Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul;156(1):139-149.e4.
doi: 10.1016/j.jaci.2025.03.029. Epub 2025 Apr 10.

Effects of inflammatory endotypes on disease trajectory in chronic rhinosinusitis with nasal polyps

Christina Dorismond  1 , Yash Trivedi  2 , Mason R Krysinski  1 , Rory J Lubner  1 , Li-Ching Huang  3 , Sandeep Goswami  4 , Quanhu Sheng  3 , Rakesh K Chandra  1 , Naweed I Chowdhury  1 , Justin H Turner  5
Affiliations
Free article

Effects of inflammatory endotypes on disease trajectory in chronic rhinosinusitis with nasal polyps

Christina Dorismond et al. J Allergy Clin Immunol. 2025 Jul.
Free article

Abstract

Background: Although phenotypic features have traditionally guided treatment in chronic rhinosinusitis, recent research has favored categorization on the basis of inflammatory endotype. However, the impact of endotypic differeces on clinical outcomes remains largely unknown.

Objective: We sought to compare disease trajectory, primarily time-to-polyp recurrence, between chronic rhinosinusitis with nasal polyp (CRSwNP) endotypes.

Methods: Samples were obtained from patients with CRSwNP undergoing surgery between 2015 and 2023, and cytokine levels were measured using a multiplex bead assay. Principal-component analysis followed by hierarchical cluster analysis was used to identify endotype clusters. Clinical outcomes were subsequently compared between clusters.

Results: Six CRSwNP disease clusters were identified among the 269 included patients. Cluster 1 (46.5%) was characterized by relatively low inflammation. Cluster 4 (13.3%) and cluster 6 (7.1%) also exhibited low inflammation but with elevated levels of IL-12/IL-21 and CCL5, respectively. Cluster 2 (4.5%) represented a mixed type 1/3 inflammatory endotype (IFN-γHigh/IL-4High/IL-17AHigh), and cluster 3 (10.0%) was characterized by an innate, proinflammatory response (IL-1βHigh/IL-6High/IL-8High). Cluster 5 (18.9%) exhibited type 2-dominant inflammation (IL-5High/IL-9High/IL-13High). When comparing disease trajectory, cluster 2 (IFN-γHigh/IL-4High/IL-17AHigh) and cluster 4 (IL-12High/IL-21High) had the shortest time-to-polyp recurrence, whereas cluster 3 (IL-1βHigh/IL-6High/IL-8High) demonstrated the longest time-to-recurrence (P < .001). Time-to-oral steroid course (P = .13) and time-to-biologic therapy (P = .43) were similar across clusters.

Conclusions: The study highlights the heterogeneous nature of CRSwNP and differences in disease trajectory between endotypes, notably that patients with mixed type 1 and type 3 inflammation demonstrate more recalcitrant disease. These findings suggest that therapies beyond traditional type 2 inflammation treatments may be needed to effectively reduce CRSwNP disease recurrence.

Keywords: Chronic rhinosinusitis; biologics; cluster; cytokine; dupilumab; endotype; hierarchical cluster analysis; nasal polyp; outcomes; polyp recurrence; principal-component analysis.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement This project was supported by the National Institutes of Health (NIH) (grant nos. R01 AG065550 and K24 AI177947 to J.H.T.) and the Clinical and Translational Science Awards (CTSA) (award no. UL1TR000445) from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the NIH. Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this work the authors used ChatGPT to improve readability and language. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Disclosure of potential conflict of interest: R. K. Chandra consultant to Sanofi, Regeneron, Optinose, and Lyra Therapeutics. J. H. Turner has received grant support from the NIH/National Institute of Allergy and Infectious Diseases and NIH/National Institute on Aging; and has received personal fees from Regeneron. N. I. Chowdhury has received grant support from the Burroughs Wellcome Fund, the NIH/National Cancer Institute, NIH/National Institute of Allergy and Infectious Diseases (NIAID). C. Dorismond is a consultant for Myelin Healthcare. The rest of the authors declare that they have no relevant conflicts of interest.

LinkOut - more resources