Olfactory cleft mucus galectin-10 predicts olfactory loss in chronic rhinosinusitis.

BACKGROUND: Eosinophils have been reported to be involved in the pathogenesis of olfactory fluctuation in chronic rhinosinusitis (CRS). Galectin-10 is more frequently associated with type 2 inflammation and potentially a sign of intense eosinophil activation. OBJECTIVE: To explore olfactory cleft mucus and olfactory mucosa galectin-10 level and its association with olfactory dysfunction (OD) in CRS. METHODS: We prospectively enrolled 50 patients with CRS and 15 healthy controls. Olfactory cleft mucus and superior turbinate biopsy specimens were collected to analyze galectin-10 levels and quantify tissue eosinophils. Psychophysical olfactory testing, olfactory cleft endoscopy scale, and olfactory cleft computed tomography scores were obtained. The predictability of galectin-10 levels for OD in patients with CRS was analyzed by multivariable logistic regression analysis. RESULTS: Both olfactory cleft mucus and olfactory mucosa galectin-10 levels in patients with CRS with OD were significantly higher than those in patients with CRS without OD (all P < .001). Mucus galectin-10 levels were positively correlated with tissue eosinophils (r = 0.541, P = 0.002), olfactory cleft endoscopy scale (r = 0.498, P = 0.006), and olfactory cleft computed tomography scores (r = 0.432, P = 0.019) in patients with CRS. Mucus galectin-10 levels were negatively correlated threshold, discrimination, and identification (r = -0.589,  P = 0.001), olfactory threshold (r = -0.522, P = 0.003), olfactory discrimination (r = -0.488, P = 0.007), and olfactory identification (r = -0.466, P = 0.011) scores. After adjusting for patient demographics and comorbidities, mucus galectin-10 levels were significantly associated with OD in patients with CRS (odds ratio, 1.299; P = .008). Mucus galectin-10 levels greater than 8.975 ng/mL were the best predictor of OD in CRS. CONCLUSION: Olfactory cleft mucus galectin-10 is highly associated with OD in CRS.

Association between cognition and olfaction-specific parameters in patients with chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) have reported significantly cognitive and olfactory dysfunction. This study aimed to explore the relationship between cognitive function and olfaction-specific parameters in patients with CRS. METHODS: A cross-sectional survey method was used to investigate 98 participants, including 75 patients with CRS and 23 healthy controls. Cognitive function and psychophysical olfactory tests were performed. Olfactory cleft endoscopy scale and olfactory cleft computed tomography (CT) scores were obtained. Multivariate logistic regression was used to analyze the risk factors of Mild Cognitive Impairment (MCI) in patients with CRS. RESULTS: There are significant differences in age, Montreal Cognitive Assessment (MoCA) scores, number of MCI, Lund-Mackay olfactory cleft (LM-OC) score, and blood eosinophil count between CRS with and without olfactory dysfunction groups (all P < 0.05). Total MoCA scores were positively correlated with thresholds-discrimination-identification (TDI) score (r = 0.541, P < 0.001), olfactory threshold (OT) (r = 0.440, P < 0.001), olfactory discrimination (OD) (r = 0.541, P < 0.001), and olfactory identification (OI) (r = 0.382, P = 0.001) scores. Furthermore, total MoCA scores were negatively correlated with LM-OC scores (r = - 0.351, P = 0.002). After adjusting for patient demographics, only the OD score was an independent risk factor for MCI among patients with CRS (odds ratio = 0.792; P = 0.039). The OD scores less than 11.5 were the best predictor of MCI in patients with CRS. CONCLUSION: Olfaction-specific clinical parameters were highly correlated with cognitive function in patients with CRS and the OD score was an independent risk factor for MCI in patients with CRS.

Development of an apparatus and procedure for evaluating the efficiency of nasal irrigation.

