Predictive significance of the blood eosinophilia for chronic sinusitis with nasal polyp recurrence: A systematic review and meta-analysis.

Chronic sinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition characterized by recurring nasal polyps, often necessitating repeated interventions. Blood eosinophilia has emerged as a potential biomarker for predicting disease recurrence. The present study aims to assess the predictive significance of blood eosinophilia for the recurrence of nasal polyps. To accomplish this objective, we employed the appropriate search keywords to explore international databases such as Web of Science, PubMed, Embase, and Scopus. Through this process, we extracted scholarly articles that assessed the prognostic value of blood eosinophilia in the recurrence of nasal polyps. The statistical software STATA (version 15) was employed, along with random and fixed-effects models, to appraise the compiled data. Nine articles met inclusion criteria, with a total sample size of 1279 individuals (569 recurrent polyp individuals and 710 non-recurrent polyp individuals). Cumulative Odds ratio analysis revealed that CRSwNP is associated with high blood eosinophile percentage compared to the non-CRSwNP group (p=0.01, OR=1.26, 95%Cl (1.15,1.36). The cut-off value of blood eosinophil percentage (>0.78) had relatively good, and statistically significant predictive potential. No significant publication bias was observed for the included studies. Our findings indicate that the utilization of blood eosinophils holds significant predictive value and can serve as a valuable tool for detecting recurrence in patients with CRSwNP. Based on the outcomes of our comprehensive analysis, we propose a threshold of >0.78 as a reliable indicator for assessing the probability of recurrence in CRSwNP patients.

Blood eosinophilia and a higher ethmoid sinus/maxillary sinus score ratio predict new-onset asthma in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUD: Presently, the impact of Chronic rhinosinusitis with nasal polyps (CRSwNP) on asthma onset is unknown. AIMS: To evaluate the role of CRSwNP in asthma onset. MATERIALS AND METHODS: A total of 3107 CRSwNP patients were retrospectively screened from 1 January 2018, to 31 May 2021; 624 patients were enrolled. Clinical data regarding nasal symptoms, Lund-Mackay scores, blood eosinophil percentage, and onset of asthma were analyzed. Patients were divided into different groups according to past history of nasal polyps, Lund-Mackay score, and the extent of blood eosinophilia. Asthma-free rates between these subgroups were analyzed by Kaplan-Meier curves and Cox regression models. RESULTS: The prevalence of asthma was 10.90% in patients with CRSwNP, and new-onset asthma occurred in 3.14% of these patients. Higher Lund-Mackay scores for ethmoid sinus and maxillary sinus (E/M) and blood eosinophil percentages were two independent risk factors for new-onset asthma, with hazard ratios of 1.267 (95%CI, 1.155-1.390) and 1.224 (95%CI, 1.054-1.422), respectively. CRSwNP patients with an E/M ratio > 2.33 or a blood Eos percentage > 5.5% were at risk for asthma onset. CONCLUSIONS AND SIGNIFICANCE: Blood eosinophilia and a higher E/M score ratio were associated with new-onset asthma in patients with CRSwNP.

Serum Aspergillus fumigatus-Specific IgG as a Complementary Biomarker in Differentiating Endotypes of Chronic Rhinosinusitis: A Study on Its Role and Diagnostic Efficacy in Type 2 Inflammation.

BACKGROUND: Aspergillus is one of the most common pathogens causing fungal allergy in the respiratory tract. Serum Aspergillus fumigatus-specific immunoglobulin G (Af-sIgG) levels have been used as a biomarker for the diagnosis and treatment response monitoring in airway allergic diseases such as allergic bronchopulmonary aspergillosis and allergic fungal rhinosinusitis. However, its role in common primary chronic rhinosinusitis (CRS) was unclear. OBJECTIVE: This study aims to evaluate whether serum Af-sIgG level could serve as a biomarker for the disease presentation of primary CRS. METHODS: We obtained serum Af-sIgG levels from patients diagnosed as bilateral primary CRS refractory to medical treatment and evaluated the correlations between serum Af-sIgG levels and disease severity in patients with type 2 (T2) and non-T2 CRS. RESULTS: Patients with T2 CRS exhibited significantly higher serum Af-sIgG levels than non-T2 CRS patients. The cut-off value of serum Af-sIgG in T2 CRS was 20.9 mg/L, with an odds ratio of 3.8 (95% CI 1.17-12.20, P = .026). Furthermore, serum Af-sIgG levels were positively correlated with symptom scores evaluated by the Sino-Nasal Outcome Test-22 (SNOT-22) scores in T2 patients (P = .009). While stratified by SNOT-22 total scores, patients with severe disease had higher serum Af-sIgG levels only in T2 CRS (P = .034). In individual domains of SNOT-22 analysis, serum Af-sIgG levels showed a significant correlation with "ear/facial" symptom scores in the T2 group (P < .001). CONCLUSIONS: Serum Af-sIgG levels may serve as a supplementary objective biomarker that correlates with identification and subjective measurements of T2 CRS, and may be associated with symptoms arising from Eustachian tube dysfunction.

