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The Journal of Allergy and Clinical... 2016Chronic rhinosinusitis with nasal polyps (CRSwNP) is an important clinical entity diagnosed by the presence of both subjective and objective evidence of chronic... (Review)
Review
Chronic rhinosinusitis with nasal polyps (CRSwNP) is an important clinical entity diagnosed by the presence of both subjective and objective evidence of chronic sinonasal inflammation. Symptoms include anterior or posterior rhinorrhea, nasal congestion, hyposmia, and/or facial pressure or pain that last for a duration of more than 12 weeks. Nasal polyps are inflammatory lesions that project into the nasal airway, are typically bilateral, and originate from the ethmoid sinus. Males are more likely to be affected than females, but no specific genetic or environmental factors have been strongly linked to the development of this disorder to date. CRSwNP is frequently associated with asthma and allergic rhinitis, but the cellular and molecular mechanisms that contribute to the clinical symptoms are not fully understood. Defects in the sinonasal epithelial cell barrier, increased exposure to pathogenic and colonized bacteria, and dysregulation of the host immune system are all thought to play prominent roles in disease pathogenesis. Additional studies are needed to further explore the clinical and pathophysiological features of CRSwNP so that biomarkers can be identified and novel advances can be made to improve the treatment and management of this disease.
Topics: Biomarkers; Chronic Disease; Comorbidity; Humans; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 27393770
DOI: 10.1016/j.jaip.2016.04.012 -
The Journal of Allergy and Clinical... May 2020Chronic rhinosinusitis (CRS) is a complex heterogeneous disease with different phenotypes and endotypes. Recent advances in our understanding of the pathogenetic... (Review)
Review
Chronic rhinosinusitis (CRS) is a complex heterogeneous disease with different phenotypes and endotypes. Recent advances in our understanding of the pathogenetic mechanisms of CRS endotypes have led to the introduction of effective biologic agents for CRS management. Traditionally, CRS phenotypes have been divided into with or without nasal polyps depending on the presence of polyps. Although this classification does not reflect the various endotypes that are recently emerging, it is simple and easily recognized by clinicians. Other phenotypes of CRS are fungal rhinosinusitis (including invasive and noninvasive subtypes), infectious rhinosinusitis, aspirin-exacerbated respiratory disease, cystic fibrosis, pediatric CRS, and CRS associated with systemic diseases. This article reviews the diagnostic approaches and up-to-date treatment strategies for each CRS phenotype with the hope that a better understanding of endotypes will result in a more scientific understanding of phenotypes and precise, personalized treatments.
Topics: Child; Chronic Disease; Humans; Nasal Polyps; Phenotype; Rhinitis; Sinusitis
PubMed: 32389275
DOI: 10.1016/j.jaip.2019.12.021 -
Archivos de Bronconeumologia Mar 2019The aim of this review is to assist pulmonologists in the management of diseases involving both the upper and lower respiratory tract that are linked by a common,... (Review)
Review
The aim of this review is to assist pulmonologists in the management of diseases involving both the upper and lower respiratory tract that are linked by a common, interrelated epidemiology, clinical signs and symptoms, and inflammatory mechanism - asthma, in particular. The document discusses the definitions of the various sinonasal phenotypes associated with asthma: allergic and non-allergic rhinitis and chronic rhinosinusitis with or without nasal polyps. Diagnostic criteria and severity levels are also listed. Particular attention has been given to the 2 main syndromes associated with asthma: (i)allergic rhinitis, the most common, and (ii)chronic rhinosinusitis with nasal polyps, the disease most closely associated with severe asthma. To summarize, the upper respiratory tract should always be evaluated in order to achieve a single diagnosis and comprehensive treatment of the "united airway".
Topics: Algorithms; Asthma; Humans; Multimorbidity; Nasal Polyps; Practice Guidelines as Topic; Rhinitis
PubMed: 30449614
DOI: 10.1016/j.arbres.2018.09.001 -
Annual Review of Pathology Jan 2017Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost... (Review)
Review
Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. The two main forms of CRS that have been long recognized, with and without nasal polyps, are each now known to be heterogeneous, based on underlying mechanism, geographical location, and race. Loss of the immune barrier, including increased permeability of mucosal epithelium and reduced production of important antimicrobial substances and responses, is a common feature of many forms of CRS. One form of CRS with polyps found worldwide is driven by the cytokines IL-5 and IL-13 coming from Th2 cells, type 2 innate lymphoid cells, and probably mast cells. Type 2 cytokines activate inflammatory cells that are implicated in the pathogenic mechanism, including mast cells, basophils, and eosinophils. New classes of biological drugs that block the production or action of these cytokines are making important inroads toward new treatment paradigms in polypoid CRS.
