Nasal Polyps Research Articles

Chronic rhinosinusitis with nasal polyps: predictors of recurrence 5 years after surgery

Backgrounds Chronic rhinosinusitis with nasal polyps (CRSwNP) is a medical condition characterized by persistent inflammation of the nasal mucosa and sinuses, accompanied by the presence of nasal polyps. When medical treatments prove ineffective, endoscopic sinus surgery (ESS) is recommended, yielding variable outcomes and recurrence rates ranging from 5% to 60%. Aims/Objectives The primary objectives of this study were to evaluate the outcomes of ESS and to identify independent predictors of recurrence and revision surgery. Material and Methods Retrospective cross-sectional study, focusing on patients diagnosed with CRSwNP who underwent ESS with a minimum follow-up period of 60 months. Various variables were collected. Multivariate and regression analyses were employed to assess the predictors associated with both recurrence and revision surgery. Results The study analyzed 130 patients. The 5-year recurrence rate was 35.4%, and 17.7% of patients required revision surgery. These variables included asthma (p < 0.001), frontal sinus involvement (p < 0.001), Lund–Mackay score (p < 0.001), Endoscopic Nasal Polyps Score (p < 0.001), and eosinophilia in peripheral blood (p < 0.001). All the variables mentioned above were identified as predictors of recurrence and revision surgery. Conclusions and Significance Asthma, frontal sinus involvement, increased eosinophilia in peripheral blood, and a higher score on the LM system and NPS are poor prognostic factors in CRSwNP.

Hypoxia-reducedYAP phosphorylation enhances expression of Mucin5AC in nasal epithelial cells of chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an upper respiratory disease characterized by persistent inflammation of the nasal mucosa. However, the mechanism of abnormal Mucin5AC expression by CRSwNP epithelial cells is not fully understood. We investigated the potential role of yes-associated protein (YAP) underlying the mechanism of excessive epithelial Mucin5AC expression in CRSwNP in a hypoxic model. Tissue biopsies of CRSwNP (n = 60), chronic rhinosinusitis without nasal polyps (CRSsNP) (n = 9) and healthy controls (n = 30) were investigated together with a well-established hypoxic model of primary human nasal epithelial cells (hNECs). The expression levels of hypoxia inducible factor (HIF)-1α and YAP, and the effect of the signaling axis on mucus secretion in hNECs were analyzed. We observed a significant elevated expression levels of YAP in patients with CRSwNP and CRSsNP compared to controls. In addition, HIF-1α expression of CRSwNP was higher than that of control group. Under hypoxic conditions, HIF-1α was found to regulate the upregulation of YAP in hNECs. Further investigations revealed that HIF-1α facilitated the activation and nuclear localization of active-YAP by reducing the phosphorylation of YAP. This mechanism appeared to be linked to HIF-1α-mediated inhibition of LATS 1 phosphorylation and subsequent YAP degradation. HIF-1α was shown to promote the expression of P63 and the levels of Mucin5AC in hNECs by enhancing YAP activation. Our findings indicated that hypoxia enhances YAP activation by decreasing p-LATS 1 and YAP phosphorylation. This has the potential to impact on the proliferation of basal cells and the differentiation of goblet cells in CRSwNP, ultimately leading to a pathological condition characterized by excessive Mucin5AC expression.

Real-world predictors of dupilumab prescription in patients with chronic rhinosinusitis with nasal polyps.

