Title: High Flow humidified oxygen as an early intervention in children with Acute Severe Asthma. A feasibility study (HiFlo ASA).
Funder: Department of Health and Social Care

Abstract: Acute severe asthma (ASA) is a leading cause of hospital attendance in children, accounting for up to 7% of all paediatric emergency visits(16) and 8.5% of paediatric admissions from emergency departments(17) - the most common single reason. Standard first-line emergency treatment(11) for ASA is high dose inhaled bronchodilators (&quot;burst therapy&quot;) plus oral corticosteroids. When this fails, children require hospital admission - often to a critical care facility - for second line rescue treatments (a range of intravenous bronchodilators). These have limited effectiveness and significant side effects(13). There is little evidence or consensus on choice of intravenous bronchodilator(11), and some children go on to need respiratory support. There is therefore a need to investigate other options for children who fail first-line treatment for ASA. High flow, highly humidified oxygen therapy (HiFlo) is an innovative technology which supports breathing by supplying a warm, humidified air/oxygen mixture at high flow rates, is effective in other acute respiratory conditions in infants and children(14), and has shown some promise in ASA (29, 30). We propose to carry out a feasibility study of early HiFlo - started in the emergency department (ED) as soon as burst therapy has failed - to inform definitive randomised controlled trial (RCT). This feasibility study has been planned with extensive input from parents and young people, and this will continue throughout the study. We plan to recruit 70 children aged 2-11 years at three sites over 18 months. Children attending the emergency department with ASA who fail to respond to burst therapy (using standardised criteria) will be randomised to standard therapy or early HiFlo, which will be initiated in the ED. Deferred consent will be sought within 24 hours according to well-established guidelines for emergency research in children. The trial protocol will be pragmatic allowing the use of clinical discretion to escalate therapy in either arm, and analysis will follow intention to treat principles. Clinical outcome data will be collected in order to assess candidate primary and secondary outcomes. The candidate primary outcomes will be (a) time to readiness for hospital discharge and (b) treatment failure requiring escalation of therapy. Parent, patient (for children four years and above) and staff experience will be assessed using a short questionnaire at hospital discharge and telephone interview within two weeks of discharge. The results will be analysed and disseminated both to professionals and service users in order to plan and obtain funding for a definitive multicentre RCT, provided that pre-determined criteria for proceeding to a full trial are met. We will identify and refine outcome criteria, recruitment strategies and trial protocol, and estimate sample size and number of centres required. We have discussed and obtained backing from research networks of respiratory and emergency care paediatricans, who will help to identify sites for the full RCT.

Lay abstract: Asthma affects 1 in 11 British children. Attacks of Acute Severe Asthma (ASA) are among the commonest reasons for children to attend hospital emergency departments. Many children do not respond to initial treatment, and need to stay in hospital for rescue therapy. Current rescue therapy is unsatisfactory and has unpleasant side effects. High flow humidified oxygen (HiFlo) is a new treatment which helps children breathe by delivering lots of moist air enriched with oxygen down into the airways of the lungs, through short soft tubes that fit snugly into the nostrils. We think it works by: keeping secretions moist and easy to clear keeping the airways open helping to get medicines deeper into the airways It is more comfortable than other methods of breathing support and has a good safety record. HiFlo is already being used in: premature babies with breathing problems babies with virus lung infections ASA, later on when rescue therapy has failed We believe that starting HiFlo early on in ASA will speed up recovery and reduce the need for unpleasant rescue therapy. If effective, HiFlo could quickly be introduced into routine emergency care in children, and could save money. HiFlo is already used in the NHS for other breathing difficulties. However, we do not yet have enough evidence to say that early HiFlo should be used routinely in children with ASA. Before starting a large national trial to decide whether early HiFlo is effective, we need to run a feasibility study (a small test version of the full trial). We have designed this together with children and parents. 70 children (2&ndash;11 years) with ASA will be in the study from the emergency department until they go home. Half will receive standard care and half will receive early Hi-Flo; no extra blood tests will be needed. We will compare, between children on standard care and on early Hi-Flo: how quickly they improve and are ready to go home how many have side effects or complications how many end up needing rescue treatment what children, parents and healthcare staff think about being involved in the research Things need to move quickly during emergency treatment, and children and parents are often very distressed. Because of this we will delay asking for consent for the research until the emergency has passed, but we will let families know the research is taking place. We will share and discuss the information we collect with parents, young people and healthcare staff. This information and discussion will be vital in planning the full trial to see if early HiFlo is better than standard treatment in children with ASA.

Research activity codes: 6.7 PHYSICAL
Health categories: RESPIRATORY