Vitamin D decreases the secretion of eotaxin and RANTES in nasal polyp fibroblasts derived from Taiwanese patients with chronic rhinosinusitis with nasal polyps

Background and Objectives The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored.Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells.Results NLRP3 showed a high level of expression in nasal polyps than in the control group (p<0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (p<0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (p<0.05).Conclusion The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.

Download Full-text

Involvement of the Extracellular Matrix Proteins Periostin and Tenascin C in Nasal Polyp Remodeling by Regulating the Expression of MMPs

10.21203/rs.3.rs-118180/v1 ◽

2020 ◽

Author(s):

Kun Du ◽

Min Wang ◽

Nan Zhang ◽

Ping Wang ◽

Pei Yu ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyp ◽

Nasal Polyps ◽

Ex Vivo ◽

Tissue Remodeling ◽

Tenascin C ◽

Protein Levels ◽

Control Subjects

Abstract Background: Tissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of two ECM proteins in the expression of MMPs in nasal polyps.Methods：The concentrations of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, TIMP-1, TIMP-2, TIMP-3, TIMP-4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and their correlations were analyzed. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real-time PCR.Results: The protein levels of MMP-3, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. Periostin was positively correlated with MMP-3 and TIMP-2, and tenascin C was positively correlated with MMP-3, MMP-7, MMP-8, MMP-9 and TIMP-2. Periostin stimulated the gene expression of MMP-3, MMP-7, and MMP-9 in fibroblasts and MMP-7 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP-3, MMP-8, and MMP-9 in epithelial cells, but not in fibroblasts. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C. Conclusions：Periostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.

Download Full-text

Efficacy of Short-Term Systemic Corticosteroid Therapy in Chronic Rhinosinusitis With Nasal Polyps: A Meta-Analysis of Randomized Controlled Trials and Systematic Review

American Journal of Rhinology and Allergy ◽

10.1177/1945892419851312 ◽

2019 ◽

Vol 33 (5) ◽

pp. 567-576 ◽

Cited By ~ 1

Author(s):

Yunyun Zhang ◽

Chengshuo Wang ◽

Yanran Huang ◽

Hongfei Lou ◽

Luo Zhang

Keyword(s):

Randomized Controlled Trials ◽

Chronic Rhinosinusitis ◽

Nasal Polyp ◽

Nasal Polyps ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Polyp Size ◽

Randomized Controlled ◽

Systemic Corticosteroids

Background Corticosteroids are considered the most effective medication to control chronic rhinosinusitis with nasal polyps (CRSwNP); however, the studies of systemic corticosteroids in this field are relatively few and meta-analyses are lacking. Objective We aimed to systematically review the efficacy and safety of systemic corticosteroids for patients with CRSwNP via meta-analysis. Methods Data were extracted from relevant and appropriate randomized controlled trials (RCTs) of systemic corticosteroids for patients with CRSwNP from PubMed, MEDLINE, Ovid, Embase, the Cochrane Central Register of Controlled Trials, and Google Scholar. Efficacy was assessed based on clinical outcomes, while safety was assessed based on adverse events (AEs). Results A total of 337 relevant publications were identified, of which 7 RCTs including 414 participants were included in the meta-analysis. Compared to placebos or nonsteroid treatments, systemic corticosteroids significantly improved nasal obstruction scores standardized mean difference (SMD −2.81; 95% confidence interval [CI], −4.68 to −0.95; P = .003), reduced the nasal polyp size (SMD −4.76; 95% CI, −6.99 to −2.52; P < .0001), and improved peak nasal inspiratory flow (PNIF) (SMD 42.39; 95% CI, 28.95 to 55.84; P < .00001). The high-dose (more than or equal to 50 mg/day prednisone) and low-dose subgroups (less than 50 mg/day prednisone) experienced similar benefits. However, insomnia and gastrointestinal disturbances were noted more frequently in patients treated with high doses of prednisone. Other AEs were infrequent and were not significantly different between the subgroups. Conclusion Systemic corticosteroids provide significant improvements in nasal symptoms and PNIF as well as a reduction in nasal polyp size for patients with CRSwNP. Prednisone doses less than 50 mg/day were recommended when the efficacy of oral corticosteroids in CRSwNP was balanced against potential adverse effects.

