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Current concepts of severe asthma
Anuradha Ray, Mahesh Raundhal, Timothy B. Oriss, Prabir Ray, Sally E. Wenzel
Anuradha Ray, Mahesh Raundhal, Timothy B. Oriss, Prabir Ray, Sally E. Wenzel
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Review

Current concepts of severe asthma

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Abstract

The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development.

Authors

Anuradha Ray, Mahesh Raundhal, Timothy B. Oriss, Prabir Ray, Sally E. Wenzel

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Figure 1

Severe asthma phenotypes based on clinical, molecular, and immunological characteristics.

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Severe asthma phenotypes based on clinical, molecular, and immunological...
Disease onset at early age is usually associated with atopy, but type 2 inflammation is suppressed in only a subset of patients. Disease with late-age onset is highly heterogeneous in nature, as shown. The type 2 inflammatory response is undetectable in the airways of many of these subjects with low serum IgE, and this phenotype is associated with comorbidities such as obesity and smoking. Type 2 immune response with variable IgE, eosinophilia, and high FeNO is also a feature of late-onset disease with nasal polyps, which are detected in many of these subjects. Another patient subset includes extremely sick subjects with mixed granulocytic response, variable FeNO, and granulomas in their airways, suggesting autoimmune responses.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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