Article

Effects of Olfactory Training in Patients with Olfactory Loss

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Abstract

Olfactory function is known to be modulated by repeated exposure to odors. The aim of this investigation was whether patients with olfactory loss would benefit from "Training" with odors in terms of an improvement of their general olfactory function. It was hypothesized that olfactory Training should produce both an improved sensitivity towards the odors used in the Training process and an overall increase of olfactory function. The prospective study was performed in patients with olfactory dysfunction. One group of patients performed the Training (n = 40), whereas another part did not (n = 16). Exclusion criteria for patients were sinunasal disease. Olfactory training was performed over a period of 12 weeks. Patients exposed themselves twice daily to four intense odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the "Sniffin' Sticks" (thresholds for phenyl ethyl alcohol, tests for odor discrimination and odor identification) in addition to threshold tests for the odors used in the training process. Compared to baseline, training patients experienced an increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. In contrast, olfactory function was unchanged in patients who did not perform olfactory training. The present results indicate that the structured, short-term exposure to selected odors may increase olfactory sensitivity.

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... Olfactory Training Details: Treatment regimen (type of odor used -traditional odors by Hummel et al., 2009 or others), frequency, mean duration of training, follow-up duration, quality of odors. ...
... In the majority of the reviewed research, the traditional olfactory training regimen proposed by Hummel et al. (2009) was applied. Bimodal patient-preferred training showed promising results (Khan et al., 2023), but further studies are needed to confirm its effectiveness. ...
... In most studies (10 out of 14), the traditional treatment regimen proposed by Hummel et al. (2009) was applied. An alternative approach was used by Pires et al. (2022). ...
Article
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Background Chronic olfactory disorders are some of the most frequent post-COVID-19 presentations. Olfactory training (OT) is currently the most popular method used for treating post-viral olfactory dysfunction (PVOD). We evaluated the effect of olfactory training on the chronic olfactory disorders of patients infected with COVID-19. Methodology A systematic literature search was performed per PRISMA guidelines in PubMed, Scopus, Web of Science, EBSCOhost, and the Cochrane Library. Only patients with chronic olfactory disorders of 30 days or more were included. The primary outcome was the olfactory score at the end of follow-up. In all studies, improvement was defined as a positive change over time in the results of objective psychophysical olfactory tests. The most commonly used test was the Sniffin' Sticks. Typically, outcome measures involved comparing the mean olfactory scores. In the Sniffin' Sticks test, an improvement was also indicated by a change of 5.5 points or more in the Threshold, Discrimination, and Identification scores. Results Fourteen studies (1.596 participants) were included in this review. Among the included studies, up to 10 were RCTs. Nine studies assessed the combined effects of adjuvant therapy and olfactory training, while five studies assessed only OT. Conclusions In our assessment, olfactory training alone produces significant improvements in chronic olfactory dysfunctions. However, a combined therapy approach is essential to achieve more effective outcomes. Integrating olfactory training with adjuvants like CoUltraPEALut, Cerebrolysin, and oral Vitamin A has demonstrated substantial benefits in enhancing post-COVID-19 olfactory function. Strict adherence to the OT protocol and extending the duration of OT to 3 months or more significantly enhance treatment outcomes.
... Postinfectious OD (PIOD) can recover spontaneously, but in patients with PIOD, spontaneous recovery does not always equate to full recovery. In a study by Hummel et al., [9] the rates of incomplete spontaneous recovery within four months were reported between 6 and 8%, and in another study, this rate was 21% within seven months. [10] The recovery of ≥4 points in smell tests was observed in 67% of persistent PIOD patients in a mean follow-up of 37±3.8 months. ...
... [12,13] However, as olfactory training (OT), which involves short-term exposure to smells, has been shown to have increased recovery rates, this is currently the most recommended modality in OD treatment. Hummel et al. [9] reported that OT applied for ≥12 weeks increased olfactory function by 28%. In another randomized study, the period of OT application was increased to 18 weeks, and similar results were reported. ...