Download Full-text

Pediatric Endoscopic Sinus Surgery in a Tertiary Government Hospital: Patient Profile and Surgical Indications

Philippine Journal of Otolaryngology Head and Neck Surgery ◽

10.32412/pjohns.v24i1.705 ◽

2009 ◽

Vol 24 (1) ◽

pp. 13-17

Author(s):

Michael Joseph C. David ◽

Gil M. Vicente ◽

Antonio H. Chua

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyp ◽

Endoscopic Sinus Surgery ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Sinus Surgery ◽

Government Hospital ◽

Female Ratio ◽

Sinus Disease ◽

The Mean

Objective: To describe the clinical and demographic profile of patients who underwent pediatric Endoscopic Sinus Surgery (ESS), and the indications for which the procedure was performed. Methods: Design: Cross-sectional Study Setting: Tertiary Government Hospital Subjects: Using the medical record registry, all patients below 18 years of age who underwent ESS under the Department of Otorhinolaryngology – Head and Neck Surgery of a tertiary government hospital in Metro Manila between December 31, 1999 and January 1, 2008 were reviewed. The age, sex, clinical presentation, and indications for doing ESS, and extent of surgery done were described. The Lund MacKay Grading for nasal polyposis and Scoring for sinusitis were also applied and cross-referenced. Results: Twenty-seven children aged 7 to 17 years underwent ESS. The mean age was 12.9 years, with most (15 patients) belonging to the adolescent age group (13-17 years). Male to female ratio was 1.45:1. The mean interval from onset of symptoms to the first outpatient consultation was 1.5 years; the most common presenting symptoms were nasal obstruction (85.2%) and discharge (59.3%). All of the patients who underwent pediatric ESS had chronic rhinosinusitis: either with nasal polyposis (85.2%), an antrochoanal polyp (11.1%), or both (3.7%). The Lund Mackay Grading for nasal polyps and sinusitis scores were cross-referenced: patients with larger, grade III nasal polyps tended to have more extensive sinus disease than those with grade II polyps. On their first consultation, the patients tended to present with extensive nasal polyp and sinus disease, indicating the need for surgery. All patients with CRS and nasal polyposis underwent polypectomy with ethmoidectomy, uncinectomy and maxillary antrostomy, with additional frontal sinusotomy for a 17 year old male and a 17 year old female, both with grade 3 polyposis. The three patients who had antrochoanal polyps underwent polypectomy with uncinectomy and maxillary antrostomy. There were no operative complications such as cerebrospinal fluid leak and orbital injury reported. Conclusion: Most of the patients who underwent pediatric ESS were older children who were brought for consultation with long-standing, extensive nasal polyp and sinus disease or with antrochoanal polyps, necessitating surgical management. Patients with larger polyps tended to have more extensive sinus disease. They all underwent conservative surgery, with extent of the procedure limited to the extent of the disease present. Efforts to raise public awareness about chronic rhinosinusitis and nasal polyposis in children may result in seeing such cases at an earlier, conservatively treatable stage Keywords: Pediatric Endoscopic Sinus Surgery, Nasal Polyposis in Children

Download Full-text

TIM-3–Expressing Mast Cells Are Present in Chronic Rhinosinusitis with Nasal Polyps

Otolaryngology ◽

10.1177/0194599818774560 ◽

2018 ◽

Vol 159 (3) ◽

pp. 581-586 ◽

Cited By ~ 2

Author(s):

Erica Corredera ◽

Binh L. Phong ◽

John A. Moore ◽

Lawrence P. Kane ◽

Stella E. Lee

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Chronic Rhinosinusitis ◽

Disease Severity ◽

Nasal Polyp ◽

Nasal Polyps ◽

Staging System ◽

Sinus Surgery ◽

Epithelial Layer ◽

Polyp Tissue

Objectives To identify whether TIM-3 expression is present in the mast cell population within nasal polyps and to determine its correlation with clinical severity in patients with chronic rhinosinusitis with nasal polyposis. Study Design Basic science, translational study. Setting Nasal polyp tissue collected from patients seen at a tertiary care hospital (2015-2016). Subjects and Methods Nasal polyp tissue obtained during functional endoscopic sinus surgery (n = 24) was enzymatically digested into epithelial and stromal fractions. Viable mast cells expressing TIM-3 were identified using flow cytometry for the following: CD45, Live/Dead, c-kit, FcεR1, TIM-3. Disease severity was assessed using the Sino-Nasal Outcome Test, Lund-Mackay staging system, Lund-Kennedy staging system, and complete blood counts. Results Mast cells were found in both the epithelial and stromal layers of polyps, with a greater %TIM-3+ mast cells in the epithelial layer compared with that of the stromal layer ( P = .001). As the percentage of mast cells increased, there was a comparative worsening in endoscopic severity after comparing pre- and postoperative LK scores (ρ = −0.455, P = .029). In a subgroup of patients with concomitant asthma, increased epithelial %TIM-3+ mast cells also correlated with worsening endoscopic appearance postoperatively (ρ = 0.866, P = .001, n = 11). Oral corticosteroid treatment did not change the viability of mast cells nor their influence on the increased postoperative endoscopic disease severity (ρ = −0.544, P = .020, n = 18). Conclusion Viable mast cells were found to be present in polyps with increased TIM-3 expression at the epithelial layer. This suggests that TIM-3 may play a role in chronic inflammation in CRSwNP via mast cell activation.

