Outcomes In Chronic Rhinosinusitis Research Articles

The impact of middle meatal steroid-eluting implants on the postoperative outcomes of chronic rhinosinusitis: A systematic review and meta-analysis

Endoscopic sinus surgery (ESS) has become an established surgical option in refractory chronic rhinosinusitis (CRS). The goal of this review is to assess the impact of steroid-eluting middle meatal implants after ESS. Cochrane Central Register of Controlled Trials (CENTRAL), SCOPUS, PUBMED, and GOOGLE SCHOLAR were searched from inception to November 2022. All randomised controlled trials (RCTs) involving adult patients receiving ESS for CRS utilising a steroid-eluting middle meatal implants were eligible. The primary outcome was adhesion or synechiae. The secondary outcomes were mucosal inflammation, polyp reformation, the need for oral steroids and additional surgery, postoperative bleeding, sinus pain and discomfort, postoperative sinus-related infection, and change in intraocular pressure. Fourteen full articles were examined out of 496 potential abstracts. Seven RCTs satisfied the criteria. At 30days, steroid-eluting implants reduced adhesion (OR: 0.28, 95% CI: 0.14 to 0.56; P<0.001), mucosal inflammation (MD: −13.09, 95% CI: −18.22 to −7.97; P<0.001), polyp reformation (OR: 0.31; 95% CI: 0.22 to 0.44; P<0.001), and requirement of additional oral steroid (OR: 0.44; 95% CI: 0.25 to 0.78; P=0.005) or surgery (OR: 0.25; 95% CI: 0.12 to 0.50; P<0.001). While their use for adhesion (OR: 0.24; 95% CI: 0.11 to 0.54; P<0.001) and polyp reformation (OR: 0.24; 95% CI: 0.12 to 0.51; P<0.001) were favourable, there was no difference in mucosal inflammation (MD: −5.68, 95% CI: −12.39 to 1.03; P=0.100) or the need for surgery (OR: 0.96; 95% CI: 0.07 to 12.37; P=0.980) when evaluated after 30days. Overall, the findings suggest that steroid-eluting middle meatal implants improve ESS outcomes by lowering rates of adhesion formation, postoperative medical and surgical interventions, recurrent polyposis, and inflammation, while having no significant negative impact in the immediate postoperative period. More research is needed into the long-term impacts.

Health care disparities and chronic rhinosinusitis: Does neighborhood disadvantage impact outcomes in sinonasal disease?

Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes. A total of 642 study participants with CRS were prospectively enrolled and self-selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. 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 pre- and post-treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φc ) with 95% confidence interval (CI) were calculated. A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc =0.18; 95% CI: 0.10, 0.25; p<0.001). Baseline total SNOT-22 (Rs=0.14; 95% CI: 0.06, 0.22; p<0.001) and SF-6D values (Rs=-0.20; 95% CI: -0.27, -0.12; p<0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within-subject improvement, or achievement of>1 minimal clinically important difference, in SNOT-22 or SF-6D scores after treatment were found. Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease-specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation.

Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 μg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 μg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels &gt;17.0 μg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

MicroRNA-125b Is a Potential Predictor of Surgical Outcomes in Chronic Rhinosinusitis with Nasal Polyps.

Despite advances in surgical techniques, recurrence rates after endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) remain high and difficult to predict. This study aimed to evaluate the potential role of microRNA 125b (miR-125b) in predicting disease evolution following ESS. We conducted a prospective study including patients undergoing first ESS for CRSwNP in our department between January 2020 and November 2021. We determined miR-125b levels from nasal polyps and pursued a standardized follow-up for at least 18 months for each patient. A total of 86 patients were included in the study. Higher postoperative endoscopy scores were associated with more severe disease at presentation on computed tomography scan, presence of concomitant asthma, and higher values of miR-125b. Even after multivariate repeated measures analysis and adjustments for confounders, miR-125b remained statistically significant. Moreover, miR-125 was the most important factor in predicting disease evolution at 18 months. A clear, robust relation between nasal polyp control evaluated through objective measures and miR-125b values was observed. This finding indicates the potential role of miR-125b in predicting the course of the disease following ESS.

