Hugo Andres Farne, Ernie Hoi Cheung Wong
Abstract
The diagnostic criteria for asthma, and its management, are evolving. This article, to accompany the more detailed 2023 review, focuses on recent updates, particularly the recommendation that the treatment regimen for all patients with asthma include an inhaled corticosteroid (ICS). In individuals with a low symptom burden (‘mild asthma’), initial treatment should be with a combination inhaler containing an ICS and formoterol, a fast-acting β-adrenoceptor agonist, used on an as required basis. A major change is that salbutamol should no longer be prescribed as monotherapy. To put it another way, all types of symptomatic asthma should be on treatment including an ICS, as an anti-inflammatory reliever or for maintenance therapy. Other notable updates include: (1) the use of the blood eosinophil count and/or fractional exhaled nitric oxide (FeNO) testing to assess for eosinophilic airways inflammation and aid diagnosis; (2) the addition of tezepelumab as a biologic treatment for severe asthma, which uniquely can be prescribed to patients without evidence of ‘type 2’ inflammation (raised blood eosinophils and/or FeNO); (3) guidance when choosing an asthma biologic given the lack of head-to-head trials; (4) guidance on the use of biologics in pregnancy; and (5) updated thoughts on future developments.
Keywords
Anti-inflammatory reliever; asthma; biologic agents; fractional exhaled nitric oxide (FeNO); inhaled cortico-steroids; leukotriene receptor antagonists; tezepelumab
Key points
• All individuals with asthma should be prescribed a treatment containing an inhaled corticosteroid, even if it is used only intermittently when they are symptomatic
• An asthma diagnosis should include an objective measure in addition to the clinical history; in some guidelines a raised blood eosinophil count or fractional exhaled nitric oxide test suffices
• Asthma biologics are highly effective at reducing the need for systemic corticosteroids and the adverse effects associated with long-term systemic corticosteroid use
Background
This journal previously reviewed the diagnosis and management of asthma (see Wong EHC, Farne HA. Asthma: diagnosis and management in adults. Medicine 2023; 51: 726–36). This briefer article is intended to be read in conjunction with that review, which remains relevant. However we wish to highlight significant updates since then, for example in the latest 2024 UK asthma guidelines (co-authored by the UK National Institute for Health and Care Excellence, British Thoracic Society and Scottish Intercollegiate Guidelines Network).
Update to diagnosis
A diagnosis of asthma has traditionally been a clinical one, and an objective confirmation of the diagnosis (including measurement of airways inflammation, reversible airways obstruction on spirometry and/or response to asthma treatment) was not always performed. However, when patients with a physician diagnosis of asthma are subjected to objective testing, a third are found not to have asthma.
This was demonstrated in a Canadian study of 613 patients with recent (within the last 5 years) physician-diagnosed asthma who had their inhaled treatment halved and then stopped if sequential bronchial provocation testing was negative.1 Of the 203 patients who had a negative bronchial provocation test off treatment, 181 remained symptom-free off treatment a year later.
Guidelines therefore advise some form of objective testing to accompany a clinical picture suggestive of asthma. The history should include some or all of:
• typical symptoms such as breathlessness, chest tightness, wheeze and/or a dry cough, worse at night and/or early in the morning
• typical triggers, for example respiratory viral infections, extremes of temperature, airborne allergens (house dust mite, pollens, animal dander), exercise and/or non-steroidal anti-inflammatory drugs
• improvement in the symptoms with asthma treatment (e.g. bronchodilators and/or systemic corticosteroids)
• a history of atopy (hay fever, eczema)
• a family history of asthma or atopy.
There is no single gold standard diagnostic test for asthma. The tests used to diagnose asthma assess for defining features of the disease: airways inflammation (blood eosinophils, fractional exhaled nitric oxide (FeNO)); reversible airways obstruction (spirometry with bronchodilator reversibility); diurnal variation in airway obstruction (peak flow diary); and airway hyperresponsiveness (bronchoprovocation challenge). However, the intermittent nature of asthma in particular results in false-negative results if the individual is tested during periods of disease stability (spirometry is normal in around 70% of cases at presentation).
Guidelines differ in the order in which investigations are performed, but there is consensus that an objective marker is required to avoid overdiagnosis. The 2024 UK guidelines suggest first assessing for airways inflammation: either a raised blood eosinophil count (above the upper limit of normal at the testing laboratory, e.g. >0.5 cells × 109 per litre) or a raised FeNO (typically defined as >50 parts per billion).
Eosinophil counts in the blood correlate with those in lower airways samples (e.g. sputum, bronchoalveolar lavage), but are much more readily available (although up to 25% of individuals with sputum eosinophilia do not have blood eosinophilia).
FeNO is produced by the bronchial epithelial cells that line the lower airways in response to inflammatory cytokines (e.g. interleukin (IL)-13) and is also associated with airway eosinophilia.
