Dr Mark L Levy highlights updated recommendations on asthma management from the 2021 Global Initiative for Asthma report

Levy mark

Dr Mark L Levy

Read this article to learn more about:

  • clarification on the definition of severe asthma
  • the importance of a personalised management approach
  • treatment tracks for adults and adolescents, and steps for children aged 6–11 years and 5 years and younger.

Implementation actions for STPs and ICSs

This article focuses on the 2021 update of the Global Initiative for Asthma (GINA) report and recommendations.1 The main changes include:

  • clarification on the definition of severe asthma
  • revision of the treatment figures for adults and children
  • recommendation for primary prevention in children
  • updated advice for managing asthma during the COVID-19 pandemic.

Some of these changes are described in detail in this article; however, readers are advised to refer to the materials and documents on the GINA website (www.ginasthma.org).

Asthma is a global problem—in 2019, asthma affected more than 250 million people and caused nearly half a million deaths.2 GINA is an independent organisation, funded solely by the sale and licensing of its reports and figures. It was established by the World Health Organization and the National Heart, Lung, and Blood Institute in 1993. It aims to increase awareness about asthma, and to improve asthma prevention and management through a coordinated worldwide effort.

The annually updated GINA report is a global, evidence-based strategy that is downloaded each year by clinicians in at least 100 countries. The strategy can be adapted for local use, and the 2019 recommendations have been adopted by at least 35 countries. The recommendations are updated following an extensive literature search and detailed review of asthma research publications. In contrast with UK guidelines, the recommendations are not framed as answers to specific, isolated, PICOT (patient, intervention, comparison, outcome, and time) questions. On the website (www.ginasthma.org), in addition to the main strategy, there is a shorter booklet, as well as timely news bulletins, podcasts, videos, a course on asthma, and other useful, practical information.

The UK has been the subject of reports detailing the failure to care for people with asthma: it has the fifth worst record among comparable countries for asthma deaths in people aged 5–34 years.3 The Healthcare Safety Investigation Branch report on the management of asthma in children aged 16 years and younger4 and the All-Party Parliamentary Group for Respiratory Health inquiry into asthma outcomes in the UK5 called for implementation of the outstanding 18 recommendations published in the National Review of Asthma Deaths (NRAD).6 Similarly, at least four coroners’ regulation 28 reports to prevent asthma deaths have called for national action to improve asthma outcomes, including reduction of preventable deaths.7–10

The UK has two contradictory sets of asthma guidelines,11,12 which are updated every 3–5 years. In contrast with GINA, the process for updating these guidelines is focused on specific questions rather than an overarching review of all asthma research literature.

Clarification on the definition of severe asthma

In the UK, treating people with severe asthma accounts for a substantial proportion of the cost of asthma treatment. Two key issues underlie the inadequate care provided to people with asthma: failure to diagnose asthma severity—that is, as mild, moderate, or severe; and failure to refer patients with severe or difficult-to-control asthma to respiratory specialists for assessment and treatment advice. In my experience of auditing clinical records, which mirrors findings in the NRAD,6 severity is hardly ever recorded. Bloom et al. reported that a minority of people with high-risk asthma in the UK were referred to specialists.13

In the 2021 report, GINA has clarified the definition of severe asthma:1Severe asthma is asthma that is uncontrolled despite high dose inhaled corticosteroids (ICS)-long-acting beta2-agonist (LABA), or that requires high dose ICS-LABA to remain controlled.’

Most importantly, asthma severity should not be simply imputed from prescribed treatment without considering control.1 Furthermore, asthma control has been defined by GINA for many years in two domains: symptoms, for example, as assessed using the Asthma Control Test; and previous attacks and other risk factors for future attacks.1 So, even if a patient has no current symptoms during a review, a history of a serious exacerbation/attack requiring hospitalisation in the previous 12 months would classify the person’s asthma as uncontrolled.

Management of asthma

The GINA ‘assess, adjust, and review’ infographic (see Figure 1)1 summarises the processes involved in an asthma review: confirmation of the diagnosis; identification of modifiable risk factors and assessment of inhaler technique; and ensuring that the patient’s preferences and goals are considered. The continuous cycle ensures that treatment is adjusted accordingly and that timely reviews are performed to establish its efficacy and if there is a need for change.

GINA 2021 Figure 1

Figure 1: GINA assess, adjust, and review management cycle for personalised asthma management1

Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf Reproduced with permission.

Unfortunately, in the UK—largely due to the Quality and Outcomes Framework—many clinicians simply perform an annual ‘tick-box’ review of their patients with asthma. As a result, opportunities to identify modifiable risk factors following attacks, for example, are missed. In essence, the point is that the management of asthma is not limited to drug prescription and is not ‘one size fits all’.

