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Severe asthma phenotyping

A range of asthma subtypes exist that align with differences in disease processes. Case history assessment, specific tests and tailored treatments have always been factors in appropriate diagnosis and management of severe asthma. Recent years have seen increasing interest in severe asthma subtype classification, or ‘phenotyping’, particularly with the advent of diagnostic biomarkers and novel tailored treatments. 1As such, there is the potential to take a more personalised approach to treatment.

Phenotyping in severe asthma could lead to improved treatment outcomes, because it could allow physicians to tailor therapy to the underlying cause of a patient’s disease. 2

Defining and differentiating severe asthma phenotypes in current practice

The relevance of phenotyping in severe asthma

Hekking PP, Wener RR, Amelink M et al. The Prevalence of Severe Refractory Asthma. J Allergy Clin Immunol 2015 Apr; 135(4):896-902. [PubMed]

What is a phenotype?

It is becoming ever more obvious that not all asthma is the same. Heterogeneity characterisation has given rise to the concept of distinct phenotypes in severe asthma23

A phenotype is defined as:

The composite, observable characteristics of an organism, resulting from interaction between its genetic make-up and environmental influences, which are relatively stable, but not invariable, with time. 2

The concept of phenotypes in severe asthma is gaining wide acceptance, and many physicians now consider asthma phenotyping key to the future of disease prevention and treatment. 4

Phenotyping combines biological and clinical features that can be outwardly observed or measured, such as morphological, functional and patient-oriented characteristics. 13 Although phenotypes do not necessarily relate to a disease’s underlying mechanisms, they can highlight clinically recognisable patient groups to act as a basis for determining underlying molecular disease processes. This is known as endotyping, which refers to identifying the distinct functional or pathobiological mechanism behind the disease. 5The end goal of phenotyping in severe asthma is to ultimately determine endotypes, and therefore improve therapy by targeting specific underlying causes of disease.2

Established identification of severe asthma phenotypes

Historically, asthma has typically been divided into non-allergic and allergic phenotypes (also known as non-atopic and atopic): 2 6-7

Comparison of historical asthma phenotypes

Non-allergic asthma (previously known as intrinsic asthma) 8

Allergic asthma (also known as extrinsic asthma) 8

Does not appear to be associated with allergic sensitisation; serum IgE levels are low to normal 6

Is associated with allergy and characterised by high levels of IgE 8

Often begins later in life 8-9

Often begins in childhood 8

Comprises 10–33% of individuals with asthma 6

Is the most common asthma phenotype: approximately two-thirds of patients with asthma show allergic features 8

Patients have a history of comorbidities, e.g. nasal polyps, rhinosinusitis, gastroesophageal reflux disease 6

Is associated with increased comorbidities, such as allergic rhinitis and allergic dermatitis 9

Is thought to be more severe than allergic asthma 6

Patients are likely to report seasonal variation in symptoms in response to allergen exposure 6

Has a lack of family allergy history 6


Has a female predominance 6


IgE, immunoglobulin E.

Further severe asthma phenotypes have been identified in recent years. Strong evidence now exists for severe allergic asthma, characterised by a high IgE titre, and severe asthma with eosinophilic inflammation, characterised by elevated blood eosinophil counts. 1–4 6 7 10There is also emerging evidence for additional severe asthma phenotypes, including those associated with neutrophilic inflammation or related to physical characteristics such as obesity or age. 1

Phenotyping has been approached in multiple ways. Different analyses have studied combinations of clinical characteristics, factors that associate with or trigger asthma, and pathobiologic characteristics, which has led to the realisation that more phenotypes exist than previously thought. 3

Current understanding of severe asthma phenotypes

Our current understanding of phenotypes in severe asthma stems from an integration of genetics, biology and clinical characteristics which have been uncovered by hypothesis-driven and unbiased approaches.2

Future understanding of phenotypes, and eventually endotypes, will require continued integration of genetic, biologic and clinical data, which should ultimately lead to development of phenotype-specific and molecularly targeted therapies. 2 3


  1. Wenzel SE. Nat Med 2012;18:716–25.
  2. Chung KF, et al. Eur Respir J 2014;43:343–73.
  3. Wenzel S. Clin Exp Allergy 2012;42:650–8.
  4. Holgate ST, Sly PD. Asthma Pathogenesis. Middleton's Allergy: Principles and Practice. Saunders Elsevier, Philadelphia, PA, USA: 2014.
  5. Fahy JV. Nat Rev Immunol 2015;15:57–65.
  6. Peters SP. J Allergy Clin Immunol 2014;2:650–2.
  7. Hekking PPW, Bel EH. J Allergy Clin Immunol Pract 2014;2:671–80.
  8. Kumar RK, Jeffery PK. Pathology of Asthma. Middleton's Allergy: Principles and Practice. Saunders Elsevier, Philadelphia, PA, USA: 2014.
  9. Barnes PJ. Asthma in Harrison's Principles of Internal Medicine. Chapter 254. Available at http://accessmedicine.mhmedical.com/ (Last accessed August 2015)
  10. GINA 2016 © 2016 Global Initiative for Asthma, all rights reserved.  Use is by express license from the owner. www.ginasthma.org (Last accessed December 2016)