Prevalence and Magnitude of Olfactory Dysfunction in Allergic Rhinitis.

BACKGROUND: Although allergic rhinitis (AR) can negatively impact the ability to smell, the degree to which this occurs is not clear and prevalence estimates vary among studies. This study had 4 main objectives: (1) To estimate the prevalence and the degree of olfactory dysfunction in AR patients; (2) To compare olfactory perception between AR patients with different persistence and severity of symptoms and determine if olfactory testing may aid in differentiating among Allergic Rhinitis and its Impact on Asthma (ARIA) groups; (3) To determine whether allergic reactions to different allergens differentially impact olfactory function, and (4) Verify possible changes in the olfactory epithelium (OE) caused by AR. METHODS: One hundred thirty-three patients with AR and one hundred controls were tested. The main outcome was the score in University of Pennsylvania Smell Identification Test (UPSIT®). The OE was examined using immunofluorescence markers for neuronal activity, apoptosis, oxidative stress, signal transduction, eosinophils, and epithelial thickness. RESULTS: Prevalence of olfactory dysfunction in the AR patients was higher (AR: 42.9% vs controls: 9%, P < .001). No difference was found either between intermittent and persistent disease cases (P = .58) or between cases with mild and those with moderate/severe symptomatology (P = .33). Lower olfactory capacity was not associated with the reaction to more (P = .48) or diverse types of allergens (Ps > .05). Although not significant, patients with AR had a greater amount of eosinophilia and a lower amount of cAMP (cyclic adenosine monophosphate) in the OE. CONCLUSION: The study highlights a higher prevalence of olfactory dysfunction in AR patients compared to controls, but olfactory testing may not effectively differentiate AR severity or allergen sensitivities. Although trends suggest potential pathophysiological changes in the OE of AR patients, further research is needed to validate these findings.

High prevalence of olfactory dysfunction detected in treatment-naive patients with head and neck cancer.

BACKGROUND: Previous studies demonstrated the difficulty of patients with Head and Neck Cancer (HNC) in sensing food taste, a function in which olfaction has a significant role. However, neither study employed psychophysical tests or control groups to establish the veracity of such complaints. AIMS/OBJECTIVES: In this study, we quantitatively tested the olfactory function of HNC individuals and compared their function to that of healthy controls. METHODS: Thirty-one HNC naïve treatment patients and thirty-one controls, matched for sex, age, schooling, and smoking, were tested with the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: The olfactory function was significantly worse among the patients diagnosed with head and neck cancer [UPSIT cancer = 22.9(CI 95%: 20.5-25.4) vs. UPSIT controls = 29.1(CI 95%: 26.9-31.3); p < .001]. Most patients with HNC had olfactory disorders (n = 29, 93.5%). The risk of olfactory loss was higher in the cancer group [OR: 10.5(CI 95%: 2.1-51.9; p = .001)]. CONCLUSION AND SIGNIFICANCE: Olfactory disorders can be detected in more than 90% of patients with head and neck cancer when evaluated using a well-validated olfactory test. Smell disorders may be a potential marker for early diagnosis of HNC.

Chemosensory Dysfunction 3-Months After COVID-19, Medications and Factors Associated with Complete Recovery.

OBJECTIVES: To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures. METHODS: Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits. RESULTS: During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection. CONCLUSIONS: When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants. LEVEL OF EVIDENCE: 3.

Alzheimer and Parkinson diseases, frontotemporal lobar degeneration and amyotrophic lateral sclerosis overlapping neuropathology start in the first two decades of life in pollution exposed urbanites and brain ultrafine particulate matter and industrial nanoparticles, including Fe, Ti, Al, V, Ni, Hg, Co, Cu, Zn, Ag, Pt, Ce, La, Pr and W are key players. Metropolitan Mexico City health crisis is in progress.

