Chronic Rhinosinusitis With Nasal Polyps Patients Research Articles

Latent class analysis of structured histopathology in prognosticating surgical outcomes of chronic rhinosinusitis with nasal polyps in Singapore.

Structured histopathology profiling is recommended when reporting chronic rhinosinusitis with nasal polyp (CRSwNP) tissue. The objective of this study is to identify features in structured histopathology that predict outcome after functional endoscopic sinus surgery (FESS) in a cohort of CRSwNP patients from Singapore. Latent class analysis was performed on structured histopathology reports of 126 CRSwNP patients who had undergone FESS. Outcome measures were polyp recurrence, need for systemic corticosteroids, revision surgery or biologics, and disease control at 2 years post-FESS. Three classes were identified. Class 1 was characterised by mild, predominantly lymphoplasmacytic inflammation. Class 2 comprised of 100 eosinophils/HPF, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals. Classes 2 and 3 were significantly associated with uncontrolled disease at 2 years post-FESS. Class 3 was additionally associated with the need for systemic corticosteroids. Eosinophil count, degree of inflammation, predominant inflammatory type, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals predicted need for systemic corticosteroids and uncontrolled disease at 2 years post-FESS. The presence of >100 eosinophils/HPF should be reported, as this subset of tissue eosinophilia was associated with less favourable outcomes after FESS.

Impaired local VD3 metabolism contributes to tissue neutrophilic inflammation in chronic rhinosinusitis with nasal polyps

Abstract Objective: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation of VD3 function and its effect on local inflammation in CRSwNP. Methods: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzymes converting 25VD3 to the active 1,25VD3, and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence. HNECs and polyp tissue explants were treated with 1,25VD3. Tissue ECP +eosinophils and MPO +neutrophils were stained and quantified by immunofluorescence. Results: 25VD3 levels in serum and nasal tissue lysates were decreased in CRSwNP patients compared to control subjects. The expression of VDR and CYP27B1 were reduced in CRSwNP. VDR and CYP27B1 expression in HNECs were downregulated by IFN-γ and poly (I:C). 1,25VD3 suppressed neutrophilic inflammation in HNECs and polyp tissues. Tissue 25VD3 levels negatively correlated with neutrophilic inflammation in CRSwNP. Conclusion: Reduced 25VD3 level and decreased CYP27B1 and VDR expression may impair local VD signaling activation, and thus exaggerate neutrophilic inflammation in CRSwNP.

Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving “Ciliated epithelial cells” were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab.

Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients' quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-Grunwald-Giemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-high-group showed a greater change of eosinophils over time (Δ17.82) compared to the Eo-low-group (Δ10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method.

Effect of recombinant human acidic fibroblast growth factor on nasal mucosal healing after endoscopic sinus surgery

BackgroundPostoperative nasal treatment is an important factor affecting the outcomes of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). This study aimed to determine the effect of recombinant human acidic fibroblast growth factor (rh-aFGF) on nasal mucosal healing after ESS. MethodsThis study is a prospective, single-blind, and randomized controlled clinical study. Fifty-eight CRS patients with nasal polyps (CRSwNP) with bilateral ESS were enrolled and randomly given 1 mL of budesonide nasal spray and 2 mL of rh-aFGF solution (rh-aFGF group) or 1 mL of budesonide nasal spray and 2 mL of rh-aFGF solvent (budesonide group)-infiltrated Nasopore nasal packing after ESS. Preoperative and postoperative scores for Sino-Nasal Outcome Test (SNOT-22), Visual Analogue Scale (VAS), and Lund-Kennedy were collected and analyzed. ResultsForty-two patients completed the 12-week follow-up. Postoperative SNOT-22 scores and VAS scores showed no significant differences between the two groups. In terms of the Lund-Kennedy scores, there was a statistically significant difference between the two groups at the 2-, 4-, 8-, and 12-week postoperative visits, but not at the 1-week visit. Twelve weeks after surgery, the nasal mucosa had completely epithelialized in 18 patients in the rh-aFGF group and in 12 patients in the budesonide group (χ2 = 4.200, P = 0.040). ConclusionThe combined application of rh-aFGF and budesonide significantly improved postoperative endoscopic appearance in the nasal mucosal healing process.

