Severe Asthma

It is estimated that 5 - 10 % of asthma patients suffer from a severe form of disease that is usually managed with high-dose ICS and bronchodilators².

• GINA step 4-5 treatment (cumulative total 23.5 % of all asthma patients).
• Difficult to treat asthma = poor asthma control + GINA step 4-5 treatment (cumulative total 17.4 % of all asthma patients).
• Severe asthma = poor asthma control + GINA step 4-5 treatment + good adherence and inhaler technique (3.7 % of all asthma patients) ³.

Patients with severe asthma need to be systematically evaluated and assessed by specialist care. A severe asthma service provides a systematic approach to manage the disease and aim in confirming the correct diagnosis, managing comorbidities that may mimic or aggravate asthma. It also provides the platform to optimize the treatment and asthma self-management skills.

Purpose of Severe Asthma Service

The core objective of the severe asthma service is to improve patient outcomes, including decreased exacerbation frequency, measured by reductions in emergency visits, hospital admissions and oral corticosteroid steroid use, as well as improved lung function and improved quality of life.

The following diagnostic testing will be required:

1. Lung function tests

• Full pulmonary function tests (PFT)
• Bronchodilator reversibility (BDR)
   

2. Biomarkers 

• Lung function tests
• Immunoglobulin E (IgE)
• Exhaled nitric oxide (FeNO) to quantify airway inflammation

3. Other necessary blood tests if indicated 

• Allergy tests to identify atopy and allergic triggers or diseases (eg. Allergic bronchopulmonary aspergillosis)
• Autoantibodies to look for connective tissue disease (eg. Esinophilic granulomatosis with polyangiitis)
• Immunoglobulin test for immune function screen
   

4. Image tests

• X-Ray test
• High resolution computed tomography (HRCT) thorax and sinus

Extra-pulmonary comorbidities in severe asthma are common, which make the severe asthma management complicate and affect patient outcome. Extrapulmonary comorbidities were identified by clinical symptoms, such as sino-nasal disease (allergic rhinitis and chronic rhino-sinusitis, obstructive sleep apnea (OSA), gastroesophageal reflux disease (GERD), anxiety/depression (Anx/Dep), dysfunctional breathing (DB) and vocal cord dysfunction (VCD)⁴. Comorbidities may frequently interact, contribute to poor disease control and mimic symptoms of asthma. They may also increase the cost of treatment for people with severe asthma and lead to overtreatment. It is therefore recommended that comorbidities be addressed in severe asthma.

Treatment Strategies

When the diagnosis of severe asthma is confirmed, treatment emphasis shifts from a stepped approach to a targeted approach for treatment. Add-on therapies would be considered to enhance symptom control or as a dose-reduction strategy to limit the side effects of primary therapies (e.g. high-dose corticosteroids or long-term oral corticosteroids). Therapeutic trials of add-on therapies, e.g. long-acting muscarinic antagonists and leukotriene receptor antagonist can be undertaken for defined periods of time ⁵. 

The biological processes underlying asthma are heterogeneous, so detailed characterisation of the individual patient phenotype and an individual risk/benefit assessment should be carried out before considering add-on therapies. Monoclonal antibodies (biologics) are increasingly emerging as targeted therapies that block specific molecular pathways in severe asthma. Monoclonal antibodies, e.g. anti-IgE, anti-interleukin 5 (anti-IL5) and anti-interleukin-5 receptor alpha (anti-IL5Rα), work by binding to and blocking the function of a specific target molecule, resulting in improvement of asthma outcome, like reduction in exacerbation rate ⁶. 

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2020. https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf. Date last accessed: 06 April 2020.
2. Chung, K.F., et al., International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal, 2014. 43(2): p. 343-373.
3. Hekking, P.-P.W., et al., The prevalence of severe refractory asthma. 2015. 135(4): p. 896-902.
4. Radhakrishna, N., et al., Profile of difficult to treat asthma patients referred for systematic assessment. 2016. 117: p. 166-173.
5. 2019 GINA pocket guide: Diagnosis and Management of Difficult-to-treat and Severe Asthma in adolescent and adult patients V2.0 April 2019. https://ginasthma.org/wp-content/uploads/2019/04/GINA-Severe-asthma-Pocket-Guide-v2.0-wms-1.pdf. Date last accessed: 06 April 2020.
6. Holguin, F., et al., Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. European Respiratory Journal, 2020. 55(1): p. 1900588.