Despite advances in diagnosis and management, many patients with respiratory disease may still experience sub-optimal disease control.1
Significant unmet need exists for patients with severe asthma1
Improved disease stability and consideration of remission as a management goal for patients living with asthma remains a long-term aspiration to improve patient care.17,18
1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2024. Available from: https://ginasthma.org/2024-report/ (Accessed 29 May 2025); 2. Rogliani P, et al. Pulm Ther. 2020;6:47–66; 3. Wang E, et al. Chest. 2020;157:790–804; 4. Trevor J, et al. Ann Allergy Asthma Immunol. 2021;127:579–587; 5. Ambrose CS, et al. Pragmat Obs Res. 2020;11:77–90; 6. Price DB, et al. J Asthma Allergy. 2018;11:193–204; 7. Chen H, et al. J Allergy Clin Immunol. 2007;120:396–402; 8. Busse WW, Kraft M. Eur Respir Rev. 2022;31:210176; 9. Chen S, et al. Curr Med Res Opin. 2018;34:2075–2088; 10. Nunes C, et al. Asthma Res Pract. 2017:3:1; 11. Stubbs MA, et al. J Asthma Allergy. 2021;14:1527–1537; 12. Stanescu S, et al. NPJ Prim Care Respir Med. 2019 Oct 21;29(1):37; 13. Usmani OS, Levy ML. NPJ Prim Care Respir Med. 2023;33(1):24; 14. Bleecker ER, et al. Am J Respir Crit Care Med. 2020;201:276–293; 15. Canonica GW, et al. World Allergy Organ J. 2019;12:100007; 16. Volmer T, et al. Eur Respir J. 2018;52(4):1800703;
17. Menzies-Gow A, et al. J Allergy Clin Immunol. 2020;145:757–765; 18. Thomas D, et al. Eur Respir J. 2022;60:2102583.
Overview of severe asthma
Asthma affects approximately 300 million people worldwide,4 of whom ~5–10% have severe or uncontrolled asthma.3
Severe asthma is defined by the Global Initiative for Asthma (GINA) as a subset of difficult-to-treat asthma that remains uncontrolled despite adherence with maximal optimised high-dose inhaled corticosteroids (ICS) and long-acting β2-agonist (LABA) therapy and the treatment of contributory factors, or asthma that worsens when high-dose therapy is decreased.4
The long-term goals of severe asthma management include achieving good symptom control and minimising the future risk of exacerbations and disease progression (eg, decline of lung function and persistent airflow limitation).4 In many cases where patients have poor symptom control and/or exacerbations despite medium- or high-dose ICS and LABA therapy, their asthma may appear difficult-to-treat because of contributory factors, such as incorrect inhaler technique, poor adherence, smoking or comorbidities, or because of incorrect diagnosis.4 For these patients, GINA recommends assessment of these contributory factors and consideration of an add-on therapy, eg a long-acting muscarinic antagonist (LAMA).4 If problems persist, referral to a specialist centre for phenotypic assessment and consideration for add-on biologic targeted treatments are recommended.4 Even though there is guidance on when patients with asthma should be referred to a specialist, a large proportion of patients are not referred despite experiencing poor symptom control.5 Referral to specialist care is associated with a substantial impact on disease prognosis and patient health status.6 In an observational cohort study in the UK, 4% (n=723/16875) of patients who were eligible for specialist care were referred.5 Similarly, in a telephone-based survey in the US that included 2500 patients with asthma, only 22% of patients visited specialists for usual asthma care.6 Furthermore, a retrospective claim data analysis from 2017 to 2018 in Germany, with more than 300,000 asthma patients, found that while 41% of patients with severe asthma were referred to a pulmonologist, 89% of the population were receiving long-term oral corticosteroids (OCS), despite the side effects and recommendations against such therapy as a maintenance treatment.7
To learn more about identifying patients who may be eligible for referral using our Asthma Referral Identifier tool, ReferID, please click here.