Reduction in healthcare resource use through 24 months following sinus surgery with steroid-eluting implants in chronic rhinosinusitis patients with and without nasal polyps: a real-world study

Objective To investigate the impact of steroid-eluting implants after endoscopic sinus surgery (ESS) on health care resource use (HCRU) in chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps. Methods This retrospective, observational cohort study using real-world evidence data included adult patients with CRS who underwent ESS in 2015–2019 with at least 24 months of data before and after ESS. Patients who received implants were matched to patients who did not based on a propensity score developed using baseline characteristics and NP status. HCRU was compared between cohorts within each CRSwNP and CRSsNP subgroup using chi-square tests (binary variables). Results The implant cohort in the CRSwNP subgroup had fewer all-cause outpatient (90.0% vs. 93.9%, p < .001) and all-cause otolaryngology (64.3% vs. 76.4%, p < .001) visits as well as fewer endoscopy (40.5% vs. 47.4%, p = .005) and debridement (48.8% vs. 55.6%, p = .007) procedures than the non-implant cohort. The implant cohort in the CRSsNP subgroup had fewer all-cause outpatient (88.9% vs. 94.2%, p < .001) and all-cause otolaryngology (53.5% vs. 74.4%, p < .001) visits as well as fewer endoscopy (31.8% vs. 41.7%, p < .001) and debridement (36.7% vs. 53.4%, p <.001) procedures than the non-implant cohort. Revision sinus surgery was reduced in the implant cohort in both subgroups, and reached statistical significance in the CRSwNP subgroup (3.8% vs. 6.0%, p = .039) but not in the CRSsNP subgroup (3.6% vs. 4.2%, p = .539). Conclusions Overall, patients receiving implants had lower HCRU for 24 months after sinus surgery independent of nasal polyp status, and revision surgery was reduced in CRSwNP patients. These findings provide additional evidence that long-term reductions in HCRU may be achieved with steroid-eluting implant use during sinus surgery. What is known on this topic Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a disproportionately higher burden of disease and consume greater healthcare resources than chronic rhinosinusitis patients without nasal polyps (CRSsNP). CRSwNP patients represent approximately 30% of CRS patients who undergo surgery, but their clinical course is disproportionally complicated by disease recurrence and revision surgery. Steroid-eluting sinus implants have been shown in clinical trials to improve short-term postoperative outcomes after endoscopic sinus surgery (ESS) in CRS patients in general. A recent real-world evidence study reported that steroid-eluting sinus implants following ESS were associated with a reduction in HCRU in CRS patients followed for 18 months, but the impact of implants on HCRU in CRSwNP and CRSsNP patients separately remains unknown. What this study adds In this observational study, reduced HCRU was observed in CRSwNP and CRSsNP patients who receive steroid-eluting sinus implants. Use of implants in CRSwNP and CRSsNP patients was associated with a significant reduction in healthcare visits (all-cause outpatient, all-cause otolaryngology), and sinus procedures (endoscopy, debridement). Revision surgery was significantly reduced in the implant cohort of CRSwNP patients and trended lower in the implant cohort of CRSsNP patients. Use of implants had no significant impact on all-cause ER/urgent care visits or sinus-related imaging.

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.

Oncostatin M Contributes to Airway Epithelial Cell Dysfunction in Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a typical type-2 inflammation involving several cytokines and is associated with epithelial cell dysfunction. Oncostatin M (OSM) (belonging to the interleukin(IL)-6 family) could be a key driver of epithelial barrier dysfunction. Therefore, we investigated the presence of OSM and IL-6 and the expression pattern of tight junctions (TJs) in the nasal tissue of CRSwNP patients and controls using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Then, their potential role in the epithelial barrier was evaluated in vitro in 27 different primary cultures of human nasal epithelial cells (HNECs) by measuring TJ expression and transepithelial electric resistance (TEER) with or without OSM or IL-6 (1, 10, and 100 ng/mL). The effect on ciliary beating efficiency was evaluated by high-speed videomicroscopy and on repair mechanisms with a wound healing model with or without OSM. OSM and IL-6 were both overexpressed, and TJ (ZO-1 and occludin) expression was decreased in the nasal polyps compared to the control mucosa. OSM (100 ng/mL) but not IL-6 induced a significant decrease in TJ expression, TEER, and ciliary beating efficiency in HNECs. After 24 h, the wound repair rate was significantly higher in OSM-stimulated HNECs at 100 ng/mL. These results suggest that OSM could become a new target for monoclonal antibodies.

