scholarly journals Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence

2020 ◽  
pp. 014556131989663
Author(s):  
Germano Guerra ◽  
Domenico Testa ◽  
Francesco Antonio Salzano ◽  
Domenico Tafuri ◽  
Eleonora Hay ◽  
...  

Chronic rhinosinusitis with nasal polyps is a multifactorial disease of the nasal and paranasal sinus mucosa and it includes, as comorbidities, anatomic and morphologic alterations, allergic rhinitis, and immunologic diseases. We investigated matrix metalloproteinases (MMP-2, MMP-7, and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) concentration in different etiopathogenetical groups of patients with nasal polyposis (NP) in relation to recurrence after sinonasal surgery. The study group consisted of 45 patients with NP (those with allergic rhinitis, nonallergic rhinitis and asthma or nonallergic rhinitis, and obstruction of osteomeatal complex [OMC]) who underwent endonasal sinus surgery. We also collected 10 patients who underwent septoplasty as control. Immunohistochemistry of nasal mucosa fragments, Western blotting, and polymerase chain reaction analysis showed increased MMPs levels (MMP-9 more than MMP-2 and MMP-7) and decreased tissue inhibitors of MMPs levels (TIMP-1 less than TIMP-2), in patients with chronic rhinosinusitis with nasal polyps compared with control group, in particular in patients with nonallergic rhinitis and asthma compared to those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC. We observed a higher risk of recurrence in patients with nonallergic rhinitis and asthma than in those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC after 36 months from surgery. In this research, we evaluated pathogenesis of NP related to MMPs and their inhibitors concentrations in polypoid tissue.

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1059
Author(s):  
Yu-Tsai Lin ◽  
Wei-Chih Chen ◽  
Ming-Hsien Tsai ◽  
Jing-Ying Chen ◽  
Chih-Yen Chien ◽  
...  

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.


2015 ◽  
Vol 129 (9) ◽  
pp. 865-869 ◽  
Author(s):  
D G Ioannidis ◽  
V A Lachanas ◽  
Z Florou ◽  
J G Bizakis ◽  
E Petinaki ◽  
...  

AbstractIntroduction:The role played byMycoplasma pneumoniaeandChlamydophila pneumoniaein the pathogenesis of chronic rhinosinusitis with nasal polyps has been the object of ongoing debate. We used real-time polymerase chain reaction to investigate the prevalence of both microorganisms in the nasal tissue samples of patients and controls.Methods:We extracted DNA from nasal polyp samples obtained during functional endoscopic sinus surgery and the inferior turbinate samples of controls undergoing septoplasty. We used the highly sensitive real-time polymerase chain reaction to detect the presence ofM pneumoniaeandC pneumoniaeDNA.Results:Patients with chronic rhinosinusitis with nasal polyps consisted of 62 individuals (39 men; mean age 51 years); the control group consisted of 24 individuals (13 men; mean age 45 years). All samples from both groups were negative forM pneumoniaeandC pneumoniaeDNA.Conclusion:We have demonstrated that the likelihood ofM pneumoniaeandC pneumoniaeacting as an ongoing inflammatory stimulus in chronic rhinosinusitis with nasal polyps is slim.


2020 ◽  
Vol 34 (5) ◽  
pp. 610-617 ◽  
Author(s):  
Joseph S. Schertzer ◽  
Joshua M. Levy ◽  
Sarah K. Wise ◽  
Kelly R. Magliocca ◽  
John M. DelGaudio

