Chronic Rhinosinusitis Disease Severity Research Articles

The relationship between blood eosinophilia and disease severity in chronic rhinosinusitis with nasal polyps.

The relationship between blood eosinophilia and disease severity in chronic rhinosinusitis with nasal polyps.

S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis

Staphylococcus aureus mucosal biofilms are associated with recalcitrant chronic rhinosinusitis (CRS). However, S. aureus colonisation of sinus mucosa is frequent in the absence of mucosal inflammation. This questions the relevance of S. aureus biofilms in CRS etiopathogenesis. This study aimed to investigate whether strain-level variation in in vitro-grown S. aureus biofilm properties relates to CRS disease severity, in vitro toxicity, and immune B cell responses in sinonasal tissue from CRS patients and non-CRS controls. S. aureus clinical isolates, tissue samples, and matched clinical datasets were collected from CRS patients with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. B cell responses in tissue samples were characterised by FACS. S. aureus biofilms were established in vitro, followed by measuring their properties of metabolic activity, biomass, colony-forming units, and exoprotein production. S. aureus virulence was evaluated using whole-genome sequencing, mass spectrometry and application of S. aureus biofilm exoproteins to air-liquid interface cultures of primary human nasal epithelial cells (HNEC-ALI). In vitro S. aureus biofilm properties were correlated with increased CRS severity scores, infiltration of antibody-secreting cells and loss of regulatory B cells in tissue samples. Biofilm exoproteins from S. aureus with high biofilm metabolic activity had enriched virulence genes and proteins, and negatively affected the barrier function of HNEC-ALI cultures. These findings support the notion of strain-level variation in S. aureus biofilms to be critical in the pathophysiology of CRS.

Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor

Introduction: Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied.Methods: 30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6–16y). MRI were evaluated using the CRS-MRI score.Results: After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275–0.999).Conclusions: ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

Tissue Interleukin-33: A Novel Potential Regulator of Innate Immunity and Biomarker of Disease Severity in Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease of real interest for researchers due to its heterogenicity and complex pathophysiological mechanisms. Identification of the factors that ensure success after treatment represents one of the main challenges in CRSwNP research. No consensus in this direction has been reached so far. Biomarkers for poor outcomes have been noted, but nonetheless, their prognostic value has not been extensively investigated, and needs to be sought. We aimed to evaluate the correlation between potential prognostic predictors for recalcitrant disease in patients with CRSwNP. The study group consisted of CRSwNP patients who underwent surgical treatment and nasal polyp (NP) tissue sampling. The preoperative workup included Lund-Mackay assessment, nasal endoscopy, eosinophil blood count, asthma, and environmental allergy questionnaire. Postoperatively, in subjects with poor outcomes, imagistic osteitis severity was evaluated, and IL-33 expression was measured. IL-33 expression in NP was positively and significantly correlated with postoperative osteitis on CT scans (p = 0.01). Furthermore, high osteitis CT scores were related to high blood eosinophilia (p = 0.01). A positive strong correlation was found between postoperative osteitis and the Lund-Mackay preoperative score (p = 0.01), as well as the nasal endoscopy score (p = 0.01). Our research analyzed the levels of polyp IL-33, relative to blood eosinophilia, overall disease severity score, and osteitis severity, in patients with CRSwNP. These variables are prognostic predictors for poor outcomes and recalcitrant disease. Considering the importance of bone involvement in CRSwNP, this research aims to provide a better insight into the correlations of osteitis with clinical and biological factors.

Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence

Objectives Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown. The breathing pattern assessment tool (BPAT) can identify BPD. Our objective was to thus investigate the prevalence of BPD, nasal airflow obstruction and measures of airway disease severity in CRS with (CRSwNP) and without nasal polyps (CRSsNP) in severe asthma. Methods We determined whether CRS status, peak nasal inspiratory flow (PNIF) or polyp disease increased BPD prevalence. Demographic factors, measures of airway function and breathlessness in relation to BPD status and CRS subtypes were also evaluated. Results 130 Patients were evaluated (n = 69 had BPD). The prevalence of BPD in CRS with severe asthma was 53.1%. There was no difference between BPD occurrence between CRSwNP and CRSsNP. The mean polyp grade and PNIF were not statistically different between the BPD and non-BPD group. The presence of nasal polyps did not increase breathlessness. Conclusions BPD and CRS are commonly co-associated. CRS status and nasal obstruction per se does not increase BPD prevalence.

