scholarly journals Comparative analysis of inflammatory signature profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyposis

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Yao Yao ◽  
Chunguang Yang ◽  
Xing Yi ◽  
Shaobing Xie ◽  
Hong Sun

Abstract Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents a heterogeneous disorder that can be classified into either eosinophilic or noneosinophilic endotypes. However, the immunological mechanisms of each remain unclear. The purpose of the present study was to compare and analyze inflammatory signatures of eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). Cytokine antibody array was used to identify inflammatory mediators that were differentially expressed among ECRSwNP, NECRSwNP, and control groups. Then, bioinformatics approaches were conducted to explore biological functions and signaling pathways. In addition, pairwise correlation analyses were performed among differential levels of inflammatory mediators and tissue eosinophil infiltration. The results showed that nine mediators were significantly up-regulated in ECRSwNP, including eotaxin-2, eotaxin-3, CCL18, IL-4, IL-5, IL-10, IL-12p70, IL-13, and IL-15. Bioinformatics analysis indicated that these mediators were mainly enriched in leukocyte chemotaxis and proliferation, JAK-STAT cascade, asthma, and Th1 and Th2 cell differentiation. Furthermore, seven mediators were identified to be significantly up-regulated in NECRSwNP, including CCL20, resistin, transforming growth factor (TGF)-β2, triggering receptor expressed on myeloid cells 1 (TREM-1), CD14, glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), and lipocalin-2. These mediators were closely associated with LPS responses, neutrophil chemotaxis and migration, and IL-17 signaling pathway. In addition, pairwise correlation analyses indicated that differential levels of inflammatory mediators in ECRSwNP and NECRSwNP were broadly correlated with each other and with tissue eosinophil infiltration. In conclusion, we found that ECRSwNP and NECRSwNP exhibited different patterns of inflammatory signatures. These findings may provide further insights into heterogeneity of CRSwNP.

Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.


2004 ◽  
Vol 18 (5) ◽  
pp. 267-272 ◽  
Author(s):  
Jean-Baptiste Watelet ◽  
Cindy ◽  
Claudina Perez-Novo ◽  
Philippe Gevaert ◽  
Paul Van Cauwenberge ◽  
...  

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Gargi Rai ◽  
Shukla Das ◽  
Mohammad Ahmad Ansari ◽  
Praveen Kumar Singh ◽  
Sajad Ahmad Dar ◽  
...  

Abstract Background T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. Results The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-β levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. Conclusions Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.


2008 ◽  
Vol 149 (37) ◽  
pp. 1737-1746 ◽  
Author(s):  
Imre Gerlinger ◽  
András Fittler ◽  
Anna Mayer ◽  
Ágnes Patzkó ◽  
Fruzsina Fónay ◽  
...  

A krónikus rhinosinusitis (KRS) a felnőttpopuláció 1–4%-át érintő, jelentős életminőség-romlást okozó idült, multifaktoriális, gyakran orrpolipképződéssel járó, etiológiáját illetően azonban pontosan nem tisztázott megbetegedés. Az elmúlt évtizedben felmerült, hogy az orrüregi nyálkahártya jellegzetes eozinofil sejtes beszűrődését okozó megbetegedésnek az orrüregi nyákban található gombák elleni fokozott – nem IgE típusú klasszikus allergiás – immunválasz a kiváltó oka. Célkitűzés: Ha igaz ez a feltételezés, akkor kézenfekvőnek tűnik, hogy az endoszkópos orrpolypectomiákat követően megfelelő ideig és koncentrációban adott amphotericin B-tartalmú orrspray kedvező hatású lehet a betegek számára, akár csökkentve a recidívák számát. Módszer: A feltételezés igazolá­sára a szerzők 33 beteg bevonásával prospektív, randomizált, placebokontrollált, kettős vak klinikai tanulmányt végeztek. A tanulmányt végül 30 beteg fejezte be. A 2005. november 1-je és 2006. október 1-je között orrpolyposissal endoszkópos műtétre került betegek egyik csoportja (A csoport, 14 beteg) egy évig 5 mg/ml koncentrációjú amphotericin B-tartalmú orrsprayt kapott, míg a placebo­csoport (B csoport, 16 beteg) hatóanyag nélküli orrsprayt. Az eredmények értékeléséhez a módosított Lund–Mackay-féle CT-értékelő pontrendszert, a tüneti változásokat vizsgáló pontrendszert (SNAQ-11), életminőségtesztet és endoszkópos kiértékelést végeztek. A műtétek előtt és a műtéteket követően egy évvel elvégzett vizsgálatok eredményeit SPSS 14.0 for Windows program segítségével értékelték. Eredmények: Az A csoport betegeinek CT-értékelő pontrendszere egy év elteltével jelentős szórást mutatott, a javulás jelei nélkül. A B csoportban a CT-értékelő pontrendszere enyhe javulást mutatott, azonban ez az A csoporttal összehasonlítva nem volt szignifikáns (p = 0,052). A tüneti változásokat vizsgáló pontrendszer (SNAQ-11), valamint az életminőségteszt mindkét betegcsoportban lényeges javulást mutatott, a két tesztben a változások mértékét összehasonlítva azonban egyik betegcsoport javára sem találtak szignifikáns különbséget. Az endoszkópos lelet az amphotericin B-csoport javára mutatott mérsékelt javulást 12 hónappal a műtéteket követően. Következtetések: A szerzők megállapítják, hogy az orrpolyposis miatt operált betegekben az amphotericin B-tartalmú orrcsepp egy évig történő adása nem okoz szignifikáns változást a CT-pontszámok, a klinikai tünetek, valamint az életminőség vonatkozásában. A betegek endoszkópos követése során az amphotericin B-csoportban észlelt kedvezőbb kép a klinikai tünetek javulásában nem nyilvánult meg. A szerzők a tanulmány eredményeiből levont tanulságok tükrében tárgyalják a gombaelméletről rendelkezésre álló eddigi ismeretanyagot. Kritikusan elemzik az elmúlt években publikált 7, ellentmondásos konklúziót mutató klinikai tanulmány tapasztalatait is.


