Dr Mark L Levy presents five key learning points to help GPs diagnose and manage patients with difficult-to-treat and severe asthma and identify those who need referral to specialist care

Levy mark

Dr Mark L Levy

Read this article to learn more about:

  • why deaths from asthma in the UK remain high compared with other high-income countries
  • key points for the effective management of most patients with asthma
  • how to recognise when a patient with asthma should be referred to a specialist.

Implementation actions for STPs and ICSs

Implementation actions for clinical pharmacists in general practice

The UK has the fourth highest asthma mortality in high-income countries worldwide1 and persisting high preventable admission rates for asthma attacks.2 UK healthcare costs per patient for severe refractory asthma are higher than for type 2 diabetes, stroke, or chronic obstructive pulmonary disease (COPD).3

In November 2018, the Global Initiative on Asthma (GINA) published practical guidance on the diagnosis and management of difficult-to-treat and severe asthma.2 This pocket guidance is intended for use by all clinicians (that is, from primary to tertiary care) involved in the management of asthma.

This article focuses on five key issues, which in the author’s view need to be addressed by GPs in the UK to effectively manage most patients with asthma and also to identify those patients with difficult-to-treat and severe asthma who need referral to a specialist asthma service.


GINA defines uncontrolled, difficult-to-treat, and severe asthma as follows:2

  • uncontrolled asthma includes one or both of the following—
    • poor symptom control: that is, frequent symptoms or reliever use, activity limited by asthma, and night waking due to asthma. In the UK, poor symptom control is measured by either the Royal College of Physicians (RCP) 3 Questions4,5 or sometimes the Asthma Control Test,6 which provides a validated objective score (<20 = poor symptom control). However, the Quality and Outcomes Framework (QOF), AST indicator 003, requires that GPs ask the RCP 3 Questions in order to receive payment7
    • frequent or serious asthma attacks/exacerbations (that is, >1 a year) requiring oral corticosteroids (OCS) or one or more hospital admissions for asthma a year. In May 2014, the National Review of Asthma Deaths (NRAD)8 recommended that anyone experiencing two or more asthma attacks in a year should be referred to a specialist asthma service; this recommendation has not yet been implemented nationally in the UK
  • difficult-to-treat asthma (affecting about 17% of people with asthma) is uncontrolled asthma despite treatment with medium- or high-dose inhaled corticosteroids (ICS) plus a second controller drug or maintenance oral corticosteroids (OCS). Many patients appear ‘difficult-to-treat’ because of modifiable risk factors9
  • severe asthma (affecting about 5% of people with asthma) is a subset of ‘difficult-to-treat’ asthma, which is uncontrolled despite adherence to maximal optimised therapy; or that is controlled and then worsens when high-dose treatment is reduced.9

The key reason for recording a diagnosis of difficult-to-treat or severe asthma is that these patients should be referred to severe and difficult asthma specialist teams for characterisation and optimisation of management, sometimes requiring biological treatment with anti-immunoglobulin E (IgE) or anti-interleukin-5 (IL-5) medication.2 The GINA guidance spans the diagnosis, monitoring, and management of difficult-to-treat or severe asthma and should be used in conjunction with the full GINA strategy document and any local guidelines in place.2

1. Record evidence for diagnosis of asthma

The diagnosis of asthma is complicated by the fact that there isn’t a single confirmatory test. Guidelines are available and helpful in this regard; however, the UK now has two contradictory sets, which results in confusion.5,10,11

The medical record should reflect the basis upon which the diagnosis of asthma was made; including medical and family history, results of investigations as well as response to treatment. As reversible airflow obstruction is a fundamental component of the definition of asthma, it is logical that either quality-assured spirometry, with reversibility, or peak expiratory flow measurements are recorded when diagnosing asthma. These details will be helpful to colleagues with whom the patient consults subsequently, particularly where the patient’s symptoms remain poorly controlled or where the diagnosis is in doubt.

2. Assess asthma control and identify risk

In the UK, mainly due to the QOF requirements,7 assessment of asthma control is often limited to use of the RCP 3 Questions.4,5 This questionnaire simply determines whether the patient has current asthma symptoms, based on their symptoms during the previous 4 weeks. This and the practice of only doing one asthma review a year, for this chronic disease, may explain the poor UK asthma outcomes compared with other countries. Asthma control assessment should include both current symptoms and also risk of future attacks, both modifiable and non-modifiable.2

Furthermore, these assessments should be performed whenever patients present with respiratory symptoms, when medication is changed, and most importantly, within 2 days of onset of treatment for asthma attacks or discharge from hospital.5 The objectives of the post-attack review are to:2

  • determine whether the attack is over or whether additional oral corticosteroid or re-admission to hospital is required; and
  • optimise care by identifying and acting on modifiable risk factors with the aim of preventing further attacks.

