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Background: Nasal and paranasal sinus abnormalities may be related to nasolacrimal duct obstructive disease but are strongly debated. Data of acute disease stage are lacking. Objective: The purpose of this study was to determine if there are correlations between radiologic signs of sinus inflammation and acute dacryocystitis (AD). Methods: This cross-sectional controlled study was conducted at Wenzhou, Zhejiang Province, China from February 2021 to November 2023. Forty-four consecutive patients with AD and 50 consecutive patients with orbital tumors (the control group), who completed preoperative computed tomography scans, were enrolled to evaluate the extent of their inflammatory sinonasal disease by the modified Lund-Mackay score system. Results: The inflammation signs of the paranasal sinuses (total mean sinus scores, 95% CI [0.00, 2.00]; P < 0.001), namely the anterior ethmoid sinus(95% CI [0.00, 1.00]; P < 0.001), the posterior ethmoid sinus(95% CI [0.00, 0.00]; P = 0.003), the frontal sinus (95% CI [0.00, 0.00]; P = 0.02), and the ostiomeatal complex (P < 0.001) were more extensive in patients with AD when compared with the controls. The disease course was negatively correlated with the anterior ethmoid (P = 0.03) and frontal scores (P = 0.01). The symptom of eyelid swelling was positively correlated with the anterior ethmoid (P = 0.03), ostiomeatal complex (P = 0.004), and total sinus scores (P = 0.005). Conclusion: Inflammatory sinus disease was found to be more frequent in patients with AD, which was gradually alleviated with the prolongation of the disease course. The mutual spread of inflammation particularly in the acute course may play an important role in lacrimal duct obstructive disease. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim of this study was to assess disparities in nasal nitric oxide (NO) levels between individuals diagnosed with eosinophilic chronic rhinosinusitis (ECRS) and those without ECRS. The second aim was to ascertain the comparative predictive efficacy of these nasal NO levels for the presence of ECRS. Methods: A systematic analysis was conducted on relevant studies that compared nasal NO levels in individuals with ECRS and those without. Furthermore, the discriminatory capacity of nasal NO in distinguishing ECRS from non-ECRS cohorts was quantified. The risk of bias across studies was evaluated utilizing the Newcastle-Ottawa scale. Results: The comprehensive review encompassed a total of 5 studies involving 470 participants. Findings revealed that patients diagnosed with ECRS exhibited significantly higher levels of nasal NO, as measured in parts per billion (ppb), compared to their non-ECRS patients. The mean difference was 130.03 ppb (95% confidence interval: [66.30, 193.75], I2 = 58.7%). The diagnostic odds ratio for nasal NO in identifying ECRS was 9.29 ([5.85, 14.75], I2 = 26.4%). The area under the summary receiver operating characteristic curve was 0.82. The correlation between sensitivity and false positive rate was 0.53, suggesting a lack of heterogeneity. Sensitivity, specificity, negative predictive value, and positive predictive value were 69% ([0.55, 0.79], I2= 77.0%), 83% ([0.73, 0.90], I 2 = 68.5%), 77% ([0.69, 0.83], I 2 = 50.1%), and 75% ([0.67, 0.82], I 2 = 41.5%), respectively. Conclusion: Nasal NO has the potential as a noninvasive diagnostic measure and endotype tool for ECRS. [ABSTRACT FROM AUTHOR]

Background: Endoscopic sinus surgery (ESS) could significantly improve olfactory function among patients with chronic rhinosinusitis (CRS). This study aimed to perform a meta-analysis to evaluate the effect of ESS on the olfactory bulb volume (OBV) among patients with CRS. Methods: A systemic search of PubMed, Medline, Embase, Web of Science, and other databases was conducted to identify studies assessing OBV changes in patients with CRS after ESS utilizing magnetic resonance imaging. Results: A total of four studies with 168 participants were included. Comparing the changes in OBV of patients with CRS before and after surgery within 3-6 months, the ESS significantly improved the overall OBV (P = 0.005, I2 = 66%), with the left OBV increased by 5.57mm3 (P = 0.84, I2 = 0%), and the right OBV increased by 8.63mm3 (P = 0.09, I2 = 53%). A difference in OBV persists between healthy controls and patients with CRS 3-6 months after ESS. The overall OBV of patients with CRS after ESS was significantly smaller than controls (mean difference = -3.84, P = 0.04), with a mean difference of 4.13mm3 on the left side (P = 0.72, I2 = 0%), and a mean difference of 3.22mm3 on the right side (P = 0.0001, I2 = 89%). Conclusions: ESS significantly increases the OBV among patients with CRS. [ABSTRACT FROM AUTHOR]

Background: Central compartment atopic disease (CCAD) is a recently described variant of chronic rhinosinusitis (CRS) strongly associated with atopy. The association between central compartment disease (CCD) and inhalant allergy is not well established in South-East Asia, where perennial allergic rhinitis is common. Objectives: The primary objective was to evaluate endoscopic and radiologic CCD as predictors of perennial allergen sensitization in primary CRS. The secondary objective was to compare clinical characteristics of CCAD with other CRS subtypes (CRSwNP and CRSsNP). Methods: A retrospective study of consecutive patients with primary CRS who underwent endoscopic sinus surgery at our institution was performed. Allergen sensitization was confirmed by skin or serum testing. Endoscopy records and computed tomography scans of paranasal sinuses were reviewed for CCD. The diagnostic accuracy of endoscopic and radiologic CCD in predicting atopy was calculated. Results: There were 104 patients (43 CCAD, 30 CRSwNP and 31 CRSsNP). Endoscopic CCD was significantly associated with aeroallergen sensitization (odds ratio (OR) 3.99, 95% confidence interval (CI) 1.65-9.67, P = 0.002). Endoscopic CCD predicted atopy with 57% sensitivity, 72% specificity, 69% positive predictive value and positive likelihood ratio of 2.05. Radiologic CCD was not associated with aeroallergen sensitization (OR 0.728, 95%CI 0.292-1.82, P = 0.496). There were more CCAD patients who reported hyposmia (86% vs 42%, P < 0.001) and had anosmia on olfactory testing than CRSsNP (65% vs 14%, P = 0.015). The prevalence of atopy was significantly higher in CCAD than CRSwNP and CRSsNP (70% vs 37% and 42%, P = 0.015 and P = 0.05, respectively). Median serum total immunoglobulin E was higher in CCAD (283 IU/ml) and CRSwNP (127 IU/ml) than CRSsNP (27 IU/ml, P = 0.006 and P = 0.042, respectively). Conclusions: Endoscopic CCD was a better predictor of inhalant allergy than radiologic CCD in primary CRS, in a locale of perennial allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is one of the most common health disorders in humans and has a major impact on health-related quality of life (HRQoL). Of the many factors contributing to the etiology of CRS, less is known about the correlation between CRS and bacterial biofilms and their impact on HRQoL. Objective: The aim of this prospective study was to investigate the relationship between biofilm-producing bacteria and patients' objective findings and HRQoL. Methods: Forty-eight patients with CRSwNP were enrolled in a 12-month prospective study. The Lund-Mackay (LM) CT and endoscopic Lund-Kennedy (LK) scores were obtained before endoscopic sinus surgery (ESS), and patients completed the HRQoL instruments: the 22-item Sinonasal Outcome Test (SNOT−22), the 36-item Short Questionnaire (SF−36), and the visual analog scale (VAS). A sinus culture was obtained at ESS, bacteria were isolated, and in vitro quantification of the biofilm was performed. The LK score and HRQoL were determined postoperatively at months 1, 3, 6, and 12. Results: The most common bacterial isolates in patients with CRSwNP were Staphylococcus aureus (28%), coagulase-negative staphylococci (52%), and Pseudomonas aeruginosa (8%). Preoperatively, the highest LM and LK scores were found in patients with strong biofilm producers. Postoperative LK scores were significantly reduced in all patients. Postoperative VAS scores were significantly reduced from month 1 to month 12 postoperatively. Patients with strong biofilm producers had significantly worse nasal blockage, secretion, headache, facial pressure and pain, and loss of smell preoperatively, compared to patients with low biofilm producers. The most significant reduction in preoperative scores SNOT−22 and SF−36 (excluding physical functioning) was seen in patients with S. aureus and P. aeruginosa. Conclusions: Patients with strong biofilm producers had higher LK and LM scores preoperatively, and greater improvement in LK and HRQoL scores postoperatively. Microbiologic surveillance of all CRS patients is recommended. [ABSTRACT FROM AUTHOR]