Despite increasing dupilumab use for chronic rhinosinusitis with nasal polyps (CRSwNP), little is known about the factors influencing its use in real-world practice. We aimed to identify factors that may predict dupilumab prescription in CRSwNP patients who have undergone endoscopic sinus surgery (ESS). A single-institution, retrospective cohort study of patients who underwent ESS for CRSwNP between 2015 and 2023 was conducted. Demographics, comorbidities, 22-item sinonasal outcome test (SNOT-22) scores, and dupilumab prescription date were extracted from patient records. Intraoperative nasal mucus cytokine levels were measured using a multiplex bead assay. Univariate logistic regression analysis was performed to identify factors associated with dupilumab prescription, and multivariate logistic regression was used to adjust for surgery date. A total of 299 CRSwNP patients were included, including seventy (23.4%) who were prescribed dupilumab postoperatively. Patients were more likely to be prescribed dupilumab if they had asthma (odds ratio [OR] 2.304), aspirin-exacerbated respiratory disease (AERD, OR 3.375), elevated tissue eosinophils (OR 1.005), and higher 3-month postoperative SNOT-22 scores (OR 1.027). Patients prescribed dupilumab also had greater odds of having elevated mucus interleukin (IL)-5 (OR 1.128) and IL-13 (OR 1.213). When adjusting for surgery date, associated factors included: asthma (OR 2.444), AERD (OR 3.750), allergic rhinitis (OR 1.833), higher tissue eosinophils (OR 1.005), elevated 3-month SNOT-22 scores (OR 1.028), and higher IL-5 (OR 1.123) and IL-13 (OR 1.202) levels. Asthma, AERD, allergic rhinitis, and elevated tissue eosinophil, IL-5, and IL-13 levels are predictive of dupilumab prescription in CRSwNP patients. These may serve as clinical and inflammatory biomarkers and can aid in counseling patients about expected disease trajectory.

The Effect of the Nasal Structure on the Olfactory Cleft Airflow: A Systematic Review.

Conductive olfactory losses mainly involve obstruction of the olfactory cleft (OC) and diminished OC airflow. This study investigated the association between abnormal nasal structure and OC airflow. A systematic search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis to identify studies on the effect of the nasal structure on the OC airflow and olfaction. A total of 11 studies were included. Nasal vestibule morphological variabilities directly impact the transport of molecules in odorant-laden air to the OC. A greater airflow vortex and a narrower vestibule region intensified the airflow vortex toward the olfactory region. Middle turbinectomy significantly increased the average flux to the OC. The location of the major airflow and airflow velocity maxima shifted towards the OC in patients with septal deviation. The airflow has been redirected into the upper part of the nasal airway in patients with inferior turbinate hypertrophy. For patients with unilateral cleft lip, unilateral nasal airflow on the cleft side has a lower rate and flow. The mean velocity in the posterior OC correlated well with olfaction compared to that in the anterior OC. The nasal polyps (NP) within the middle meatus increased the olfactory airflow but did not enhance the olfaction. NP in the olfactory region or anterior to the olfactory region significantly decreased the olfactory airflow and olfaction. Furthermore, obstruction of the OC did not change the nasal patency. When the OC shape presented with a stenotic slit or lumen structure among patients with conductive olfactory dysfunction without NP, the inspiratory velocity and flow rate within OC were significantly lower than in the healthy control group. Various nasal structural factors affect patterns of OC airflow and olfaction. Identifying the related airflow-limiting structures may promote the comprehensive evaluation of conductive olfactory losses in patients with olfactory dysfunction.

Enlarged Frontal Sinusotomy and Chronic Rhinosinusitis with Nasal Polyps: An Effective Strategy to Control the Disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with a strong impact on the quality of life (QoL) which treatment is based on local intranasal corticosteroids (ICS) and iterative courses of systemic corticosteroids (SCS) in case of relapse. When medical treatment is insufficient, surgery is indicated. We investigated the impact of enlarged frontal sinusotomies (EFS: Draf IIb or Draf III) on QoL and annual SCS consumption of patients with severe uncontrolled CRSwNP. This is a retrospective cohort study of 38 patients, who underwent EFS at Lariboisière University Hospital (CHU) in Paris, France, between 2006 and 2020. All patients were asked to complete SNOT-22 questionnaires concerning pre- and post-op status. Patients' medical and sinus surgery history as well as the number of SCS treatments per year before and after surgery were also collected. Of the 38 patients, 33 underwent a Draf III procedure and 5 a Draf IIb, with no major complications reported. Surgery resulted in a significant improvement in SNOT-22 scores (-32.7 ± 19.3, P < 0.001), with 19/22 items improving significantly. The number of annual SCS treatments decreased significantly from a mean of 4.8 ± 4.3 to 0.6 ± 1.2 (P < 0.001). During the follow-up (mean 88 months), 95% of our patients showed a satisfying disease control and only 2 patients required revision surgery for poor disease control 5 years after EFS. EFS appears to be an effective and durable therapeutic option to improve the QoL of patients with severe CRSwNP and to reduce their SCS consumption without major complications.

Topical Therapies for Management of Olfactory Dysfunction in Chronic Rhinosinusitis with Nasal Polyps: Steroid-Eluting Stents.

