To Assess the Management of Patients on Global Initiative of Asthma (GINA) Step 4 and 5 Treatment in Hong Kong

Background Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the 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.1 The World Health Organization estimates that 300 million people worldwide have asthma with an associated 250,000 asthma deaths annually.2 In Hong Kong, the prevalence rates of physician-diagnosed asthma in 13- to-14-year-olds were 10.2% in 2002,3 and 5.8% in the elderly (aged >70 years) in 2003.4 The crude mortality rate of asthma in 2005 in Hong Kong was 1.4/100,000.5

Severe asthma is not very common but casts a considerable burden on the healthcare system and patients. According to a Dutch survey which included adult asthma patients, 17.4% and 3.6% of them had difficult-to-treat asthma and severe asthma respectively.6 Although severe asthma involves only a small proportion of the asthma population, it generates a huge amount of asthma-related healthcare expenditure.7 An observational cohort by a French study group found that 83% of patients with severe asthma experienced at least one exacerbation and 14% were hospitalised for asthma over the past 12 months.8 Also, patients with severe asthma experience a different spectrum and more severe symptoms, with higher functional and psychological limitation than the general asthma population.9

Asthma is considered as difficult-to-treat if it remains uncontrolled despite Global Initiative for Asthma (GINA) step 4 or 5 treatment (e.g. medium or high dose inhaled corticosteroids [ICS] plus a second controller), or that requires such treatment to maintain good symptom control and reduce the risk of exacerbation.1 Various modifiable factors may contribute to difficult-to-treat asthma, that includes incorrect inhaler technique, suboptimal medication adherence, associated comorbid conditions and even wrong diagnosis. Severe asthma is considered as a subset of difficult-to-treat asthma after exclusion of the modifiable factors other than poorly controlled asthma itself. It is defined as asthma that is uncontrolled despite adherence with maximal optimised therapy and treatment of contributory factors, or that worsens when high dose treatment is decreased.1 Disease phenotyping has revolutionised the management of asthma from stepwise treatment to phenotype-based treatment. As asthma is a clinical syndrome comprising of several spectrums of symptom, different molecular pathways may be involved. Most of these are associated with evidence of cellular inflammation in the airway.10 Identifying treatable traits may potentially guide the choice and predict the outcome of treatment, e.g. blood or airway eosinophilia, is usually a good indicator of corticosteroid responsiveness.11 12 The process of characterising observable treatable traits is termed phenotyping, and this allows physicians to select the most appropriate add-on therapies for patients with severe asthma. Phenotype identification is usually performed in patients on high dose ICS, as most clinical trials on an add-on or biologic treatments were performed in this group of patients.

Among the various inflammatory phenotypes, Type 2 inflammation is the most important one, and its mechanism forms the basis of several biologic treatments. This inflammation pathway is characterised by the presence of interleukin (IL)-4, IL-5 and IL-13. IL-4 and IL-5 promote the production of immunoglobulin E (IgE) and eosinophils respectively, thus the occurrence of eosinophilic inflammation and atopic phenomenon in asthma.1, 13

Five biologics have been approved by the US Food and Drug Administration (FDA) for antagonising the Type 2 inflammatory mechanisms in severe asthma. They are omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. In general, severe asthma patients with clinical and laboratory features manifesting Type 2 inflammation (e.g. allergen-driven, high IgE level, high eosinophil activity) and exacerbations are good candidates for such treatment.