Dataset Information

Inflammatory Endotypes and Microbial Associations in Chronic Rhinosinusitis.

ABSTRACT: A complex mix of inflammatory and microbial associations underscores the chronic inflammatory condition chronic rhinosinusitis (CRS), and the etiology remains poorly understood. Recent work has begun to delineate between variants (endotypes) of CRS on the basis of inflammatory biomarkers. This study aimed to assess inflammatory patterns in CRS phenotypes, identify putative endotypes of CRS, and to assess inflammatory associations with the sinonasal microbiota. Ten cytokines and six inflammatory cell types were assessed in mucosal biopsies from 93 CRS subjects and 17 controls via cytometric bead array and immunohistochemical techniques. Putative endotypes were identified via cluster analysis of subjects on the basis of inflammatory markers and comorbidities including polyposis, asthma, and aspirin sensitivity. Finally, previously published bacterial data for this cohort were reanalyzed to evaluate associations with inflammatory markers and CRS subtypes. Inflammatory patterns were highly variable within standard CRS phenotypes. Cluster analysis identified eight subject clusters, with strong delineation on the basis of polyposis and asthma, but also subtle distinctions in inflammatory markers. An association was also identified between depletion of several "health-associated" bacterial taxa, reduced bacterial diversity and increased overall bacterial load, with markers of inflammation and clinical severity. This study contributes to ongoing efforts to define distinct endotypes of CRS on the basis of underlying inflammatory processes, and also offers compelling evidence of a link between bacterial community dysbiosis and inflammation in CRS. Further resolving the heterogeneity of CRS is vital to inform clinical management and personalized treatment approaches.

SUBMITTER: Hoggard M

PROVIDER: S-EPMC6157407 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Inflammatory Endotypes and Microbial Associations in Chronic Rhinosinusitis.

Hoggard Michael M Waldvogel-Thurlow Sharon S Zoing Melissa M Chang Kevin K Radcliff Fiona J FJ Wagner Mackenzie Brett B Biswas Kristi K Douglas Richard G RG Taylor Michael W MW

Frontiers in immunology 20180919

A complex mix of inflammatory and microbial associations underscores the chronic inflammatory condition chronic rhinosinusitis (CRS), and the etiology remains poorly understood. Recent work has begun to delineate between variants (endotypes) of CRS on the basis of inflammatory biomarkers. This study aimed to assess inflammatory patterns in CRS phenotypes, identify putative endotypes of CRS, and to assess inflammatory associations with the sinonasal microbiota. Ten cytokines and six inflammatory ...[more]

PMID: 30283438

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Project description:BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence.MethodsThe present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence.ResultsThe levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability.ConclusionOur results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.

Project description:BackgroundChronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi-institutional cohort.MethodsAdults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin' Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification.ResultsSixty-two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSwNP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSwNP group, C-C motif ligand 2 (CCL2), interleukin-5 (IL-5), IL-6, IL-13, IL-10, IL-9, tumor necrosis factor-? (TNF-?), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSsNP), only C-X-C ligand 5 (CXCL5) showed a correlation. In CRSwNP, IL-6, IL-10, vascular endothelial growth factor-A, and immunoglobulin E (IgE) correlated with OC opacification, whereas, in CRSsNP, only CXCL5 showed a correlation. OC mucus proteins and Lund-Mackay score correlated only in the CRSsNP group (CXCL5, IL-5, IL-13, IgE).ConclusionSeveral OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSsNP and CRSwNP subgroups, suggesting different mechanisms between groups, but further study is required.

Dataset Information

Inflammatory Endotypes and Microbial Associations in Chronic Rhinosinusitis.

Publications

Inflammatory Endotypes and Microbial Associations in Chronic Rhinosinusitis.

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