2021 ◽  
pp. 194589242098743
Author(s):  
Nyssa F. Farrell ◽  
Jess C. Mace ◽  
David A. Sauer ◽  
Andrew J. Thomas ◽  
Mathew Geltzeiler ◽  
...  

Background Chronic rhinosinusitis (CRS) is often differentiated by histopathologic phenotypes (eosinophilic versus neutrophilic), which may impact disease severity measures and outcomes. As such, it has been suggested that counts of cellular elements be included as part of a standard pathological report following endoscopic sinus surgery (ESS). Objectives This cross-sectional study evaluated associations of mucosal eosinophilia and neutrophilia with measures of quality-of-life (QoL) and olfactory function. Methods Patients with medically refractory CRS completed the SNOT-22 survey and Brief Smell Identification Test (BSIT) at enrollment. In addition, baseline Lund-Mackay computed tomography (CT) and Lund-Kennedy endoscopy scores were collected. Ethmoid mucosa was biopsied during ESS and reviewed using microscopy to quantify densest infiltrate of eosinophils or neutrophils per high-powered-field (HPF). Eosinophilic CRS (eCRS) and neutrophilic CRS (nCRS), both with and without nasal polyposis (NP), were compared across SNOT-22 and BSIT scores. Results 77/168 patients demonstrated mucosal eosinophilia (eCRS) while a total of 42/168 patients demonstrated mucosal neutrophilia (nCRS). After adjusting for polyp status, 35/168 had eCRSsNP, 42/168 eCRSwNP, 75/168 non-eCRSsNP, 16/168 non-eCRSwNP. Additionally, 22/161 were noted to have nCRSsNP, 20/161 nCRSwNP, 84/161 non-nCRSwNP, and 35/161 non-nCRSsNP. A small subset of patients demonstrated both eosinophilia and neutrophilia: 14 CRSwNP and 7 CRSsNP. When evaluating average Lund-Mackay Scores (LMS), significant differences existed between non-eCRSsNP and eCRSsNP (p = 0.006). However, after controlling for nasal polyps, eosinophilia did not significantly associate with differences in the Lund-Kennedy Score. Neutrophilia did not significantly associate with any changes in LMS or LKS after controlling for NP. Eosinophilic and neutrophilic histopathologic subtypes did not significantly associate with differences in baseline SNOT-22 or BSIT measures after controlling for NP. Conclusion Neither the presence of mucosal eosinophilia nor mucosal neutrophilia demonstrated significant associations with SNOT-22 quality-of-life or BSIT olfactory function scores when controlling for comorbid nasal polyposis.


2014 ◽  
Vol 151 (1_suppl) ◽  
pp. P252-P253
Author(s):  
David Hernandez ◽  
Kathryn E. Hulse ◽  
James E. Norton ◽  
Bruce K. Tan ◽  
Robert C. Kern ◽  
...  

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