Dr Mark L Levy highlights updated recommendations on asthma therapy from the 2020 Global Initiative for Asthma (GINA) report and signposts resources for online learning

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Dr Mark L Levy

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Read this article to learn more about:

  • why Global Initiative on Asthma (GINA) no longer recommends short-acting beta2-agonists for first-line therapy in asthma
  • as-needed inhaled corticosteroid-formoterol in mild asthma
  • diagnosis and initial treatment of people with asthma and COPD
  • the importance of regularly assessing and reviewing asthma control.

COVID-19 considerations

Implementation actions for STPs and ICSs

Implementation actions for clinical pharmacists in general practice

The Global Initiative on Asthma (GINA) updates its evidence-based documents annually, based on research published in the previous year. The methodology underpinning the development and annual updates of these documents is described on the GINA website; in summary, all asthma papers published in the previous year are reviewed by the GINA science committee and relevant findings are incorporated in the updates. In the case of new therapies, GINA makes recommendations based on the best available evidence, after approval by at least one major regulatory agency (such as the European Medicines Agency [EMA] and US Food and Drug Administration [FDA]). For existing medications with evidence for new regimens or populations, GINA may make recommendations not covered by a regulatory indication in any country at the time if satisfied with the evidence for safety and effectiveness.

Members of the GINA board of directors and science committee are all experts in the field of asthma drawn from countries across the globe. The GINA strategy documents are intended mainly for generalists as well as people with expertise in asthma and are incorporated in many countries’ asthma guidelines. In the last few years, GINA has made new recommendations both for the management of severe and difficult-to-treat asthma and for the management of mild to moderate asthma.1 This article summarises some of the key changes in the 2020 update of the GINA strategy documents. These relate to therapy for asthma, diagnosing asthma combined with chronic obstructive pulmonary disease (COPD; asthma–COPD overlap, ACO) and management of severe and difficult-to-treat asthma. Readers are also advised to refer to the pocket guide and full documents available on the GINA website (www.ginasthma.org).

Therapy for asthma

For over 40 years, guideline developers have recommended short-acting beta2 -agonist (SABA) bronchodilators, such as salbutamol, as first-line treatment for asthma; the NICE asthma guideline continues to recommend this approach.2 There are a number of studies on the risks of poor outcome (including death) due to regular use of SABAs, and also studies demonstrating that even small doses of inhaled corticosteroids (ICSs) can prevent asthma attacks (and deaths).3

The key changes in the GINA recommendations are that:3

  • all patients with asthma should be treated with ICSs either regularly or as needed; and as a therapeutic trial in children under 5 years with review after 3 months
  • GINA no longer recommends SABAs for first-line use in asthma3 except in children aged under 5 years (where evidence is lacking) and where a trial of ICS should be used in those not responding to as-needed SABA
  • for as-needed relief of symptoms, GINA’s preferred choice of reliever is ICSs in combination with formoterol for adults and adolescents over the age of 12, and ICS taken as needed together with a SABA in children aged 6–11 years (ICS-formoterol is a long-acting bronchodilator with rapid action)
  • in people with mild asthma, defined where the person needs relief treatment no more than twice a month, the preferred treatment is as-needed ICS-formoterol in combination
  • regular asthma review should include assessment (including diagnosis and patient preference for treatment), adjustment (including increasing or decreasing doses), and review of response to any changes (see Figure 1, which was updated in 2020).

Figure 1 The GINA assess, adjust, and review management cycle for personalised care

Figure 1: The GINA assess, adjust, and review management cycle for personalised care3

© 2020 Global Initiative for Asthma, reprinted with permission. Available from www.ginasthma.org

GINA is not a ‘one size fits all’ approach.

