2 or 3 times a week 
4 or more times a week 
 
 
 
 
 
 
Question 4: Was your child treated with inhaled or oral corticosteroids? 
Yes 
No 
 
 
If yes, what was the dose, frequency and duration? 
Dose: __________ 
Frequency: ____________ 
Duration: ______________ 
 
Question 5: Was your child given β2 agonists (blue inhaler, rescue therapy)? 
Yes 
No 
 
 
If yes, what was the dose, frequency and duration? 
Dose: __________ 
Frequency: ____________ 
Duration: ______________ 
 
Question 6: Did you have to take days off work because your child had wheezing or breathing 
difficulties? 
Yes 
No 
 
 
If yes, how many days did you take? Specify number: ______________ (days) 
 
Survey’s ending message: “We thank you for your time spent taking this survey. 
Your response has been recorded.” 

 
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19.5.  APPENDIX 5: EXIT QUESTIONNAIRE   
 
Introduction: Thank you for participating in this study. We are really grateful for your 
willingness to help and volunteer for a study that aims to provide better wheezing 
treatment for our children in the future. Please take a moment to give us your feedback 
relating to the 3 biomarkers that were tested in this study as well as some comments 
on what you think the future definitive study should entail? 
 
Question 1: How satisfied are you with this whole 1-year follow-up period study?  
Very Dissatisfied 
Dissatisfied 
Neutral 
Satisfied 
Very Satisfied 
 
 
 
 
 
 
Question 2: As a parent would you be interested in having the biomarker-based 
approach for your child in the future? 
Yes 
No 
Maybe 
 
 
 
 
Question 3: Did the study’s 1-year follow up period help you change your mind on 
the 3 biomarkers (blood eosinophil count, FeNO and atopic sensitisation) being used 
in clinical settings for personalising treatment? 
Not at all 
Slightly 
Moderately 
Quite a lot 
 
 
 
 
 
Question 4: Would you recommend this approach to other parents with children 
experiencing the same wheezing conditions? 
Not at all 
Maybe 
Recommend 
Highly recommend 
 
 
 
 
 
Question 5: What else would you like to see in the future clinical trial? Would you 
change anything on the current process? What was good, what was not good? 
Comment: 
 
 
 
Survey’s ending message: “Thank you for participating in our survey!”