Steroid-eluting stent implantation after endoscopic sinus surgery (ESS) effectively alleviates postoperative symptoms and polyp recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the efficacy of steroid-eluting stents for the treatment of olfactory dysfunction in CRSwNP and the influencing factors therein have not been studied. Fifty-nine patients with CRSwNP with olfactory dysfunction from Peking University Third Hospital who were hospitalized for ESS were recruited and randomly divided into a stent group (n = 30) and a control group (n = 29), and were assessed for symptom scores, olfactory function, endoscopic findings, and type 2 inflammatory mediators (IL-4, IL-5, IL-13, IL-33, eotaxin-3, periostin) expression. Postoperative olfactory Visual Analogue Scale (VAS) scores, T&T olfactometer scores, SNOT-22 scores, and Lund-Kennedy (LK) scores were reduced in patients with CRSwNP (P < .01). Postoperative olfactory VAS scores, T&T olfactometer scores, SNOT-22 scores, and LK scores, IL-5, IL-13, and periostin were significantly lower in the stent group than in the control group (P < .05). Correlation analysis was performed and found that the postoperative olfactory VAS scores were strongly correlated with IL-5 and IL-13 (r = .496, P < .001 and r = .289, P = .026), and the postoperative T&T olfactometer scores were strongly correlated with IL-5 and IL-13 (r = .553, P < .001 and r = .398, P = .002). Steroid-eluting stent implantation after ESS is an effective treatment for olfactory deficits in patients with CRSwNP and may be related to the stent's more effective reduction of local type 2 inflammatory mediators in the nasal cavity.

Assessing the predictive potential of ADAM8 for disease control in chronic rhinosinusitis with nasal polyps

BackgroundA disintegrin and metalloproteinase 8 (ADAM8) has been implicated in eosinophilic inflammation; however, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains to be elucidated. This study aimed to investigate the predictive significance of ADAM8 levels in nasal secretions for the endotypes and disease control status of CRSwNP.MethodsA cohort comprising 120 CRSwNP patients and 45 healthy controls (HCs) was assembled, delineating 53 non-eosinophilic CRSwNP (neCRSwNP) and 67 eosinophilic CRSwNP (eCRSwNP) patients. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were utilized to measure ADAM8 levels in nasal mucosal tissues and secretions from all participants. The receiver operating characteristic (ROC) curves and Pearson correlation analysis were employed to assess the predictive capability of ADAM8 levels in predictiving CRSwNP endotypes and disease control status.ResultsADAM8 levels in nasal secretions were elevated in CRSwNP patients compared to HCs, with a more pronounced increase observed in eCRSwNP patients. Elevated ADAM8 concentrations in nasal secretions were positively correlated with peripheral blood eosinophil counts and percentages, tissue eosinophil counts, serum total IgE, Lund–Mackay scores, and Lund-Kennedy scores. Ultimately, 103 CRSwNP patients completed the follow-up protocol, with 72 classified as the controlled group and 31 as the uncontrolled group. Uncontrolled CRSwNP patients exhibited significantly higher ADAM8 levels in nasal secretions compared to the controlled group. The ROC curves indicated that ADAM8 in nasal secretions exhibits robust discriminatory capacity for eCRSwNP and postoperative disease control status.ConclusionADAM8 in nasal secretions emerges as a potential novel biomarker for the prognostication of CRSwNP endotypes and the postoperative disease control status.

Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps.

Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes. Patients (aged 12-80years) with severe, uncontrolled asthma were randomized to tezepelumab 210mg or placebo subcutaneously every 4weeks for 52weeks. SNOT-22 total, domain, and item scores were assessed in patients with a history of CRSwNP. Annualized asthma exacerbation rate (primary efficacy outcome), pre-bronchodilator forced expiratory volume in 1s, and Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients 12years and older, and Asthma Symptom Diary scores were also assessed in patients with and without a history of CRSwNP. Of 1059 patients with severe asthma, 165 (15.6%) had a history of CRSwNP. Tezepelumab treatment resulted in sustained improvements versus placebo in SNOT-22 total score throughout the 52-week study period [least-squares mean difference (95% confidence interval) - 11.08 (- 17.80, - 4.35)]. Tezepelumab improved all five SNOT-22 domain scores (sleep, nasal, function, ear/facial, and emotion) and the five SNOT-22 item scores of most clinical interest (decreased sense of smell/taste, nasal blockage, reduced productivity, waking up tired, and cough). Tezepelumab improved asthma-related clinical outcomes in patients with and without a history of CRSwNP. In patients with severe, uncontrolled asthma and a history of CRSwNP, tezepelumab improved rhinosinusitis symptoms across multiple domains, as well as asthma exacerbations, lung function, asthma control, and health-related quality of life. NCT03347279 ( https://classic. gov/ct2/show/NCT03347279 ).

