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

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