Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.

Objectives: Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods: Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results: Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL-4 and IL-13 signaling, IL-10 signaling, and rhodopsin-like receptors. Conclusions: RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL-10, rhodopsin-like receptors, and IER3 in the pathogenesis of olfactory dysfunction.

Comparison of trigeminal lateralization with differing stimulants.

Trigeminal-specific stimulants have been shown to activate different receptors preferentially and this likely accounts for variation in sensory perception. It is unclear whether trigeminal sensitivity is similar across different transient receptor potential (TRP) receptors or if dysfunction of different receptors results in differing patient symptoms. Therefore, a prospective cohort study was conducted, consisting of trigeminal lateralization testing with three different stimulants (eucalyptol, isothiocyanate, acetic acid), olfaction testing with Sniffin' Sticks, and measurement of various patient-reported outcome measures (PROMs). A total of 50 participants were enrolled across the olfactory spectrum. Mean TDI score was 27.1 ± 8.3 (range 7.0-39.5) with 38% normosmic and 62% dysosmic. Mean trigeminal lateralization scores out of 20 in the overall cohort were 16.18 (2.78) for eucalyptol, 14.94 (3.49) for mustard oil, and 15.28 (3.68) for vinegar. Eucalyptol showed a significant correlation with threshold scores of Sniffin' Sticks. A significant correlation was found between acetic acid and various PROMs. None of the lateralization scores of the trigeminal stimulants correlated to each other significantly and there was no correlation to age. The lack of correlation suggests that the measured sensitivity of one type of TRP receptor may not translate to similar sensitivity of the other receptors. Additional investigations with TRPV1 and TRPA1 agonists are needed to corroborate our findings.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

The Impact of Acute Peri-operative Particulate Matter Exposure on Endoscopic Sinus Surgery Outcomes: A Preliminary Multi-site Investigation.

BACKGROUND: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown. OBJECTIVE: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS). METHODS: Participants with CRS who self-selected ESS were prospectively enrolled. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility values scores were recorded. Using residence zip codes, a secondary analysis of patient exposure to PM <2.5 µm and <10 µm (PM2.5 and PM10, respectively) was performed for the month of surgery utilizing data from Environmental Protection Agency air quality monitors. Spearman's correlation coefficients (ρ), 95% confidence intervals (CIs), and effect estimates (ß) were used to determine the magnitudes of association. Simple, multivariate regression analysis was also completed. RESULTS: One hundred and seven patients from four geographically unique institutions across the US were enrolled with a follow-up of 6 months. Patients with higher peri-operative PM2.5 exposure had less improvement in their SNOT-22 scores after ESS compared to those with less exposure using both univariate analysis (ρ = 0.26, 95% CI: 0.08, 0.43; P = .01) and after covariate adjustment with multivariate analysis (B = 1.06, 95% CI: 0.001, 2.14, P = .05). Similar associations were not found with SF-6D outcomes or with PM10 as an exposure of interest. No significant correlations were found between peri-operative PM levels and Lund-Kennedy endoscopy scores post-operatively. CONCLUSION: Preliminary data from this pilot study reveal that PM exposure at the time of ESS may negatively associate with post-operative improvement in sinonasal quality-of-life. Larger, population-based studies with more standardized PM exposure windows are needed to confirm the clinical significance of the present findings.

The Inflation Reduction Act: Implications for Medicare spending and access to biologic therapies for chronic rhinosinusitis with nasal polyposis and asthma.

KEY POINTS: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA). Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%. Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%-60%.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

BACKGROUND: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. METHODS: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019-2023). Participants were administered the 22-SinoNasal Outcome Test (SNOT-22) survey and a modified SNOT-22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT-22 symptom importance subdomains in two sets of subgroups-those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. RESULTS: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post-nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT-22 total symptom importance scores to non-ETI users (p = 0.14). Non-ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055). CONCLUSIONS: Nasal congestion and post-nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre-operative discussions. Non-ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required.

Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022.

KEYPOINTS: Between 2007 and 2022, the FDA received 119 US-based reports mentioning budesonide nasal irrigation. Most reports were submitted by patients and alerted FDA to off-label usage of budesonide. Notable adverse events reported to the FDA included headache, dyspnea, and blurred vision.

Challenges to medication adherence with intranasal corticosteroid irrigations.

BACKGROUND: The purpose of this study was to investigate real-world adherence to intranasal corticosteroid irrigations using pharmacy data and assess factors associated with low adherence. METHODS: Patients undergoing treatment with corticosteroid irrigations for any diagnosis during a 2-year period were prospectively recruited. Subjects completed a one-time set of questionnaires including the Barriers to Care Questionnaire (BCQ), 22-item Sino-Nasal Outcome Test (SNOT-22), and a questionnaire assessing their experience with corticosteroid irrigations. Pharmacy data was used to calculate the medication possession ratio (MPR), a measure of medication adherence graded from 0 to 1. RESULTS: Seventy-one patients were enrolled. Patient diagnoses included chronic rhinosinusitis (CRS) without nasal polyps (n = 37), CRS with nasal polyps (n = 24), or a non-CRS diagnosis, most commonly chronic rhinitis (n = 10). The MPR for the overall group was 0.44 ± 0.33. Just 9.9% of patients had a perfect MPR of 1. Despite low MPR, only 19.7% of patients reported problems taking the medication when directly asked. Lower education resulted in lower MPR (unstandardized B = 0.065, p = 0.046). Increasing BCQ score, indicating higher barriers to care, was associated with lower MPR (unstandardized B = -0.010, p = 0.033). The lower the MPR, the worse the patient SNOT-22 scores (unstandardized B = -15.980, p = 0.036). CONCLUSION: Adherence to corticosteroid irrigations was low and patients underreported issues with their medication. Education and barriers to care were associated with lower adherence, which, in turn, was associated with worse sinonasal quality of life.

