Interactive Effects of IL-33 and CCL-11 in the Recurrence of Nasal Polyps in Patients with Allergic Rhinitis
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摘要:
目的 探讨伴变应性鼻炎的鼻息肉患者血清白介素-33（interleukin-33，IL-33）、CC修饰趋化因子11（CC-chemokine ligand 11，CCL-11）在鼻息肉复发中的交互作用。 方法 选取2020年1月至2023年5月成都市新都区人民医院145例伴变应性鼻炎的鼻息肉患者，均行鼻内镜手术，根据患者术后1年检查结果将其分为复发组（n = 42）与未复发组（n = 103）。比较两组基线资料、术前、术后1周血清IL-33、CCL-11水平，分析血清IL-33、CCL-11水平与视觉模拟评分（visual analogue scale，VAS）、改良Lund-Kennedy内镜评分（Lund-Kennedy score，LKS）的相关性，Logistic回归分析伴变应性鼻炎的鼻息肉患者鼻息肉复发相关因素及血清IL-33、CCL-11交互作用对伴变应性鼻炎的鼻息肉患者鼻息肉复发的影响，ROC曲线分析血清IL-33、CCL-11水平对伴变应性鼻炎的鼻息肉患者鼻息肉复发的预测价值。 结果 复发组术后1周VAS、LKS评分及血清IL-33、CCL-11水平及术后1周/术前比值高于未复发组，差异均有统计学意义（P < 0.05）；经相关性分析可知，伴变应性鼻炎的鼻息肉患者血清IL-33、CCL-11比值均与VAS、LKS评分比值呈正相关（P < 0.05）；术后1周血清IL-33、CCL-11均为伴变应性鼻炎的鼻息肉患者鼻息肉复发独立影响因素（P < 0.05）；血清IL-33、CCL-11比值均对伴变应性鼻炎的鼻息肉患者鼻息肉复发有影响（P < 0.05）；血清IL-33、CCL-11比值间并无相乘交互效应（P > 0.05）；血清IL-33、CCL-11比值同时暴露，伴变应性鼻炎的鼻息肉患者鼻息肉复发风险是非暴露的4.221倍；血清IL-33、CCL-11比值同时暴露时，伴变应性鼻炎的鼻息肉患者鼻息肉复发风险高于血清IL-33、CCL-11比值单独暴露风险之和（RERI = 2.807，95%CI = 1.734～5.639），协同效应为二者单独效应之和的2.840倍（SI = 2.840，95%CI = 1.882～6.137），二者同时存在时致鼻息肉复发风险中有49%归因于二者在相加尺度上协同作用（AP = 0.494，95%CI = 0.207～0.613）；血清IL-33、CCL-11比值预测伴变应性鼻炎的鼻息肉患者鼻息肉复发的AUC值分别为0.758、0.766，具有一定预测效能；血清IL-33、CCL-11比值联合预测鼻息肉复发的AUC值最大，为0.873，明显高于二者单独预测AUC值，此时最佳敏感度、特异度分别为78.57%、79.61%；另选取2022年5月至2024年5月成都市新都区人民医院收治的80例伴变应性鼻炎的鼻息肉患者作为外部验证集，入院后均行鼻内镜手术，术后1年复发24例，未复发56例；术后1周血清IL-33、CCL-11联合预测鼻息肉复发22例，未复发58例，预测准确率为95.00%（76/80），模型预测结果与实际结果一致性良好（χ2=10.824，P < 0.05）。 结论 血清IL-33、CCL-11与伴变应性鼻炎的鼻息肉患者鼻息肉复发的存在紧密联系，且二者在相加尺度上可能存在协同效应，通过监测术后血清IL-33、CCL-11水平变化为临床预测鼻息肉复发提供参考依据，以针对性制定后续干预方案。 Abstract:Objective To investigate the interaction effects of serum interleukin-33 （IL-33） and CC-modified chemokine 11 （CCL-11） on the recurrence of nasal polyps in patients with nasal polyps complicated by allergic rhinitis. Methods A total of 145 patients with nasal polyps complicated by allergic rhinitis admitted to Xindu District People's Hospital of Chengdu from January 2020 to May 2023 were selected, all of whom underwent endoscopic sinus surgery. Based on the examination results at 1 year postoperatively, the patients were divided into a recurrence group （n = 42） and a non-recurrence group （n = 103）. Baseline data and preoperative and 1-week postoperative serum IL-33 and CCL-11 levels were compared between the two groups. The correlations of serum IL-33 and CCL-11 levels with the visual analogue scale （VAS） score and the modified Lund-Kennedy endoscopic score （LKS） were analyzed. Logistic regression was used to analyze factors associated with nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis, as well as the interaction between serum IL-33 and CCL-11 on nasal polyp recurrence in these patients. Receiver operating characteristic （ROC） curve analysis was performed to evaluate the predictive value of serum IL-33 and CCL-11 levels for nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis. Results The 1-week postoperative VAS and LKS scores, serum IL-33 and CCL-11 levels, and the ratios of 1-week postoperative to preoperative values in the recurrence group were all higher than those in the non-recurrence group, with statistically significant differences （P < 0.05）. Correlation analysis showed that the ratios of serum