Project description:Chronic rhinosinusitis without nasal polyps (CRSsNP) is more prevalent than chronic rhinosinusitis with nasal polyps (CRSwNP). Certain diseases predispose to whereas others are associated with CRSsNP. Predisposing diseases include allergic and nonallergic upper and lower airway diseases, epithelial cell disorders, immunodeficiencies, autoimmune diseases, and some infectious diseases. In addition, environmental and host factors, examples of which include smoking, a higher incidence of abnormal biofilms, and innate immune defects, play a role in the pathogenesis of this disease. CRSsNP is characterized by histologic abnormalities, including basement membrane thickening (fibrosis) and goblet cell hyperplasia. Neutrophils and several chemokines, TGF-β and C-X-C motif chemokine ligand (CXCL)-8, play a role in CRSsNP remodeling. However, there are conflicting data about CRSsNP endotypes, for example, whether it is characterized by neutrophilia or eosinophilia or both. In spite of advancements and the understanding of the pathogenesis of this disease, additional study is necessary to better comprehend its underlying mechanisms, endotypes, and evidence-based treatment strategies.
Project description:Purpose of reviewWe aimed to review the latest evidence regarding the value of tissue histopathological analysis in chronic rhinosinusitis with nasal polyps (CRSwNP) and to facilitate tissue analysis by proposing a pragmatic checklist for clinical settings.Recent findingsCRSwNP is a chronic inflammatory disease that severely impairs the patient's quality of life. The severity of the disease can be correlated with nasal polyps enriched in eosinophils/IL-5 and, although ≥ 10 eosinophils per high power field are considered enough to determine an eosinophilic CRS, this cut-off value, the biopsy method, and the sampling location are still a matter of debate. Besides, tissue eosinophil values might also have some added value when combined with other cellular counts (e.g., eosinophil-to-lymphocyte ratio, Charcot-Leyden crystals). Structured histopathology analysis of sinonasal tissue-including, for instance, tissue remodelling biomarkers, fibrosis, and eosinophilic aggregates-has proven to be a valuable tool for healthcare professionals to identify different pheno-endotypes of CRSwNP and to improve the prioritisation of candidates to targeted therapies. Patients with CRSwNP are treated according to their severity with corticosteroids (intranasal and systemic), endoscopic sinus surgery, and/or biological therapy. A panel of expert ear, nose, and throat specialists and pathologists proposed a pragmatic checklist to improve the clinical practice around tissue analysis in CRSwNP, to facilitate communication between hospital-based healthcare professionals, and to standardize the evaluation of inflammatory biomarkers.
Project description:Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.
Project description:PurposeTo describe the self-reported practices on the diagnosis, treatment, and follow-up of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by ear, nose, and throat (ENT) specialists in Spain to identify potential areas for management optimization.MethodsA cross-sectional online survey with 16 questions was carried out. Recruitment was performed by emailing registered ENT specialists in the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC).ResultsIn total, 127 ENT specialists completed the survey. Fifty-one percent of respondents combined clinical criteria and objective evidence of mucosal inflammation to diagnose CRSwNP. Patient interview and, to a lower degree, a visual analogue scale were the most employed diagnostic tools to quantify symptom severity. Less than half (45%) routinely used the 22-item sino-nasal outcomes test (SNOT-22) to assess the impact of CRSwNP disease in quality of life. The use of patient-reported outcomes and other clinical evaluation tools showed a larger uptake among ENT specialists that worked at an ENT department with an available rhinology unit. Almost all the specialists surveyed (95%) recommended biological treatment, particularly in patients with uncontrolled CRSwNP with respiratory comorbidities (76%), as well as in candidates for revision surgery (66%).ConclusionSpanish otorhinolaryngologists showed a trend toward incorporating CRSwNP guideline recommendations in their clinical practice. The observed low uptake of patient-reported outcomes and objective clinical evaluation tools in routine clinical practise have been identified as areas for optimizing the management of patients with CRSwNP.
Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP.
Project description:Considering the complex and multifarious features of Chronic rhinosinusitis (CRS) including immunologic patterns, novel modalities are needed to reflect clinical and pathophysiological endotypes beyond nasal polyps.We aimed to investigate the proteome of nasal secretions on filter paper from CRS patients to characterize endotypes.
Project description:BackgroundThe airway epithelium plays a central role in the pathogenesis of chronic respiratory diseases such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), but the mechanisms by which airway epithelial cells (EpCs) maintain inflammation are poorly understood.ObjectiveWe hypothesized that transcriptomic assessment of sorted airway EpCs across the spectrum of differentiation would allow us to define mechanisms by which EpCs perpetuate airway inflammation.MethodsEthmoid sinus EpCs from adult patients with CRS were sorted into 3 subsets, bulk RNA sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets from eosinophilic and non-eosinophilic CRSwNP and bulk RNA-seq of EpCs from mild/moderate and severe asthma were assessed. Immunofluorescent staining and ex vivo functional analysis of sinus EpCs were used to validate our findings.ResultsAnalysis within and across purified EpC subsets revealed an enrichment in glycolytic programming in CRSwNP vs CRSsNP. Correlation analysis identified mammalian target of rapamycin complex 1 (mTORC1) as a potential regulator of the glycolytic program and identified EpC expression of cytokines and wound healing genes as potential sequelae. mTORC1 activity was upregulated in CRSwNP, and ex vivo inhibition demonstrated that mTOR is critical for EpC generation of CXCL8, IL-33, and CXCL2. Across patient samples, the degree of glycolytic activity was associated with T2 inflammation in CRSwNP, and with both T2 and non-T2 inflammation in severe asthma.ConclusionsTogether, these findings highlight a metabolic axis required to support epithelial generation of cytokines critical to both chronic T2 and non-T2 inflammation in CRSwNP and asthma.