Background: Priming is a psychological phenomenon where subconscious cues in the environment impact our behavioral responses in certain situations. Well studied in the worlds of business, marketing, and even politics, it is unclear how the priming phenomenon impacts patient perception of their own disease state nor how they report that perception using tools like the Sinonasal Outcomes Test (SNOT-22), used to measure that perception in chronic rhinosinusitis. Objective: To determine the impact of positive or negative priming on self-reported patient perception of their chronic rhinosinusitis disease using the SNOT-22 disease-specific quality of life instrument. Methods: Single-blind, randomized, prospective cohort pilot study of 206 consecutive adult patients with a clinical diagnosis of chronic rhinosinusitis presenting to a university rhinology clinic. Patients were randomized to receive "positive priming" (103) or "negative priming" (103) by reading a passage about the positive or negative aspects of chronic sinusitis and its treatment respectively. Patients were then asked to fill out the SNOT-22 and results between the two groups were compared. Results: The negative priming group had a higher median SNOT-22 score of 49 [IQR = 39] compared to the positive priming groups' score of 22 [IQR = 27], p < 0.0001), a difference of nearly three times the minimal clinical impactful difference (MCID). This effect was consistent regardless of age or sex of the patient. Subgroup analysis revealed a greater impact when priming was performed by the senior male attending regardless of patient age or sex (p < 0.001), while priming performed by the younger female research fellow had greater impact on older patients (>59 years, p = 0.001) and female patients (p = 0.003). Conclusions: Priming impacts how patient's perceive their chronic rhinosinusitis as determined by the SNOT-22. It is imperative that the rhinologist understand this when using this instrument in research applications and in clinical decision-making for patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that respiratory diseases are associated with an increased risk of rheumatoid arthritis (RA). However, whether there is a correlation between chronic rhinosinusitis (CRS) and RA is not known. Due to the high incidence of CRS, it remains to be clarified whether we should pay additional attention to RA risk in the huge population of CRS. Methods: We used a 2-sample Mendelian randomization (MR) analysis to explore the causal effects of CRS on the incidence of RA. The inverse variance weighted (IVW) approach was used as the main analysis in the MR randomization study. Then, we used the data from the U.K. Biobank to examine the association between RA and CRS at the individual level in a prospective cohort. We identified patients with CRS at the time of recruitment and further followed the incidence of RA until 2021. The risk of developing RA in patients with CRS was determined by a multivariate Cox regression model. We used 3 multivariate Cox models to adjust for individual characteristics, lifestyle factors and concomitant diseases, respectively. Results: The MR analysis by the IVW model suggested that the odds ratio of RA associated with genetically predicted CRS was 2.39 (95% CI [1.08-5.30]; p =.032). In the first multivariate model adjusting for individual characteristics, CRS was associated with a 47% increase of risk of developing RA (hazard ratio [HR] = 1.47; 95% CI [1.12-1.90]). In the second multivariate model adjusting for lifestyle factors, the HR of RA associated with CRS was 1.48 (95% CI [1.15-1.90]). In the third multivariate model, chronic sinusitis was associated with a 32% increase in RA risk (HR = 1.32; 95% CI [1.03-1.70]). Conclusion: CRS has a genetically causal effect on the incidence of RA, and the risk of RA is greatly higher in CRS at the individual level. This is the first study to reveal an association between CRS and RA. Due to the high incidence of CRS, it is recommended that additional attention should be paid to the increased RA risk in patients with CRS compared to that in common people. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: This study aimed to evaluate the potential role of microRNA 125b (miR-125b) in predicting disease evolution following ESS. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic chronic rhinosinusitis (eCRS) is a type 2 inflammatory disease that frequently recurs after surgery. In recent years, dupilumab has been available for the treatment of refractory chronic rhinosinusitis since 2020 in Japan. Although there are some reports of its usefulness, there are not enough reports of its clinical efficacy for longer than 1 year, especially for olfactory recovery. Methods: Twenty patients with eCRS who had recurrence after surgery and had been receiving dupilumab were enrolled retrospectively. The nasal polyp score (NPS), computed tomography (CT) score, T&T olfactometer, and olfactory cleft opacification on CT were evaluated at baseline, at an average of 5.1 months later (short term), and at an average of 18.3 months later (long term). Results: At the short-term evaluation, there were significant improvements in the NPS and CT scores (P <.001, P =.008, respectively). The CT score was further improved at the long-term evaluation compared to the short-term evaluation (P =.018) and baseline (P =.008). T&T detection/recognition thresholds and olfactory cleft opacification showed significant improvements only at the long-term evaluation compared to baseline (P =.002, P =.006, and, P =.006, respectively). Conclusion: The NPS remained improved, and the CT score showed further improvement with long-term treatment, whereas olfactory function and olfactory cleft opacification showed significant improvement only after long-term treatment. There was a dissociation between the time to improve in the NPS and CT scores and the time to improve in olfactory function and olfactory cleft opacification. Based on these results, dupilumab should be administered for longer than 1 year, especially for olfactory function. [ABSTRACT FROM AUTHOR]

Background: Over the last few decades, reflux diseases, such as laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD), have been identified as significant contributors to inflammatory upper aerodigestive tract diseases. Establishing a direct relationship between reflux disease and chronic rhinosinusitis (CRS) is challenging due to the high prevalence of both diseases and their potential for independent coexistence. Objective: The purpose of this study is to review the existing literature and evaluate the evidence of an association between reflux diseases and CRS. Methods: A comprehensive electronic search was conducted across multiple databases to identify all studies that investigated the relationship between LPR, GERD, and CRS from January 1, 1950, to June 16, 2022. Only studies with English manuscripts involving adult populations were included, while case series, case reports, and in vitro studies were excluded. The risk of bias was evaluated using The Newcastle-Ottawa Scale for case-control studies and the NIH quality assessment tool for observational cohort and cross-sectional studies. Results: The search strategy yielded a total of 427 articles, out of which 25 studies examined the correlation between reflux diseases and CRS. The meta-analysis indicated a significant association between the presence of GERD and CRS compared to control groups (P <.001; CI 3.56 [2.25, 5.65]), as well as significantly higher pH values and pepsin detection in CRS patients when compared to healthy individuals (P =.003). Furthermore, all studies that evaluated proton pump inhibitor (PPI) therapy in CRS patients reported positive outcomes, with 93% of CRS patients showing improvement on PPIs. Conclusion: The existing literature provides suggestive evidence of an association between reflux diseases and CRS, with regards to both prevalence and treatment. Nonetheless, further studies are required to confirm this relationship. [ABSTRACT FROM AUTHOR]

Background: Frontal sinus surgery remained a challenge of restenosis or obliteration of the drainage pathway caused by the scarring and neo-osteogenesis after mucosal stripping and bone drill-out. The pedicled or free nasal mucosal flap is typically used to repair the exposed bone surface to avoid or reduce recurrence. Objective: This study aimed to explore the histopathological mechanism of mucosal flaps repairing bare bone after mucosal resection and bone drill-out in the rabbit model. Methods: Thirty New Zealand white rabbits were used. Sixteen rabbits were selected as the experimental group, and Staphylococcus aureus was used to establish the CRS model (CRS group). Fourteen healthy rabbits were allocated to the control group (NCRS group). Each group was divided into two subgroups with or without mucosal flap repair (CRS-FLAP, CRS-NFLAP, NCRS-FLAP, and NCRS-NFLAP, respectively). The bony anterior and lateral walls of the maxillary sinus of each rabbit were abraded by the drill. The bare bone was then covered with a flap in FLAP subgroups. Bone remodeling and mucosal morphological changes were observed and compared by histopathological hematoxylin and eosin and Masson staining. Results: In the CRS-NFLAP subgroup, the regenerated epithelium lacked typical structure, accompanied by numerous inflammatory cell infiltration and collagen deposition. Conversely, the inflammatory reaction was mild in the CRS-FLAP subgroup, and there was less collagen deposition. The restored mucosal structure was like the normal mucosa. The epithelium in the NCRS-NFLAP subgroup was partially exfoliated, with few cilia, goblet cells, and glandular structures. Compared with the NCRS-NFLAP subgroup, the CRS-NFLAP subgroup showed significant bone remodeling with enhanced activity of osteoblast and osteoclast cells. Conclusions: Pedicled mucosal flap repair could significantly reduce local mucosal and bone remodeling in a rabbit model of CRS. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to characterize the presentation, outcomes, and barriers to care for White and non-White patients undergoing endoscopic sinus surgery (ESS). Background: ESS is often successful in providing long-term relief for patients suffering from chronic rhinosinusitis (CRS). Literature that uses robust measures of socioeconomic status (SES) and barriers to care to assess ESS outcomes is limited. Methods: A retrospective matched cohort study of patients who underwent ESS for CRS between 1/1/2015 and 6/1/2021 at a single tertiary care academic center was conducted. White and non-White patients were matched 1-to-1 by sex and age (± 5 years). SES was evaluated using the area of deprivation index (ADI). Results: Of the 298 patients included in the study, 149 are White and 149 are non-White, 111 (37.2%) have CRS with nasal polyposis (CRSwNP), 141 (47.3%) had allergic rhinitis, 90 (30.2%) had asthma and 22 (7.4%) required revision ESS. Non-White patients were 3.62 times more likely to present with CRSwNP (95% confidence interval [CI] 2.2-5.96) and had 2.87 times increased odds for requiring revision ESS than age and sex-matched White patients (95% CI 1.090-7.545). The median ADI for non-White (6.00) patients was higher than for White patients (3.00) (P <.001) and 21.5% more non-White patients presented with Medicaid (P <.001). Conclusion: Non-White patients undergoing ESS for CRS are more likely to present from areas with fewer resources and be underinsured. Using robust measures of SES, such as ADI, may allow for care to be tailored to patients with barriers to care. [ABSTRACT FROM AUTHOR]

