Smell Identification Test Research Articles

Predicting Post-Mortem α-Synuclein Pathology by the Combined Presence of Probable REM sleep behavior disorder and Hyposmia.

Idiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α-synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post-mortem LTS. To assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post-mortem presence of LTS in a broader, less-selected, volunteer elderly population. We studied 652 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders, which were evaluated for PRBD, had completed annual movement and cognitive assessments, and had at least one the University of Pennsylvania Smell Identification Test (UPSIT) olfactory test. Histological evidence of LTS was significantly more frequent in those who had PRBD (112/152: 73.7%) than those without (177/494: 35.8%) (P < 0.001). LTS was more frequent in cases with PRBD and a low UPSIT score (90.8%) compared to cases with PRBD only (73.7%) (P < 0.001) or cases with a low UPSIT score only (69.4%) (P < 0.001). Sensitivity of PRBD diagnosis for predicting LTS was 38.8% and specificity 88.8%, whereas sensitivity of a low UPSIT score was 74.4% and specificity 73.4% (Youden's index = 0.276 for PRBD, 0.478 for UPSIT). When combining both measures, sensitivity was 34.3% and specificity increased to 97.2%. PRBD, diagnosed without sleep study confirmation, combined with a reduced olfactory performance is highly specific for predicting post-mortem presence of LTS. The combination of both measures may provide a cost-effective means of predicting LTS in a broader community.

Preservation of Olfactory Function After Pediatric Endoscopic Endonasal Skull Base Surgery with Nasoseptal Flap Reconstruction

ObjectiveEndoscopic endonasal surgery is a feasible approach to lesions of the pediatric skull base. Olfactory outcomes following endoscopic endonasal approach (EEA) have been reported in the adult literature, but pediatric outcome data is lacking. The purpose of this preliminary study is to evaluate post-operative olfactory outcomes in pediatric patients who underwent EEA through transsphenoidal and/or transclival corridors. MethodsRetrospective chart review of patients < 18 years of age who underwent EEA with nasoseptal flap skull base reconstruction between March 2019-January 2022. Following their first post-operative debridement and 6 months following surgery, patients were administered the University of Pennsylvania Smell Identification Test (UPSIT) to assess olfactory function. ResultsFifteen patients (7 female, 8 male) with a mean age of 14.9 years met inclusion criteria. Thirteen (86.7%) patients required a transsphenoidal approach and 2 (13.3%) patients underwent a combined transsphenoidal and transclival approach. Mean time between surgical resection and first olfactory testing was 6.3 weeks (range 4.6-7.3 weeks). Nine patients (60.0%) had normosmia following EEA while 3 (20.0%) had mild microsmia, and 3 (20.0%) had moderate microsmia at 6 weeks following surgery. Results improved at their 6 month follow up visits. No patients experienced post-operative severe microsmia or anosmia. ConclusionsOlfactory preservation is possible following pediatric EEA, though 40% of patients will develop some degree of microsmia in the immediate post-operative period and 20% will have some persistent dysfunction at 6 months. Long-term data is necessary to determine if microsmia continues to improve over time.

Clinical progression of Parkinson’s disease in the early 21st century: Insights from the Accelerating Medicine Partnership (AMP-PD) data

BackgroundParkinson’s disease (PD) therapeutic strategies have evolved since levodopa introduction in mid 1900s. To understand their impact and research gaps, this study delineated the clinical progression of PD in recent years. MethodsUsing Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores. Age at diagnosis was set as 0 years, and data were tracked for 15 subsequent years. ResultsAmong 3,001 PD cases identified to be suitable for this study, 2,838 are white, 1,843 are males, with a mean age at diagnosis was 60.2±10.3 years. At baseline evaluation, the disease duration was 9.9±6.0 years overall, 1915 within 0-5, 541 with 6-10, 254 within 11-15, and 163 greater than 15 years. Participants largely reported independence (S&E, 5y: 86.6±12.3; 10y: 78.9±19.3; 15y: 78.5±17.0) and good quality of life (PDQ-39, 5y: 15.5±12.3; 10y: 22.1±15.8; 15y: 24.3±14.4). Motor scores displayed a linear progression, whereas non-motor scores plateaued ∼10-15 years. Younger onset age and female correlated with slower progression. ConclusionsTwenty-first century PD patients remain largely independent in the first decade of disease at tertiary subspecialty care and research centers. There are data gaps for those who are non-whites or longer PD duration, and sensible metrics that can gauge non-motor progression when PD is beyond 10 years.

