L28:
Effects of Reslizumab on Nasal Polyp Inflammation in Aspirin Exacerbated Respiratory Disease
Monday, March 5, 2018
South Hall A2 (Convention Center)
Whitney W. Stevens, MD PhD, Anna G. Staudacher, MS, Anju T. Peters, MD FAAAAI, Lydia A Suh, BS, Roderick G. Carter, BS, Stephanie R. Fischer, BS, Kathryn E. Hulse, PhD, Julie A. Poposki, MS, James E Norton, MS, Atsushi Kato, PhD, Leslie C. Grammer, MD FAAAAI, David B. Conley, MD, Robert C. Kern, MD, Stephanie Shintani-Smith, MD, Bruce K. Tan, MD, MS, Kevin C. Welch, MD, Robert P. Schleimer, PhD FAAAAI

Rationale: Targeting IL-5 can improve clinical symptoms in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The mechanisms by which anti-IL-5 drugs exert their clinical effects remain unclear. This is the first study, to our knowledge, to assess the inflammatory environment in NP before and during Reslizumab treatment in the same patient with Aspirin Exacerbated Respiratory Disease (AERD).

Methods: NP tissue and blood were collected from an AERD patient pre-Reslizumab and then 8 months post-Reslizumab initiation. Gene expression, protein levels, and cellular infiltrates were assessed using RT-PCR, ELISA, flow cytometry, and immunohistochemistry. NP and blood isolated from AERD patients not taking Reslizumab served as comparators.

Results: On Reslizumab, the patient’s asthma improved, but sinonasal disease required revision surgery. NP ECP protein levels and CCR3 and CLC gene expression levels were reduced by 90-fold, 25-fold, and 300-fold respectively post-Reslizumab compared to pre-Reslizumab. Few peripheral eosinophils were detected post-Reslizumab. NP eosinophils (CD45+Siglec8+FcERI-) were detected post-Reslizumab (1,801 cells/mg tissue) at similar levels to AERD controls (7,645 ± 4,101 cells/mg tissue). NP eosinophils had lower CD69 expression post-Reslizumab (MFI 372) compared to AERD controls (MFI 21,095 ± 5,694). NP basophils were elevated post-Reslizumab (515 cells/mg tissue), with lower 2D7 intensity (MFI 206), compared to untreated AERD NP (155 ± 37 cells/mg tissue; MFI 1,986 ± 675).

Conclusions: In this patient, Reslizumab reduced peripheral eosinophilia and markers of eosinophil activation and granular proteins in NP. However, revision sinus surgery was required suggesting that other cell types (including basophils) may play an important role in AERD pathogenesis in this individual.