S. aureus biofilm metabolic activity correlates positively with patients’ eosinophil frequencies and disease severity in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinus mucosa. Recalcitrant CRS patients are unresponsive to medical and surgical interventions and often present with nasal polyps, tissue eosinophilia, and Staphylococcus aureus dominant mucosal biofilms. However, S. aureus sinonasal mucosal colonisation occurs in the absence of inflammation, questioning the role of S. aureus in CRS pathogenesis. Here, we aimed to investigate the relationship between S. aureus biofilm metabolic activity and virulence genes, innate immune cells, and disease severity in CRS. Biospecimens, including sinonasal tissue and nasal swabs, and clinical datasets, including disease severity scores, were obtained from CRS patients and non-CRS controls. S. aureus isolates were grown into biofilms in vitro, characterised, and sequenced. The patients’ innate immune response was evaluated using flow cytometry. S. aureus was isolated in 6/19 (31.58%) controls and 23/53 (43.40%) CRS patients of 72 recruited patients. We found increased S. aureus biofilm metabolic activity in relation to increased eosinophil cell frequencies and disease severity in recalcitrant CRS cases. Mast cell frequencies were higher in tissue samples of patients carrying S. aureus harbouring lukF.PV, sea, and fnbB genes. Patients with S. aureus harbouring lukF.PV and sdrE genes had more severe disease. This offers insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.

Does air pollutant exposure impact disease severity or outcomes in chronic rhinosinusitis?

Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS-specific disease severity. We assessed the impact of air pollutants on sinonasal-specific and general quality-of-life (QOL) measures in a multi-institutional cohort of patients with CRS. Participants with CRS were prospectively enrolled in a cross-sectional study and self-selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association. A total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation [SD]±2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT-22 or SF-6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ=0.12, [95% confidence interval {CI}: 0.003, 0.234]; p=0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m3) did not correlate with change in total SNOT-22 or SF-6D scores after treatment. Nevertheless, sulfur dioxide (SNOT-22: ρ=-0.121 [95% CI: -0.210, -0.030]; p=0.007; SF-6D: ρ=0.095 [95% CI: 0.002, 0.186]; p=0.04) and carbon monoxide (SNOT-22: ρ=-0.141 [95% CI: -0.230, 0.050]; p=0.002) exposure did correlate with these outcome measures. Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship.

Distinct eicosanoid patterns in severe recalcitrant nasal polyposis.

Although altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent nasal polyps (NPs) is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence (NPR) and explored potential endotypes based on pre-surgical eicosanoid levels. Levels of leukotriene (LT) E4 , LTB4 , prostaglandin (PG) D2 , PGE2 and 15(S) hydroxyeicosatetraenoic acid (15[S]-HETE) were measured in nasal secretions with specific immunoassays at pre-surgery (n=38) and 6 and 12 months post-surgery (n=35), with NPR identified endoscopically. Pre- and post-surgical levels were compared between patients with and without NPR. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters. Patients with recurrent NPs had pronounced pre-surgical levels of nasal 15(S)-HETE, PGD2 and LTE4 . From pre-surgery to 12 months post-surgery, NPR was associated with significant decreases of 15(S)-HETE and PGD2 relative to non-recurrence, whereas levels of LTE4 decreased at 6 months but increased again at 12 months. Clustering revealed three potential endotypes. Clusters 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2 , lower levels of PGE2 and LTB4 , and more cases of recurrent NPs and previous NP surgeries. Elevated nasal LTE4 12 months post-surgery in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies.

MicroRNAs: Potential Biomarkers of Disease Severity in Chronic Rhinosinusitis with Nasal Polyps

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRwNP) has multiple clinical presentations, and predictors of successful treatment are correlated to different parameters. Differentially expressed microRNAs in nasal polyps emerge as possible facilitators of precise endotyping in this disease. We aimed to evaluate the correlation between the clinical parameters of CRSwNP and two different microRNAs. Materials and Methods: The expression of miR-125b and miR-203a-3p in nasal polyps (n = 86) and normal nasal mucosa (n = 20) was determined through microarray analysis. Preoperative workup included CT scan, nasal endoscopy, blood tests, symptoms and depression questionnaires. Results: MiR-125b showed significant overexpression in NP compared to the normal nasal mucosa. miR-125b expression levels were positively and significantly correlated with blood eosinophilia (p = 0.018) and nasal endoscopy score (p = 0.021). Although high CT scores were related to miR-125b overexpression, the correlation did not reach statistical significance. miR-203a-3p was underexpressed in nasal polyps and was significantly underexpressed in CRSwNP patients with environmental allergies. Conclusions: Both miR-125b and miR-203a-3p are potential biomarkers in CRSwNP. miR-125b also correlates with the clinical picture, while miR-203a-3p could help identify an associated allergy.