Development and validation of the four-item Concise Aging adults Smell Test to screen for olfactory dysfunction in older adults.

Olfactory dysfunction (OD) in the elderly is common and associated with numerous comorbidities, yet often underrecognized. This study sought to develop an instrument for widespread screening of this condition. Demographic factors, comorbidities, and olfactory-related questions were examined in a focus group (N=20) and development cohort (N=190). The 4-item Concise Aging adults Smell Test (4-CAST) screening instrument was then developed to predict OD on Sniffin Sticks testing. An independent validation cohort (N=147) was then examined to confirm ability of the 4-CAST to predict OD on Smell Identification Test 40 (SIT40). The most important variables for predicting olfactory loss in older subjects were age, type II diabetes status, Visual Analog Scale (VAS) of overall rating of smell, and VAS of impact of smell upon safety. In the development cohort, the 4-CAST model yielded predictive probability (area under the curve) of 0.805 (p<0.001) for predicting the bottom 25th percentile on Sniffin Sticks. Results were similar in the validation cohort, as the 4-CAST accurately classified 83.8% subjects (area under the curve [AUC] 0.789, p<0.001) in the bottom 25th percentile of SIT40 testing. The 4-CAST was able to accurately classify 89.4% of subjects with anosmia. The 4-CAST is a quick screening instrument for predicting OD in older adults and has similar performance characteristics in independent populations using the two most common validated olfactory tests. Given the high prevalence of unrecognized olfactory loss in this population, this can be a useful tool for practitioners to determine which subjects may benefit from more extensive olfactory testing.

The Effect of Platelet-Rich Plasma and Hyaluronic Acid Nasal Injections in the Treatment of Traumatic Olfactory Dysfunction.

Objective: Platelet-rich plasma (PRP) has been injected into the olfactory cleft to treat olfactory dysfunction related to coronavirus disease 2019. In this study, we aimed to evaluate the effect of PRP combined with hyaluronic acid (HA) nasal injection in the treatment of traumatic olfactory dysfunction. Methods: Patients who had lost olfactory function after experiencing head trauma and were willing to receive PRP and HA nasal injections for treatment were enrolled. Before nasal injection, 10 cc of blood was drawn from the patients. The drawn blood was injected into a centrifuge tube for processing, and finally, 5 cc of the PRP mixed with HA was drawn out using an empty syringe. The PRP mixed with HA was injected into the upper part of the middle nasal septum and the medial side of the middle turbinate of the patient's nasal cavity under a nasal endoscope. The olfactory function of each patient was evaluated by the phenyl ethyl alcohol (PEA) odor detection threshold test before and at both 1 and 3 months after nasal injection and the traditional Chinese version of the University of Pennsylvania Smell Identification Test at 3 months after nasal injection. Results: A total of 28 patients received PRP and HA nasal injections between August and December of 2023 and came back for evaluation of the effect. In all, 20 (71.4%) patients felt their olfactory function improved 1 month after injection, and 24 of 28 (85.7%) patients reported their olfactory function improved at 3 months after injection. The bilateral or unilateral PEA threshold decreased in 22 (78.6%) patients 1 month after injection, and decreased in 15 (53.6%) patients 3 months after injection. Conclusions: Our results show that PRP and HA nasal injections were associated with favored patient-reported outcomes and improved the olfactory threshold in the treatment of traumatic olfactory dysfunction.

Comparison of brief olfactory and cognitive assessments to neuroimaging biomarkers in the prediction of cognitive decline and dementia in the MCSA cohort.