... In postviral OD, the treatment to obtain normal and correct perception of odors is a difficult process, particularly in cases that experienced COVID-19 infection. Olfactory training was first defined by Hummel et al., [9] and the beneficial effects of the treatment and various modifications were reported in several meta-analyses. [17][18][19] In a meta-analysis including 16 studies, Kattar et al. [19] evaluated the response of PIOD patients to OT treatment, and the efficacy of OT treatment was determined to increase in direct proportion to a mean treatment period of 5.5±2.2 ...
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Objectives: The study aimed to evaluate the effect of long-term olfactory training (OT) in patients with persistent olfactory dysfunction (OD) following coronavirus disease 2019 (COVID-19) infection. Patients and Methods: The study included patients who developed OD after COVID-19 infection between March 2021 and January 2022. Following the initial examination, olfactory Visual Analog Scale (VAS) scores were recorded before treatment and at 3, 6, and 12 months after treatment. Olfactory training was applied for a period of 12 months to all the patients diagnosed with persistent OD. The procedure was explained in a written document, and four intense smells (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronella [lemon], and eugenol [cloves]) in amber-colored jars were used. The OT scoring was interpreted as follows: 9-10 points, full recovery; 7-8 points, almost full recovery; 5-6 points, semi-recovery; 3-4 points, partial recovery; 1-2 points, no recovery. Kruskal-Wallis one-way analysis of variance was used to compare patients’ VAS scores, with post hoc analysis with Bonferroni correction. Results: Eighty-three patients (57 females, 26 males; mean age: 30.6±11.3 years; range, 17 to 62 years) were included in the analyses. The VAS score of all the patients was 0 before treatment. The mean VAS scores were 6.95±2.3 at three months, 7.59±2.13 at six months, and 7.96±1.97 at 12 months (p=0.0001). Full recovery of OD was obtained with OT in 41 (50%) patients, and one patient showed no recovery. Conclusion: Long-term OT is an effective treatment for persistent OD that developed after COVID-19 infection.
... Uma das abordagens mais promissoras é o treinamento olfativo, que envolve a exposição repetida a diferentes odores para estimular a regeneração dos neurônios olfativos (Damm et al., 2014). Estudos têm mostrado que o treinamento olfativo pode melhorar significativamente a função olfativa em pacientes com anosmia pós-viral (Hummel et al., 2009). Além disso, terapias farmacológicas, como corticosteroides, têm sido utilizadas para reduzir a inflamação e promover a recuperação olfativa (Boscolo-Rizzo et al., 2020). ...
... Estudos longitudinais são necessários para entender melhor os fatores que influenciam a recuperação a longo prazo e para desenvolver intervenções mais eficazes (Parma et al., 2020). A pesquisa futura também deve focar em identificar biomarcadores que possam prever a recuperação olfativa e desenvolver terapias direcionadas para acelerar este processo (Hummel et al., 2009). ...
... Essa abordagem baseia-se na neuroplasticidade, ou seja, na capacidade do cérebro de reorganizar-se e adaptar-se a novos estímulos. Estudos demonstraram que o treinamento olfativo pode ser eficaz para a recuperação do olfato em pacientes com anosmia pós-viral, incluindo aqueles com COVID-19 (Hummel et al., 2009). O protocolo típico envolve a exposição a quatro odores distintos (rosas, limão, cravo e eucalipto) duas vezes ao dia durante vários meses. ...