Common Cold Coronavirus 229E Induces Higher Interferon Stimulating Gene Responses in Human Nasal Epithelial Cells from Patients with Chronic Rhinosinusitis with Polyposis.

Viral infections have long been implicated in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Given widespread exposure to the common cold coronavirus 229E (HCoV229E), we sought to investigate how HCoV-229E is cleared and stimulates interferon pathways in air-liquid interface (ALI) cultures from patients with CRSwNP. The objective of this study was to identify whether viral clearance and ISG expression is different in ALI cultures from donors with CRSwNP compared with controls. Plaque assays were used to quantify infectious virus released by infected air-liquid interface (ALI) cultures derived from patients with CRSwNP compared to patients without CRS (controls). Additionally, mock and induced levels of Interferon Stimulated Genes (ISGs) mRNA following HCoV-229E infection were quantified by RT-qPCR. Quantification of infectious virus by plaque assay reveals that CRSwNP ALI cultures were equally susceptible to HCoV-229E infection, and surprisingly viral titers dropped significantly faster than in the control ALI cultures. We further demonstrate that this accelerated viral clearance correlates with increased mRNA expression of at least 4 ISGs following viral infection in the CRSwNP ALIs compared to the control ALIs. This study paradoxically demonstrates that ALI cultures from patients with CRSwNP are more efficient at clearing the common cold HCoV-229E virus compared to controls. We also demonstrate significantly increased ISG mRNA expression following HCoV-229E infection in CRSwNP. These findings call for further investigation into the effect of unimpaired interferon signaling on the type 2 inflammatory environment in patients with CRSwNP.

Global Incidence and Prevalence of Chronic Rhinosinusitis: A Systematic Review.

Data on the global prevalence of chronic rhinosinusitis (CRS) is significantly varied and limited across countries and over time. Therefore, we aimed to conduct a comprehensive investigation into the global, regional, and national burden of CRS from the years 1980 to 2021, as well as identify those factors that influence levels of such burden. We conducted a systematic review and meta-analysis of general population-based observational studies focusing on CRS. We calculated pooled estimates of CRS prevalence and incidence with 95% confidence intervals (CIs). Subgroup analyses were conducted stratifying by sex, age cohorts, geographic regions, smoking status, obesity, and comorbid conditions. PubMed/MEDLINE, EMBASE, CINAHL, Google Scholar, and Cochrane databases. We included general population-based observational studies on CRS published from database inception through October 20, 2023. A total of 28 eligible studies, encompassing more than 237 million participants and 11,342,923 patients with CRS from 20 countries across four continents, were included in the analysis. Global pooled prevalence of CRS and CRS with nasal polyps (CRSwNP) was found to be 8.71% (95% CI, 6.69-11.33; number of studies, 20) and 0.65% (95% CI, 0.56-0.75; number of studies, 4), respectively. The prevalence of CRS was greater in Europe compared with North America, South America, and Asia; adults compared with children; smokers compared with never-smoker; those with obesity compared with normal weight; and those with comorbidities such as asthma, diabetes mellitus, eczema, and nasal septal deviation. Pooled prevalence of CRS increased from 1980 to 2020 (1980-2000: 4.72%; 95% CI, 2.12-10.49; 2014-2020: 19.40%; 95% CI, 12.12-31.07). Similar patterns were observed in CRS incidence. Our study provides valuable insights into CRS prevalence and incidence across diverse demographic and clinical factors, highlighting its increasing global burden. The reported prevalence of CRS varies internationally, and may be increasing over time. To enhance data quality and comparability, standardization of reporting methodologies is imperative. PROSPERO (registration no. CRD42024527805).

