4 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

4.1 Mediators of anaphylactic reactions

Aside from mast cell tryptase, which other chemical inflammatory mediators offer potential as indicators of anaphylaxis?

Why this is important

Although mast cell tryptase is widely used to support the diagnosis of anaphylaxis, it is not universally suitable. Mast cell tryptase is not always elevated in children, when food is the allergen, or when the main severe feature is respiratory.

It is recommended that a cross-sectional study be carried out into the diagnostic accuracy of other potential chemical inflammatory mediators. The study should be conducted in both adults and children who have had a suspected anaphylactic reaction. The sensitivity and specificity of the proposed mediator should be compared against mast cell tryptase, using clinical assessment in conjunction with immuno-allergic study as the reference standard for both. The diagnostic accuracy of any mediator should be carried out for a range of potential allergens.

4.2 The frequency and effects of biphasic reactions

What are the frequency, timing, severity and predictors of biphasic reactions in people who have received emergency treatment for anaphylaxis?

Why this is important

Limited evidence was found on the frequency, timing severity and predictors of biphasic reactions and the resulting effect of these on morbidity and mortality.

It is recommended that a UK-based prospective cohort study be conducted that follows patients up after emergency treatment for anaphylaxis.

The study should follow people up for 7 days after discharge from the emergency department. The aim is to collect data on the predictors (for example, the person's response to the initial treatment), the time to any reaction, the severity of any biphasic reaction and the effect of the biphasic reaction on morbidity and mortality.

4.3 Length of observation period following emergency treatment for anaphylaxis

For how long should a person who has received emergency treatment for anaphylaxis be observed?

Why this is important

No studies were found that compared different observational periods or the effect of these on relevant patient outcomes.

It is recommended that a cluster randomised controlled trial is conducted for people who have received emergency treatment for anaphylaxis.

The interventions for the trial should be differing time periods of observation, within the secondary care setting, ranging from 1 hour to 24 hours after symptom resolution of the index reaction. Patients should then be followed up for 7 days following the end of the observational period to determine if a biphasic reaction has occurred and the effects of any reaction. The aim is to determine whether differing periods of observation have a detrimental effect on morbidity and mortality and to gather information about resource use.

4.4 Prevalence of anaphylactic reactions and related outcomes

What is the annual incidence of anaphylaxis and its related outcomes within the UK?

Why this is important

Limited evidence exists on the annual incidence of anaphylactic reactions and their associated outcomes within the UK.

It is recommended that a prospective observational study be conducted that records the annual incidence of anaphylactic reactions within the UK.

The overall number of anaphylactic reactions that occur in adults and children should be recorded and these should be classified into those that are first-time reactions, recurrent reactions or biphasic reactions. A clear, pre-defined, definition of what constitutes an anaphylactic reaction should be used, in order to avoid the misclassification of milder reactions. Data should also be collected on any emergency treatment that was delivered (by a clinician, use of an adrenaline injector) and the associated outcomes (morbidity, mortality, adverse events). Data should also be collected on any previous treatment received, such as that from a specialist allergy service or the provision of adrenaline injectors.

4.5 Effect of specialist services on health-related quality of life

For people who have experienced suspected anaphylaxis, what is the effect on health-related quality of life of (a) referral to specialist allergy services and (b) provision of adrenaline injectors, when compared with emergency treatment alone?

Why this is important

The GDG believed that referral to specialist services and/or the provision of adrenaline injectors was likely to provide day-to-day HRQoL benefit for people who have experienced suspected anaphylaxis, as a result of decreased anxiety and ongoing support. However, the health economic model relied on GDG opinion alone to quantify this benefit. Future economic analyses would be greatly improved by a reliable demonstration of this effect and an estimate of its magnitude. It is recommended that data are collected using validated measure(s) of HRQoL, including EQ-5D.

  • National Institute for Health and Care Excellence (NICE)