Gain Effective Control of Mild Asthma to Avoid Fatal Exacerbations

Dr Mark L Levy Explores the Updated Recommendations of the 2022 Global Initiative for Asthma Strategy on the Management and Prevention of Asthma

The Global Initiative for Asthma (GINA) was established by the World Health Organization and the National Heart, Lung, and Blood Institute in 1993 to improve the awareness, prevention, and management of asthma worldwide.¹ The GINA strategy report is a global document that can be adapted for local health systems according to locally available medicines and resources;² over 500,000 copies of the report are downloaded each year in more than 100 countries. The strategy is focused on practical implementation, and includes multiple flowcharts and tables. Alongside this, the GINA website (ginasthma.org) provides educational materials, such as regularly updated podcasts. Unlike some guideline documents that are revised infrequently, GINA is updated annually following a cumulative review of new evidence, and the strategy report undergoes extensive external review by end-users and stakeholders before publication.

In this article, I discuss some of the key changes in the 2022 update. Readers interested in the evidence and rationale underpinning the recommendations may wish to access the full document and its appendix for more background, as well as the executive summary published in 2021.^2,3

Identification and Diagnosis of Asthma

In the 2022 GINA strategy report, the section on diagnosis has been updated as a result of feedback stating that the approach to diagnosis should depend on whether the patient has already been prescribed a controller treatment.²

Asthma is a clinical diagnosis based on a combination of a detailed medical history of respiratory symptoms that vary over time and in intensity, and evidence of variable airflow limitation.² Family history of asthma and response to treatment can also be informative.² There is no single test for diagnosing asthma.

Although asthma is a condition characterised by inflammation, the diagnosis cannot be reliably ruled in or out using inflammatory markers alone, such as fractional exhaled nitrous oxide (FeNO) or raised blood eosinophil count.^2,4 This is because inflammatory markers can be elevated in conditions other than asthma, and are not elevated in all asthma phenotypes.² Therefore, although inflammatory markers are useful for monitoring medication adherence, assessing response to treatment, and choosing biologic treatments in those with severe asthma, they should not be relied upon alone in the new asthma diagnosis clinics that have been set up in the UK.

In the UK, great emphasis has been placed on FeNO testing for ‘diagnosis’ of asthma in severe asthma clinics.⁵ FeNO is not a diagnostic test for asthma, although elevated FeNO in exhaled breath, like raised blood eosinophil count, can identify the presence of type 2 inflammation.² GINA emphasises that, because test results for type 2 inflammation fluctuate considerably, they should be repeated up to three times at least 1–2 weeks after discontinuing oral corticosteroids (OCSs) or on the lowest possible OCS doses.²

Use Lung Function Testing to Support a Diagnosis of Asthma Whenever Possible

Spirometry-based testing should be used to identify variable airflow limitation if available;² however, the results may often be normal when testing asymptomatic patients. To avoid inaccurate diagnosis of airflow limitation, the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network guidance recommends use of the lower limit of normal when interpreting spirometry findings, rather than an arbitrary fixed forced expiratory volume in 1 second (FEV₁):forced vital capacity (FVC) ratio of 70%.^2,6 In addition, the normal FEV₁:FVC ratio can be a lot higher in children than in adults,⁶ so use of the fixed ratio may considerably underestimate diagnosis and/or the risk of an attack.

Clinicians should also be aware that, although in-line filters markedly reduce the risk of viral transmission in people undergoing spirometry, COVID-19 and other viruses may be transmitted when patients cough during the procedure, so adequate precautions are still required.²

In my experience as a GP, peak expiratory flow (PEF) is extremely useful and practical in primary care, where access to spirometry may be limited and where airflow limitation or reversibility is not always demonstrated during a consultation. Twice-daily PEF recordings with a variability greater than 10% in adults and greater than 13% in children support a diagnosis of variable airflow limitation (see the diagnostic criteria in Box 1-2 in the GINA strategy).² A significant improvement in lung function and PEF results from baseline after 4 weeks of anti-inflammatory treatment also supports a diagnosis of asthma.²

Confirm the Diagnosis Before Initiating Treatment Whenever Possible

Because many patients are initiated on asthma treatment before the diagnosis has been confirmed and because many of these individuals will not be offered reviews,⁷ GINA has updated its advice on confirming a diagnosis of asthma in people already started on medication. In summary, the new recommendations are as follows: confirm the diagnosis if there is evidence of variation in symptoms over time and in intensity, and of variable airflow limitation.² If not, and there are symptoms but no evidence of variable airflow limitation, try repeating lung function testing after withholding bronchodilators before testing, or consider stepping treatment down and retesting.² If there are few symptoms and no variability in lung function, try stepping down and retesting; finally, if symptoms and airflow limitation persist, refer for expert opinion (for the full recommendations, refer to Box 1-3 of the GINA strategy).²

Effective Treatment of Asthma

Treat With an ICS, Either Regularly or as Needed, in All People Diagnosed With Asthma

Two major misconceptions are that people with so-called ‘mild’ asthma are at low risk of severe exacerbations, and that a short-acting beta₂ agonist (SABA) is an effective treatment for chronic asthma.² In fact, patients with mild asthma can have severe or fatal exacerbations,^2,8,9 and almost two-thirds of those who died from asthma in the UK in 2012 were treated with BTS step 1–3 medications.¹⁰

The risk of severe exacerbations in people with so-called mild asthma is substantially reduced by use of inhaled corticosteroid (ICS)-containing treatment,^11,12 particularly compared with use of a SABA alone.¹³ Conversely, it has been suggested that regular use of SABAs for asthma is associated with deterioration in asthma control and increased inflammation,^14,15 an elevated risk of exacerbations and greater unscheduled utilisation of healthcare,^16,17 and increased asthma deaths.^16,18 In my view, SABAs should only be used in asthma for temporary relief of symptoms and in emergencies to relieve bronchospasm; therefore, someone with well-controlled asthma should not need more than one SABA inhaler a year.