Considerations for shared decision-making in treatment of chronic rhinosinusitis with nasal polyps.

Shared decision-making is an approach where physicians and patients work together to determine a personalized treatment course. Such an approach is integral to patient-centered care in chronic rhinosinusitis with nasal polyps (CRSwNP). CRSwNP is a chronic inflammatory condition of the sinonasal cavity that can severely impact physical health, smell, and quality of life (QOL). Traditional standard-of-care treatment options include topical (i.e. sprays) and oral corticosteroids and endoscopic sinus surgery, but more recently, novel corticosteroid delivery methods (i.e. high volume irrigations, recently-approved exhalation breath-powered delivering devices, and drug-eluting steroid implants) and 3 new FDA approved biologics directed against type II immunomodulators have become available. The availability of these therapeutics offers exciting new opportunities in CRSwNP management but requires personalized and shared-decision making as each modality has variable impacts on CRSwNP and related comorbid conditions. Studies have published treatment algorithms, but the practical use of these lean guidelines is heavily influenced by the lens of the treating physician, the most common being otolaryngologists and allergy immunologists. Clinical equipoise occurs when there is no basis for one intervention to be regarded as "better" than another. While most guidelines, in general, support the use of topical corticosteroids with or without oral corticosteroids followed by ESS for the majority of unoperated CRSwNP patients, there are situations of clinical equipoise that arise particularly in CRSwNP who have failed surgery or those with severe comorbid conditions. In the shared decision-making process, clinicians and patients must consider symptomatology, goals, comfort, compliance, treatment efficacy, and treatment cost when determining the initial choice of therapy and escalation of therapy with the potential use of multiple modalities for recalcitrant CRSwNP. A summary of salient considerations that might constitute shared decision-making is presented in this summary.

Determination of orally administered 1,8-Cineol in nasal polyp tissues from chronic rhinosinusitis patients using gas chromatography: mass spectrometry

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease causing considerable disease burden. The anti-inflammatory monoterpene 1,8-Cineol is a natural plant-based therapeutic agent that is well established to treat chronic and acute airway diseases. Aim of this study was to investigate whether the herbal drug 1,8-Cineol reaches the nasal tissue via the gut and the blood stream upon its oral administration. A highly sensitive gas chromatography mass spectrometry-based method with stir bar sorptive extraction (SBSE) for sample preparation has been developed and validated for the extraction, detection and quantification of 1,8-Cineol in tissue samples of nasal polyps from 30 CRSwNP patients. Data revealed a highly sensitive detection of 1,8-Cineol in nasal tissue samples after 14 days of oral administration of 1,8-Cineol prior to surgical treatment. There was no significant correlation between the measured 1,8-Cineol concentrations and bodyweight or BMI values of the analyzed patients, respectively. Our data indicate a systemic distribution of 1,8-Cineol in the human body after its oral administration. Individual differences in terms of metabolic characteristics and have to be further investigated. The study increases our understanding of the systemic effects of 1,8-Cineol upon its therapeutic application and benefit in patients with CRSwNP.

Dupilumab for chronic rhinosinusitis with nasal polyps: real-life retrospective 12-month effectiveness data.

Dupilumab, an IL-4/13 receptor inhibitor, is approved for the treatment of uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). We evaluated the effectiveness and safety of dupilumab for CRSwNP based on retrospective 12-month follow-up data of 41 patients. We analysed nasal endoscopy scores, patient-reported outcome measures (PROMs), 12-item SniffinSticks odor identification test (SSIT-12), total serum IgE, serum Eosinophilic Cationic Protein (ECP), and total blood eosinophil count (BEC). We performed statistical analysis using non-parametric ANOVA-type models and Spearman's correlation. At month 1, endoscopy scores, PROMs and SSIT-12 showed meaningful improvements that were maintained until month 12. Initial elevations in both median ECP and BECs returned to near baseline levels by month 12. The percentage of patients withBEC ≤ 0.6 remained increased at month 12 (42.1%) compared to baseline (19.5%). Total serum IgE levels decreased progressively and correlated with nasal polyp scores at month 12. "Adequate response" was reached in 86.8% of our cohort. Our data suggest that dupilumab is effective for the treatment of CRSwNP. The potential for short- and long-term BEC elevations in some CRSwNP patients should be carefully monitored.

