Allergy Asthma Immunol Res.  2019 Jul;11(4):482-497. 10.4168/aair.2019.11.4.482.

Comparison of Corticosteroids by 3 Approaches to the Treatment of Chronic Rhinosinusitis With Nasal Polyps

Affiliations
  • 1Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. dr.luozhang@139.com, wangcs830@126.com
  • 2Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
  • 3Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Abstract

PURPOSE
Corticosteroids are regarded as the mainstay of medical treatment of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). To date, a head-to-head comparison of the efficacy and safety of glucocorticoid preparations administered via different routes for the treatment of chronic rhinosinusitis with nasal polyps has not been reported. To compare the efficacy and safety of steroids administered via the oral, intranasal spray and transnasal nebulization routes in the management of ECRSwNP over a short course.
METHODS
Overall, 91 patients with ECRSwNP were recruited prospectively and randomized to receive either oral methylprednisolone, budesonide inhalation suspension (BIS) via transnasal nebulization, or budesonide nasal spray (BNS) for 2 weeks. Nasal symptoms and polyp sizes were assessed before and after the treatment. Similarly, nasal polyp samples were evaluated for immunological and tissue remodeling markers. Serum cortisol levels were assessed as a safety outcome.
RESULTS
Oral methylprednisolone and BIS decreased symptoms and polyp sizes to a significantly greater extent from baseline (P < 0.05) than BNS. Similarly, BIS and oral methylprednisolone significantly reduced eosinophils, T helper 2 cells, eosinophil cationic protein, interleukin (IL)-5, and expression of matrix metalloproteinases 2 and 9, and significantly increased type 1 regulatory T cells, IL-10, transforming growth factor-β, and tissue inhibitor of metalloproteinases 1 and 2 in nasal polyps to a greater extent than BNS. Post-treatment serum cortisol levels were significantly decreased by oral methylprednisolone compared to BIS or BNS, which did not significantly alter the cortisol levels.
CONCLUSIONS
A short course of BIS transnasal nebulization is more efficacious compared to BNS in the management of ECRSwNP and is safer than oral methylprednisolone with respect to hypothalamic-pituitary-adrenal axis function.

Keyword

Chronic rhinosinusitis; glucocorticoids; nasal polyps; nasal spray; transnasal nebulization

MeSH Terms

Adrenal Cortex Hormones*
Budesonide
Eosinophil Cationic Protein
Eosinophils
Glucocorticoids
Humans
Hydrocortisone
Inhalation
Interleukin-10
Interleukins
Matrix Metalloproteinases
Methylprednisolone
Nasal Polyps*
Polyps
Prospective Studies
Steroids
T-Lymphocytes, Regulatory
Tissue Inhibitor of Metalloproteinases
Adrenal Cortex Hormones
Budesonide
Eosinophil Cationic Protein
Glucocorticoids
Hydrocortisone
Interleukin-10
Interleukins
Matrix Metalloproteinases
Methylprednisolone
Steroids
Tissue Inhibitor of Metalloproteinases

Figure

  • Fig. 1 Flow diagram of patients enrolled in the study. CRSwNP, chronic rhinosinusitis with nasal polyps.

  • Fig. 2 Effect of different treatments on clinical outcomes as primary end points: (A) nasal obstruction, (B) rhinorhea, (C) loss of smell, (D) facial pain, (E) TNSS, (F) polyp score, (G) FEV1/FVC, (H) FeNO. VAS, visual analogue scale TNSS, total nasal symptom score; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FeNO, fractional nitric oxide. *P < 0.05 compared to baseline (before treatment).

  • Fig. 3 Effect of different treatments on inflammatory cytokines and mediators in tissue homogenates: (A) ECP, (B) IFN-γ, (C) IL-5, (D) IL-10, (E) IL-17, (F) TGF-β. ECP, IL-5, IL-10, IL-17, and IFN-γ were determined using cytometric bead array, and TGF-β using enzyme-linked immunosorbent assay. ECP, eosinophil cationic protein; IFN-γ, interferon-γ; IL, interleukin; TGF-β, transforming growth factor-β. *P < 0.05 compared to baseline (before treatment).

  • Fig. 4 Effect of different treatments on inflammatory cells in nasal polyp tissue: (A) percentage of tissue eosinophils in the total cell count, (B) nTreg cells, (C) Th1 cells, (D) Th2 cells, (E) Th17 cells, (F) TR1 cells. Eosinophils were determined using hematoxylin and eosin staining and T-cell subsets using flow cytometric analysis. EOS, eosinophil; nTreg, natural regulatory T; Th, T helper. *P < 0.05 compared to baseline (before treatment).

  • Fig. 5 Remodeling pattern shifts in nasal polyp tissues following different treatments: (A) collagen, (B) albumin, (C) MMP-2, (D) MMP-9, (E) TIMP-1, (F) TIMP-2. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase. *P < 0.05 compared to baseline (before treatment).


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Mu Xian, Siyuan Ma, Kuiji Wang, Hongfei Lou, Yang Wang, Luo Zhang, Chengshuo Wang, Cezmi A. Akdis
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