Chronic Rhinosinusitis with Nasal Polyps: Age and Disease Severity Differences in the Levels of Inflammatory Markers

Background and objectives: The aim of our study was to analyze the concentrations of inflammatory markers in the nasal tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls of different age groups, as well as to find associations between age, inflammation development, and NPs. Materials and methods: Patients were divided into two groups—patients with CRSwNPs and control subjects who had nasal surgery for another reason beside CRS. Our analysis was performed across three different age groups (18–30 years, 31–50 years, and 51 years and more). Tissue biopsies from the sinus cavity for all study participants were taken and frozen at −80 °C, until use. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IL-21, and IL-22, were quantified using a magnetic bead-based multiplex assay. Results: In the group aged 18–30 years, the levels of inflammatory markers IL-1, IL-2, IL-5, and IL-22 were significantly higher in patients with CRSwNPs than the control subjects. Among patients aged 31–50 years, significantly higher concentrations of IL-2, IL-4, IL-5, and IL-22 were recorded in patients with CRSwNPs, as compared to the control subjects. In the oldest group (aged 51 years and more), patients with CRSwNPs had significantly higher concentrations of IL-2, IL-4, and IL-22, as compared to the control group. In the CRSwNP group, only the concentration of IL-21 was significantly higher among patients aged 31–50 years, as compared with those aged 51 years and older (p = 0.013). Conclusions: IL-2 and IL-22 levels were significantly higher in patients with CRSwNP than the control, across all age groups. Only the concentration of IL-21 was higher among patients with CRSwNP in the middle age group, as compared to the oldest group. IL-2, IL-4, and IL-22 levels correlated with the severity of CRSwNPs. Elevated concentrations of IL-2, IL-4, and IL-22 were determined in patients’ groups with higher sinonasal outcome test (SNOT-22) scores, pointing to more severe clinical symptoms.

Download Full-text

γδT cells contribute to type 2 inflammatory profiles in eosinophilic chronic rhinosinusitis with nasal polyps

Clinical Science ◽

10.1042/cs20190481 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2301-2315 ◽

Cited By ~ 1

Author(s):

Xia Li ◽

Zhiyuan Wang ◽

Lihong Chang ◽

Xiaohong Chen ◽

Luoying Yang ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Murine Model ◽

Inflammatory Markers ◽

Nasal Polyps ◽

Γδt Cells ◽

Control Subjects ◽

Nasal Tissue ◽

Type 2 Cytokines ◽

Eosinophilic Chronic Rhinosinusitis

Abstract Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS) is a condition linked with type 2 inflammation, poor treatment outcomes, and high recurrence tendency. Although γδT cells have been reported to induce type 2 immune responses and eosinophilic infiltration in several diseases, their role in ECRS has not been fully explored. We aimed to evaluate the association of γδT cells with the type 2 inflammatory profiles in ECRS. Nasal tissue samples obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (51 eosinophilic and 48 non-eosinophilic), 50 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 58 control subjects were examined for γδT cells, inflammatory markers and eosinophils using HE, RT-qPCR, ELISA, immunofluorescence, and flow cytometry. In parallel, studies were also conducted in an ECRS murine model induced by anti-γδT cells neutralizing antibody administration. γδT cells expression was significantly increased in tissues from patients with ECRS compared with non-ECRS, CRSsNP and control subjects. Moreover, inflammatory markers including type 2 proinflammatory cytokines (IL-4, IL-5, IL-13), GATA3, eosinophil cationic protein (ECP), and eotaxin levels were also increased in nasal tissues of patients with ECRS, and Vγ1+ γδT cells mRNA expression was positively correlated with type 2 cytokines, GATA3, and ECP. In the ECRS murine model, anti-Vγ1+ γδT antibody treatment reduced the infiltration of eosinophils and expression of type 2 cytokines, GATA3, and ECP in nasal mucosae. In conclusion, the results of the present study suggest that γδT cells play a crucial role in the type 2 inflammatory profiles and nasal tissue eosinophilic infiltration in patients with ECRS.

Download Full-text

Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-019-0389-3 ◽

2019 ◽

Vol 15 (1) ◽

Author(s):

Jingyun Li ◽

Jian Jiao ◽

Yunbo Gao ◽

Yuan Zhang ◽

Luo Zhang

Keyword(s):

Dna Methylation ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Inferior Turbinate ◽

Nasal Resistance ◽

Total Ige ◽

Control Subjects ◽

Human Nasal Epithelial Cells ◽

Serum Total Ige ◽

And Control

Abstract Background This study was performed to determine whether there was any association between abnormal DNA methylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS). Methods A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and 21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal resistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients and inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human nasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA methylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER. Results A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased methylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false discovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated with olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04; r = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum total IgE levels were not correlated with the methylation ratios at either CpG unit. Conclusions Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis; however these findings need to be confirmed in larger multicentre group studies.

Download Full-text

The comparison of total capacity antioxidant in the serum of people with pterygium and control subjects

International Eye Research ◽

10.18240/ier.2020.01.02 ◽

2020 ◽

Vol 1 (1) ◽

pp. 7-12

Author(s):

Heydari Behrooz ◽

◽

Zarban Asghar ◽

Hosseini Rad Abbas ◽

Feizmohammadi Akram ◽

...