Comparison of histopathological diagnoses of ENT diseases in the COVID-19 pandemic with other periods

Abstract OBJECTIVE. It is aimed to reveal the frequency of histopathological diagnosis in ENT diseases during the COVID-19 period and whether it is different from diagnoses in other periods. MATERIAL AND METHODS. The files of 1442 patients diagnosed with pathological material in the ENT clinic between 2017 and 2022 were retrospectively scanned. Two groups were created: the 1st group of patients between 2017-2019 (non-COVID-19 period) (Group 1) and the 2nd group of patients between 2020-2022 (COVID-19 period) (Group 2). RESULTS. Pathological samples were sent from 1163 patients in Group 1 and from 279 patients in Group 2. Of 1442 patients, 815 were male and 627 were female, and the mean age was 25 (3-94 years). There was a statistically significant difference between the groups in terms of age (p=0.001). There was no significant difference in terms of gender (p=0.756). The most common histopathological diagnoses in both periods were chronic tonsillitis lymphoid hyperplasia (bilateral tonsillectomy + adenoidectomy) (19.5%), chronic inflammation lymphoid hyperplasia (adenoidectomy) (19.3%) and nasal polyp (19.2%). The incidence of malignant tumors was found to be 1.4% in Group 1 and 2.8% in Group 2. The incidence of benign tumors was found to be 7.6% in Group 1 and 12.8% in Group 2. In terms of frequency, the ratio of malignant and benign tumors was higher in Group 2. CONCLUSION. The number of patients with histopathological diagnoses decreased due to the decrease in hospitalizations during the COVID-19 period. Delayed diagnosis in malignant pathologies significantly worsens the prognosis. All these results show that new cancer diagnostic strategies are needed for epidemic diseases such as COVID-19.

Nasal dermoid sinus cyst with intracranial extension and atretic sinus tract in an adult patient

Nasal dermoid sinus cyst (NDSC) is a rare congenital lesion due to cephalic neural tube defect. It may also have been seen in other parts of the body. NDSC constitutes 1–3% of all dermoid cysts and 11–12% of those in the head and neck. A NDSC is located in the median line of the nasofrontal region from the glabella to the columella. The differential diagnosis based on location includes epidermal inclusion cyst, glioma, meningomyelocele, meningoencephalocele, teratoma, teratoid cyst, thyroglossal duct cyst, branchial cleft cyst, and benign lymphadenopathy. Intracranial extension causes serious complications such as meningitis, osteomyelitis, abscess formation, hydrocephalus, seizures, and personality changes. All patients with NDSC should be considered to have a potential intracranial extension and should, therefore, undergo pre-operative radiological evaluation. Herein, the authors report an unusual adult patient with NDSC with intracranial extension.

FERMT1 contributes to the epithelial-mesenchymal transition of chronic rhinosinusitis with nasal polyps via PI3K/Akt signaling

BackgroundEpithelial-mesenchymal transition (EMT) is a key process of chronic rhinosinusitis with nasal polyps (CRSwNP). The molecular mechanism of EMT in CRSwNP remains unknown. In this study, we aimed to investigate the role of FERMT1 during the EMT process in CRSwNP. MethodsWestern blotting, qRT-PCR, and immunohistochemistry (IHC) were performed to examine the expression of related proteins and mRNAs. The migration ability of human nasal epithelial cells (HNEpCs) was evaluated with wound scratch assay. RNA sequencing was performed to investigate the downstream genes of FERMT1. The CRSwNP mouse model was established to study the effect of FERMT1 in vivo. ResultsWe found that FERMT1 was increased in nasal polyp tissues and correlated with the symptom scores of CRSwNP patients. Knockdown of FERMT1 inhibited the EMT process and cell migration induced by TGF-β1 through the PI3K/Akt pathway, and Akt inhibitor partially blocked the EMT induced by FERMT1 overexpression. In the CRSwNP mouse model, FERMT1 knockdown reduced nasal polyp formation and reversed the EMT process. ConclusionsOur data indicate that knockdown of FERMT1 inhibits migration and EMT process of HNEpCs via PI3K/Akt signaling pathway, suggesting that FERMT1 may be a novel and potential therapeutic target for CRSwNP treatment.

Prostaglandin E Receptor 2 (EP2) Dysregulation in Allergic Fungal Rhinosinusitis Nasal Polyp Epithelium.

