Introduction

The National Institute for Health and Clinical Excellence (NICE) launched the first joint Guideline for asthma diagnosis, monitoring and chronic asthma management with the Scottish Intercollegiate Guideline Network (SIGN) and British Thoracic Society (BTS)in November 20241. Prior to this date BTS/SIGN and NICE had produced separate guidelines with differing recommendations in some areas. This article compares the key areas of diagnosis and pharmacological management in the BTS/NICE/SIGN Guideline with the Global Initiative for Asthma (GINA) Strategy report 20242 and the implications for international primary respiratory care.

Methodology and scope

The GINA Strategy report was first produced in 1995, updated annually since 2002 and provides a comprehensive review of acute and chronic asthma across a range of severities. The 2024 NICE/BTS/SIGN Guideline, principally, as the title suggests, focuses on diagnosis, monitoring and chronic asthma management. It is important to note that management of acute and chronic severe asthma is excluded.

Updated relevant clinical evidence is reviewed by the GINA scientific committee (composed of respiratory interested physicians) based on criteria2 developed by the National Heart, Lung and Blood Institute in the USA. The BTS/NICE/SIGN Asthma Guideline Committee is composed of multidisciplinary members (such as primary and secondary care physicians, nurses and pharmacists) and includes patient members. Evidence is analysed and recommendations made using NICE methodology3 which significantly, in contrast to GINA, places additional emphasis on economic data, particularly cost-effectiveness. A critical value is the cost of an intervention expressed as the cost per Quality-adjusted life year (QALY) An intervention with a cost per-QALY of less than 20,000 pounds sterling (24,000 Euros) is considered as being cost-effective.

Diagnosis of asthma in adults, young people and children age 5–16 (BTS/NICE/SIGN) and in adults, adolescents and children age 6–11(GINA)

Both BTS/NICE/SIGN and GINA documents emphasise that a diagnosis of asthma should be made on basis of a characteristic history and confirmed by objective evidence. However their recommendations for objective testing differ significantly.

  • BTS/NICE/SIGN: Emphasises tests for eosinophilic airway inflammation such as Fractional Exhaled Nitric Oxide (FeNO), blood eosinophil counts and (in children) skin-prick testing.

  • GINA: Focuses on identifying variable expiratory airflow limitation, primarily using spirometry with bronchodilator reversibility2.

The recommended tests, criteria for positivity and recommended sequence of testing are shown in Fig. 1.

Fig. 1: Objective tests for asthma in primary care and diagnostic criteria.
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(in sequence if the previous test is negative).

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FeNO testing has moderate sensitivity (reflecting the number of false negative results) in children and adults and high specificity (reflecting a low number of false positive results)4. The order of diagnostic tests recommended by BTS/NICE/SIGN is largely based on economic analysis derived from United Kingdom costs. However, as pointed out in the GINA strategy document, the sensitivity of FENO is reduced in smokers1 and obese individuals. Also it has questionable utility in identifying non-eosinophilic asthma which may account for 48% adults with asthma5. Evidence regarding the diagnostic value of bronchodilator testing, particularly in children, remains surprisingly limited. The evidence shows that bronchodilator reversibility has high specificity, but low sensitivity in adults4. (for example may be normal when a patient is asymptomatic) Peak flow variability also shows low sensitivity, but has very high specificity and is readily available in primary care internationally.

Peak flow variability is defined as the mean daily variability of twice daily peak flow readings taken over a 2-week period. Daily variability is calculated as highest-lowest reading/mean daily reading x100%.

However, this method does rely on the reliability of patient readings and the mean variability is time-consuming to calculate manually in a short consultation. However, calculators are available on line which can significantly shorten the process. (https://www.asthmaandlung.org.uk/healthcare-professionals/adult-asthma/diagnosis-testing/perf-calc).

Pragmatically, but without evidence, both GINA and BTS/NICE/SIGN recognise that reversibility of peak expiratory flow rate (PEFR) post-bronchodilator ≥20% (>15% in children GINA) during an acute attack can be used as a confirmatory diagnostic test.

