---
title: "Type 2‑low Asthma: Epidemiology, Mechanisms, Multiomics, and Emerging Treatments"
id: "pubmed-42747714"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42747714"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42747714/"
doi: "10.1007/s11882-026-01294-1"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Type 2‑low Asthma: Epidemiology, Mechanisms, Multiomics, and Emerging Treatments
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42747714
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42747714/)
- **DOI:** [10.1007/s11882-026-01294-1](https://doi.org/10.1007%2Fs11882-026-01294-1)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- **Type 2‑low asthma** is defined by low blood and sputum eosinophils and low fractional exhaled nitric oxide (FeNO) and remains a major unmet clinical need due to frequent corticosteroid insensitivity and limited targeted therapies. - Prevalence estimates vary: approximately **14%–39% of adults** with current asthma and **up to 60% of children** may have T2‑low disease. - Pathogenesis reflects complex non‑T2 biology, with contributions from **IL‑17 signaling**, innate immune activation via **IL‑1β** and **IL‑33**, and **neutrophilic inflammation**. - Heterogeneity in T2‑low asthma is influenced by systemic factors such as **obesity** and **immunosenescence**, and by environmental exposures including **ozone**. - Available therapeutic options showing benefit include long‑term **macrolide** therapy and the anti‑TSLP biologic **tezepelumab**, both reported to reduce exacerbation risk; many other pathway‑specific interventions have had inconsistent results. - Emerging metabolic strategies, for example **GLP‑1 receptor agonists**, are highlighted as potential additional therapeutic avenues, though evidence remains early. - Advances require mechanism‑based patient classification and development of clinically deployable **biomarkers** to match targeted therapies to specific biological drivers. - The review emphasizes the role of **multiomics** approaches to dissect heterogeneity and to inform biomarker and therapeutic development for T2‑low asthma.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Division of Allergy, Asthma and Immunology, Department of Pediatrics, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, Eastern Virginia Medical School, Norfolk, VA, USA. philip.mendez@chkd.org. * 2 Division of Allergy, Asthma and Immunology, Children's Hospital of The King's Daughters, Norfolk, VA, USA. philip.mendez@chkd.org. * 3 Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, FL, USA. * 4 Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, USA. * PMID: **42747714** * DOI: [ 10.1007/s11882-026-01294-1 ](https://doi.org/10.1007/s11882-026-01294-1) Item in Clipboard Review # Type 2-low Asthma: Epidemiology, Multiomics, and Emerging Therapies Philip Mendez et al. Curr Allergy Asthma Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Curr Allergy Asthma Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Curr+Allergy+Asthma+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Curr+Allergy+Asthma+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) . 2026 Sep 16;26(1):51. doi: 10.1007/s11882-026-01294-1. ### Authors [Philip Mendez](https://pubmed.ncbi.nlm.nih.gov/?term=Mendez+P&cauthor_id=42747714)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42747714/#short-view-affiliation-1 "Division of Allergy, Asthma and Immunology, Department of Pediatrics, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, Eastern Virginia Medical School, Norfolk, VA, USA. philip.mendez@chkd.org.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42747714/#short-view-affiliation-2 "Division of Allergy, Asthma and Immunology, Children's Hospital of The King's Daughters, Norfolk, VA, USA. philip.mendez@chkd.org."), [Alanis Rosado](https://pubmed.ncbi.nlm.nih.gov/?term=Rosado+A&cauthor_id=42747714)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42747714/#short-view-affiliation-3 "Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, FL, USA."), [Juan Carlos Cardet](https://pubmed.ncbi.nlm.nih.gov/?term=Cardet+JC&cauthor_id=42747714)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42747714/#short-view-affiliation-4 "Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, USA.") ### Affiliations * 1 Division of Allergy, Asthma and Immunology, Department of Pediatrics, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, Eastern Virginia Medical School, Norfolk, VA, USA. philip.mendez@chkd.org. * 2 Division of Allergy, Asthma and Immunology, Children's Hospital of The King's Daughters, Norfolk, VA, USA. philip.mendez@chkd.org. * 3 Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, FL, USA. * 4 Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, USA. * PMID: **42747714** * DOI: [ 10.1007/s11882-026-01294-1 ](https://doi.org/10.1007/s11882-026-01294-1) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Purpose of review:** Type 2-low (T2-low) asthma, characterized by low blood and sputum eosinophils and low fractional exhaled nitric oxide (FeNO), remains a major unmet need because of frequent corticosteroid insensitivity and a lack of targeted therapies. This review summarizes recent advances in its epidemiology, multiomics, and therapeutic landscape. **Recent findings:** T2-low inflammation is highly prevalent, affecting approximately 14%-39% of adults with current asthma and up to 60% of children. Its pathogenesis reflects complex non-T2 mechanisms, including IL-17 signaling, innate immune activation through IL-1β and IL-33, and neutrophilic inflammation. Heterogeneity is further shaped by systemic factors such as obesity and immunosenescence and by environmental exposures such as ozone. Among available therapies, long-term macrolides and the anti-TSLP biologic tezepelumab have shown significant efficacy in reducing exacerbations, whereas other pathway-specific interventions have yielded inconsistent clinical benefits. Emerging metabolic approaches, including GLP-1 receptor agonists, may offer additional promise. Progress in T2-low asthma will require mechanism-based classification and clinically deployable biomarkers to align targeted therapies with specific biological drivers. **Keywords:** Biomarkers; Neutrophilic asthma; Non-T2 asthma; Non-eosinophilic asthma; T2-low asthma. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Competing interests: The authors declare no competing interests. ## References 1. 1. Grunwell JR, Fitzpatrick AM. Asthma Phenotypes and Biomarkers. Respir Care. 2025;70(6):649–74. . - [DOI](https://doi.org/10.1089/respcare.12352) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/40013975/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/12408891/) 2. 1. Oppenheimer J, Hoyte FCL, Phipatanakul W, Silver J, Howarth P, Lugogo NL. Allergic and eosinophilic asthma in the era of biomarkers and biologics: similarities, differences and misconceptions. Ann Allergy Asthma Immunol. 2022;129(2):169–80. . - [DOI](https://doi.org/10.1016/j.anai.2022.02.021) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35272048/) 3. 1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2026 [Internet]. [cited 2026 Aug 4]. Available from: . [www.ginasthma.org](http://www.ginasthma.org) 4. 1. Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007;62(12):1043–9. . PubMed PMID: 17356056; PubMed Central PMCID: PMC2094295. - [DOI](https://doi.org/10.1136/thx.2006.073429) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/17356056/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/2094295/) 5. 1. Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, et al. Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level. N Engl J Med. 2019;380(21):2009–19. . PubMed PMID: 31112384; PubMed Central PMCID: PMC6711475. - [DOI](https://doi.org/10.1056/nejmoa1814917) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/31112384/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/6711475/) Show all 102 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) ## MeSH terms * Anti-Asthmatic Agents / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Anti-Asthmatic+Agents%2Ftherapeutic+use%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Anti-Asthmatic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Asthma* / diagnosis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Asthma%2Fdiagnosis%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Asthma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Asthma* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Asthma%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Asthma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Asthma* / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Asthma%2Fepidemiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Asthma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Asthma* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Asthma%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Asthma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Asthma* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Asthma%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Asthma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Biomarkers / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biomarkers%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Biomarkers) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Eosinophils* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eosinophils%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Eosinophils) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Multiomics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Multiomics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Multiomics) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) * Nitric Oxide / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Nitric+Oxide%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Nitric+Oxide) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747714/) ## 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