Topics: Adult; Chronic Disease; Humans; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 27959637
DOI: 10.1146/annurev-pathol-052016-100401 -
The Journal of Allergy and Clinical... Jun 2022Chronic rhinosinusitis (CRS) affects up to 12% of the general population and is traditionally divided into two main phenotypic subsets, based on the presence of nasal... (Review)
Review
Chronic rhinosinusitis (CRS) affects up to 12% of the general population and is traditionally divided into two main phenotypic subsets, based on the presence of nasal polyps (CRSwNP) or their absence. It is well-established that many patients with CRSwNP report poor quality of life (QoL), which is further compromised by comorbidities (eg, asthma, bronchiectasis, aspirin-exacerbated respiratory disease). Chronic rhinosinusitis CRS with nasal polyps is managed with a combination of medical therapy and surgical interventions, and biologics are emerging as a promising new treatment option for patients with inadequate response to the standard of care. A range of patient-reported outcome measures have been used to assess QoL for patients with CRSwNP in clinical trials, including disease-specific questionnaires (eg, Sino-Nasal Outcome Test-22) and generic ones (eg, Short Form-36). Significantly impaired QoL has been identified as a criterion for the indication to use biologics in patients with CRSwNP. This review summarizes clinical evidence (2010-2021) on QoL outcomes with currently available treatments for CRSwNP and assesses the improvement in QoL after biologic treatments, especially for patients with comorbidities reported in interventional studies (randomized controlled trials and real-world experience).
Topics: Biological Products; Chronic Disease; Humans; Nasal Polyps; Quality of Life; Rhinitis; Sinusitis
PubMed: 35306180
DOI: 10.1016/j.jaip.2022.03.002 -
Allergy Mar 2022Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an... (Review)
Review
Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an era focused on phenotype to include endotype-based information. Phenotypic classification has identified clinical heterogeneity in CRS based on endoscopically observed features such as presence of nasal polyps, presence of comorbid or systemic diseases, and timing of disease onset. More recently, laboratory-based findings have established CRS endotype based upon specific mechanisms or molecular biomarkers. Understanding the basis of widespread heterogeneity in the manifestations of CRS is advanced by findings that the three main endotypes, Type 1, 2, and 3, orchestrate the expression of three distinct large sets of genes. The development and use of improved methods of endotyping disease in the clinic are ushering in an expansion of the use of biological therapies targeting Type 2 inflammation now and perhaps other inflammatory endotypes in the near future. The purpose of this review is to discuss the phenotypic and endotypic heterogeneity of CRS from the perspective of advancing the understanding of the pathogenesis and improvement of treatment approaches and outcomes.
Topics: Chronic Disease; Humans; Inflammation; Nasal Polyps; Phenotype; Rhinitis; Sinusitis
PubMed: 34473358
DOI: 10.1111/all.15074 -
The Journal of Allergy and Clinical... Apr 2022Loss of smell (LoS) is one of the most troublesome and difficult-to-treat symptoms of severe chronic rhinosinusitis with nasal polyps (CRSwNP). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Loss of smell (LoS) is one of the most troublesome and difficult-to-treat symptoms of severe chronic rhinosinusitis with nasal polyps (CRSwNP).
OBJECTIVE
To assess the impact of dupilumab on sense of smell in severe CRSwNP.
METHODS
In the randomized SINUS-24 and SINUS-52 studies, adults with severe CRSwNP received dupilumab 300 mg subcutaneously or matching placebo every 2 weeks for 24 or 52 weeks, respectively. Smell was assessed using daily patient-reported LoS score (0-3) and University of Pennsylvania Smell Identification Test (UPSIT; 0-40). Data from the 2 studies were pooled through week 24. Relationships between patient phenotypes and smell outcomes were also assessed.
