Title: SPIROMAC – SPIROmetry to Manage Asthma in Children
Funder: Medical Research Council

Abstract: Asthma affects 1.1 million children in the UK. When asthma attacks occur, they are frightening for children and their families. Every twenty minutes a child is admitted to hospital in the UK due to an asthma attack. Doctors think that that recent asthma symptoms should guide treatment choices to prevent attacks. However, doctors need a reliable test to measure how well children’s lungs are functioning to be used alongside symptoms to guide treatment and reduce the number of asthma attacks. Lung function is important because it measures how easy it is to move air into and out of the lungs._x000D_ _x000D_ Spirometry measures lung function. Children do spirometry by taking a big breath in and breathing out through a tube as hard as they can. The amount of air they can breathe out in the first second is called the FEV1 (forced expiratory volume in one second). _x000D_ _x000D_ Currently, doctors disagree about how to best use spirometry to monitor asthma because of a lack of research evidence and conflicting guidance from experts. We know that about 25% of hospital doctors in the UK use spirometry regularly in their asthma clinics. Our recent research shows that a change in FEV1 over a three-month period is followed with what parents tell us is a meaningful increased risk of an asthma attack in the next three months. We think that using spirometry to guide treatment will lead to reduced attacks. Our study is designed to test this. Our study will also explore the link between treatment guided by spirometry and symptoms, and the number of attacks. _x000D_ _x000D_ We will recruit 550 children aged six to 15 years with asthma who have had an asthma attack in the last year. All children will meet the research team at the hospital or at a family doctor’s premises every three months (this interval is commonly used in hospital asthma clinics). At the first meeting, permission to take part in the study will be obtained. Everyone that takes part has an equal chance of getting either treatment guided by spirometry plus symptoms or symptoms alone (our control group). For all children, a computer programme will guide treatment decisions based on their current symptoms and treatment. But in the spirometry-guided group the computer programme will also use spirometry measurements. All children will have spirometry measured at every visit so we can better understand the relationship between lung function, asthma symptoms, changes in treatment and asthma attacks. We will collect asthma symptoms and details of any attacks from questionnaires which are completed at hospital clinic visits. At three-month intervals over a year, children will meet the research team, complete the symptom questionnaire and spirometry and have their treatment changed according to symptoms and spirometry or symptoms alone. We will measure asthma attacks and other outcomes over 12 months. We already have a network of recruiting centres and have identified asthma clinics in hospitals and general practices who will recruit participants._x000D_ _x000D_ In partnership with Asthma UK we have discussed study design with parents and young people. They have told us what is a meaningful reduced risk for asthma attacks (i.e. 30%). Parents and young people have also contributed to this plain English summary._x000D_ _x000D_ We will write a report which gives all our results. Our report will be published in a medical journal, given to the NHS, to participants and asthma guideline groups around the world.

Lay abstract: Background. There are 1.1 million UK children with asthma. One child has an asthma attack each 2-3 minutes in the UK. Asthma attacks cause morbidity and occasionally mortality, and cost the NHS £2 million per week. Asthma attack risk is reduced by taking asthma preventer treatment. Some guidelines say spirometry should be used alongside symptoms to objectively guide prescribing preventer treatment, but do not say how change in spirometry should guide treatment change. Spirometry can be reproducibly measured in children aged over 5 years. Our research has shown how a change in spirometry, even within “normal” limits and with controlled asthma symptoms, predicts risk of a future asthma attack in asymptomatic children. We have also shown that some UK doctors looking after children with asthma use spirometry routinely, but most do not. _x000D_ _x000D_ Research questions. In children with asthma does spirometry and symptom guided treatment, compared to symptom guided treatment alone, reduce the number of asthma attacks? What is the mechanistic relationship between treatment guided by spirometry and the risk for an asthma attack?_x000D_ _x000D_ Aims. To evaluate the efficacy of asthma treatment guided by spirometry plus symptoms, compared to symptoms alone, on asthma attacks in 550 children. _x000D_ _x000D_ Objectives. _x000D_ 1. To recruit children aged 6-15 years with asthma who have had an asthma attack in the last year._x000D_ 2. At the baseline assessment, to take consent and collect demographic and asthma related data._x000D_ 3. To randomise participants to receive treatment guided by symptoms alone (control arm) or spirometry plus symptoms (intervention arm). _x000D_ 4. To use an algorithm to guide treatment decisions based on a validated symptom score, current treatment, treatment adherence and, in half the children, spirometry. _x000D_ 5. For all children to have spirometry measured on every visit._x000D_ 6. To re-apply the algorithm at 3-month intervals over a year and adjust treatment where indicated by symptoms and, in half the children, spirometry plus symptoms._x000D_ 7. To determine primary and secondary outcomes over the 12 months post randomisation. The primary outcome is number of asthma attacks. Secondary outcomes include any attack (yes/no) and time to first attack. _x000D_ 8. To understand the mechanistic relationship between treatment guided by spirometry, lung function and eosinophilic airway inflammation and the risk for an asthma attack._x000D_ _x000D_ Methods. A randomised controlled trial with mechanistic component. We will recruit from approximately 57 sites. Our existing network already includes 42 sites prepared recruit participants to SPIROMAC. We know from our previous trial (RAACENO) that these centres can recruit and already have lists of eligible participants. We will modify a computer-based algorithm, whose use proved feasible and acceptable in RAACENO. Analysis will be by intention to treat. Negative binomial regression will be used to compare the primary outcome between trial arms._x000D_ _x000D_ Timelines. Participant recruitment starts in month 7. Our internal pilot will assess recruitment progress in month 15. Follow up will end in month 42. The monograph will be submitted in month 48._x000D_ _x000D_ Impact and dissemination. Our intervention could reduce asthma attacks and will give insight into the relationship between spirometry and attacks. Dissemination will include a summary to participants, publications in peer-reviewed journals, a report to funder and to asthma guideline committees.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RESPIRATORY