The neuropathological hallmarks of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) are present in urban children exposed to fine particulate matter (PM2.5), combustion and friction ultrafine PM (UFPM), and industrial nanoparticles (NPs). Metropolitan Mexico City (MMC) forensic autopsies strongly suggest that anthropogenic UFPM and industrial NPs reach the brain through the nasal/olfactory, lung, gastrointestinal tract, skin, and placental barriers. Diesel-heavy unregulated vehicles are a key UFPM source for 21.8 million MMC residents. We found that hyperphosphorylated tau, beta amyloid1-42, α-synuclein, and TAR DNA-binding protein-43 were associated with NPs in 186 forensic autopsies (mean age 27.45 ± 11.89 years). The neurovascular unit is an early NPs anatomical target, and the first two decades of life are critical: 100% of 57 children aged 14.8 ± 5.2 years had AD pathology; 25 (43.9%) AD+TDP-43; 11 (19.3%) AD + PD + TDP-43; and 2 (3.56%) AD +PD. Fe, Ti, Hg, Ni, Co, Cu, Zn, Cd, Al, Mg, Ag, Ce, La, Pr, W, Ca, Cl, K, Si, S, Na, and C NPs are seen in frontal and temporal lobes, olfactory bulb, caudate, substantia nigra, locus coeruleus, medulla, cerebellum, and/or motor cortical and spinal regions. Endothelial, neuronal, and glial damages are extensive, with NPs in mitochondria, rough endoplasmic reticulum, the Golgi apparatus, and lysosomes. Autophagy, cell and nuclear membrane damage, disruption of nuclear pores and heterochromatin, and cell death are present. Metals associated with abrasion and deterioration of automobile catalysts and electronic waste and rare earth elements, i.e., lanthanum, cerium, and praseodymium, are entering young brains. Exposure to environmental UFPM and industrial NPs in the first two decades of life are prime candidates for initiating the early stages of fatal neurodegenerative diseases. MMC children and young adults-surrogates for children in polluted areas around the world-exhibit early AD, PD, FTLD, and ALS neuropathological hallmarks forecasting serious health, social, economic, academic, and judicial societal detrimental impact. Neurodegeneration prevention should be a public health priority as the problem of human exposure to particle pollution is solvable. We are knowledgeable of the main emission sources and the technological options to control them. What are we waiting for?

Adaptation of the Pediatric Smell WheelTM to evaluate olfactory function in Brazilian children

Abstract Objective: Olfaction influences nutrition, safety, and the cognitive development of children. Presently there are few olfactory tests for children, and normative reference values are generally lacking. In this study, we validate the Pediatric Smell WheelTM (PSW) to evaluate olfactory function in Brazilian children. Methods: We modified and validated the PSW, a test developed in the United States, for administration in Brazil, and established normative data for Brazilian children. The validation process consisted of five phases. First, we identified odorants familiar to Brazilian children. Second, we established the test-retest reliability of the Brazilian PSW test that employed these odorants. Third, we compared the test scores of healthy children to those microsmic from adenoid hypertrophy. Fourth, we examined the test's ability to detect improvement in olfactory function before and after adenoidectomy. Finally, we determined a normative 10th percentile cut point for defining microsmia in a sample of 169 healthy Brazilian children between 5 and 12 years of age. Results: Eleven odors were identified for inclusion in the test. The test-retest reliability was modest (r = 0.54, p < 0.001), although likely attenuated based on the inclusion of only data from children with normal function. The test clearly differentiated the olfactory function of children with adenoid hypertrophy from that of healthy children and demonstrated the return of function after adenoidectomy. An overall score <7 was found useful in defining hyposmia, although additional age-related cut-points were also defined. Conclusion: A Brazilian version of the PSW was developed and validated and found to be efficacious in detecting smell dysfunction in children ranging in age from 5 to 12 years. Level of evidence: 1b (Diagnosis).

Biopsy of the olfactory epithelium from the superior nasal septum: is it possible to obtain neurons without damaging olfaction? / Biópsia do epitélio olfatório do septo nasal superior: é possível obter neurônios sem prejudicar o olfato?

