慢性鼻窦炎伴鼻息肉生物制剂治疗反应的预测性生物标志物：一项系统综述。

文献信息

中文摘要

背景： 生物制剂治疗已改变重度慢性鼻窦炎伴鼻息肉（CRSwNP）的管理，但治疗反应仍存在差异。基线生物标志物可能识别最可能获益的患者，然而尚无标志物被验证可用于常规临床。本系统综述评估了预测成人CRSwNP患者对生物制剂治疗临床及内镜反应的基线生物标志物。
方法： 通过系统检索识别报告成人CRSwNP患者基线生物标志物与生物制剂（dupilumab、omalizumab、抗IL-5药物）治疗反应的研究。共10项研究、489名参与者符合纳入标准。数据提取包括生物标志物类型、阈值、结局[SNOT-22、鼻息肉评分（NPS）、影像学评分]及随访时间。对基线嗜酸性粒细胞计数高与低的二分类数据进行随机效应荟萃分析。采用GRADE评估证据确定性。
结果： 荟萃分析显示，嗜酸性粒细胞升高（>300 cells/µL或研究定义的高值）增加SNOT-22改善的比值比（OR 3.07，95% CI 2.00-4.72，p < 0.00001，I² = 0%）及NPS降低≥1分的比值比（OR 2.83，95% CI 1.86-4.30，p < 0.00001，I² = 0%）。血清IgE及其他生物标志物（ECP、细胞因子组合、影像学标志物）在各研究中与治疗反应的关联不一致。由于观察性设计、异质性及不精确性，证据确定性为低至极低。漏斗图对称性及Egger检验（p = 0.36）提示发表偏倚较小。
结论： 当前证据虽受低确定性限制，但提示基线外周血嗜酸性粒细胞计数是CRSwNP生物制剂治疗反应最一致的预测因素。这些发现支持进一步研究嗜酸性粒细胞作为潜在预测性生物标志物，但在临床实施前需要前瞻性验证。其他生物标志物在各研究中显示出不一致的预测价值。
系统综述注册： PROSPERO CRD420251251904。

英文摘要

BACKGROUND: Biologic therapies have transformed management of severe chronic rhinosinusitis with nasal polyps (CRSwNP), but response variability persists. Baseline biomarkers may identify patients most likely to benefit, yet no marker is validated for routine clinical use. This systematic review evaluated baseline biomarkers predicting clinical and endoscopic response to biologic therapy in adults with CRSwNP.
METHODS: A systematic search identified studies reporting baseline biomarkers and response to biologics (dupilumab, omalizumab, anti-IL-5 agents) in adult CRSwNP. Ten studies with 489 participants met inclusion criteria. Data extraction included biomarker type, thresholds, outcomes [SNOT-22, nasal polyp score (NPS), radiologic scores], and follow-up duration. Random-effects meta-analysis was performed for dichotomized high vs. low baseline eosinophil counts. Certainty of evidence was assessed using GRADE.
RESULTS: Meta-analysis demonstrated that elevated eosinophils (>300 cells/µL or study-defined high) increased odds of SNOT-22 improvement (OR 3.07, 95% CI 2.00-4.72, p < 0.00001, I 2 = 0%) and ≥1-point NPS reduction (OR 2.83, 95% CI 1.86-4.30, p < 0.00001, I 2 = 0%). Serum IgE and other biomarkers (ECP, cytokine panels, radiologic markers) showed inconsistent associations with response across studies. Certainty of evidence was low to very low due to observational designs, heterogeneity, and imprecision. Funnel plot symmetry and Egger's test (p = 0.36) suggested minimal publication bias.
CONCLUSION: Current evidence, though limited by low certainty, suggests baseline peripheral eosinophil count is the most consistent predictor of biologic response in CRSwNP. These findings support further investigation of eosinophils as a potential predictive biomarker, but prospective validation is needed before clinical implementation. Other biomarkers showed inconsistent predictive value across studies.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420251251904.