Levels of eicosanoids in nasal secretions associated with nasal polyp severity in chronic rhinosinusitis

Severe nasal polyposis and mucosal inflammation, in patients with chronic rhinosinusitis (CRS) may include a dysregulated eicosanoid profile, but a clinical role for eicosanoids in CRS with nasal polyps (NP; CRSwNP) remains to be elucidated. This study focused on assessing levels and clinical implications of inflammatory mediators in nasal secretions and urine from patients with different NP severity or Aspirin Exacerbated Respiratory Disease (AERD). Levels of leukotrienes E4 and B4, prostaglandins D2 and E2 as well as 15(S)-hydroxyeicosatetraenoic acid were measured with enzyme immunoassays and cytokines with magnetic bead immunoassays. Patients with CRSwNP were subdivided based on NP score; CRSwNP-low (NP score ≤ 4, n = 11) or CRSwNP-high (NP score ≥ 5, n = 32) and compared to CRS without polyps (CRSsNP, n = 12), CRSwNP-AERD (n = 11) and individuals without CRS (n = 25). Smell test score, fractional exhaled nitric oxide (FeNO), blood eosinophils and Sinonasal outcome test-22 were assessed as clinical markers. Leukotriene E4, prostaglandin D2 and 15(S)-hydroxyeicosatetraenoic acid in nasal secretions correlated with NP score. Nasal leukotriene E4 also correlated with FeNO and smell test score, with highest levels found in CRSwNP-AERD. Levels of prostaglandin D2 in nasal secretion as well as urinary levels of the prostaglandin D2 metabolite 11β-prostaglandin F2α differed between CRSNP-high and CRSwNP-low. Urinary 11β-prostaglandin F2α was associated with asthma comorbidity whereas a similar association with prostaglandin D2 in nasal secretions was not observed. In conclusion, subdividing patients based on NP severity in combination with analysis of eicosanoids in non-invasively collected nasal secretions, may have clinical implications when assessing CRS disease severity.

CDHR3 rs6967330 risk allele influences CRS disease severity

Cadherin Related Family Member 3 (CDHR3) is the receptor for Rhinovirus-C and expressed in sinonasal epithelial cells. We have previously determined that the CDHR3 (rs6967330) base change from G to A causes a two-fold increase in the odds of adults with chronic rhinosinusitis (CRS) and that RV-C infections result in increased CRS severity. However, the influence of the rs6967330 SNP on CRS disease is not known.

Effect of Bacterial Biofilms on Disease Severity in Chronic Rhinosinusitis

Introduction: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting nose and para nasal sinuses for more than 12 weeks. Bacterial biofilms are emerging as an important etiological factor in CRS. The bacteria within the biofilm is resistant to treatment and adds to the severity of the disease in addition to posing difficulty in treating the disease. Objective: The aim of the present study was to compare the Severity of disease in CRS Patients with and without bacterial biofilms. Methods: Samples were taken from the patients and subjected to microbiological examination for biofilm detection. Lund Kennedy endoscopic scores and Lund Mackey CT scores were compared pre- treatment and at multiple follow ups. Results: out of 60 patients 46 (32 (69.6%) patients were biofilm positive. Median MLK endoscopic scores for biofilm positive and biofilm negative patients were calculated and compared at pre-treatment, 1 month, 3 months and 6 months post treatment respectively P &lt;0.001. Lund Mackay CT score at pre-treatment and at 6 month post treatment follow up of biofilm positive and biofilm negative CRS patients was calculated. P value &lt; 0.001. Percentage improvement in Modified Lund Kennedy (MLK) endoscopic score was more for biofilm negative patients compared to biofilm negative patients. Conclusion: Presence of biofilm on sinonasal mucosa is associated with more severe disease. Response to treatment is less in biofilm positive CRS patients. Presence of biofilms in CRS patients is an indication for more aggressive treatment.

Relationship between socioeconomic status, exposure to airborne pollutants, and chronic rhinosinusitis disease severity.