Pharmacological treatment

GINA made a fundamental change to its recommendations for the pharmacological treatment of asthma in 2019.14 GINA no longer recommends regular use of short-acting beta2 -agonists (SABAs) for people diagnosed with asthma; they should all be prescribed ICSs, either regularly or as needed for respiratory symptoms. This is a risk-reduction strategy aimed at reducing the probability of serious untoward outcomes at a population level.

Following some colleagues’ confused perception of the 2019–2020 updates, the treatment figures for adults and adolescents over the age of 12 years have been revised (see Figure 2). Based on the recommended reliever medication, this now takes the form of two tracks. The reliever preferred by GINA in track 1 is an ICS in combination with formoterol, whereas in track 2, the alternative reliever is a SABA—for example, salbutamol or terbutaline.1

GINA 2021 Figure 2

Figure 2: Personalised asthma management for adults and adolescents aged 12 years and older1

ICS=inhaled corticosteroid; SABA=short-acting beta2 -agonist; LAMA=long-acting muscarinic antagonist; IgE=immunoglobulin-E; IL5=interleukin-5; IL5R=interleukin-5 receptor; IL4R=interleukin-4 receptor; LABA=long-acting beta2 -agonist; LTRA=leukotriene receptor antagonist; HDM=house dust mite; SLIT=sublingual immunotherapy; OCS=oral corticosteroid

Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf Reproduced with permission.

Track 1: controller and preferred reliever

In track 1, GINA has recommended an ICS-formoterol as the reliever and the drug of choice, with increasing regularity (maintenance) and doses of ICS across the steps. Formoterol is a rapid-onset LABA: it takes effect within 1–3 minutes and lasts about 12 hours. The ICS-formoterol is taken whenever the person has respiratory symptoms; help should be sought if there is no relief or if the maximum number of daily doses specified by the manufacturer is reached. The clear advantage of taking this ICS-formoterol combination for relief is that the patient gets more doses of ICS, which have the capacity to prevent worsening of an asthma attack, while at the same time providing the immediate relief afforded by bronchodilation.

There is considerable evidence supporting the recommendation for as-needed use of an ICS-formoterol at step 2 compared with a SABA alone, with reduction of severe exacerbations by approximately half to two-thirds,15,16 non-inferiority compared with maintenance low-dose ICS with as-needed SABA,15,17 and superiority with regard to severe exacerbations in two open-label randomised controlled trials.16,18 Furthermore, the ICS dose taken as needed by patients in these trials compared with regular maintenance use was 17–75% lower.15,17

Further support for this approach at step 2 is that severe exacerbations (and deaths) can occur even in patients with mild asthma;6,19 ICSs are highly effective, but patients are often poorly adherent;20 and even occasional short courses of oral corticosteroids are associated with increased risk of adverse outcomes, such as cataracts and osteoporosis.21 It is clearly best to prevent these exacerbations in the first place.

The evidence for using an as-needed ICS-formoterol rather than a SABA at step 1 is inferred from the trials with step 2 patients in whom, for example, the combination was significantly superior in preventing severe and moderate attacks.15 In addition, there is no evidence for safety or efficacy of a SABA alone in asthma; patients with mild asthma are at risk of poor outcomes, including death; and there is considerable evidence that regular use of, and excess prescriptions for, salbutamol are associated with increased unscheduled care for asthma attacks and deaths.22–24

At steps 3–5, regular use of an ICS-formoterol is recommended, together with an as-needed low-dose ICS-formoterol—that is, maintenance and reliever therapy (MART)—with increasing doses of ICS rather than adding another drug. At step 5, GINA recommends continuing an ICS-formoterol because of the potential risk of exacerbations if patients are changed to an ICS-LABA with a SABA for relief. At step 5, where referral to a specialist is recommended, there are options for adding a long-acting muscarinic antagonist (LAMA).

Track 2: controller and alternative reliever

In track 2, a SABA is the reliever drug taken for respiratory symptoms. Before deciding to prescribe according to track 2, the likelihood that the patient will adhere to a regimen requiring a regular maintenance ICS or an ICS-LABA should be considered; if it is thought unlikely, the patient may rely only on their SABA with the risks as described above.

At step 1, an ICS is recommended whenever a patient takes their SABA for reasons similar to those stated above, and at steps 2–5, the recommendation is for increasing doses of the ICS in combination with one of the LABAs, with an as-needed SABA for relief. Warn patients that the SABA is only effective for 4 hours and, if no relief is afforded by its use or relief does not last 4 hours, medical assistance should be sought urgently. At step 5, where referral to a specialist is recommended, there are options for adding a LAMA either separately or in a combination triple inhaler.

The recommendations for initial treatment steps in newly diagnosed patients are shown in Figure 3.