The value of biomarkers in the therapy of CRSwNP with biologicals-a long-term follow-up of dupilumab therapy.

PURPOSE: Since its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12 months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings. METHODS: The follow-up was performed with 104 patients retrospectively up to 22 months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed. RESULTS: There was substantially improvement in all clinical parameters up to 1 year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5 billion/L) had a trend of better SNOT-22 development after 1 year (- 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events. CONCLUSION: Dupilumab has considerably reduced symptoms and disease severity even beyond 1 year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.

Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Evaluation of Serum Levels of Vitamin D3 and IgE in Patients with Chronic and Allergic Sinusitis: A Cross-sectional Study.

BACKGROUND: Chronic rhinosinusitis is known as a common problem with inflammatory and allergic causes. Several factors are associated with developing chronic rhinosinusitis, including immunoglobulin E (IgE) production and vitamin D deficiency. OBJECTIVE: In this study, we investigated the role of IgE and Vitamin D deficiency and differences between patients with chronic, allergic sinusitis and controls. METHODS: A total of 90 subjects were included in 3 groups (n=30) in this cross-sectional, correlational descriptive study. The subjects were divided into three groups, including control (healthy subjects), chronic sinusitis patients, and allergy patients. A checklist was used to collect the necessary data, including age, gender, and body mass index (BMI). To evaluate serum levels of vitamin D3 and IgE, ELISA kits were used. RESULTS: The mean vitamin D was 22 g/ml. Fifty-four participants (60%) out of all included people had insufficient vitamin D, 13% had a deficiency, and the high deficiency and insufficiency were in the group of allergic sinusitis. Our results indicated that gender (female) was significantly associated with vitamin D deficiency (p =0.01). Thirty-nine participants (43.3%) out of all studied subjects had high IgE, and the highest level of abnormality of IgE was in the allergic sinusitis group. Furthermore, it was found that gender and IgE were not significantly related. However, IgE was significantly associated with vitamin D deficiency in the allergic sinusitis group. CONCLUSION: Our findings highlighted that most of the patients with chronic and allergic sinusitis had insufficient vitamin D. A possible association was also found between low vitamin D and IgE levels and the prevalence of allergic sinusitis. This study showed that patients with allergic sinusitis may be more vulnerable to lower serum levels of vitamin D. Therefore, vitamin D supplementation as an adjunctive therapy may be considered in these patients.

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

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms. METHODS: A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed. RESULTS: In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-ß, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-ß1 and CCL-24 production, contributing to CRSwNP recurrence. CONCLUSIONS: Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.

Predictive Values of Serum IL-33 and sST2 in Endotypes and Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence. Methods: The present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Results: The levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability. Conclusion: Our results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.

Circulating BAFF as novel biomarker in distinguishing chronic rhinosinusitis with nasal polyps endotypes and predicting postoperative recurrence.

