The Use of Inflammatory Markers to Guide Therapy in Children With Severe Asthma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether using non-invasive measurements of airway inflammation can improve clinical decision making in children with severe asthma compared to conventional management (British Thoracic Society Guidelines)

Detailed Description
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Children with severe asthma pose a management dilemma; it is difficult to reduce their treatment while they are symptomatic, but the plateau of the dose response curve for inhaled corticosteroids (ICS) may have been reached. Studies in symptomatic adults and asymptomatic children with asthma suggest measuring induced sputum eosinophils allows better asthma management. We will recruit 80 children with severe asthma (treated with at least 500 mcg/day inhaled fluticasone or equivalent). We will see them every three months for a year, and perform sputum induction and measurements of exhaled nitric oxide (eNO). Half will be randomised to conventional management; half will have a reduction of ICS if there are no sputum eosinophils, or (if a sample cannot be produced) eNO is normal. The trial endpoint is whether there is a significant reduction in the median dose of ICS in the inflammatory markers group, with no increase in total number of asthma exacerbations. This study is also hypothesis generating. We will use our panel of markers (a) to try to improve clinical monitoring; and (b) to determine the molecular mechanisms of relapse of severe asthma.

Official Title
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Prospective, Randomised Controlled Trial of the Use of Inflammatory Markers to Guide Therapy in Children With Severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Other: Non invasive measurement of airway inflammation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children >8 years with severe asthma defined as: Taking at least 500mcg fluticasone propionate (or equivalent) per day, plus a long acting beta agonist plus a leukotriene antagonist or previous trial Exclusion Criteria: Children taking steroid sparing agent (cyclosporin, azathioprine, methotrexate) Children with other major respiratory diagnoses such as bronchiectasis -

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>This arm will have treatment changed based on measures of inflammation | Other: Non invasive measurement of airway inflammation<br>* Airway inflammation will be assessed non-invasively using induced sputum and exhaled nitric oxide. In the active group the results of these tests will be used to determine if asthma treatment should be changed. In the comparator group treatment changes will be based according to conventional symptom based management<br>|
| Active Comparator: 2<br>Treatment will be changed on the basis of reported asthma symptoms | Other: Non invasive measurement of airway inflammation<br>* Airway inflammation will be assessed non-invasively using induced sputum and exhaled nitric oxide. In the active group the results of these tests will be used to determine if asthma treatment should be changed. In the comparator group treatment changes will be based according to conventional symptom based management<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of exacerbations; |  | 1 year | 
| Number of symptom free days and bronchodilator use per week |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Doses of inhaled and oral corticosteroid used per year |  | 1 year | 
| Comparison of daily versus single visit measures of eNO to predict an asthma exacerbation |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Pediatrics, Airway, Inflammation