3. Identify modifiable risks and optimise care

Modifiable risk factors present in a high proportion of patients with difficult-to-treat asthma and include lack of adherence by patients to medical advice, excess prescription of reliever medication (short-acting beta2 -agonist bronchodilators [SABAs]), and failure by prescribers to recognise that controller prescriptions are not being collected or requested. A patient with controlled asthma needs less than four puffs of SABA per week (<2 inhalers a year) and therefore anyone prescribed more than six SABAs a year should be reviewed by someone trained in asthma care.12,13

Other modifiable risk factors include, for example, poor inhaler technique (someone unable to use their inhaler properly won’t benefit from treatment), and patients taking medications such as beta-blockers or non-steroidal anti-inflammatory drugs (NSAIDs), which may make asthma worse. Co-morbid conditions, such as symptomatic gastro-oesophageal reflux or rhinosinusitis, should be treated.2

Non-modifiable risks should also be identified, for example pregnancy, previous attacks, food allergy, or past near-fatal asthma attacks, all of which may reduce control and increase the chance of poor outcomes. See also Box 2.2 in chapter 2 of the GINA strategy guidance2 and Table 11 in BTS/SIGN 153.5

4. Differentiate difficult-to-treat from severe asthma

Once modifiable risk factors have been identified and addressed, in ‘difficult-to-treat asthma’ a small group of patients with severe asthma remain. Their asthma:

  • is uncontrolled despite high doses of ICS plus other classes of anti-asthma medication (long-acting beta-agonist bronchodilators [LABAs], leukotriene modifier/leukotriene receptor antagonist [LM/LTRAs], or long-acting muscarinic antagonists [LAMAs]); or
  • becomes uncontrolled when medication is reduced.

These patients require referral to severe asthma services for advice and further management.

5. Refer to specialists early

Tragic outcomes occur when the diagnosis of severe or difficult-to-treat asthma is not recognised and there is failure to refer to specialists.8 Recent coroners’ regulation 28 statements on preventable asthma deaths14,15 illustrate this clearly where children with multiple, recurrent asthma attacks are simply treated for acute attacks without anyone diagnosing underlying severity and making a specialist referral.

Another recent inquest heard evidence in the matter of an asthma death of a 10-year-old girl (personal communication), who had suffered 48 attacks in her short life, including the fact that she was discharged from hospital care on three occasions because her parents failed to bring her to outpatient appointments, despite her having been diagnosed with ‘severe brittle asthma’, and having had a previous near-fatal asthma attack.

Forty-five percent of the patients who were investigated by the NRAD hadn’t recognised the signs of impending fatal asthma before they died; this is unsurprising, because only 23% of all those who died had been issued with personal asthma action plans.8

General practitioners, trained asthma nurses, and clinical pharmacists with asthma training should be able to maintain control in the majority of patients with difficult-to-treat asthma through management of modifiable risk factors and detailed patient education.

Patients whose asthma remains difficult-to-treat or with possible severe asthma should be referred to specialist asthma services, ideally severe/difficult-to-treat asthma clinics for detailed characterisation, phenotyping, and management of their disease, sometimes requiring biological agents. Those people diagnosed with severe asthma need ongoing supervision, possibly for the rest of their lives, by specialists as well as GPs, trained asthma nurses, and clinical pharmacists with asthma training.

Dr Mark L Levy

Locum General Practitioner London

Chairman Dissemination and Implementation Committee Global Initiative on Asthma (GINA)

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources.

  • Consider the challenges associated with implementing recommendations from the different guidelines within the available financial and human resources
  • Decide which asthma guideline to adopt locally and build recommendations into care pathways to ensure accurate diagnosis of asthma
  • Identify severe asthma as a clinical priority and make plans to target resources to patients most at risk of death or hospital admission (for example, patients presenting to emergency services or having rescue steroids and antibiotics)
  • Establish pathways for the referral of individuals for whom biological agents might be a suitable
    • these new treatments are expensive so funding will also need to be considered. 

STP=sustainability and transformation partnership; ICS=integrated care system

Implementation actions for clinical pharmacists in general practice

written by Gupinder Syan, Training and Clinical Outcomes Manager, Soar Beyond Ltd

The following implementation actions are designed to support clinical pharmacists in general practice with implementing the guidance at a practice level. 