The placebo effect in randomized-controlled trials of medical treatments for chronic rhinosinusitis: A systematic review and meta-analysis.

The placebo effect observed in clinical trials evaluating medical treatments for chronic rhinosinusitis (CRS) is not well understood. This systematic review and meta-analysis sought to characterize the placebo effect present within CRS outcomes. A systematic review of PubMed, Scopus, and Cumulated Index in Nursing and Allied Health Nursing (CINAHL) was performed. Randomized controlled trials (RCTs) evaluating medical treatments for CRS versus placebo were included. We assessed patient-reported (sino-nasal outcome test 22 [SNOT-22], nasal obstruction, sense of smell, nasal obstruction visual analogue score [VAS], sense of smell VAS, anterior rhinorrhea, and postnasal drip) and objective (Lund-Mackay Computed tomography (CT) score, peak nasal inspiratory flow [PNIF], nasal polyp scores, 40-item Smell Identification Test, serum IgE, and blood eosinophil levels) outcomes. Twenty-one RCTs were included, comprising 1437 patients (mean age 49.2 years). Biologics were the most common treatment investigated (n=9). Eleven studies administered background steroids along with placebo. Following placebo administration, multiple patient-reported outcomes significantly decreased, including SNOT-22 (mean difference -9.49, 95% confidence interval [CI] [-11.26, -7.73]), nasal obstruction (-0.33 [-0.54, -0.13]), sense of smell (-0.22 [-0.33, -0.11]), nasal obstruction VAS (-2.47 [-2.87, -2.06]), and loss of smell VAS (-2.31 [-4.14, -0.47]) scores. For objective measures, significant changes occurred in Lund-Mackay CT score (-0.82, [-1.48, -0.16]) and PNIF (4.70, [4.76, 24.64]) with placebo. Placebo arms had the greatest impact when no background medications were used. Placebo treatments have a statistically and potentially clinically significant effect on patient-reported and some objective CRS outcomes. Further investigation is required to fully understand placebo effect, which could improve assessment of RCTs and impact patient care.

Elexacaftor-Tezacaftor-Ivacaftor Therapy for Chronic Sinus Disease in Cystic Fibrosis

Cystic fibrosis (CF) is a multiorgan genetic disease with progressive upper and lower airway involvement. The effects of CF transmembrane conductance regulator (CFTR) modifier therapies on CF-related upper airway disease, specifically chronic rhinosinusitis (CRS), are not characterized. To determine the outcome of elexacaftor-tezacaftor-ivacaftor (ETI) on CRS as measured by changes in sinus computed tomography (CT) metrics and on clinical parameters in individuals with CF. This prospective longitudinal cohort study was conducted at the CF center of a tertiary care hospital between October 1, 2019, and July 31, 2021. A total of 64 participants with CF were included in the analysis. Sinus CT was obtained within 1 month of initiation of ETI therapy (baseline), and within 1 month of 1 year of ETI therapy. Images were independently analyzed by pulmonology, radiology, and otolaryngology physicians, using the Lund-Mackay and Sheikh-Lind scoring systems. Percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), and microbiologic data collected at initiation of ETI therapy and 3-month intervals for 1 year were also measured. The study hypothesis was that ETI therapy will improve CRS as measured by changes in sinus CT at initiation and 1 year after ETI therapy and clinical parameters in individuals with CF. Among the 64 participants (39 [60.9%] female; median age, 18.5 [IQR, 16.0-28.5] years; 64 [100%] White), improvement in CRS was noted by improvements in sinus CT scans using both sinus CT scoring systems after 1 year of ETI therapy. The reduction in the median total score using the Lund-Mackay sinus CT scoring system (from 5.8 [IQR, 5.0-7.0] to 3.3 [IQR, 2.6-4.2]) and the Sheikh-Lind scoring system (from 3.8 [IQR, 3.0-5.0] to 2.2 [IQR, 2.0-2.5]) was noted. Increases in ppFEV1 and BMI were also observed by 3 months of ETI therapy with persistent improvement through 1 year of treatment. Similarly, after 1 year of ETI therapy, participants with CF had reductions in positivity for Pseudomonas aeruginosa and Staphylococcus aureus in oropharyngeal cultures. This cohort study found that use of ETI therapy was associated with improved CRS outcomes in participants with CF as quantified by improved sinus CT scans measured by 2 radiographic scoring systems and was also associated with improved clinical outcomes. Despite improvement in CT scan scores, most people with CF continue to have scores that indicate severe sinus disease.