BACKGROUND: B cell-activating factor (BAFF) is a proinflammatory cytokine involved in inflammatory and allergic diseases, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aims to explore the predictive value of circulating BAFF in CRSwNP endotypes and postoperative recurrence. METHODS: We recruited 120 CRSwNP patients, including 68 non-eosinophilic CRSwNP (neCRSwNP) patients, 52 eosinophilic CRSwNP (CRSwNP) patients, and 60 healthy controls (HCs). Circulating BAFF levels of all participants were measured by enzyme-linked immunosorbent assay (ELISA), and receiver-operating characteristic (ROC) and logistic regression analyses were applied to assess the predictive ability of BAFF levels in distinguishing CRSwNP endotypes. All CRSwNP patients were followed for more than 3 years, and the predictive value of circulating BAFF for postoperative recurrence was evaluated. RESULTS: Serum BAFF levels were elevated in CRSwNP patients compared with the HCs (P < 0.01) and significantly higher in eCRSwNP patients. The increased serum BAFF concentrations positively correlated with blood eosinophil counts and percentages, tissue eosinophil counts, and serum total IgE (P < 0.05). The ROC curve showed that serum BAFF exhibited strong discriminative ability for eCRSwNP. Finally, 99 CRSwNP patients completed the follow-up schedule, 65 patients were classified into non-recurrence group and the other 34 patients were categorized into recurrence group. Serum BAFF levels were significantly higher in recurrence group than non-recurrence group (P < 0.001), and the ROC curve suggested a high predictive value of serum BAFF in predicting postoperative recurrence. Moreover, logistic regression and Kaplan-Meier curves showed that serum BAFF was an independent risk factor for postoperative recurrence (P < 0.05). CONCLUSION: Our data suggested that serum BAFF levels were upregulated in CRSwNP patients and correlated with mucosal eosinophil infiltration severity. Serum BAFF seemed to be a novel biomarker for preoperatively distinguishing CRSwNP endotypes and predicting postoperative recurrence.

Dysregulated Maresin Concentrations in Plasma and Nasal Secretions From Patients With Chronic Rhinosinusitis.

The mechanisms that lead to disease onset and propagation in patients with chronic rhinosinusitis (CRS) are not fully elucidated. Maresins (MaR) are a family of essential fatty acid-derived lipid mediators that play a central role in the regulation of inflammation with several studies demonstrating that these mediators display protective activities in airway inflammation. Therefore, in the present studies we evaluated whether concentrations of these mediators were altered in both peripheral blood and nasal secretions from CRS patients. Herein, we focused on patients with CRS that also develop nasal polyps (CRSwNP), given that therapeutic options for the treatment of these patients are limited. Thereby, insights into disease mechanisms in these patients may help design more effective treatments. For this purpose, we compared maresin concentrations from CRSwNP patients with those found in healthy volunteers or patients with an upper respiratory tract infection (URTI), as a self-resolving inflammatory condition. Using liquid chromatography tandem mass spectrometry, we found that MaR concentrations were significantly decreased in plasma from patients with CRSwNP when compared to healthy volunteers. MaR concentrations were observed to be significantly upregulated in nasal secretions from patients with CRSwNP when compared with both healthy volunteers and URTI subjects. Concentration of these mediators in both plasma and nasal secretions from CRSwNP patients were positively correlated with quality-of-life scores in these patients. Assessment of the concentrations of other pro-resolving and pro-inflammatory lipid mediators (LM) demonstrated that there was a general shift in LM levels in both plasma and nasal secretions from CRSwNP when compared with healthy volunteers and URTI subjects. Of note, incubation of peripheral blood cells from CRSwNP patients with MaR1 downregulated the expression of activation markers on peripheral blood phagocytes, including CD41 and CD62P, markers of platelet-leukocyte heterotypic aggregates. Together these findings demonstrate that both local and systemic LM concentrations, in particularly those of the MaR family, become altered in patients with CRSwNP. They also suggest that therapeutics designed around MaR1 may be useful in regulating the activation of phagocytes in patients with CRSwNP thereby potentially also limiting the local inflammatory response in these patients.