Confirming the diagnosis of asthma, assessing contributory factors and optimising treatment strategy are the key steps for consideration in the diagnosis and management of severe asthma.4 Preventing exacerbations is important in the treatment of asthma and being able to identify and proactively treat at risk patients forms a central component of this strategy.8
Many tools can be used to assess the risk of exacerbation e.g., Asthma Control Questionnaire (AIRQ), which is a composite measure of asthma control based on a series of yes/no questions answered by the patient, and ReferID+, a digital tool used to review patients with asthma which has led to improved clinical outcomes including fewer exacerbations.9–11
To date, there has been great progress in the diagnosis and management of severe asthma,12,13 with biologics representing a major advancement in the treatment landscape.14 However, many patients with severe asthma are still poorly controlled.15
Sub-optimal control of severe asthma
A study found that approximately 60% of patients with severe asthma remained sub-optimally controlled despite treatment with standard-of-care medications.15 This significant finding was described following a retrospective and prospective analysis of the International Severe Asthma Registry – a data set of 4990 patients receiving GINA Step 5 treatment or with severe asthma remaining uncontrolled at GINA Step 4 (December 2014 to December 2017). Poorly controlled asthma was defined in this study according to Asthma Control Test (score 5–15; ‘very poorly controlled’) or Asthma Control Questionnaire (score >1.5; ‘poorly controlled’) categorisations.15 In the same study, 41% of patients experienced at least one or more asthma exacerbations per year despite receiving treatment.15
Healthcare resource utilisation and specifically OCS use is higher among patients with uncontrolled asthma.16 Sub-optimal management of patients can also influence the likelihood of hospital readmissions. In a US database of 5167 patients, 9.2% of those who had an asthma-related emergency department visit or hospitalisation were readmitted within 30 days. Similarly, in the UK database of 2904 patients, 4.7% of patients were re-admitted within 30 days.17 In Canada, nearly 20% of patients with asthma (n=12456) were readmitted into the ED within 30 days following an initial asthma-related ED visit.18 Readmissions were associated with increased disease severity, exacerbation frequency and a higher GINA step.17 Many patients are prescribed SCS when attending the ED with an exacerbation.19
To find out more about the current burden and guidelines of severe asthma in the ED, click here.
Impact of poorly controlled severe asthma
Below is an example of a typical patient with severe asthma and comorbid upper airways disease. Despite adherence to daily ICS-LABA treatment, he continues to experience symptoms that hinder his quality of life. Furthermore, the upper airway symptoms that the patient experiences are only partially improved with treatment. Co-occurrence of upper and lower airway disease is frequent,20–22 and the treatment and control of these comorbidities is essential to achieve asthma control in some patients.21
To learn more about the link between upper and lower airways disease, please click here.
Sub-optimal asthma control can have a significant impact on patient outcomes:
Beyond the implications for patients, sub-optimal asthma control has wider implications:
Challenges associated with existing treatments for poorly controlled asthma
OCS are the primary therapy for resolution of acute exacerbations.35 However, patients with severe asthma are often exposed to multiple courses of OCS,36 and cumulative and chronic exposure is associated with an increased risk of side effects.6,37,38 In a cross-sectional observation study (n=808), 93% of patients with severe asthma, morbidities related to potential corticosteroid use have been identified.39 Many OCS-related morbidities (eg, osteoporosis, diabetes and hypertension) are associated with decreased lung function and reduced asthma control.40 As little as 0.5–1 g (or up to four short courses) of OCS can cause serious adverse effects, including cataracts, pneumonia, type 2 diabetes, cardiovascular disease, renal impairment and osteoporosis.6 Increased OCS exposure was also associated with increased risk of mortality.41
Globally, 20–60% of patients with severe or uncontrolled asthma have received long-term OCS.37 The annual cost of OCS-related adverse events per person with severe asthma is estimated to be €1958, in Italy.38 On a population level the cost of OCS-related adverse events to the Italian National Health System is €243 million annually.38 Corticosteroid use was also associated with higher healthcare resource utilisation.42 Updated GINA guidelines recommend minimising OCS use and only using short courses of OCS for patients with an acute asthma exacerbation.4
As such, there is a clear need to avoid maintenance OCS treatment where other options are available (in line with updated recommendations by GINA4) and to continue to develop and identify alternative steroid-sparing treatments for asthma exacerbations and for patients with severe asthma.6 To protect patients from the potential harm of SCS use, a structured and collaborative SCS stewardship approach is required.43
To find out more about oral corticosteroid stewardship, click here to view the oral corticosteroid stewardship infographic and an overview of oral corticosteroid use in severe asthma.
Asthma is heterogeneous; patients often show activation of multiple innate and adaptive inflammatory pathways.44–46 This contributes to a significant unmet need in the management of severe uncontrolled asthma.4 Targeting specific steps of the immune-inflammatory cascade through highly selective biologic therapies offers the potential of achieving optimal disease control in several severe asthma across inflammatory phenotypes.1
To learn more about the heterogeneity of severe asthma, please click here.
However, major unmet needs persist owing to lack of access to biologic treatments.1 As an example, in UK primary care, out of ~207,000 asthma patients that were selected, 8% of those were found to have potential severe asthma, and of these, 72% were not referred to a specialist.47 In an analysis of the International Severe Asthma Registry (n=4990), approximately 75% of patients with poorly controlled severe asthma (GINA Step 4/5) were not receiving biologics.15 Furthermore, patients with asthma often experience comorbidities,20–22 and the treatment of these is essential to achieve asthma control.21
Summary of current challenges in the diagnosis and management of severe asthma.
For patients living with asthma, improved disease stability and consideration of remission as an attainable treatment goal remains a long-term aspiration to improve patient care.48,49
Like this page? We have a host of other resources available in the ‘Scientific and Resource Library’ where you can find out more.