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.

Asthma and Allergic Rhinitis in Surgical Outcomes of Chronic Rhinosinusitis

Asthma and Allergic Rhinitis in Surgical Outcomes of Chronic Rhinosinusitis

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

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

The Impact of Social Determinants and Air Pollution on Healthcare Disparities in Chronic Rhinosinusitis With Nasal Polyps.

Multiple factors affect healthcare disparities in chronic rhinosinusitis (CRS) with and without nasal polyps. These factors include access to care, economic burdens to treatment, and differences in air pollution and air quality. In this paper, we will discuss how socioeconomic status, race, and air pollution burden influence healthcare disparities in the diagnosis and treatment outcomes of chronic rhinosinusitis with nasal polyps (CRSwNP). A literature search was performed via PubMed for articles related to CRSwNP, healthcare disparities, race, socioeconomic status, and air pollution in September 2022. Original studies from 2016 to 2022, landmark articles, and systematic reviews were included. We summarized these articles to cohesively discuss factors contributing to healthcare disparities in CRSwNP. Literary search produced 35 articles. Individual factors such as socioeconomic status, race, and air pollution influence CRSwNP severity and treatment outcomes. Correlations were noted with socioeconomic status, race, and air pollution exposure and CRS severity and post-surgical outcomes. Air pollution exposure was also associated with histopathologic changes in CRSwNP. Lack of access to care was a notable contributor to healthcare disparities in CRS. Healthcare disparities in the diagnosis and treatment of CRSwNP differentially affect racial minorities and individuals of lower socioeconomic status. Increased air pollution exposure in areas of lower socioeconomic status is a compounding factor. Clinician advocacy for greater healthcare access and reductions in environmental exposures for patients, among other societal changes, may help improve disparities.

IL-13–associated epithelial remodeling correlates with clinical severity in nasal polyposis

Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described. We sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS. Using cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls. The airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures. These results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.

Loss of SENP3 mediated the formation of nasal polyps in nasal mucosal inflammation by increasing alternative activated macrophage

Small ubiquitin-like modifier (SUMO)-specific protease (SENP)3 is a protease molecule that responds to reactive oxygen species (ROS) with high sensitivity. However, the role of ROS and SENP3 in the formation of nasal polyps (NPs) remains unclear. This study aimed to explore how SENP3 influenced the outcome of chronic rhinosinusitis (CRS) by altering macrophage function, that is, the formation of NPs. The alternative activation of macrophage (M2) was detected with CD68+ CD206+ in humans and CD206+ in mice. The nasal mucosa of patients with CRS was tested using flow cytometry (CD68, CD80, and CD206) and triple-color immunofluorescence staining (CD68, CD206, and SENP3). The bone marrow-derived macrophages from SENP3 knockout and control mice were stimulated with interleukin (IL)-4 and IL-13 to analyze alternative macrophage polarization in vitro. An animal model of allergic rhinitis was constructed using SENP3 knockout mice. CD206 was detected by immunofluorescence staining. The thickening of eosinophil-infiltrated mucosa was detected by Luna staining. The number of CD68+ CD206+ M2 increased in the nasal mucosa of patients with CRS with NP (CRSwNP) compared with patients with CRS without NP (CRSsNP), but with no significant difference between the groups. SENP3 knockout increased the polarization of F4/80+ CD206+ M2. Meanwhile, the number of CD206+ M2 significantly increased in the allergic rhinitis model constructed using SENP3 knockout mice and controls, with a more obvious proliferation of the nasal mucosa. Downregulation of SENP3 promotes the formation of nasal polyps mediated by increasing alternative activated macrophage in nasal mucosal inflammation.

