Identification of clinically relevant chronic rhinosinusitis endotypes using cluster analysis of mucus cytokines.
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ABSTRACT:
SUBMITTER: Turner JH
PROVIDER: S-EPMC5938108 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Identification of clinically relevant chronic rhinosinusitis endotypes using cluster analysis of mucus cytokines.
Turner Justin H JH Chandra Rakesh K RK Li Ping P Bonnet Kemberlee K Schlundt David G DG
The Journal of allergy and clinical immunology 20180213 5
Similar Datasets
Project description:Traumatic brain injury (TBI) is a complex condition where heterogeneity impedes the advancement of care. Understanding the diverse presentations of TBI is crucial for personalized medicine. Our study aimed to identify clinically relevant patient endotypes in TBI using latent class analysis based on comorbidity data. We used the Medical Information Mart for Intensive Care III database, which includes 2,629 adult TBI patients. We identified five stable endotypes characterized by specific comorbidity profiles: Heart Failure and Arrhythmia, Healthy, Renal Failure with Hypertension, Alcohol Abuse, and Hypertension. Each endotype had distinct clinical characteristics and outcomes: The Heart Failure and Arrhythmia endotype had lower survival rates than the Renal Failure with Hypertension despite featuring fewer comorbidities overall. Patients in the Hypertension endotype had higher rates of neurosurgical intervention but shorter stays in contrast to the Alcohol Abuse endotype which had lower rates of neurosurgical intervention but significantly longer hospital stays. Both endotypes had high overall survival rates comparable to the Healthy endotype. Logistic regression models showed that endotypes improved the predictability of survival compared to individual comorbidities alone. This study validates clinical endotypes as an approach to addressing heterogeneity in TBI and demonstrates the potential of this methodology in other complex conditions.
| S-EPMC10788338 | biostudies-literature
Project description: Not available
| S-EPMC6910924 | biostudies-literature
Project description:BackgroundDiagnostic nasal endoscopy is a routine measure of sinonasal inflammation in patients with chronic rhinosinusitis (CRS). Although multiple staging systems have been proposed and evaluated, evidence of association between concurrent symptoms and endoscopic findings remains discordant. The goal of this study is to identify the relevant endoscopic attributes associated with symptom burden, and to systematically derive a weighted endoscopic scale that optimizes prediction of concurrent symptoms.MethodsReported baseline symptom (22-item Sino-Nasal Outcome Test [SNOT-22]) and endoscopic evaluation scores (Lund-Kennedy [LK]) were obtained from patients with CRS enrolled in a prospective cohort study. Canonical correlation analysis of the SNOT-22 subdomains and LK variables was completed.ResultsA total of 629 patients were included in analysis including 343 with prior endoscopic sinus surgery. Significant canonical correlations outperformed aggregate correlations in explaining variance of the data (33% vs 3%, respectively). The first canonical correlation was dominated by the rhinologic symptom domain and the endoscopic polyp score (r = 0.54; p < 0.05) whereas additional significant canonical correlation was found between the extra-rhinologic symptom subdomain and the edema score in patients without prior ESS (r = 0.21; p < 0.05), and discharge in patients with prior ESS (r = 0.22; p < 0.05). All other domains and endoscopic variables did not significantly contribute to the canonical correlation.ConclusionAlthough aggregate symptoms and endoscopic scores demonstrate minimal correlation, a weighted combination of symptom domains and endoscopic attributes greatly improves this correlation. A simple approximation of the weights of each of the endoscopic variables of polyps, edema, discharge, scarring, and crusting, is an approximate ratio of 4:2:1:0:0, respectively.
| S-EPMC4856574 | biostudies-literature
Project description: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.
| S-EPMC6157407 | biostudies-literature
Project description:BackgroundChronic 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.ObjectiveTo identify associations between inflammatory endotypes and clinical presentations in CRS.MethodsWe compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-γ (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.ResultsThe 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.ConclusionsClinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.
| S-EPMC6842686 | biostudies-literature
Project description:BackgroundThe expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.MethodsA total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1-year postoperative follow-up. Difficult-to-treat CRS was characterized in each generated cluster.ResultsSeven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well-defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult-to-treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult-to-treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL-8 and high proportions of difficult-to-treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL-10 and lacked difficult-to-treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult-to-treat CRS, and low inflammation load. Finally, we found that difficult-to-treat CRS was associated with distinct clinical features and biomarkers in the different clusters.ConclusionsDistinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult-to-treat CRS.