GINA 2021 Figure 3

Figure 3: Starting treatment in adults and adolescents with a diagnosis of asthma1

For recommendations about initial asthma treatment in adults and adolescents, see Boxes 3-4A and 3-4B of the GINA report at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf

ICS=inhaled corticosteroid; SABA=short-acting beta2 -agonist; LAMA=long-acting muscarinic antagonist; OCS=oral corticosteroids; IgE=immunoglobulin-E; IL5=interleukin-5; IL5R=interleukin-5 receptor; IL4R=interleukin-4 receptor; LABA=long-acting beta2 -agonist

Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf Reproduced with permission.

Children aged 6–11 years

In children aged 6–11 years, the figures have been slightly modified in keeping with the text in the document, which is unchanged (see Figures 4 and 5). At step 1, where children have symptoms less than twice a month, taking an ICS whenever a SABA is used is the preferred option. At steps 2–4, increasing doses of a daily ICS are preferred, with the option of changing to MART at steps 3 and 4 (as in the NICE guideline).11 Referral to a specialist is recommended at step 4, where the child is prescribed a medium-dose ICS-LABA or low-dose ICS-formoterol MART.

GINA 2021 Figure 4

Figure 4: Treatment for children aged 6–11 years1

For initial asthma treatment in children aged 6–11 years, see Boxes 3-4C and 3-4D of the GINA report at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf

ICS=inhaled corticosteroid; SABA=short-acting beta2 -agonist; LABA=long-acting beta2 -agonist; IgE=immunoglobulin-E; IL5=interleukin-5; OCS=oral corticosteroids; BUD-FORM=budesonide-formoterol

Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf Reproduced with permission.

GINA 2021 Figure 4b

Figure 5: Starting treatment in children aged 6–11 years with a diagnosis of asthma1

For initial asthma treatment in children aged 6–11 years, see Boxes 3-4C and 3-4D of the GINA report at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf

ICS=inhaled corticosteroid; SABA=short-acting beta2 -agonist; LABA=long-acting beta2 -agonist; IgE=immunoglobulin-E; OCS=oral corticosteroids; IL5=interleukin-5; BUD-FORM=budesonide-formoterol

Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf Reproduced with permission.

Children aged 5 years and younger

It is important to consider the risks of both under- and overtreatment in children aged 5 years and younger; therefore, diagnosis is important. A child experiencing repeated episodes (at least three per year) of wheezing, irrespective of triggers—including so-called ‘viral-associated wheeze’—should be suspected to have asthma, which should be recorded. Once asthma is confirmed, which may require specialist input, the recommended treatment is shown in Figure 6. Preferred medication in these children is a low-dose ICS at steps 2–4, with specialist referral at step 4.1

GINA 2021 Figure 5

Figure 6: Treatment for children aged 5 years and younger1

For initial asthma treatment in children aged 6–11 years, see Boxes 3-4C and 3-4D of the GINA report at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf

ICS=inhaled corticosteroid; SABA=short-acting beta2 -agonist

Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf Reproduced with permission.

Other new recommendations

Other new recommendations include: primary prevention of early life asthma by identifying and treating vitamin D insufficiency in women with asthma who are pregnant or planning pregnancy; checking eosinophils repeatedly if low at initial assessment in patients with severe asthma, as this may affect eligibility for biologic therapy; new criteria for biologic therapy indications; and LABA-withholding advice for spirometry testing.1

Readers are advised to refer to the full document or summary booklet at www.ginasthma.org. In addition, the tables detailing low, medium, and high dosages of inhaled steroids should be consulted in both the GINA1 and SIGN12 documents.

In this author’s opinion, the UK’s poor asthma outcomes could be substantially improved if the recent fundamental GINA recommendations were implemented. This is the case in several other countries, many of whom have a better record in caring for their asthma populations.

Dr Mark L Levy FRCGP

Member GINA Board of Directors; part-time GP and appraiser, London

Note: At the time of publication (June 2021), some of the drugs discussed in this article did not have UK marketing authorisation for the indications discussed. Prescribers should refer to the individual summaries of product characteristics for further information and recommendations regarding the use of pharmacological therapies. For off-licence use of medicines, the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Good practice in prescribing and managing medicines and devices for further information.

Declaration of interests

For 2018–2021, Dr Levy reports, consultancy fees for Novartis, AstraZeneca, GlaxoSmithKline, Orion Pharmaceuticals, Menarini, National Services for Health Improvement, TEVA, and Chiesi; lecture fees for TEVA, Novartis, Orion, AstraZeneca, NAPP, Chiesi; travel expenses and accommodation as a GINA Board and Dissemination Committee member; member of the Honoraria ADMIT Group (www.inhalers4u.org)—Consorzio Ferrara Richerche

Want to learn more about this guideline?

GLNs G Logo small

Read the related Guidelines summary

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 in implementing new guidance at a system level. Our aim is to help you to consider how to deliver improvements to healthcare within the available resources.