BACKGROUND: Although different methods of nasal irrigation have been utilized, irrigation efficiency in nasal cavities has not been well assessed. The objective of this study was to develop an apparatus and procedure for evaluating the irrigation efficiency and to explore the optimal head position during irrigation. METHODS: Casts of the left sinonasal cavity from a healthy volunteer were made from high-resolution-computed tomography data using 3D printing with composite materials. An adjustable apparatus that allowed cast fixation at the different head positions was built. The yogurt was used to simulate mucus. The cast with 5 ml yogurt filled around the superior, middle, and inferior turbinate was fixed in six head positions including head tilt 10°, 45°, and 60° forward with or without leaning 30° to the right. The cast was irrigated with 120 ml, 175 ml, and 240 ml dyed water and was video recorded. The irrigation efficiency was calculated based on the weight difference of the cast before and after the irrigation. RESULTS: Most residual yogurt was located around the superior meatus after the irrigation under different volumes and head positions. The irrigation efficiency of the rinse bottle or the pulsatile device was volume dependent, with the highest irrigation efficiency under 240 ml water. When the left sinonasal cavity was irrigated, the head position of tilt 45° forward with leaning 30° to the right was the optimal head position for these two devices when compared to other positions. The pulsatile device with 240 ml water performed better than the rinse bottle with 240 ml water regarding the irrigation efficiency under the optimal head position (0.8700 ± 0.0138 vs 0.7536 ± 0.0099, p = 0.003). CONCLUSIONS: The developed apparatus provided a potential method for evaluating the irrigation efficiency. The head position of tilt 45° forward with leaning 30° was suitable for patients to perform the nasal irrigation.

Clinical significance of the cognition-related pathogenic proteins in plasma neuronal-derived exosomes among normal cognitive adults over 45 years old with olfactory dysfunction.

OBJECTIVES: Exosomal Phospho-Tau-181(P-T181-tau), Total tau (T-tau), and amyloid-ß peptide 42 (Aß42) have been proved the capacity for the amnestic mild cognitive impairment (MCI) and the diagnosis of Alzheimer's disease (AD). This study aimed to explore the cognitive function and the levels of P-T181-tau, T-tau, and Aß42 in neuronal-derived exosomes (NDEs) extracted from plasma in normal cognitive adults over 45 years old with olfactory dysfunction. METHODS: A cross-sectional survey of 29 participants aged over 45 was conducted. Plasma exosomes were isolated, precipitated, and enriched by immuno-absorption with anti- L1 cell adhesion molecule (L1CAM) antibody. NDEs were characterized by CD81, and extracted NDE protein (P-T181-tau, T-tau, and Aß42) biomarkers were quantified by enzyme-linked immunosorbent assay (ELISAs). Olfactory performance was assessed by Sniffin' Sticks and cognitive performance was assessed by Montreal Cognitive Assessment (MoCA). RESULTS: There was no significant difference between adults with olfactory dysfunction and without olfactory dysfunction regarding the cognitive function as measured by MoCA and all the participants showed normal cognition. Adults with olfactory dysfunction showed a higher concentration of P-T181-tau in plasma NDEs than did adults without olfactory dysfunction (P = 0.034). Both the levels of P-T181-tau (r = - 0.553, P = 0.003) and T-tau (r = - 0.417, P = 0.034) negatively correlated with the odor identification scores. In addition, the level of T-tau negatively correlated with MoCA scores (r = - 0.597, P = 0.002). The levels of P-T181-tau (r = - 0.464, P = 0.022) and T-tau (r = - 0.438, P = 0.032) negatively correlated with the delayed recall scores. CONCLUSIONS: This study demonstrated that cognition-related pathogenic proteins including P-T181-tau in plasma NDEs were significantly increased in adults over 45 years old with olfactory dysfunction before the occurrence of cognitive impairment. The impaired odor identification and the delayed recall function were highly associated with the increased levels of P-T181-tau and T-tau in plasma NDEs.

Patterns of Olfactory Impairment Among Patients with Uncontrolled Chronic Rhinosinusitis.

OBJECTIVES: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test. METHODS: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS. RESULTS: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS. CONCLUSION: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2341-2348, 2024.

Olfactory cleft mucus eosinophil-derived neurotoxin better reflects olfactory loss than blood eosinophil counts in patients with chronic rhinosinusitis.