We evaluated impaired odor identification and global cognition as simple, cost-effective alternatives to neuroimaging biomarkers to predict cognitive decline and dementia in the Mayo Clinic Study of Aging. Six hundred forty-seven participants (mean 8.1, standard deviation 3.4 years' follow-up) had the following baseline procedures: modified Blessed Information Memory Concentration Test (BIMCT), 12-item Brief Smell Identification Test (BSIT), structural brain magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging with 11C-Pittsburgh compound B (11C-PiB) and fluorodeoxyglucose (FDG; subset). Cognitive decline developed in 102 participants and dementia in 34 participants. In survival analyses, PiB PET showed robust prediction for cognitive decline. Impaired BSIT, impaired BIMCT, MRI, and FDG measures were also significant predictors. The combination of demographics + BSIT + BIMCT showed strong predictive utility (C-index 0.81), similar to demographics + PiB PET (C-index 0.80). Similar but stronger results were obtained for prediction of dementia. Impairment in both odor identification test and global cognition was comparable to PiB PET for predicting cognitive decline and dementia. In 647 participants in the population-based Mayo Clinic Study of Aging, several clinical markers and biomarkers each predicted cognitive decline or dementia during an average 8 years of follow-up. The combination of the demographic variables of age, sex, and education with a brief odor identification test (BSIT) and a global cognitive test (Blessed Information Memory Concentration Test) showed strong predictive utility (C-index 0.81) for cognitive decline that was similar to the demographic variables combined with Pittsburgh Compound B amyloid imaging (C-index 0.80). Combining a brief odor identification test with a brief cognitive test needs consideration as a simple, cost-effective option in the clinical assessment of individuals at risk of cognitive decline and dementia, as well as a potential tool to identify individuals who may benefit from disease-modifying treatments and to screen participants for prevention trials.

Sinonasal Complications of Combined Transseptal–Transnasal and Bilateral Transnasal Approaches for Endoscopic Endonasal Transsphenoidal Pituitary Surgery

BackgroundThe endoscopic combined transseptal–transnasal technique for pituitary adenoma excision is notable for enhanced postoperative functional outcomes. Our study compared the incidence of anterior nasal septal perforation and the resulting sinonasal complications between this method and the bilateral transnasal approach. MethodsUtilizing a retrospective cohort from a preeminent tertiary referral center, we analyzed 141 cases of endoscopic endonasal transsphenoidal surgery performed between March 2018 and May 2023. Outcomes for the transseptal–transnasal group (n = 71) and the conventional bilateral transnasal group (n = 70) were compared. Nasal endoscopy and computed tomography were used to assess anterior nasal septal perforation. Functional outcomes were assessed preoperatively and at 6 months postoperatively using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, Cross-Cultural Smell Identification Test (CCSIT), Sino-Nasal Outcome Test-22 (SNOT-22), and nasal obstruction symptom evaluation (NOSE) ResultsThe transseptal–transnasal approach exhibited reduced rates of postoperative ear fullness (p < 0.001), along with fewer subjective complaints of smell/taste loss (p = 0.022) and thick nasal discharge (p = 0.008), compared to the conventional approach. However, objective smell test results were not significantly different between the two approaches (p = 0.243 and p = 0.454 for CCCRC and CCSIT, respectively). Additionally, although statistically insignificant, a higher incidence of anterior septal perforation was observed with the transseptal–transnasal approach (p = 0.067). ConclusionFor the surgical treatment of pituitary adenomas, the transseptal–transnasal approach offers several advantages over the bilateral transnasal method, particularly in reducing postoperative complications. However, this technique requires careful attention for preventing the occurrence of anterior septal perforation.

A Pilot Study of the Computerized Brief Smell Identification Test

Objectives: A self-administered Computerized Brief Smell Identification Test (cB-SIT) was developed recently to perform the olfactory identification test under computer control. The aim of this study was to evaluate the clinical applicability of the cB-SIT as compared with the traditional Brief Smell Identification Test (B-SIT). Methods: Sixty healthy volunteers with self-reported normal olfactory function, 30 hyposmic patients, and 30 anosmic patients were enrolled from June 2023 to May 2024. All enrolled participants received both B-SIT and cB-SIT in a random order to measure their odor identification ability. Thirty healthy volunteers took the second B-SIT and cB-SIT at least one week later. Results: The score was significantly different in both B-SIT and cB-SIT among healthy volunteers, hyposmic, and anosmic patients. The correct answer rate was significantly different in 10 items of the B-SIT and in 7 items of the cB-SIT among the three groups, but the post hoc test showed significant differences in correct answer rates between healthy volunteers and hyposmic patients in 7 items of both the B-SIT and cB-SIT. Test–retest results showed the score of the second B-SIT test was significantly higher than that of the first test, but the scores of the two tests of the cB-SIT were not significantly different. In the B-SIT, the lemon odorant had a higher correct answer rate in the second test than in the first test, but in the cB-SIT, the correct answer rate was not significantly different between the first and second tests in all 12 items. Conclusions: Our findings demonstrate that the cB-SIT was similar to the B-SIT and can be administered in the diagnosis of patients with olfactory dysfunction.

