Increased Expression of Acidic Mammalian Chitinase in Chronic Rhinosinusitis with Nasal Polyps

2006 ◽  
Vol 20 (3) ◽  
pp. 330-335 ◽  
Author(s):  
Murugappan Ramanathan ◽  
Won-Kyung Lee ◽  
Andrew P. Lane

Background Chitin is an abundant polysaccharide found in fungi, insects, and parasitic nematodes. Innate immune host defense against chitin-containing pathogens include production of chitinases. In human lower airways, acidic mammalian chitinase (AMCase) is produced in epithelial cells via a Th2-specific, IL-13–dependent pathway, and may act as an inflammatory mediator in asthma. The role of AMCase in chronic rhinosinusitis (CRS) has not been studied previously. Methods Eleven controls and 22 subjects with medically recalcitrant CRS were prospectively enrolled before undergoing endoscopic sinus surgery. RNA was extracted from surgically obtained ethmoid mucosa, and real-time PCR was used to determine expression of AMCase, eotaxin, and IL-13. Subjects were followed for at least 6 months postoperatively to assess for polyp recurrence. Based on the presence or absence of polyps, the subjects were classified as either recalcitrant or responsive to therapy. Results AMCase mRNA was detected in the sinus mucosa of 72% of control subjects and in 72% of patients with eosinophilic CRS with nasal polyps (CRSwNP). The expression of AMCase was significantly greater in recalcitrant CRSwNP than it was in treatment-responsive CRSwNP. There was no significant difference in IL-13 expression between these two groups. Conclusion AMCase may be an important mediator in the pathogenesis of Th2 inflammatory diseases of the respiratory tract. Failure of medical and surgical therapy in CRSwNP is associated with significantly increased expression of AMCase, but not the Th2 cytokines IL-13 and eotaxin. Additional studies are needed to determine the potential of AMCase as a therapeutic target in CRSwNP.

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.


2019 ◽  
Vol 33 (5) ◽  
pp. 478-482 ◽  
Author(s):  
Kristin A. Seiberling ◽  
Stephanie C. Kidd ◽  
Grace H. Kim ◽  
Christopher A. Church

Background Topical nasal steroids are commonly prescribed to patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) following endoscopic sinus surgery (ESS). They are found to be effective in improving symptoms and quality of life as well as reducing the incidence of nasal polyps recurrence. Objective We sought to determine whether a higher concentration of topical nasal steroid spray is more effective than the standard nasal steroid spray in controlling symptoms and preventing recurrence of polyps in patients with CRSwNP who underwent ESS. Method A double-blind randomized controlled trial was performed on patients with CRSwNP after ESS. Patients were randomized into 2 treatment groups: one received topical nasal dexamethasone 0.032% and the other, fluticasone proprionate. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy nasal endoscopy scores were measured at the initiation of topical nasal steroid treatment and then at approximately 4-, 8-, and 12-week intervals. Results Thirty-nine patients were enrolled in the study. Eighteen patients continued using the medications prescribed to them for the duration of the study. There were 8 patients in the dexamethasone group and 10 patients in the fluticasone group. Both groups saw significant improvements in postoperative SNOT-22 and Lund-Kenney scores over time. There was no significant difference in improvement between the groups. Conclusion There is no significant increased benefit in using a higher dose nasal steroid spray compared to the standard dose nasal steroid spray after ESS.


2020 ◽  
Vol 8 ◽  
pp. 205031212093380
Author(s):  
Haitham Odat ◽  
Maulla Alali ◽  
Mohannad Al-Qudah

Objectives: The aim of this study is to report the aeroallergen sensitization profile in medically resistant chronic rhinosinusitis with or without nasal polyps and its relationship to asthma. Methods: Retrospective charts review of 402 chronic rhinosinusitis patients who failed to respond to medical treatment and scheduled for surgery at a tertiary academic center was performed. One hundred and fifty-five patients had chronic rhinosinusitis with nasal polyps and 247 patients had chronic rhinosinusitis without nasal polyps, furthermore; the two phenotypes were subdivided according to the presence or absence of asthma. Allergen-specific immunoglobulin E to 24 inhalant allergens was measured to all patients by the enzyme allergo-sorbent test. Results: The average age was 35 years ( SD ± 13) with 236 males and 166 females. Two hundred and fifty-three patients (63%) were tested positive for at least one allergen with no significant difference between patients with or without polyp (in chronic rhinosinusitis with nasal polyps, 103 patients (66%) were positive compared with 150 patients (61%) in chronic rhinosinusitis without nasal polyps). There were no significant differences in the prevalence, type, and number of positive allergens between the two phenotypes. The prevalence of asthma was found to be 19% in patients with chronic rhinosinusitis without nasal polyps versus 46% in those with chronic rhinosinusitis with nasal polyps ( p = 0.001), and the prevalence of high eosinophils was 27%, and 47% in both phenotypes, respectively ( p = 0.0001). Conclusions: The prevalence of inhalational allergy in medically resistant chronic rhinosinusitis is high, however, this profile does not differ based on the presence of polyp. Patients with chronic rhinosinusitis with nasal polyps had a higher prevalence of asthma and blood eosinophils as compared with chronic rhinosinusitis without nasal polyps. Our results showed a little role of inhalant allergens in nasal polyps or asthma comorbidity in refractory sinusitis patients.