Project description:IntroductionChronic rhinosinusitis with nasal polyps is a multifactorial disease with a complex pathophysiology involving multiple genetic and environmental factors.ObjectiveThe purpose of this work review is to focus on the importance of genetic studies in chronic rhinosinusitis with nasal polyps besides the several barriers that exists for its understanding.MethodsA systematic review on studies of association between single nucleotide polymorphisms and chronic rhinosinusitis with nasal polyps based on a PubMed/Medline and Periódicos CAPES search of all articles published between January 2005 and January 2015 was made. The search was guided on studies containing the terms polymorphisms, rhinosinusitis, and polyps.ResultsTwo studies found an association of MMP-9 and MMP-2 polymorphisms and chronic rhinosinusitis with nasal polyps, but not in patients with recurrent nasal polyps. Other studies found an association of nasal polyps with MMP-9 polymorphisms, but not with MMP-2 ones. There is evidence of an association of LTC4S, NOS2A, PTGDR, MET, COX-2, OSF-2, and LF polymorphisms and the risk of developing nasal polyps, especially when combined with chronic allergic rhinitis and asthma.ConclusionGenetic studies on chronic rhinosinusitis with nasal polyps are promising and may offer insights into its pathophysiology, which is likely affected by multiple genetic factors.
Project description:BackgroundChronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. Nasal polyps (NPs) are one of the main manifestations that cause diverse clinical symptoms of CRS.ObjectiveWe sought to conduct a bibliometric and visual analysis of articles on CRS and NPs published between 2003 and 2022 to provide researchers with the current state of research and potential directions.MethodsWe searched relevant articles from 2003 to 2022 in the Web of Science database. VOSviewer and the Bibliometrix R package were used to perform the bibliometric analysis.ResultsA total of 3907 publications were retrieved. The United States made the highest contributions to global research, followed by China. Northwestern University had the most publications. The most published author was C. Bachert, followed by R. P. Schleimer and R. J. Schlosser. The authors with the most co-citations were C. Bachert, W. J. Fokkens, and P. Gevaert. Moreover, the journal with the most publications was the International Forum of Allergy & Rhinology, and the Journal of Allergy and Clinical Immunology was the most cited. "Covid-19," "biologics," and "type 2 inflammation" were the top current research hotspots.ConclusionsThe United States and Northwestern University were the leading country and institution in researching CRS and NPs. C. Bachert was the most influential expert. The International Forum of Allergy & Rhinology and the Journal of Allergy and Clinical Immunology were leading journals. "Covid-19," "biologics," and "type 2 inflammation" were the trending topics.
Project description:BackgroundMolecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage-associated diagnostic signature for CRSwNP.MethodsTranscriptome data from 54 patients with CRSwNP and 37 healthy controls across GSE136825, GSE36830, and GSE72713 were used to identify differentially expressed genes (DEGs) between two groups. Gene Set Enrichment Analysis and Weighted Gene Co-Expression Network Analysis pinpointed crucial pathways and gene clusters. A diagnostic model was created from these analyses and receiver operating characteristic curve (ROC), and further validated in our transcriptome data from 29 samples. Immune cell infiltration analysis was performed and linked those diagnostic genes to macrophages and verified by single-cell RNA sequencing data. Immunofluorescence co-staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow-derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated.ResultsDEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four-gene diagnostic model (HMOX1, ALOX5, F13A1 and ITGB2) was developed and demonstrated high diagnostic precision with an area under ROC curve of 0.980 for training dataset and 0.895 for test dataset. M2 macrophage presence and HMOX1 expression significantly correlated with CRSwNP (p < 0.001). Single-cell RNA sequencing data underscored the altered cellular composition in CRSwNP, with HMOX1 notably expressed in M2 macrophages. Immunofluorescence staining highlighted the increased infiltration of CD163+ M2 macrophages in nasal mucosa samples of eosinophilic CRSwNP, which correlated with HMOX1 protein levels (p < 0.05). The HMOX1 inhibitor zinc protoporphyrin reduced the ratio of CD163 + HMOX1 + M2 macrophages in mouse BMDM cultures (p < 0.05). HMOX1 expression showed a strong positive correlation with the expression of eotaxin genes (CCL11, CCL24, and CCL26; p < 0.05 respectively).ConclusionM2 macrophage-derived HMOX1 can be used as an innovative diagnostic signature for CRSwNP, which might be a potential regulator of eosinophilic inflammation.