  • Establish a multiprofessional team to review and update current local asthma guidelines, drawing from the 2021 GINA report and UK guidance
  • Publish clear local pathways for the diagnosis of asthma, detailing which diagnostic tests are required and possible during the COVID-19 outbreak
  • Update local formularies with the new regimens and algorithms for treatment, placing ICS/LABA combination treatment at step 1,, in line with the 2021 GINA report
  • Plan and initiate an education campaign aimed at GPs and practice nurses encouraging them to assess severity in annual asthma reviews as required by the QOF, and review all patients after hospital admission
  • Make clear the indications for referral to a specialist, and ensure such referrals are responded to promptly.

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

References

  1. Global Initiative for Asthma. Global strategy for asthma management and prevention (2021 update). Fontana, WI, USA: GINA, 2021. Available at: ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
  2. World Health Organization. Asthma. www.who.int/news-room/fact-sheets/detail/asthma (accessed 20 May 2021).
  3. Global Asthma Network. The Global Asthma Report 2018. Auckland, New Zealand: Global Asthma Network, 2018. Available from: globalasthmareport.org/Global%20Asthma%20Report%202018.pdf
  4. Healthcare Safety Investigation Branch. Management of chronic asthma in children aged 16 years and under. Farnborough: HSIB, 2021. Available at: www.hsib.org.uk/investigations-cases/management-chronic-asthma-children-aged-16-years-and-under
  5. All-Party Parliamentary Group for Respiratory Health. Improving asthma outcomes in the UK. London: APPG for Respiratory Health, 2020. Available at: www.ed.ac.uk/files/atoms/files/appg-asthma-report-2020.pdf
  6. Royal College of Physicians. Why asthma still kills: the National Review of Asthma Deaths (NRAD) Confidential Enquiry report. London: RCP, 2014. Available at: www.rcplondon.ac.uk/sites/default/files/why-asthma-still-kills-full-report.pdf
  7. Carney T. Regulation 28—report to prevent future deaths. London: Office of the Chief Coroner, 2015. Available at: www.judiciary.uk/wp-content/uploads/2016/01/Mills-2015-0416.pdf
  8. Radcliffe S. Regulation 28—report to prevent future deaths. London: Office of the Chief Coroner, 2017. Available at: www.judiciary.uk/wp-content/uploads/2017/03/Uriely-2017-0069_Redacted.pdf
  9. Radcliffe S. Regulation 28—report to prevent future deaths. London: Office of the Chief Coroner, 2019. Available at: www.judiciary.uk/wp-content/uploads/2019/05/Sophie-Holman-2019-0035_Redacted.pdf
  10. Persaud N. Regulation 28—report to prevent future deaths. London: Office of the Chief Coroner, 2020. Available at: www.judiciary.uk/wp-content/uploads/2021/01/Kalila-Griffiths-2020-0299_Redacted.pdf
  11. NICE. Asthma: diagnosis, monitoring and chronic asthma management. NICE Guideline 80. NICE, 2017 (updated 2021). Available at: www.nice.org.uk/ng80
  12. Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. SIGN 158. Edinburgh: SIGN, 2019. Available at: www.sign.ac.uk/media/1773/sign158-updated.pdf
  13. Bloom C, Walker S, Quint J. Inadequate specialist care referrals for high-risk asthma patients in the UK: an adult population-based cohort 2006–2017. J Asthma 2021; 58 (1): 19–25.
  14. Reddel H, FitzGerald J, Bateman E et al. GINA 2019: a fundamental change in asthma management. Eur Respir J 2019; 53 (6): 1901046.
  15. O’Byrne P, FitzGerald J, Bateman E et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med 2018; 378 (20): 1865–1876.
  16. 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.
  17. Bateman E, Reddel H, O’Byrne P et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med 2018; 378 (20): 1877–1887.
  18. 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.
  19. Dusser D, Montani D, Chanez P et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations. Allergy 2007; 62 (6): 591–604.
  20. Bender B, Pedan A, Varasteh L. Adherence and persistence with fluticasone propionate/salmeterol combination therapy. J Allergy Clin Immunol 2006; 118 (4): 899–904.
  21. Price D, Trudo F, Voorham J et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy 2018; 11: 193–204.
  22. Nwaru B, Ekström M, Hasvold P et al. Overuse of short-acting β2 -agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J 2020; 55 (4): 1901872.
  23. Bloom C, Cabrera C, Arnetorp S et al. Asthma-related health outcomes associated with short-acting β2 -agonist inhaler use: an observational UK study as part of the SABINA global program. Adv Ther 2020; 37 (10): 4190–4208.
  24. Suissa S, Blais L, Ernst P. Patterns of increasing β-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J 1994; 7 (9): 1602–1609.