Understanding the CRSwNP Patient as Whole.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a distinct inflammatory disease of the upper airways with a significant impact on the health and quality of life of affected patients. Several comorbid conditions such as allergic rhinitis, asthma, sleep disorders, and gastroesophageal reflux disease are commonly reported in patients with CRSwNP. In this article, we intended to review the UpToDate information on how these comorbidities can impact CRSwNP patients' health and well-being. A PUBMED search was performed to review relevant recent article on the topic. While there have been significant advances in the knowledge and management options for CRSwNP in the past few years, additional studies are needed to understand the underlying pathophysiologic mechanisms of these associations. In addition, awareness of the impact of CRSwNP on mental health, quality of life, and cognition is paramount to treating this condition. Recognition and addressing CRSwNP comorbidities such as allergic rhinitis, asthma, sleep disorders, gastroesophageal reflux disease, and cognitive function impairment are important to optimally understand and manage the patient with CRSwNP as a whole.

Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps.

To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA(mRNA) levels of superoxide dismutase 2(SOD2), aldehyde dehydrogenase 1(ALDH1A1), and microsomal glutathione S-transferase 1 (MGST1) were examined using quantitative real-time polymerase chain reactionin the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients. The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by thearea under the curve. These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

Real-Life Effectiveness of Mepolizumab in Refractory Chronic Rhinosinusitis with Nasal Polyps

The aim of this study was to evaluate the efficacy of mepolizumab in patients affected by chronic rhinosinusitis with nasal polyps (CRSwNP) in real-life. A single-center retrospective observational study was conducted on severe CRSwNP patients treated with mepolizumab. Nasal endoscopic polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), asthma control test (ACT) score, fractional exhaled nitric oxide (FeNO), eosinophils blood cells and prednisone intake were assessed at baseline and after 6 months. A total of 55 patients were included; 49 patients (89%) presented with asthma; aspirin exacerbated respiratory disease (AERD) in 28 patients (51%). A statistically significant decrease in the SNOT-22 score was observed (median difference -63; 95% CI: -68; -58; p < 0.001) with median t0 76 and IQR (61;90) to t6 10 (5;15). A reduction in NPS, median t0 NPS 4; (IQR:4;6), median t6 NPS 1; (IQR:0;1) p < 0.001, was greater in patients with AERD. The median baseline VAS score was 6 (IQR:6;7) and the differences between t0 and t6 were statistically significant p < 0.001. Significant changes in blood eosinophils cells, median t0 500 cell/mcl (IQR:340;830), median t6 97 cell/mcl (IQR:60;160) p < 0.001, were greater in patients with AERD. Mepolizumab treatment effects have been demonstrated with significantly reduced symptoms, polyp scores, blood eosinophils and systemic corticosteroid use, resulting in an increased health-related quality of life in patients with severe CRSwNP, regardless of the presence or absence of asthma or AERD.

Measuring Nasal Patency and the Sense of Smell in CRSwNP Patients Treated with Dupilumab.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the most severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with dupilumab in different rhinological units were followed up at 1, 3, 6 and 12 months from the first administration and were considered for this study. At baseline (T0) and at each follow-up, patients underwent nasal endoscopy and completed the sinonasal outcome test (SNOT)-22, a visual analogue scale (VAS) for smell/nasal obstruction, peak nasal inspiratory flow (PNIF) and the Sniffin' Sticks identification test (SSIT). The aim of the present study was to evaluate the effects of dupilumab in patients with severe uncontrolled CRSwNP on recovering nasal obstruction and smell impairment. Moreover, the method between PNIF and SSIT with the highest correlation with patients' response to dupilumab was evaluated. One hundred forty-seven patients were included. All parameters improved during treatment (p < 0.001). At T0, no correlations were found between PNIF and nasal symptoms. Nevertheless, during the following evaluations significant correlations between PNIF changes and both nasal symptoms and NPS were observed (p < 0.05). At T0, SSIT did not correlate with SNOT-22. Similarly to PNIF, during the follow-up SSIT changes significantly correlated with nasal symptom and NPS (p < 0.05). Comparing PNIF and SSIT correlations with SNOT-22 and NPS, PNIF showed a higher correlation with both. Dupilumab improves nasal obstruction and the sense of smell. PNIF and SSIT are effective tools in monitoring patients' response to dupilumab.

