The Mixed Neutrophilic–Eosinophilic Endotype of CRSwNP Blunts Postsurgical Improvement as Determined by the Completeness of Surgery Index

Background The Completeness of Surgery Index (CoSI) is a novel metric for assessing surgical quality in chronic rhinosinusitis with nasal polyps (CRSwNP). Structured histopathology (SHP) is helpful for characterizing drivers of inflammation. Integrating these two tools to identify patients at higher risk for surgically recalcitrant disease has not been explored. Methods CRSwNP patients with a preoperative CoSI < 70 undergoing primary or revision functional endoscopic sinus surgery (FESS) followed by steroid irrigations from 2018 to 2025 were included. CT images and data about comorbidities, SHP, biologic use, and SNOT‐22 scores were retrospectively reviewed. Logistic regression, Mann–Whitney U , and Chi‐squared tests were used for analysis. Results The cohort comprised 207 patients achieving significant SNOT‐22 improvement 12 months post‐FESS (−29.1 ± 22.1; p < 0.001). Mean age was 48.4 years; 53 (25.2%) had aspirin‐exacerbated respiratory disease (AERD), and 114 (54.3%) were revision cases. Mean preoperative CoSI was 37.2 among revisions. Mean postoperative CoSI was 80.0. Among SHP variables, only neutrophilic infiltrate correlated with less improvement in SNOT‐22 at 12 months (median −22.4 vs. −33.8; p = 0.007). The effect of neutrophils was seen only with high tissue eosinophilia, with a statistically significant interaction term in the multivariable model. Neutrophil infiltrates were not associated with increased postoperative biologic use. Conclusion Complete surgery affords significant, sustained SNOT‐22 improvement even with high tissue eosinophilia or abnormal tissue architecture. Comorbid tissue neutrophilia and eosinophilia may represent a mixed endotype of CRSwNP with reduced improvement in SNOT‐22 after FESS. Combining SHP with CoSI may be helpful for decision‐making regarding adjunct medical therapy postoperatively to optimize patient outcomes.