The 2023 GINA Strategy: Implications for Primary Care

Dr Kevin Gruffydd-Jones Compares the Latest International and UK Guidance on Asthma, Reviewing Recommendations on Diagnosis and Pharmacological Management

In 2022, asthma was estimated to affect 262 million people worldwide, with 6.6% of adults and 9.1% of children affected by asthma symptoms globally.¹ In the UK, more than 8 million people have been diagnosed with asthma, and over 5.4 million people are currently receiving treatment.² Consequently, asthma accounts for 2–3% of primary care consultations.²

The Global Initiative for Asthma (GINA) first produced a strategy report in 1995, and has updated it annually since 2002.³ This annual update separates the GINA report from asthma guidelines produced by NICE⁴ and by the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN),⁵ which were last significantly updated in 2021 and 2019, respectively.

Similar to the BTS/SIGN guideline, GINA’s recommendations are graded according to an expert review of the published literature supporting them.³ The highest grade (A) is given to recommendations that are based on a wealth of high-quality data, including randomised controlled trials and systematic reviews, and the lowest grading (D) is given to recommendations based on expert opinion.³ Unlike NICE, GINA does not look at the cost-effectiveness of interventions in its core methodology, instead recommending that cost-effectiveness should be assessed whenever an asthma programme is being planned at a local or national level.³ 

In comparison with the 2022 report, there are few significant changes in the 2023 GINA strategy.³ This article discusses the key recommendations for UK primary care.

Definition

GINA considers asthma to be ‘a heterogeneous disease, usually characterized by chronic airflow inflammation.’³ The report defines asthma by a ‘history of respiratory symptoms, such as wheeze, shortness of breath, chest tightness, and cough, that vary over time and in intensity, together with variable expiratory airflow limitation.’³

This definition highlights that people with asthma do not just exhibit the classic phenotype of allergic asthma with eosinophilic inflammation, which usually presents in childhood.³ They may instead present with another form of asthma, which can be nonatopic, present later in adulthood, or be associated with obesity, occupation, or another risk factor.³

Diagnosis

Regarding asthma diagnosis, the GINA strategy states: 'The diagnosis of asthma [in adults and children aged 6 years and over] is based on the history of characteristic symptom patterns and evidence of variable expiratory airflow limitation. This should be documented from bronchodilator reversibility testing or other tests.’³

When supporting a diagnosis with objective testing, GINA recommends first performing spirometry or peak expiratory flow measurements, with a reversibility test.³ If these tests are inconclusive, they can be repeated when the patient is symptomatic, or other tests, such as exercise or bronchial challenge tests, can be undertaken.³

To some extent, this diagnostic approach aligns with the BTS/SIGN and NICE guidelines, as a diagnosis is made on the basis of both objective testing and a structured clinical history and examination.^3–5 However, GINA prioritises different tests from the British guidelines (see Figure 1), as it considers airway hyper-reactivity and inflammation to be ‘not necessary or sufficient to make the diagnosis [of asthma]’, and so does not recommend testing their associated markers.³ Notably, the strategy advises against the use of fractional exhaled nitric oxide testing, which is favoured in the NICE guideline.^3,4

In addition, the cut-off points given for positive tests of airflow variability are different in the separate guidelines. See Table 1 for details. 

Figure 1: Diagnosis of Asthma in Adults, Young People, and Children Aged 6 Years and Over^3–5

Table 1: Positive Results for Airflow Variability Testing^3–5

Diagnosis for People Already Using Inhaled Corticosteroids

A new section in the 2023 strategy clarifies GINA’s advice on carrying out diagnostic spirometry in someone who is already taking inhaled corticosteroids (ICSs).³ Crucially, it is recommended that clinicians:³ 

• ensure that short-acting bronchodilator treatment has been stopped for at least 4 hours before diagnostic spirometry is undertaken, or at least 24 hours for twice-daily long-acting bronchodilator treatment and 36 hours for once-daily long-acting bronchodilator treatment (including in combination with an ICS)
• slowly reduce a patient’s ICS dosage by 25–50% if repeat spirometry is still negative, and review again after 2–4 weeks.