Background: Epigenetics studies mechanisms such as DNA methylation, histone modifications, non-coding RNAs, and alternative polyadenylation that can modify gene activity without changing the underlying DNA nucleotide base-pair structure. Because these changes are reversible, they have potential in developing novel therapeutics. Currently, seven pharmaceutical agents targeting epigenetic changes are FDA approved and commercially available for treatment of certain cancers. However, studies investigating epigenetics in chronic rhinosinusitis (CRS) have not been undertaken previously in the United States. Objectives: The goal of this study was to investigate sinonasal DNA methylation patterns in CRS versus controls, to discern environmentally-induced epigenetic changes impacting CRS subjects. Methods and Results: Ethmoidal samples from CRS and inferior turbinate mucosal tissue samples from controls without CRS were studied. DNA methylation was studied by Reduced Representation Bisulfite Sequencing. RADMeth® biostatistical package was used to identify differentially methylated regions (DMRs) between CRS and controls. Ingenuity Pathway analysis of DMRs was performed to identify top upstream regulators and canonical pathways. Ninety-three samples from 64 CRS subjects (36 CRSwNP; 28 CRSsNP) and 29 controls were studied. CRS and control samples differed in 13 662 CpGs sites and 1381 DMRs. Top upstream regulators identified included: 1. CRS versus controls: TGFB1, TNF, TP53, DGCR8, and beta-estradiol. 2. CRSwNP versus controls: TGFB1, CTNNB1, lipopolysaccharide, ID2, and TCF7L2. 3. CRSsNP versus controls: MYOD1, acetone, ID2, ST8SIA4, and LEPR. Conclusions: Differential patterns of methylation were identified between controls and CRS, CRSwNP, and CRSsNP. Epigenetic, environmentally-induced changes related to novel, inflammatory, immunologic, and remodeling pathways appear to affect epithelial integrity, cell proliferation, homeostasis, vascular permeability, and other yet uncharacterized pathways and genes. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection. Objective: This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes. Methods: We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed. Results: We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity. Conclusion: We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid. We registered this study in PROSPERO (CRD42022302787). [ABSTRACT FROM AUTHOR]

Background: Mometasone-eluting poly-L-lactide-coglycolide (MPLG) is available commercially for frontal sinus ostium (FSO) stenting. An alternative chitosan polymer-based drug delivery microsponge is also available at a lower cost per unit. Objective: To compare the outcomes of MPLG stents versus triamcinolone-impregnated chitosan polymer (TICP) microsponge in frontal sinus surgery. Methods: Patients who underwent endoscopic sinus surgery from December 2018 to February 2022 were reviewed to identify those with the intraoperative placement of TICP microsponge or MPLG stent in the FSO. FSO patency was evaluated by endoscopy at follow-up. Twenty-two-item sinonasal outcome test (SNOT-22) was also recorded, and complications were noted. Results: A total of 68 subjects and 96 FSOs were treated. TICP was first used in August 2021 and MPLG in December 2018. MPLG placement in a Draf 3 cavity was excluded since TICP had not been used during Draf 3 procedure. Both cohorts (TICP 20 subjects, 35 FSOs; MPLG 26 subjects, 39 FSOs) had similar clinical characteristics. At a mean total follow-up of 249.2 days for TICP and 490.4 days for MPLG, FSO patency was 82.9% and 87.1%, respectively (P =.265). At an equivalent follow-up of 130.6 days in TICP and 154.0 days in MPLG, patency was 94.3% and 89.7%, respectively (P =.475). Both groups showed significant reductions in SNOT-22 (P <.001). MPLG demonstrated crusting within the FSO at 1 month (none in TICP). Conclusion: FSO patency for both stents was similar, although TICP had significantly lower costs per unit. Additional comparative trials may be helpful for guiding clinicians on the appropriate clinical situations for the use of these devices. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease with no known single cause, but it is thought that bacteria play a role in the disease process. Objective: This pilot study aims to assess the longitudinal effect of corticosteroid therapy on sinus microbiota in chronic rhinosinusitis patients with nasal polyposis (CRSwNP). Methods: A longitudinal prospective case-control study was done on patients with CRSwNP and healthy controls. Patients with CRSwNP were randomly allocated to a corticosteroids and antibiotics treatment group (CRSwNP-SA) or a corticosteroid-only treatment group (CRSwNP-S). Data were collected at three-time points (before treatment, 1, and 3 months after treatment). Specimens were cultured and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) was used as a bacterial detection method. Results: Data from 29 patients with CRSwNP (16 CRSwNP-SA and 13 CRSwNP-S) was compared to 15 healthy subjects. Patients reported significant symptom improvement initially (1 month), but not in the long-term (3 months). This result was found in both treatment groups, whether or not antibiotics were used. After 3 months from treatment, the prevalence of Corynebacterium genera tended to increase in the CRSwNP-SA, while Staphylococcus and Gram-negative genera (Pseudomonas) tended to increase in the CRSwNP-S. Smoking, aspirin sensitivity, and previous endoscopic sinus surgery were found to be co-factors significantly associated with the response to systemic corticosteroid therapy. Conclusion: In this pilot study, both treatment options were effective to improve symptoms in the short-term but not in the long-term, and were not linked to any clear sinus microbiota response. As a result, this study supports the avoidance of systemic antibiotics without evidence of active infection. [ABSTRACT FROM AUTHOR]

Objectives: Transplant patients are high risk for surgery due to their immunocompromised state. There is a paucity of evidence concerning the differences in incidence of chronic rhinosinusitis (CRS) in solid versus non-solid organ transplant. Our aim is to analyze the difference in incidence of CRS requiring endoscopic sinus surgery (ESS) between non-solid and solid transplant populations and determine if certain risk factors are associated with increased incidence of recalcitrant CRS in non-solid versus solid transplants. Study Design: Retrospective cohort. Setting: Multisite tertiary academic center. Methods: This is a retrospective chart review of 1303 transplant recipients who were seen in our rhinologic clinic for CRS between 2017 and 2022. A total of 224 patients underwent ESS and were further analyzed for risk factors associated with recalcitrant disease requiring sinus surgery. Subgroup analysis based on solid and non-solid organ transplant was performed. Results: Of the 224 patients in the study, 171/224 (76.3%) had solid transplants while 53/224 (23.6%) had non-solid transplants. 17.19% of all transplant recipients required ESS. The incidence of ESS in non-solid transplants was 28.2% versus 57% in solid transplant. The risk of recalcitrant CRS in solid transplant recipients was almost 1.78 times greater than those with non-solid organ transplant (95% CI, 1.27-2.54, p = 0.0005). Individual factors such as certain immunotherapy drugs, pancytopenia, and rejection appear to correlate with the risk of ESS in both non-solid and solid organ transplant. Conclusion: Risk of ESS was greater in the solid transplant recipients compared to those who received non-solid organ transplant. [ABSTRACT FROM AUTHOR]

