Recommendations for research

Diagnosis and monitoring

The guideline committee has made the following recommendations for research on diagnosing and monitoring asthma. The committee's full set of research recommendations is detailed in the full guideline on asthma: diagnosis and monitoring.

1 Diagnosing asthma in children and young people aged 5 to 16

What is the acceptability and diagnostic accuracy of objective tests that could be used to comprise a diagnostic pathway for asthma in children and young people aged 5 to 16 (for example, exercise challenge, direct bronchial challenge with histamine or methacholine, indirect bronchial challenge with mannitol and peripheral blood eosinophil count)?

Why this is important

Asthma is a common condition, diagnosed in nearly 1 in 10 children. There are no validated and reliable objective criteria for diagnosing asthma, so the vast majority of asthma diagnoses are currently based on symptoms and signs. However, symptoms and signs consistent with a diagnosis of asthma are not specific to the condition and can be present in other illnesses. This diagnostic uncertainty results in many children being incorrectly diagnosed with asthma, and many children with asthma in whom the diagnosis is delayed or missed. A single objective measure, or set of objective measures, that can be performed easily in non-specialist clinical settings (although it is noted that challenge tests need to be performed in specialist settings) will help improve diagnostic certainty and reduce the proportion of children treated inappropriately for asthma. This would ensure that children with the condition are identified and treated early.

2 Diagnosing asthma in adults (aged 17 and over)

What is the clinical and cost effectiveness of using an indirect bronchial challenge test with mannitol to diagnose asthma in adults (aged 17 and over)?

Why this is important

Chronic airway inflammation is associated with bronchial hyper-responsiveness, which is integral to defining asthma. Bronchial challenge testing can help diagnose asthma and assess response to inhaled corticosteroid therapy. It can also be used to monitor asthma control, alongside assessing symptoms and lung function. It is increasingly used in asthma management, although currently most tests are performed only in specialised centres or research settings.

Indirect challenge tests with inhaled mannitol act via active inflammatory cells and mediators, whereas direct challenge tests with inhaled histamine or methacholine act directly on bronchial smooth muscle. Indirect challenge testing is more specific but less sensitive than direct challenges.

Direct challenge testing may not identify a person whose asthma will respond to inhaled corticosteroids. A positive result to an indirect challenge may reflect active airway inflammation that is likely to respond to inhaled corticosteroid therapy. Because a response to mannitol indicates active airway inflammation, identifying non-responsiveness in treated patients may help demonstrate good asthma control with inhaled corticosteroid therapy and identify people whose asthma is less likely to deteriorate after a dose reduction.

Mannitol bronchial challenge testing is quicker and simpler than current direct tests (which are generally confined to specialist respiratory centres), and uses a standardised inhaler device, so is potentially more useful in primary care.

3 Monitoring adherence to treatment

What is the clinical and cost effectiveness of using electronic alert systems designed to monitor and improve adherence with regular inhaled maintenance therapy in people with asthma?

Why this is important

Adherence with regular maintenance inhaled corticosteroids, on their own or in combination with long-acting beta agonists, is of paramount importance to achieve control of asthma and prevent asthma attacks. Published evidence in patients with severe asthma suggests that at least 30% of patients are partially or non-adherent with their prescribed medications, and the Royal College of Physicians' National Review of Asthma Deaths (NRAD) demonstrated that poor adherence was associated with 38% of asthma deaths.

4 Monitoring inhaler technique

What is the current frequency and the current method being used to check the inhaler technique of people with asthma? What is the optimal frequency and the best method of checking inhaler technique to improve clinical outcomes for people with asthma?

Why this is important

Knowing and understanding how to use an inhaler properly is the cornerstone of asthma management and symptom control. There has been an increase in the types of inhaler devices and the types of delivery system available. The various types of drugs for asthma control are also available in different inhaler devices on their own and in a combination of 2 drugs. It is therefore vital for patients to learn the proper inhaler technique for their device to ensure optimum drug delivery to the lungs for asthma control.

5 Monitoring asthma control using tele-healthcare

What is the long-term (more than 12 months) clinical and cost effectiveness of using tele-healthcare as a means to monitor asthma control in adults, young people and children? Methods of tele-healthcare can include telephone interview (with healthcare professional involvement) and internet or smartphone-based monitoring support (no healthcare professional involvement).

Why this is important

Asthma outcomes have not improved in the past 15 years, and the personal and economic costs of poor control are high. Computers and smartphones play an ever-greater role in modern life, with a growing proportion of people using them regularly for work, leisure, communication and information. The efficient use of distance monitoring systems and the integration of new technologies into healthcare are important for patients and for healthcare systems in terms of convenience, costs and outcomes.