Adherence

Although regular use of ICSs is effective in reducing attacks,^11,12 many people do not adhere to their regular treatment regimen;¹⁹ thus, a new approach for managing asthma is clearly needed.

There is now strong evidence that ‘as-needed’ ICS-formoterol treatment for the relief of symptoms of mild asthma reduces severe attacks more effectively than use of an as-needed SABA.^20–22 Compared with regular use of an ICS alone, the risk of severe exacerbations was similar^22,23 or lower²⁰ with as-needed ICS-formoterol therapy; furthermore, as-needed ICS-formoterol treatment was more effective at preventing severe exacerbations than a low-dose ICS plus an as-needed SABA.²⁴ This evidence underpins the groundbreaking GINA recommendation that as-needed ICS-formoterol therapy is the preferred treatment for adults and adolescents with mild asthma, and that ICS-formoterol should be used instead of salbutamol for symptom relief (for boxes summarising these recommendations, see chapter 3 of the GINA strategy).² Please note that as-needed ICS-formoterol therapy is not licensed for this indication in the UK, although at least one integrated care system has now included this in its adult asthma guideline based on the evidence.²⁵

Use an ICS Whenever a SABA is Taken in Children Aged 6–11 years

In children aged 6–11 years, GINA continues to recommend that an ICS is taken whenever a SABA is used for symptom relief in step 1.^2,26,27 GINA has updated the chronic treatment figure (Box 3-4Di in the GINA strategy) to include ‘other controller options’, such as leukotriene receptor antagonists (LTRAs) in step 2, a low-dose ICS plus an LTRA in step 3, and add-on tiotropium or an LTRA in step 4.² These ‘other’ therapies have limited indications, or less evidence about efficacy and/or safety, than the ‘preferred ICS controller’ for daily treatment in step 2, maintenance and reliever therapy²⁸ in steps 3 and 4, and referral to a specialist in step 4 if asthma remains uncontrolled and in step 5 for phenotypic assessment.²

Difficult-to-treat and Severe Asthma

Approximately 3–10% of people with asthma have severe asthma.² Severe asthma has physical, mental, emotional, social, and economic consequences for patients, and is often associated with multimorbidity.² Extracts from GINA’s definitions of difficult-to-treat and severe asthma are provided in Table 1.²

Following feedback, GINA has upgraded its advice on the management of severe asthma by increasing the size of the stand-alone difficult-to-treat and severe asthma guide (ginasthma.org/severeasthma/), which encompasses management across primary and specialist care.

Table 1: Definitions of Different Severities of Asthma²

GINA recommends that modifiable risk factors should be optimised in patients with difficult-to-treat asthma, and that those whose asthma does not respond or who have suspected severe asthma should be referred for expert advice.² Most patients with difficult-to-treat asthma can be successfully treated in primary care following diligent identification and management of modifiable risk factors (including excess SABA use, insufficient ICS use, poor inhaler technique, and poor adherence—see Box 2-2 in the GINA strategy for the full list),² but those with suspected severe asthma (whose asthma fails to respond despite correct inhaler technique and good adherence to step 4 treatment) should be referred to a specialist service for further investigation and management,² possibly with biologic medications (monoclonal antibodies for severe asthma).

Of note, the specialist section details the investigations needed to exclude conditions associated with raised blood eosinophil count that may be inappropriately treated as asthma—such as Strongyloides infection or eosinophilic granulomatosis with polyangiitis (formerly called Churg–Strauss syndrome).²

Asthma and COVID-19

The 2022 update also includes guidance about COVID-19 and asthma; notably, new evidence confirms that patients with well-controlled, mild-to-moderate asthma are not at increased risk of severe COVID-19, and that the risk is higher in patients requiring OCSs and in hospitalised patients with severe asthma.² Therefore, it’s important to ensure that there is appropriate monitoring and education by trained individuals for these patients, to maintain control and reduce attacks through optimisation of care.

Summary

The GINA strategy report is updated annually based on new evidence. In 2022, this evidence supports the inclusion of a new recommendation favouring as-needed ICS-formoterol therapy for mild asthma instead of a SABA. Excess SABA reliever prescribing is a major problem in the UK, and has been implicated in the high rate of preventable deaths and utilisation of unscheduled care. Implementation of GINA’s evidence-based recommendations for the management of mild asthma may improve asthma control and, in turn, reduce unscheduled care and preventable deaths in the UK.

Dr Mark L Levy FRCGP

Locum GP, London; Board Member and Chair Dissemination and Implementation Task Group, GINA