The role of serum macrophage migration inhibitory factor in preoperative prediction of chronic rhinosinusitis with nasal polyps endotypes.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease and can be categorized into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). Exploring effective biomarkers to distinguish endotypes is important for personalized therapies. The present study aims to evaluate the predictive value of serum MIF in CRSwNP endotypes. METHODS: One hundred and twenty CRSwNP patients, including 51 eCRSwNP and 69 neCRSwNP, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients and 40 healthy controls (HC) were enrolled. Serum MIF levels were determined by enzyme-linked immunosorbent assay (ELISA). The patients' clinical variables were analyzed for correlations with serum MIF. Receiver operating characteristic (ROC) curve and multivariate analysis were utilized to assess the predictive value of serum MIF in CRSwNP endotypes. RESULTS: The serum MIF levels were significantly higher in CRSwNP group than CRSsNP group and HC group (P < 0.001), and the serum MIF levels were increased in eCRSwNP compared to neCRSwNP group (P = 0.006). Elevated serum MIF levels were significantly correlated with blood eosinophil (B-EOS) count (r = 0.411, P < 0.001), B-EOS percentage (r = 0.377, P < 0.001), visual analog scale score (r = 0.204, P = 0.025), tissue eosinophil (T-EOS) count (r = 0.705, P < 0.001) and T-EOS percentage (r = 0.671, P < 0.001) in CRSwNP patients. ROC curve demonstrated that serum MIF exhibited good preoperative prediction in CRSwNP endotypes (area under the curve = 0.925, P < 0.001). Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotypes. CONCLUSIONS: This was the first study identifying serum MIF as a possible specific biomarker for preoperatively distinguishing CRSwNP endotypes. Furthermore, the serum MIF levels were found to be closely associated with the degree of mucosal eosinophil infiltration.

Comparison of Blood and Tissue Eosinophil Count and Blood IgE in Patients with Chronic Sinusitis and Nasal Polyps.

BACKGROUND: The inflammatory mucosa of the sinus cavities is called sinusitis and is divided into various types based on its appearance and sign. Chronic rhinosinusitis is an inflammatory-infectious disease that involves the frontal, sphenoid, ethmoid, and maxillary sinuses. Chronic sinusitis is a multifactorial disease and the range of causes varies from environmental factors to genetic factors. The purpose of this study was to compare blood and tissue eosinophils and serum IgE levels in patients with chronic sinusitis with nasal polyp in Vali-e-Asr hospital in 1397. METHODS: In this descriptive-analytical study, the population under study included those with chronic sinusitis referred to Birjand Valiasr Hospital in 1397.3 cc of blood samples were taken 1 day before surgery to evaluate eosinophil counts and serum IgE levels. Also, samples taken from patients during surgery were counted, and then, 100 cells were counted, and eosinophil counts and percentages were calculated. The data were entered into the SPSS software after data collection. RESULTS: This study was performed on 70 patients with chronic rhinosinusitis which included 43 men (61.4%) and 27 women (38.6%) with mean age of 39.11 ± 13 13.72 years. There was no significant difference between sex of patients and mean serum IgE level (P < 0.05). The mean percentage of eosinophils in blood samples and tissues of patients with chronic sinusitis was significantly increased with the increase in CT scan (P < 0.05). CONCLUSIONS: Tissue or blood eosinophilia was not observed in patients with chronic rhinosinusitis. Also, the mean eosinophil percentage of blood and tissue increased significantly in patients with increased scanning computed tomography (P < 0.05).

Peripheral blood eosinophil levels in chronic rhinosinusitis and its predictive value in eosinophilic chronic rhinosinusitis.

BACKGROUND: The prevalence of eosinophilic CRSwNP in China has increased significantly over the last 20 years, noninvasive methods that could assist in diagnosis are urgently needed. AIMS: The aim of this study is to explore the clinical significance of peripheral blood eosinophil in diagnosing ECRS. MATERIALS AND METHODS: We conducted a prospective study of 221 patients diagnosed with CRS. Lund-Mackay score, peripheral blood eosinophil absolute count, peripheral blood eosinophil percentage were detection to compare the clinical features with ECRS and non-ECRS. ROC curve was performed to assess the efficiency of clinical index to predict ECRS. RESULTS: The ECRS group of patients had significantly higher scores compared with those of the non-ECRS group. Different extent and severity of mucosal thickening on total Lund-Mackay scores, anterior ethmoidal, posterior ethmoidal and ostiomeatal complex have confirmed different blood eosinophil levels in CRS patients. The combination of peripheral blood eosinophil percentage and posterior ethmoidal score to predict ECRS was 0.807. CONCLUSIONS AND SIGNIFICANCE: The increase in peripheral blood eosinophil percent indicates the deterioration the inflammation of chronic rhinosinusitis and the level of posterior ethmoidal score and peripheral blood eosinophil percentage have a positive predictive value regarding ECRS identification.

