Research Identifies Asthma Endotypes Suggesting Different Treatment Strategies

An in-press study detailed the characteristics of 4 asthma endotypes and their association with asthma-related healthcare outcomes and responsiveness to treatment.

An in-press study detailed the characteristics of 4 asthma endotypes and their association with asthma-related healthcare outcomes and responsiveness to treatment.

The research used data from the National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP), which aims to identify clinical and pathophysiological differences between mild-to-moderate and severe asthma. Previous studies in 3 SARP cohorts identified several relationships between asthma type and outcomes; for instance, higher levels of interleukin-6 (IL-6) are correlated with lower lung function and more frequent asthma exacerbations, whereas higher fractional exhaled nitric oxide (FeNO) levels are associated with type 2 inflammatory asthma and better response to corticosteroid treatment.

The current research, published ahead of print by the Journal of Allergy and Clinical Immunology, aimed to investigate whether several clinical biomarkers, including the combination of FeNO and blood eosinophil count (type 2) and IL-6 (non—type 2) levels, are associated with clinical and cellular characteristics of asthma.

Investigators identified some demographic and clinical differences among the SARP cohorts; for example, adults in SARP3 were older and less likely to be African American than those in SARP1-2, and the SARP3 cohort had a higher percentage of severe asthma and systemic corticosteroid use in the past year (P <.0001 for all). However, because the cohorts had similar levels of FeNO, blood eosinophils, serum sIL-6R, and plasma or serum IL-6, a merged set of SARP1-3 data was used for the current analyses.

The analyses showed that higher plasma or serum IL-6 levels were significantly associated with being older, being female, and having a higher body mass index (BMI), but there was no significant difference by race. IL-6 levels were also correlated with higher blood neutrophil counts and likelihood of asthma hospitalizations or systemic corticosteroid use in the past year. There were no correlations between IL-6 levels and the cellular characteristics of type 2 asthma (higher blood eosinophil counts, percentage of sputum eosinophils, serum immunoglobulin E levels, and FeNO levels), leading the study authors to conclude, “IL-6 levels are correlated with asthma phenotypes but not type 2 asthma biomarkers.”

In contrast, higher FeNO levels were associated with younger age and lower BMI, as well as asthma hospitalizations, intensive care unit admissions for asthma, and systemic corticosteroid use in the last year. Both FeNO levels and blood eosinophil count were positively correlated with the cellular characteristics of type 2 asthma, and the investigators noted that they may be useful biomarkers for severe asthma and asthma exacerbations.

Combinations of each of the biomarker levels could be used to create 4 distinct endotypes: high FeNo and high blood eosinophil (HH), low FeNO and low blood eosinophil, high FeNO and low blood eosinophil (HL), and low FeNO and high blood eosinophil (LH). The study authors suggested that the HH endotype of asthma may be more effectively treated using a combination of anti—type 2 and anti–IL-6 drugs, whereas those drug types individually may be more effective in treating patients with the LH or HL endotypes, respectively.

“It will be critical to develop and test potential biomarkers that will predict responsiveness or lack of responsiveness to the biologic therapies, in order to advance stratified therapy in asthma,” the authors concluded.


Li X, Hastie AT, Peters MC, et al; NHLBI Severe Asthma Research Program (SARP) Networks. Investigation of the relationship between IL-6 and type 2 biomarkers in severe asthma [published online September 9, 2019]. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2019.08.031.