These groundbreaking recommendations for as-needed ICS-formoterol in mild asthma and for relief of symptoms, are supported by a number of studies all detailed in the GINA documentation. That SABA used alone is unsafe is supported by numerous studies linking poor outcomes (including asthma deaths) with excess use of SABA. In the UK, excess SABA use was highlighted as a major factor in the deaths of patients studied in the National Review of Asthma Deaths (NRAD).3–5 Astonishingly, from my personal experience as expert witness in inquests related to preventable asthma deaths, excess SABAs continue to be prescribed by UK clinicians.6–8

In view of the risk that patients with mild or intermittent asthma may not use ICS or may rely entirely on SABAs for asthma treatment, the GINA recommendation for as-needed ICS-formoterol offers a practical safety net ensuring they are treated with an anti-inflammatory drug with added relief from the formoterol rather than only administering a short-acting reliever when asthma flares up.3 This approach was initially supported by two large studies of non-inferiority for severe exacerbations versus daily low-dose ICS plus as-needed SABA9,10and direct evidence from one large study of 64% reduction in severe exacerbations versus SABA-only treatment.9 Two further 12-month real life studies11,12 found that as-needed ICS-formoterol produced significant reduction in severe exacerbations compared with SABA alone, and compared with maintenance ICS. A key finding of these two studies was that subjects using as-needed ICS formoterol used less ICS compared with those using regular ICS during the studies. At the time of writing (June 2020), these recommendations have been supported by studies involving nearly 10,000 people with asthma, and ‘as-needed’ ICS-formoterol as sole therapy in mild asthma has been licensed by regulators in at least six countries.

In the UK, there is as yet no regulatory licence for as-needed ICS-formoterol alone. I suggest one of the six licensed products for maintenance and reliever therapy13–18 (SMART or MART) are prescribed so that if a patient fails to comply with the ‘maintenance’ aspect, at least they will have the safer option for relief of symptoms rather than SABA alone, which poses risk of severe or life-threatening attacks. Figure 2 summarises this approach and Figure 3 has been added to help clinicians decide on initial treatment—please note that these figures refer to adults and adolescents; please refer to the full GINA strategy document for figures regarding children.3

Figure 2 The asthma management cycle for personalised asthma care

Figure 2: The asthma management cycle for personalised asthma care3

ICS=inhaled corticosteroid; LABA=long-acting beta2 -agonist; IgE=immunoglobulin-E; IL5=interleukin-5; IL4R=interleukin-4 receptor; SABA=short-acting beta2 -agonist; LTRA=leukotriene receptor antagonist; BDP=beclomethasone dipropionate; HDM=house dust mite; SLIT=sublingual immunotherapy; FEV1 =forced expiratory volume in 1 second
© 2020 Global Initiative for Asthma, reprinted with permission. Available from www.ginasthma.org

For a Figure relating to children aged 6–11 years, see the GINA strategy document, Box 3-5B (p.55)

Figure 3 Selecting initial controller treatment in adults and adolescents with a diagnosis of asthma

Figure 3: Selecting initial controller treatment in adults and adolescents with a diagnosis of asthma3

OCS=oral corticosteroid; ICS=inhaled corticosteroid; LABA=long-acting beta2 -agonist; IgE=immunoglobulin-E; IL5=interleukin-5; IL4R=interleukin-4 receptor; SABA=short-acting beta2 -agonist; LTRA=leukotriene receptor antagonist; BDP=beclomethasone dipropionate; HDM=house dust mite; SLIT=sublingual immunotherapy; FEV1 =forced expiratory volume in 1 second
© 2020 Global Initiative for Asthma, reprinted with permission. Available from www.ginasthma.org

For a Figure relating to children aged 6–11 years, see the GINA strategy document, Box 3-4D (p.53)

Diagnosing asthma combined with COPD

One of the problems facing generalists caring for patients is to differentiate asthma from chronic obstructive pulmonary disease (COPD). The treatment for these two conditions is very different; asthma should always be treated with ICS, and conversely most people with COPD should be treated with bronchodilators. People with features of both asthma and COPD, so-called asthma and COPD overlap (ACO), are at increased risk of dying and their treatment must include ICS.3,19 Therefore it is essential that those with ACO are identified. To this end, the 2020 GINA update includes a rewritten section with a simplified figure summarising the approach to diagnosis and initial treatment of people with asthma and/or COPD (see Figure 4).3

Approach to initial treatment in patients with asthma and-or COPD

Figure 4: Approach to initial treatment in patients with asthma and/or COPD3

ICS=inhaled corticosteroid; LABA=long-acting beta2 -agonist; LAMA=long-acting muscarinic antagonist GOLD=Global Initiative for Chronic Obstructive Lung Disease
© 2020 Global Initiative for Asthma, reprinted with permission. Available from www.ginasthma.org