RESULTS
We randomized 724 patients (286 placebo, 438 dupilumab); mean CRSwNP duration was 11 years; 63% had prior sinonasal surgery. Mean baseline LoS was 2.74. Dupilumab produced rapid improvement in LoS, evident by day 3, which improved progressively throughout the study periods (least squares mean difference vs placebo -0.07 [95% CI -0.12 to -0.02]; nominal P < .05 at day 3, and -1.04 [-1.17 to -0.91]; P < .0001 at week 24). Dupilumab improved mean UPSIT by 10.54 (least squares mean difference vs placebo 10.57 [9.40-11.74]; P < .0001) at week 24 from baseline (score 13.90). Improvements were unaffected by CRSwNP duration, prior sinonasal surgery, or comorbid asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. Baseline olfaction scores correlated with all measured local and systemic type 2 inflammatory markers except serum total immunoglobulin E.
CONCLUSIONS
Dupilumab produced rapid and sustained improvement in sense of smell, alleviating a cardinal symptom of severe CRSwNP.
Topics: Adult; Antibodies, Monoclonal, Humanized; Chronic Disease; Humans; Nasal Polyps; Quality of Life; Rhinitis; Sinusitis; Smell; Treatment Outcome
PubMed: 34628065
DOI: 10.1016/j.jaip.2021.09.037 -
Frontiers in Immunology 2022Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the...
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP.
METHODS
The expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results.
RESULTS
A total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP.
CONCLUSION
These findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.
Topics: Humans; Nasal Polyps; Sinusitis; Genes, fms; Chronic Disease; Macrophages
PubMed: 36466903
DOI: 10.3389/fimmu.2022.1047930 -
Acta Bio-medica : Atenei Parmensis Oct 2022Rhinosinusitis (RS) is a common disease and is currently classified into two main types: acute RS (ARS) and chronic RS (CRS), which in turn includes CRS with or without...
Rhinosinusitis (RS) is a common disease and is currently classified into two main types: acute RS (ARS) and chronic RS (CRS), which in turn includes CRS with or without nasal polyps. Different guidelines consider this classification. However, in clinical practice, other phenotypes exist. The current article would propose new clinical-based phenotyping of RS, including the following clinical phenotypes: simple catarrhal RS, Acute RS, acute bacterial RS, severe (complicated) acute RS, chronic RS, and recurrent chronic RS. Treatment strategy should be tailored considering the clinical phenotype and could include phytomedicines, intranasal non-pharmacological remedies, and local bacteriotherapy. In conclusion, RS requires thorough diagnostic work-up, and the therapeutic approach should be mainly based on appropriate management.
Topics: Humans; Rhinitis; Sinusitis; Nasal Polyps; Acute Disease; Chronic Disease
PubMed: 36300245
DOI: 10.23750/abm.v93i5.12633 -
European Annals of Otorhinolaryngology,... Feb 2018Chronic nasal dysfunction is a clinical concept in the diagnostic and therapeutic management of sinonasal diseases, based on the evo-devo theory of formation of the nose... (Review)
Review
Chronic nasal dysfunction is a clinical concept in the diagnostic and therapeutic management of sinonasal diseases, based on the evo-devo theory of formation of the nose according to which the nose is not a single organ but rather an association of three organs: olfactory nose, respiratory nose and paranasal sinuses. In chronic nasal dysfunction theory, etiological diagnosis takes account of the possible pathophysiological independence of nasal symptoms, in accordance with the different origins and physiology of the three organs constituting the nose. The diagnostic approach of the chronic nasal dysfunction concept breaks down the pathology so as to propose treatment(s) adapted to the diseased organ(s) and to the capacity for physiological resolution of dysfunction induced in one organ by pathology in a neighboring nasal organ. The ethmoid is not a sinus according to evo-devo, and therefore functional endoscopic endonasal surgery (FEES) cannot be restricted to functional endoscopic sinus surgery (FESS). Evo-devo theory and the chronic nasal dysfunction concept offer an alternative to the concept of chronic rhinosinusitis with or without polyps for the management of sinonasal diseases.
Topics: Chronic Disease; Humans; Laryngoscopy; Nasal Obstruction; Nasal Polyps; Nasal Surgical Procedures; Rhinitis; Sinusitis; Smell; Treatment Outcome
PubMed: 29249643
DOI: 10.1016/j.anorl.2017.11.006