IL-33 and CCL-11 in patients with nasal polyps complicated by allergic rhinitis were both positively correlated with the ratios of VAS and LKS scores（P < 0.05）. Serum IL-33 and CCL-11 levels at 1 week postoperatively were both independent influencing factors for nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis （P < 0.05）. The ratios of serum IL-33 and CCL-11 both had an effect on nasal polyp recurrence in these patients （P < 0.05）. There was no multiplicative interaction between the ratios of serum IL-33 and CCL-11 （P > 0.05）. When both the serum IL-33 and CCL-11 ratios were exposed, the risk of nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis was 4.221 times that of non-exposure. When both serum IL-33 and CCL-11 ratios were exposed simultaneously, the risk of nasal polyp recurrence was higher than the sum of the risks of exposure to each alone （RERI = 2.807, 95%CI = 1.734～5.639）, and the synergistic effect was 2.840 times the sum of the individual effects （SI = 2.840, 95%CI = 1.882～6.137）; when both were present, 49% of the risk of nasal polyp recurrence was attributable to their synergistic effect on the additive scale （AP = 0.494, 95%CI = 0.207～0.613）. The AUC values of the serum IL-33 and CCL-11 ratios for predicting nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis were 0.758 and 0.766, respectively, indicating certain predictive efficacy. The combined prediction of nasal polyp recurrence using the serum IL-33 and CCL-11 ratios yielded the largest AUC value of 0.873, which was significantly higher than the AUC values of each alone, with the optimal sensitivity and specificity being 78.57% and 79.61%, respectively. In addition, 80 patients with nasal polyps complicated by allergic rhinitis admitted to Xindu District People's Hospital of Chengdu from May 2022 to May 2024 were selected as an external validation set; all underwent endoscopic sinus surgery after admission, with 24 cases of recurrence and 56 cases of non-recurrence at 1 year postoperatively. The combined prediction using serum IL-33 and CCL-11 levels at 1 week postoperatively identified 22 cases of recurrence and 58 cases of non-recurrence, with a prediction accuracy of 95.00% （76/80）, indicating good agreement between the model predictions and the actual outcomes （χ2=10.824, P < 0.05）. Conclusion Serum IL-33 and CCL-11 are closely associated with nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis, and a synergistic effect between the two may exist on the additive scale. Monitoring postoperative changes in serum IL-33 and CCL-11 levels can provide a reference basis for the clinical prediction of nasal polyp recurrence and for the development of targeted follow-up intervention plans. -
Key words:
- Allergic rhinitis /
- Nasal polyps /
- Nasal endoscopic resection /
- Recurrence /
- Interleukin-33 /
- CC modifies chemokine 11
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图 1 血清IL-33、CCL-11比值与VAS、LKS评分比值的相关性
A：IL-33比值与VAS评分比值的相关性；B：CCL-11比值与VAS评分比值的相关性；C：IL-33比值与LKS评分比值的相关性；D：CCL-11比值与LKS评分比值的相关性。
Figure 1. Correlation between the serum IL-33/CCL-11 ratio and the VAS/LKS score ratio
图 2 血清IL-33、CCL-11比值预测伴变应性鼻炎的鼻息肉患者鼻息肉复发的ROC曲线
Figure 2. ROC curve of the serum IL-33/CCL-11 ratio for predicting nasal polyp recurrence in patients with nasal polyps accompanied by allergic rhinitis