Download Full-text

IL-5Rα marks nasal polyp IgG4 and IgE-secreting cells in aspirin-exacerbated respiratory disease

10.1101/527762 ◽

2019 ◽

Author(s):

Kathleen M. Buchheit ◽

Daniel F. Dwyer ◽

Jose Ordovas-Montanes ◽

Howard R. Katz ◽

Erin Lewis ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Respiratory Disease ◽

Disease Severity ◽

Nasal Polyp ◽

Nasal Polyps ◽

Mrna Levels ◽

Aspirin Exacerbated Respiratory Disease ◽

Polyp Tissue ◽

Antibody Levels ◽

Antibody Secreting Cells

AbstractBackgroundThe cause of nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but the upstream drivers and cellular mechanisms of local antibody production in AERD remain to be investigated.ObjectiveWe sought to identify the upstream drivers and phenotypic properties of local antibody-secreting cells in nasal polyps and to understand their clinical relevance in AERD.MethodsSinus tissue was obtained from subjects with AERD, aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP), aspirin-tolerant chronic rhinosinusitis without nasal polyps (CRSsNP), and healthy controls. Tissue antibody levels were quantified via ELISA and immunohistochemistry, and were correlated with clinical markers of disease severity. Tissue cytokine mRNA levels were measured with quantitative PCR (qPCR). Antibody-secreting cells were profiled with a combination of single-cell RNA-sequencing (scRNA-seq), flow cytometry and immunofluorescence.ResultsTissue IgE and IgG4 were elevated in AERD compared to controls (p<0.01 for IgE and p<0.001 for IgG4, vs. CRSwNP). Total IgG and IgG4 positively correlated with the number of polyp surgeries per subject (r=0.48, p=0.011 and r=0.58, p=0.0003, respectively). Polyp IL-10 mRNA expression was higher in AERD vs. CRSwNP (p<0.05), but there were no differences in mRNA expression of type 2 cytokines. ScRNA-seq revealed increased IL5RA, IGHG4, and IGHE in the antibody-associated cells of subjects with AERD compared to CRSwNP. Total plasma cells and IL-5Rα+ plasma cell numbers in the polyp tissue from AERD exceeded those in polyps from CRSwNP (p=0.0051 and p=0.026, respectively) by flow cytometry. With immunofluorescence, we determined that IL-5Rα and IgG4 are co-expressed in antibody-secreting cells in AERD.ConclusionsOur study identifies unique clusters of antibody-secreting cells in AERD defined by enrichment of transcripts encoding IL5RA, IGHG4 and IGHE. We confirm surface expression of IL-5Rα on these cells, and identify T cells as a unique transcriptional source of IL-5. Tissue antibody levels are elevated in AERD and correlate with disease severity. Our findings suggest a role for IL-5 in facilitating local antibody production that may drive features of severe sinus disease.Key MessagesIgG4 and IgE levels are markedly increased in nasal polyp tissue from subjects with AERD compared to aspirin-tolerant CRSwNP.Tissue IgG4 levels positively correlate with disease recurrence.IL-10 mRNA levels are significantly higher in AERD polyp tissue compared to CRSwNP tissue, but differences were not noted for type 2 cytokines or cytokines involved in class switch recombination.IL-5Rα transcript and protein surface expression is elevated in antibody-secreting cells from subjects with AERD and may play a role in facilitating class switching and/or survival of antibody-secreting cells.Capsule SummarySingle-cell RNA-sequencing (scRNA-seq) of whole nasal polyp tissue identified increased IL5RA, IGHE, and IGHG4 expression in the antibody-secreting cell compartment of subjects with aspirin-exacerbated respiratory disease (AERD) compared to aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). IgE and IgG4 levels are elevated in nasal polyp tissue from subjects with AERD compared to CRSwNP and correlate with disease recurrence.