Air pollution directly interacts with airway mucosa, yet little is known about how pollutants affect upper airway inflammation. Studies have shown increased incidence of chronic rhinosinusitis (CRS), rhinitis, and asthma in areas with higher traffic pollution, and these neighborhoods are often associated with lower socioeconomic status (SES). The Area Deprivation Index (ADI) assesses neighborhood-level SES by zip code. The purpose of this study was to assess the relationship between SES and exposure to inhaled pollutants and CRS disease severity. CRS patients with and without nasal polyps (CRSwNP and CRSsNP, respectively) were identified (total patients=234; CRSwNP patients=138; CRSsNPpatients =96). Pollutant concentrations, including particulate matter 2.5 (PM2.5 ), black carbon (BC), and nitrogen dioxide (NO2 ), were measured at 70 sites within the defined countywide sites and used to estimate patient exposures. SES was measured by ADI state deciles. Disease severity metrics included the modified Lund-Mackay score (LMS), the need for systemic steroids, and functional endoscopic sinus surgery (FESS). Associations were analyzed and identified using linear, logistic, and Poisson multivariable regression. The distribution of CRSsNP and CRSwNP patients across ADI state deciles was similar. ADI, however, was a predictor of exposure to airborne pollutants (PM2.5 , BC, and NO2 ) with a 1.39%, 2.39%, and 2.49% increase in PM2.5 , BC, and NO2 per increasing decile increment (p<0.0001), respectively, which demonstrated a direct correlation between deprived neighborhoods and higher levels of exposure to PM2.5 , BC, and NO2 with an increase in pollutant levels per increase in ADI decile. Furthermore, ADI was a predictor for increased steroid treatment. Lower SES predicted higher exposure to air pollution and increased disease severity in patients with CRS as demonstrated by the increased need for steroid treatment.

Corrigendum: Correlation of Bromodomain Protein BRD4 Expression With Epithelial–Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps

[This corrects the article DOI: 10.3389/fmed.2020.00413.].

Correlation of Bromodomain Protein BRD4 Expression With Epithelial-Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

Objectives: This study aimed to explore the relationship between bromodomain-containing protein 4 (BRD4), epithelial–mesenchymal transition (EMT), and disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods: We performed immunofluorescent (IF) staining to evaluate the expression of BRD4 in the polyp tissues of CRSwNP and inferior turbinate mucosa of healthy controls. The relationship between BRD4 and EMT was evaluated by the BRD inhibitor JQ1 and BRD4 siRNA in primary human nasal polyp–derived epithelial cells. Disease severity was scored by using the Lund–Mackay scores of paranasal sinus computed tomography (CT) scans.Results: The expression of BRD4 in patients with CRSwNP was significantly higher than that in healthy controls. The loss of BRD4 function by the BRD inhibitor JQ1 and BRD4 siRNA resulted in the reduction of E-cadherin, increasing vimentin, and Snai1 mRNA expression. Moreover, the expression of BRD4 was related to the total CT scan scores (r = 0.4682, P = 0.0210).Conclusions: BRD4 had higher expression in CRSwNP than in healthy controls and might be associated with EMT in CRSwNP. BRD4 mRNA expression was associated with disease severity in CRSwNP.

Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps.

Background: The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host–environment interaction through a reaction with reactive oxygen species (ROS) production. Objective: We hypothesized possible roles of two major SRs in CRS pathology that can translate to clinical phenotypes or histological subtypes: lectin-like oxidized low-density lipoproteins (LDL) receptor-1 (LOX-1) and scavenger receptor class B type 1 (SR-B1). Patients and Methods: We collected ethmoid sinus mucosa specimens and blood samples from patients with CRS with nasal polyps (CRSwNP; n = 31) or CRS without NP (CRSsNP; n = 13) and 19 control subjects. We performed an RT-PCR analysis, ELISA assay, and immunostaining to determine the expressions and distributions of LOX-1 and SR-B1. Results: The CRSwNP group showed a significant increase in LOX-1 mRNA expression compared to the control group. There was no significant difference in SR-B1 mRNA levels among the three groups. The LOX-1 mRNA levels were positively correlated with the sinus computed tomography (CT) scores. Sinus tissue, but not serum samples, showed elevated concentrations of LOX-1 protein in the CRSwNP group versus the control group. The LOX-1 protein distribution was localized in inflammatory cells and vascular endothelial cells. Conclusion: LOX-1 is a major receptor for oxidized low-density lipoprotein produced by oxidative stress. This is the first study to report alterations in LOX-1 expression and production triggered by persistent inflammatory processes in CRSwNP patients. Our findings reveal complex but important roles for SRs that may contribute to the onset of different CRS phenotypes.

Correlation of Serum Vitamin D Levels with Chronic Rhinosinusitis Disease Severity.