Background Respiratory epithelial adenomatoid hamartoma (REAH) is a benign lesion of the sinonasal tract that may mimic more concerning pathology. Clinical factors associated with REAH have not been well characterized. Objective To report our findings on patients with this pathologic diagnosis. Methods A retrospective chart review of patients with REAH between September 2006 and November 2019 was conducted. Data collected included clinical allergic rhinitis and asthma history, additional sinonasal diagnoses, prior sinus surgery, and the location of the REAH within the sinonasal cavity. Results Twenty-six patients were identified (53.8% male, mean age 62 years [range, 29–93]). Bilateral REAH occurred in 50%. REAH was located at the superior nasal septum in 84.6% cases, with the remainder identified in sinus contents submitted for pathology, making definitive site uncertain. Concurrent sinonasal inflammatory disorders were identified in 18 patients (69.2%), including chronic rhinosinusitis with nasal polyps—not otherwise specified (6), chronic rhinosinusitis without nasal polyps (4), aspirin-exacerbated respiratory disease (2), allergic fungal rhinosinusitis (1), central compartment atopic disease (5), and IgG4-related sclerosing disease (1). Eight patients had isolated REAH. Adequate allergy records were available for 19 patients, of which 18 of 19 (94.7%) had clinical allergic rhinitis. Conclusions REAH is a benign sinonasal lesion commonly located within the central compartment of the nasal cavity, a site of significant allergen exposure. Affected patients have a high incidence of allergy along with chronic inflammatory conditions. The coexistence of REAH within inflammatory nasal mucosa in a consistent anatomic location, suggests REAH may have a similar etiology to central compartment atopic disease, with resultant respiratory glandular ingrowth within long-standing reactive changes of mucosa derived from ethmoid embryologic origin.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Dae Woo Kim ◽  
Kyoung Mi Eun ◽  
Eun Youn Roh ◽  
Sue Shin ◽  
Dong-Kyu Kim

Chronic rhinosinusitis (CRS) shows heterogeneous immunologic features. Western studies revealed that CRS without nasal polyps (CRSsNP) showed a predominantly type 1 immune response and CRS with nasal polyps (CRSwNP) was characterized by type 2 immune response; however, the detailed immunologic profile of CRSsNP in Asian patients has not been thoroughly investigated. Therefore, we investigated the inflammatory endotypes of CRSsNP in Asian patients. Patients with CRSsNP (N=57), patients with CRSwNP (N=13), and a control group (N=10), who underwent endoscopic sinus surgery, were enrolled; uncinate process (UP) tissues were harvested from all patients. Homogenates were prepared from the UP of each group, and immunologic profiles were analyzed, including major cytokines (32 inflammatory mediators). When comparing the UPs between groups, CRSsNP patients showed higher levels of Th2 cytokines (IL-4 and IL-13), eosinophilic chemokines (CCL-11 and CCL-24), ECP, and total IgE expression than control subjects. In addition, several neutrophilic markers (IL-1α, IL-6, IL-8, CXCL-1, CXCL-2, and MPO), IL-17A, IL-22, and TNF-α were dominant in CRSsNP patients. Among these inflammatory mediators, IL-17A showed higher expression levels in CRSsNP patients than in the control group and CRSwNP patients. However, IFN-γ expression was not significantly elevated in CRSsNP patients. The levels of neutrophil-associated cytokines were well correlated with each other; of which, CXCL2, IL-8, and MMP-9/TIMP-1 levels were significantly correlated with disease extent (r=0.338, r=0.317, and r=0.424, respectively). However, the levels of eosinophil-associated cytokines showed little correlation with each other and were not correlated with disease extent. Our study revealed that Asian CRSsNP patients showed a mixed (types 2 and 17) immune response, but neutrophil-related markers were dominant and associated with disease extent. Knowledge of this immunologic feature may help clinicians make better individual treatment decisions for Asian CRSsNP patients.


2021 ◽  
pp. 000348942199503
Author(s):  
Michael A. Belsky ◽  
Erica Corredera ◽  
Hridesh Banerjee ◽  
John Moore ◽  
Li Wang ◽  
...  

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.


2021 ◽  
Vol 12 ◽  
pp. 215265672110038
Author(s):  
Markus Jukka Lilja ◽  
Anni Koskinen ◽  
Paula Virkkula ◽  
Seija Inkeri Vento ◽  
Jyri Myller ◽  
...  