Download Full-text

Associations between the Quality of Life and Nasal Polyp Size in Patients Suffering from Chronic Rhinosinusitis without Nasal Polyps, with Nasal Polyps or Aspirin-Exacerbated Respiratory Disease

Journal of Clinical Medicine ◽

10.3390/jcm9040925 ◽

2020 ◽

Vol 9 (4) ◽

pp. 925 ◽

Cited By ~ 2

Author(s):

Sven Schneider ◽

Nicholas J. Campion ◽

Sergio Villazala-Merino ◽

David Tianxiang Liu ◽

Tina Bartosik ◽

...

Keyword(s):

Quality Of Life ◽

Chronic Rhinosinusitis ◽

Respiratory Disease ◽

Nasal Polyp ◽

Nasal Polyps ◽

Common Disease ◽

Polyp Size ◽

Aspirin Exacerbated Respiratory Disease ◽

The Impact

Chronic rhinosinusitis (CRS) is a common disease that substantially impairs the quality of life (QoL). Here, we aimed to assess patients’ QoL in different subtypes of CRS and correlated this with nasal polyp size to improve the clinical understanding of the burden of disease. In this retrospective single-center study, 107 patients with the following diagnoses were analyzed: CRS without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP), or aspirin-exacerbated respiratory disease (AERD). Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) scores and their correlation with endoscopic Total Polyp Scores (TPS) were evaluated. The mean SNOT-20 GAV scores were highest in patients with AERD (AERD = 43.4, CRSwNP = 36.3, CRSsNP = 30.9). A statistically significant correlation of total SNOT-20 GAV score with TPS was observed in CRSwNP patients (r = 0.3398, p = 0.0195), but not in AERD patients (r = 0.2341, p = 0.1407). When analyzing single SNOT-20 parameters, a strong correlation with TPS was observed for blockage/congestion of the nose, particularly in AERD patients (r = 0.65, p < 0.0001). The impact of nasal polyp size on the QoL differs amongst the subgroups of CRS. Nasal symptoms have the greatest impact on QoL in patients suffering from AERD. CRSwNP and AERD patients should be separately analyzed in clinical investigations and interpretations due to significant differences in QoL.

Download Full-text

Protein Microarray Analysis of Nasal Polyps from Aspirin-Sensitive and Aspirin-Tolerant Patients with Chronic Rhinosinusitis

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2009.23.3314 ◽

2009 ◽

Vol 23 (3) ◽

pp. 268-272 ◽

Cited By ~ 19

Author(s):

Kelly A. Zander ◽

Milene T. Saavedra ◽

James West ◽

Victor Scapa ◽

Linda Sanders ◽

...

Keyword(s):

Protein Expression ◽

Western Blot ◽

Chronic Rhinosinusitis ◽

Nasal Polyp ◽

Blot Analysis ◽

Western Blot Analysis ◽

Nasal Polyps ◽

Protein Microarray ◽

Control Group ◽

Microarray Technology

Background The purpose of this study was to apply protein microarray technology to the study of sinonasal tissue and to identify differential protein expression in nasal polyps from aspirin-sensitive (AS) versus aspirin-tolerant (AT) patients with chronic rhinosinusitis (CRS) and CRS with nasal polyps (CRSwNPs). Methods Nasal polyp specimens were prospectively obtained from two groups of patients with CRSwNP. The test group (AS) consisted of five patients that were diagnosed with CRSwNP and intolerance to aspirin based on medical history and physical exam. The control group (AT) consisted of four AT patients with CRSwNP. Protein was extracted and labeled from harvested polyps and the Sigma Panorama Antibody Microarray–Cell Signaling Kit was used to identify differences in protein expression between the two polyp groups. Western blot analysis was used to validate the results of the protein microarray. Results The protein microarray showed a greater than twofold change in expression of both beta-adaptin and heat shock protein 70 (HSP70). Western blot analysis confirmed up-regulation of beta-adaptin and HSP70 in nasal polyp tissue from AS patients. Conclusion Pooled samples of AS and AT nasal polyps evaluated by protein microarray show distinct protein expression profiles in the stress response and receptor-mediated endocytosis pathways. This study establishes the successful application of protein microarray technology to study nasal polyposis, which in turn can be validated by Western blot analysis.

Download Full-text

Nasal Polyp Score and CT Findings in Patients with Chronic Rhinosinusitis with Nasal Polyps

Practica Oto-Rhino-Laryngologica ◽

10.5631/jibirin.114.723 ◽

2021 ◽

Vol 114 (10) ◽

pp. 723-732

Author(s):

Shigeharu Fujieda ◽

Rinako Takegawa ◽

Yuki Kamaya

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyp ◽

Nasal Polyps ◽

Ct Findings

Download Full-text