As highlighted, no single test serves as a “gold-standard” test for asthma diagnosis and in many parts of the world, including the United Kingdom, there are problems in accessing objective tests such as FeNO.

There is agreement that a diagnosis of asthma should be based on a characteristic history, exam and backed up by objective tests where possible. However, where access to objective tests is limited then a more pragmatic approach is needed. The International Primary Care Group(IPCRG) has produced a consensus document “The ‘jigsaw puzzle’ approach” to building a diagnostic picture of asthma in primary care over time6 which offers a pragmatic solution to the lack of universal availability of recommended tests. It emphasises that there is no one gold standard objective test and a diagnosis may not be able to made in a single consultation, but over time. In particular if an initial test is negative then it may need to be repeated when the patient is symptomatic. Methacholine challenge testing has high specificity and sensitivity, but is relatively patient unfriendly and not readily available in primary care.

It is good practice to record the basis of diagnosis in the medical records.

Diagnosis of asthma in children under 5 (BTS/NICE/SIGN) and under 6 (GINA) in primary care

It is generally accepted that a diagnosis of asthma in a young child is difficult and should be strictly questioned under the age of 2 when an alternative diagnosis is more likely.

A diagnosis of asthma is suggested by the presence of:

  • Characteristic variable symptoms of recurrent wheeze, breathlessness or cough with multiple triggers (other than just with viral infections), a family or past history of atopic disease, absence of symptoms to suggest an alternative diagnosis (e.g. failure to thrive).

  • A positive trial of Inhaled Corticosteroids (ICS).

    • ○ Beclometasone or equivalent7 to 50–100 mcg daily delivered standard aerosol particle metered -dose-inhaler(MDI)plus spacer with mask is given twice a day for 8–12 weeks. The ICS is then withdrawn.

    • ○ A trial is deemed positive if there is symptomatic improvement whilst the child is on the ICS and there is symptomatic worsening when the ICS is withdrawn.

If the child remains symptomatic and has not responded to the ICS then referral to a respiratory paediatrician is recommended.

The BTS/NICE/SIGN Guideline also recommends that any pre-school child with an admission to hospital or 2 or more admissions to an emergency department with wheeze within a 12- month period should be referred to a respiratory paediatrician and that objective tests are carried out when the child reaches the age of 5.

Pharmacological management in people with asthma age 12 and over

The 2019 GINA Strategy8 heralded a major shift in asthma management amongst concerns about the overuse of short-acting Beta -2 agonists increasing the risk of severe asthma exacerbations9.

A large-scale randomised controlled trial10 demonstrated the superiority of as-needed inhaled anti-inflammatory reliever(AIR)therapy using low-dose budesonide/formoterol in reducing asthma exacerbations compared to short-acting beta-2 agonists (SABA) alone. Similarly, a large real -world study11 showed that AIR therapy significantly reduced severe exacerbations compared to traditional ICS plus SABA reliever therapy. In patients with moderate asthma, regular maintenance and as-needed reliever therapy (MART) with budesonide/formoterol further reduced exacerbations compared to traditional therapy with maintenance ICS or ICS/long-acting beta-2 agonist (LABA) plus on-demand SABA12. As a result, GINA recommends a major shift in asthma management from maintenance ICS with SABA reliever therapy to ICS/formoterol as single reliever therapy (AIR) in mild asthma and as maintenance and reliever therapy(MART) in more symptomatic patients.

The BTS/NICE/SIGN Guideline group has also carried out an economic analysis of the interventions and has found that AIR and MART are “dominant” i.e. more effective and cost less, han corresponding SABA therapy alone or maintenance ICS or ICS/LABA plus SABA therapy.

This analysis gives major support by BTS/NICE/SIGN for the GINA recommendations and shows that AIR and MART therapy are not only effective,but also cost-effective. (albeit based on United Kingdom costs).

