Project description:Persistent mucosal inflammation and microbial infection are characteristic of Chronic Rhinosinusitis (CRS). Though mucosal microbiota dysbiosis is a characteristic feature of other chronic inflammatory diseases, the relationship between sinus microbiota composition and CRS is unknown. Here we demonstrate, using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, that the sinus microbiota of CRS patients exhibit significantly reduced bacterial diversity. Characteristic of this community collapse is the depletion of multiple, phylogenetically distinct, Lactic Acid Bacteria and the concomitant increase in relative abundance of a single species, Corynebacterium tuberculostearicum. Recapitulating the conditions observed in our human cohort in a murine model confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, we provide evidence that Lactobacillus sakei, identified from our comparative microbiome analyses as a potentially protective species, affords defense against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota, and identifies a new sino-pathogen and a strong bacterial candidate for therapeutic intervention. A total of 14 samples were profiled for microbiome composition: 7 from non-sinusitis patients, and 7 from patients with clinically diagnosed chronic sinusitis.
Project description:Persistent mucosal inflammation and microbial infection are characteristic of Chronic Rhinosinusitis (CRS). Though mucosal microbiota dysbiosis is a characteristic feature of other chronic inflammatory diseases, the relationship between sinus microbiota composition and CRS is unknown. Here we demonstrate, using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, that the sinus microbiota of CRS patients exhibit significantly reduced bacterial diversity. Characteristic of this community collapse is the depletion of multiple, phylogenetically distinct, Lactic Acid Bacteria and the concomitant increase in relative abundance of a single species, Corynebacterium tuberculostearicum. Recapitulating the conditions observed in our human cohort in a murine model confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, we provide evidence that Lactobacillus sakei, identified from our comparative microbiome analyses as a potentially protective species, affords defense against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota, and identifies a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.
Project description:Our data demonstrates an increased number of submucosal glands in the sinus mucosa of pediatric patients with chronic rhinosinusitis (CRS). Additionally, data in the literature indicates differentially altered expression of innate markers of immunity and of inflammatory mediators in the sinus mucosa of adult patients with cystic fibrosis, non-CF controls, and controls. Experiment Overall Design: Analyses will focus on inflammatory/immune response genes to identify genes in CRS or CF patients that are involved in pathways that impact on pathogenesis in these diseases. Analysis will also focus on genes in developmental pathways to identify mediators implicated in the development of submucosal glandular hyperplasia in pediatric patients with CRS.
Project description:The study should create data for the selection of a clinically relevant primary endpoint to assess the efficacy and safety of Buparid/PARI SINUS as compared to Budes Nasal Spray in the therapy of chronic rhinosinusitis (CRS) with polyposis nasi in adult patients. Ideally, the selected parameter should allow a correlation between an objective methodology and the clinical outcome of the study patients.
Project description:Patients with chronic rhinosinusitis (CRS) have abnormal immune responses triggered by a variety of infectious agents, airborne toxins and fungi. Respiratory epithelial cells serve as relay stations capable of amplifying or augmenting cues received from external stimuli to nearby immune cells located in the sinus mucosa. Previous studies have identified increases in complement components and complement gene expression in the mucosa of patients with atopic CRS with nasal polyps (CRSwNP). As part of a larger study, we used shotgun proteomics to quantify changes in mucus proteins between patients with and without nasal polyps.
Project description:This study will assess the effectiveness of MEDIHONEY sinus rinses (alone or in combination with intranasal corticosteroids) vs. intranasal corticosteroid sinus rinses on mucosal healing and polyp recurrence in the post-operative period following functional endoscopic sinus surgery.
Project description:Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of the JAK-STAT and helper T cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.