The role of interleukin 36γ in the epithelial-mesenchymal transition process of chronic rhinosinusitis: A pilot study.

Epithelial-mesenchymal transition (EMT) is an important characteristic in the remodelling of chronic rhinosinusitis with nasal polyps (CRSwNP). IL-36γ and fibroblast activation protein (FAP) may exacerbate remodelling in CRS. Here, we aimed to determine whether IL-36γ and FAP expression are associated with EMT and may be a predictor for CRSwNP prognosis. Fifty-two non-Eos CRSwNP patients and 12 control patients were obtained and were followed up for more than 1 year after surgery. IL-36γ, FAP and EMT markers expression were evaluated by real-time polymerase chain reaction and western blot. Masson trichrome staining was adopted to assess tissue fibrotic changes. Furthermore, the soluble form of IL-36γ and FAP in nasal secretions was detected by ELISA. While basal expression of E-cadherin decreased, the expression of IL-36γ, vimentin and FAP increased in nasal polyps. In well-prognosis patients, the expression of IL-36γ, vimentin and FAP were significantly decreased than in poor-prognosis patients, while the protein expression of E-cadherin was increased. The protein expression of IL-36γ was notably increased in recurrent nasal polyps than in preoperation specimens. A positive relationship between IL-36γ and FAP expression, a negative relationship between IL-36γ and E-cad expression was noted. The soluble form of IL-36γ and FAP increased during the development of non-Eos CRSwNP, with the highest level in poor-prognosis patients after surgery. Non-Eos CRSwNP have partially undergone EMT under baseline conditions. IL-36γ and FAP expression were related with EMT, the soluble form of IL-36γ and FAP in nasal secretions may predict the prognosis of patients.

Predictive Significance of Claudin-3 for Epithelial Barrier Dysfunction in Chronic Rhinosinusitis With Nasal Polyps.

The abnormal expression of tight junction (TJ) plays a vital role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, there is no appropriate tool to distinguish and diagnose epithelial barrier defects in clinical practice. This study aimed to evaluate the predictive value of claudin-3 for epithelial barrier dysfunction in CRSwNP. In this study, TJ protein levels were evaluated by real-time quantitative polymerase chain reaction, immunofluorescent, and immunohistochemistry staining in control subjects and CRSwNP patients. The receiver operating characteristic (ROC) curve was created to assess the predictive value of TJ breakdown in clinical outcomes. In vitro, human nasal epithelial cells were cultured at the air-liquid interface to analyze the transepithelial electrical resistance (TER) level. The expression levels of occludin, tricellulin, claudin-3, and claudin-10 were decreased (all P < 0.05), and those of claudin-1 was increased (P < 0.05) in CRSwNP patients as compared to healthy subjects. Additionally, claudin-3 and occludin levels were negatively correlated with the computed tomography score in CRSwNP (all P < 0.05), and the ROC curve indicated that the claudin-3 level had the most predictive accuracy in evaluating epithelial barrier disruption (area under the curve = 0.791, P < 0.001). Finally, the time-series analysis showed the highest correlation coefficient between TER and claudin-3 (cross-correlation function = 0.75). In this study, we suggest that claudin-3 could be a valuable biomarker for predicting nasal epithelial barrier defects and disease severity in CRSwNP.