Dupilumab Versus Mepolizumab for Chronic Rhinosinusitis With Nasal Polyposis: An Indirect Treatment Comparison

BackgroundDupilumab and mepolizumab have shown efficacy and safety in treating chronic rhinosinusitis with nasal polyps (CRSwNP). ObjectiveWithout available results from head-to-head randomized control trials (RCTs) comparing dupilumab with other biologics, we conducted an indirect treatment comparison (ITC) with mepolizumab. MethodsA systematic literature review identified RCTs of biologics in CRSwNP. A Bucher ITC was performed, including nasal polyp score (NPS; range 0–8), nasal congestion (NC; 0–3), loss of smell (LOS; 0–3), University of Pennsylvania Smell Identification Test (UPSIT; 0–40), visual analog score (VAS; 0–10), Sino-Nasal Outcome Test (SNOT-22; 0–110), systemic corticosteroids (SCS) use or surgery for nasal polyps (NPs), and binary responder analyses for NPS and SNOT-22 improvement by ≥1/≥2 and ≥8.9, respectively. Matching-adjusted indirect comparisons (MAIC) were conducted as supporting analyses. ResultsSINUS-24/-52 (SYNAPSE-like subpopulation only) and SYNAPSE were identified for ITC. At 24 weeks, change from baseline in NPS and proportion of patients with a binary responder outcome of NPS improvement ≥1 were significantly (P<0.05) greater in patients receiving dupilumab versus mepolizumab. At 52 weeks, improvements in NPS, NC, LOS, UPSIT, and VAS were significantly (P<0.05) greater for dupilumab versus mepolizumab. Proportion of patients achieving binary responder outcomes of NPS and SNOT-22 improvement by ≥1/≥2 and ≥8.9, respectively, was significantly (P<0.05) higher, while SCS use was significantly (P<0.05) reduced, for dupilumab versus mepolizumab. Surgery rate was numerically reduced with dupilumab versus mepolizumab. The MAIC analyses confirmed these results. ConclusionsDupilumab was associated with greater improvements in CRSwNP-related outcomes versus mepolizumab.

Influence of Single Nucleotide Polymorphisms on CRS Outcomes: A Preliminary Observational Study.

To conduct a preliminary investigation into the relationship between specific SNP variants, type II inflammation, and the effectiveness of dupilumab therapy and surgery in patients with CRS. In this prospective study, 48 subjects were enrolled, comprising 32 CRS patients and 16 healthy controls. The CRS patients were subjected to either dupilumab therapy or endoscopic surgery according to EPOS guidelines. SNP variants were identified using the TaqMan SNP genotyping technique. The identified SNP profiles were compared between the control group and CRS patients, and their potential influence on treatment outcomes was evaluated. Treatment responses were assessed based on symptom scores, such as SS-I, SNOT-22, disease progression using the NPS findings, and SNP profiles at a 6-month follow-up. The primary measures included the Nasal Polyp Score, Smell Identification Test (SIT) score, and SNOT-22 outcomes. Dupilumab therapy and surgery significantly decreased NPS, with the last showing superior results. However, dupilumab therapy resulted in a significantly improved SIT score. Significant differences were observed in SNP profiles, particularly with rs1800629 (TNFA), rs2856838 (IL1a), rs17561 (IL1a), and rs1805011 (IL4R). In particular, the expression of rs2856838 and rs1805011 variants in the dupilumab group was associated with significantly better SIT and SNOT-22 outcomes than non-expressors. Also, the surgery group patients expressing the rs2856838 variant reported significant improvements in SNOT-22 scores. These preliminary findings suggest that SNP genotypes may guide personalized treatment strategies for CRS. Further larger prospective studies are required to confirm these initial observations. 2 Laryngoscope, 2024.

