Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma

Abstract

Background: Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency and degree of overlap among these subtypes is unclear.

Objective: To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes.

Methods: Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935) and (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick-positive and/or positive serum-specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cut-off ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cut-off of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition.

Results: In the non-subtype-selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma-selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cut-off values.

Conclusions and clinical relevance: In this post hoc analysis in adults with moderate-to-severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding the degree of overlap across phenotypes will help patient management and guide treatment options.

Trial registration: ClinicalTrials.gov NCT00314574 NCT01922037 NCT01545440 NCT01545453 NCT01867125 NCT01868061.

Conflict of interest statement

M. Chen has received fellowship grant support from Genentech, Inc., and is an employee of Southwest Asthma and Allergy Associates. K. Shepard II has no conflicts of interest to disclose. M. Yang, P. Raut, H. Pazwash and C. T. J. Holweg are employees of Genentech, Inc., and stockholders in Roche. E. Choo has acted as a paid consultant to GlaxoSmithKline and a speaker to AstraZeneca and Teva Pharmaceutical Industries Ltd.

© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Figures

FIGURE 1

(A‐C) Baseline total IgE, EOS counts and FeNO levels in the non‐subtype–selected and (D‐F) allergic asthma–selected populations. For each box plot, the top and bottom box edges correspond to the third and first quartiles. The line inside the box represents the median. The top and bottom whisker lines represent maximum and minimum values that are within the 1.5× the interquartile range distance from the third and first quartiles, respectively. Outliers are not shown for visualization purposes. EOS, eosinophils; FeNO, fractional exhaled nitric oxide; IgE, immunoglobulin E; T2, type 2

FIGURE 2

Overlap among (A) allergic, (B) eosinophilic and (C) T2 asthma subtypes in the non‐subtype–selected population. Definitions: eosinophilic asthma, eosinophil count ≥ 300 cells/µL; T2 asthma, FeNO level ≥ 35 ppb. FeNO, fractional exhaled nitric oxide; T2, type 2

FIGURE 3

Overlap among allergic, eosinophilic and T2 asthma subtypes in the allergic asthma–selected population. Definitions: eosinophilic asthma, eosinophil count ≥300 cells/µL; T2 asthma, FeNO level ≥ 35 ppb. FeNO, fractional exhaled nitric oxide; T2, type 2