表 1 两组基线资料及血清IL-33、CCL-11水平比较[（$ \bar x \pm s $）/n（%）]
Table 1. Comparison of baseline characteristics and serum IL-33 and CCL-11 levels between the two groups[（$ \bar x \pm s $）/n（%）]
临床资料 复发组（n = 42） 未复发组（n = 103） χ2/t P 性别 0.213 0.645 男 25（59.52） 57（55.34） 女 17（40.48） 46（44.66） 年龄（岁） 36.44 ± 6.07 34.83 ± 5.12 1.626 0.106 BMI（kg/m2） 22.17 ± 0.59 22.09 ± 0.74 0.624 0.534 变应性鼻炎病程（年） 5.42 ± 0.59 5.27 ± 0.60 1.372 0.172 鼻息肉个数 2.730 0.098 单发 28（66.67） 82（79.61） 多发 14（33.33） 21（20.39） 合并哮喘 2.091 0.149 有 37（88.10） 80（77.67） 无 5（11.90） 23（22.33） 吸烟 0.695 0.404 有 24（57.14） 51（49.51） 无 18（42.86） 52（50.49） 饮酒 0.064 0.800 有 35（83.33） 84（81.55） 无 7（16.67） 19（18.45） 术后鼻腔粘连 0.191 0.662 有 34（80.95） 80（77.67） 无 8（19.05） 23（22.33） VAS评分 术前 18.59 ± 3.03 18.87 ± 2.94 0.516 0.607 术后1周 12.32 ± 3.85 9.87 ± 2.41 4.619 <0.001* 比值 0.66 ± 0.17 0.52 ± 0.15 4.902 <0.001* LKS评分 术前 9.74 ± 0.62 9.59 ± 0.57 1.401 0.163 术后1周 5.02 ± 1.43 3.57 ± 0.69 8.231 <0.001* 比值 0.52 ± 0.17 0.37 ± 0.12 6.014 <0.001* IL-33（ng/L） 术前 84.76 ± 15.33 86.23 ± 14.87 0.535 0.593 术后1周 67.82 ± 9.41 56.83 ± 7.42 7.465 <0.001* 比值 0.80 ± 0.25 0.66 ± 0.20 3.548 0.001* CCL-11（pg/mL） 术前 81.27 ± 9.42 82.05 ± 8.87 0.472 0.638 术后1周 70.43 ± 6.59 62.87 ± 5.98 6.702 <0.001* 比值 0.87 ± 0.27 0.77 ± 0.25 2.135 0.035* 比值是指术后1周/术前比值；*P < 0.05。 
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表 2 伴变应性鼻炎的鼻息肉患者鼻息肉复发相关因素的Logistic回归分析
Table 2. Logistic regression analysis of factors associated with nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis
因素 β S.E. Waldχ2 OR 95%CI P 常量 −1.414 0.359 15.514 <0.001* IL-33比值 1.472 0.157 6.060 1.472 1.074～2.017 <0.001* CCL-11比值 1.533 0.162 6.951 1.533 1.122～2.094 <0.001* *P < 0.05。
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表 3 相乘交互作用
Table 3. Multiplicative interaction
自变量 模型1 模型2 OR（95%CI） P OR（95%CI） P IL-33比值 1.472（1.074～2.017） <0.001* 1.715（1.465～2.007） <0.001* CCL-11比值 1.533（1.122～2.094） <0.001* 1.519（1.140～2.025） <0.001* IL-33与CCL-11比值乘积 1.449（0.694～3.025） 0.323 1.090（0.779～1.257） 0.480 注：模型1未调整其他变量；模型2调整其他变量；*P < 0.05。
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表 4 相加交互作用
Table 4. Additive interaction
交互项 复发组
（n = 42）未复发组
（n = 103）模型1 模型2 OR（95%CI） P OR（95%CI） P 高IL-33比值/高CCL-11比值 −/- 4 45 1.000 1.000 -/+ 7 30 1.533（1.122～2.094） <0.001* 1.519（1.140～2.025） <0.001* +/- 11 18 1.472（1.074～2.017） <0.001* 1.715（1.465～2.007） <0.001* +/+ 20 10 5.690（3.275～9.886） <0.001* 4.221（2.402～7.419） <0.001* 注：模型1未调整其他变量；模型2调整其他变量；*P < 0.05。
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表 5 血清IL-33、CCL-11比值对伴变应性鼻炎的鼻息肉患者鼻息肉复发的预测价值
Table 5. Predictive value of serum IL-33/CCL-11 ratio for nasal polyp recurrence in patients with nasal polyps complicated by allergic rhinitis
指标 AUC 95%CI Z统计 截断值 敏感度（%） 特异度（%） P IL-33比值 0.758 0.680～0.826 5.989 0.81 71.43 77.67 <0.001* CCL-11比值 0.766 0.689～0.833 6.203 0.77 78.57 67.96 <0.001* 联合预测 0.873 0.810～0.924 12.143 0.25 78.57 79.61 <0.001* *P < 0.05。
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表 6 外部验证
Table 6. External validation
模型 实际结果 合计 符合率（%） Kappa值（95% CI） χ2 P 复发 未复发 复发 21 1 22 95.00 0.878（0.762～0.995） 10.824 <0.001* 未复发 3 55 58 合计 24 56 80 *P < 0.05。
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