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Subjective and objective effects of radioiodine therapy on the sense of smell.

Evaluating the impact of radioiodine therapy (RIT) on olfactory function in thyroid cancer patients through quantitative and qualitative olfactory tests. In this cohort study, patients with thyroid cancer were included. Demographic, clinical, and laboratory data were collected. To subjectively evaluate the olfactory changes aftter RIT, the Visual Analog Scale (VAS), Self-Reported Mini-Olfactory Questionnaire (self-MOQ), and the University of Washington Quality of Life Questionnaire (UW-QOL) were assessed. Out of UW-QOL questions those related to saliva, taste, and overall health condition were analysed. For objective assessment, patients underwent both the Butanol Threshold Test (BTT) and the a version of Smell Identification Test (SIT). Patients were assessed before, one month, and six months after RIT. Ninety eight patients were included (Male = 17). A statistically significant decrement was observed in olfaction based on the VAS, between the baseline and one (pvalue = 0.015) and six months (pvalue = 0.031) of follow-up. Additionally, saliva (pvalue = 0.001), taste (pvalue = 0.000), and overall health condition (pvalue = 0.010) significantly decreased one-month after RIT. The measures were not different between the baseline and 6-month follow up and the improvement of index of taste was significant from 1-month to 6-months follow ups (pvalue = 0.000). However, none of the objective tests (the BTT and the SIT) indicated a significant decline in olfaction during the follow up. A subjective RIT related decrease in smell function, taste, and saliva production was documented without any objective olfactory dysfunction.

Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated with Olfactory Dysfunction.

Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. To identify the genetic loci associated with olfactory dysfunction in the general population. This genome-wide association study meta-analysis (GWMA) included participants of European ancestry (N = 22,730) enrolled in four different large population-based studies, followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). The data analysis was performed from March 2023 through June 2024. Genome-wide single nucleotide polymorphisms. Olfactory dysfunction was the outcome and assessed using a 12-item smell identification test. GWMA revealed a novel genome-wide significant locus (tagged by rs11228623 at 11q12) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes. These findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health.

Predicting Cerebrospinal Fluid Alpha-Synuclein Seed Amplification Assay Status from Demographics and Clinical Data.

To develop and externally validate models to predict probabilities of alpha-synuclein (a-syn) positive or negative status in vivo in a mixture of people with and without Parkinson's disease (PD) using easily accessible clinical predictors. Uni- and multi-variable logistic regression models were developed in a cohort of participants from the Parkinson Progression Marker Initiative (PPMI) study to predict cerebrospinal fluid (CSF) a-syn status as measured by seeding amplification assay (SAA). Models were externally validated in a cohort of participants from the Systemic Synuclein Sampling Study (S4) that had also measured CSF a-syn status using SAA. The PPMI model training/testing cohort consisted of 1260 participants, of which 76% had manifest PD with a mean (± standard deviation) disease duration of 1.2 (±1.6) years. Overall, 68.7% of the overall PPMI cohort (and 88.0% with PD of those with manifest PD) had positive CSF a-syn SAA status results. Variables from the full multivariable model to predict CSF a-syn SAA status included age- and sex-specific University of Pennsylvania Smell Identification Test (UPSIT) percentile values, sex, self-reported presence of constipation problems, leucine-rich repeat kinase 2 (LRRK2) genetic status and pathogenic variant, and GBA status. Internal performance of the model on PPMI data to predict CSF a-syn SAA status had an area under the receiver operating characteristic curve (AUROC) of 0.920, and sensitivity/specificity of 0.881/0.845. When this model was applied to the external S4 cohort, which included 71 participants (70.4% with manifest PD for a mean 5.1 (±4.8) years), it performed well, achieving an AUROC of 0.976, and sensitivity/specificity of 0.958/0.870. Models using only UPSIT percentile performed similarly well upon internal and external testing. Data-driven models using non-invasive clinical features can accurately predict CSF a-syn SAA positive and negative status in cohorts enriched for people living with PD. Scores from the UPSIT were highly significant in predicting a-syn SAA status.