Background: Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. Objective: We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma. Methods: We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund–Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications. Results: FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P <.05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P <.001) and FEV1/FVC (r = −0.324, P =.001). A FeNO level of 27 ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68 ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36 ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%). Conclusion: FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment. [ABSTRACT FROM AUTHOR]

Background: Adult and elderly patients with chronic rhinosinusitis (CRS) undergo similar therapeutic management. Few studies have undertaken sinonasal tissue-level comparisons of these groups. This study examines histopathological differences between adults (>18, <65 years) and the elderly (≥65 years) with CRS, with the goal of optimizing medical management. Methods: In a retrospective cohort analysis, demographic factors, comorbidities, and a structured histopathological report of 13 variables were compared across adult and elderly patients with CRS who underwent functional endoscopic sinus surgery. These cohorts of adult and elderly patients included patients with and without nasal polyps (NP). Results: Three hundred adult (158 aCRSsNP, 142 aCRSwNP) and 77 elderly (38 eCRSsNP, 39 eCRSwNP) patients were analyzed. Mean age of the adult cohort was 44.4 ± 12.4 years, while that of the elderly cohort was 71.9 ± 5.9 years (P <.001). Significantly more adults compared to elderly individuals demonstrated a positive atopic status (79.7% vs 64.0%, P =.004). Elderly patients exhibited higher rates of comorbid diabetes mellitus than adult patients (21.6% vs 10.3%, P =.009). Adults exhibited more tissue eosinophilia (43.4% vs 28.6%, P =.012) and presence of eosinophil aggregates (25.0% vs 14.3%, P =.029) compared to elderly patients, regardless of NP status. Conversely, the elderly demonstrated significantly more fungal elements (11.7% vs 3.0%, P =.004), and trended toward increased overall inflammation (63.6% vs 55.3%, P =.118) and tissue neutrophilia (35.1% vs 27.3%, P =.117), compared to adults. Conclusion: Sinonasal tissue of adult and elderly patients with CRS demonstrates clear histopathological differences. Patient comorbidities, in addition to histopathological characterizations, may provide further context for management optimization. Level of Evidence: 2. Short Summary: Sinonasal tissue samples from adult and elderly patients with CRS demonstrate clear histopathological differences. These patient populations also exhibit unique comorbidities. These distinctions have the potential to inform and optimize management of this condition. [ABSTRACT FROM AUTHOR]

Background: Endoscopic sinus surgery with a middle meatal antrostomy is a common intervention in the treatment algorithm for maxillary sinus pathologies. However, this procedure has its origins in a time when simple ventilation of the sinus cavity was the primary (and only often) goal of surgery. In some patients, persistent mucociliary dysfunction occurs despite ventilatory surgery. Although the endoscopic modified medial maxillectomy (MMM) was originally described for tumour surgery, it provides a radical yet still functional option to overcome chronic sinus dysfunction. Objective: The goal of this study was to describe the functional status of a post-MMM sinus cavity. Methods: A consecutive series of patients who underwent at least a unilateral MMM by three tertiary rhinologists were retrospectively reviewed. Prospectively collected data included patient demographics (including age, gender, smoking status and comorbidities), disease-specific factors, microbiology, and preoperative patient-reported symptoms based on the 22-item Sinonasal Outcome Test-22 (SNOT-22) and radiology. The primary outcome of the study was the presence of sinus dysfunction, defined by mucostasis or pooling on endoscopic examination at the last follow-up. Secondary outcomes included the need for revision surgery as a result of sinus dysfunction and the improvement in SNOT-22 score. Results: A total of 551 medial maxillectomies (47.0% female, 52.9 ± 16.8 years) were performed. Very few patients experienced post-operative sustained mucostasis following MMM (10.2%) and even fewer required revision surgery (5.0%). Chronic obstructive pulmonary disease (odds ratio (OR) = 6.82, P < 0.002.) and asthma (OR = 2.48, P = 0.03) were associated with mucostasis. Patients who underwent an MMM experienced a notable postoperative improvement in SNOT-22 score (45.9 ± 23.7 (pre-op) vs. 23.6 ± 19.4 (post-op); paired t -test, P < 0.0001). Conclusion: The MMM, whether performed for access to pathology or with the intent to avoid mucous 'sumping' with the sinus, can provide a long-term functional maxillary sinus cavity with minimal morbidity. [ABSTRACT FROM AUTHOR]

Background: Endoplasmic reticulum stress (ER stress) is activated in chronic sinusitis with nasal polyps (CRSwNP) and leads to increased expression of C/EBP homologous protein (CHOP). However, the role of CHOP in the pathogenesis of CRSwNP remains unclear. Methods: CHOP expression was detected by immunohistochemistry staining in nasal mucosa of control and CRSwNP patients. Co-localization of CHOP and cleaved caspase3, p-MLKL, and CD68 was detected by immunofluorescence staining in CRSwNP patients. TNFα, IFNγ, IL1β, LPS, and tunicamycin were added to primary dispersed nasal polyp cells (DNPCs) to explore their roles in cell death. Western blot, CCK8 assay, and flow cytometry were employed to detect cell death. Results: CHOP was specifically activated in CRSwNP compared to controls. It was mainly macrophages that highly expressed CHOP, some of which underwent apoptosis and the other underwent necroptosis. IL1β induced increased CHOP and apoptosis, and a slight p-MLKL. In addition, ER stress could also promote p-MLKL expression. Whereas classical TNFα plus IFNγ and LPS did not induce increased necroptosis in DNPCs. Conclusion: IL1β induced the apoptotic pathway and minor necroptosis. And ER stress also plays a role in the occurrence of necroptosis in CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Previous research has shown diminished nasal immune function following nasal saline irrigation (NSI), returning to baseline at 6 hours. The aim of this study was to examine the immune nasal proteome before and after 14 days of nasal irrigation. Methods: Seventeen healthy volunteers received either isotonic (IsoSal) or low salt (LowNa) NSI. Nasal secretions were collected before and 30 min after NSI at baseline and again after 14 days. Specimens were analyzed using mass spectrometry to detect proteins of relevance to nasal immune function. Results: One thousand eight hundred and sixty-five proteins were identified with significant changes in 71 proteins, of which 23 were identified as part of the innate immune system. Baseline analysis demonstrated an increase of 9 innate proteins after NSI, most after IsoSal. After 14 days, a greater increase in innate peptides was present, with most now in the LowNa group. When NSI solutions were compared, a significant increase in 4 innate proteins, including a 211% in lysozyme, was detected in the LowNa group. Conclusion: LowNa NSI demonstrates evidence of improving the innate immune secretions, especially lysozyme, in healthy volunteers. [ABSTRACT FROM AUTHOR]