Difficult-to-treat and severe asthma

Severe asthma is defined as asthma that is uncontrolled despite adherence with maximal optimised therapy and treatment of contributory factors, or that worsens when high-dose treatment is decreased.20 About two-thirds of those who died from asthma in the NRAD5 were thought to have had mild to moderate asthma; however only about one-fifth had evidence of assessment of asthma control, and therefore assessment of the severity of these patients’ asthma is questionable. It is really important that general practitioners identify those patients who have severe asthma (about 3–5% of people with asthma), code them as such in the records (SNOMED-CT code 370221004), and refer them to a specialist severe asthma clinic. Neither of the two UK asthma guidelines focuses on severe asthma.2,21

In 2019, GINA published a booklet on diagnosis, investigations, and management in difficult-to-treat and severe asthma in primary, secondary, and tertiary care. This information has now been incorporated in the main GINA strategy document (Part E, p.94).3

Summary

This article summarises some of the key changes in the 2020 GINA recommendations. Healthcare professionals caring for people with asthma are urged to refer to the GINA material online, which includes the full strategy and summary booklets, podcasts, advice during the COVID-19 pandemic, and (hot off the press) the GINA Academy, which offers a suite of courses that are accredited for Continuing Medical Education (CME), with certificates for those attaining a pass mark.22

Dr Mark L Levy

Member GINA Board of Directors and of the Dissemination and Implementation Committee; Sessional GP, London; Clinical Lead National Review of Asthma Deaths (NRAD, 2011–2014)

COVID-19 considerations

  • During the COVID-19 pandemic, GINA made the following recommendations for the management of people with asthma (as of 3 April, 2020):3
    • advise patients with asthma to continue taking their prescribed asthma medications, particularly ICS, and OCS if prescribed
      • asthma medications should be continued as usual. Stopping ICS often leads to potentially dangerous worsening of asthma
      • for patients with severe asthma: continue biologic therapy, and do not suddenly stop OCS if prescribed
  • Make sure that all patients have a written asthma action plan with instructions about:
    • increasing controller and reliever medication when asthma worsens
    • taking a short course of OCS for severe asthma exacerbations
    • when to seek medical help
    • see the GINA 2020 report for more information about treatment options for asthma action plans
  • Avoid nebulisers where possible
    • nebulisers increase the risk of disseminating virus to other patients and to healthcare professionals
    • pressurised metered dose inhaler via a spacer is the preferred treatment during severe exacerbations, with a mouthpiece or tightly fitting face mask if required.

GINA=Global Initiative for Asthma; ICS=inhaled corticosteroid; ORS=oral corticosteroid

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.

  • Review the GINA strategy and identify how its advice differs from that provided by NICE and local guidelines
  • Establish a local multi-professional review group to examine the differences and adapt local recommendations
  • Update local formularies with their recommendations and run education programmes for primary care, with explanations for any changes to current practice
  • Encourage primary care to identify patients with severe asthma and refer them for specialist care
  • Support primary care to limit prescription of SABAs, including by identifying patients with asthma using high quantities of SABAs who may need a review of their asthma control
  • Ensure at asthma reviews that each patient has a written asthma plan (now required for the QOF AST007 indicator).

STP=sustainability and transformation partnership; ICS=integrated care system; GINA=Global Initiative for Asthma; SABA=short-acting beta2 -agonist; QOF=Quality and Outcomes Framework

Implementation actions for clinical pharmacists in general practice

written by Nipa Patel, Pharmacist Independent Prescriber, PCN Senior Pharmacist, Soar Beyond i2i Faculty member