Keyword(s):

Antioxidant Capacity ◽

Clinical Symptoms ◽

Venous Blood ◽

Power Measurement ◽

Control Group ◽

Antioxidant Power ◽

Control Subjects ◽

Significant Difference ◽

The Mean ◽

And Control

AIM: To investigate the comparison of total antioxidant capacity in the serum of patients with pterygium and control subjects. METHODS: This case-control study was conducted on all persons referred to Ophthalmology Clinic of teaching Hospital of Vali-Asr (peace upon to him) with clinical symptoms of pterygium during the year 2016. The control group was selected among patients referred to the Ophthalmology Clinic of Vali-Asr (peace without pterygium) that the two groups were matched in terms of age, gender and place of residence. Sixty-six persons [31 people (47%) in patient group and 35 people (53%) in the control group] were enrolled by convenience sampling. Venous blood sample was taken from all patients after the sampling using ferric reducing antioxidant power (FRAP); FRAP- as a quick 10min measurement, the antioxidant power measurement of samples according to the conversion of ferric iron (Fe3+) to ferrous iron (Fe2+) was checked. The collected data ware entered to software SPSS 21 and were analyzed by chi-square and Mann-Whitney tests at the level of α =0.05. RESULTS: The mean of antioxidant capacity in patients was 842/55±161/46 μmol/L and antioxidant capacity in healthy controls was 856/77±209/41 μmol/L (P=0.8). In the comparison of mean serum antioxidant capacity in healthy individuals and in the serum of people with pterygium based on gender the results showed that the antioxidant capacity mean in male control subjects has been 894/05± 176/82 μmol/L and in females control 780/01±118/33 μmol/L that the observed difference have been reported statistically significant (P=0.008) but the other comparison according the gender between cases and control does not show any significant difference. CONCLUSION: The results of this study showed that the full level of serum antioxidant capacity in patients has been less than the mean of antioxidant capacity in control subjects; however, the observed difference has not been significant. The results of this study were consistent with basic results carried out on the damaging effects of oxidative stress in the pterygium pathogenesis. Recommending diet with minerals and vitamins containing antioxidants may be preventing the onset and progression of pterygium.

Download Full-text

Staphylococcus aureus impairs sinonasal epithelial repair: Effects in patients with chronic rhinosinusitis with nasal polyps and control subjects

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2018.05.035 ◽

2019 ◽

Vol 143 (2) ◽

pp. 591-603.e3 ◽

Cited By ~ 11

Author(s):

Fabiana C.P. Valera ◽

Manon Ruffin ◽

Damien Adam ◽

Émilie Maillé ◽

Badr Ibrahim ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Epithelial Repair ◽

Control Subjects ◽

And Control

Download Full-text

Sinus Microbiota in Patients With Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis With Nasal Polyps

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.672355 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tingting Feng ◽

Ping Miao ◽

Bin Liu ◽

Yao Liu ◽

Ximing Bao ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Pathogenic Bacteria ◽

Quantitative Polymerase Chain Reaction ◽

Bacterial Community Composition ◽

Community Diversity ◽

Control Group ◽

Rrna Gene ◽

Control Subjects ◽

Healthy Control

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2-skewed inflammation and increased colonization by Staphylococcus aureus. CRSwNP can be distinguished as eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP) by the infiltration of eosinophils. The local microbiota plays an important role in the persistent inflammation of CRSwNP. To evaluate the bacterial community composition on the distinct types of CRSwNP patients, we collected nasal swabs from 16 ECRSwNP patients, 18 NECRSwNP patients, and 39 healthy control subjects. The microbiome structure for all the samples were analyzed by high-throughput 16S rRNA gene sequencing. Concentration of S. aureus was determined using TaqMan quantitative polymerase chain reaction (qPCR) targeting the nuclease (nuc) gene. The result showed significant differences in the sinus microbiome among healthy control subjects and CRSwNP patients. Microbiota community diversity was significantly lower in NECRSwNP samples compared to that of healthy control subjects. Interestingly, the abundance of several pathogenic bacteria was diverse between ECRSwNP and NECRSwNP patients. Although Staphylococcus prevailed in all groups, the abundance of Staphylococcus was significantly higher in the healthy control group than the ECRSwNP group. More importantly, the abundance of S. aureus was much higher in NECRSwNP patients. This study highlights that microbiota composition may contribute to the different clinical types of CRSwNP, inspiring new therapeutic strategies to resolve this chronic inflammation process.

Download Full-text

Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Diagnostics ◽

10.3390/diagnostics11010135 ◽

2021 ◽

Vol 11 (1) ◽

pp. 135

Author(s):

Wioletta Pietruszewska ◽

Wojciech Fendler ◽

Marta Podwysocka ◽

Adam J. Białas ◽

Piotr Kuna ◽

...

