The Pathogenesis of CRS: An Update (original) (raw)
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Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps
Journal of Allergy and Clinical Immunology, 2021
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Proceedings of The American Thoracic Society, 2009
The purpose of this review is to discuss recent findings made during studies of the upper airways and sinuses of people with chronic rhinosinusitis (CRS) in the context of the literature. CRS is a chronic inflammatory disorder affecting nearly 30 million Americans and is generally resistant to therapy with antibiotics and glucocorticoids (Meltzer EO and coworkers, J Allergy Clin Immunol 2004;114:155-212). We have formed a collaboration that consists of otolaryngologists, allergists, and basic scientists to address the underlying immunologic and inflammatory processes that are occurring in, and possibly responsible for, this disease. The main emphasis of our work has been to focus on the roles that epithelium, in the sinuses and upper airways, plays as both a mediator and regulator of immune and inflammatory responses. It is not our intention here to provide a comprehensive review of the literature in this area, but we will try to put our work in the context of the findings of others (Kato A and Schleimer RP, Curr Opin Immunol 2007;19:711-720; Schleimer RP and coworkers, J Allergy Clin Immunol 2007;120:1279-1284. In particular, we discuss the evidence that epithelial cell responses are altered in CRS, including those relevant to regulation of dendritic cells, T cells, B cells, and barrier function.
Is there a future for biologics in the management of chronic rhinosinusitis?
International Forum of Allergy & Rhinology, 2016
Background-Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the sinonasal mucosa consisting of poorly defined subtypes and characterized by variable clinical manifestations, responses to therapy, and underlying pathophysiologies. In the related disorder of asthma, progress has been made in defining disease subtypes on both clinical and pathophysiologic levels, facilitating the development of targeted biologic pharmacotherapy. The potential role of these drugs for the management of CRS will be reviewed. Objective-To highlight the emerging therapeutic targets in CRS in light of evolving treatment options for asthma and enhanced understandings of the clinical manifestations and pathophysiology of CRS. Methods-The article is a review of recent studies regarding current and future advances in biomarker-directed therapies in the medical treatment of CRS. Results-Various biologic therapies used in the management of asthma have demonstrated clinical promise for CRS, particularly within the CRS with nasal polyposis (CRSwNP) phenotype. Several randomized, double-blind, placebo-controlled studies increasingly support the targeting of immunoglobulin E and interleukin (IL)-5 pathways to improve outcome measures in CRSwNP patients. The IL-4/IL-13 pathway and other type 2 inflammatory pathways have also shown potential as targets for CRSwNP, but all pathways require further investigation. Conclusion-Recalcitrant CRS in the United States and Europe is most commonly associated with nasal polyposis and a type 2 cytokine skewing in the tissue, resulting in tissue infiltration of eosinophils, mast cells, and basophils. Targeting biomarkers of the associated type 2 pathways may be a practical treatment option for recalcitrant CRSwNP in the future.
Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps
International Journal of Molecular Sciences, 2021
Cytokines are well known to play a central role in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in maintenance of the inflammatory response and the recruitment of eosinophils. The pathophysiological concepts concerning the involvement of inflammatory cytokines in CRSwNP have gradually evolved. Although the Th2 cytokines environment associated with an eosinophilic infiltration has retained a central role in the genesis of polyps, the role of other cytokine subpopulations has also and more recently been detailed, leading to a specific and complex signature in CRSwNP. The purpose of this review is to summarize the current state of knowledge about the cytokine signature in CRSwNP, the role of cytokines in the pathogenesis of this disease and in the intercellular dialog between epithelial cells, fibroblasts and inflammatory cells. Knowledge of this precise cytokine signature in CRSwNP is fundamental in the perspective of potential targeting biotherapies.
Highlights in the advances of chronic rhinosinusitis
Allergy, 2021
Chronic rhinosinusitis (CRS) is a protracted inflammatory condition with global societal and financial burden. 1-3 Its prevalence is estimated to be 10-28% based on self-reported symptoms alone, 4,5 and about 4-9% when endoscopy 6 or imaging is applied. 7,8 Real world data suggest that nearly half of CRS patients have uncontrolled disease based on visual analogue scale for rhinosinusitis. 9 This subgroup has significant disease burden as these patients require longterm follow-up, medication and often repeat sinus surgeries. 10 Traditionally, CRS is classified based on the presence or absence of nasal polyps. It is evident that this classification based on a visual trait is probably an overly simplistic representation of a heterogenous condition with a spectrum of clinical presentations and severity. Hence in recent years, there is increasing interest in uncovering the inflammatory mechanisms, or endotypes, of CRS. With the advent of novel treatment options, including biologicals, the ability to accurately define endotypes and predict response to specific treatments via biomarkers is important in order to provide individualised patient care. 11 Research in CRS is a continually evolving field. The objective of this review is to update readers on the recent, important developments in the field of CRS in adults. This includes the changes in the latest edition of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020), novel biomarkers, biologicals in the treatment of CRSwNP and the implications of the COVID-19 on the
Pathophysiological and Clinical Aspects of Chronic Rhinosinusitis: Current Concepts
Frontiers in Allergy, 2021
Adult chronic rhinosinusitis (CRS) is a chronic inflammation of the mucosa of the nose and paranasal sinuses. According to the latest EPOS guidelines CRS should be regarded as primary or secondary with distinction between diffuse and localized disease. Further pathophysiologic research identified different inflammatory patterns leading to the term “endotyping of CRS.” The primary focus of endotyping is to define a dominant inflammatory type allowing for better orientation of therapy. The current approach proposes the differentiation between type 2 (eosinophilic) and non-type 2 inflammatory responses. In this review pathophysiological concepts of CRS will be discussed, focusing on the different inflammatory endotypes of T cells with special attention to the eosinophilic type 2 inflammatory response. The contribution of innate and adaptive immune system responses is presented. The possibility of endotyping based on sinonasal secretions sampling is brought to attention because it is in...
Clinical severity and epithelial endotypes in chronic rhinosinusitis
International Forum of Allergy & Rhinology, 2012
Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease defined by epithelial inflammation. The link between measures of traditional disease severity and markers of epithelial inflammation is poorly understood as prior research has focused on presence of polyps or degree of eosinophilia. The expression of 3 epithelial derived cytokines implicated in initiation of T-helper 2 (Th2) inflammation and an eosinophil chemoa ractant were compared with clinical measures used in CRS.