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

current GINA Report1

According to GINA

Patients with severe asthma may benefit from phenotyping into categories such as severe allergic, aspirin-exacerbated, or eosinophilic asthma. Also, patients ≥6 years with severe allergic asthma with elevated IgE levels may benefit from anti-IgE therapy (Evidence A), those ≥12 years of age with severe eosinophilic asthma may benefit from anti–IL-5 therapy (Evidence B), and LTRAs [leukotriene receptor antagonists] may be helpful for patients found to be aspirin sensitive (Evidence B).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


Patient Characteristics

  • Adults, aged 20 or older1,2
  • Not associated with allergy1
  • More common in women1


  • Increased FeNO (>50 parts per billion)1
  • Increased IL-52
  • Greater numbers of eosinophils and mast cells2

Late onset non-allergic asthma is often corticosteroid-refractory1

Patient Characteristics

  • Often presents in childhood1
  • Associated with history of allergic disease1
  • More common in females3


  • Specific IgE2
  • Increased blood neutrophil counts4
  • Increased blood and sputum eosinophil counts4,5
  • Increased FeNO5

Patients with severe allergic (atopic) asthma have higher amounts of TH2 cytokines2

Patient Characteristics

  • Present with childhood-onset asthma and remain symptomatic in adolescence6
  • History of smoking and prolonged exposure to allergens in the workplace6,7
  • Fixed obstruction related to bronchial inflammation (worsens after exacerbations)6


  • Increased sputum neutrophil counts8

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

Patient Characteristics

  • Airway dysfunction and significant number of exacerbations9
  • Late-onset disease5,9
  • Often associated with sinus disease2


  • Increased blood and sputum eosinophil counts5,10
  • Increased FeNO levels5
  • Increased levels of IL-5 and IL-135

Patients with severe eosinophilic asthma usually experience recurrent exacerbations5

Patient Characteristics

  • Higher body mass index11
  • History of smoking and cardiovascular complications11
  • Associated with low pre-bronchodilator and postbronchodilator FEV112


  • Increased sputum neutrophil counts2,13
  • Increased levels of IL-8, TH17, plasma IL-62,11
  • Increased C-reactive protein levels11

Patients with severe neutrophilic asthma usually have systemic inflammation and reduced lung function11,12

References: 1. Global Initiative for Asthma. Global strategy for asthma management and prevention, 2017. Accessed July 26, 2017. 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, FENO 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.

825106R0 August 2017