Determinants Of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth

Study Overview
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Brief Summary
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The aim of the prospective cohort study is to: (1) document the magnitude of response to oral corticosteroids administered to children presenting to the emergency department with moderate or severe asthma and (2) quantify clinically available potential determinants of the response to corticosteroids, such as age, gender, triggers of the index exacerbation, environmental tobacco smoke (ETS), gene polymorphisms, and their interactions.

Detailed Description
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The objective of the large multicentre cohort study is to quantify the response to oral corticosteroids in children aged 1 to 17 years presenting to the ED with a moderate or severe asthma exacerbation. The main outcome is hospital admission within 72 hours of the oral corticosteroid administration. Secondary outcomes include the change in Pediatric Respiratory Assessment Measure (PRAM), length of active treatment and other markers of response to therapy in the ED as well as markers of recovery over the next 10 days.

Official Title
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Determinants Of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth

Conditions
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Asthma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject will be eligible if he/she: is aged 1 to 17 years, has not received any oral, IM or IV corticosteroid within the last 5 days? Presents to the hospital emergency department with an acute episode of cough, wheezing and/or dyspnea? Has asthma as defined as one or more of the following 6 criteria: (i) prior diagnosis of asthma made by a physician; OR (ii) prior documented episode of acute cough, wheezing and/or dyspnea with significant response to inhaled β2-agonists or to oral corticosteroids; OR (iii) in a child aged <2 years, 3 or more episodes of cough, wheezing and/or dyspnea, including the index visit; OR (iv) previous lung function tests showing significant reversibility post-bronchodilation (≥12% FEV1 or ≥25% Rrs at 4 to 8 Hz); OR (v) a positive provocation test (PC20 ≤8 mg/mL or Provocation Dose (to increase Rrs by 50% or more (PD50) ≤8 mg/mL), OR (vi) the current episode diagnosed or suspected of asthma by the emergency physician? have moderate or severe airway obstruction, defined as a Paediatric Respiratory Asthma Measure (PRAM) score >3 at baseline, Exclusion Criteria: Patient will be excluded if : he/she has another chronic respiratory condition (such as bronchopulmonary dysplasia or cystic fibrosis); there is a reasonable suspicion of bronchiolitis or foreign body aspiration; he/she has a prior history of hypersensitivity to salbutamol, ipratropium bromide or oral prednisone/prednisolone; he/she has a relative or absolute contraindication to receiving oral corticosteroids such as recent exposure to varicella or live vaccine in past 14 days, there is confirmed or suspected pregnancy.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Oral corticosteroids (OCS)<br>All patients receive: Prednisone or Prednisolone at 1 mg/kg (in 1 site) or 2 mg/kg (in all other sites) (max. 50 mg); if vomiting prednisone/prednisolone: they receive dexamethasone (0.3 mg/kg, max. 10 mg) 2 to 3 doses of salbutamol within the first hour of therapy according to severity Those with severe exacerbations receive 3 treatments with salbutamol and ipratropium bromide within the initial hour of therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital admission | Hospital admission or Length of active treatment for 8 or more hours after the oral corticosteroid administration or ED return visit associated with hospital admission within 72 hours after the oral corticosteroid administration or ED return visit associated within 72 hours with length of active treatment for 8 or more hours after the oral corticosteroid administration | 72 hours after oral corticosteroids administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of active treatment in hospital |  | 8 hours after oral corticosteroid administration | 
| Meeting the severity criteria for admission | Proportion of children with a PRAM score ≥4 within 4 hours of oral corticosteroid administration | Within 4 hours of oral corticosteroid administration | 
| PRAM profile in the ED | Area under the curve of the PRAM measured hourly for the time of oral corticosteroid (OCS) until 4 hours after OCS | Within 4 hours of oral corticosteroid administration | 
| Time to meeting discharge criteria | Time until PRAM score ≤ 3 | Within 8 hours of oral corticosteroid administration | 
| Change in respiratory resistance | Change in respiratory resistance between baseline and disposition will be documented on the MasterScreen Impulse Oscillometry (Cardinal Health Canada, Montreal, Canada) using previously described standardized techniques in cooperative children aged ≥3 years. (measured in a subset of individuals) | Within 4 hours of oral corticosteroid administration | 
| Unscheduled visits for asthma | unscheduled visits for asthma as reported by parents and confirmed by medical charts. | Within 7 days of the index ED exacerbation | 
| Symptom score | Area under the curve of symptoms measured daily on the validated Asthma flare-up diary for children | Within 7 days of the index ED exacerbation | 
| Duration of asthma symptoms | Duration of symptoms measured daily on the validated Asthma flare-up diary for children | Within 7 days of the index ED exacerbation | 
| Cumulative reliever use | Cumulative number of puffs of reliever medication as recorded daily on the Asthma flare-up diary for children | Within 7 days of the index ED exacerbation | 
| Duration of use of rescue ß2-agonists | Duration of use of rescue ß2-agonists as recorded on the Asthma flare-up diary for children | Within 7 days of the index ED exacerbation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma; Children; Cohort study; Corticosteroids