Wheezing
Conditions
Keywords
Preschool, Wheeze, Wheezing, Inhaled Corticosteroids, ICS, Biomarkers
Brief summary
Wheezing is common in preschool children and affects quality of life. Although asthma treatments such as inhaled steroids (ICS), which reduce swelling (inflammation) in the airways are used in this age group, they are often ineffective. That is because only some preschool children have the type of inflammation (known as Type 2 inflammation) that responds to ICS, thus many children are being unnecessarily exposed to side effects. It is difficult diagnosing Type 2 inflammation through history and examination, thus other indicators are needed to ensure ICS are only given to children who will benefit. These indicators are commonly known as biomarkers, and we are trying to find out if they are useful. We want to measure three biomarkers, without changing children's treatment. The first is blood eosinophils. which can be measured using a finger prick sample (like the blood drop used for measuring sugar levels in diabetic children). The second is to determine if allergic sensitization is present to allergens that are breathed in; these will be house dust mite, grass pollen, tree pollen, cat and dog hair. The final biomarker is a molecule that is produced in the airways of preschool children with Type 2 inflammation, called nitric oxide (NO). This is easily obtained, by having children breathe through a mask and collecting their breath in a bag, measuring NO later on. The children will be followed up with monthly electronic questionnaires and 3-monthly visits (virtual or face-to-face) for a year to evaluate whether these markers individually or in combination relate to subsequent wheezing outcomes, and how acceptable the measurements are to families using a questionnaire and focus group approach. The results will form the basis of the design of a national trial of biomarker-driven therapy in such children.
Interventions
DIAGNOSTIC_TESTBlood eosinophil count
Peripheral blood eosinophil count will be measured from a finger prick blood sample, using the Haemocue machine, allowing a result in approximately 2 minutes. The test will allow to assess the presence or not of eosinophilia and if it can predict future wheezing exacerbations and response to inhaled corticosteroids (ICS).
DIAGNOSTIC_TESTAtopic sensitization
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 which will act as negative and positive controls respectively. In addition, skin prick tests will allow the assessment of which aeroallergen is the most useful predictor of outcomes in preschool children.
DIAGNOSTIC_TESTFeNO (offline method)
The child will breathe normally into a sample bag that will be collected for later analysis of FeNO levels. The test will be performed twice.
Sponsors
Asthma UK Centre for Applied Research
Imperial College London
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged one to five years old presenting to primary care or emergency department or urgent care centre 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wheeze Attacks | 1-year follow-up | Defined as requiring an unscheduled healthcare visit to the ED or GP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days Out of Nursery | 1 year follow-up period | Children unable to attend childcare facility due to a wheeze attack. There were no arms in this study, only a single group followed in an identical manner. |
| Parents Days Out of Work | 1 year follow-up period | Days out of work parents needed to take because of their child's wheeze attack. There were no arms in this study, only a single group followed in an identical manner. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Acceptability of Biomarker Tests by Parents | 12-months | The acceptability of the three biomarker tests by parents to be used in clinical practice was assessed through focus group discussions. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Only children 1-5 years old were considered enrolled. Their parents/guardians were not considered as enrolled. They signed the consent form for enrolment and complete the monthly questionnaires during follow-up on behalf of their child. No interventions were performed in this study. There were no arms in this study, only a single group followed in an identical manner.
Participants by arm
| Arm | Count |
|---|---|
| Preschool Children Aged 1 to 5 Years Old Preschool children with a history of ≥1 doctor-diagnosed acute wheeze attack of any severity, in the year prior to baseline measurement. | 95 |
| Total | 95 |
Baseline characteristics
| Characteristic | Preschool Children Aged 1 to 5 Years Old |
|---|---|
| Age, Continuous | 35 months |
| Atopy | 45 Participants |
| Blood eosinophil count | 400 cells/μL |
| Fractional exhaled nitric oxide | 8 ppb |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 86 Participants |
| Region of Enrollment United Kingdom | 95 participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 95 |
| other Total, other adverse events | 0 / 95 |
| serious Total, serious adverse events | 0 / 95 |
Outcome results
Primary
Wheeze Attacks
Defined as requiring an unscheduled healthcare visit to the ED or GP.
Time frame: 1-year follow-up
Population: Data only applies to children aged 1-5 years old. There were no arms in this study, only a single group followed in an identical manner.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preschool Children Aged 1-5 Years | Wheeze Attacks | 1 Wheeze attacks |
Secondary
Days Out of Nursery
Children unable to attend childcare facility due to a wheeze attack. There were no arms in this study, only a single group followed in an identical manner.
Time frame: 1 year follow-up period
Population: Data only applies to children aged 1-5 years old and not their parents. There were no arms in this study, only a single group followed in an identical manner.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preschool Children Aged 1-5 Years | Days Out of Nursery | 3 days |
Secondary
Parents Days Out of Work
Days out of work parents needed to take because of their child's wheeze attack. There were no arms in this study, only a single group followed in an identical manner.
Time frame: 1 year follow-up period
Population: Data only apply to parents of preschool children. There were no arms in this study, only a single group followed in an identical manner. Every month parents would be asked to state whether they needed to take any days of work due to their child's wheeze.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preschool Children Aged 1-5 Years | Parents Days Out of Work | 3 days |
Other Pre-specified
Acceptability of Biomarker Tests by Parents
The acceptability of the three biomarker tests by parents to be used in clinical practice was assessed through focus group discussions.
Time frame: 12-months
Population: Only 16 out of 95 parents agreed to participate in these focus group discussions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Preschool Children Aged 1-5 Years | Acceptability of Biomarker Tests by Parents | 16 Participants |