Article
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A pesquisa aborda os mecanismos fisiopatológicos, impactos psicossociais, métodos de diagnóstico, intervenções terapêuticas e fatores que influenciam a recuperação da função olfativa. A anosmia na COVID-19 é causada pela infecção das células sustentaculares no epitélio olfatório pelo SARS-CoV-2, resultando em inflamação local e disfunção dos neurônios olfativos. A prevalência da anosmia é alta, com recuperação variada entre os pacientes. Métodos de diagnóstico incluem testes de identificação de odores e auto-relatos. Intervenções terapêuticas como o treinamento olfativo e o uso de corticosteroides têm mostrado resultados promissores, embora a eficácia varie. O impacto psicossocial da anosmia é significativo, afetando a qualidade de vida, saúde mental e interações sociais dos pacientes. O artigo enfatiza a necessidade de diagnósticos precoces e intervenções personalizadas para melhorar os resultados de recuperação. Estudos longitudinais e pesquisas sobre biomarcadores são necessários para aprimorar as estratégias terapêuticas e entender melhor os mecanismos de recuperação. Conclui-se que a anosmia, embora frequentemente temporária, pode ser debilitante, requerendo atenção médica e psicológica contínua.
... At the same time, plasticity is also found in the central nervous olfactory system (9)(10)(11)(12)(13) . Olfactory training (OT), a simple and inexpensive therapy involving daily exposure to distinctive odours, has emerged as a promising approach to harness this neuroplastic potential (13)(14)(15) . Direct human studies examining the effects of OT on the molecular and cellular composition of the olfactory system are currently lacking; however, animal studies suggest that OT may upregulate the expression of olfactory receptors, anti-apoptotic genes, neurotrophic factors, stem cell, and synaptic plasticity genes, possibly aiding neurogenesis (13) . ...
... While the efficacy of OT has been demonstrated in various olfactory disorders (14,(16)(17)(18)(19) , its application in the context of post-CO-VID-19 OL has been met with variable outcomes, potentially attributable to suboptimal adherence to the prescribed regimen, the timing of the training relative to the onset of symptoms and the severity of the OL (20)(21)(22)(23)(24)(25)(26) . ...
... Participants were invited to sniff, twice a day for 4 months, the 4 essential oils of rose, lemon, eucalyptus, and clove placed in amber-coloured jars for 10 seconds, with a 15-second rest between odours (14) . ...
Article
Background: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL. Methodology: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas. Results: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (≥5.5 points), compared to 22% of non-adherents. In retronasal olfactory identification, 56% of adherents achieved a clinically significant improvement (≥4 points), compared to 16% of non-adherents. Conclusion: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.
... Currently, olfactory training is the intervention of choice for olfactory dysfunction following a viral infection of the upper respiratory tract (Hummel et al., 2009;Vance et al., 2023). During olfactory training, participants typically self-administer four odorants twice a day for at least twelve weeks (Hummel et al., 2009). ...
... Currently, olfactory training is the intervention of choice for olfactory dysfunction following a viral infection of the upper respiratory tract (Hummel et al., 2009;Vance et al., 2023). During olfactory training, participants typically self-administer four odorants twice a day for at least twelve weeks (Hummel et al., 2009). The exact underlying mechanism is unclear, but olfactory training may induce plasticity of the olfactory receptor neurons in the olfactory mucosa (Doty, 2019;Pieniak et al., 2022). ...
... Classical olfactory training: In the COT group, participants received an olfactory training kit consisting of amber opaque glass vials (30 ml; Fisherbrand Inc., Waltham, MA, USA), each of which contained 5 ml, of one of four different odors (strawberry, cheese, coffee, lemon; all food grade odorants from Foodarom Glanbia Nutritionals, St. Hubert, QC, Canada) soaked in cotton pads to prevent spilling. Each training session consisted sniffing each odorant deeply for 10 s, with 10-s rest intervals between each odorant; we instructed participants to do this for a total of 5 mins, in line with Hummel et al. (2009). ...
