嗅觉丧失持续时间与类固醇反应性作为预测慢性鼻窦炎伴鼻息肉患者对度普利尤单抗治疗反应的指标

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中文摘要

背景： 嗅觉功能障碍影响60%-80%的慢性鼻窦炎伴鼻息肉（CRSwNP）患者。度普利尤单抗可改善CRSwNP患者的嗅觉结局，但改善程度在患者间存在差异。本研究探讨嗅觉丧失持续时间、类固醇反应性及基线嗅觉波动是否与度普利尤单抗治疗反应相关。
方法： 开始使用度普利尤单抗的CRSwNP患者被纳入一项单臂前瞻性研究。记录嗅觉丧失持续时间、类固醇反应性和基线嗅觉波动。在基线和度普利尤单抗治疗12周后，使用Sniffin' Sticks进行嗅觉测试（阈值、辨别、识别及复合TDI评分）并记录患者报告的嗅觉能力。分析这些临床特征与嗅觉结局之间的关系。
结果： 报告嗅觉丧失持续时间较短的患者在度普利尤单抗治疗后TDI改善更大（R2 = 0.089，p = 0.02）。具体而言，嗅觉丧失少于10年的患者与持续时间较长者相比，TDI改善显著更大（10.9 vs. 4.5分，p = 0.01），该差异超过了5.5分的最小临床重要差异。类固醇反应性患者在多项指标上显示出更高的变化评分，包括患者报告的嗅觉和气味识别评分，尽管TDI改善总体无差异。报告基线嗅觉波动的患者在整个治疗期间TDI评分较高，但变化幅度相似。
结论： 嗅觉丧失持续时间与CRSwNP患者对度普利尤单抗的治疗反应相关，10年阈值可识别出较不可能获得临床有意义改善的患者。类固醇反应性提供额外的预后价值。这些易于获取的临床特征可指导患者咨询和治疗预期。

英文摘要

BACKGROUND: Olfactory dysfunction affects 60%-80% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab improves olfactory outcomes in CRSwNP, but the degree of improvement varies among patients. This study examined whether duration of olfactory loss, steroid responsiveness, and baseline smell fluctuation are associated with dupilumab treatment response.
METHODS: CRSwNP patients initiating dupilumab were enrolled in a single-arm, prospective study. Duration of olfactory loss, steroid responsiveness, and baseline smell fluctuation were recorded. Olfactory testing using Sniffin' Sticks (threshold, discrimination, identification, and composite TDI score) and patient-reported smell ability were documented at baseline and after 12 weeks of dupilumab. The relationship between these clinical features and olfactory outcomes was analyzed.
RESULTS: Patients who reported a shorter duration of olfactory loss had greater TDI improvement (R2 = 0.089, p = 0.02) after dupilumab. Specifically, patients with less than 10 years of olfactory loss demonstrated significantly greater TDI improvement compared with those with longer duration (10.9 vs. 4.5 points, p = 0.01), a difference which exceeded the minimal clinically important difference of 5.5 points. Steroid-responsive patients showed higher change scores across several measures, including patient-reported olfaction and smell identification scores, although there was no overall difference in TDI improvement. Patients reporting baseline smell fluctuation had higher TDI scores throughout treatment but showed similar magnitude of change.
CONCLUSIONS: Duration of olfactory loss is associated with dupilumab treatment response in CRSwNP, with a 10-year threshold identifying patients less likely to achieve clinically meaningful improvement. Steroid responsiveness provides additional prognostic value. These readily available clinical features can guide patient counseling and treatment expectations.