All Chronic Rhinosinusitis Endotype Clusters Demonstrate Improvement in Patient Reported and Clinical Outcome Measures after Endoscopic Sinus Surgery

Background It is unclear if chronic rhinosinusitis (CRS) endotypes show differential response to endoscopic sinus surgery (ESS). We explored mucus inflammatory cytokine expression in a cohort with CRS and associations with both patient-reported and clinically measured postoperative outcome measures. Methods Patients with CRS were prospectively recruited between 2016-2021 into a multi-center observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient reported outcome measures included the 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’ Stick testing and Lund-Kennedy endoscopic scores (LKES). Results A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, non-inflammatory, and 2 indeterminate clusters based upon individual protein levels. Overall, the type 2 inflammatory cluster was found to report the highest mean improvement in both SNOT-22 (-28.3 [SD±16.2]) and TDI (6.5 [SD±7.9]) scores 6 months after ESS. However, all endotype clusters demonstrated improvement in all outcome measures after ESS on average, 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 respond favorably to surgery and show improvement 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

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

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

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

Abstract 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

Abstract 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

American Rhinologic Society expert practice statement: Postoperative pain management and opioid use after sinonasal surgery

Summary The goal of this American Rhinologic Society expert practice statement (EPS) is to provide clinically applicable, evidence‐based recommendations regarding pain management in sinonasal surgery. This EPS was developed following the recommended methodology and approval process as previously outlined. The topics of interest included preoperative counseling, local anesthesia, use of opioids for postoperative pain, use of nonopioid medication for postoperative pain, nonsteroidal anti‐inflammatory drugs and bleeding, and use of gabapentin for pain control. Following a modified Delphi approach, 6 statements were developed, 5 of which reached consensus and 1 that did not. These statements and accompanying evidence are summarized along with an assessment of future needs