A review of current biomarkers in chronic rhinosinusitis with or without nasal polyps.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a heterogeneous disease with a variety of cellular and molecular pathophysiologic mechanisms. Biomarkers have been explored in CRS using various phenotypes, such as polyp recurrence after surgery. Recently, the presence of regiotype in CRS with nasal polyps (CRSwNP) and the introduction of biologics for the treatment of CRSwNP has indicated the importance of endotypes, and there is a need to elucidate endotype-based biomarkers. AREAS COVERED: Biomarkers for eosinophilic CRS, nasal polyps, disease severity, and polyp recurrence have been identified. Additionally, endotypes are being identified for CRSwNP and CRS without nasal polyps using cluster analysis, an unsupervised learning technique. EXPERT OPINION: Endotypes in CRS have still being established, and biomarkers capable of identifying endotypes of CRS are not yet clear. When identifying endotype-based biomarkers, it is necessary to first identify endotypes clarified by cluster analysis for outcomes. With the application of machine learning, the idea of predicting outcomes using a combination of multiple integrated biomarkers, rather than a single biomarker, will become mainstream.

Retinoic acid promotes fibrinolysis and may regulate polyp formation.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells. OBJECTIVES: This study sought to determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in patients with CRSwNP and AERD. METHODS: NP tissue was collected from patients with AERD or CRSwNP, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial cells were stimulated alone or in combination with RA and IL-13 for 24 hours. RESULTS: This study observed lower retinoid levels in nasal polyps of patients with AERD than those with CRSwNP or healthy controls (P < .01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P < .01), which is consistent with lower tPA expression (P < .01). In vitro, all-trans RA upregulated tPA levels in normal human bronchial epithelial cells by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P < .01). CONCLUSIONS: RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from patients with AERD, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating patients with CRSwNP and/or AERD.

Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations.

BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. OBJECTIVE: Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). METHODS: We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. RESULTS: Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. CONCLUSION: NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.

A Covered Lateral and Posterior Wall Flap of the Maxillary Sinus Prevents Reocclusion of the Postoperative Maxillary Cyst.

Although the number of postoperative maxillary cyst (POMC) cases has declined recently, a few reports of refractory cases have also been reported. The indications for endoscopic sinus surgery (ESS) for POMC removal are broadening and attempts to prevent postoperative recurrence at the cyst opening site have been widely investigated. Here, we have advocated our original pedunculated mucoperiosteal flap (CLAP flap; covered lateral and posterior wall flap of the maxillary sinus), where the bony area exposed intraoperatively is covered, to prevent postoperative recurrence. We have also presented the method for creating the CLAP flap. We classified the POMC as being medial, lateral, or anterior superior type and performed ESS. We introduced the CLAP flap after 2015 for the lateral type and some of the medial types of POMCs. We examined the cyst opening rate using computed tomography, age, sex, cyst position, and a follow-up period in four patients (five sides) who did not undergo flap surgery, but who were managed in our hospital in 2015, and in eight patients (nine sides) who underwent the CLAP flap technique in our hospital. In the group with the CLAP flap, the cyst opening rate was significantly higher (P < 0.05). The CLAP flap was effective for preventing postoperative bony regrowth. It may be one of the options for covering the exposed bone surface as widely as possible. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12070-021-02658-x.

A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To assess the efficacy and safety of benralizumab in patients with ECRS. METHODS: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. RESULTS: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. CONCLUSION: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

Predictors of Visual Acuity and Usefulness of a Treatment Algorithm in Rhinogenous Optic Neuritis.

