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Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

ABSTRACT: BACKGROUND:Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail. OBJECTIVE:To identify associations between inflammatory endotypes and clinical presentations in CRS. METHODS:We compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-? (T1), eosinophil cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3). We collected clinical parameters from medical and surgical records and examined whether there were any associations between endotype and clinical features. RESULTS:The presence of nasal polyps, asthma comorbidity, smell loss, and allergic mucin was significantly associated with the presence of T2 endotype in all patients with CRS. The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS. We further analyzed these associations in CRSsNP and CRSwNP separately and found that smell loss was still associated with T2 endotype and pus with the T3 endotype in both CRSsNP and CRSwNP. Importantly, patients with CRS with T2 and T3 mixed endotype tended to have clinical presentations shared by both T2 and T3 endotypes. CONCLUSIONS:Clinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.

SUBMITTER: Stevens WW

PROVIDER: S-EPMC6842686 | biostudies-literature | 2019 Nov - Dec

REPOSITORIES: biostudies-literature

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Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

Stevens Whitney W WW Peters Anju T AT Tan Bruce K BK Klingler Aiko I AI Poposki Julie A JA Hulse Kathryn E KE Grammer Leslie C LC Welch Kevin C KC Smith Stephanie S SS Conley David B DB Kern Robert C RC Schleimer Robert P RP Kato Atsushi A

The journal of allergy and clinical immunology. In practice 20190522 8

<h4>Background</h4>Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail.<h4>Objective</h4>To identify associations between inflammatory endotypes and ...[more]

PMID: 31128376

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Project description:ObjectiveDescribe detailed histopathologic findings from a cohort of patients with chronic rhinosinusitis and evaluate whether histologic measures correlate with baseline clinical factors.Study designCross-sectional study with planned data collection.SettingTertiary medical center.Subjects and methodsAdult patients with chronic rhinosinusitis were prospectively enrolled and demographic data and medical comorbidities recorded. Disease severity was measured by computed tomography (CT), endoscopy, Smell Identification Test (SIT), the Chronic Sinusitis Survey, Rhinosinusitis Disability Index, and SF-36 General Health Survey. Mucosal specimens were assessed for the presence of mucosal inflammation, including cellular (eosinophils, neutrophils, lymphocytes, mast cells, plasma cells, macrophages), epithelial (squamous metaplasia, basement membrane thickening, goblet cells), and stromal markers (subepithelial edema, fibrosis). Histopathologic findings were correlated to baseline clinical factors.ResultsA total of 147 subjects were enrolled with histologic samples available for review. Presence of inflammatory markers was diverse, with lymphocytes present in 100 percent of subjects, eosinophils in 49.7 percent, and neutrophils found in 0.7 percent. Total eosinophil counts correlated with the presence of nasal polyposis (r = -0.367; P < 0.001), asthma (r = 0.264; P = 0.001), and aspirin intolerance (r = 0.279; P = 0.001). Mucosal eosinophilia correlated with worse disease severity on CT (r = 0.414; P < 0.001), endoscopy (r = 0.376; P < 0.001), and SIT (r = -0.253; P = 0.002), with the highest correlations seen in subgroups without nasal polyps. Histopathologic findings did not significantly correlate with any quality-of-life measure.ConclusionMucosal eosinophilia correlates with objective disease severity as defined by CT, endoscopy, and SIT scores. Although other histologic markers of inflammation are present, none show similar correlations. The presence of mucosal eosinophils does not correlate with quality-of-life scores.

Project description:BackgroundThe relationship between asthma, atopy, and underlying type 2 (T2) airway inflammation is complex. Although the bacterial airway microbiota is known to differ in asthmatic patients, the fungal and bacterial markers that discriminate T2-high (eosinophilic) and T2-low (neutrophilic/mixed-inflammation) asthma and atopy are still incompletely identified.ObjectivesThe aim of this study was to demonstrate the fungal microbiota structure of airways in asthmatic patients associated with T2 inflammation, atopy, and key clinical parameters.MethodsWe collected endobronchial brush (EB) and bronchoalveolar lavage (BAL) samples from 39 asthmatic patients and 19 healthy subjects followed by 16S gene and internal transcribed spacer-based microbiota sequencing. The microbial sequences were classified into exact sequence variants. The T2 phenotype was defined by using a blood eosinophil count with a threshold of 300 cells/μL.ResultsFungal diversity was significantly lower in EB samples from patients with T2-high compared with T2-low inflammation; key fungal genera enriched in patients with T2-high inflammation included Trichoderma species, whereas Penicillium species was enriched in patients with atopy. In BAL fluid samples the dominant genera were Cladosporium, Fusarium, Aspergillus, and Alternaria. Using generalized linear models, we identified significant associations between specific fungal exact sequence variants and FEV1, fraction of exhaled nitric oxide values, BAL fluid cell counts, and corticosteroid use. Investigation of interkingdom (bacterial-fungal) co-occurrence patterns revealed different topologies between asthmatic patients and healthy control subjects. Random forest models with fungal classifiers predicted asthma status with 75% accuracy for BAL fluid samples and 80% accuracy for EB samples.ConclusionsWe demonstrate clear differences in bacterial and fungal microbiota in asthma-associated phenotypes. Our study provides additional support for considering microbial signatures in delineating asthma phenotypes.

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.

Dataset Information

Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

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Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

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