The Association of TSLP and IL-4 with Patient-Reported Outcome Measures in Chronic Rhinosinusitis with Nasal Polyps

Sophie E Yu; Tolani F Olonisakin; John A Moore; Simon Chiang; Stella E Lee

doi:10.1177/19458924241311354

The Association of TSLP and IL-4 with Patient-Reported Outcome Measures in Chronic Rhinosinusitis with Nasal Polyps

Am J Rhinol Allergy. 2025 Jan 10:19458924241311354. doi: 10.1177/19458924241311354. Online ahead of print.

Authors

Sophie E Yu¹, Tolani F Olonisakin², John A Moore³, Simon Chiang¹, Stella E Lee^{1

4}

Affiliations

¹ Division of Otolaryngology - Head & Neck Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Otolaryngology - Head & Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
³ Department of Otolaryngology - Head and Neck Surgery, University of Pittsburgh Medical Center, Mercy Hospital, Pittsburgh, PA, USA.
⁴ Center for Surgery and Public Health, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

PMID: 39791191
DOI: 10.1177/19458924241311354

Abstract

Background: Thymic stromal lymphopoietin (TSLP) plays an important role in mediating the type-2-inflammatory response. This study examined how TSLP and interleukin (IL)-4 levels in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) correlated with clinical and postoperative outcomes.

Methods: Solid-phase sandwich ELISA was used to analyze TSLP and IL-4 levels in mucus (n = 47), plasma (n = 17), polyp (n = 30), inferior (n = 25), and middle (n = 26) turbinate tissue collected during functional endoscopic sinus surgery (FESS) in CRSwNP patients (n = 76) and controls (n = 11). Inclusion criteria includes patients with medical treatment refractory CRSwNP confirmed by endoscopy or maxillofacial CT. Exclusion criteria include history of immunodeficiency, coagulation disorders, fungal sinusitis, or cystic fibrosis. Levels of TSLP and IL-4 were correlated with SNOT-22, UPSIT, and fractional exhaled nitric oxide (FeNO) using MannWhitney U two-tailed test and linear regression with Spearman correlation coefficient test.

Results: TSLP is elevated in the inferior turbinates (effect size = 2.695, p = 0.0007) of CRSwNP patients compared to controls. IL-4 is expressed at elevated levels in the inferior (effect size = 3.092, p < 0.0001) and middle turbinates (effect size = 2.041, p = 0.019) compared to controls. Mucus TSLP (r = 0.4013, p = 0.0153) and IL-4 (r = 0.6138, p < 0.0001) positively correlate with preoperative FeNO levels. Lower TSLP in the inferior (r = -0.5179, p = 0.0231) and middle turbinates (r = -0.5075, p = 0.0224) and lower IL-4 in the inferior turbinates (r = -0.5205, p = 0.0223) correlate with a greater improvement in SNOT-22 post-FESS.

Conclusion: TSLP and IL-4 are elevated in patients with CRSwNP and correlated with increased preoperative FeNO levels and decreased sinonasal quality of life benefit after FESS. Expression of TSLP and IL-4 may play a role in guiding postoperative expectations in patients with treatment refractory CRSwNP.

Keywords: SNOT-22; UPSIT; chronic rhinosinusitis (CRS); chronic rhinosinusitis with nasal polyps (CRSwNP); endotype; fractional exhaled nitric oxide; functional endoscopic sinus surgery; interleukin-4; patient reported outcome measures (PROMs); thymic stromal lymphopoietin (TSLP).