Rhinogenous optic neuritis, which causes neuropathy associated with visual dysfunction, greatly reduces patient quality of life and requires suitable early treatment. This study aimed to analyze visual outcome predictors in patients with rhinogenous optic neuritis and to develop and investigate the usefulness of an algorithm to facilitate early treatment. Prospective and retrospective investigations were conducted at the Department of Otorhinolaryngology. The visual outcomes after sinus surgery of 24 of 53 patients suspected of having rhinogenous optic neuritis were analyzed. Furthermore, the usefulness of the treatment algorithm was evaluated in 27 of these 53 patients. Data from 24 patients who underwent surgery were included in a multiple regression analysis to investigate the associations between visual outcomes and concomitant symptoms and the time from symptom onset to surgery. The mean time from the initial examination to a request for otorhinolaryngological examination to assess the usefulness of the treatment algorithm was compared in 27 patients who did not undergo an initial otorhinolaryngological examination. Visual acuity improved in 23 participants who underwent surgery. Multivariate analysis identified the time from onset to surgery and headache as significant predictors of postoperative visual acuity. The mean time from the initial examination to a request for otorhinolaryngological examination was significantly shorter after the algorithm was introduced (1.13 days, 8 patients; P = .008). Early surgical treatment is essential to avoid further postoperative visual acuity decreases in patients with rhinogenous optic neuritis. Patients who experience headache may have poorer postoperative outcomes.

Comparison of Current Staging Systems for Sinonasal Inverted Papilloma.

BACKGROUND: A staging system is essential for determining the optimal surgical approach and predicting postoperative outcomes for inverted papilloma (IP). Although staging systems based on the extent to which the location is occupied by an IP have been widely used, an origin site-based classification of IP using unsupervised machine learning algorithms has recently been reported. OBJECTIVE: To determine the most appropriate of five staging systems for sinonasal IP by comparing recurrence rates for each stage according to each of those systems. METHODS: Eighty-seven patients with sinonasal IP were enrolled in the study. Their tumors were retrospectively categorized according to the Krouse, Oikawa, Cannady, and Han staging systems, which are based on the extent of IP, and the Meng system, which is based on the site of origin. The rates of recurrence for each stage of the five systems were compared. RESULTS: Seven of the 87 patients (8.0%) had recurrences during an average 45.5 months (12-138 months) of follow-up. There were significant differences in disease-free survival between the stages specified by Han and Meng (p = 0.027 and p < 0.001, respectively), but not between the stages specified by Krouse, Oikawa, and Cannady (p = 0.236, 0.062, and 0.130, respectively). Cox proportional hazard models revealed that Meng system (adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.10-17.04) and presence of dysplasia (aHR 7.42, 95% CI 1.15-47.85) were significantly associated with recurrence. CONCLUSION: The staging systems proposed by Han and Meng were found to be accurate in terms of tumor recurrence. We recommend use of the Han staging system before surgery and the Meng system after intraoperative identification of the origin of the tumor.

Prelacrimal approach vs conventional surgery for inverted papilloma in the maxillary sinus.

BACKGROUND: The prelacrimal approach, termed endoscopic modified medial maxillectomy (EMMM), has recently been applied for treatment of inverted papilloma (IP) in the maxillary sinus. EMMM provides wider access to the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct. METHODS: We reviewed patients with IP in the maxillary sinus to compare the surgical results obtained by conventional surgery (ie, endoscopic maxillary sinus antrostomy or in combination with the Caldwell-Luc approach) with those obtained by EMMM. RESULTS: All patients had a T3 on the Krouse staging system, and the average follow-up time was 46.0 months. Of the 18 patients in the conventional group, recurrence was seen in 3 patients (16.6%). No recurrence was seen in the 27 patients who showed preservation of the inferior turbinate and nasolacrimal duct, and no complications occurred in the EMMM group. CONCLUSIONS: EMMM is an effective surgical approach that reduces recurrence with fewer complications.

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis.

BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.

Consensus guidance of nebulizer therapy for acute rhinosinusitis.

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions.

Postoperative evaluation of olfactory dysfunction in eosinophilic chronic rhinosinusitis - comparison of histopathological and clinical findings.

