February 2022

ENT

IMPROVEMENT IN PATIENT-REPORTED "TASTE" AND ASSOCIATION WITH SMELL IN DUPILUMAB-TREATED PATIENTS WITH CRSwNP

Featuring: ​ Robert C Kern, MD, Anju T Peters, MD​
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Read the full study, published in Clinical and Experimental Allergy, here.


Abstract
Background: Aspirin-exacerbated respiratory disease (AERD) patients regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells.

Objective: To determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in CRSwNP and AERD patients.

Methods: NP tissue was collected from AERD or CRSwNP patients, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial (NHBE) cells were stimulated alone or in combination with RA and interleukin (IL)-13 for 24 h.

Results: We observed lower retinoid levels in nasal polyps of AERD patients than in CRSwNP patients or healthy controls (P<0.01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P<0.01), consistent with lower tPA expression (P<0.01). In vitro, all-trans RA upregulated tPA levels in NHBE by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P<0.01).

Conclusion: RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from AERD patients, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating CRSwNP and/or AERD patients.
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Keywords: aspirin-exacerbated respiratory disease (AERD); chronic rhinosinusitis with nasal polyps (CRSwNP); retinoic acid (RA); tissue plasminogen activator (tPA).


This abstract was originally published in the Clinical and Experimental Allergy on February 12, 2022. ​
 Robert C Kern MD headshot
Robert C Kern, MD, chair of the department of Otolaryngology - Head and Neck Surgery, George A. Sisson, MD, and professor of Otolaryngology - Head and Neck Surgery and Allergy and Immunology in the Department of Medicine.
Anju T Peters, MD​, professor of Otolaryngology - Head and Neck Surgery  and Allergy and Immunology in the Department of Medicine.

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