Article
Approximately 30–60% of people suffer from olfactory dysfunction (OD) such as hyposmia or anosmia after being diagnosed with COVID-19; 15–20% of these cases last beyond resolution of the acute phase. Previous studies have shown that olfactory training can be beneficial for patients affected by OD caused by viral infections of the upper respiratory tract. The aim of the study is to evaluate whether a multisensory olfactory training involving simultaneously tasting and seeing congruent stimuli is more effective than the classical olfactory training. We recruited 68 participants with persistent OD for two months or more after COVID-19 infection; they were divided into three groups. One group received olfactory training which involved smelling four odorants (strawberry, cheese, coffee, lemon; classical olfactory training). The other group received the same olfactory stimuli but presented retronasally (i.e., as droplets on their tongue); while simultaneous and congruent gustatory (i.e., sweet, salty, bitter, sour) and visual (corresponding images) stimuli were presented (multisensory olfactory training). The third group received odorless propylene glycol in four bottles (control group). Training was carried out twice daily for 12 weeks. We assessed olfactory function and olfactory specific quality of life before and after the intervention. Both intervention groups showed a similar significant improvement of olfactory function, although there was no difference in the assessment of quality of life. Both multisensory and classical training can be beneficial for OD following a viral infection; however, only the classical olfactory training paradigm leads to an improvement that was significantly stronger than the control group.
... First, olfaction may need to be trained to achieve expertise. Such a training in its formalized form is based on a structured, daily exposure to a predetermined set of odors [52]. However, even everyday olfactory experiences, active search for olfactory cues, reliance on odors and their appreciation all likely enrich the smell expertise [53]. ...
... Olfaction contributes to food perception, acceptance and enjoyment [15,17,67], making it a viable channel for interventions aimed at modifying feeding-related behaviors. Importantly, olfactory abilities, including those in children [68]), can be enhanced through targeted olfactory training [52]. Moreover, such training has been shown to affect children's functioning in non-olfactory domains, like emotional categorization [69]. ...
Article
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Background Child food neophobia, i.e., rejection or avoidance of novel foods at a young age, is a prevalent nutrition problem that affects the quality of children’s diet and impedes the development of healthy food preferences. Sensory sensitivity can relate to the degree of food neophobia, but previous studies rarely focused on the olfactory component of this problem in children. Objective We aimed to thoroughly examine the relationship between various aspects of olfactory sensitivity and food neophobia in children. Methods 246 children aged between three and nine years took part in a food neophobia assessment as well as in a comprehensive, psychophysical olfactory testing. Results We found that certain smell perception aspects such as lower odor liking, poorer odor identification ability as well as lower sensitivity to an unknown non-food odor all significantly predicted higher food neophobia in children. Among individual characteristics of either a child or a caregiver, only the child’s age significantly and positively predicted food neophobia. The exploratory model looking into the role of family environment factors predicting self-reported food neophobia in children revealed that food neophobia was associated with lower control given to a child in this child’s feeding process, as well as with a more frequent use of food as a reward in feeding. Conclusions We suggest that suppressed olfactory perception and performance can play a unique role in child nutritional difficulties. The study inspires further considerations of olfaction-engaging interventions to counteract food-neophobia in children.
... Social and physical environments can effectively stimulate the human olfactory system to improve olfactory sensitivity (Oleszkiewicz et al. 2021). Conscious focus on and short-term exposure to selected odors may increase olfactory sensitivity (Hummel et al. 2009;Oleszkiewicz et al. 2021). Smell training can improve the sense of smell and alleviate the depression associated with smell loss in humans (von Bothmer 2006; Hummel et al. 2009). ...
... Conscious focus on and short-term exposure to selected odors may increase olfactory sensitivity (Hummel et al. 2009;Oleszkiewicz et al. 2021). Smell training can improve the sense of smell and alleviate the depression associated with smell loss in humans (von Bothmer 2006; Hummel et al. 2009). This suggests that the odor characteristics of the environment in which people live, as well as the experience and memory of odors, have a significant impact on the sensitivity and perception of smell. ...