Keyword(s):

Healthy Volunteers ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Direct Sequencing ◽

Adult Patients ◽

Control Group ◽

Reliable Test ◽

Aggressive Disease ◽

Transcript Variants

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = −0.134; p = 0.0490), COX1.3 (R = −0.1429; p = 0.0400) and COX1.5 (Rs = −0.1499; p = 0.032). The expression of COX1.1 (Rs = −0.098; p = 0.049) and COX1.5 (Rs = −0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = −0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.

Download Full-text

Characterization of Cytokines and Proliferation Marker Ki67 in Chronic Rhinosinusitis with Nasal Polyps: A Pilot Study

Medicina ◽

10.3390/medicina57060607 ◽

2021 ◽

Vol 57 (6) ◽

pp. 607

Author(s):

Rudolfs Janis Viksne ◽

Gunta Sumeraga ◽

Mara Pilmane

Keyword(s):

Connective Tissue ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Cellular Proliferation ◽

Rank Correlation ◽

Control Group ◽

Relative Distribution ◽

Proliferation Marker ◽

Ki 67 ◽

Stimulation Of

Background and Objectives: Chronic rhinosinusitis (CRS) is a condition that affects as much as 10.9% of the population and, along with presence of nasal polyps, is associated with significant morbidity and decreased quality of life. Studies on molecular pathways that have been activated in nasal polyp tissue are mainly based on cytokine concentration detection. Therefore, our aim is to investigate the complex appearance, relative distribution and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki 67 in chronic rhinosinusitis with nasal polyps (CRSwNP) affected human nasal mucosa. Materials and Methods: Samples of nasal polyps were obtained from 12 patients with previously diagnosed CRSwNP and no prior surgery. Control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviation. Tissues were stained for IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki67 immunohistochemically. Non-parametric statistic, Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Results: All factors, except connective tissue cytokine IL-10 and proliferation marker Ki-67, had increased presence in connective tissue and decreased presence in epithelium of nasal polyps when compared to controls. Very strong and strong positive correlations between factors were observed. Conclusions: Decreased appearance of IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 positive structures in the nasal epithelium with selective increase of IL-1α and IL-12 in nasal subepithelial connective tissue characterize the cytokine endotype with dysfunctional epithelial barrier and local stimulation of immune response in the connective tissue in case of chronic rhinosinusitis with polyps. Decrease of IL-6 in both—epithelium and connective tissue with strong correlation between it and IL-7 and IL-10 in connective tissue suggests significant stimulation of this regulatory cytokine and, possibly, the important role in pathogenesis of the development in nasal polyps. Correlations between Ki67 and cytokines indicate possible involvement of IL-4, IL-7 and IL-12 in regulation of cellular proliferation.

Download Full-text

Association between obesity and chronic rhinosinusitis with nasal polyps: a national population-based study

BMJ Open ◽

10.1136/bmjopen-2020-047230 ◽

2021 ◽

Vol 11 (5) ◽

pp. e047230

Author(s):

Jae-Sung Nam ◽

Yun Ho Roh ◽

Wasan Almazouq Fahad ◽

Hae-Eun Noh ◽

Jong-Gyun Ha ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Chronic Rhinosinusitis ◽

Logistic Regression Analysis ◽

Central Obesity ◽

Nasal Polyps ◽

Control Group ◽

Cross Sectional ◽

Cross Sectional Analysis ◽

Sectional Analysis

ObjectivesWe performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).DesignRetrospective cross-sectional analysis of health survey data.SettingVoluntary survey of representative South Korean populations.ParticipantsIn total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.Primary and secondary outcome measuresDiagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.MethodsA multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.ResultsThe prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p<0.001) and central (OR, 1.251; 95% CI, 1.031 to 1.520; p=0.033) obesity groups than in the control group. Prevalence of CRSsNP was not correlated with obesity. In a logistic regression analysis, olfactory dysfunction (OR, 1.329; 95% CI, 1.137 to 1.553; p<0.001) and purulent discharge (OR, 1.383; 95% CI, 1.193 to 1.603; p<0.001) showed a higher incidence in the central obesity group than in the control group.ConclusionsWe demonstrated an association between CRSwNP and general and central obesity. Further investigations on the mechanism underlying this correlation are necessary for an improved understanding of the pathogenesis of CRSwNP.

Download Full-text

CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

International Archives of Otorhinolaryngology ◽

10.1055/s-0041-1726043 ◽

2021 ◽

Author(s):

Wagner Vargas Souza Lino ◽

André Luis Lacerda Bachi ◽

José Arruda Mendes Neto ◽

Gabriel Caetani ◽

Jônatas Bussador do Amaral ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Transforming Growth Factor ◽

Middle Turbinate ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Histologic Analysis ◽

Aspirin Intolerance ◽

Tgf Β1

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.

Download Full-text

JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

Biomolecules ◽

10.3390/biom11071059 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1059

Author(s):

Yu-Tsai Lin ◽

Wei-Chih Chen ◽

Ming-Hsien Tsai ◽

Jing-Ying Chen ◽

Chih-Yen Chien ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Disease Severity ◽

Nasal Polyps ◽

Inflammatory Diseases ◽

Janus Kinase ◽

Sinus Surgery ◽

Control Group ◽

Jak2 Inhibitor ◽

Ifn Γ ◽

Snot 22

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

Download Full-text