Type 2 Inflammatory Shift in Chronic Rhinosinusitis During 2007-2018 in Belgium.

OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS) is a heterogenic disease with different inflammatory patterns depending on the presence (CRSwNP) or absence (CRSsNP) of polyps and geographical location. A shift toward type 2 endotype has been seen in Asia. We aim to investigate whether there has been type 2 shift in Belgium and to further endotype CRS based on clinical markers. STUDY DESIGN: Prospective descriptive study. METHODS: Four hundred and thirty eight patients with CRS undergoing sinus surgery at Ghent University Hospital between 2007 and 2018 were included and stratified based on phenotype, comorbidities, inflammatory markers in tissue, and two different time points of surgery. Tissue samples from surgery were analyzed for type 2 markers. In a subgroup of CRSwNP blood eosinophils (EBC) was available. RESULTS: There was an increase in type 2 inflammatory markers in the latter group versus the earlier, in non-asthmatic, non-allergic CRS patients regardless of phenotype. The proportion of IL-5+ patients was elevated in the latter group in CRSwNP. Inflammatory markers and comorbidities differ between IL-5+ CRSsNP and CRSwNP subjects, no difference was seen in IL-5- CRS. EBC can together with information on comorbidities help identify type 2 CRSwNP in a clinical setting. CONCLUSION: There is a shift toward type 2 inflammation within the CRS population over recent 8 years also in Belgium. This shift implies that we expect to see more cases of severe and difficult to treat CRS in the future. Polyp formation is not directly linked to the presence or concentrations of type 2 inflammatory markers. Clinical parameters and EBC > 300 cells/µL can be used to identify type 2 CRSwNP. LEVEL OF EVIDENCE: 3. Laryngoscope, 131:E1408-E1414, 2021.

Elevated Urine Leukotriene E4 Is Associated With Worse Objective Markers in Nasal Polyposis Patients.

OBJECTIVES: Urine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS: A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS: Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P < .001), aspirin sensitivity (P < .001), worse Lund-Mackay CT scores (P = .002) and other objective markers of disease severity including serum IgE (P = .05), presenting blood eosinophil level (P < .001), and the highest recorded eosinophil level (P < .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (R range 0.31-0.52) than the aspirin tolerant CRSwNP group (R range -0.30-0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores). CONCLUSION: Elevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient-reported symptom measures. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:961-966, 2021.

Systemic Immune Profile in Patients With CRSwNP.

The immune pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains obscure. Our aim was to compare humoral immunity and white blood cell counts in patients with CRSwNP and controls. A prospective case-control study was carried out in 37 patients with CRSwNP and 34 controls without CRS. Clinical data were gathered through a systematic interview. Computed tomography scan, skin prick test, spirometry, and immunological parameters (leukocyte differential count, immunoglobulin classes, and immunoglobulin [Ig] G subclasses) in serum specimens were obtained. Statistical analysis was performed using SPSS v.23. The prevalence of chronic lower respiratory diseases was greater in the CRSwNP group (P < .001), but atopic disease had no significant difference. A significantly higher eosinophil (P < .001) and basophil relative count (P = .022) and a lower relative neutrophil count (P = .013) were found among CRSwNP group. Patients with CRSwNP had higher IgG1 (P = .022), but lower IgG2 (P = .014) and IgG3 (P = .018) serum levels compared to controls; IgG4, total IgG, IgA, IgM, and IgE serum levels did not differ between groups, as well as the prevalence of immunoglobulin classes or IgG subclasses deficiency. The variation observed in peripheral relative leukocyte count and the systemic IgG1 subclass shift are similar to what is known to happen in nasal polyp tissue. A unique systemic immune profile seems to be present in patients with CRSwNP.

Anti-phage serum antibody responses and the outcome of phage therapy.

We examined the appearance of serum anti-phage antibodies in 25 patients with chronic sinusitis treated with phage therapy (PT). Approximately 30% of patients with weak antibody responses responded positively to PT, which was similar to the results of treatment achieved in a group of patients with high antibody production. In addition, there was no correlation between antibody level and the outcome of PT. These data, derived from a homogenous group of patients, confirm our earlier findings suggesting that the prognostic significance of serum anti-phage antibodies for the outcome of PT should be determined by relevant clinical trials.