Chronic Rhinosinusitis With Nasal Polyps Recurrence Research Articles

Correlation among post-surgery recurrence of CRSwNP and TCM syndromes and tissue inflammatory cell infiltration type: a study protocol

BackgroundFunctional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types.Methods and analysisThis is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People’s Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients’ pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches.DiscussionThis is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP.Systematic review registrationPROSPERO ChiCTR2100041646.

Long-Term Perspectives on Chronic Rhinosinusitis with Nasal Polyps: Evaluating Recurrence Rates after Functional Endoscopic Sinus Surgery in the Biologics Era-A 5-Year Follow-Up Study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with multifactorial etiopathogenesis. This study investigated the recurrence rate and risk factors predicting recurrence in patients subjected to Functional Endoscopic Sinus Surgery (FESS) for CRSwNP. Patients affected by CRSwNP who underwent FESS between January 2015 and March 2020 were enrolled. The recurrence rate and the influence of risk factors were assessed. A total of 154 patients were included, 100 males and 54 females, aged 14-82 years (mean age 51.96 ± 16.27; median 52 years). Of 154 patients, 28 presented CRSwNP recurrence in a follow-up period ranging from 6 months to 69 months, with a recurrence rate of 18.2%. The recurrence rate was higher in patients aged between 31 and 50 years and between 51 and 70 years at the time of surgery than in those aged between 14 and 30 years and over 70 years. Furthermore, most patients with recurrence were men (61%), while 39% were women. A higher recurrence rate was observed between non-smokers (50%) and ex-smokers (36%), while only 14% declared themselves habitual smokers. Only four subjects (14%) had a positive family history of CRSwNP. To date, no specific biomarkers have been identified in order to determine the appropriate therapy for the patients affected by CRSwNP. Based on our results, we suggest that it is necessary for an accurate assessment of the CRSwNP patients to identify which phenotype/endotype each subject manifests based on medical history, endoscopy, computed tomography, and a laboratory evaluation.

Elevated MIF identified by multiple cytokine analyses facilitates macrophage M2 polarization contributing to postoperative recurrence in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms. A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed. In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-β1, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-β1 and CCL-24 production, contributing to CRSwNP recurrence. Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.

Aberrant expressions of TAM receptors are associated with postoperative recurrence in chronic rhinosinusitis with nasal polyps.

TAM receptors (TYRO3, AXL, and MER) play important roles in inflammatory responses, but their effects in chronic rhinosinusitis with nasal polyps (CRSwNP) remain elucidated. We aim to evaluate the values of TAM receptors in disease severity and postoperative recurrence of CRSwNP. We initially enrolled 160 patients with CRSwNP who were treated with functional endoscopic sinus surgery (FESS) and postoperative recurrence was evaluated during the follow-up period. Circulating TAM receptor levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue expressions were measured by real-time polymerase chain reaction (RT-PCR) and immunohistochemical (IHC). The relationships between TAM receptor levels and postoperative recurrence were examined. A total of 150 patients completed the follow-up schedule, 49 patients experienced postoperative recurrence and the remaining 101 patients were non-recurrent. In recurrent CRSwNP patients, serum levels of TAM receptors were increased compared to those in non-recurrent patients and were positively correlated with disease severity scores (P < 0.05). Circulating TYRO3 and MER were identified as potential predictors of postoperative recurrence based on receiver operating characteristics (ROC) and Kaplan-Meier plots (P < 0.05). Furthermore, tissue TAM receptor levels, as determined by both RT-PCR and IHC, were enhanced in the recurrent group than in the non-recurrent group (P < 0.05) and were predictive of postoperative recurrence (P < 0.05). Interestingly, circulating TYRO3 and MER concentrations, as well as tissue TYRO3 expression, were found to be significantly increased in patients who experienced postoperative recurrence (P < 0.05). IHC images from the same patients revealed that TAM expressions were enhanced in the recurrent tissues compared to their baseline tissue levels. Our laboratory results demonstrated that TAM receptors were increased in recurrent CRSwNP patients and associated with postoperative recurrence. Moreover, the new laboratory findings suggested that measuring circulating levels of TAM receptors might serve as a promising new approach to assess disease progression and predict the risk of postoperative recurrence.