Introduction:The present study was conducted to investigate the association between the serum vitamin D levels and severity of disease in chronic rhino sinusitis (CRS) patients.Materials and Methods:This prospective cross-sectional study was conducted on a total of 93 patients suffering from chronic rhino sinusitis with nasal polyposis (CRS w NP). Serum level of 25-hydroxyvitamin D was detected using a simple blood test. A22-item questionnaire, namely the sinonasal outcome test-22 (SNOT-22), was used to assess the subjective disease severity and patients' quality of life. In addition, the radiographic signs of the disease severity were evaluated using the Lund-Mackay Scale (LMS).Results:The mean age and serum vitamin D level of the patients were measured at 37.7±13.6 years and 24.6±16.9 ng/ml, respectively. Moreover, the mean of LMS and SNOT-22 scores were calculated at 14.2±11.2 and 40.8±17.6, respectively. There was a negative correlation between the SNOT-22 and serum levels of vitamin D (P=0.034). Similarly, LMS and serum vitamin D levels were correlated negatively (P=0.027). Furthermore, the results revealed a direct relationship between LMS and SNOT-22 (P<0.0001).Conclusion:According to the obtained results, there was a significant relationship between the serum vitamin D levels and severity of disease in patients with CRS w NP. Therefore, serum vitamin D levels could be added to the routine workup of the patients suffering from CRS w NP.

Association of air pollutants, airborne occupational exposures, and chronic rhinosinusitis disease severity

Previous work has shown that chronic rhinosinusitis (CRS) severity may be associated with particulate matter 2.5 (PM2.5 ) and black carbon (BC) in CRS patients without nasal polyps (CRSsNP). Data regarding occupational exposures, however, are lacking. We assessed the impact of PM2.5 , BC, as well as occupational airborne exposure on CRS disease severity. Patients with CRS with nasal polyps (CRSwNP), CRSsNP, and aspirin-exacerbated respiratory disease (AERD) were identified from an institutionwide database. Spatial modeling from 37 pollutant monitoring sites in Allegheny County was used to estimate exposures. Patient occupations using the 2010 Standard Occupation Classification (SOC10) and airborne occupation exposures to vapors, gases, dusts, fumes, fibers and mists (VGDFFiM) or diesel fumes were recorded. Disease severity was measured by modified Lund-Mackay score (LMS), systemic corticosteroid therapy, and incidence of functional endoscopic sinus surgery (FESS). Two hundred thirty-four patients were included (CRSwNP, n = 113; CRSsNP, n = 96; AERD, n = 25). The prevalence ofAERDamong those with CRSwNP was 18%. Patients exposed to VGDFFiM or diesel fumes required higher steroid doses vs nonexposed patients (p = 0.015 and p = 0.03, respectively); patients with VGDFFiM levels >5% were more likely to undergo FESS vs nonexposed patients (p = 0.0378). There was no difference in PM2.5 and BC with regard to disease severity and FESS between CRSwNP, CRSsNP, and AERD patients. Steroid use was significantly higher in CRSwNP and AERD vs CRSsNP (p = 0.001). LMS was significantly higher in AERD as compared with CRSwNP and CRSsNP (p = 0.001). Occupational airborne exposure to VGDFFiM correlated with increased prevalence of FESS and need for corticosteroids in CRS patients. There was no difference in PM2.5 and BC levels and disease severity outcome measures between CRS subtypes in this subset.

Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund–Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r  =  0.83, p  < 0.001) regardless of the presence of NPs. Patients with more EETs demonstrated higher Lund–Mackay scores (r  =  0.51, p  = 0.009), blood eosinophilia (r  =  0.80, p  < 0.001), and decreased olfactory function (r  = −0.65, p  < 0.001). No correlation between the extent of EET formation and the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs. Formation of EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS, regardless of NP status.

Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity.

Background: Pseudomonas aeruginosa causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). P. aeruginosa exoproteins contain virulence factors and play important roles in the pathogenicity of P. aeruginosa, however their role in CRS pathophysiology remains unknown.Methods: We isolated P. aeruginosa clinical isolates (CIs) and obtained clinical information from 21 CRS patients. Elastase activity of the CIs was measured at different phases of growth. Primary human nasal epithelial cells (HNECs) were cultured at air-liquid interface (ALI) and challenged with P. aeruginosa exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence.Results: 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the in vitro elastase activity of P. aeruginosa CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans (r = 0.95, p = 0.0004) and decreased TEER (r = −0.9333, P < 0.01) after 4 h of challenge. Western blot showed a significant degradation of ZO-1, Occludin and β-actin in relation to the elastase activity of the exoproteins. There was a highly significant correlation between the in vitro elastase activity of P. aeruginosa CIs and CRS disease severity (for log phase, r = 0.5631, p = 0.0097; for stationary phase, r = 0.66, p = 0.0013) assessed by CT imaging of the paranasal sinuses.Conclusion: Our results implicate P. aeruginosa exoproteins as playing a major role in the pathophysiology of P. aeruginosa associated CRS by severely compromising mucosal barrier structure and function.