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

W G Gan, X C Liu, F Liu
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Abstract

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-γ 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-γ, 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.

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[鼻腔微生物多样性对慢性鼻窦炎和鼻息肉患者术后预后的影响]。
目的研究慢性鼻窦炎伴鼻息肉(CRSwNP)患者的鼻腔微生物多样性,以及术后复发的鼻腔微生物组特征、炎症细胞和因素,以了解微生物组因素对 CRSwNP 术后预后的影响。研究方法收集2017年12月至2018年12月四川大学华西医院耳鼻咽喉头颈外科77例CRSwNP患者的鼻腔分泌物和鼻息肉组织。其中男性34人,女性43人,年龄在29岁至76岁之间。从棉拭子中提取微生物DNA,基于16SrRNA进行高通量测序,检测细菌群落组成,并使用Luminex分析息肉组织中的IL-5、IL-8、IL-17a、IL-17e、IL-18、IL-27和IFN-γ等细胞因子。对外周血和息肉组织中的嗜酸性粒细胞和中性粒细胞进行计数。对 CRSwNP 患者进行术后 1 年随访,记录鼻息肉复发情况。分析了鼻息肉复发与炎性细胞因子、炎性细胞计数和鼻腔微生物多样性之间的相关性。二分类变量采用卡方检验(Chi-square test),连续变量采用曼-惠特尼U检验(Mann-Whitney U test),两组平均相对丰度差异的比较采用Wilcoxon秩和检验(Wilcoxon rank sum test)。结果随访一年后,12 名患者复发,其中男性 5 人,女性 7 人。复发组与未复发组在年龄、性别、哮喘、过敏性鼻炎和湿疹方面无明显差异。复发组的鼻部症状总分(TNSS)[42.3(30.2,67.1),M(Q1,Q3)]明显高于非复发组[37.8(29.4,50.3)]。在鼻息肉组织中,复发组的嗜酸性粒细胞[40.83(22.33,102.00)/HP]和中性粒细胞[30.83(20.33,56.44)/HP]数量明显高于非复发组[13.72(13.50,48.33)/HP]和[18.50(12.00,26.08)/HP],Z值分别为-6.997和-8.243,PP均=0.638)。未复发组葡萄球菌的平均相对丰度为(8.17±27.70)%,明显低于复发组(8.99±15.89)%,但差异无统计学意义(FDR P=0.638)。结论中性粒细胞介导的炎症反应与鼻息肉复发有关。内窥镜手术后鼻息肉复发可能与保护性微生物数量减少和病原微生物数量增加有关。
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