Abnormal S100A8 expression associates with postoperative recurrence in chronic rhinosinusitis with nasal polyps

ObjectiveTo investigate the role of S100A8 in chronic rhinosinusitis with nasal polyps (CRSwNP) and assess its value in predicting disease recurrence after surgery. MethodsThirty healthy controls (HC), 30 patients with chronic rhinosinusitis without nasal polyp (CRSsNP), and 60 patients with CRSwNP were enrolled. Serum S100A8 concentration was measured by ELISA. Immunohistochemistry (IHC), western blotting (WB), and reverse transcription-polymerase chain reaction (RT-PCR)were performed to examine tissue expression levels of S100A8. The potential values of S100A8 in predicting postoperative recurrence of CRSwNP were assessed by the receiver operating characteristic (ROC)curve. ResultsSerum S100A8 concentrations in the CRSwNP group were higher than the HC group and the CRSsNP group， especially in the recurrent CRSwNP group (P < 0.05). Serum S100A8 levels were positively correlated with peripheral blood eosinophil numbers (r = 0.263, P = 0.043) and percentages (r = 0.336, P = 0.009), tissue eosinophil percentages (r = 0.273, P = 0.035), VAS score (r = 0.385, P = 0.002) and Lund-Kennedy score (r = 0.283, P = 0.029). IHC, WB, and RT-PCR results showed tissue S100A8 expression was significantly enhanced in the CRSwNP group, especially in the recurrence group (P < 0.05). Binary regression analysis showed that serum S100A8 concentration and tissue eosinophil percentage were correlated with postoperative recurrence of CRSwNP. ROC curve analysis showed that compared with tissue eosinophil percentage, the S100A8 level had a higher value for postoperative recurrence of CRSwNP. ConclusionSerum and tissue S100A8 levels were elevated in patients with CRSwNP， especially in the recurrent CRSwNP patients, and were correlated with the degree of peripheral blood and tissue eosinophilic inflammation. S100A8 seemed to be a potential objective biomarker to predict the postoperative recurrence of CRSwNP.

Effects of Metabolic Syndrome and its components on the postoperative recurrence in Chronic Rhinosinusitis with Nasal Polyps’ patients

ObjectivesMetabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. MethodsA retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. ResultsA total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (p < 0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (p < 0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (p < 0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (p < 0.05). ConclusionOur findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. Level of evidenceLevel 4.

Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps

Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved. Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence. S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence. S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development.

Serum metabolomics identifies uric acid as a possible novel biomarker for predicting recurrence of chronic rhinosinusitis with nasal polyps.

Metabolomics has proven to be a valuable tool in gaining new insights into disease progression and prognosis, the specific metabolic alterations in the serum of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) patients remain unknown. This study aims to explore the serum metabolomic profiles of recurrent CRSwNP and identify potential predictive biomarkers. A prospective, single-center study was conducted on CRSwNP patients prior to endoscopic sinus surgery. Serum samples were subjected to untargeted metabolomic profiling. Patients were followed up for over 2 years and categorized into recurrence and non-recurrence groups. Metabolite differences between the two groups were compared, and the identified differentially regulated metabolites were subsequently validated in a large clinical cohort. 67 CRSwNP patients completed the follow-up schedule, with 47 classified into the non-recurrent group and 20 into the recurrent group. Significant differences were found in the metabolomic profiles between both groups, and serum uric acid (SUA) showed promising predictive potential for postoperative recurrence in both positive and negative ion models. A validation cohort comprising 398 non-recurrent and 142 recurrent CRSwNP patients was recruited, and a significant elevation in SUA levels was observed in recurrent cases. Patients were stratified into tertiles based on the distribution of baseline SUA levels. Multivariate Cox regression analysis showed that higher tertiles of SUA were associated with an increased risk of CRSwNP recurrence compared to lower tertiles, even after adjusting for potential confounding factors. The receiver operating characteristic curve and Kaplan-Meier survival analysis highlighted that elevated SUA levels exhibited potential predictive values for postoperative recurrence. Serum metabolic signatures might predict postoperative recurrence in CRSwNP patients. Increased SUA concentrations were found to be associated with a higher risk of future postoperative recurrence in CRSwNP, independent of traditional risk factors.