  • Identify patients with uncontrolled asthma, difficult to treat asthma, and severe asthma
  • Agree the types of patient that you will see in your clinic with your supervising GP. Communicate the decision with all healthcare professionals in the practice so that appropriate patients are booked in to your clinic
  • Utilise the practice skill mix appropriately and avoid duplication of work
  • Familiarise yourself with guidelines, the RCP 3 Questions, the asthma control test, the NRAD report findings, and your local guidelines, formularies, and referral pathways
  • Ensure that:
    • people who have had asthma attacks, or have had a change in treatment, are assessed, monitored, and followed-up in appropriate timeframes 
    • patients with a diagnosis of difficult-to-treat or severe asthma are appropriate appropriately coded on the practice register and that they are referred to asthma specialists for characterisation and optimisation of management
  • Deliver clinic
    • check and reinforce inhaler technique
    • identify modifiable and non-modifiable risk factors and triggers
    • complete system templates to code all the information and interventions so that outcomes can be measured 
    • update asthma action plans at each patient contact
  • Evaluate outcomes
    • how many patients have you seen in clinic? 
    • how many asthma-related hospital admissions have been prevented?
    • how have you contributed to QOF income?
    • how many patients have been correctly coded with ‘severe’ or ‘difficult-to-treat asthma’ to create correct patient registers?
    • how many patients have been referred to specialist services in an appropriate and timely manner?
    • audit to check if asthma coding has improved in relation to asthma, and if internal systems improved to ensure timely follow up of patients
    • patient satisfaction questionnaires on supply and treatment regimen choice.

For more information refer to the Guidelines in Practice article on Asthma: the role of the practice pharmacist.

SABA=short-acting beta2 agonist; RCP=Royal College of Physicians; NRAD=National Review of Asthma Deaths; QOF=quality and outcomes framework


  1. Shah R, Hagell A, Cheung R. International comparisons of health and wellbeing in adolescence and early adulthood. London: Nuffield Trust, 2019. Available at: www.nuffieldtrust.org.uk/files/2019-02/1550657729_nt-ayph-adolescent-health-report-web.pdf.
  2. Global Initiative for Asthma (GINA). www.ginasthma.org (accessed 25 March 2019).
  3. O’Neill S, Sweeney J, Patterson C, Menzies-Gow A et al. The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry. Thorax 2015; 70 (4): 376–378. Available at: dx.doi.org/10.1136/Thoraxjnl-2013-204114
  4. Pearson M, Bucknall C, editors. Measuring clinical outcomes in asthma: a patient focused approach. London: Royal College of Physicians, 1999.
  5. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. SIGN 153. BTS/SIGN, 2016. Available at: www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2016/
  6. QualityMetric Incorporated, GlaxoSmithKline. Asthma control test. Updated January 2018. Available at: www.asthmacontroltest.com (accessed 25 March 2019).
  7. NHS Employers. 2018/19 General Medical Services (GMS) contract Quality and Outcomes Framework (QOF). Guidance for GMS contract 2018/19. April, 2018. Available at: www.nhsemployers.org/QOF201819
  8. Levy M, Andrews R, Buckingham R et al. Why asthma still kills—the National Review of Asthma Deaths (NRAD). Confidential Enquiry report. London: Royal College of Physicians, 2014. Available at: www.rcplondon.ac.uk/sites/default/files/why-asthma-still-kills-full-report.pdf (accessed 25 March 2019).
  9. Hekking P, Wener R, Amelink M et al. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015; 135 (4): 896–902.
  10. NICE. Asthma: diagnosis, monitoring and chronic asthma management. NICE Guideline 80. NICE, 2017. Available at: www.nice.org.uk/ng80
  11. Keeley D, Baxter N. Conflicting asthma guidelines cause confusion in primary care BMJ 2018; 360: k29. 10.1136/bmj.k29
  12. Levy M, Garnett F, Kuku A et al. A review of asthma care in 50 general practices in Bedfordshire, United Kingdom. NPJ Prim Care Respire Med 2018; 28 (1): 29.
  13. Levy M, Ward A, Nelson S. Management of children and young people (CYP) with asthma: a clinical audit report. NPJ Prim Care Respire Med 2018; 28 (1): 16.
  14. Dr Shirley Radcliffe. Regulation 28 Statement in the matter of Michael Uriely (deceased). 2017. Available at: www.judiciary.gov.uk/wp-content/uploads/2017/03/Uriely-2017-0069_Redacted.pdf
  15. Terrence Carney. Regulation 28 statement in the matter of Tamara Mills (deceased). 2015. Available at: www.judiciary.gov.uk/wp-content/uploads/2016/01/Mills-2015-0416.pdf