Allergic fungal rhinosinusitis (AFRS) is an eosinophilic subtype of chronic rhinosinusitis with nasal polyposis (CRSwNP). This study aimed to investigate the transcriptome of AFRS nasal polyp epithelium. Sinonasal epithelial cells were harvested from healthy nasal mucosa and polyp tissue collected from participants undergoing elective sinonasal surgery. Primary epithelial cells were subsequently grown in air/liquid interface and subjected to RNA-seq analysis, RT-qPCR, immunoblotting, and immunostaining. A total of 19 genes were differentially expressed between healthy and AFRS sample epithelium. The second top candidate gene, ranked by adjusted p-value, was prostaglandin E receptor 2 (PTGER2). The upregulation of PTGER2 was confirmed by RT-qPCR and immunoblot. The presence of the EP2 receptor, encoded by the PTGER2 gene, was confirmed by immunocytochemistry. PTGER2 is a potential novel therapeutic target for AFRS. EP2 dysregulation is associated with aspirin-exacerbated respiratory disease, potentially giving insight into common mechanisms of disease in severe CRSwNP. NA Laryngoscope, 2024.

Nasal Polyposis and Fitness to Fly

INTRODUCTION: When a pilot is referred for nasal polyposis, his/her flight fitness may be questionable. The objective of this retrospective study was to describe a case series of barotrauma in a pilot population exhibiting nasal polyposis and to discuss the decisions about their flight fitness. METHODS: There were 17 pilots with nasal polyposis who were referred to the Head and Neck Department of the National Pilot Expertise Center. The study was declarative on the occurrence of ear and sinus barotrauma during the last 5 yr. Nasofibroscopy was performed to determine the stage of the nasosinus polyposis. RESULTS: Out of 17 pilots, 1 did not obtain flight fitness clearance. Among the 16 who received fitness clearance to fly, 2 had restrictions on their flight fitness. Out of 17 patients, 8 had sinus barotrauma and 13 had middle ear barotrauma. A total of 21 cases of sinus barotrauma were reported, 17 involving the frontal sinus and 4 involving the maxillary sinus. Also reported were 48 cases of middle ear barotrauma. DISCUSSION: Flight fitness was based on the recurrence of barotrauma episodes, their severity, in-flight incapacitation due to hyperalgesic sinusitis or otitis, and the failure of medical and/or surgical treatments. In our series, nasal polyposis did not seem to be a risk factor for severe barotrauma. The results made it possible to determine a patient’s fitness to fly and any restrictions. The published studies on the resumption of flight for patients who have nasal polyposis and our experience suggest that nasal polyposis may allow a safe pursuit of aviation activity. Crambert A, Marchi Y, Pons Y, Podeur P, Allali L, Ballivet de Régloix S. Nasal polyposis and fitness to fly. Aerosp Med Hum Perform. 2024; 95(11):841–844.

Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NPs) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear. ObjectiveTo reveal the roles and heterogeneity of neutrophils in NP tissue by single cell RNA-Sequencing (scRNA-Seq) analysis. MethodsWe developed a novel microwell-based scRNA-Seq assay (BD Rhapsody platform) using granulocyte enriched samples from 5 control sinus tissues (CTs), 5 NP tissues and patient matched peripheral blood (PB) samples. This approach allowed for the examination of differential expression of genes in NP neutrophils by the Benjamini-Hochberg algorithm and predicted the overall function of NP neutrophils by pathway and gene ontology (GO) enrichment analyses. ResultsAfter all QC steps, we successfully detected neutrophils. We identified 333 down-regulated and 128 up-regulated genes in NP neutrophils (1,151 cells) compared to all PB neutrophils (13,591 cells) (>1.5-fold, q<0.05), and found commonly dysregulated genes in NP neutrophils compared to both all PB and CT neutrophils (3,136 cells). Commonly down-regulated genes in NP neutrophils were associated with the innate immune system, and up-regulated genes were associated with NF-κB signaling, cytokine activity and cellular response to oxygen-containing compounds. NP neutrophils displayed 4 clusters revealing potential heterogeneity of neutrophils in NP tissue. ConclusionsElevated neutrophils in NP tissue appear to exist in several subphenotypes that may play important pathogenic roles in CRSwNP.