Individual exposure of ambient particulate matters and eosinophilic chronic rhinosinusitis with nasal Polyps: Dose-Response, mediation effects and recurrence prediction

PurposeWe evaluated the association between ambient particulate matter (PM) exposure and eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), and predicted the CRSwNP recurrence risk using machine learning algorithms. MethodsIn total, 1,086 patients with CRSwNP were recruited from nine hospitals in China during 2014–2019. The average annual concentrations of ambient PMs before surgery were assessed using satellite-based daily concentrations of PM2.5 and PM10 for a 1 × 1-km2 area. Linear regression and logistic regression models were used to evaluate the associations of PM exposure with eosinophilia and risks of eosinophilic CRSwNPs. In addition, mediation effect analysis was used to validate the interrelationships of the aforementioned factors. Finally, machine learning algorithms were used to predict the recurrence risks of CRSwNPs. ResultsThere was a significantly increased risk of eosinophilic CRSwNPs with each 10 μg/m3 increase in PMs, with odds ratios (ORs) of 1.039 (95% confidence interval [CI] = 1.007–1.073) for PM10 and 1.058 (95% CI = 1.007– 1.112) for PM2.5. Eosinophils had a significant mediation effect, which accounted for 52% and 35% of the relationships of CRSwNP recurrence with PM10 and PM2.5, respectively. Finally, we developed a naïve Bayesian model to predict the risk of CRSwNP recurrence based on PM exposure, inflammatory data, and patients’ demographic factors. ConclusionsIncreased PM exposure is associated with an increased risk of eosinophilic CRSwNP in China. Therefore, patients with eosinophilic CRSwNP should reduce PM exposure to mitigate its harmful impacts.

Therapeutic Strategies to Prevent the Recurrence of Nasal Polyps after Surgical Treatment: An Update and In Vitro Study on Growth Inhibition of Fibroblasts.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine-acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine-acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence.

How to manage recurrences after surgery in CRSwNP patients in the biologic era: a narrative review.

This narrative review analyses factors affecting recurrence of Chronic rhinosinusitis with nasal polyps (CRSwNP) after surgery, such as type, extension and completeness of endoscopic sinus surgery (ESS). We also described new implications in the management of recurrences after the advent of biologics. We identified four topics: definition of disease state; factors linked to recurrence of polyps; evaluation and management of recurrence in clinical practice. We analysed the differences between exacerbation and recurrence, as well as the concept of "controlled disease". We focused on potential predictors of recurrence after ESS, such as type 2 inflammation, asthma, aspirin-exacerbated respiratory disease, incomplete initial surgery and lack of adherence to long-term post-operative local corticosteroids. We discussed the new aspects of diagnosis and treatment of recurrences after surgery, summarising our suggestions in a detailed algorithm for practical management of patients with recurrent disease. The results emphasised the importance of accurate evaluation of patients with CRSwNP recurrence, focusing on the reasons of failure and risk of disease progression, in order to guide personalised interventions. It is crucial to define the concept of appropriate surgery, which affects the choice between starting a biologic or repeating surgery.

