Identification of the heterogeneity and classification of asthma by sample phenotypes may provide a foundation from which to understand disease causality.1
In severe asthma, identification of phenotypes has commonly been approached through:
Several research groups have developed cluster analyses of phenotypes in severe asthma. While their findings differ in groupings and classification, the clusters support the importance of disease heterogeneity in asthma and suggest differences in pathophysiologic mechanisms that determine cluster assignments.1,2
*Individual figure size is proportional to the frequency of a specific cluster. The percentage of subjects from that cluster who are correctly assigned is indicated numerically within the shape.
Reprinted from the American Journal of Respiratory and Critical Care Medicine. Vol 181. Moore WC, Meyers DA, Wenzel SE, et al; Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program, pp 315-323, 2009, with permission from The American Thoracic Society.
CLUSTER 1: Mild allergic asthma—early onset; atopic; normal lung function; ≤2 controller medications; minimal healthcare use; minimal sputum eosinophilia
CLUSTER 2: Mild-moderate allergic asthma—most common cluster; early onset; atopic; borderline FEV1, but reverse to normal; ≤2 controller medications; low healthcare use; infrequent need for oral corticosteroids; minimal sputum eosinophilia
CLUSTER 3: More severe older-onset asthma—older; very late onset; higher BMI (obese); less atopic; slightly decreased FEV1 with some reversibility; frequent need for oral corticosteroids, despite ≥3 controller medications, including high doses of inhaled corticosteroids; sputum eosinophilia
CLUSTER 4: Severe variable allergic asthma—early onset; atopic; severely decreased FEV1, but very reversible to near normal; high frequency of symptoms and albuterol use; “variable” with need for frequent oral corticosteroids; high healthcare use; sputum eosinophilia
CLUSTER 5: Severe fixed-airflow asthma—older; longest duration; less atopic; severely decreased FEV1 with less reversibility (COPD similarities); high frequency of symptoms and albuterol use despite oral corticosteroids; high healthcare use; comorbidities; both sputum eosinophilia and neutrophilia
Reprinted with permission from the American Thoracic Society. 1
References: 1. 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. 2. Holgate ST, Sly PD. Asthma pathogenesis. In: Adkinson Jr NF, Bochner BS, Burks AW, et al, eds. Middleton’s Allergy Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:812-841. 3. 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.