Abstract Introduction Olfactory epithelium biopsy has been useful for studying diverse otorhinolaryngological and neurological diseases, including the potential to better understand the pathophysiology behind COVID-19 olfactory manifestations. However, the safety and efficacy of the technique for obtaining human olfactory epithelium are still not fully established. Objective This study aimed to determine the safety and efficacy of harvesting olfactory epithelium cells, nerve bundles, and olfactory epithelium proper for morphological analysis from the superior nasal septum. Methods During nasal surgery, 22 individuals without olfactory complaints underwent olfactory epithelium biopsies from the superior nasal septum. The efficacy of obtaining olfactory epithelium, verification of intact olfactory epithelium and the presence of nerve bundles in biopsies were assessed using immunofluorescence. Safety for the olfactory function was tested psychophysically using both unilateral and bilateral tests before and 1 month after the operative procedure. Results Olfactory epithelium was found in 59.1% of the subjects. Of the samples, 50% were of the quality necessary for morphological characterization and 90.9% had nerve bundles. There was no difference in the psychophysical scores obtained in the bilateral olfactory test (University of Pennsylvania Smell Identification Test [UPSIT®]) between means before biopsy: 32.3 vs. postoperative: 32.5, p= 0.81. Also, no significant decrease occurred in unilateral testing (mean unilateral test scores 6 vs. 6.2, p= 0.46). None out of the 56 different odorant identification significantly diminished (p> 0.05). Conclusion The technique depicted for olfactory epithelium biopsy is highly effective in obtaining neuronal olfactory tissue, but it has moderate efficacy in achieving samples useful for morphological analysis. Olfactory sensitivity remained intact.

Resumo Introdução A biópsia do epitélio olfatório tem sido útil para estudar diversas doenças otorrinolaringológicas e neurológicas, incluindo seu potencial para melhor compreender a fisiopatologia por trás das manifestações olfatórias na COVID‐19. No entanto, a segurança e eficácia da técnica de obtenção de epitélio olfatório humano ainda não estão totalmente estabelecidas. Objetivos Este estudo teve como objetivo determinar a segurança e eficácia da coleta de células do epitélio olfatório, feixes nervosos e epitélio olfatório adequados para análise morfológica, no septo nasal superior. Método Durante a cirurgia nasal, 22 indivíduos sem queixas olfatórias foram submetidos a biópsias de epitélio olfatório do septo nasal superior. A eficácia da obtenção de epitélio olfatório, a verificação de epitélio olfatório íntegro e a presença de feixes nervosos nas biópsias foram avaliadas por imunofluorescência. A segurança da função olfatória foi testada psicofisicamente usando testes unilaterais e bilaterais antes e um mês após o procedimento cirúrgico. Resultados Epitélio olfatório foi encontrado em 59,1% dos sujeitos. Das amostras, 50% apresentaram a qualidade necessária para a caracterização morfológica e 90,9% continham feixes nervosos. Não houve diferença nos escores psicofísicos obtidos no teste olfatório bilateral (University of Pennsylvania Smell Identification Test [UPSIT®]) entre as médias antes da biópsia: 32,3 vs. pós‐operatório: 32,5, p = 0,81. Além disso, nenhuma diminuição significante ocorreu no teste unilateral (escore médio do teste unilateral 6 vs. 6,2, p = 0,46). Não houve redução significante na identificação de nenhum dos 56 odorantes diferentes (p > 0,05). Conclusão A técnica descrita para biópsia de epitélio olfatório é altamente eficaz na obtenção de tecido olfatório neuronal, mas tem eficácia moderada na obtenção de amostras adequadas para análise morfológica. A capacidade olfativa permaneceu intacta.

Adaptation of the Pediatric Smell WheelTM to evaluate olfactory function in Brazilian children.

OBJECTIVE: Olfaction influences nutrition, safety, and the cognitive development of children. Presently there are few olfactory tests for children, and normative reference values are generally lacking. In this study, we validate the Pediatric Smell WheelTM (PSW) to evaluate olfactory function in Brazilian children. METHODS: We modified and validated the PSW, a test developed in the United States, for administration in Brazil, and established normative data for Brazilian children. The validation process consisted of five phases. First, we identified odorants familiar to Brazilian children. Second, we established the test-retest reliability of the Brazilian PSW test that employed these odorants. Third, we compared the test scores of healthy children to those microsmic from adenoid hypertrophy. Fourth, we examined the test's ability to detect improvement in olfactory function before and after adenoidectomy. Finally, we determined a normative 10th percentile cut point for defining microsmia in a sample of 169 healthy Brazilian children between 5 and 12 years of age. RESULTS: Eleven odors were identified for inclusion in the test. The test-retest reliability was modest (r = 0.54, p < 0.001), although likely attenuated based on the inclusion of only data from children with normal function. The test clearly differentiated the olfactory function of children with adenoid hypertrophy from that of healthy children and demonstrated the return of function after adenoidectomy. An overall score <7 was found useful in defining hyposmia, although additional age-related cut-points were also defined. CONCLUSION: A Brazilian version of the PSW was developed and validated and found to be efficacious in detecting smell dysfunction in children ranging in age from 5 to 12 years. LEVEL OF EVIDENCE: 1b (Diagnosis).