Factors Impacting Follow-Up Care in Allergic Fungal Rhinosinusitis.

OBJECTIVE: The purpose of this study was to analyze barriers to medical care and follow-up in patients with allergic fungal rhinosinusitis (AFRS). STUDY DESIGN: Cross-sectional questionnaire-based study with retrospective chart review. SETTING: Tertiary Medical Center. METHODS: Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review. RESULTS: Fifty-nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow-up within 6 months of surgery (35.6% vs 17.7%, P = 0.04) and no-show at least 1 appointment (20.3% vs 5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow-up visit (37.0% vs 3.1%, P < 0.001) and be lost to follow-up (66.7% vs 9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs 35.1%, P = 0.034), lost to follow-up (77.3% vs 10.8%, P < 0.0001), and have a single follow-up visit (40.9% vs 5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow-up visit (odds ratio 1.143, 95% CI 1.022-1.276). CONCLUSION: Young, male AFRS patients are more frequently lost to follow-up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow-up in these at-risk groups.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

INTRODUCTION: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. METHODS: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. RESULTS: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). CONCLUSION: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Gray matter and episodic memory associations with olfaction in middle-aged to older adults.

BACKGROUND: Age-related declines in olfaction contribute to low quality of life and appear to occur with declines in cognitive function, including diminished episodic memory. We tested the hypothesis that low gray matter volume within cortical regions that support olfaction and episodic memory can explain age-related differences in olfactory and episodic memory functions. METHODS: T1-weighted images, Sniffin' Sticks olfactory measures, and the NIH Toolbox-Cognition Battery were administered to 131 middle-aged to older adults (50-86 years; 66% female). Correlation was used to examine the associations between these measures. A network-based image processing approach was then used to examine the degree to which spatial patterns of gray matter variance were related to the olfactory and cognitive measures. Structural equation modeling was used to characterize the relative specificity of olfactory, cognitive, gray matter, and aging associations. RESULTS: Olfactory threshold, discrimination, and identification exhibited small to medium effect size associations with episodic memory performance (rs = 0.27-0.42, ps < 0.002). Gray matter volume within medial temporal and orbitofrontal cortex was also related to olfactory (discrimination and identification) and episodic memory function (rs = 0.21-0.36, ps < 0.019). Age and episodic memory explained the same variance in olfaction that was explained by the medial temporal and orbitofrontal pattern of gray matter volume. CONCLUSIONS: The results of this cross-sectional study suggest that identifying mechanisms contributing to differences in medial temporal and orbitofrontal cortex will advance our understanding of co-morbid olfactory and cognitive declines.

Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy.

BACKGROUND: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. METHODS: Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. RESULTS: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p = 0.004) was associated with pursing medical therapy. CONCLUSIONS: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden.

Potential Role for Diet in Mediating the Association of Olfactory Dysfunction and Cognitive Decline: A Nationally Representative Study.

In the context of a growing body of evidence associating olfactory dysfunction (OD) with cognitive decline, this cross-sectional study used data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) sample in order to explore the role of dietary intake in this association. Leveraging a nationally representative sample of U.S. adults aged 60 years and older, this study analyzed dietary patterns using exploratory factor analysis. OD was categorized based on the NHANES Pocket Smell Test, and cognitive function was measured with a battery of tests. Survey-weighted multivariable regressions and causal mediation analysis were used to examine the relationship between dietary patterns, OD, and cognitive function. Results indicated that a poor adherence to a diet rich in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs) was independently associated with both cognitive and olfactory dysfunctions, after adjusting for sociodemographic and health factors. Moreover, the relationship between OD and cognitive decline was found to be partly mediated by adherence to such a diet. This study proposes a potential link between diet, olfactory function, and cognitive decline, highlighting the role of nutritional interventions in mitigating cognitive decline, particularly in individuals with olfactory impairment.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Accessing the Eustachian tube: Conventional nasal spray vs. exhalation delivery system and the impact of targeted endoscopic sinus surgery on topical distribution patterns.

BACKGROUND: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). METHODS: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0- to 3-point scale, with ratings averaged for analysis. RESULTS: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21-10.09; p = 0.021) and post-ESS (OR, 9.00; 95% CI, 1.95-41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44-104.85; p = 0.001). CONCLUSIONS: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery.

All chronic rhinosinusitis endotype clusters demonstrate improvement in patient-reported and clinical outcome measures after endoscopic sinus surgery.

BACKGROUND: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures. METHODS: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund-Kennedy endoscopic score (LKES). RESULTS: A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (-28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures. CONCLUSIONS: All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes.