Systemic prednisone administration selectively alters granulocyte subsets in nasal polyps from aspirin-exacerbated respiratory disease and chronic rhinosinusitis patients

Authors

  • Justin A. Edward MS,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA
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  • Mrinmoy Sanyal PhD,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA
    2. Department of Pathology, Pathology, Medicine, Stanford University School of Medicine, Stanford, CA
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  • Vijay R. Ramakrishnan MD,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, University of Colorado School of Medicine, Aurora, CO
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  • Wei Le MD,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA
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  • Alan L. Nguyen BA,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA
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  • Todd T. Kingdom MD,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, University of Colorado School of Medicine, Aurora, CO
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  • Peter H. Hwang MD,

    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA
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  • Jayakar V. Nayak MD, PhD

    Corresponding author
    1. Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA
    • Correspondence to: Jayakar V. Nayak, MD, PhD, Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305; e-mail: jnayak@ohns.stanford.edu

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  • Funding sources for the study: Stanford University Department of Otolaryngology; University of Colorado Department of Otolaryngology; American Academy of Otolaryngology–Head and Neck Surgery.

  • Potential conflict of interest: None provided.

Abstract

Background

Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis. Despite the spectrum of NP conditions, cellular differences between NPs from patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) are poorly understood. NPs are associated with abundant eosinophils; the contributions of neutrophil and basophil granulocytes are less defined. We therefore sought to assess granulocyte subpopulations, and differential effects following prednisone pretreatment, within NPs of CRSwNP and AERD patients.

Methods

NPs, adjacent ethmoid sinus tissue, and peripheral blood mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus surgery. Samples from 5 cohorts: CRSwNP ± prednisone (n = 6 each), AERD ± prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional flow cytometry to gate granulocyte populations. Specimens were also assessed using immunohistochemistry (IHC) staining.

Results

Systemic prednisone administration was associated with a lower frequency of eosinophils (p < 0.0001, n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils (p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone treatment. In contrast, steroids do not alter basophil proportions (p = 0.48, n = 6) within NPs from either group. No significant shift in granulocyte subsets after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs from the same patients. Immunohistochemistry (IHC) staining supported these findings.

Conclusion

Granulocyte subpopulations are focally affected within NPs by systemic steroid exposure, without notable granulocyte alterations in the surrounding regional tissues. These data provide direct insights into the cellular effects of routine prednisone exposure in CRS patients, and highlight a unique microenvironment present within NP lesions.

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