Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.
Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC; Department of Surgery, Ralph H. Johnson VA Medical Center, Charleston, SC.
J Allergy Clin Immunol. 2021 May;147(5):1732-1741.e1. doi: 10.1016/j.jaci.2021.01.021. Epub 2021 Feb 4.
Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss.
The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach.
Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters.
A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/T17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test, χ=178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all).
Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes.
尽管慢性鼻-鼻窦炎（CRS）被认为是最可治疗的嗅觉功能障碍形式，但针对与嗅觉丧失相关的表型，相对较少关注评估内型。
本研究旨在通过非监督聚类分析无表型方法中嗅裂（OC）生物标志物，探讨 CRS 中的炎症内型。
前瞻性招募 CRS 患者，并进行嗅觉心理物理学测试、嗅觉障碍问卷（QOD-NS）和双侧 OC 内镜检查。从 OC 采集黏液，使用主成分分析评估 26 种生物标志物。仅使用 OC 生物标志物进行聚类分析，并比较不同聚类中嗅觉测量值的差异。
共评估了 198 例患者（128 例 CRS 和 70 例对照）。OC 生物标志物的评估表明存在 6 个主成分，解释了 69.50%的方差，具有 2 型、混合 1 型/T17 细胞型、生长因子和中性粒细胞趋化因子炎症特征。共确定了 10 个聚类，这些聚类在对照组、伴有鼻息肉的 CRS 患者和不伴鼻息肉的 CRS 患者的频率方面存在显著差异（似然比检验，χ=178.64；P<.001）。聚类在嗅觉测量值方面存在显著差异，包括嗅觉测试、QOD-NS 和 OC 内镜检查（P<.001）。
仅基于 OC 生物标志物的聚类可以将患者分为具有临床意义的内型，这些内型可以区分 CRS 患者和对照者。需要进行验证研究来确认这些发现，并进一步细化嗅觉内型。