Children Aged 5 Years or Younger

In young children aged up to 5 years, it is extremely difficult to provide objective testing in primary care.³ Therefore, GINA recommends making a presumptive diagnosis of asthma based on a suggestive history, the presence of wheeze on normal examination, and a trial of ICS therapy.³ Features that are suggestive of asthma include:³

• recurrent episodes of cough, wheeze, or shortness of breath—these can occur upon exposure to triggers such as allergens, tobacco smoke, air pollution, or exercise, as well as when laughing or crying
• an absence of ‘red-flag’ symptoms that suggest an alternative diagnosis and require further investigation, such as failure to thrive, neonatal wheeze, or persistent wheeze
• past or family history of atopic disease, such as rhinitis or atopic dermatitis.

In younger people, a major differential diagnosis of asthma is viral-induced wheeze; however, in asthma, wheeze symptoms tend to be recurrent and occur with other triggers, such as exercise.³ 

If there is a high probability of asthma in a patient aged 5 years or younger, GINA recommends that a trial of ICSs should be given, in which the ICS—using a low dose, equivalent to 100 mcg beclometasone dipropionate per day (as opposed to NICE’s recommended 200–400 mcg/day)—is given to the patient for 8–12 weeks.^3,4 If the patient has a positive symptomatic response, the ICS should then be stopped, as the trial is only considered positive if there is a resumption of symptoms on cessation of therapy.³

Asthma Management

Preference for ICS–Formoterol Over an As-Needed SABA

A major change in asthma management was heralded by the 2019 update to the GINA strategy, when GINA announced that its reliever of choice would no longer be a short-acting beta₂ agonist (SABA), but an ICS–formoterol combination instead.^3,6 The rationale behind this change mainly concerns the relative safety of SABAs and other treatment options, as there is evidence that unopposed beta₂ agonists may actually be pro-inflammatory and increase the risk of exacerbations, emergency care, and mortality.^3,6–11 Notably, overuse of SABAs (three or more canisters per year) has been linked to an increased risk of asthma exacerbations and asthma-related deaths.⁷

In contrast, the long-acting beta₂ agonist (LABA) formoterol provides long-acting bronchodilation, but also has a rapid onset of action (2–3 minutes), and can therefore be used as reliever medication.^3,12 When LABAs are used in combination with ICSs, there is a suppression of inflammation, and thus a lessening of the risk of a severe exacerbation.³

GINA therefore recommends the use of as-needed anti-inflammatory reliever (AIR) therapy (in the form of an ICS and a fast-acting beta₂ agonist) as the sole therapy in mild asthma.³ This approach has been shown to reduce the risk of severe exacerbations compared with as-needed SABAs, both alone and in conjunction with regular low-dose ICSs.^3,13 In more severe asthma, GINA recommends regular maintenance and reliever therapy (MART) with ICS–formoterol,³ which has also been shown to reduce the risk of severe exacerbations compared with a combination of ICS–LABA maintenance therapy and an as-needed SABA as a reliever.¹⁴ 

Therapies in People Aged 12 Years and Older

Table 2 shows GINA’s therapeutic pathway for chronic asthma management in adults and young people aged 12 years and older.³ An alternative treatment pathway is also suggested for patients for whom this pathway is ineffective or inappropriate, which is similar to the traditional approach based on a regular ICS and an as-needed SABA that is recommended by BTS, SIGN, and NICE.^3–5 GINA emphasises that the goals of asthma management should be to maintain good symptom control and reduce the risks of future side effects, exacerbations, and death.³ Within GINA's therapeutic pathways, treatment can be stepped up or down according to level of asthma control (see the section Considerations When Escalating Therapy).³

Table 2: GINA’s Pharmacological Treatment Pathway for Asthma in Adults and Young People Aged 12 Years and Over³