Perioperative Mepolizumab in Aspirin-Exacerbated Respiratory Disease Does Not Prevent Nasal Polyp Regrowth: A Case Series

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a defining feature of aspirin-exacerbated respiratory disease (AERD) and leads to impairment in quality of life. Endoscopic sinus surgery (ESS) is standard-of-care treatment for patients with refractory CRSwNP, but disease often recurs after ESS in those with AERD. We hypothesized that perioperative use of an anti-interleukin-5 antibody, mepolizumab, would prevent CRSwNP recurrence post-ESS.

Neutrophils Play an Important Role in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Despite the heterogeneity of chronic rhinosinusitis (CRS), a clear link exists between type 2 immunity and the severity of CRS with nasal polyps (CRSwNP). However, recent studies have demonstrated that patients with severe type 2 CRSwNP also display abundant neutrophilic inflammation. Therefore, we investigated the factors associated with the recurrence of CRSwNP following sinus surgery using a machine-learning algorithm. We collected the demographics, clinical variables, and inflammatory profiles of 210 patients with CRSwNP who underwent sinus surgery. After one year, we evaluated whether each patient showed recurrence. Machine-learning methods, such as decision trees, random forests, and support vector machine models, have been used to predict the recurrence of CRSwNP. The results indicated that neutrophil inflammation, such as tissue and serum neutrophils, is an important factor affecting the recurrence of surgical CRSwNP. Specifically, the random forest model showed the highest accuracy in detecting recurrence among the three machine-learning methods, which revealed tissue neutrophilia to be the most important variable in determining surgical outcomes. Therefore, our machine-learning approach suggests that neutrophilic inflammation is increased in patients with difficult-to-treat CRSwNP, and the increased presence of neutrophils in subepithelial regions is closely related to poor surgical outcomes in patients with CRSwNP.

Predictive value of S100A4 in eosinophilic chronic rhinosinusitis with nasal polyps.

S100A4 is a pro-inflammatory mediator which has been implicated in airway inflammatory diseases. However, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. The purpose of this study is to determine the expression of S100A4 and evaluate its potential value in distinguishing its endotypes. Sixty CRSwNP patients, 30 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 30 healthy controls (HC) were enrolled in this study, and serum and tissue samples were collected. Serum and tissue S100A4 levels were detected by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, western blotting and immunofluorescence. Their clinical values in predicting postoperative recurrence of CRSwNP were evaluated by multivariate analysis and ROC curves. Serum levels of S100A4 were notably increased in the CRSwNP group than in the CRSsNP and HC groups (p < 0.05), and positively correlated with tissue and peripheral eosinophil count and percentage (p < 0.05). The serum S100A4 concentrations were significantly elevated in the Eos CRSwNP group in comparison with the non-Eos CRSwNP group (p < 0.05). Multivariate analysis and ROC curve presented that serum S100A4 levels were associated with CRSwNP endotypes. Additionally, tissue S100A4 mRNA and protein levels were significantly enhanced in the CRSwNP group than in the HC group and CRSsNP group, especially in the Eos CRSwNP group. Our results demonstrated that the S100A4 expression was increased in CRSwNP patients and associated with the endotypes. S100A4 could be a serologic biomarker for evaluating tissue eosinophilic inflammation and predicting endotypes in CRSwNP patients.

The importance of follow-up examinations in chronic rhinosinusitis with nasal polyposis

PurposeClinical examinations following functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) are critical for physicians to assess results of the intervention and to early identify recurrences. However, no clear consensus on the frequency and timing of clinical examinations following surgery exists. The aim of this study was to analyze CRSwNP recurrences after FESS with a specific focus on the adherence to follow-up examinations. Materials and methodsSixty patients who underwent FESS for CRSwNP were enrolled. Clinical parameters were recorded. Adherence to follow-up examinations with nasal fiber optic endoscopy and regular administration of nasal steroids were analyzed. ResultsAdherence to periodic clinical examinations and regular treatment with nasal steroids was 25 %. CRSwNP recurrence was observed in 56.7 % of cases at the last follow-up examination. No statistically significant difference concerning nasal symptoms was observed between patients with and without current recurrence (p > 0.05). Subjects who underwent regular examinations and prompt treatment of small recurrences had a lower probability of relapse at their last examination (7.7 % versus 38.2 %, respectively; p < 0.001). Polyp grade > 2 in patients with or without adherence were seen in 15.4 % and 42.9 % of cases, respectively (p < 0.05). ConclusionsAdherence to follow-up examinations with nasal optic fiber endoscopy is crucial to early identify recurrence after surgery and promptly treat it with medical therapy.