The expression of MUC5AC in patients with rhinosinusitis: A systematic review and meta-analysis.

To understand the connection between Muc5AC expression and the likelihood of rhinosinusitis, with the goal of providing insights into its prospective use as a biomarker. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies up to November 2023 to conduct a literature review. After screening and quality assessment, eligible studies meeting the criteria were included. Muc5AC expression and rhinosinusitis association was analyzed by STATA 14.0. Including weighted mean difference and 95% confidence interval, were reported. The meta-analysis included 16 studies with 1448 rhinosinusitis patients. MUC5AC expression was significantly up-regulated in both chronic rhinosinusitis with nasal polyps (CRSwNP; WMD: 0.52; 95% CI: 0.41-0.63) and chronic rhinosinusitis without nasal polyps (CRSsNP; WMD: 0.42; 95% CI: 0.28-0.56) patients compared to controls. IHC positive area analysis corroborated these findings, with elevated MUC5AC levels in CRSwNP (WMD: 25.61; 95% CI: 22.41-28.81) and CRSsNP (WMD: 39.74; 95% CI: 25.6-53.88) patients. Subgroup analysis based on tissue type (nasal tissue fluid and sinus mucosa) consistently supported the overall results. Our meta-analysis robustly demonstrates a significant association between elevated MUC5AC expression and rhinosinusitis risk. This finding underscores the potential of MUC5AC as a molecular marker, providing valuable insights for future research and potential therapeutic interventions in rhinosinusitis management. CRD42024518932.

Quality of Life in Symptomatic Septal Perforation.

The aim of this study is to investigate the impact of septal perforation (SP) on quality of life (QoL). SP is compared to the general population and patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) using the Sino-Nasal Outcome Test 22 (SNOT-22). Prospective single-center study in a referral Rhinology Unit from January 2014 to March 2023. A total of 392 patients were included in three groups: controls (n = 141), CRSwNP (n = 118), and SP (n = 133). The mean score of the SNOT-22 was significantly higher in the CRSwNP group (42.4, SD = 24.4) and SP (46.5, SD = 22) compared to the control group (6.2, SD = 8.4). Scores by either items or domains were significantly higher in the CRSwNP and SP groups compared to the control group. There were no significant differences in the mean SNOT-22 between the CRSwNP and SP groups (p = 0.26; 95% CI -1.68-9.99). Domain-specific analysis of overall SNOT-22 scores revealed that patients with SP experienced higher levels of disturbances in sleep, function, and psychological domains (p ≤ 0.001). SP produces a negative impact on QoL similar to CRSwNP. Moreover, sleep, psychological, and function domains are significantly worse in SP. Etiology and area of SP influence nasal and emotion domain, though more studies on SP using SNOT-22 and specific questionnaires are needed. 3 Laryngoscope, 134:4480-4487, 2024.

The Association of Nasal and Blood Eosinophils with Serum IgE Level in Allergic Rhinitis and Asthma: A Case-Control Study.

Allergic rhinitis and asthma are two common respiratory diseases with allergic etiology in the world's population. Eosinophils and serum IgE levels have been known as inflammatory allergy markers for many years. This study aimed to evaluate the correlation of nasal and blood eosinophils with serum IgE levels in allergic rhinitis and asthma patients. This prospective study was done on patients (n = 78) diagnosed with asthma (n = 20), allergic rhinitis (n = 49), and chronic rhinosinusitis with nasal polyposis (CRSwNP) (n = 9) at our hospital in Ahvaz City, Iran. The age of participants in our study ranged from 3 to 73 years, and all of them were subjected to a complete blood count (CBC) test, nasal smear, and determination of serum IgE levels after their consent. There was no correlation between serum IgE level and nasal eosinophil count (p = 0.728) or between serum IgE level and blood eosinophil count (p = 0.657); however, a positive correlation was detected between blood and nasal eosinophil levels (p = 0.003). There is no significant relationship between serum IgE level and eosinophil count in the blood and nasal secretions. Serum IgE level and blood or nasal eosinophil count are both useful biomarkers for monitoring allergic rhinitis and asthma individually, but no diagnostic conclusion can be drawn from their correlation.

Anti-IgE therapy in chronic rhinosinusitis with nasal polyps

Anti-IgE therapy in chronic rhinosinusitis with nasal polyps