Platelet-to-lymphocyte ratio might predict the response to dupilumab treatment for patients with nasal polyposis

BackgroundDupilumab is a monoclonal antibody against interleukin 4 receptor alpha and has proven to be clinically effective in treating patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, a certain number of patients are non- or partial responders. This study aims to investigate the relevance of inflammatory markers with regard to therapy response to dupilumab in CRSwNP patients.MethodsAll patients with CRSwNP treated with dupilumab at a tertiary healthcare center with available pretreatment inflammatory markers were included. The values of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with the outcome. Patients were stratified according to the respective median value (> median was considered high). The binary logistic regression was performed with regard to total treatment response (post-treatment total nasal polyp score (NPS) 0).ResultsA total of 65 CRSwNP patients with available pretreatment peripheral blood values were included in the study. The mean pre- and post-treatment total NPS values were 4.3 ± 1.9 and 1.2 ± 1.6, respectively. High PLR (> 131.2) was independently associated with a 3.9-fold higher probability of reaching the NPS value of 0 in the multivariable analysis. On the other hand, High NLR (> 1.9) did not significantly associate with the outcome.ConclusionsThe current study provides insights into the potential positive predictive value of the high PLR (> 131.2) in CRSwNP patients regarding treatment with dupilumab. There is a need for further prospective studies for validation of these results, especially in cohorts of patients with severe CRSwNP.

Effect of Chronic Rhinosinusitis on the Risk of Development of Rheumatoid Arthritis.

Several studies have reported a possible link between chronic rhinosinusitis (CRS) and rheumatoid arthritis (RA). However, it remains unclear whether CRS could influence the risk of developing RA. Therefore, in this study, we focused on examining the association between CRS and RA. A total of 14,867 individuals with CRS and 14,867 without CRS were enrolled after 1:1 propensity score match from a nationwide longitudinal cohort database in South Korea. RA incidence was assessed using person-years at risk, and the hazard ratio (HR) was examined using the Cox proportional hazards model. The incidence of RA (per 1,000 person-years) was 6.51 for those with CRS, 6.55 for those with CRS without nasal polyps (CRSsNP), and 5.96 for those with CRS with nasal polyps (CRSwNP). We found that CRS individuals had a significantly increased risk of subsequent RA development with an adjusted HR of 1.41, regardless of the phenotype (adjusted HR was 1.42 in CRSsNP and 1.37 in CRSwNP patients). Moreover, the risk of developing RA over time was relatively higher within the first 4 years after the diagnosis of CRS. Our nationwide population-based cohort study suggests that CRS may be associated with a subsequent increase in RA events, regardless of the phenotype. Therefore, physicians should consider RA risk when diagnosing and treating CRS patients.

Development, Validation and Comparison of Artificial Neural Network and Logistic Regression Models Predicting Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) can be classified into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (non-eCRSwNP) by tissue biopsy, which is difficult to perform preoperatively. Clinical biomarkers have predictive value for the classification of CRSwNP. We aimed to evaluate the application of artificial neural network (ANN) modeling in distinguishing different endotypes of CRSwNP based on clinical biomarkers. Clinical parameters were collected from 109 CRSwNP patients, and their predictive ability was analyzed. ANN and logistic regression (LR) models were developed in the training group (72 patients) and further tested in the test group (37 patients). The output variable was the diagnosis of eCRSwNP, defined as tissue eosinophil count > 10 per high-power field. The receiver operating characteristics curve was used to assess model performance. A total of 15 clinical features from 60 healthy controls, 60 eCRSwNP and 49 non-eCRSwNP were selected as candidate predictors. Nasal nitric oxide levels, peripheral eosinophil absolute count, total immunoglobulin E, and ratio of bilateral computed tomography scores for the ethmoid sinus and maxillary sinus were identified as important features for modeling. Two ANN models based on 4 and 15 clinical features were developed to predict eCRSwNP, which showed better performance, with the area under the receiver operator characteristics significantly higher than those from the respective LR models (0.976 vs. 0.902, P = 0.048; 0.970 vs. 0.845, P = 0.011). All ANN models had better fits than single variable prediction models (all P < 0.05), and ANN model 1 had the best predictive performance among all models. Machine learning models assist clinicians in predicting endotypes of nasal polyps before invasive detection. The ANN model has the potential to predict eCRSwNP with high sensitivity and specificity, and is superior to the LR model. ANNs are valuable for optimizing personalized patient management.