Exploration of Predictive Biomarkers for Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps Based on Serum Multiple-Cytokine Profiling.

Background Functional nasal endoscopic surgery (FESS) is an effective treatment approach for chronic rhinosinusitis with nasal polyps (CRSwNP) patients, but some patients still suffer from postoperative recurrence. This study is aimed at investigating the expression of multiple cytokines in CRSwNP and revealing their relationships with postoperative recurrence. Methods A total of 72 patients with CRSwNP, including 36 primary and 36 recurrent patients, were enrolled. Serum samples were obtained, 30 cytokine levels were measured by multiplex analysis, and the association between cytokine levels and recurrence was assessed. The most potential cytokines were further validated in another independent cohort with 60 primary and 60 recurrent CRSwNP patients. Results The results of multiple cytokine profiling exhibited that the levels of eotaxin, G-CSF, IFN-α, IL-13, IL-17A, IL-5, MCP-1, and RANTES were vastly changed in the recurrent group in comparison with the primary group. Receiver-operating characteristic (ROC) curves highlighted that serum levels of eotaxin, IL-17A, and RANTES were strongly predictive of postoperative recurrence (area under the curve (AUC) > 0.7, P < 0.05). Further validation results showed that elevated serum eotaxin, IL-17A, and RANTES levels were enhanced in the recurrent group. The ROC curve showed that serum eotaxin (AUC = 0.729, P < 0.001) and RANTES (AUC = 0.776, P < 0.001) exhibited stronger ability than serum IL-17A (AUC = 0.617, P = 0.027) in predicting CRSwNP recurrence. Conclusion Our data suggested that serum multiple cytokine profiling was associated with postoperative recurrence of CRSwNP, and eotaxin and RANTES might serve as potential biomarkers for predicting postoperative recurrence. These results might contribute to the understanding of the underlying mechanisms of recurrence and provide novel clues for precision therapy in CRSwNP.

Increased B Cell-Activating Factor Expression Is Associated with Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper airway inflammatory disease with a high postoperative recurrence rate. This study is aimed at exploring the expression of B cell-activating factor (BAFF) in CRSwNP and its association with postoperative recurrence. Methods A total of 80 CRSwNP patients, including 40 primary CRSwNP patients and 40 recurrent CRSwNP patients, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 40 healthy controls (HC) were enrolled in this study, and the serum and tissue samples were collected. The circulating and tissue BAFF expressions were detected by enzyme-linked immunosorbent assay reverse transcription-polymerase chain reaction and immunohistochemistry. Their clinical values for predicting postoperative recurrence of CRSwNP were evaluated. Results We determined serum levels of BAFF were remarkably increased in the CRSwNP group than the CRSsNP and HC groups (P < 0.05), and higher concentrations of BAFF were associated with peripheral eosinophil percentage (r = 0.614, P < 0.001). The serum BAFF concentrations were significantly higher in the recurrent CRSwNP group in comparison with the primary group (P < 0.05). Multivariate analysis and receiver operating characteristic (ROC) curve presented that serum BAFF levels were associated with the postoperative recurrence in CRSwNP patients (P < 0.05). Moreover, tissue BAFF levels were significantly increased in the CRSwNP group than the HC group, especially in the recurrent CRSwNP group (P < 0.05), and enhanced BAFF RNA expressions were correlated with serum BAFF levels (r = 0.703, P < 0.001). Conclusion Our results elucidated that the BAFF expression was enhanced in CRSwNP patients and associated with postoperative recurrence. BAFF could be a serologic biomarker for predicting postoperative recurrence in CRSwNP patients.