Background: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. Objective: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. Methods: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. Results: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τ b = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00–6.00] vs 6.00[6.00–6.75], p = 0.015). Other outcomes were similar. Conclusions: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disorder and effective treatment remains a major challenge. Some antibiotics with anti-inflammatory properties are reported to have potential to be used as an adjunct therapy in the management of chronic airway inflammation. Objective: The aim of this study was to evaluate the efficacy of doxycycline in CRSwNP. Methods: In this randomized, double-blind, placebo-control study, we assessed the efficacy of doxycycline in patients with moderate to severe CRSwNP. A total of 100 patients were randomly assigned to receive either doxycycline (200 mg on the first day followed by 100 mg daily) or placebo for 6 weeks. All patients received baseline therapy with fluticasone, montelukast, and nasal irrigation during the study. The primary outcome was quality of life based on the sino-nasal outcome test (SNOT-22) questionnaire. We measured peak nasal inspiratory flow (PNIF) and severity of symptoms by visual analogue scale (VAS). Baseline blood eosinophil count, serum IgE level, eosinophil in nasal secretions, and Lund-Mackay score based on low dose paranasal CT scan were also recorded. Results: Treatment with doxycycline significantly improved SNOT-22 (P =.037) and sense of smell (P =.048). The baseline SNOT-22 score had no effect on outcomes. The effect of doxycycline on quality of life in patients with or without nasal eosinophilia was not significantly different. Change in SNOT-22 score was also not correlated with serum IgE (P =.220, r = −0.186) and the eosinophil count (P =.190, r = −0.198). Conclusion: Doxycycline improves the quality of life in patients with CRSwNP. It also has temporarily beneficial effects in improving the sense of smell. The levels of eosinophil in the blood and nasal secretions do not affect the response to treatment. Hence, doxycycline can be used in both eosinophilic and non-eosinophilic nasal polyps. This study was registered at Iranian Registry of Clinical Trials. https://www.irct.ir/ IRCTID: IRCT20210403050817N1. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the upper airways. MicroRNAs (miRs) are reported to regulate several diverse physiological and pathological processes. Objective: This study aimed to evaluate the impact of miR-214 on lipopolysaccharide (LPS)-mediated inflammation, and mucin 5AC (MUC5AC) expression in human nasal epithelial cells. Methods: The expression of miR-214 was detected in CRS with polyps (CRSwNP) and CRS without polyps (CRSsNP) tissues. Cells were treated with LPS and a miR-214 inhibitor. The level of miR-214 was detected by quantitative real-time reverse transcriptase-PCR (qRT-PCR). The inflammatory cytokines (IL-6, IL-8, TNF, and IL-1β) and MUC5AC production were determined by qRT-PCR and ELISA. MUC5AC protein level was detected using western blot. Similarly, we determined the relationship between miR-214 and Sirtuin 1 (SIRT1) using the Dual luciferase activity assay. Results: miR-214 was increased in CRSwNP and CRSsNP tissues. LPS triggered the expression of miR-214, while miR-214 inhibition diminished the level of miR-214. MiR-214 inhibition prevented LPS-mediated the production of inflammatory cytokines. LPS treatment augmented MUC5AC mRNA, protein levels, and secretion, whereas miR-214 loss inhibited MUC5AC production in the presence of LPS. SIRT1 is a direct target of miR-214. Impairing SIRT1 by siRNA (siSIRT1) or EX527 (a selective SIRT1 inhibitor) reversed the effects of miR-214 inhibitor on inflammation and MUC5AC expression. Furthermore, miR-214 depression inhibited the STAT3/GDF15 pathway via targeting SIRT1. Upregulation of STAT3 or GDF15 partly abolished the anti-inflammatory roles of miR-214 inhibitor. Conclusion: Taken together, miR-214 regulates LPS-mediated inflammation and MUC5AC expression via targeting SIRT1, and STAT3/GDF15 may involve in the regulation of miR-214 inhibitor on inflammation and MUC5AC expression. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction is a common disease and it may be caused by sinonasal inflammation, toxin inhalation, or neurological disorders. After sinonasal inflammation, if both olfactory neuroinflammation and olfactory dysfunction occur still under investigation. Objective: This study aimed to investigate whether neuroinflammation and olfactory dysfunction occur after lipopolysaccharide (LPS)-initiated rhinosinusitis. Methods: Adult C57BL/6 mice were intranasally administered with LPS for 3 weeks. The olfactory function was evaluated with a buried food test. The inflammatory status of sinonasal cavity and olfactory bulb was evaluated with histology and biochemistry. Results: After 3-week LPS treatment, mice developed olfactory dysfunction, sinonasal cavity, and olfactory bulb inflammation. LPS-treated mice had greater sinonasal mucosal thickness. Besides, pro-inflammatory interleukin-6, the number of goblet cells and neutrophils in the sinonasal cavity was increased after LPS administration. The olfactory sensory neurons in the olfactory epithelium and the olfactory bulb were decreased, and the olfactory function was impaired by LPS administration. Inflammatory cytokines such as interferon-γ and tumor necrosis factor-α were increased in the olfactory bulb. Conclusion: This study showed that LPS-initiated rhinosinusitis caused olfactory neuroinflammation and olfactory dysfunction in mice. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy. Objective: The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers. Methods: A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further. Results: Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1β), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell–cell or cell–matrix interaction. Conclusion: Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative "liquid biopsy" for rhinosinusitis. [ABSTRACT FROM AUTHOR]

Heterogeneity in outcomes used in clinical trials prevents meta-analysis and contributes to research waste. Core outcome sets aim to address this by defining a small number of essential outcomes that should be measured in all effectiveness trials. Adoption in routine clinical practice can further improve outcomes for patients. There has been a rapid growth in therapeutic options available for patients with chronic rhinosinusitis with nasal polyps, but difficulty comparing results leads to uncertainty into optimum management, and there is a need to define a core outcome set. We consider whether work already undertaken needs to be modified for patients with nasal polyps. We recommend that a core outcome set should include assessment of disease specific quality of life, nasal polyp score, evaluation of sense of smell, alongside need for OCS and surgical treatment and complications from the disease or treatment. Further work is required to achieve international consensus regarding the choice of nasal polyp scoring system. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP) is a chronic inflammatory condition with significant patient morbidity and associated healthcare costs. While the economic burden of CRS overall has been previously described, the economic impact of CRSwNP has received less attention. Patients with CRSwNP have higher disease burden and healthcare resource utilization than those with CRS without nasal polyposis. Rapid evolution of medical management in recent years with the use of targeted biologics warrants further investigation into the economic burden of CRSwNP. Objective: Provide an updated review of the literature on the economic impact of CRSwNP. Methods: A literature review. Results: Research shows that patients with CRSwNP have higher direct costs and usage of ambulatory services compared to matched non-CRS controls. Patients undergoing functional endoscopic sinus surgery (FESS) incur roughly $13,000 in costs which is particularly relevant given the rate of disease recidivism and need for revision surgery associated with CRSwNP. Disease burden additionally leads to indirect costs through loss of wages and productivity due to work absenteeism and presenteeism, with estimates of up to roughly $10,000 lost in mean annual productivity cost in refractory CRSwNP. Several studies have shown FESS to be more cost-effective in intermediate and long-term management than medical therapy with biologics, despite similar long-term outcomes with respect to quality-of-life metrics. Conclusion: CRSwNP is a chronic condition with high recurrence rates making it a challenge to manage over time. Current research suggests that FESS is more cost-effective than medical management, including use of newer biologics. Further investigation into both direct and indirect costs associated with medical management is warranted to perform accurate cost-effectiveness analyses and allow for the best allocation of limited healthcare resources. [ABSTRACT FROM AUTHOR]