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

  • Agree patient scope by identifying and reviewing:
    • adult asthma patients in the practice, and undertaking notes reviews for those who are receiving only SABA inhalers with a view to initiate ICS at the appropriate strength
    • patients with ACO and review them to ensure their treatment plan includes ICS
    • patients with severe asthma; ensure they are coded appropriately and refer them to specialist severe asthma clinics if they have not already been referred
  • Gain buy-in from the practice and establish who will manage asthma reviews and set accountabilities, e.g. PCN/GP pharmacist or nurse to undertake asthma reviews, including of inhaler technique and the PAAP 
  • Conduct preparations before seeing patients to ensure personal competence, for example:
    • familiarise yourself with relevant asthma guidelines 
    • understand your role in managing asthma, e.g. optimising treatment, demonstrating inhaler technique 
    • collate supporting resources for patients, e.g. from Rightbreathe, Asthma UK
    • know how to complete a PAAP 
    • know red flags and when to refer or escalate to GPs/colleagues
  • Deliver clinics and ensure that an agreed PAAP is put in place, with a date for reviewing asthma treatment as appropriate:
    • code all interventions
    • refer more complex cases to secondary care teams as appropriate
  • Evaluate your outcomes, for example by assessing the number of patients:
    • with asthma still receiving only SABA inhalers 
    • in whom ICS/formoterol has been initiated
    • with ACO that have ICS as part of their treatment regimen
    • with severe asthma that have been referred to specialist clinics.

If you have clinical pharmacists in your practice or organisation, contact Soar Beyond to see how we can support with their clinical delivery, training and development.

SABA=short-acting beta2 -agonist; ICS=inhaled corticosteroids; ACO=asthma–chronic obstructive pulmonary disease overlap; PCN=Primary Care Network; PAAP=personalised asthma action plans

References

  1. Reddel H, FitzGerald J, Bateman E et al. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J 2019; 53 (6): 1901046.
  2. NICE. Asthma: diagnosis, monitoring and chronic asthma management. NICE Guideline 80. NICE, 2017 (updated 2020). Available at: www.nice.org.uk/ng80
  3. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (2020 update). GINA, 2020. Available at: ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf
  4. Levy M. The national review of asthma deaths: what did we learn and what needs to change? Breathe (Sheff) 2015; 11 (1): 14–24.
  5. 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
  6. 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
  7. 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
  8. Dr Shirley Radcliffe. Regulation 28 Statement in the matter of Sophie Holman (deceased). 2019. Available at: www.judiciary.uk/wp-content/uploads/2019/05/Sophie-Holman-2019-0035_Redacted.pdf
  9. O’Byrne P, FitzGerald J, Bateman E et al. Inhaled combined budesonide–formoterol as needed in mild asthma. New Engl J Med 2018; 378 (20): 1865–1876.
  10. Bateman E, Reddel H, O’Byrne P et al. As-needed budesonide–formoterol versus maintenance budesonide in mild asthma. New Engl J Med 2018; 378 (20): 1877–1887.
  11. Beasley R, Holliday M, Reddel H et al. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med 2019; 380 (21): 2020–2030.
  12. Hardy J, Baggott C, Fingleton J et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial. Lancet 2019; 394 (10202): 919–928.
  13. Orion Pharma (UK) Limited. Fobumix Easyhaler 160 micrograms/4.5 micrograms, inhalation powder. Summary of product characteristics. www.medicines.org.uk/emc/product/8706/smpc
  14. Chiesi Limited. Fostair 100/6 micrograms per actuation pressurised inhalation solution. Summary of product characteristics. www.medicines.org.uk/emc/product/6318
  15. Chiesi Limited. Fostair NEXThaler 100 micrograms/6 micrograms per actuation inhalation powder. Summary of product characteristics. www.medicines.org.uk/emc/product/3317
  16. Teva Pharma B.V. DuoResp Spiromax 160 micrograms/4.5 micrograms inhalation powder. Summary of product characteristics. www.medicines.org.uk/emc/product/3323/smpc
  17. AstraZeneca UK Limited. Symbicort® Turbohaler® 100 micrograms/6 micrograms/inhalation, inhalation powder. Summary of product characteristics. www.medicines.org.uk/emc/product/1326
  18. AstraZeneca UK Limited. Symbicort® Turbohaler® 200 micrograms/6 micrograms/inhalation, inhalation powder. Summary of product characteristics. www.medicines.org.uk/emc/product/1327/smpc
  19. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2020 report). GOLD, 2020. Available at: goldcopd.org/wp-content/uploads/2019/12/GOLD-2020-FINAL-ver1.2-03Dec19_WMV.pdf
  20. Chung K, Wenzel S, Brozek J et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43 (2): 343–373.
  21. Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. SIGN 158. SIGN, 2019. Available at: www.sign.ac.uk/assets/sign158.pdf
  22. Global Initiative on Asthma (GINA) Academy. 2020. Available at: gina-academy.org