Background: Olfactory dysfunction in eosinophilic chronic rhinosinusitis (ECRS) is poorly understood. Objective: To compare olfactory mucosal injury due to eosinophil infiltration in ECRS with postoperative olfactory function. Methods: Seventeen ECRS patients (ECRS group) and 18 bilateral rhinosinusitis (non-ECRS group) patients were compared. At 3 and 12 months post-endoscopic sinus surgery (ESS), all patients were evaluated for subjective symptoms (nasal obstruction, nasal discharge and olfactory dysfunction), endoscopic nasal findings, CT score and T&T olfactometer recognition threshold test. The eosinophil count, OMP-positive cells and epithelial erosion in olfactory mucosa collected during ESS were compared with the postoperative olfactory function. Results: The non-ECRS group showed significant improvement in all clinical findings at 3 and 12 months, but the ECRS group showed worsening of the olfactory dysfunction symptoms and T&T olfactometer recognition threshold at 12 months because of recurrence of sinusitis. The groups differed significantly in the ΔT&T value (i.e. pre-ESS T&T recognition threshold - post-ESS T&T recognition threshold) at both 3 and 12 months, and the degree of olfactory improvement differed. Histologically, the ECRS group showed significantly more eosinophils, fewer OMP-positive cells and greater epithelial erosion than the non-ECRS group. Conclusions: Eosinophilic inflammation was thought to cause olfactory mucosal injury/dysfunction.

Increased expression of L-plastin in nasal polyp of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

BACKGROUND: Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD. METHODS: We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection. RESULTS: L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor. CONCLUSION: Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.

Long-term postoperative control of eosinophilic chronic rhinosinusitis recurrence by inserting a steroid-eluting, sinus-bioabsorbable device reduces the dosage of oral steroid.

OBJECTIVE: We employed a steroid-eluting, sinus-bioabsorbable device for local treatment after surgery for eosinophilic chronic rhinosinusitis (ECRS). One year later, we investigated its efficacy in suppressing recurrence and reducing the use of oral steroids. METHODS: At one year after ECRS surgery, both 18 cases treated with a postoperative steroid-eluting, sinus-bioabsorbable device (Post-ST group) and 25 cases receiving conventional postoperative therapy (Post-Con group) showed significant improvement in the nasal symptoms (nasal obstruction, nasal discharge and olfactory dysfunction), CT score and threshold test (discrimination test). RESULTS: The olfactory dysfunction, CT score and threshold test were significantly improved in the Post-ST group compared with the Post-Con group, but the polyp score was not. The mean total number of oral steroid tablets ingested during one year after surgery was 24.3±2.8 tablets in the Post-ST group, which was significant lower than the 36.3±3.7 tablets used in the Post-Con group. CONCLUSION: The above results indicate that insertion of a steroid-eluting, sinus-bioabsorbable device after ECRS surgery can reduce the oral steroid intake while maintaining long-term suppression of disease recurrence.

JESREC score and mucosal eosinophilia can predict endotypes of chronic rhinosinusitis with nasal polyps.