Background/Objective: 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). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogenous group of inflammatory conditions impacting the nose and paranasal sinuses. Our understanding of the underlying pathobiology of CRSwNP has substantially improved due to ongoing translational research efforts. Advances in treatment options, including targeted respiratory biologic therapy for CRSwNP, allow for more personalized approaches for CRSwNP patient care. Patients with CRSwNP are typically classified to one or more endotype based on the presence of type 1, type 2, and type 3 inflammation. This review will discuss recent advances in our understanding of CRSwNP and how this may impact current and future treatment approaches for patients with CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Acute invasive fungal sinusitis (AIFS) is an aggressive and dangerous disease of the paranasal sinuses with high morbidity and mortality. The immune response at the level of the nasal mucosa, the site of entry, has not been previously evaluated. Objective: To evaluate differential gene expression in the sinonasal mucosa of AIFS patients as compared to control patients using RNA sequencing. Methods: Sinonasal tissue samples were prospectively obtained from consenting patients undergoing surgery between November, 2020 and November, 2021. RNA extraction and sequencing were performed and differential expression was analyzed to detect transcriptional differences between patient groups. Results: Tissue samples were collected from 4 patients with active AIFS diagnoses, 2 patients with recovered AIFS, 1 patient with a diagnosis of non-invasive fungal ball, and 4 healthy controls. 255 genes were differentially expressed in AIFS patients as compared to control patients. Specific Gene Ontology (GO) biological processes that were identified as differentially expressed in AIFS patients as compared to controls included the following: 1. GO:0007155 (cell adhesion), 2. GO:0030199 (collagen fibril organization) and 3. GO:0001525 (angiogenesis). Conclusion: Transcriptional differences were noted between AIFS and control patients in sinonasal tissue samples. Future work is necessary to determine causes of the differential gene expressions between AIFS and control patients, specifically those who are immunosuppressed, or with preexisting non-invasive forms of fungal sinusitis, to guide treatment and prevention strategies. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) remains still inconclusive. Recent studies identified an increased expression of BAFF (a B cell-activating factor) and its receptor TACI (Transmembrane Activator and cAML Interactor) in nasal polyp samples, while TNFRSF13B/TACI mutations have been found in patients with benign lymphoproliferative disorders and primary antibody deficiencies. Objective: The aim of our study was to evaluate the possible contribution of TNFRSF13B/TACI mutations in CRSwNP pathogenesis. Methods: Forty-four (44) patients with CRSwNP (male/female: 33/11, mean age: 52.5 years, range: 16-83) were analyzed for TNFRSF13B/TACI mutations by PCR-sequencing. Results: No pathogenic TNFRSF13B/TACI mutations were identified in our cohort study of CRSwNP patients. We detected two common missense mutations (p.P251L and p.V220A), along with other common silent mutations and intronic polymorphisms in an identical prevalence to healthy control population. Conclusion: TNFRSF13B/TACI mutations might not play a role in the pathogenesis of CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory condition of the paranasal sinuses characterized by intractable nasal polyps with prominent eosinophil infiltration. These eosinophils are presumably recruited from peripheral blood via vessels expressing peripheral lymph node addressin (PNAd), a set of glycoproteins decorated with 6-sulfo sialyl Lewis x (sLex) glycans that serve as L-selectin ligands. Based on the severity classification algorithm proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group, ECRS is divided into mild, moderate and severe groups; however, as yet there are few reports comparing the clinicopathological differences among these groups. Objective: Our goal was to elucidate clinicopathological differences among the three different severities of ECRS with special reference to eosinophils and PNAd-expressing vessels. Methods: We performed quantitative immunohistochemical analysis of PNAd-expressing vessels using surgical specimens of nasal polyps from patients exhibiting varying severity of ECRS (n = 35) and from individuals with non-ECRS (n = 10). To this end, we immunostained tissue sections with anti-PNAd and anti-CD34 monoclonal antibodies, and then determined the number of vessels immunolabeled with each antibody. Results: The number of eosinophils infiltrating nasal polyps was correlated with ECRS severity. We also found that the PNAd + /CD34 + vessel ratio, namely, the percentage of PNAd-expressing vessels among all vessels, was positively correlated not only with ECRS severity but also with the number of eosinophils infiltrating nasal polyps formed in ECRS. Conclusion: These results strongly suggest that PNAd-expressing vessels play at least a partial role in eosinophil recruitment to nasal polyps and consequent severity of ECRS. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) and eosinophilic esophagitis (EoE) are immune-mediated inflammatory conditions that share common histopathologic features. Once considered two separate pathologies, preliminary data has suggested that a higher prevalence of EoE may exist in patients with CRS. Objectives: We aimed to expand the base of evidence across geographic regions and investigate the association between EoE and CRS, including CRS with nasal polyposis (CRSwNP). Methods: Quantitative data detailing the prevalence of CRS, CRSwNP, and EoE were pooled from 6 large academic institutions spread across the United States using Epic electronic medical record system. One-way analysis of variance was then used to analyze the data. Results: The mean prevalence of EoE in our general population sample of over 26 million individual records was 0.058% (range, 0.013%-0.103%). The mean prevalence of EoE in our sub-populations of individual with diagnoses of CRS and CRSwNP was 0.43% (F(1,12) = [8.194], P =.01) and 0.84% (F(1,12) = [23.61], P <.01) respectively. Conclusion: This study reveals an 8-fold greater prevalence of concurrent EoE in patients with CRS. Importantly, this is the first study to describe the association of EoE and the CRSwNP subtype, and we demonstrate a 14-fold greater prevalence of EoE in patients with CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Hypersecretion of mucin 5AC (MUC5AC) is a prominent feature of chronic rhinosinusitis with nasal polyps (CRSwNP) and autophagy plays a pivotal role in this process. TNF receptor-associated factor 6 (TRAF6) functions as a signal transducer in many inflammation diseases, whereas the correlation between TRAF6 and autophagy in CRSwNP remains unclear. Objective: To investigate the role of TRAF6 in the human neutrophil elastase (HNE)-induced autophagy and mucin MUC5AC over-expression in CRSwNP. Methods: Tissue specimens were obtained from control subjects and patients with CRSwNP. The relationships between HNE, TRAF6, autophagy, and MUC5AC were investigated. The effect of TRAF6 on HNE-mediated autophagy and hypersecretion of MUC5AC was assessed by in-vitro culture of HNECs treated with human recombinant HNE. Results: Patients with CRSwNP had more protein expression of HNE, MUC5AC, TRAF6, and light chain (LC3B), and increased levels of Beclin-1(BECN1) and autophagy-related gene 5 (ATG5) in mRNA level. Treatment of nasal epithelial cells with recombinant HNE induced the upregulation of TRAF6, autophagy, and MUC5AC. Alternatively, si-TRAF6 or autophagy inhibitor treatment mitigates the hyperexpression of MUC5AC before incubating with recombinant HNE. Conclusion: HNE promotes autophagy through TRAF6, resulting in hyperexpression of MUC5AC in CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Orbital, intracranial, and osseous extra-sinus complications can arise from bacterial or fungal sinusitis. Odontogenic sinusitis (ODS) can cause extra-sinus complications, but its prevalence remains poorly characterized. Objective: To determine the frequency of ODS as a cause of operative extra-sinus infectious complications and describe clinical features of all complicated sinusitis cases. Methods: A multi-institutional retrospective review was performed on all operative sinusitis-related extra-sinus complications from 2011 to 2020. ODS was diagnosed by sinus computed tomography (CT) and dental evaluations when available. Demographics, complication types, sinusitis etiologies, and various clinical features were analyzed. Results: Forty-five patients were included (mean age 55.5 years, 56% male). Of the extra-sinus complications, 40% were orbital only, 22% intracranial only, 13% osseous only, and 25% involved combined complications. The 2 most common causes of extra-sinus complications were ODS (40%) and mucopyocele (27%). When invasive fungal etiologies were excluded, and only unilateral maxillary opacification on CT was considered, nearly 60% of extra-sinus complications were due to ODS. Unilateral maxillary sinus opacification on CT was present in 100% of complicated ODS compared to 44% of nonodontogenic cases, and oral anaerobes were only identified in ODS cases. No complicated ODS patients underwent dental interventions during hospitalization. Conclusion: ODS was the most common cause of operative extra-sinus infectious complications. Clinicians should consider ODS high on the differential diagnosis of all patients presenting with complicated sinusitis, especially when sinusitis is unilateral and invasive fungal infection is not suspected. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are chronic type 2 inflammatory diseases that are frequently associated with each other. Dupilumab inhibits the dual signaling pathways of interleukin (IL)-4 and IL-13, which are key and central drivers of type 2 inflammation in CRSwNP. Omalizumab blocks the action of immunoglobulin E. Head-to-head studies are required to investigate the comparative efficacy and safety of these interventions. EVEREST (EValuating trEatment RESponses of dupilumab vs omalizumab in Type 2 patients) trial is designed to evaluate whether the efficacy of dupilumab is superior to omalizumab in treating patients with CRSwNP and comorbid asthma (ClinicalTrials.gov Identifiers: NCT04998604). Objective: Here, we describe the EVEREST study design to compare the efficacy and safety of dupilumab compared to omalizumab over 24 weeks of treatment in patients with severe CRSwNP and comorbid asthma. Methods: EVEREST is a global, phase 4 multicenter, randomized (1:1), double-blind, active-controlled trial. Approximately 422 adult patients with severe CRSwNP, symptoms of nasal congestion and loss of smell, and coexisting asthma will be recruited across 15 countries. The primary objective is to assess the efficacy of dupilumab compared to omalizumab in reducing the nasal polyp size and improving the sense of smell. The key secondary objectives are to evaluate the comparative efficacy in improving CRSwNP symptoms (eg, nasal congestion) and lung function. The safety will be evaluated in terms of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest. Conclusions: EVEREST is the first head-to-head trial assessing the comparative efficacy and safety of 2 biologics in patients with severe CRSwNP and comorbid asthma. The study will provide evidence to help optimize treatment plans for patients that suffer from severe CRSwNP and comorbid asthma. [ABSTRACT FROM AUTHOR]

Background: Nasal mucus is proving to be a useful means by which to study the pathogenesis of chronic rhinosinusitis (CRS). Given the increase in publications examining nasal mucus and the lack of a review on this topic, we will focus on this noninvasive approach to studying CRS. Particular attention will be drawn towards inflammatory cytokines and biomarkers and their influence on disease severity. Methods: A literature review of papers published in English pertaining to nasal mucus was performed using the PubMed database. The search utilized combinations of the following keywords: sinusitis, polyps, sample collection, nasal mucus, or nasal secretion. Studies solely on acute or bacterial sinusitis, allergic rhinitis, or cystic fibrosis were not included. Results: A wide variety of materials and methods have been used to collect nasal mucus. Numerous assay types have been performed with the most common being ELISA, cytometric bead array, and proteomics. Most studies have focused on examining the levels of Th1/Th2 cytokines along with chemokines associated with type 2 immunity. Other factors identified include growth factors, senescence-associated proteins, complement, and antimicrobial defenses have also been identified. Nasal mucus cytokines have proven useful in cluster analysis and predicting postoperative improvement in Sino-nasal Outcome Test (SNOT-22) scores. One limitation of the use of nasal mucus is that some studies have suggested that nasal mucus does not always reflect the tissue microenvironment. Conclusions: Nasal mucus represents a critical tool by which to examine the sinonasal microenvironment in a noninvasive manner. Unlike studies of tissue, it can be utilized in both surgically and medically managed patients and avoids the trauma of biopsies. However, studies are still needed to determine the most effective method for nasal mucus collection. Studies should also take care to confirm that nasal mucus markers do, in fact, reflect the levels of the product studied in the tissue. [ABSTRACT FROM AUTHOR]