GINA and BTS/NICE/SIGN both recommend similar preferred management pathways and are shown in Fig. 2. Initial treatment should be commenced with AIR therapy if symptoms are relatively infrequent and with low or medium -dose MART if symptoms are more persistent, there is night waking or post-exacerbation, although the evidence for the efficacy of this treatment approach is relatively lacking.

Fig. 2: Preferred pharmacological management.
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Preferred pharmacological management of asthma in adults and adolescents (12 and over GINA)1 and adults and young people (12 and over BTS/NICE/SIGN)2.

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They both emphasise the need for checking factors such as adherence, inhaler technique, trigger factors and diagnosis before escalating therapy and also considering of stepping -down therapy when a patient is “stable’ (after 3 months-GINA).

However, there are some differences:

GINA recommends an alternative treatment pathway (“Track 2”) to AIR and MART therapies, based on the traditional maintenance ICS and SABA relief therapy. However there is no Track 2 in the NICE/BTS/SIGN guidance for people with asthma age 12 and over.

GINA does not recommend adding LTRA or LAMA to moderate-dose MART (≤ 800 mcg per day of Beclometasone or equivalent7 via DPI or standard-particle MDI before specialist referral. However, BTS/NICE/BTS suggest trying these options before referral unless FeNO is raised. (suggesting poor adherence with ICS or a need for additional anti-eosinophilic inflammatory drugs)

Overall the NICE/BTS/SIGN Guideline for management of asthma in people age 12 and over gives support for the GINA approach of single ICS/formoterol AIR and MART therapy as the core asthma treatment for chronic asthma management. However, this may not be applicable in lower economy countries where availability and cost of combination ICS/LABA inhalers may be problematic. In these case GINA’s alternative treatment pathway centred around maintenance ICS and relief SABA use may be more relevant.

The recommended pharmacological management by GINA and BTS/NICE/SIGN is shown in Fig. 3. The GINA approach is always to use inhaled corticosteroids in addition to bronchodilator when the child is symptomatic, progressing to regular ICS and SABA as needed and MART with increased asthma severity. The BTS/NICE/SIGN approach advocates regular ICS and SABA as-needed for mild asthma progressing to MART therapy. Both strategies recommend low-dose MART therapy as an initial treatment for highly symptomatic children.

Fig. 3: Preferred pharmacological management.
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Preferred pharmacological management of asthma in children age 6–11(GINA)2 and children age5–11(NICE/BTS/SIGN)1.

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There are limited studies on the use of MART in this age group13 although an economic analysis was carried out by NICE which shows that MART therapy is cost-effective. At the time of writing (December 2024) MART is not licensed for younger children in the United Kingdom. In view of the concerns about the effects of SABA therapy without concomitant ICS in adults the GINA approach of always giving a form of ICS (either separately or in combination with bronchodilator) with relief medication does seem sensible although evidence to support this is limited14

Summary

The GINA Strategy 2024 and BTS/NICE/SIGN Guideline for asthma 2024 both emphasise the importance of making a diagnosis of asthma in school-age children, young people and adults on the basis of a characteristic history, confirmed by objective tests. BTS/NICE/SIGN place an emphasis on markers of eosinophilic inflammation such as FeNO and blood eosinophil levels whilst GINA emphasises the use of tests of reversible expiratory flow. None of these tests has both high sensitivity and specificity and repeat testing or testing by a different method may be needed. In areas where access to objective tests is restricted the IPCRG “jigsaw puzzle” approach can be particularly helpful.

In children age 5–12 with asthma there is a diminishing role of SABA alone as reliever therapy and an emerging role for MART.

Clinical and economic evidence reviewed by BTS/NICE/SIGN has added further weight to the GINA recommendation that single inhaler ICS/Formoterol on an as needed basis (AIR) and as maintenance and reliever therapy (MART) is now the cornerstone. of pharmacological asthma management in adults and young people 12 and over.