Biopsy of the olfactory epithelium from the superior nasal septum: is it possible to obtain neurons without damaging olfaction?

INTRODUCTION: Olfactory epithelium biopsy has been useful for studying diverse otorhinolaryngological and neurological diseases, including the potential to better understand the pathophysiology behind COVID-19 olfactory manifestations. However, the safety and efficacy of the technique for obtaining human olfactory epithelium are still not fully established. OBJECTIVE: This study aimed to determine the safety and efficacy of harvesting olfactory epithelium cells, nerve bundles, and olfactory epithelium proper for morphological analysis from the superior nasal septum. METHODS: During nasal surgery, 22 individuals without olfactory complaints underwent olfactory epithelium biopsies from the superior nasal septum. The efficacy of obtaining olfactory epithelium, verification of intact olfactory epithelium and the presence of nerve bundles in biopsies were assessed using immunofluorescence. Safety for the olfactory function was tested psychophysically using both unilateral and bilateral tests before and 1 month after the operative procedure. RESULTS: Olfactory epithelium was found in 59.1% of the subjects. Of the samples, 50% were of the quality necessary for morphological characterization and 90.9% had nerve bundles. There was no difference in the psychophysical scores obtained in the bilateral olfactory test (University of Pennsylvania Smell Identification Test [UPSIT®]) between means before biopsy: 32.3 vs. postoperative: 32.5, p = 0.81. Also, no significant decrease occurred in unilateral testing (mean unilateral test scores 6 vs. 6.2, p = 0.46). None out of the 56 different odorant identification significantly diminished (p > 0.05). CONCLUSION: The technique depicted for olfactory epithelium biopsy is highly effective in obtaining neuronal olfactory tissue, but it has moderate efficacy in achieving samples useful for morphological analysis. Olfactory sensitivity remained intact.

Chemosensory Dysfunction in COVID-19: Prevalences, Recovery Rates, and Clinical Associations on a Large Brazilian Sample.

OBJECTIVE: Our study aimed to measure the percentage of reported olfactory or taste losses and their severity, recovery time, and association with other features in a large cohort of patients with COVID-19. STUDY DESIGN: Prospective survey. SETTING: Quaternary medical center and online survey. METHODS: The perceived chemosensory capacities of 655 patients with confirmed COVID-19 were assessed with 11-point category rating scales (0, no function; 10, normal function). Patients were contacted in hospital, by phone calls, or by internet regarding their ability to smell or taste, and 143 were interviewed by phone 1 to 4 months later to assess the recovery of their chemosensory abilities. RESULTS: The prevalence of self-reported olfactory, general taste, and taste quality-specific disturbances (sweet, sour, bitter, and salty) in the patients with COVID-19 were 82.4% (95% CI, 79.5%-85.3%), 76.2% (95% CI, 72.9%-79.4%), and 52.2% (95% CI, 48.3%-56.1%), respectively. The majority reported anosmia (42.9%). The presence of chemosensory symptoms was not associated with COVID-19 severity. At a median time >2 months after the onset of symptoms, rates of total and partial olfaction recovery were 53.8% and 44.7%, while complete or partial return to previous taste function was 68.3% and 27.6%. Less than 5% of the patients reported no chemosensory function improvement at all. CONCLUSION: The prevalence of self-reported chemosensory dysfunction is high among patients with COVID-19. Almost all patients seem to recover a significant part of their smell and taste abilities in the first 4 months after the onset of symptoms.

Olfactory dysfunction from acute upper respiratory infections: relationship to season of onset.