The Surgical Outcome of Chronic Rhinosinusitis with Emphasis on Rhinogenic Headache

The Surgical Outcome of Chronic Rhinosinusitis with Emphasis on Rhinogenic Headache

Associations of alcohol consumption with the risk and surgical outcomes of chronic rhinosinusitis in China: A case-control study.

To investigate the associations between weekly alcohol consumption and the risk and surgical outcome of Chronic Rhinosinusitis (CRS). A case-control study. The study population consisted of 1095 CRS patients and 909 healthy collected from the first affiliated hospital of Zhengzhou University between May 2018 and December 2019. Unconditional multivariate logistic regression analysis and Cox proportional hazards regression analysis were performed to estimate the association of alcohol consumption with the risk and surgical outcomes of CRS. Odds ratios (OR) or hazard ratio (HR) with 95% confidence intervals (CI) were calculated separately. The Kruskal-Wallis test was used to explore the possible molecular mechanisms. As compared with nondrinkers, the multivariable-adjusted OR (95% CI) values of current drinkers consuming 7.5-22 drinks and >22 drinks per week were 2.158 (1.249-3.729) and 5.373 (2.912-9.911), respectively. The rate of mucosal epithelialization after CRS surgery for patients who drank 7.5-22 drinks and >22 drinks per week was lower than that of nondrinkers [HR (95% CI)=0.487 (0.351-0.675) and 0.252 (0.184-0.346), respectively]. The association of alcohol consumption with the risk and surgical outcome of CRS was dose dependent (p < .01). Alcohol consumption increased the risk of CRS and extended the time of mucosal epithelialization after CRS surgery by possibly increasing serum IgE levels (p < .05). Higher alcohol consumption of >7.5 drinks per week was an independent risk factor for CRS and extended the time of mucosal epithelialization after surgery. As a potential underlying mechanism, alcohol consumption increases serum IgE levels.

Mepolizumab Improves Outcomes of Chronic Rhinosinusitis with Nasal Polyps in Severe Asthmatic Patients: A Multicentric Real-Life Study.

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.

The Role of Allergen-Specific Immunotherapy in ENT Diseases: A Systematic Review.

Previous studies have demonstrated that both subcutaneous (SCIT) and sublingual specific immunotherapy (SLIT) are effective in treating allergic rhinitis (AR). Further studies have evaluated the efficacy of allergen-specific immunotherapy (AIT) on different ear, nose, and throat (ENT) manifestations, in which allergy might have an etiopathogenetic role, such as local allergic rhinitis (LAR), rhinosinusitis (RS), otitis media (OM), and adenotonsillar (AT) disease. Nevertheless, the management of allergy in ENT diseases is still debated. To the best of our knowledge, this is the first systematic review assessing the efficacy of AIT in ENT diseases aside from AR. Literature data confirmed that AIT might be an effective therapeutic option in LAR, although its effect is restricted to studies with short-term follow-up. Furthermore, previous research demonstrated that AIT may improve symptoms and surgical outcomes of chronic rhinosinusitis when used as an adjunctive treatment. Few studies supported the hypothesis that AIT may exert positive therapeutic effects on recurrent upper airway infections as adenotonsillar disease. Finally, some clinical observations suggested that AIT may add some benefits in the management of otitis media with effusion (OME). The results of this systematic review allow us to conclude that the efficacy of AIT in ENT disorders has been only slightly investigated and additional studies are needed.

Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells

Background: Glucocorticoid (GC) resistance results in unsatisfactory outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Previous studies have shown that calcitriol, the active form of vitamin D, alone or in combination with corticosteroids, exerts crucial immunomodulatory effects on inflammatory responses. However, whether vitamin D can improve the effect of GCs to attenuate inflammation in the epithelium of CRSwNP remains unclear. Methods: A human bronchial epithelial cell line (Beas-2B) and primary human nasal epithelial cells (HNECs) obtained from 10 patients with CRSwNP were exposed to lipopolysaccharide (LPS) for 24 h to establish an inflammation model. LPS-stimulated HNECs and Beas-2B cells were treated with/without dexamethasone in the presence or absence of calcitriol pretreatment for 24 h. The expression levels of interleukin-6 (IL-6) mRNA and protein were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Toll-like receptor 4 (TLR4)/NF-κB pathway related markers were examined by western blotting. One-way ANOVA or the Kruskal-Wallis test with post hoc analysis were used for multiple comparisons among groups. Results: The production of IL-6 in Beas-2B cells and primary HNECs after LPS stimulation was significantly increased, which could be inhibited by dexamethasone or calcitriol alone. However, significant inhibition of IL-6 production was observed in the calcitriol plus dexamethasone group. Further analysis showed that calcitriol could enhance the effect of dexamethasone in inhibiting LPS-induced overexpression of TLR4, Myd88, and phosphorylation of p65. Conclusion: Our findings demonstrated that vitamin D could improve the effect of GCs to alleviate the level of IL-6 induced by LPS via the TLR4/NF-κB pathway in human respiratory epithelial cells.

Race and ethnicity define disparate clinical outcomes in chronic rhinosinusitis

BackgroundChronic rhinosinusitis (CRS) is a common upper airways inflammatory disease requiring multidisciplinary care. ObjectiveTo evaluate if African Americans (AA), Latinxs, and nonLatinx White (White) patients have different chronic rhinosinusitis outcomes and to identify associated factors impacting these outcomes. MethodsWe conducted a large prospective cohort study of CRS patients who were evaluated and followed for several clinical variables at the initial encounter and after continuous management of CRS for a mean of 40 months. The Sinonasal Outcome Test (SNOT-22) and Lund-MacKay scores were measured on initial visits, and SNOT-22 was repeated at the end of follow-up. Logistic regression was used to compare outcomes between the different groups adjusted for comorbidities and demographics. ResultsAmong the 977 enrolled CRS cases, 615 (63.0%), 235 (24.1%) and 138 (13.0%) were White, AA and Latinx respectively. There was no difference in severity of CRS based on Lund-MacKay scores and SNOT-22 scores, and frequency of other comorbidities at presentation among the 3 groups. During the follow-up period, compared with Whites, AA and Latinx were less frequently evaluated by an allergist. AAs had less frequent CRS related visits and lower final SNOT-22 score compared with Whites. ConclusionAlthough our enrolled patients from the 3 ethnic groups had similar clinical characteristics and disease burden at baseline, AAs had less frequent follow-up visits and worse final SNOT-22 after 40 months of follow-up. The observed poorer outcomes in AAs are likely owing to inequity in healthcare access evidenced by differences in insurance and suboptimal management of CRS.

Evaluating Distance Bias in Chronic Rhinosinusitis Outcomes

The distance traveled by patients for medical care is associated with patient outcomes (ie, distance bias) and is a limitation in outcomes research. However, to date, distance bias has not been examined in rhinologic studies. To evaluate the association of distance traveled by a cohort of patients with chronic rhinosinusitis with baseline disease severity and treatment outcomes. A total of 505 patients with chronic rhinosinusitis were prospectively enrolled in a multi-institutional, cross-sectional study in academic tertiary care centers between April 2011 and January 2020. Participants self-selected continued appropriate medical therapy or endoscopic sinus surgery. The 22-item Sinonasal Outcome Test (SNOT-22) and Medical Outcomes Study Short Form 6-D (SF-6D) health utility value scores were recorded at enrollment and follow-up. Data on the distances traveled by patients to the medical centers, based on residence zip codes, and medical comorbid conditions were collected. Distance traveled by patient to obtain rhinologic care. SNOT-22 and SF-6D scores. Scores for SNOT-22 range from 0 to 110; and for SF-6D, from 0.0 to 1.0. Higher SNOT-22 total scores indicate worse overall symptom severity. Higher SF-6D scores indicate better overall health utility; 1.0 represents perfect health and 0.0 represents death. The median age for the 505 participants was 56.0 years (IQR, 41.0-64.0 years), 261 were men (51.7%), 457 were White (90.5%), and 13 were Hispanic or Latino (2.6%). These categories were collected according to criteria described and required by the National Institutes of Health and therefore do not equal the entire cohort. Patients traveled a median distance of 31.6 miles (50.6 km) (IQR, 12.2-114.5 miles [19.5-183.2 km]). Baseline (r = 0.00; 95% CI, 0.00-0.18) and posttreatment (r = 0.01; 95% CI, -0.07 to 0.10) SNOT-22 scores, as well as baseline (r = -0.12; 95% CI, -0.21 to -0.04) and posttreatment (r = 0.07; 95% CI, -0.02 to 0.16) SF-6D scores, were not associated with distance. There was no clinically meaningful correlation between distance traveled and mean comorbidity burden. Nevertheless, patients with a history of endoscopic sinus surgery were more likely to travel longer distances to obtain care (Cliff delta = 0.28; 95% CI, 0.19-0.38). Although this cross-sectional study found that some patients appear more willing to travel longer distances for chronic rhinosinusitis care, results suggest that distance traveled to academic tertiary care centers was not associated with disease severity, outcomes, or comorbidity burden. These findings argue for greater generalizability of study results across various cohorts independent of distance traveled to obtain rhinologic care. ClinicalTrials.gov Identifier: NCT02720653.

CRS-PRO and SNOT-22 correlations with type 2 inflammatory mediators in chronic rhinosinusitis.

Middle meatal mucus data were collected and the SNOT-22 and CRS-PRO were administered to 123 patients (71 CRS without nasal polyps [CRSsNP], 52 CRS with nasal polyps [CRSwNP]) with CRS before and 6 to 12 months after undergoing ESS. Interleukin (IL)-4, IL-5, IL-13, and eosinophilic cationic protein (ECP) were measured using a multiplexed bead assay and enzyme-linked immunoassay. Pre- and post-ESS SNOT-22 and CRS-PRO were compared with T2 biomarkers. Before ESS neither PROM correlated with any biomarker. After ESS, CRS-PRO showed a correlation with 2 mediators (IL-5 and IL-13: p=0.012 and 0.003, respectively) compared with none for the SNOT-22. For CRSwNP patients, pre-ESS CRS-PRO and SNOT-22 correlated with IL-4 (p=0.04 for both). However, after ESS, CRS-PRO correlated with 3 biomarkers (IL-5, IL-13, and ECP: p=0.02, 0.024, and 0.04, respectively) and SNOT-22 with 2 biomarkers (IL-5 and IL-13: p=0.038 and 0.02, respectively). There were no significant relationships between any of the T2 biomarkers pre- or post-ESS among patients with CRSsNP. Exploratory analyses of the subdomains showed the SNOT-22 rhinologic and CRS-PRO rhinopsychologic subdomains correlated better with the T2 biomarkers. On individual item analysis, IL-13 correlated significantly post-ESS with 8 of 12 items on the CRS-PRO vs 6 of 22 items on the SNOT-22. The CRS-PRO total score showed a significant correlation with T2 biomarkers especially when assessed post-ESS and among CRSwNP patients.