Preprint
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Pheromones are chemicals released outside the body by organisms to transmit information between individuals of the same species, thereby regulating behavior and physiology. Many biological and psychological studies have shown that human sweat does indeed contain chemical information related to gender, sex, emotion, etc., but there is no convincing answer to its chemical components. We conducted a GC-MS analysis of the chemical composition of adult and child sweat of Han Chinese, and found that the main components were squalene and fatty acids, and there were sex differences in adults, but not in children. Based on our long-term research on the coding rules of pheromones in a variety of animals, especially rodents, as well as men having more sweat glands and sebaceous glands, we speculate that squalene and many common fatty acids are likely to encode olfactory information such as sex and emotion in one component or a mix of components or in a dose-dependent manner. We also discussed that the main olfactory system and olfactory learning in social interactions should play an important role in human pheromone perception.
... Such training is performed twice a day for a certain time period (usually between 4 and 6 months). Hummel et al. pointed out that a structured, short-term exposure to odorants over 12 weeks increased olfactory sensitivity in 28% of participants [41], OT was also found to be an effective approach in different studies [32,37,39]. ...
... Usually, the recommended training period is 12 weeks [41]. Yet, a subsequent multicenter follow-up study [57] demonstrated even greater enhancement in olfactory performance following a training period lasting a minimum of 18 weeks. ...
Article
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Purpose: This study aims to highlight the feasibility of an olfactory training program entirely monitored through online media in COVID-19 patients. Methods: Classic olfactory training was performed with a sample with olfactory loss due COVID-19 (n = 11). Participants were engaged on a weekly video call in order to improve adherence and collect information regarding the number of correct answers and the individuals’ perception of olfactory function. The olfactory status after training was compared to two groups, one composed of participants who contracted COVID-19 but did not report olfactory loss (n = 11) and a sample composed of healthy participants (n = 11). Results: The experimental group showed improvements throughout the training period (TDI score on week 0 was 20.3 (5.6) and 24.6 (4.3) for week 12, and on week 24 was 25.4 (6.2) (F = 5.115, df = 2, 20, p = 0.016), and post hoc tests showed that participants significantly improved their TDI score in W12 compared to W0 (SMD = 0.869, p = 0.041) and in W24 compared to W0 (SMD = 0.859, p = 0.041). The experimental group showed lower scores when compared with both groups, and the no OT COVID-19 group showed lower scores than the healthy control group, even though they did not report olfactory alterations. Conclusions: Findings suggest that the strategies applied to improve adherence were successful since 100% of the sample completed the training adherence, offering a valuable framework for future olfactory training studies.
... Apart from the challenges in the latency issue of OGs, a number of technical difficulties still exist, including miniaturizing the size, optimizing the power consumption, and building up high channel counts/ density 18 . For instance, the state of art odors generating methods generally require a whole set of bulky equipment with limited odors supplied and professional operation, forcing users to visit a specific place to experience olfactory feedback every time, which is unfriendly to users 19 . So, olfactory interfaces simultaneously exhibiting subsecond response time, centimeter-scale size, tens of OGs array, and micro-watt low power consumption is challenging (Supplementary Table 1) 2,3,[16][17][18][20][21][22] . ...
... The odorous chemicals used in Figs. 5, 6 are ethanol (1), pineapple (2), grape (3), osmanthus (4), rice (5), tobacco (6), gardenia (7), watermelon (8), vanilla (9), coffee milk (10), candy (11), coconut milk (12), coconut (13), milk (14), peach (15), figue (16), orange (17), green tea (18), caramel (19), durian (20), lemon (21), strawberry (22), morning (23), ginger (24), clary sage (25), rosemary (26), lavender (27), clove (28), mojito (29), cake (30), cream (31), and pancake (32). ...
Article
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Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.
... Olfactory training (OT) is a medical intervention that involves systematic stimulation of the olfactory system with a set of selected odorants twice daily for approximately 12 weeks. OT is widely used in the otorhinolaryngological clinical practice to treat olfactory dysfunction (Hummel et al., 2009;Pieniak et al., 2022). OT has been shown to increase olfactory functions in patients with smell loss due to various etiologies (Nguyen & Patel, 2018;Oleszkiewicz et al., 2018Oleszkiewicz et al., , 2022Poletti et al., 2016). ...