Background: Social determinants of health (SDOH) and comorbid conditions (CMCs) influence the setting of presentation for care; however, few studies have explored this relationship in the context of sinus disease. Objective: This study aims to characterize the relationship of SDOH and CMCs with acuity of health care presentation setting in adults with sinusitis. Methods: A retrospective analysis based on medical records (demographics, visit types, and ICD-10 codes) of 1842 adult patients presenting with sinusitis to an urban academic medical center was conducted. Chi-square analysis was used to assess bivariate associations of SDOH (age, race/ethnicity, sex, insurance type, and employment status) and CMCs (depression, body mass index [BMI], allergy, and gastroesophageal reflux disease [GERD]) with high-acuity visit types—including emergency department (ED) and inpatient visits. Multivariable binary logistic regression was performed to examine the adjusted associations between SDOH and high-acuity visits. Results: The sample's mean age was 46.8 years, with 68.5% females and 31.5% males. In adjusted models, the odds of high-acuity visit presentation was higher for males than females (odds ratio [OR]: 1.57; confidence interval [CI]: 1.22–2.01); non-Hispanic Blacks (OR: 2.21; CI: 1.58–3.09) as well as Hispanics/Latinos (OR: 2.10; CI:1.43–3.08) than Whites; unemployed (OR: 1.90; CI: 1.47–2.46.) than employed. Age was positively associated with high-acuity presentation. While GERD was associated with increased odds of high-acuity presentation (OR: 2.80; CI: 1.64–4.78), BMI, allergy, and depression did not have a statistically significant association with these visit types. These associations were independent of insurance coverage, which was not statistically associated with high-acuity visits. Conclusion: SDOH and CMCs were associated with high-acuity healthcare presentation in adults with sinusitis. While this study highlights how SDOH affect healthcare usage patterns among people with sinusitis, further investigation is needed to identify and address the causes of these patterns. [ABSTRACT FROM AUTHOR]

Background: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. Objective: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. Methods: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. Results: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. Conclusion: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months. [ABSTRACT FROM AUTHOR]

Background: Large epidemiologic studies have suggested that a history of tobacco use may be associated with an increased risk of developing chronic rhinosinusitis (CRS). The impact of tobacco use on revision rates of endoscopic sinus surgery (ESS), however, remains limited. Objective: This study seeks to define the independent risk of tobacco use (active or prior) on revision rates of ESS among a large cohort of patients with CRS. Methods: A state population database was queried for patients age ≥18 years with CRS who underwent at least one ESS between 1996 and 2018. Demographic characteristics, history of ESS, and tobacco use status were compared across patients with CRS, using t tests for continuous variables and χ2 tests for categorical variables. Unadjusted and adjusted logistic regression models were used to understand the impact of tobacco status on revision surgery. Results: The final analysis included 34 350 patients (29 916 CRS with no revision surgery and 4434 CRS with revision surgery). Unadjusted regression analysis demonstrated an increased odds of undergoing revision ESS (OR 1.12, 95% CI: 1.00–1.25, P =.05) among males with a history of tobacco use and CRS. Adjusted regression analysis demonstrated that the risk of revision ESS among CRS patients with a history of asthma and tobacco use was 1.72-fold, while the risk among CRS patients who were tobacco users without asthma was 1.11-fold. Conclusion: History of tobacco use is an independent risk factor for revision ESS among patients with CRS. [ABSTRACT FROM AUTHOR]

Background: The pathophysiologic mechanisms of human chronic rhinosinusitis (CRS) are highly complex, and sinonasal colonization with pathogens is the first and most important step in this process. NLRP3, the main receptor activated by pathogen-associated molecular patterns (PAMPs), is associated with a variety of inflammatory diseases, including airway inflammation; however, the understanding of its role in CRS is limited. Objective: By detecting the differential expression of the NLRP3 inflammasome and its downstream cytokines IL-1β and IL-18 between CRS patients and controls, between different CRS phenotypes (CRSsNP and CRSwNP), between mucosal tissue and polyp tissue, and further its relationship with neutrophilic/eosinic infiltration, we aimed to elucidate the biological role of the NLRP3 inflammasome in the pathophysiologic mechanisms of CRS. Methods: Fifteen cases in each control, CRSsNP, and CRSwNP groups (subdivided into mucosa tissue and polyp tissue) were included in this study. Differential expression of NLRP3/caspase-1 and its downstream cytokines IL-1β and IL-18 was investigated, and its relationship with neutrophilic and eosinophilic infiltration was analyzed. Fluorescent immunohistochemistry (F-IHC) was used to assess NLRP3 and caspase-1 expression, RT-PCR was used for mRNA level quantitation, and western blotting was employed to analyze the protein concentrations. Results: NLRP3 and cleaved caspase-1 were expressed at higher levels in both the CRSsNP and CRSwNP phenotypes than in the control nasal mucosa and at much higher levels in polyp tissue of CRSwNP (P <.05), which was in line with the expression of cleaved IL-1β and cleaved IL-18 (P <.05). Higher expression of NLRP3 had a mild correlation with neutrophilic infiltration but highly correlated with eosinophilic infiltration (R = 0.607, P <.01). Conclusions: NLRP3 is involved in the pathogenesis of CRS, most likely by the NLRP3/caspase-1/IL-1β and IL-18 response. It induced eosinophilic infiltration in CRSwNP, especially in polyp tissue. As for whether NLRP3 induces neutrophilic infiltration, further experiments are needed to confirm. [ABSTRACT FROM AUTHOR]

Background: Air pollution is a serious health concern and affects inflammatory sinonasal diseases such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Clarifying the relationship between air pollutants and upper respiratory diseases could help the patients. Objective: To evaluate the association between the concentration of air pollutants and the prevalence of AR and CRS among South Koreans. Methods: In this cross-sectional study, nationwide data were reviewed for participants of the Korean National Health and Nutrition Examination Survey (KNHANES) 2008 to 2012. Participants were surveyed with health questionnaires, examined with endoscopies by otolaryngologists, and tested with serum immunoglobulin E levels. The concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and particulate matter with aerodynamic diameters ≤10 µm (PM10) were measured in 16 areas of South Korea. Air pollutant concentrations of geographic districts were matched to each participant's residence. Logistic regression analysis was performed. Results: Among 27 863 eligible adults, 3359 and 1606 participants had AR or CRS, respectively. In multivariable logistic regression analysis for AR, PM10 showed statistically significant results (odds ratio [OR] = 1.145, 95% confidence interval [CI] = 1.042–1.258). No air pollutants showed statistically significant differences in the prevalence of CRS. In AR, PM10 (OR = 1.458, 95% CI = 1.201–1.770) was associated with endoscopic findings of watery rhinorrhea, whereas SO2 (OR = 1.202, 95% CI = 1.100–1.313) was associated with pale mucosa. Conclusion: The prevalence of AR was significantly associated with PM10 concentration. In patients with AR, endoscopic findings of watery rhinorrhea were associated with PM10. However, CRS was not associated with the air pollutant concentrations. Lower concentration of PM10 might help managing the clinical symptoms in patients of AR. [ABSTRACT FROM AUTHOR]

