Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps

Klingler, Aiko I.; Stevens, Whitney W.; Tan, Bruce K.; Peters, Anju T.; Poposki, Julie A.; Grammer, Leslie C.; Welch, Kevin C.; Smith, Stephanie Shintani; Conley, David B.; Kern, Robert C.; Schleimer, Robert P.; Kato, Atsushi

doi:10.1016/j.jaci.2020.11.037

Cited by 80 publications

(86 citation statements)

References 51 publications

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“…These cytokines promote macrophage activation, nitric oxide production, and cytotoxic T-cells proliferation, leading to the phagocytosis and destruction of microbial pathogens. Expression of Th1 cytokines is mainly found in patients with CRSsNP [ 107 ]. Although weakly expressed in nasal polyps, these cytokines play a role in the inflammatory cascade of CRSwNP.…”

Section: Type 1 Inflammatory Cytokinesmentioning

confidence: 99%

Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps

Carsuzaa

Béquignon

Dufour

et al. 2021

IJMS

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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.

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Section: Type 1 Inflammatory Cytokinesmentioning

confidence: 99%

Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps

Carsuzaa

Béquignon

Dufour

et al. 2021

IJMS

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“…More recently, single cell gene expression studies have also revealed distinct populations of epithelial cells and lymphocytes uniquely contributing to CRS pathophysiology (117,118) . Transcriptional changes have largely been validated by proteomic studies (119)(120)(121) as well as cellular and histologic studies of sinonasal mucosa which have highlighted not only importance of inflammatory dysregulation, but tissue remodeling in CRS pathophysiology (122)(123)(124)(125)(126) .…”

Section: Recent Multiomic Approaches Applied To Crs Have Revealed Novel Insights Into the Pathophysiologic Mechanisms Of Crsmentioning

confidence: 99%

“…Multiomic characterization of CRS pathophysiology also extends beyond the host to include the microbiome (129,130) with the most recent studies showing that there are common alterations in the sinonasal microbiome of CRS patients found throughout the world (131) . Supported by the aforementioned multiomic approaches, endotypes of CRS-although potentially quite numerous-have been shown to be broadly characterized as being dominated by type-2 inflammation or not (92,120,121) . In fact, the most recent guidance from the 2020 European Position Paper on Rhinosinusitis and Nasal Polyps is that primary inflammatory CRS be classified based on whether the patient's disease is due to type-2 inflammation or not, rather than using phenotypic classifications such as the presence of nasal polyps (43) .…”

Section: Recent Multiomic Approaches Applied To Crs Have Revealed Novel Insights Into the Pathophysiologic Mechanisms Of Crsmentioning

confidence: 99%

Rhinology in review: from COVID-19 to biologicals

Fokkens¹,

Landis²,

Hopkins³

et al. 2021

Rhin

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We look back at the end of what soon will be seen as an historic year, from COVID-19 to real-world introduction of biologicals influencing the life of our patients. This review describes the important findings in Rhinology over the past year. A large body of evidence now demonstrates loss of sense of smell to be one of the most common symptoms of COVID-19 infection; a meta-analysis of 3563 patients found the mean prevalence of self-reported loss to be 47%. A number of studies have now shown long-term reduced loss of smell and parosmia. Given the high numbers of people affected by COVID-19, even with the best reported recovery rates, a significant number worldwide will be left with severe olfactory dysfunction. The most prevalent causes for olfactory dysfunction, besides COVID-19 and upper respiratory tract infections in general, are trauma and CRSwNP. For these CRSwNP patients a bright future seems to be starting with the development of treatment with biologics. This year the Nobel prize in Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch which has greatly enhanced our understanding of nasal hyperreactivity and understanding of intranasal trigeminal function. Finally, a new definition of chronic rhinitis has been proposed in the last year and we have seen many papers emphasizing the importance of endotyping patients in chronic rhinitis and rhinosinusitis in order to optimise treatment effect.

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“…Numerous hypotheses have been proposed as the underlying mechanism for nasal polyps, including the role of chronic infections, aspirin intolerance, trapping of contaminants due to aerodynamic changes, or aerodynamic changes, or changing in Sodium-ion uptake (3)(4)(5). Some hereditary factors also seem to play an important role (6,7).…”

Section: Introductionmentioning

confidence: 99%

Relationship between plasma cyclin-dependent kinase 5 levels and local immunoglobulin levels in patients with nasal polyps

Liu¹,

Luo²,

Yan³

et al. 2021

Cell Mol Biol (Noisy-le-grand)

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Nasal polyps are the most common benign nasal tumors that can lead to nasal obstruction and other annoying problems for the patient. Several hypotheses have been proposed as the basic mechanism of nasal polyps. In order to investigate one of the possible causes that can be a disorder in the regulation of systemic immune responses, the present study was designed to investigate the relationship between plasma cyclin-dependent kinase 5 (CDK5) levels and local immunoglobulin levels in patients with nasal polyps. A cross-section study was used to evaluate concentrations of local immunoglobulin levels (IgE, IgM, IgA, and IgG) on blood and polyp specimens from 60 patients with nasal polyps, and 60 control groups. Western Blot Analysis was done for CDK5 in plasma cells. IgA, IgG and IgE concentrations were significantly higher in polyp tissue specimens, but not in blood, of nasal polyp patients compared to the control group. Furthermore, plasma CDK5 levels were significantly higher in nasal polyp tissue compared with control. The difference in IgA, IgE and IgG expression between nasal polyp tissue and blood, supported by increased numbers of plasma cells, suggests a local production of these local immunoglobulins in nasal polyps in response to chronic antigens. Among local immunoglobulins, only there was a significant correlation between CDK5 with IgG (positive correlation) and IgE (negative correlation). The exact explanation for the relationship between plasma CDK5 and local immunoglobulins in nasal polyps needs further studies.

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Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps

Cited by 80 publications

References 51 publications

Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps

Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps

Rhinology in review: from COVID-19 to biologicals

Relationship between plasma cyclin-dependent kinase 5 levels and local immunoglobulin levels in patients with nasal polyps

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