BACKGROUND: Acute viral upper respiratory tract infections are the most common cause of chronic olfactory dysfunction. In light of the seasonality of numerous viruses, the question arises as to whether the frequency and magnitude of postviral olfactory disorders (PVODs) are similarly seasonal. We sought to determine whether olfactory deficits due to influenza and non-influenza-related viruses (I-PVODs and NI-PVODs) vary in frequency or magnitude across seasons in a North American population and whether they are more prevalent or produce more severe olfactory dysfunction during colder months when host susceptibility may be increased. METHODS: This was a retrospective study of 587 patients presenting to an academic smell and taste center with either I-PVOD-related or NI-PVOD-related olfactory deficits. Chi-square and analysis of covariance (age = covariate) compared dysfunction prevalence frequencies and scores on the University of Pennsylvania Smell Identification Test (UPSIT) across calendar months and between months with the coldest and warmest air temperatures. RESULTS: For I-PVOD-related cases, both the prevalence and magnitude of smell dysfunction were highest in the colder months. However, for NI-PVOD-related cases, prevalence was higher in warmer months but, paradoxically, the magnitude of dysfunction was higher in colder months. CONCLUSION: This study shows that seasonal variations occur in both the prevalence and magnitude of PVOD-related olfactory deficits in a North American population, and that such variations differ between NI-PVOD and I-PVOD cases. The findings suggest multiple viruses are involved in producing PVOD-related olfactory deficits.

Safety and efficacy of superior turbinate biopsies as a source of olfactory epithelium appropriate for morphological analysis.

PURPOSE: There is no standardized approach for preserving olfactory function in the side of the nose where biopsy of the olfactory epithelium (OE) is performed. Moreover, a gold standard technique for obtaining human OE in vivo is still lacking. We determined the efficacy of obtaining good-quality OE specimens suitable for pathological analysis from the lower half of the superior turbinate and verified the safety of this procedure in maintaining bilateral and unilateral olfactory function. METHODS: In 21 individuals without olfactory complaints and who had undergone septoplasty and inferior turbinectomy OE biopsy was made during septoplasty. Olfactory function, both unilateral and bilateral, was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) before and 1 month after the procedure. Specimens were marked with the olfactory marker protein for confirmation of OE presence. RESULTS: Ninety percent of the samples contained OE, although clear histological characterization was possible from only 62%. There was no deterioration of UPSIT scores either bilaterally or unilaterally on the side of the biopsy. Patients also maintained the ability to identify individual odorants. CONCLUSION: Biopsies of the lower half of the superior turbinate do not affect olfactory function and show strong efficacy in yielding OE tissue and moderate efficacy for yielding tissue appropriate for morphological analysis. Future studies are needed to assess the safety of this procedure in other OE regions.

Clinical validation of the olfactory detection threshold module of the Snap & Sniff® olfactory test system.

BACKGROUND: Quantitative olfactory testing is essential to determine the validity and nature of a patient's complaint, accurately monitor changes in function over time (including influences of pharmacological, surgical, or immunological interventions), detect malingering, and establish disability compensation. This work describes the clinical validation of an advanced rapid odor detection threshold test that standardizes odorant delivery and eliminates unsanitary sniff bottles, the need for blindfolds, and the possibility of touching an odorant stimulus to the nose. METHODS: Snap & Sniff® single-staircase phenyl ethyl alcohol detection thresholds (S&S-Ts) were assessed bilaterally in 736 patients with chemosensory complaints; 421 received both bilateral and unilateral testing. The results were correlated with scores from the University of Pennsylvania Smell Identification Test (UPSIT) and the Smell Threshold Test (STT), a widely-used standardized threshold test. Test-retest reliability data were obtained for 50 patients. RESULTS: S&S-Ts were highly reliable (Spearman r = 0.84), correlated with the other olfactory test measures (rs > 0.65, ps < 0.0001), and required significantly shorter administration times than the STT (<10 minutes). Bilateral thresholds were systematically lower than unilateral thresholds, a phenomenon independent of presentation order but dependent upon the better functioning side of the nose. The S&S-Ts were sensitive to age and sex. No systematic left:right nasal side threshold differences were evident. CONCLUSION: The present study validates the use of Snap & Sniff® technology in the clinic setting. High test-retest reliability and brief administration times were evident. The S&S-T test allows for a reliable, valid, inexpensive, and rapid clinical means for quantitatively assessing human olfactory sensitivity.