Background: Acute invasive fungal rhinosinusitis has been associated with high mortality rates. Objective: We aimed to explore the contribution of novel detection and treatment methods on the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis. Methods: The records of all children with a hematologic or oncologic disease who developed acute invasive fungal rhinosinusitis between 2005–2020 were reviewed. Results: Thirty-four patients were included. Aspergillosis and mucormycosis were diagnosed in 20 patients (59%) and 12 patients (35%), respectively. Panfungal polymerase chain reaction (PCR) was associated with a change of treatment in 36% of patients. A more aggressive surgical approach as well as treatment with liposomal amphotericin B and novel antifungals were adopted in recent years. Overall, 26% of patients died of disease, however no disease-specific death occurred since 2012. Diagnosis using panfungal PCR (p =.04) and treatment with novel antifungal medications (p =.017) were significantly associated with disease-specific survival. Conclusion: Enhanced fungal detection using panfungal PCR and treatment with novel antifungal agents, combined with rapid diagnosis and treatment, aggressive surgical approach and better control over the underlying oncological disease, may significantly improve the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is often associated with other comorbidities due to chronic inflammation. However, no population-based, longitudinal study has investigated the relationship between CRS and chronic skin inflammation. Objective: To investigate the potential relationship between CRS and chronic skin inflammatory diseases, such as atopic dermatitis (AD), vitiligo, and psoriasis. Methods: A total of 5638 patients with CRS and 11 276 without CRS as a comparison group, were included from the Korean National Health Insurance Service database from 2002–2013. A propensity score matching (1:2) was performed using the nearest neighbor matching method, sociodemographic factors, and enrollment year. The Cox proportional hazards model was used to analyze the hazard ratio of CRS for AD, vitiligo, and psoriasis. Results: Results from this study showed that patients with CRS had no significant risk of the subsequent development of vitiligo or psoriasis compared to patients without CRS. However, we found a significantly higher incidence of AD in CRS patients than in those without CRS. The incidence of AD was 63.59 per 1000 person-years in the CRS group and 45.38 per 1000 person-years in the comparison group. Additionally, young and middle-aged CRS patients were independently associated with a higher incidence of subsequent AD events, but we could not find a significantly higher incidence of AD events in the elderly group. Conclusions: Our findings suggest there are no significant differences in the overall risk of vitiligo and psoriasis events in patients with CRS; however, we detected a higher risk of AD in young and middle-aged CRS patients. Therefore, clinicians should consider the risk of developing AD in specific patients who are newly diagnosed with CRS. [ABSTRACT FROM AUTHOR]

Background: Implantological procedures aimed at rehabilitating upper jaw edentulous patients (dental implant placement and/or maxillary sinus grafting) can sporadically result in sinusitis. In these patients, endoscopic sinus surgery is the most commonly employed treatment, but clinical scenarios and comprehensive management strategies are extremely heterogeneous across studies. Objective: We sought to systematically define treatment strategies and related success rates for sinusitis following dental implantation, detailing different current treatment choices and concepts. Methods: Adopting a PRISMA–compliant review framework, systematic searches were performed in multiple databases using criteria designed to include all studies published until November 2020 focusing on the treatment of human sinusitis following dental implantation. We selected all original studies, excluding case reports, specifying treatment modalities with objective treatment success definitions. Following duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates, which were pooled in a random-effects meta-analysis. Results: Among 581 unique citations, eight studies (181 patients) were selected. Seven studies were retrospective case series. All studies relied on endoscopic sinus surgery, often coupled with intraoral accesses, and assessed therapeutic success endoscopically. The pooled treatment success rate was 94.7% (95% confidence interval, 91.5%–98%). Failures were treated in seven of 15 cases with further antibiotic therapies and in another seven cases with surgical revision. A single patient was lost to follow-up. Conclusions: Endoscopic sinus surgery appears to be the most frequent treatment of choice for sinusitis following dental implantation, with excellent success rates. The protean clinical picture drawn from the selected studies calls for the standardization of diagnostics and definitions in this field to enable direct comparisons between the results of different studies. The role of postoperative antibiotic therapies, which have been employed unevenly across studies, should also be prospectively investigated. [ABSTRACT FROM AUTHOR]

Background: Mental health conditions are common in the United States, and recent efforts have examined the development of mental health conditions among patients with sinusitis. Objectives: The purpose of this study was to investigate the association between depression, anxiety, and financial hardship among patients with sinusitis. Methods: Cross-sectional study using the 2018 National Health Interview Survey (NHIS). Data regarding demographics, perceived financial hardship, self-reported depression and anxiety, mental healthcare utilization, and treatment compliance were obtained. Results: Among patients with sinusitis (N = 28 million adults), 9% reported depression and 24% reported anxiety. Sinusitis patients with depression and anxiety reported an increased severity of financial insecurity (p < 0.001). On multivariable logistic regression, worsening financial insecurity increased the odds of depression and anxiety. Patients reporting the highest financial insecurity severity had the highest odds of depression (OR = 3.88, 95% CI = 3.84–3.93, p < 0.001) and anxiety (OR = 2.09, 95% CI = 2.08–2.10, p < 0.001) among measures of financial stress. Specific financial stressors were independently associated with patient-reported depression and anxiety. Sinusitis patients with increased financial insecurity were more likely to require mental health services and treatment (p < 0.001), but were also more likely to report cost-related treatment noncompliance (p < 0.001) and reduced access to mental healthcare due to costs (p < 0.001). Conclusion: Perceived financial hardship is associated with self-reported depression and anxiety among patients with sinusitis. Sinusitis patients with financial hardship also face challenges in accessing and maintaining mental health services and treatment due to costs. Understanding the burden of financial insecurity on mental health and access to treatment may improve quality of care through the development of screening tools and individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a common condition that affects patients' quality of life. Standard treatments for CRS have known side effects and variable efficacy rates. Thus, complementary and integrative (CIM) treatments for CRS such as crenotherapy, which utilizes high mineral content water or vapor as an inhalation therapy, are of continued interest. Objectives: To summarize and evaluate the current research investigating crenotherapy's therapeutic potential and clinical outcomes for the treatment of CRS. Study Design: Systematic review and qualitative analysis. Methods: A systematic review was performed, with a comprehensive search strategy applied to 6 databases from inception to March 2021: CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science. Studies with at least 10 patients, which investigated crenotherapy as the sole or adjunctive treatment for CRS in humans were included. Results: In total, 10 articles out of 756 were included. Of these, 6 were randomized controlled trials. The remaining four articles were non-randomized prospective cohort studies. Six studies assessed clinical symptoms in response to crenotherapy, and there were unanimous improvements in Visual Analog Scale (VAS), Sino-Nasal Outcome Test-20 (SNOT-20), and other quality of life metrics. The studies that assessed inflammatory markers, cytology, or other measures showed significant improvement in neutrophil count, spores, ciliary motility, IgE, and manometry. Minimal to no adverse events were reported across all 10 studies. Conclusion: There is limited data to support crenotherapy's effectiveness in treating patients with CRS. However, published studies suggest that for certain patients crenotherapy can both improve CRS symptoms and objective measures of nasociliary function with minimal side effects. Findings must be interpreted with caution due to study heterogeneity, inconsistent use of standard CRS definitions and outcomes measures, as well as other study design flaws. Given these results, as well as a growing interest in CIM, crenotherapy treatments for CRS deserve further investigation. [ABSTRACT FROM AUTHOR]

Background: Fractional exhaled nitric oxide (FeNO) is a cost-effective, noninvasive point-of-care test that has proven valuable in identifying patients with lower airway inflammation and predicting the likelihood of responsiveness to inhaled corticosteroid therapy in asthma. The utility of FeNO in upper airway disease, specifically in CRS, remains to be determined. Objective: The goal of this study was to test whether FeNO could serve as a noninvasive marker of sinonasal mucosal inflammation in CRS patients. Methods: FeNO was obtained using a nitric oxide analyzer (NIOX VERO) as well as nasal mucus, the 22-item Sinonasal Outcome Test (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and Lund-Kennedy endoscopic scores concurrently in 112 CRS patients. Nasal mucus was analyzed for cytokine expression using solid-phase sandwich ELISA. Linear regression with Spearman correlation coefficient was used to determine strength of relationship between variables. Results: CRS patients showed elevated FeNO levels with asthma (47.12 ± 5.21 ppb) or without asthma (43.24 ± 9.810 ppb). Elevated FeNO levels correlated with sinonasal mucosal inflammation, as determined by increased levels of CCL26 and TNFα in nasal mucus obtained from CRS patients. Furthermore, elevated FeNO levels selectively correlated with worsened SNOT-22 nasal symptoms (P = 0.03) and Lund-Kennedy endoscopic scores (P = 0.007), but did not correlate with UPSIT scores. Conclusions: FeNO levels correlated with increased sinonasal mucosal inflammation and symptom severity in CRS regardless of asthma status. FeNO measurements may serve as a quick and noninvasive marker in evaluating CRS patients. [ABSTRACT FROM AUTHOR]