Toll-like Receptor Expression and Inflammatory Cytokine Profiles in Smokers and Non-Smokers with Chronic Rhinosinusitis with Nasal Polyps and Their Associations with Clinical Disease Severity

Background: Cigarette smoking may modulate inflammatory and innate immune responses in individuals with chronic rhinosinusitis with nasal polyps (CRSwNP). This study compared inflammatory cytokine profiles and Toll-like receptor (TLR) expression between smoking and non-smoking patients with CRSwNP and examined their associations with clinical disease severity. Methods: A total of 25 non-smoking patients with CRSwNP and 24 active smokers with CRSwNP (CRSwNP + Smoker) were enrolled. Disease severity was assessed using Lund–Mackay computed tomography (LMK-CT), total polyp score (TPS), and the 22-item Sinonasal Outcome Test (SNOT-22). Cytokine levels in nasal polyp tissues were measured using a Bio-Plex multiplex cytokine assay, while the expressions of TLR2, TLR3, TLR4, TLR7, and NF-κB were assessed via immunohistochemistry (IHC). Results: IFN-γ and TNF-α levels were significantly higher in smokers, while IFN-α and IFN-β were also increased. TLR3 and TLR7 expression was significantly stronger in smokers, whereas TLR2, TLR4, and NF-κB did not differ significantly between groups. TPS and SNOT-22 scores were significantly higher in smokers, while LMK-CT scores were comparable. TLR3, TLR7, IFN-α, and IFN-β levels were positively correlated with SNOT-22 scores. Conclusions: Smoking is associated with increased TLR3/TLR7 expression, altered inflammatory cytokine profiles, and greater subjective disease severity in CRSwNP. These findings suggest that TLR3/TLR7-associated innate immune responses may contribute to smoking-related inflammation and symptom burden.