Thus, both blood eosinophil counts and FeNO assess for the lower airways inflammation that defines asthma. Neither is currently validated for diagnosing asthma, but their addition to clinical suspicion strengthens the basis for a diagnosis without over stretching lung function testing facilities. If a diagnosis cannot be made on blood eosinophils or FeNO, the 2024 UK guidelines advise proceeding to spirometry with reversibility, peak flow diary monitoring and bronchial provocation challenge, in that order.
Update to management
Anti-inflammatory reliever therapy
Asthma is recognized as an inflammatory condition. The cornerstone of therapy is therefore suppression of airways inflammation with inhaled corticosteroids (ICSs). There is now broad agreement that all patients with asthma should be treated with an ICS, even those with mild symptoms needing treatment only intermittently.
Historically, patients with mild asthma were treated with salbutamol reliever monotherapy, taken on an as-required basis when symptomatic. Salbutamol provides effective symptom relief but does not treat the underlying cause – airways inflammation. Worryingly, salbutamol overuse is associated with worse outcomes, including death, most likely because it delays presentation to healthcare services and is associated with poor adherence to ICSs. Indeed 15–20% of fatal and 16% of near-fatal asthma exacerbations are in patients with symptoms occurring less than weekly.2 As a result, most national and international recommendations have moved on from this in recent years.
Adding an ICS to a fast-acting bronchodilator reliever (e.g. formoterol) reduces the number of exacerbations by over half compared with a fast-acting bronchodilator reliever alone.3 This is termed ‘anti-inflammatory reliever’ therapy and should be the starting point for all patients with mild asthma.
The choice of ICS–formoterol varies depending on national licensing, local formulary arrangements, patient preference and shelf-life (if the inhaler is needed only infrequently, it should ideally have a longer expiry to ensure it is in date when required). This also makes any step up in treatment intensity easier, as the same inhaler can simply be prescribed regularly and as a reliever (maintenance and reliever therapy).
Patients with an existing diagnosis of asthma who are on salbutamol monotherapy should be transitioned to an ICS–formoterol inhaler as required to ensure they are given an ICS. However, patients with asthma currently treated with ICS maintenance therapy and a salbutamol reliever should not have their treatment changed without consultation if their asthma is well controlled.
Inhaler devices
Our last review noted the involvement of the tobacco firm Phillip Morris in the inhaler market via its acquisition of Vectura, who develop inhaler devices for many pharmaceutical companies. After the acquisition, sales of inhalers developed by Vectura incurred royalty payments to Phillip Morris, leading to a campaign to switch away from these inhalers. Phillip Morris has since divested Vectura and so this is no longer a concern in inhaler choice.
As per our last review, the carbon footprint of inhalers remains a consideration. The propellants in metered dose inhalers are greenhouse gases, although newer propellants with minimal climate impact are becoming more common. For now, dry powder inhalers generally have a lower carbon footprint and, all else being equal, are preferred in patients being newly started on inhalers. Patients already on a metered dose inhaler with good control should not be switched without consultation.
Leukotriene receptor antagonists (LTRAs)
The oral LTRA Montelukast is a popular add-on therapy for treating asthma. It is generally well tolerated but can be associated with neuropsychiatric adverse effects. These usually take the form of vivid dreams that patients may or may not find upsetting. However, suicidal ideation and behaviour has been noted and patients should be counselled about this before starting, as noted in a recent communication from the UK’s Medicines and Health-care products Regulatory Agency.
Montelukast improves asthma in only around 66% of patients, of whom 8% have a dramatic response. No criteria have been identified for reliably defining responders so this is necessarily by a treatment trial. It is therefore imperative to review the response to montelukast after 8–12 weeks and stop it in those for whom it is not effective.
Biologic therapies
In asthma, the aim of biologic treatments is to reduce the morbidity associated with systemic corticosteroids. In the original clinical trials, biologics reduced the frequency of asthma exacerbations requiring systemic corticosteroids by around half. The response to biologic treatment is therefore defined as a 50% reduction in prednisolone over a year, although many patients report much more dramatic improvements. There are also impressive response rates: 79% of 501 patients at least halved their prednisolone use in the Danish severe asthma registry.4 Asthma biologics, however, have limited effect on lung function or symptoms.
Asthma biologics have an extremely favourable adverse effect profile, unlike systemic corticosteroids. This is their main point of difference – asthma biologics are no more effective at treating asthma symptoms or preventing exacerbations than systemic corticosteroids. However, by acting as steroid-sparing agents, they reduce the burden of disease relating to the long-term use of systemic corticosteroids (note that the long-term use of ICSs does not result in the same morbidity, certainly at a low or medium dose).