Learn more about how sub-optimal asthma control can impact outcomes and quality of life.
Explore the impact of ReferID in identifying patients with controlled or severe asthma who may benefit from specialist review.
Discover how to reduce the burden of asthma in the emergency department, the guidelines for managing asthma and practical solutions.
Find out more about oral corticosteroid stewardship, the tools to support this, and how oral corticosteroids can be used in patients with asthma.
Learn more about the assessment and measurement of patient experience in severe asthma.
References
1. Caminati M, et al. J Asthma Allergy. 2021;14:457–466;
2. Global Asthma Network. Int J Tuberc Lung Dis. 2022;26(Suppl. 1):1–104;
3. Rogliani P, et al. Pulm Ther. 2020;6:47–66;
4. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2024. Available from: https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf (Accessed 29 May 2025);
5. Blakey JD, et al. BMJ Open. 2019;9:e031740; 6. Price D, et al. J Asthma Allergy. 2017;10:209–223; 7. Hardtstock F, et al. J Asthma. 2023;60:1280–1289; 8. Castillo JR, et al. J Allergy Clin Immunol Pract. 2017;5:918–927;
9. Murphy KR, et al. J Allergy Clin Immunol Pract. 2020;8:2263–2274;
10. Beuther DA, et al. J Allergy Clin Immunol Pract. 2022;10:3204–3212;
11. Dhruve H, et al. Thorax. 2023;78(Suppl. 4):A66 (Abstract);
12. Charriot J, et al. Eur Respir Rev. 2016;25:77–92;
13. Zervas E, et al. ERJ Open Res. 2018;4:00125–02017;
14. Djukanovic R, et al. Eur Respir J. 2018;52:1801671;
15. Wang E, et al. Chest. 2020;157:790–804;
16. Sadatsafavi M, et al. Can Respir J. 2010;17:74–80;
17. Suruki RY, et al. BMC Pulm Med. 2017;17:74;
18. Mayers I, et al. Eur Respir J. 2022;60(Suppl. 66):2306 (Abstract);
19. Halner A, et al. PLoS One. 2021;16:e0254425;
20. Chen S, et al. Curr Med Res Opin. 2020;36:1897–1911;
21. Nunes C, et al. Asthma Res Pract. 2017;3:1;
22. Nissen F, et al. Br J Gen Pr. 2018;68:e775–e782;
23. Soong W, et al. Ann Allergy Asthma Immunol. 2020;125(5 Suppl.):S27 (Abstract P203);
24. Ambrose CS, et al. Pragmat Obs Res. 2020;11:77–90;
25. Jackson DJ, Bacharier LB. Ann Allergy Asthma Immunol. 2021;127:524–529;
26. Hellings PW, Steelant B. J Allergy Clin Immunol. 2020;145:1499–1509;
27. Rutting S, et al. Front Physiol. 2022;13:898208;
28. Pavord ID. Curr Opin Pulm Med. 2019;25:51–58;
29. Price DB, et al. J Asthma Allergy. 2018;11:193–204;
30. Chen H, et al. J Allergy Clin Immunol. 2007;120:396–402;
31. Stubbs MA, et al. J Asthma Allergy. 2021;14:1527–1537;
32. Busse WW, Kraft M. Eur Respir Rev. 2022;31:210176;
33. Chen S, et al. Curr Med Res Opin. 2018;34:2075–2088;
34. Usmani OS, Levy ML. NPJ Prim Care Respir Med. 2023;33:24;
35. Chung LP, et al. Respirology. 2020;25:161–172;
36. Papapostolou G, et al. Eur Clin Respir J. 2020;8:1856024;
37. Bleecker ER, et al. Am J Respir Crit Care Med. 2020;201:276–293;
38. Canonica GW, et al. World Allergy Organ J. 2019;12:100007;
39. Sweeney J, et al. Thorax. 2016;71:339–346;
40. Scelo G, et al. Ann Allergy Asthma Immunol. 2024;132:42–53;
41. Skov IR, et al. Eur Respir J. 2022;60:2103054;
42. Voorham J, et al. Allergy. 2019;74:273–283;
43. Bleecker ER, et al. World Allergy Organ J. 2022;15:100726;
44. Tran TN, et al. Ann Allergy Asthma Immunol. 2016;116:37–42;
45. Kupczyk M, et al. Allergy. 2014;69:1198–1204;
46. Canonica G. Biomarker relatability in the International Severe Asthma Network. Oral presentation at WAC, Lyon, France 12–14 December 2019 (Abstract OC35);
47. Heatley H, et al. Eur Respir J. 2019;54(Suppl. 63):PA2712 (Poster);
48. Menzies-Gow A, et al. J Allergy Clin Immunol. 2020;145:757–765;
49. Thomas D, et al. Eur Respir J. 2022;60:2102583.