Long-term evaluation of nasal polyposis recurrence: A focus on multiple relapses and nasal cytology

PurposeRecurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) is highly variable, reaching 55–60% of cases. Different results about clinical parameters as recurrence predictors has been reported. The aim of this retrospective study was to evaluate CRSwNP recurrence risk after a long-term follow-up (up to 20 years). Moreover, the role of nasal cytology was assessed. Materials and methodsSixty-one patients who underwent functional endoscopic sinus surgery for CRSwNP were enrolled. Clinical parameters were recorded. Nasal cytology was performed at follow-up examinations. The Kaplan-Meier method was used to obtain the recurrence-free survival curves. The median number of recurrences per year was evaluated. ResultsFive- and 10-year recurrence rates were 30.29% and 66.06%, respectively. Median recurrence-free survival was 106 months. Asthma and Aspirin-Exacerbated Respiratory Disease represented predictors of multiple recurrences (p < 0.05). Intranasal steroids were the main treatment to prevent relapses (p < 0.05). Patients with normal cytology at follow-up evaluation had a lower probability to have first recurrence within 10 years (59% of cases), compared to neutrophil or eosinophil infiltrate (100% and 88% of cases, respectively) (p < 0.05). ConclusionsCRSwNP has a high recurrence risk, also more than 10 years after surgery. Nasal cytology may identify subjects with a higher risk of early recurrence.

Predicting the recurrence of chronic rhinosinusitis with nasal polyps using nasal microbiota.

Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence. Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression-based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post-admission. By distinguishing recurrence-associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non-recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy. Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment.

Serum YKL-40 Levels Predict Endotypes and Associate with Postoperative Recurrence in Patients with Chronic Rhinosinusitis with Nasal Polyps.

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a global health concern with high heterogeneity and rate of postoperative recidivation. YKL-40 is a pivotal pro-inflammatory mediator to promote Th2 immune response which is involved in many inflammatory diseases. This study aimed to investigate the predictive value of serum YKL-40 in CRSwNP endotypes and postoperative recurrence.MethodsWe recruited 80 primary CRSwNP, 40 recurrent CRSwNP patients and 40 healthy controls (HCs) in this study, and the serum and tissue specimens were collected. The middle turbinate mucosa tissue collected from patients undergoing septoplasty was used as control. Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and tissue YKL-40 mRNA and protein levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The difference of YKL-40 expression was compared among different group. Multivariate analysis and receiver operating characteristic (ROC) curve were performed to evaluate the value of serum YKL-40 in discriminating eosinophilic CRSwNP (eCRSwNP) and predicting postoperative recurrence.ResultsThe serum YKL-40 levels in CRSwNP patients were higher than HCs, especially in eCRSwNP patients (p < 0.05). The elevated YKL-40 levels positively correlated with blood eosinophil percentage, tissue eosinophil counts and percentages (p < 0.05). The serum YKL-40 levels in recurrent CRSwNP patients were markedly enhanced than primary CRSwNP patients (p < 0.05). The YKL-40 mRNA and protein levels were significantly elevated in CRSwNP patients compared to HCs, especially in eCRSwNP and recurrent CRSwNP group. Multivariate analysis and ROC curve exhibited that serum YKL-40 might be a promising indicator in distinguishing CRSwNP endotypes and predicting postoperative recurrence.ConclusionOur data suggested that YKL-40 might be unregulated in CRSwNP and associated with mucosal eosinophilia and recurrence. Serum YKL-40 appeared to a novel biomarker for predicting CRSwNP endotypes and postoperative recurrence of CRSwNP.