| S-EPMC6019131 | biostudies-literature
Project description:BackgroundChronic Rhinosinusitis (CRS) affects approximately 1 in 10 UK adults and impacts quality of life quality of life significantly. Response to treatment may be driven by individual CRS endotypes and therefore work to delineate biomarker clusters that may separate responders from non-responders is needed. The ongoing MACRO three-arm parallel-group trial randomises adult CRS patients to endoscopic sinus surgery, macrolide therapy or placebo.AimThis study aims to correlate CRS endotypes with clinical parameters from the ongoing MACRO trial, including olfactory function and outcomes in terms of response to treatment using core biomarkers sets.MethodsAdult CRS patients enrolled into the MACRO trial will be recruited from participating UK otorhinolaryngology departments. Nasal tissue samples and swabs will be obtained in theatre or clinic from patients randomised to all three trial arms. Nasal tissue will be analysed with multiplex electrochemiluminescence for 32 cytokines including IL-5, IL-13, IgE and periostin. Bacterial swabs will be analysed using illumina miSeq 16S amplicon sequencing. Mean expression for each biomarker will be reported for treatment responder and non-responder groups. Correlation of biomarkers with MACRO trial outcome data such as endoscopic evaluation scores and quality-of-life improvement scores will be reported.DiscussionDefining clear endotypes in CRS will contribute to refining patient pathways for the efficient use of clinical resources. This work may lay the groundwork for future studies to predict which patients might respond to medical or surgical therapy.
| S-EPMC10395813 | biostudies-literature
Project description:IntroductionThe emergency of biologics and surgical techniques targeting the specific inflammatory endotype in chronic rhinosinusitis with nasal polyps (CRSwNP) asks for efficient identification of patients with different endotypes. Although mucosal IL-4, IL-5, IL-13, and IgE have been used to define type 2 (T2) inflammation, the optimal one remains unclear. In this study, we aimed to determine the optimal anchor for T2 inflammation and identify clinical characteristics and nasal secretion biomarkers predicting different endotypes in CRSwNP.MethodsSix mediators in sinonasal tissue and 36 mediators in nasal secretion samples were detected by the Bio-Plex suspension array system. Mucosal IFN-γ and IL-17A levels were used to define the T1 and T3 endotype, respectively. The efficacy of mucosal IL-4, IL-5, IL-13, and IgE to define the T2 endotype was compared. The power of clinical characteristics and nasal secretion biomarkers to predict the T1, T2, and T3 endotype was analyzed.ResultsAmong mucosal IL-4, IL-5, IL-13, and IgE, IL-13 was the best one to coincide with the expression of other T2 biomarkers. A combination of atopy, facial pain symptom score, ethmoid/maxillary computed tomography score ratio, and blood eosinophil percentage had a moderate predictive performance for T2 endotype (area under the receiver operating curve [AUC] = 0.815), comparable to that of nasal secretion IL-5 (AUC = 0.819). For the T3 endotype, nasal secretion IL-1Rα identified it with an AUC value of 0.756. No efficient marker for the T1 endotype was found.ConclusionIL-13 is a primary anchor for the T2 endotype in CRSwNP. Clinical characteristics and nasal secretion biomarkers are helpful for identifying the T2 and T3 endotype of CRSwNP.
| S-EPMC10614570 | biostudies-literature
Project description:BackgroundAlthough 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.ObjectivesThe 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.MethodsPatients 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.ResultsA 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/Th17-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, χ182=178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all).ConclusionsClustering 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.
| S-EPMC8113080 | biostudies-literature
Project description:BackgroundChronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS.ObjectiveOur aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP.MethodsEthmoid tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray analysis and quantitative RT-PCR, and expression of proteins was measured by ELISA and Luminex analysis.ResultsMicroarray found that compared with their levels of expression in control tissue, the levels of expression of 126, 241, and 545 genes were more than 3-fold and significantly elevated in CRSsNP with type 1 (T1) endotype, type 2 (T2) endotype, and type 3 (T3) endotype, respectively. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ signaling and antiviral immunity controlled by T cells (TH1 and CD8+), natural killer cells, and antigen-presenting cells; T2 CRSsNP was associated with STAT6 signaling and IgE-mediated activation controlled by eosinophils, mast cells, TH2 cells, group 2 innate lymphoid cells, and antigen-presenting cells; and T3 CRSsNP was associated with IL-17 signaling, acute inflammatory response, complement-mediated inflammation, and infection controlled by neutrophils, TH17 cells, B cells, and antigen-presenting cells. The results suggest that T1 (CXCL9 and CXCL10), T2 (eosinophilic proteins and CCL26), and T3 (CSF3) endotypic biomarkers in NLF may be able to distinguish tissue endotypes in CRSsNP.ConclusionsInflammatory endotypes in CRSsNP were controlled by different molecular mechanisms. NLF biomarker assays may allow for more precise and personalized medical treatments in CRS.
| S-EPMC8216505 | biostudies-literature