Use this tool as an educational guide to differentiate among severe asthma phenotypes.

Differentiating Severe
Asthma Phenotypes

GINA acknowledges that phenotyping is an evolving field and clinical relevance is undetermined; however, GINA suggests that patients with severe asthma may benefit from phenotyping.¹

Asthma phenotypes in

GINA Report¹

According to GINA

Patients with severe asthma may benefit from phenotyping into categories such as severe allergic, aspirin-exacerbated, or eosinophilic asthma. Assessment of the patient’s inflammatory phenotype includes Type 2 and non-Type 2 categories. This can help clinically in selecting individualized add-on treatment.¹

Severe asthma phenotyping is still an evolving field, and consensus on the defining features of each phenotype is yet to be established.²

Examples of severe asthma phenotypes

Late Onset Non-Allergic Asthma

Patient Characteristics	Adults, aged 20 or older^1,2 Not associated with allergy¹ More common in women¹
Biomarkers	Increased Fe_NO (>50 parts per billion)¹ Increased IL-5² Greater numbers of eosinophils and mast cells²

Late onset non-allergic asthma is often corticosteroid-refractory¹

Severe Allergic Asthma

Patient Characteristics	Often presents in childhood¹ Associated with history of allergic disease¹ More common in females³
Biomarkers	Specific IgE² Increased blood neutrophil counts⁴ Increased blood and sputum eosinophil counts^4,5 Increased Fe_NO⁵

Patients with severe allergic (atopic) asthma have higher amounts of T_H2 cytokines²

Severe Asthma With Fixed Obstruction (Asthma-COPD Overlap)

Patient Characteristics	Present with childhood-onset asthma and remain symptomatic in adolescence⁶ History of smoking and prolonged exposure to allergens in the workplace^6,7 Fixed obstruction related to bronchial inflammation (worsens after exacerbations)⁶
Biomarkers	Increased sputum neutrophil counts⁸

Unlike other asthma phenotypes, patients with severe asthma with fixed obstruction often develop irreversible, persistent, and progressive obstruction⁶

Severe Eosinophilic Asthma

Patient Characteristics	Airway dysfunction and significant number of exacerbations⁹ Late-onset disease^5,9 Often associated with sinus disease²
Biomarkers	Increased blood and sputum eosinophil counts^5,10 Increased Fe_NO levels⁵ Increased levels of IL-5 and IL-13⁵

Patients with severe eosinophilic asthma usually experience recurrent exacerbations⁵

Severe Neutrophilic Asthma

Patient Characteristics	Higher body mass index¹¹ History of smoking and cardiovascular complications¹¹ Associated with low pre-bronchodilator and postbronchodilator FEV₁¹²
Biomarkers	Increased sputum neutrophil counts^2,13 Increased levels of IL-8, T_H17, plasma IL-6^2,11 Increased C-reactive protein levels¹¹

Patients with severe neutrophilic asthma usually have systemic inflammation and reduced lung function^11,12

References: 1. Global Initiative for Asthma. Global strategy for asthma management and prevention. https://ginasthma.org/gina-reports. 2. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716-725. 3. Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172(2):149-160. 4. Shaw DE, Sousa AR, Fowler SJ, et al; Severe Asthma Workgroup of the SEAIC Asthma Committee. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015;46:1308-1321. 5. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343-373. 6. Campo P, Rodríguez F, Sánchez-Garcia S, et al; Severe Asthma Workgroup of the SEAIC Asthma Committee. Phenotypes and endotypes of uncontrolled severe asthma: new treatments. J Investig Allergol Clin Immunol. 2013;23(2):76-88. 7. Le Moual N, Siroux V, Pin I, Kauffmann F, Kennedy SM. Asthma severity and exposure to occupational asthmogens. Am J Respir Crit Care Med. 2005;172(4):440-445. 8. Moore WC, Meyers DA, Wenzel SE, et al; for the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181(4):315-323. 9. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218-224. 10. Wagener AH, de Nijs SB, Lutter R, et al. External validation of blood eosinophils, FE_NO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2):115-120. 11. Wood LG, Baines KJ, Fu J, Scott HA, Gibson PG. The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma. Chest. 2012;142(1):86-93. 12. Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc. 2009;6(3):256-259. 13. Nair P, Aziz-Ur-Rehman A, Radford K. Therapeutic implications of ‘netrophilic asthma’. Curr Opin Pulm Med. 2015;21(1):33-38.

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SEVEREASTHMA

Differentiating Severe Asthma Phenotypes