2020 ◽  
Vol 182 (1) ◽  
pp. 65-75
Author(s):  
Di Wu ◽  
Bing Yan ◽  
Yang Wang ◽  
Luo Zhang ◽  
Chengshuo Wang

<b><i>Introduction:</i></b> The recurrence occurs frequently among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and predictors that could be conveniently detected during practice in outpatient service are needed. <b><i>Objective:</i></b> We aimed to illustrate that the concentration of Charcot-Leyden crystal (CLC) in nasal secretions can effectively and noninvasively predict polyp recurrence. <b><i>Methods:</i></b> 108 patients with CRSwNP were divided into recurrence (<i>n</i> = 68) and recurrence-free (<i>n</i> = 40) groups. Preoperative CLC concentrations in nasal secretions were collected and detected by ELISA. Polyp tissues were harvested during biopsy or endoscopic sinus surgery and were evaluated for inflammatory cells by histopathological staining. Demographic information and the clinical characteristics of each patient were reviewed for associations with recurrence. Binary logistic regression analysis was performed to determine predictive factors for polyp recurrence. Receiver operating characteristic (ROC) curves and the Youden index were performed to determine their predictive values. Survival analysis was performed to compare recurrence risk of patients with different CLC concentrations. <b><i>Results:</i></b> Sixty-eight (62.96%) patients developed recurrence during a 12- to 33-month postoperative follow-up. CLC concentrations in nasal secretions were positively correlated with eosinophil percent in polyp tissue and peripheral blood and were significantly higher in patients of the recurrence group than in the patients of the recurrence-free group (<i>p &#x3c;</i> 0.001). Binary logistic regression and ROC curve demonstrated that CLC protein in nasal secretions is predictive of polyp recurrence. According to the Youden index, a CLC concentration of 34.24 ng/mL can predict postoperative polyp recurrence with 92.6% sensitivity and 87.5% specificity. Patients with CLC concentrations higher than the cutoff value yielded a higher risk of recurrence (<i>p &#x3c;</i> 0.001, HR = 11.31, 95% CI: 6.41–19.98). <b><i>Conclusions:</i></b> CLC protein in nasal secretions may serve as a promising noninvasive biomarker to predict CRSwNP recurrence.


2021 ◽  
Vol 104 (2) ◽  
pp. 293-299

Background: Some chronic rhinosinusitis with nasal polyps patients undergoing endoscopic sinus surgery (ESS) have unfavorable results despite proper postoperative treatments including oral and topical steroids. Steroid-impregnated absorbable nasal dressing has been shown to improve outcomes of the surgery. In some clinical practices, budesonide-impregnated nasal dressing is used together with perioperative oral steroid but the additional benefits of it are still unknown. Objective: To determine whether budesonide-impregnated nasal dressing had any benefits following ESS when a short course of oral steroid was given in perioperative period. Materials and Methods: The present study was a prospective, double-blinded, randomized, placebo-controlled study conducted in tertiary care hospital. Eighteen consecutive patients (36 nostrils) with chronic rhinosinusitis with nasal polyps underwent bilateral ESS were enrolled. At the end of the surgery for each patient, one side of the ethmoid cavity and middle meatus was randomly given polyurethane foam soaked with 2 mL of budesonide inhalation solution (0.5 mg/2 mL) (budesonide side), while the contralateral side received 2 mL of normal saline-soaked polyurethane foam (control side). Postoperative care included a short course of oral steroid and budesonide nasal irrigations. Single assessor blinded to the randomize allocation evaluated mucosal inflammation and wound healing at 2 and 4 weeks after surgery using Perioperative Sinus Endoscopy (POSE) score. Results: A total of 36 nostrils were randomized into two groups: 18 to the budesonide side and 18 to the control side. All of them were analyzed. The preoperative Lund-Mackay computed tomography score did not show a significant difference between the groups. There was no significant difference in POSE score between budesonide and control sides at 2 and 4 weeks after surgery. Conclusion: Budesonide-impregnated polyurethane foam did not provide additional benefits on mucosal inflammation and wound healing in the patients who underwent ESS and received a short course of oral steroid perioperatively. Keywords: Chronic rhinosinusitis, Nasal polyps, Nasal dressing/packing, Budesonide, Endoscopic sinus surgery


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.


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