December 2021

ENT

RESEARCHERS INVESTIGATE ELEVATION OF ACTIVATED NEUTROPHILS IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS

Multi-omics colocalization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus.

Featuring: ​ Atsushi Kato, PhD, Robert C Kern MD, Bruce K Tan, MD​
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Read the full study here.

​​​Abstract
In a study published in The Journal of Allergy and Clinical Immunology, Bruce K. Tan, MD, associate professor of Otolaryngology – Head and Neck Surgery, Kevin C. Welch, MD, professor of Otolaryngology – Head and Neck Surgery, Stephanie Shintani Smith, MD, MS, assistant professor of Otolaryngology – Head and Neck Surgery, David B. Conley, MD, associate professor of Otolaryngology – Head and Neck Surgery, and Robert C. Kern, MD, chair of the Department of Otolaryngology – Head and Neck Surgery and George A. Sisson, MD, Professor of Otolaryngology, investigated the accumulation and inflammatory roles of neutrophils in CRSwNP.

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is well characterized by type 2 (T2) inflammation characterized by eosinophilia in Western countries. However, the presence and the roles of neutrophils in T2 CRSwNP are poorly understood.
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Objective: To clarify accumulation and inflammatory roles of neutrophils in Western CRSwNP.

Methods: Sinonasal tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS, and neutrophil markers were determined by ELISA. The presence of neutrophils in tissue was determined by flow cytometry. The gene expression profiles in neutrophils were determined by RNA-Sequencing.

Results: A neutrophil marker elastase was selectively elevated in nasal polyp (NP) tissue whereas eosinophilic cationic protein (an eosinophil marker) was elevated in both uncinate and NP tissues of CRSwNP patients. NLF myeloperoxidase (another neutrophil marker) was also significantly elevated in CRSwNP compared to control patients. Neutrophil markers were more greatly elevated in CRSwNP patients with recurrent disease. Flow cytometric analysis confirmed that neutrophil numbers were significantly elevated in NPs compared to control tissues. RNA-Sequencing analysis found that 344 genes were >3-fold and significantly elevated in NP neutrophils compared to peripheral blood neutrophils. Gene ontology analysis suggested that elevated genes in NP neutrophils were significantly associated with activation. Results suggest that neutrophils are accumulated in T2 NP tissues and that accumulated neutrophils are highly activated and contribute to inflammation in NPs.

Conclusions: Neutrophils may play a heretofore unrecognized meaningful role in the pathogenesis of CRSwNP in western countries and may be considered to be a potentially important therapeutic target in T2 CRSwNP.
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This abstract was originally published in The Journal of Allergy and Clinical Immunology on December 22, 2021 . ​
Bruce K Tan, MD​, associate professor of Otolaryngology - Head and Neck Surgery and associate professor of allergy and immunology in the Department of Medicine.
Kevin C. Welch, MD, professor of Otolaryngology - Head and Neck Surgery and Northwestern University's Feinberg School of Medicine.
Bruce K Tan, MD headshot

Stephanie Shintani Smith, MD, MS, 
​assistant professor of Otolaryngology - Head and Neck Surgery and Northwestern University's Feinberg School of Medicine.
David B. Conley, MD, ​associate professor of Otolaryngology - Head and Neck Surgery and Northwestern University's Feinberg School of Medicine.
Robert C Kern, MD, chairman of the Department of Otolaryngology - Head and Neck Surgery, and George A. Sisson, MD Professor of Otolaryngology at Northwestern University's Feinberg School of Medicine.

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