OBJECTIVE: Recently, JESREC score and mucosal eosinophil count have been used to diagnose eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, it remains unknown whether the subtypes of CRS diagnosed by these criteria have different endotypes. In the present study, we investigated whether JESREC score and mucosal eosinophil count were appropriate for classification of CRS subgroups into endotypes. METHODS: A cross-sectional study involving 71 consecutive patients with CRS with nasal polyps (CRSwNP) and 13 control patients was performed. Nasal polyp tissues from CRSwNP patients and uncinate process tissues from control patients were collected for analysis of inflammatory cells by immunohistochemistry and measurement of cytokines and chemokines by ELISA and quantitative real-time PCR. We compared the differences between subtypes according to JESREC score and mucosal eosinophil count and investigated the subgroups with different endotypes by cluster analysis and principal component analysis. RESULTS: In the 71 CRSwNP patients, 9 patients had JESREC score <11 and mucosal eosinophil count <70/HPF (Group A), 20 patients had JESREC score ≥11 and mucosal eosinophil count <70/HPF (Group C), and 42 patients had JESREC score ≥11 and mucosal eosinophil count ≥70/high-power field (HPF) (Group D). Semiquantitative analysis of inflammatory cells showed that eosinophils, neutrophils, macrophages, mast cells, and basophils differed significantly between the subgroups. At the mRNA level, CLC, IL5, IL13, CCL11, CCL24, CCL26, POSTN, CSF3, and IL8 showed significant differences. At the protein level, eotaxin-2/CCL24, eotaxin-3/CCL26, and G-CSF had significant differences. Cluster analysis using gene expression levels in 55 CRS patients and 11 control patients revealed that the patients could be classified into five clusters. Cluster 1 (n=27) contained all patients with Group D. Cluster 2 (n=11) comprised all control patients. Cluster 3 (n=4) included mixed subtypes: one with Group A and three with Group D. Cluster 4 (n=7) and Cluster 5 (n=17) contained all patients with Groups A and C, respectively. Furthermore, the principal component analysis revealed that the subtypes had different characteristics. CONCLUSION: CRS subtypes based on JESREC score and mucosal eosinophil count showed different inflammatory patterns, and unsupervised statistical analyses supported the classification that can predict endotypes. From these results, we concluded that the classification based on JESREC score and mucosal eosinophil count was useful for predicting CRS endotypes.

Prognostic value of C-reactive protein/albumin ratio for patients with hypopharyngeal and laryngeal cancer undergoing invasive surgery involving laryngectomy.

BACKGROUND: The C-reactive protein/albumin (CRP/Alb) ratio has been recently established as a prognostic indicator in various cancer types. However, few reports regarding the prognostic value of the CRP/Alb ratio in head and neck cancer exist. This study aimed to investigate the significance of the CRP/Alb ratio in clinical outcomes after invasive surgery involving laryngectomy for hypopharyngeal and laryngeal cancer. METHODS: We evaluated 56 patients who underwent total laryngectomy or total pharyngolaryngectomy between 2003 and 2012. Univariate and multivariate analyses were retrospectively performed to examine the prognostic value of the CRP/Alb ratio in these patients. RESULTS: The optimal cutoff value of the CRP/Alb ratio was 0.32. Multivariate analysis showed that the CRP/Alb ratio was a significant and independent predictor of poor overall and disease-free survival. CONCLUSION: The CRP/Alb ratio may be a novel and useful indicator for predicting postoperative outcomes in patients with hypopharyngeal and laryngeal cancer.

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps.

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.

The role of ADAM-like decysin 1 in non-eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is classified into two subtypes: eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP). Although the inflammatory patterns of ECRSwNP have been elucidated, NECRSwNP is poorly understood. AIMS/OBJECTIVES: The metalloproteinase ADAM-like decysin 1 (ADAMDEC1) has been reported to play a role in the early stages of the inflammatory response. We investigated the role of ADAMDEC1 in the pathogenesis of CRSwNP. MATERIAL AND METHODS: We compared ADAMDEC1 expression in nasal polyp tissue from CRS patients using immunohistochemistry and RT-qPCR. Macrophages were cultured and ADAMDEC1 expression was determined at baseline and after exposure to lipopolysaccharide (LPS). RESULTS: ADAMDEC1 was virtually undetectable in tissues from control patients but was highly expressed in the NECRSwNP group compared with the ECRSwNP group. In nasal polyp tissues, ADAMDEC1 was expressed by CD68-positive cells, with a positive correlation between ADAMDEC1-positive and CD68-positive cells, and also between ADAMDEC1 and CD68 mRNA levels. Furthermore, stimulation of monocyte-derived macrophages with LPS induced ADAMDEC1 expression. CONCLUSIONS AND SIGNIFICANCE: This study demonstrates that ADAMDEC1 is involved in the pathogenesis of NECRSwNP, and also bacterial endotoxin signalling in macrophages; however, the underlying mechanism remains to be elucidated.