BACKGROUND: Eosinophils are associated with olfactory dysfunction in chronic rhinosinusitis (CRS) and eosinophil-derived neurotoxin (EDN) is a sensitive marker of intense eosinophil activation. This study aimed to analyze olfactory cleft mucus and olfactory mucosa EDN levels and their association with olfactory dysfunction in CRS. METHODS: We prospectively recruited 150 patients with CRS electing endoscopic sinus surgery and 25 healthy controls. Both superior turbinate biopsy specimens and olfactory cleft mucus were collected to analyze EDN levels. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, and olfactory cleft endoscopy scale (OCES) were obtained. Multivariable logistic regression analysis was applied to analyze the predictability of EDN levels for olfactory dysfunction in CRS. RESULTS: Chronic rhinosinusitis with olfactory dysfunction presented significantly higher olfactory mucosa (p = 0.016) and olfactory cleft mucus (p < 0.001) EDN levels than CRS without olfactory dysfunction. Mucus EDN levels were positively correlated with blood eosinophils (r = 0.625, p = 0.002), olfactory cleft CT scores (r = 0.738, p < 0.001), and OCES (r = 0.605, p = 0.004) in CRS. Furthermore, mucus EDN levels were significantly negatively correlated with threshold, discrimination, and identification (TDI) (r = -0.688), olfactory threshold (r = -0.606), olfactory discrimination (r = -0.608), and olfactory identification (r = -0.697) scores. After adjusting for patient demographics and comorbidities, mucus EDN levels were significantly associated with olfactory dysfunction in CRS (odds ratio = 2.162; p = 0.027). Mucus EDN levels showed a significantly better performance for predicting olfactory dysfunction than blood eosinophil counts (area under the curve, 0.873 vs. 0.764, p = 0.024). CONCLUSION: Olfactory cleft mucus EDN level may be a better biomarker for predicting olfactory dysfunction in CRS than blood eosinophil counts.

Development of a novel centrifugal extraction device to collect the olfactory cleft mucus.

BACKGROUND: Measuring olfactory cleft mucus biomarkers provides critical insights into the pathogenesis of the olfactory dysfunction. OBJECTIVES: This study aimed to develop a novel centrifugal extraction device to collect the olfactory cleft mucus. MATERIAL AND METHODS: The olfactory cleft mucus was collected from 18 patients with chronic rhinosinusitis (CRS) and 10 healthy controls using polyvinyl alcohol (PVA) sponges. Both novel centrifugal extraction devices and traditional devices which consisted of a falcon tube and a syringe shaft were utilized. Levels of Galectin-10 were assessed using the enzyme-linked immunosorbent assay. The olfaction was evaluated with Sniffin' Sticks. RESULTS: The average extraction efficiency of recovered volume for novel centrifugal extraction devices and traditional devices was 85.44 and 79.15%, respectively. Galectin-10 levels of the olfactory cleft mucus in patients with CRS were significantly higher than that in controls when extracted through novel devices (p < .001). Furthermore, levels of Galectin-10 in patients with CRS significantly correlated with TDI score (p = .020, r = -0.546). There was no significant difference between novel and traditional devices regarding Galectin-10 levels in CRS (p = .966). CONCLUSIONS AND SIGNIFICANCE: The novel centrifugal extraction device with PVA sponges proved to be a feasible method to collect the olfactory cleft mucus.

A novel irrigation device with superior nasal irrigation efficiency to the classic rinse bottle.

BACKGROUND: The ability of saline irrigation to detach the mucous and the flow-limiting effect of the nasal valve has not been well explored. The objective of this study was to compare the removal efficiency of a novel irrigation device with an extended nozzle versus a classic rinse bottle. METHODS: Transparent casts of the unoperated sinonasal cavity were made by 3D printing. Yogurt was used to simulate mucous. The cast filled with 5 ml yogurt was fixed in six head positions and irrigated with 120 ml, 175 ml, and 240 ml dyed water through the novel device and the rinse bottle. The irrigation efficiency was the ratio of the weight of yogurt washed away divided by the total weight of yogurt. RESULTS: The irrigation stream of a long nozzle with a side opening was different from the irrigation stream of the outlet within the nasal vestibule. The novel devices presented with continuous water stream directly upwards to the anterior part of the olfactory cleft. Depending on different head positions, it was easy for the novel devices to achieve an irrigation efficiency of 100% when the cast was irrigated with 120 ml or 175 ml water. There was still a tiny amount of yogurt left in the olfactory cleft when the cast was irrigated with 240 ml water under each head position for the rinse bottle. The irrigation efficiency was volume-dependent, and the average irrigation efficiency of the rinse bottle at 240 ml only reached 69.1%. CONCLUSIONS: The novel irrigation device presented with superior nasal irrigation efficiency to the classic rinse bottle. A continuous water stream directly upwards to the anterior part of the olfactory cleft combined with an extended nozzle overcoming the flow-limiting effect of the nasal valve promotes nasal irrigation efficiency.