Gustatory disturbances occur in patients with head and neck cancer who undergo radiotherapy not directed to the oral cavity.

INTRODUCTION: Even the most modern radiation techniques still result in some degree of toxicity to adjacent normal tissues. Consequently, the radiotherapy treatment in head and neck neoplasms potentially leads to gustatory dysfunction even in cases when the treatment area is outside or adjacent to the oral cavity. In this study we quantitatively and qualitatively assessed gustatory function in patients with head and neck cancers who underwent radiotherapy inside and outside of the oral cavity. METHODS: Fifty-six patients with head and neck cancer responded to a specific questionnaire and had their gustatory function tested before, immediately after, and at 3 and 6 months following radiotherapy treatment. The irradiation field did not include the oral cavity in 29 patients and included it in 27 patients. RESULTS: All patients suffered a severe loss of taste immediately after radiotherapy. The identification of sweet and bitter tastes decreased in both groups, but the sour decrement was exclusive to those who had the oral cavity irradiated. Fourteen percent of patients complained of qualitative changes of taste, namely taste distortions. No impact of xerostomia on the taste measures was apparent. CONCLUSION: We found that patients with head and neck neoplasms submitted to radiotherapy have disturbed taste even when irradiation does not include the oral cavity. This deficit is worse immediately after the end of radiotherapy. Our findings do not support the hypothesis that decreased salivary flow is the major cause for radiation-induced changes in taste function.

Relationship of socioeconomic status to olfactory function.

Socioeconomic status can significantly impact health. To what degree education and other socioeconomic factors influence the chemical sense of olfaction is not clear. Most studies that have assessed such influences come from countries lacking large disparities in education and income and generally view such measures as nuisance variables to be controlled for statistically. In this study, we evaluated the influences of education and income on odor identification in a diverse sample of subjects from Brazil, a society where large disparities in both income and education are present. The 40-item University of Pennsylvania Smell Identification Test (UPSIT) was administered to 1572 healthy Brazilian citizens with no self-reported olfactory or gustatory deficits and for whom detailed socioeconomic and educational status data were obtained. Univariate and multivariate models were employed to examine the influence of socioeconomic status on the test scores. After controlling for age, sex, ethnicity, and smoking behavior, income and educational level were positively and independently related to the olfactory test scores (respective ps < 0.001 & 0.01). Both linear and quadratic functions described the relationship between the UPSIT scores and the levels of education and socioeconomic status. Individuals of lower socioeconomic status performed significantly worse than those of higher socioeconomic status on 20 of the 40 odorant items. This study demonstrates socioeconomic status is significantly associated with influence the ability to identify odors. The degree to which this reflects differential exposures to xenobiotic agents, cultural differences, familiarity with odors or their names, cognitive development, or other factors requires further investigation.

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer's Disease?

OBJECTIVES: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with "silent" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. METHODS: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. RESULTS: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate (r = .58, P = .002). CONCLUSION: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

The effects of adenoidectomy on the smell perception of children.

BACKGROUND: In this study, we employed a novel children's olfactory test in order to more accurately assess the relationship between nasopharyngeal obstruction and odor identification ability. We quantified the impact of adenoidectomy on olfactory function, established whether the influences of the operation were related to the preoperative amount of nasopharyngeal obstruction, and determined whether sex influenced the olfactory measures. METHODS: Fifty-three boys and 23 girls were administered a standardized children's olfactory test, the Pediatric Smell Wheel™, before and 45 days after adenoidectomy. They ranged in age from 5 to 12 years and exhibited varying degrees of adenotonsillar hypertrophy and histories of recurrent adenotonsillitis. Radiographs of the nasopharynx were used to grade the degree of nasopharyngeal obstruction. RESULTS: Significant postoperative improvement in smell function occurred more frequently in children with >50% preoperative obstruction of the nasopharynx. In this group, average function improved 50.8% after surgery (95% confidence interval [CI], 39.1% to 64%). Improvement on 9 of the 11 odors was present, with significant differences occurring for the odors of bubble gum, baby powder, mint, and cinnamon. No sex differences were evident. CONCLUSION: Olfactory dysfunction occurs primarily in children whose nasopharyngeal obstruction is >50%. Removal of the hypertrophied adenoids returned smell function back to normal in these cases. This study suggests that smell loss may be of value in decisions regarding whether or not to perform adenoidectomy in children with nasopharyngeal obstruction.

Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology.

There is growing evidence that air pollution is a risk factor for a number of neurodegenerative diseases, most notably Alzheimer's (AD) and Parkinson's (PD). It is generally assumed that the pathology of these diseases arises only later in life and commonly begins within olfactory eloquent pathways prior to the onset of the classical clinical symptoms. The present study demonstrates that chronic exposure to high levels of air pollution results in AD- and PD-related pathology within the olfactory bulbs of children and relatively young adults ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84% of the bulbs exhibited hTau (48/57), 68% LNs and vascular amyloid (39/57) and 36% (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6-13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM2.5) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.

Intranasal administration of sodium dimethyldithiocarbamate induces motor deficits and dopaminergic dysfunction in mice.

The primary etiology of Parkinson's disease (PD) remains unclear, but likely reflects a combination of genetic and environmental factors. Exposure to some pesticides, including ziram (zinc dimethyldithiocarbamate), is a relevant risk factor for PD. Like some other environmental neurotoxicants, we hypothesized that ziram can enter the central nervous system from the nasal mucosa via the olfactory nerves. To address this issue, we evaluated the effects of 1, 2 or 4 days of intranasal (i.n., 1 mg/nostril/day) infusions of sodium dimethyldithiocarbamate (NaDMDC), a dimethyldithiocarbamate more soluble than ziram, on locomotor activity in the open field, neurological severity score and rotarod performance. We also addressed the effects of four daily i.n. NaDMDC infusions on olfactory bulb (OB) and striatal measures of cell death, reactive oxygen species (ROS), tyrosine hydroxylase, and the levels of dopamine, noradrenaline, serotonin, and their metabolites. A single i.n. administration of NaDMDC did not significantly alter the behavioral measures. Two consecutive days of i.n. NaDMDC administrations led to a transient neurological deficit that spontaneously resolved within a week. However, the i.n. infusions of NaDMDC for 4 consecutive days induced motor and neurological deficits for up to 7 days after the last NaDMDC administration and increased striatal TH immunocontent and dopamine degradation within a day of the last infusion. Pharmacological treatment with the anti-parkinsonian drugs l-DOPA and apomorphine improved the NaDMDC-induced locomotor deficits. NaDMDC increased serotonin levels and noradrenaline metabolism in the OB 24 h after the last NaDMDC infusion, ROS levels in the OB 2 h after the last infusion, and striatum 2 and 24 h after the last infusion. These results demonstrate, for the first time, that i.n. NaDMDC administration induces neurobehavioral and neurochemical impairments in mice. This accords with evidence that dimethyldithio-carbamate exposure increases the risk of PD and highlights the possibility that olfactory system could be a major route for NaDMDC entry to central nervous system.

Modulation of the ultradian human nasal cycle by sleep stage and body position.

OBJECTIVE:: The nasal cycle, which is present in a significant number of people, is an ultradian side-to-side rhythm of nasal engorgement associated with cyclic autonomic activity. We studied the nasal cycle during REM/non-REM sleep stages and examined the potentially confounding influence of body position on lateralized nasal airflow. METHODS:: Left- and right-side nasal airflow was measured in six subjects during an eight-hour sleep period using nasal thermistors. Polysomnography was performed. Simultaneously, body positions were monitored using a video camera in conjunction with infrared lighting. RESULTS:: Significantly greater airflow occurred through the right nasal chamber (relative to the left) during periods of REM sleep than during periods of non-REM sleep (p<0.001). Both body position (p < 0.001) and sleep stage (p < 0.001) influenced nasal airflow lateralization. CONCLUSIONS:: This study demonstrates that the lateralization of nasal airflow and sleep stage are related. Some types of asymmetrical somatosensory stimulation can alter this relationship.