This also explains why the core criterion to be eligible for biologic therapy is the requirement for frequent or regular systemic corticosteroids for asthma. Asthma biologics are unlikely to be effective in patients who do not require or benefit from systemic corticosteroids.
Patients who respond to biologic therapy may be able to wean their other asthma medications down. Typically, the first agents that are discontinued are the add-on therapies montelukast and any long-acting muscarinic antagonist. It may also be possible to wean the ICS to a medium or low dose. However, current evidence suggests reducing the ICS further to ICS–formoterol use as required for symptoms, rather than regular maintenance, is associated with an increase in FeNO and a decrease in lung function.
Anti-thymic stromal lymphopoietin (TSLP) treatment:
since our last review, tezepelumab, a new biologic blocking an alternative signalling pathway, via the protein TSLP, has become available. In clinical trials, tezepelumab was effective in patients requiring maintenance or at least three courses of systemic corticosteroids a year despite high-dose ICS use regardless of blood eosinophil count or FeNO; however, it was more effective in patients in whom one or both of these biomarkers of type 2 inflammation were raised. Nonetheless, it provides a very welcome option for those with severe asthma in the absence of blood eosinophilia or a raised FeNO.
It must be stressed that the diagnosis of asthma must be secure, with evidence that this is driving the symptoms. Tezepelumab will not improve symptoms where they are the result of non-asthma pathology, for example a breathing pattern disorder or upper airway obstruction.
Choice of biologic:
with six commonly available asthma biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) that have over-lapping eligibility criteria and no head-to-head trials, the choice of biologic has become a conundrum.
For patients eligible for multiple biologics, biomarkers (principally blood eosinophils and FeNO), co-morbidities, current maintenance treatment and logistics are all considerations in the choice of agent. For example several, but not all, biologics (e.g. dupilumab, tezepelumab) are effective in treating chronic rhinosinusitis, a common co-morbidity in severe asthma. Similarly, some (mepolizumab, benralizumab, dupilumab) are effective in weaning patients off maintenance oral corticosteroids. The dosing schedule of biologic agents varies from every 2 to every 8 weeks.
Biomarkers are also relevant. A pronounced eosinophilia (blood eosinophil count >1 × 109 cells per litre) favours a drug targeting signalling via the eosinophil master cytokine IL-5.
A markedly raised FeNO is suggestive of greater epithelial cell involvement (nitric oxide in the breath is thought to be produced by airway epithelial cells, which are also the source of TSLP), directing the clinician towards tezepelumab. Of note, therapies targeting IL-5 signalling do not suppress FeNO.
Various decision guides have been proposed (e.g. GINA-Severe-Asthma-Guide-2024-WEB-WMS. pdf), although the decision rests with the specialist multidisciplinary team. Guidance is also being developed on what to do when a patient is not responding to the first-line agent, including assessment of persistent airways inflammation, airway infection and mimicking co-morbidities.
Pregnancy and biologic therapies:
patients who were pregnant were excluded from the clinical trials of asthma biologics, but a growing body of real-world evidence suggests these drugs are safe in pregnancy. A Delphi consensus document has there- fore recently recommended that biologics be continued in pregnancy and suggested that they can be started during pregnancy or breast-feeding if the severity of asthma or adverse effects of systemic corticosteroids warrant treatment escalation.5
This should be done on a case-by-case basis under specialist care and in accordance with the patient’s wishes, weighing up the risks and benefits of biologic treatment versus the possibility of further courses of systemic corticosteroids.
Future developments
Diagnosis
The more accurate diagnosis of asthma remains challenging. Many existing tests have low sensitivity (e.g. spirometry) and/or specificity (e.g. blood eosinophils) and often require specialist equipment and staff to perform (e.g. FeNO, spirometry); this makes them costly, onerous and variably available. In addition, many patients struggle to perform existing tests, rendering the results unreliable. This is particularly the case for spirometry, which also forms part of bronchoprovocation challenge testing, but also FeNO and even peak flow, which is effort-dependent.
Oscillometry is a lung function technique where individuals breath normally (‘tidal breathing’) through a mouthpiece while small pressure oscillations are applied. The resulting pressure–flow responses are analysed to estimate the mechanical properties of the small and large airways. Oscillometry requires less skill and effort to perform, with new devices looking to simplify interpretation of the results and bring down the cost. Other novel biomarkers are also in development, for example acoustic biomarkers in speech that use the existing hardware in smart phones and volatile organic compounds in breath.
Management
There are a large number of novel pharmacological therapies for asthma in various stages of clinical development, including but not exclusively biologic therapies.
One that is close to becoming available is depemokimab, which disrupts IL-5 signalling similar to the existing biologicals mepolizumab and benralizumab; however, it requires only 6-monthly dosing (compared with 4- or 8-weekly with mepolizumab and benralizumab, respectively). This is likely to be particularly useful for patients who require administration by a healthcare professional, reducing the resource and hence cost of administration, or those who are needle phobic.
