Around 2% of people in the UK have severe asthma that does not respond well to standard corticosteroid treatments, yet these patients account for a greater total healthcare cost than all mild and moderate asthma patients combined. The problem is that doctors often escalate corticosteroid doses for these patients without knowing whether the drugs are actually working. Two hidden issues drive this: many patients do not take their prescribed medication (non-adherence), and others receive high doses of steroids despite having no steroid-responsive lung inflammation, suffering side effects without benefit. Current guidelines take a "one size fits all" approach that is poorly targeted. This programme will tackle both issues. First, it will use remote monitoring to objectively track whether patients are taking their medication, helping non-adherent patients get back on effective treatment rather than being escalated to expensive therapies. Second, it will validate simple blood and breath tests to identify which patients genuinely respond to corticosteroids and which do not. Patients with steroid-responsive "T2-High" asthma can enter clinical trials of new targeted drugs already developed by industry. Those with "T2-Low" asthma—a group we understand much less—will be studied intensively to identify new drug targets. If successful, this stratification approach could transform severe asthma care from a blunt, harmful escalation of steroids into a precise, safe system that matches each patient to the right treatment.
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Severe refractory asthma affects approximately 2% of the UK population, and has a total healthcare cost that is greater than that for all of the 10 - 15% of the population with mild/moderate asthma. International asthma guidelines advise the 'step-wise' increase of inhaled and oral corticosteroid treatment. However, for severe refractory asthma, the response to corticosteroids is often poor, and doctors often escalate to high dose inhaled or oral corticosteroids. Recent data suggests that this "one size fits all" approach to asthma treatment is poorly targeted. Our industry partners are developing new drugs for severe asthma, which will require a targeted approach in patients to identify who will respond. We propose a two level approach: (i) In some patients with severe asthma, a key clinical problem is non-adherence with corticosteroid therapy (non-adherence is where patients, intentionally or non-intentionally, do not take their prescribed treatment). This is common and is poorly recognised by physicians. It can result in patients being inappropriately labelled as having 'corticosteroid resistant' disease, and may cause patients to be escalated to more complex and expensive therapies, when they could be controlled on inhaled corticosteroid treatment. Assessing adherence objectively is a pre-requisite to optimising corticosteroid therapy. This programme will assess adherence using remote monitoring technologies and non-adherent patients will be assisted and managed within their clinical service. (ii) Some severe asthma patients have inappropriate increases in corticosteroids in the absence of corticosteroid responsive inflammation, and this can cause significant harm due to treatment side-effects, without any treatment benefit. Our programme will validate a new way to optimise corticosteroid therapy using simple blood (blood eosinophil count, serum periostin level) and breath (exhaled nitric oxide) tests of corticosteroid response across the major United Kingdom Clinical Centres for Severe Asthma. We know that patients with low measures of these biomarkers have a low chance of having an asthma attack and we can safely reduce and optimise their corticosteroid treatment dose. This process of corticosteroid optimisation will identify two populations of severe asthma patients, with different patterns of lung inflammation, one with corticosteroid responsive disease with high eosinophils (these are inflammatory cells recruited to the lungs in asthma) which we call "T2-High"severe asthma and the other with corticosteroid unresponsive disease or "T2-Low" severe asthma. The T2-High group will be available for clinical trials of novel treatments which have already been developed by the Pharmaceutical Industry. We currently understand much less about the T2-Low group, and they will be studied intensively with measures of lung function and other tests including airway sampling using bronchoscopy (a telescope test in the lungs to get airway samples) . We will also follow them up for 12 months to see if they remain stable on their optimised corticosteroid dose and if the pattern of inflammation in the lungs changes over time. This strategy will help us identify new drug targets for this group, and these patients will then be able to enter trials of these novel treatments. This programme is the first to take this type of stratification approach in severe refractory asthma, specifically to assess objectively adherence to current treatment, and then to test a way to optimise corticosteroid therapy. It will provide a world-leading step change in the care of patients with severe asthma. It will also enable a clinical trials programme to be expanded within the UK Severe Asthma Clinical Centres to allow the safe and targeted testing of new treatments.
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