Objectives The aim was to compare the control of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS), in patients with/without nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). Study Desing: A retrospective hospital-based sample of CRSwNP patients with/without NERD with follow-up. Setting Tertiary rhinology centers. Methods Electronic patient record data from 116 CRSwNP patients (46 with NERD and 70 without NERD) undergoing ESS during 2001–17 were studied. Mean follow-up time was 9.9 years (range 1.1–15.3). Endpoints reflecting uncontrolled CRSwNP were revision ESS, and need for rescue/advanced therapy (e.g. antibiotics, oral corticosteroids and/or biological therapy) during follow-up. NERD was variable of interest and gender, age, asthma, allergic rhinitis (AR), smoking, Lund-Mackay (LM) score of sinus computed tomography scans previous ESS and baseline total ethmoidectomy were used as covariates. Results Twenty-one (49.7%) NERD patients and 18 (25.7%) non-NERD patients underwent revision ESS within a mean ± SD of 4.3 ± 2.8 and 3.7 ± 2.6 years, respectively (p = .013, by Logrank test). In Cox´s regression models, NERD, female gender, young age, asthma, AR, previous ESS, and lack of total ethmoidectomy were associated with revision-ESS. In adjusted model, only the total ethmoidectomy predicted revision-free survival. In adjusted logistic regression model, there was an insignificant trend that NERD and LM score were associated with the need for rescue/advanced therapy in the follow-up. Conclusions Patients with NERD had higher risk of uncontrolled CRSwNP than patient group without NERD, as measured by revision ESS and/or need for rescue/advanced therapy in the follow-up. In addition, baseline total ethmoidectomy was associated with revision-free survival.


Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 135
Author(s):  
Wioletta Pietruszewska ◽  
Wojciech Fendler ◽  
Marta Podwysocka ◽  
Adam J. Białas ◽  
Piotr Kuna ◽  
...  

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.


2021 ◽  
pp. 014556132110129
Author(s):  
Weiping Qi ◽  
Liang Feng ◽  
Fengyan Yang ◽  
Weihuan Ma

Objectives: To study the effects of age on the olfactory function recovery of chronic rhinosinusitis patients after endoscopic sinus surgery and related risk factors. Methods: A total of 176 chronic rhinosinusitis (CRS) patients enrolled from February 2017 to October 2019 were divided into child, youth, middle-aged, and elderly groups. Their baseline data, T&T olfactory test score, visual analogue scale (VAS) olfactory score, sinus computed tomography (CT) Lund-Mackay score, and Lund-Kennedy score were compared. Based on postoperative olfactory function, they were divided into good and poor improvement groups. Results: Complication with nasal polyps, allergic rhinitis history, and sinus surgery history had significant differences among patients of different ages ( P < .05). Three months after surgery, T&T olfactory, VAS olfactory, Lund-Mackay, and Lund-Kennedy scores all rose with increasing age, with significant differences between any 2 groups ( P < .05). The improvement of postoperative olfactory function became poorer with aging ( P < .05). T&T and VAS olfactory scores had significant positive correlations with Lund-Mackay and Lund-Kennedy scores ( P < .001). Age, preoperative Lund-Mackay and Lund-Kennedy scores, complication with nasal polyps, allergic rhinitis history, sinus surgery history, and postoperative complications were risk factors for the poor improvement of postoperative olfactory function. Doctor-directed treatment was a protective factor for good improvement. Conclusions: The improvement of olfactory function of CRS patients after endoscopic sinus surgery declines with aging. Age, preoperative Lund-Mackay and Lund-Kennedy scores, complication with nasal polyps, allergic rhinitis history, sinus surgery history, and postoperative complications are risk factors for the poor improvement of postoperative olfactory function. Doctor-directed treatment is a protective factor for good improvement.


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 607
Author(s):  
Rudolfs Janis Viksne ◽  
Gunta Sumeraga ◽  
Mara Pilmane

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.


BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047230
Author(s):  
Jae-Sung Nam ◽  
Yun Ho Roh ◽  
Wasan Almazouq Fahad ◽  
Hae-Eun Noh ◽  
Jong-Gyun Ha ◽  
...  

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.


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