... The OTG performed the training with four odors representing four categories of Henning's "odor prism"eucalyptus (eucalyptol; resinous odor), cloves (eugenol; aromatic odor), rose (phenyl ethyl alcohol; flowery odor), and lemon (citronellal; fruity odor) (Hummel et al., 2009). The PG followed the same training procedure with four pens filled with odorless propylene glycol. ...
Article
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Emotion knowledge involves the ability to recognize and express emotions and understand emotional processes. The neural substrates of emotion knowledge include i.a. the amygdala, orbitofrontal cortex, and anterior cingulate cortex. These structures are also involved in processing olfactory stimuli and their volume and functional activity have been shown to increase after a period of regular olfactory stimulation (olfactory training, OT). We verified if OT will improve one aspect of emotion knowledge — the ability to match emotional facial expressions. Eighty‐three children (39 boys) aged 6–9 years were randomly assigned either to an OT group (OTG) that smelled a set of four odors (lemon, cloves, eucalyptus, rose) twice a day for 12 weeks or to a placebo group that performed the training with odorless stimuli. Children in the OTG ( n = 40) matched emotional facial expressions significantly better after OT as compared with their baseline score. This effect was not present in the placebo group ( n = 43) whose scores remained the same after OT. Practical applications This novel finding suggests the potential of olfactory stimulation in supporting emotion knowledge in children and bridges recent findings in sensory studies, psychophysiology, and emotional development. Further studies are necessary to delineate which aspects of emotion knowledge might be enhanced by OT. In future, OT might be potentially included in programs designed for groups with specific emotion knowledge deficits.
... While spontaneous resolution occurs in most COVID-19-related cases of hypo/anosmia, therapeutic intervention may be considered if the loss persists beyond two weeks [68,69]. The efficacy of available treatments for COVID-19-related hypo/anosmia remains uncertain, encompassing pharmacological, supplementbased, and olfactory training-based therapies [69][70][71][72][73][74]. Research provides evidence of its effectiveness in enhancing olfactory function, especially with essential oils such as rose, lemon, clove, and eucalyptus, commonly selected according to the classification of primary odors, demonstrating a positive impact [75]. ...
... The effectiveness of this treatment is uncertain, and this uncertainty is accompanied by concerns about potential risks associated with prolonged use or high dosages [93]. Particularly promising, however, is the olfactory training regimen, which has shown positive results in various clinical contexts [70,72]. Its effectiveness in improving olfactory function, especially in the domains of odor discrimination and identification, suggests a crucial role in managing post-COVID-19 hypo/anosmia [71,74,75]. ...
Article
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Olfactory dysfunction (OD) is one of the most common symptoms in COVID-19 patients and can impact patients’ lives significantly. The aim of this review was to investigate the multifaceted impact of COVID-19 on the olfactory system and to provide an overview of magnetic resonance (MRI) findings and neurocognitive disorders in patients with COVID-19-related OD. Extensive searches were conducted across PubMed, Scopus, and Google Scholar until 5 December 2023. The included articles were 12 observational studies and 1 case report that assess structural changes in olfactory structures, highlighted through MRI, and 10 studies correlating the loss of smell with neurocognitive disorders or mood disorders in COVID-19 patients. MRI findings consistently indicate volumetric abnormalities, altered signal intensity of olfactory bulbs (OBs), and anomalies in the olfactory cortex among COVID-19 patients with persistent OD. The correlation between OD and neurocognitive deficits reveals associations with cognitive impairment, memory deficits, and persistent depressive symptoms. Treatment approaches, including olfactory training and pharmacological interventions, are discussed, emphasizing the need for sustained therapeutic interventions. This review points out several limitations in the current literature while exploring the intricate effects of COVID-19 on OD and its connection to cognitive deficits and mood disorders. The lack of objective olfactory measurements in some studies and potential validity issues in self-reports emphasize the need for cautious interpretation. Our research highlights the critical need for extensive studies with larger samples, proper controls, and objective measurements to deepen our understanding of COVID-19’s long-term effects on neurological and olfactory dysfunctions.