Managing chronic asthma

The guideline committee has made the following recommendations for research on managing chronic asthma. The committee's full set of research recommendations is detailed in the full guideline on chronic asthma management.

1 Starting asthma treatment

In adults, young people and children with asthma who have not been treated previously, is it more clinically and cost effective to start treatment with a reliever alone (a short-acting beta2 agonist [SABA]) or with a reliever (a SABA) and maintenance therapy (such as ICS)? Are there specific prognostic features that indicate that one of these treatment options may be more appropriate for some groups?

Why this is important

Recently best practice has shifted from starting people with asthma on a SABA as a reliever alone and starting maintenance therapy only if the person continues to have persistent asthma symptoms, to starting people on a low dose inhaled corticosteroid (ICS) as maintenance therapy alongside the SABA at the first instance. The committee agree with this shift and have included consensus-based recommendations in line with this pattern. However, the shift is not based on direct clinical evidence comparing these strategies for people with newly diagnosed asthma. There is also little evidence to support the particular groups in which one option or the other is more appropriate.

2 Second-line maintenance therapy in children and young people (under 16)

Is maintenance therapy more effective with a paediatric low dose of ICS plus a leukotriene receptor antagonist (LTRA) or with a paediatric low dose of ICS plus a long-acting beta2 agonist (LABA) in the treatment of asthma in children and young people (under 16) who have uncontrolled asthma on a paediatric low dose of ICS alone?

Why this is important

There is a lack of evidence on managing asthma in children and young people under 16. Many of the recommendations for children and young people in this guideline were made using extrapolation from the adult evidence and the consensus of the guideline committee. The guideline committee would like to encourage more research in this age group. This particular question was prioritised because it affects the early stages of the treatment pathway and could have significant clinical and cost implications for managing asthma in this age group.

3 Additional maintenance therapy for asthma uncontrolled on a moderate dose of ICS plus LABA with or without LTRA

What is the clinical and cost effectiveness of offering additional maintenance therapy to adults, young people and children with asthma that is uncontrolled on a moderate dose of ICS plus LABA with or without LTRA?

Why this is important

The evidence is insufficient in quantity and quality to support strong recommendations for the use of additional maintenance therapy beyond moderate dose ICS plus LABA. The clinical evidence tends to favour the addition of a long-acting muscarinic antagonist (LAMA) but the guideline committee did not consider this to be conclusive, particularly because the addition of a LAMA is not cost effective compared with treatment with a placebo. In current practice, the alternative treatment options to adding a LAMA at this stage are increasing ICS dose to high, addition of theophyllines or a course of oral steroids. Therefore, to truly understand the cost effectiveness of LAMAs, a randomised controlled trial and health economic analysis taking into account the impact of LAMAs on oral steroid use and comparing the addition of LAMAs to any alternative strategy (as opposed to just placebo) is needed. The guideline committee felt the body of evidence, supported by consensus agreement and current practice, was sufficient to weakly recommend the options of ICS high dose plus LABA, addition of a LAMA or theophylline or seeking advice from a healthcare professional with expertise in asthma. However, a study comparing these various strategies would be critical for stronger recommendations or a more specific order of options.

4 Decreasing pharmacological treatment

In adults, young people and children with well-controlled asthma, what are the objective measurements and prognostic factors that indicate that a decrease in regular maintenance treatment is appropriate?

Why this is important

There is consensus within the guideline committee and across healthcare professionals managing asthma that people with well-controlled asthma should not remain on high dose or multiple preventer medicines for long periods of time. However, there is little evidence available about which people might benefit most from decreasing regular maintenance therapy. This guideline identified 3 studies attempting to answer this question but none of them included a sufficiently large population, with suitable decrease in treatment throughout and assessment of multiple prognostic markers.

5 Improving adherence to asthma medication

What are the most clinically and cost-effective strategies to improve medicines adherence in adults, young people and children with asthma who are non-adherent to prescribed medicines?

Why this is important

There is a consensus within the guideline committee and across healthcare professionals that medicines adherence is an important determinant of asthma control, and that non-adherence is a common problem. However, there is a lack of high-quality evidence on methods to improve adherence to asthma medicines. The guideline identified a number of studies focusing on this question, but there was not a strong body of evidence behind any specific intervention strategy. In addition, the guideline committee had concerns about the applicability of studies that did not report outcomes after a prolonged follow‑up and studies that only used self-reported measures to assess adherence. The guideline committee felt further that higher-quality research is needed to recommend specific interventions for this common and significant problem.

  • National Institute for Health and Care Excellence (NICE)