Investigating the efficacy of melatonin, topical sodium citrate, and multivitamin with zinc as a potential treatment for postinfectious loss of smell

ObjectivesUpper respiratory tract infections, including COVID-19, are associated with olfactory dysfunction and there is a need for novel therapeutic approaches. The aim of study was evaluating the effectiveness of adding melatonin, multivitamin and sodium citrate to olfactory training for the treatment of olfactory loss caused by COVID-19. MethodsWe evaluated olfactory function using University of Pennsylvania Smell Identification Test (UPSIT ®) scores and self-reported patient outcomes in post-infectious smell loss cases. We investigated the effectiveness involved olfactory training combined with sodium citrate, melatonin, and multivitamin supplements with zinc over a three-month period compared to an olfactory training alone. ResultsA total of 66 patients were included, with 33 in each group. There was no significant difference in the proportion of participants who showed improvement in UPSIT scores between the groups (OR = 1.43, 95% CI 0.43–4.8, p = 0.56). Both groups showed improvement in average test scores, but there were no significant differences in self-reported olfactory ability or discomfort with olfactory loss. Qualitative symptoms, such as parosmia and phantosmia, were reported by a similar proportion in both groups before and after the treatment (p = 0.11, p = 1, respectively). ConclusionsOlfactory training alone and olfactory training with associated with melatonin, multivitamins and topical sodium citrate did not show significant differences in improving olfactory function in post-COVID-19 patients. Level of evidence3.

Dupilumab improved objective and patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and complete nasal obstruction

Aim: The impact of complete bilateral nasal obstruction [nasal polyp score (NPS) = 8/8] on treatment outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. This post hoc analysis assessed disease burden and dupilumab efficacy in patients with severe CRSwNP and baseline NPS = 8 in SINUS-24/-52 (NCT02912468/NCT02898454). Methods: Efficacy outcomes assessed: NPS, peak nasal inspiratory flow (PNIF), Lund-Mackay computed tomography (LMK-CT), nasal congestion/obstruction (NC), loss of smell (LoS), rhinosinusitis visual analog scale (rhino-VAS), University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22) in patients receiving dupilumab 300 mg or placebo every 2 weeks. Responder analyses evaluated clinically meaningful improvements [≥ 1 (NPS, NC, LoS); ≥ 5 (LMK-CT); ≥ 8 (UPSIT); ≥ 8.9 (SNOT-22); ≥ 20 L/min (PNIF)]. Results: Ninety-eight patients were included [59% prior NP surgery, 84% systemic corticosteroids (SCS) use in the previous 2 years, 60% coexisting asthma, 91% anosmic, 97% impaired nasal airflow]. Least squares (LS) mean differences [dupilumab vs. placebo (95% CI)] in change from baseline at week (W) 24: NPS, −2.04 (−2.67, −1.40); PNIF, 65.9 (39.4, 92.4) L/min; LMK-CT, −4.97 (−6.50, −3.44); NC, −1.30 (−1.72, −0.89); LoS, −0.96 (−1.39, −0.54); Rhino-VAS, −3.37 (−4.67, −2.07); UPSIT, 8.55 (4.91, 12.20); SNOT-22, −25.3 (−34.1, −16.4) (all P &lt; 0.0001). For all outcomes, significantly greater proportions of dupilumab vs. placebo patients achieved clinically meaningful improvements at W24. Fewer dupilumab vs. placebo patients required SCS and/or surgery through W24 (11.8% vs. 36.7%; P = 0.0005). Efficacy outcomes were similar at W52 (SINUS-52; n = 39) with P values vs. placebo of &lt; 0.0001 for NPS and NC; 0.0002 for LMK-CT; 0.0031 for LoS; 0.0014 for rhino-VAS; 0.0013 for UPSIT; 0.0012 for SNOT-22. Conclusions: In patients with CRSwNP with complete bilateral nasal obstruction, dupilumab treatment resulted in clinically significant improvements in NPS, LMK-CT, PNIF, symptoms, and health-related quality of life.

Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied. In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund-Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression. Seventy-three PwCF participated with a mean age of 34.7±10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (β=‒4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p<0.001), female sex (β=‒2.14, 95% CI [‒4.11, ‒0.17], p=0.034), and increasing age (β=‒0.14, 95% CI [‒0.22, ‒0.05], p=0.003) were associated with lower/better endoscopy scores. Private health insurance (β=17.76, 95% CI [5.20, 30.32],p=0.006) and >16 educational years (β=13.50, 95% CI [2.21, 24.80], p=0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (all p<0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p=0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores. Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF. NCT04469439.

Self-Reported Hypersensitivity to Smells: Objective Evidence for Hyposmia, not Hyperosmia.

To compare, using state-of-the-art psychophysical tests, the olfactory function of patients complaining and not complaining of olfactory hypersensitivity. Retrospective cross-sectional. The Smell and Taste Center at the University of Pennsylvania. University of Pennsylvania Smell Identification Test (UPSIT) scores were obtained from 148 patients complaining of hyperosmia and 494 patients with no such complaints; detection threshold test scores were obtained from 77 and 483 patients of these respective groups. The effects of subject group, age, and sex on the test scores were assessed using analyses of variance. Categorical variables were evaluated by χ2. Responses to items within a detailed intake questionnaire, for example, the Beck Depression Inventory (BDI-II), were also evaluated. Unexpectedly, those complaining of hyperosmia had lower olfactory test scores than those with no such complaints (respective UPSIT means [95% confidence interval [CIs]] = 27.86 (26.85, 28.87) and 32.19 (31.67, 32.71); P < .001; respective threshold means (log vol/vol) = -4.49 (-4.89, -4.09) and -5.22 (-5.36, -5.06); P < .001). Remarkably, 70.95% of the self-identified hyperosmics exhibited mild to severe microsmia. The hyposmia complainers also exhibited elevated BDI scores (11.02 [9.53, 12.51] vs7.58[6.80, 8.34]). When objectively tested, many patients who complain of hypersensitivity to odors are actually less sensitive to them. The basis of this phenomenon is unclear. It could reflect the presence of emotionally disturbing altered smell sensations, or one or more comorbidities, such as hypochondria or osmophobia. These findings point to the importance of objective testing of persons with complaints of chemosensory dysfunction and reiterate the inaccuracy of self-reports.

Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients.

Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients. The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively. After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019). In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients.

Olfactory Impairment and the Risk of Major Adverse Cardiovascular Outcomes in Older Adults.

Olfactory impairment is common in older adults and may be associated with adverse cardiovascular health; however, empirical evidence is sparse. We examined olfaction in relation to the risk of coronary heart disease (CHD), stroke, and congestive heart failure (CHF). This study included 2537 older adults (aged 75.6±2.8 years) from the Health ABC (Health, Aging, and Body Composition) study with olfaction assessed by the 12-item Brief Smell Identification Test in 1999 to 2000, defined as poor (score ≤8), moderate (9-10), or good (11-12). The outcomes were incident CHD, stroke, and CHF. During up to a 12-year follow-up, 353 incident CHD, 258 stroke, and 477 CHF events were identified. Olfaction was statistically significantly associated with incident CHF, but not with CHD or stroke. After adjusting for demographics, risk factors, and biomarkers of CHF, the cause-specific hazard ratio (HR) of CHF was 1.32 (95% CI, 1.05-1.66) for moderate and 1.28 (95% CI, 1.01-1.64) for poor olfaction. These associations were robust in preplanned subgroup analyses by age, sex, race, and prevalent CHD/stroke. While the subgroup results were not statistically significantly different, the association of olfaction with CHF appeared to be evident among participants who reported very good to excellent health (HR, 1.47 [95% CI, 1.01-2.14] for moderate; and 1.76 [95% CI, 1.20-2.58] for poor olfaction), but not among those with fair to poor self-reported health (HR, 1.04 [95% CI, 0.64-1.70] for moderate; and 0.92 [95% CI, 0.58-1.47] for poor olfaction). In community-dwelling older adults, a single olfaction test was associated with a long-term risk for incident CHF, particularly among those reporting very good to excellent health.