首页|鼻腔微生物多样性对慢性鼻窦炎伴鼻息肉患者手术预后的影响

鼻腔微生物多样性对慢性鼻窦炎伴鼻息肉患者手术预后的影响

Effect of nasal microbial diversity on postoperative prognosis of patients with chronic sinusitis and nasal polyp

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目的 探讨慢性鼻窦炎伴鼻息肉(CRSwNP)患者鼻腔微生物多样性,以及术后复发者鼻腔微生物组学特征和炎性细胞及因子特点,以了解微生物组学因素对CRSwNP手术预后的影响.方法 2017年12月至2018年12月期间,招募于四川大学华西医院耳鼻咽喉科接受手术治疗的77例CRSwNP患者,其中男34例,女43例,年龄29~76岁.收集患者的鼻腔分泌物和鼻息肉组织.于分泌物中提取鼻腔微生物DNA,基于16S核糖体RNA(16SrRNA)进行高通量测序,检测细菌群落组成.使用Luminex分析鼻息肉组织中白细胞介素(IL)-5、IL-8、IL-17A、IL-17E、IL-18、IL-27和干扰素γ(IFN-γ)等细胞因子.计数外周血和鼻息肉组织中嗜酸粒细胞和中性粒细胞含量.术后随访1年,记录鼻息肉的复发情况,分析鼻息肉复发与炎性因子、炎性细胞计数及鼻腔微生物多样性特征的相关性.对二分类变量采用卡方检验,对连续变量采用Mann-Whitney U检验,两组之间平均相对丰度的差异比较采用Wilcoxon秩和检验.结果 随访1年时复发患者12例,其中男5例,女7例.复发组与未复发组患者在年龄、性别、哮喘、变应性鼻炎、湿疹等方面的差异无统计学意义.复发组的鼻部症状总分[42.3(30.2,67.1),M(Q1,Q3),后同]明显高于未复发组[37.8(29.4,50.3)],Z=-4.930,P<0.001.鼻息肉组织中,复发组患者嗜酸粒细胞[40.83(22.33,102.00)个/HP,HP为高倍视野,后同]和中性粒细胞[30.83(20.33,56.44)个/HP]数量显著高于未复发组[13.72(13.50,48.33)个/HP 和 18.50(12.00,26.08)个/HP,Z值分别为-6.997、-8.243,P值均<0.001].复发组IFN-γ、IL-17A、IL-17E、IL-18的表达量明显高于未复发组,但阳性率差异无统计学意义.属水平上,未复发组患者鼻腔棒状杆菌属的平均相对丰度为(11.90±20.31)%,高于复发组的(0.15±0.20)%,但校正后差异无统计学意义(FDR P=0.638).未复发组葡萄球菌属平均相对丰度为(8.17±27.70)%,低于复发组的(8.99±15.89)%,但校正后差异无统计学意义(FDR P=0.638).结论 CRSwNP患者中性粒细胞介导的炎性反应与鼻息肉复发密切相关.鼻内镜术后鼻息肉的复发可能与保护性微生物丰度的减少和致病微生物数量的增加有关.
Objective To investigate the nasal microbial diversity in patients with chronic sinusitis with nasal polyps(CRSwNP),as well as the nasal microbiome characteristics,inflammatory cells and factors in postoperative relapses,in order to understand the effects of microbiome factors on the postoperative prognosis of CRSwNP.Methods The nasal secretions and nasal polyp tissues from 77 patients with CRSwNP were collected in Department of Otorhinolaryngology Head and Neck Surgery,West China Hospital,Sichuan University from December 2017 to December 2018.The cohort consisted of 34 males and 43 females,aged from 29 to 76 years.Microbial DNA was extracted from cotton swabs for high-throughput sequencing based on 16SrRNA to detect bacterial community composition,and Luminex was used to analyze cytokines such as IL-5,IL-8,IL-17a,IL-17e,IL-18,IL-27,and IFN-y in polyp tissue.Eosinophils and neutrophils in peripheral blood and polyp tissue were counted.Patients with CRSwNP were followed up for 1 year after surgery,and the recurrence of nasal polyps was recorded.The correlation between the recurrence of nasal polyps and inflammatory cytokines,inflammatory cell counts and nasal microbial diversity was analyzed.Chi-square test was used for bicategorical variables,Mann-Whitney U test was used for continuous variables,and Wilcoxon rank sum test was used to compare the difference in average relative abundance between the two groups.Results At the one year follow-up,12 patients experienced a recurrence,including 5 males and 7 females.There was no significant difference in age,sex,asthma,allergic rhinitis and eczema between the relapsing group and the non-relapsing group.The total nasal symptoms score(TNSS)in the recurrent group[42.3(30.2,67.1),M(Q1,Q3)]was significantly higher than that in the non-recurrent group[37.8(29.4,50.3)].In nasal polyp tissue,the number of eosinophils[40.83(22.33,102.00)/HP]and neutrophils[30.83(20.33,56.44)/HP]in the recurrent group were significantly higher than those in the non-recurrent group[13.72(13.50,48.33)/HP]and[18.50(12.00,26.08)/HP],Z-values were-6.997 and-8.243,respectively,all P<0.001.The expression levels of IFN-y,IL-17A,IL-17E and IL-18 in relapsed group were significantly higher than those in non-relapsed group,but there was no significant difference in positive rates.At the generic level,the mean relative abundance of Corynebacterium in the nasal passage of CRSwNP patients in the non-relapses group was(11.90±20.31)%,higher than that in the relapses group(0.15±0.20)%,but the difference was not statistically significant after correction(FDR P=0.638).The mean relative abundance of staphylococcus in the non-relapsed group was(8.17±27.70)%,significantly lower than that in the relapsed group(8.99±15.89)%,but the difference was not statistically significant(FDR P=0.638).Conclusions Neutrophil-mediated inflammatory responses are associated with recurrent nasal polyps.The recurrence of nasal polyps after endoscopic surgery may be related to the decrease in the abundance of protective microorganisms and the increase in the number of pathogenic microorganisms.

SinusitisMicrobial diversityNeutrophil inflammationSurgical prognosis

甘卫刚、刘星辰、刘锋

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四川大学华西医院耳鼻咽喉头颈外科,成都 610041

鼻窦炎 微生物多样性 中性粒细胞炎症 手术预后

四川省科技厅国际科技合作项目

2023YFH0101

2024

中华耳鼻咽喉头颈外科杂志
中华医学会

中华耳鼻咽喉头颈外科杂志

CSTPCD北大核心
影响因子:1.727
ISSN:1673-0860
年,卷(期):2024.59(8)