Therapies in Children Aged 6–11 Years

The treatment pathway for children aged 6–11 years is illustrated in Table 3. There is a paucity of evidence regarding the use of AIR therapy in this cohort, and the GINA strategy instead recommends as-needed SABAs with low-dose ICSs for mild and moderate asthma (steps 1 and 2 of the treatment pathway).³ Clinicians should note that MART is not licensed for children aged under 12 years in the UK. As for preferred therapies in people aged 12 years and over, treatment can be stepped up or down according to level of asthma control (see the section Considerations When Escalating Therapy).³

Table 3: GINA’s Treatment Pathway for Children With Asthma Aged 6–11 Years³

Considerations When Escalating Therapy

Clinicians are advised to review their patients 1–3 months after starting treatment, then every 3–12 months after that.³ A step up in treatment may be advisable if, on review, a patient has persistent uncontrolled symptoms or exacerbations, but clinicians are advised to check the following before escalating therapy:³

• adherence to therapy
• inhaler technique
• whether symptoms are likely to be caused by asthma or something else
• whether there are any modifiable triggers (such as allergens, smoking, or occupation) or comorbidities (such as rhinitis or depression) that are affecting asthma management and can be addressed.

Stepping Down Therapy

Therapy can be escalated between steps, but can also be stepped down. In general, GINA recommends considering de-escalation of therapy once lung function reaches a plateau and asthma control has been achieved and maintained for 2–3 months.³

Considering the Environmental Impact of Inhalers in Shared Decision Making 

There has been an increasing interest in the environmental impact of inhalers, especially pressurised metered-dose inhalers. GINA has updated its strategy to include environmental considerations.³ In short, GINA acknowledges that it is important to consider the environmental impact of inhalers—in terms of propellants, manufacture, and the potential for recycling—but stresses that it is more important to choose an inhaler that the patient prefers and can use correctly.³ This is because the environmental effect of incorrect inhaler usage can be great as a result of the increased risk of emergency care and hospitalisation.³

Practical Use of AIR/MART Therapy 

The 2023 update to the GINA strategy also clarifies the recommended use of ICS–formoterol therapy when a patient’s asthma worsens, detailing how this can be incorporated into a patient’s action plan.³ After as-needed ICS–formoterol is taken, an additional dose of ICS–formoterol should be taken if there is no relief of symptoms after ‘a few minutes’, up to a daily maximum total of reliever and preventer of 12 doses of budesonide–formoterol 200/6 mcg (or eight doses of beclometasone–formoterol 100/6 mcg) in adults and young people aged 12 years and over.³ 

Patients should be advised to seek medical help if their symptoms are rapidly worsening or remain uncontrolled for 2–3 days.³ More urgent medical help is required if six inhalations of reliever medication are needed ‘in a short time’ (this recommendation applies specifically to budesonide–formoterol; in practical terms, this timeframe may be considered to be within 1–2 hours).¹⁵

Management Plans and Practical Guides

The updated strategy also signposts to a practical guide on implementing MART therapy—bit.ly/3rzXx5G.¹⁶ Sample and template management plans can be found on: 

• the Asthma + Lung UK website (bit.ly/46ZMvaq)¹⁷—this template includes consideration of MART
• the National Asthma Council Australia website (bit.ly/3XTfpoz)¹⁸—this template includes consideration of AIR therapy, but would need to be adapted for UK purposes.

Barriers to Implementation

In the UK, the principal barriers to implementation of the GINA recommendations are in the areas where there are significant discrepancies with BTS/SIGN and NICE guidance, as clinicians may prefer to follow the UK-specific guidance, and NICE considers cost-effectiveness when GINA does not.

Until recently, an additional barrier to implementation was the lack of a product licence for AIR therapy. However, in March 2023, the Medicines and Healthcare products Regulatory Agency licensed a budesonide–formoterol 200/6 mcg inhaler (Symbicort^®) to be used as a dual-combination reliever inhaler for mild asthma.^15,19

Summary

BTS, SIGN, and NICE are currently collaborating to produce a new asthma guideline, which is due to be published in 2024. This guideline, the first significant update to UK guidance since 2021, will hopefully provide greater clarification on asthma management in the UK. In the meantime, the yearly update to the GINA strategy remains a useful source of evidence-based, up-to-date guidance for primary care practitioners.