Hugo Andres Farne, Ernie Hoi Cheung Wong
Hugo Andres Farne BM BCh MA(Oxon) MRCP(UK) PhD is a Consultant Respiratory Physician at Imperial College Healthcare NHS Trust and Honorary Senior Clinical Lecturer at the National Heart and Lung Institute, Imperial College London, UK. Competing interests: Dr Farne has received sponsorship to attend a conference from Chiesi Limited and GSK plc, as well as honoraria for advisory services to GSK plc
Ernie Hoi Cheung Wong MB BS BSc MRCP(UK) PhD is a Consultant Respiratory Physician, Clinical Lead for Asthma at Imperial College Healthcare NHS Trust and Honorary Senior Clinical Lecturer at the National Heart and Lung Institute, Imperial College London, UK. Competing interests: Dr Wong has received sponsorship to attend a conference from Chiesi Limited, as well as honoraria for speaking at educational sessions from Chiesi Limited and AstraZeneca plc
Key references
1. S.D. Aaron, K.L. Vandemheen, J. M. FitzGerald, et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma JAMA, 317 (2017), pp. 269-279
2. D. Dusser, D. Montani, P. Chanez, et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations Allergy, 62 (2007), pp. 591-604
3. I. Crossingham, S. Turner, S. Ramakrishnan, et al. Combination fixed-dose beta agonist and steroid inhaler as required for adults or children with mild asthma Cochrane Database Syst Rev, 5 (2021), p. CD013518
4. S. Hansen, M.B. Søndergaard, A. von Bülow, et al. Clinical response and remission in patients with severe asthma treated with biologic therapies Chest, 165 (2024), pp. 253-266
5. J. Naftel, D.J. Jackson, M. Coleman, et al. An international consensus on the use of asthma biologics in pregnancy. Lancet Respir Med, 13 (2025), pp. 80-91
6. British Thoracic Society BTS/ NICE/SIGN joint guideline on asthma: diagnosis, monitoring and chronic asthma mana-gement (November 2024) – summary of recommendations. Thorax, 80 (2025), pp. 416-424
7. S. Couillard, D.J. Jackson, I.D. Pavord, et al. Choosing the right biologic for the right patient with severe asthma Chest, 167 (2025), pp. 330-342
8. D.J. Jackson, L.G. Heaney, M. Humbert, et al. Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study Lancet, 403 (2024), pp. 271-281
9. D.J. Jackson, M.E. Wechsler, D.J. Jackson, et al. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype New Engl J Med, 391 (2024), pp. 2337-2349
10. Abdelgalil M. Shaban, Elrashedy A. Ahmed, A.K. Awad, et al. Safety and efficacy of tezepelumab vs. placebo in adult patients with severe uncontrolled asthma: a syste-matic review and meta-analysis. Sci Rep, 12 (2022), Article 2
Test yourself
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here.
Question 1
A 65-year-old man was referred with a 6-month history of nocturnal cough and wheeze and a question of whether this might be asthma. He gave a history of the onset of symptoms after a respiratory viral infection. He was given salbutamol and a nasal steroid spray which improved the cough but not the nocturnal wheeze.
What could best be used to secure a diagnosis of asthma?
A. A blood eosinophil count of 0.4 × 109 cells per litre
B. A forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio of 0.715
C. A fractional exhaled nitric oxide (FeNO) level of 126 parts per billion D. An immunoglobulin E level of 598 k units per litre
E. No further tests needed – the history and response to treatment are sufficient
Question 2
A 43-year-old woman presented with a new diagnosis of asthma. She experienced symptoms twice a week and occasional nocturnal awakenings due to respiratory symptoms. She had no previous hospital admissions or flare ups requiring oral steroids in the community.
What is the most appropriate long-term treatment for this patient?
A. Asthma biologic therapy
B. Inhaled corticosteroid regularly with salbutamol as required
C. Inhaled corticosteroid with formoterol as maintenance and reliever therapy
D. Inhaled long-acting β-agonist regularly
E. Salbutamol as required
Question 3
A 57-year-old man was reviewed in a specialist asthma centre. He had severe eosinophilic asthma. Despite high-dose combination inhaled corticosteroids with long-acting bronchodilators, he required frequent courses of oral prednisolone for exacerbations. An asthma biologic treatment was considered.
What is the main benefit of biologic treatment in this patient?
A. Greater reduction in exacerbation frequency than regular oral corticosteroids
B. Improved lung function
C. Improved symptoms
D. Reduced incidence of steroid-related adverse effects
E. Reduced need for inhalers
Credit: Farne H, Wong E. 2026 update in asthma diagnosis and management Medicine, 2026; 54, 284-287
