Sima Yutong, Zheng Ming, Zhao Yan, Ge Siqi, Liu Chengyao, Wang Ping, Wang Xiangdong, Zhang Luo
Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
World Allergy Organ J. 2024 Dec 12;18(1):101009. doi: 10.1016/j.waojou.2024.101009. eCollection 2025 Jan.
The treatment of refractory chronic rhinosinusitis with nasal polyps (CRSwNP) with omalizumab has been well studied based on clinical evaluation. Nevertheless, ideal quantitative or qualitative biomarkers for predicting a different response to biologics urgently need to be explored. We aim to identify potential biomarkers for predicting a good or poor response in patients with refractory CRSwNP.
Patients received an endoscopic and radiological evaluation, a visual analogue scale (VAS) assessment, and a 22-item sinonasal outcome test (SNOT-22). Forty-eight biomarkers involving type 1 (T1), type 2 (T2), and type 3 (T3) inflammatory factors, chemokines, and remodeling factors were detected in nasal secretion and serum samples at baseline and after 24 weeks of omalizumab treatment.
Eighteen patients with CRSwNP and 16 patients as control were enrolled. Patients with CRSwNP who received oamlizumab treatment with the SNOT-22 and VAS scores improved by 8.9 and 2 points in 72.22% and 50%, respectively. The nasal polyp score (NPS) and Lund-Mackay score were significantly improved in 55.56% of patients. The concentrations of T2 inflammatory biomarker, granulocyte-macrophage colony-stimulating factor (GM-CSF), T3 inflammatory biomarkers, granulocyte colony-stimulating factor (G-CSF), chemokine (C-X-C motif) ligand (CXCL)-1, and chemokine (C-C motif) ligand-20 (CCL-20), T1 inflammatory biomarker, IP-10 (CXCL-10), and granzyme B in nasal secretion and serum periostin were significantly decreased. Serum CCL-3 (AUC = 0.836) and CCL-4 (AUC = 0.909) levels predicted the improvement of SNOT-22 score, respectively. Serum IL-8 (AUC = 0.883) predicted poor improvement in nasal congestion score. Nasal secretion CXCL-1 (AUC = 0.812), GM-CSF (AUC = 0.813), IgE (AUC = 0.900) and IP-10 (AUC = 0.800) effectively predicted none or less improvement in nasal polyp score.
Omalizumab remarkably affects inflammatory mediators in different pathways. CCL-3 and CCL-4 in serum and IgE, CXCL-1, GM-CSF, and IP-10 in nasal secretion may be considered as preferable biomarkers for predicting favorable or ineffective response to omalizumab therapy in patients with refractory CRSwNP comorbid with asthma, based on various clinical indicators.
基于临床评估，已对奥马珠单抗治疗难治性慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）进行了充分研究。然而，迫切需要探索用于预测对生物制剂不同反应的理想定量或定性生物标志物。我们旨在确定可预测难治性CRSwNP患者反应良好或不佳的潜在生物标志物。
患者接受了内镜和影像学评估、视觉模拟量表（VAS）评估以及22项鼻窦结局测试（SNOT-22）。在基线和奥马珠单抗治疗24周后，检测鼻分泌物和血清样本中涉及1型（T1）、2型（T2）和3型（T3）炎症因子、趋化因子和重塑因子的48种生物标志物。
纳入18例CRSwNP患者和16例对照患者。接受奥马珠单抗治疗的CRSwNP患者，SNOT-22和VAS评分分别有72.22%和50%的患者改善了8.9分和2分。55.56%的患者鼻息肉评分（NPS）和Lund-Mackay评分显著改善。鼻分泌物和血清骨膜蛋白中T2炎症生物标志物粒细胞-巨噬细胞集落刺激因子（GM-CSF）、T3炎症生物标志物粒细胞集落刺激因子（G-CSF）、趋化因子（C-X-C基序）配体（CXCL）-1和趋化因子（C-C基序）配体-20（CCL-20）、T1炎症生物标志物IP-10（CXCL-10）和颗粒酶B的浓度显著降低。血清CCL-3（AUC = 0.836）和CCL-4（AUC = 0.909）水平分别预测SNOT-22评分的改善情况。血清IL-8（AUC = 0.883）预测鼻充血评分改善不佳。鼻分泌物CXCL-1（AUC = 0.812）、GM-CSF（AUC = 0.813）、IgE（AUC = 0.900）和IP-10（AUC = 0.800）有效预测鼻息肉评分无改善或改善较少。
奥马珠单抗显著影响不同途径中的炎症介质。基于各种临床指标，血清中的CCL-3和CCL-4以及鼻分泌物中的IgE、CXCL-1、GM-CSF和IP-10可被视为预测难治性CRSwNP合并哮喘患者对奥马珠单抗治疗反应良好或无效的优选生物标志物。
