Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and is historically divided into 2 main phenotypes: CRS with nasal polyps and CRS without nasal polyps. Inflammation in CRS is mainly characterized by 3 endotypes based on elevation of canonical lymphocyte cytokines: type (T) 1 (T1) by TH1 cytokine IFN-γ, T2 by TH2 cutokines IL-4, IL-5, and IL-13, and T3 by TH17 cytokines including IL-17. Inflammation in both CRS without nasal polyps and CRS with nasal polyps is highly heterogeneous, and the frequency of various endotypes varies geographically around the world. This finding complicates establishment of a unified understanding of the mechanisms of pathogenesis in CRS. Sinonasal epithelium acts as a passive barrier, and epithelial barrier dysfunction is a common feature in CRS induced by endotype-specific cytokines directly and indirectly. The sinonasal epithelium also participates in both innate immunity via recognition by innate pattern-recognition receptors and promotes and regulates adaptive immunity via release of chemokines and innate cytokines including thymic stromal lymphopoietin. The purpose of this review was to discuss the contribution of the epithelium to CRS pathogenesis and to update the field regarding endotypic heterogeneity and various mechanisms for understanding pathogenesis in CRS. 

Mechanisms and pathogenesis of chronic rhinosinusitis.

Chronic rhinosinusitis with nasal polyps is frequently managed with endoscopic sinus surgery (ESS). Prior studies describe individual clinical variables and eosinophil density measures as prognostic for polyp recurrence (PR). However, the relative prognostic significance of these have not been extensively investigated.We sought to evaluate the impact of PR on measures of disease severity post-ESS and quantify the prognostic value of various clinical variables and biomarkers.Ninety-four patients with chronic rhinosinusitis with nasal polyps and prospectively biobanked polyp homogenates at the time of ESS were recruited 2 to 5 years post-ESS. Patients were evaluated with patient-reported outcome measures and endoscopic and radiographic scoring pre- and post-ESS. Biomarkers in polyp homogenates were measured with ELISA and Luminex. Relaxed least absolute shrinkage and selection operator regression optimized predictive clinical, biomarker, and combined models. Model performance was assessed using receiver-operating characteristic curve and random forest analysis.PR was found in 39.4% of patients, despite significant improvements in modified Lund-Mackay (MLM) radiographic and 22-item Sinonasal Outcomes Test scores (both P < .0001). PR was significantly associated with worse post-ESS MLM, modified Lund-Kennedy, and 22-item Sinonasal Outcomes Test scores. Relaxed least absolute shrinkage and selection operator identified 2 clinical predictors (area under the curve = 0.79) and 3 biomarkers (area under the curve = 0.78) that were prognostic for PR. When combined, the model incorporating these pre-ESS factors: MLM, asthma, eosinophil cationic protein, anti-double-stranded DNA IgG, and IL-5 improved PR predictive accuracy to area under the curve of 0.89. Random forest analysis identified and validated each of the 5 variables as the strongest predictors of PR.PR had strong associations with patient-reported outcome measures, endoscopic and radiographic severity. A combined model comprised of eosinophil cationic protein, IL-5, pre-ESS MLM, asthma, and anti-double-stranded DNA IgG could accurately predict PR. 

Prognostic Factors for Polyp Recurrence in Chronic Rhinosinusitis with Nasal Polyps.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines-with a focus on China-will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.

/pdf/chinese-society-of-allergy-and-chinese-society-of-2pk64cfbmg.pdf

Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis

ラット椎間板皮下吸収モデルにおけるMCP-1(monocyte chemoattractant protein-1)の動向について

Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype-based classifications, owing to its potential in prognosticating disease severity and delivering precision treatment. Endotyping is especially useful in challenging CRS with nasal polyposis cases, for whom novel treatment options such as biologicals are now available. The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) reflects these changes with updated rhinosinusitis classifications and new integrated care pathways. With the Coronavirus Disease 2019 (COVID-19) pandemic, physicians and rhinologists have to balance the responsibility of managing their patients' upper airway whilst adequately protecting themselves from droplet and aerosol transmission. This review summarises the key updates from EPOS2020, endotype-based classification and biomarkers. The role of biologicals in CRS and the lessons we can draw from their use in severe asthma will be examined. Finally, the principles of CRS management during COVID-19 will also be discussed.

Highlights in the advances of chronic rhinosinusitis.

Neutrophils have traditionally been acknowledged as the first immune cells that are recruited to inflamed tissues during acute inflammation. By contrast, their importance in the context of chronic inflammation has been studied in less depth. Neutrophils can be recruited and are largely present in the nasal mucosa of patients with chronic rhinosinusitis (CRS) both in Asians and in Caucasians. Increased infiltration of neutrophils in patients with CRS has been linked to poor corticosteroid response and disease prognosis. Meanwhile, tissue neutrophils may possess specific phenotypic features distinguishing them from resting blood counterparts and are endowed with particular functions, such as cytokines and chemokines production, thus may contribute to the pathogenesis of CRS. This review aims to summarize our current understanding of the pathophysiologic mechanisms of CRS, with a focus on the roles of neutrophils. We discuss recruitment, function, and regulation of neutrophils in CRS and outline the potential therapeutic strategies targeting neutrophils.

/pdf/neutrophils-as-a-protagonist-and-target-in-chronic-2h8hgay1rw.pdf

Neutrophils as a Protagonist and Target in Chronic Rhinosinusitis

Background Previous studies have been limited to the utility of clinical features and invasive nasal mucosal biomarkers in the prediction of chronic rhinosinusitis (CRS) outcomes. This study aimed to identify noninvasive biomarkers associated with difficult- to-treat CRS, enabling physicians to subgroup patients into risk groups for poor outcome before surgery. Methods Three hundred and nine CRS patients undergoing endoscopic sinus surgery were finally enrolled. Patients treated with oral or intranasal glucocorticoids within 3 months or 1 month before surgery, respectively, were excluded. Baseline clinical charac- teristics, nasal secretions and peripheral blood samples were collected before surgery. The protein levels of 39 biological mar- kers were detected by the Bio-Plex suspension chip method. Classification and regression tree analysis was applied to establish prediction model for difficult-to-treat CRS determined one year after surgery. A random forest algorithm was used to confirm the discriminating factors that formed the classification tree. Results In the cohort with nasal secretion sample (n = 189), 21% of CRS patients were diagnosed as difficult-to-treat after 1 year of follow-up. Nasal secretion CCL17 level, hyposmia score, allergic rhinitis comorbidity, and nasal secretion MIP-1β level were found important predictors of difficult-to-treat CRS. A classification tree separated patients into 5 subgroups leading to an overall predictive accuracy of 94%. However, none of the plasma biological markers were associated with difficult-to-treat CRS in the cohort with blood sample (n = 128). Conclusions Patients with difficult-to-treat-CRS were characterized by higher nasal secretion levels of CCL17 and MIP-1β, severe hyposmia and concomitant allergic rhinitis. The classification tree could be useful to identify patients with high risk of poor outcome prior to surgery and offer more personalized interventions. However, since only patients without preoperative steroid treatments were included in this study, the generalization of our predictive model in other patient populations should be conside- red with caution.

/pdf/predicting-difficult-to-treat-chronic-rhinosinusitis-by-4c0ggidzus.pdf

Predicting difficult-to-treat chronic rhinosinusitis by noninvasive biological markers.

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Neutrophils as a Protagonist and Target in Chronic Rhinosinusitis

Predicting difficult-to-treat chronic rhinosinusitis by noninvasive biological markers.