接受手术的生物治疗2型弥漫性/嗜酸性粒细胞慢性鼻窦炎患者疾病持续存在的预测因素
2024/05/28
摘要
背景：针对2型慢性鼻-鼻窦炎伴鼻息肉患者（CRSwNP）的生物疗法大大提高了疾病控制率，但在 3 期试验和临床实践中，仍有一部分患者对该疗法无反应。本研究探讨了生物制剂治疗 CRSwNP 患者的血清和组织学变化，以预测疾病控制情况。
方法：对接受生物制剂治疗的 CRSwNP 患者进行横断面研究，这些患者在接受生物制剂治疗期间接受了鼻内镜鼻窦手术。在术后 6 个月的评估中，将接受生物制剂治疗的 CRSwNP 控制不佳的患者与接受生物制剂治疗的患者进行比较。对 6 个月前手术时采集的血液和粘膜样本进行评估，以预测疾病控制情况。
结果：共纳入 37 名患者（年龄 47.8 ± 12.4 岁，43.2% 为女性）。病情控制不佳的患者组织中嗜酸性粒细胞减少（%>100个细胞/高倍视野的百分比：8.3% vs. 50.0%，p < 0.001），血清中性粒细胞增加（5.2 ± 2.7 vs. 3.7 ± 1.1 × 10^9 cells/L，p = 0.02）。Logistic回归分析表明，组织嗜酸性粒细胞减少可预测病情控制不佳（OR = 0.21，95% CI [0.05，0.83]，P = 0.03）。ROC曲线分析表明，血清中性粒细胞临界值越低，则越需要使用全身性皮质类固醇治疗。
结论：在使用生物制剂时，组织嗜酸性粒细胞低和血清中性粒细胞增高预示着 CRSwNP 患者对生物制剂治疗的反应不佳。血清中性粒细胞水平≥5.75 × 10^9 cells/L预示着对目前的生物制剂治疗反应不佳。
Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery
Png, L. H., Kalish, L., Campbell, R. G., Seresirikachorn, K., Albrecht, T., Raji, N., Choy, C., Rimmer, J., Earls, P., Sacks, R., & Harvey, R. J.
Abstract
Background:Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control.
Methods:A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control.
Results:A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002).
Conclusion:Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.
背景：针对2型慢性鼻-鼻窦炎伴鼻息肉患者（CRSwNP）的生物疗法大大提高了疾病控制率，但在 3 期试验和临床实践中，仍有一部分患者对该疗法无反应。本研究探讨了生物制剂治疗 CRSwNP 患者的血清和组织学变化，以预测疾病控制情况。
方法：对接受生物制剂治疗的 CRSwNP 患者进行横断面研究，这些患者在接受生物制剂治疗期间接受了鼻内镜鼻窦手术。在术后 6 个月的评估中，将接受生物制剂治疗的 CRSwNP 控制不佳的患者与接受生物制剂治疗的患者进行比较。对 6 个月前手术时采集的血液和粘膜样本进行评估，以预测疾病控制情况。
结果：共纳入 37 名患者（年龄 47.8 ± 12.4 岁，43.2% 为女性）。病情控制不佳的患者组织中嗜酸性粒细胞减少（%>100个细胞/高倍视野的百分比：8.3% vs. 50.0%，p < 0.001），血清中性粒细胞增加（5.2 ± 2.7 vs. 3.7 ± 1.1 × 10^9 cells/L，p = 0.02）。Logistic回归分析表明，组织嗜酸性粒细胞减少可预测病情控制不佳（OR = 0.21，95% CI [0.05，0.83]，P = 0.03）。ROC曲线分析表明，血清中性粒细胞临界值越低，则越需要使用全身性皮质类固醇治疗。
结论：在使用生物制剂时，组织嗜酸性粒细胞低和血清中性粒细胞增高预示着 CRSwNP 患者对生物制剂治疗的反应不佳。血清中性粒细胞水平≥5.75 × 10^9 cells/L预示着对目前的生物制剂治疗反应不佳。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Int Forum Allergy Rhinol. 2024 May; DOI: 10.1002/alr.23282)
(Int Forum Allergy Rhinol. 2024 May; DOI: 10.1002/alr.23282)
Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery
Png, L. H., Kalish, L., Campbell, R. G., Seresirikachorn, K., Albrecht, T., Raji, N., Choy, C., Rimmer, J., Earls, P., Sacks, R., & Harvey, R. J.
Abstract
Background:Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control.
Methods:A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control.
Results:A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002).
Conclusion:Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.
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