Tsuda Junko

Background: Eosinophilic chronic rhinosinusitis (ECRS) is generally characterized by refractory type 2 inflammation along with severe asthma. Although tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, has broad efficacy in severe asthma, its effects on sinonasal inflammation in ECRS remain unclear. In this retrospective observational study, we investigated the radiological and clinical changes in patients with ECRS and severe asthma treated with tezepelumab. Methods: Clinical data, blood eosinophil counts, fractional exhaled nitric oxide (FeNO), total serum IgE levels, lung function, and paranasal sinus CT findings of seven patients with ECRS who received tezepelumab for comorbid severe asthma at a single tertiary care center between 2022 and 2024, were collected. Radiologic severity was assessed using the Lund-Mackay score (LMS) at baseline and ≥6 months after treatment initiation. Results: The median LMS showed a trend toward reduction from baseline to ≥6 months, although this difference did not reach statistical significance (p = 0.051). In contrast, blood eosinophil counts, serum IgE levels, FeNO levels, and the FEV_1/FVC ratio did not show statistically significant changes during the observation period. Conclusion: Tezepelumab therapy showed a trend toward reduction in the Lund-Mackay score in patients with ECRS and severe asthma, although statistical significance was not reached. Systemic biomarkers and lung function remained stable.

This study investigated the potential of adalimumab (ADA), a monoclonal antibody targeting TNF-alfa, to protect the inner ear from intense sound exposure, given that inflammatory cytokines, including TNF-alfa, are linked to hearing loss in acoustic disorders. In this study, adalimumab was administered to mice, and its effect on the inner ear was assessed. We examined the translocation of ADA to the inner ear and its ototoxicity and impact on acoustic exposure. The results showed that adalimumab partially reached the cochlea after administration but increased the susceptibility to acoustic exposure, resulting in higher hair cell loss in the inner ear. While TNF-alfa had been considered a potential therapeutic target, the results suggested that excessive TNF-alfa suppression could harm the inner ear. We acknowledged some limitations, such as the use of adalimumab instead of an anti-mouse TNF-alfa antibody and the need to explore the suppression of other cytokines for better inner ear protection. In conclusion, adalimumab administration was found to increase the inner earʼs susceptibility to acoustic exposure, potentially leading to more significant hair cell damage, possibly due to excessive TNF-alfa suppression