Treatment of Non-Th2 Asthma

In the majority of patients, asthma is driven by T-helper 2 (TH2) cells and characterized by eosinophilic inflammation, TH2-cell associated cytokine production, and airway hyperresponsiveness. The new update of the severe asthma guidelines by the European Respiratory Society and American Thoracic Society fails to address patients with Th2 asthma. Despite research recently including biologic agents that modify Th2 inflammation, this area of severe asthma continues to be an issue in clinical practice.

Diego Maselli Caceres, MD, a pulmonologist at UT Health San Antonio, recently spoke about non-Th2 asthma at CHEST2020. Here are his answers to our burning questions.

Consultant360: Your session at CHEST2020 focused on updates for the treatment of non-T-helper cell type 2 (Th2) asthma that were published by the European Respiratory Society and the American Thoracic Society. What are the current treatments for this phenotype?

Dr Maselli: There are limited approved options for type 2 low asthma (non-type 2). It is important to test for type 2 markers in the lowest possible corticosteroid dose to determine the phenotype most accurately. For patients who do not meet criteria for biological medications, chronic azithromycin therapy, and bronchial thermoplasty can be considered, particularly in those who have frequent exacerbations despite maximal inhaler therapy. Tezepelumab, a monoclonal antibody, targets thymic stromal lymphopoietin and, in its later stages of approval, has shown to be beneficial in patients with severe asthma and low T2 signatures (ie, low peripheral eosinophils and low immunoglobulin E [IgE] levels).

C360: How can clinicians choose the right biologic agent for children?

Dr Maseli: Biologic agents in children should be considered depending on their age and biomarker profile. Omalizumab is approved for patients aged 6 years or older with an elevated IgE level and positive testing for perennial allergens. Mepolizumab is approved for patients aged 6 years or older with a eosinophilic phenotype (ie, peripheral blood eosinophils >150 cells/μL). Benralizumab and dupilumab are approved for patients aged 12 years or older with an eosinophilic phenotype. Other important factors that are used to select therapy include caregiver/parent preferences and comorbid conditions.  

C360: How can clinicians choose the right biologic agent for adults?

Dr Maseli: Biologic agents are chosen based on the biomarker profile, comorbid conditions, and provider/patient preferences. Dupilumab is the only biologic agent approved for patients taking chronic oral steroids, regardless of the biomarker profile. There are no head-to-head studies to compare these agents. Although there are multiple studies with indirect comparisons evaluating cost, efficacy, and other outcomes between agents, the varying methodologies and populations make it difficult to reach meaningful conclusions

C360: What are the limitations of the guidelines?

Dr Maseli: The guidelines currently are limited because there is no exact definition of a responder, partial responder, or nonresponder to biologic agents. There is limited guidance on when to switch biologics for those patients who have partial responses.  

C360: What are the key takeaways from your session?

Dr Maseli: It is important to confirm the phenotype of asthma. This may require repeat testing at the lowest possible steroid dose. There are limited options for non-type 2 asthma, but azithromycin and bronchial thermoplasty should be considered. 



  1. Maselli Caceres D. Beyond the guidelines: updates in the treatment of non-Th2 asthma. Talk presented at: CHEST 2020; October 18-21, 2020; Virtual.