... The relatively low cost, the non-invasive nature and absence of associated complications, supports its use as firstline therapy. This therapy was firstly presented by Hummel et al., with a clinically significant improvement on olfaction in patients with post-infectious, post-traumatic, and idiopathic olfactory loss [67]. A meta-analysis of 2016 found benefit in the total TDI scores as well as odour identification and discrimination [10]. ...
Article
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Purpose of Review COVID -19 associated olfactory dysfunction is widespread, yet effective treatment strategies remain unclear. This article aims to provide a comprehensive systematic review of therapeutic approaches and offers evidence-based recommendations for their clinical application. Recent Findings A living Cochrane review, with rigorous inclusion criteria, has so far included 2 studies with a low certainty of evidence. Summary In this systematic review we list clinical data of 36 randomised controlled trials (RCTs) and non-randomised studies published between Jan 1, 2020 and Nov 19, 2023 regarding treatment options for COVID-19 associated olfactory dysfunction. Nine treatment groups were analysed, including olfactory training, local and systemic corticosteroids, platelet-rich plasma (PRP), calcium chelators, vitamin supplements including palmitoylethanolamide with luteolin, insulin, gabapentin and cerebrolysin. Primary objective was the effect of the studied treatments on the delta olfactory function score (OFS) for objective/psychophysical testing. Treatments such as PRP and calcium chelators demonstrated significant improvements on OFS, whereas olfactory training and corticosteroids did not show notable efficacy for COVID-19 associated olfactory dysfunction.
... По данным литературы, для эффективного лечения обонятельной дисфункции после COVID-19 обонятельные тренировки рекомендуются в качестве варианта лечения первой линии, наряду со здоровым питанием, изменением образа жизни (отказ от курения) и, в отдельных случаях, терапией глюкокортикостероидами [18][19][20][21][22][23][24][25]. Впервые термин «тренировка обоняния» был использован в работах Thomas Hummel, в которых описано применение ряда эфирных масел, выбранных на основе гипотезы призмы запаха, предложенной Хансом Хеннингом (роза, лимон, гвоздика и эвкалипт) для лечения нарушения обоняния [26]. По данным исследований, вдыхание эфирных масел приводило к восстановлению обоняния, подавляя воспаление и усиливая регенерацию обонятельного эпителия [27]. ...
Article
По данным литературы, распространенность нарушения обоняния различной этиологии составляет около 20%. Особенно актуален этот вопрос у пациентов после коронавирусной инфекции, распространенность нарушения обоняния у которых составляет 18–22%. В 4,7% случаев наблюдается стойкая не корректируемая медикаментозно поствирусная обонятельная дисфункция длительностью более 1 года, которая существенно влияет на качество повседневной жизни. В статье описывается клиническое наблюдение стойкой (более года) потери обоняния после перенесенной инфекции SARS-CoV-2. По данным идентификационных тестов у 20-летней пациентки диагностирована поствирусная аносмия со значительным снижением качества жизни согласно показателю опросника QOD-NS. МРТ головного мозга выявила двустороннюю атрофию обонятельных луковиц. Учитывая неэффективность медикаментозного лечения, пациентке проведен 6-месячный курс обонятельных тренировок с применением технологии виртуальной реальности. Контрольная оценка обоняния после курса тренировок с применением субъективных и объективных методов исследования показывает восстановление обоняния до нормосмии, увеличение размера обонятельных луко According to the literature, the prevalence of olfactory disorders of various etiologies is about 20%. This issue is especially relevant in patients after coronavirus infection, whose prevalence of olfactory impairment is 18–22%. In 4.7% of cases, persistent, drug- induced, post-viral olfactory dysfunction lasting more than 1 year is observed, which significantly affects the quality of daily life. The article describes the clinical observation of persistent (over a year) loss of sense of smell after undergoing SARS-CoV-2. According to identification tests, a 20-year-old patient was diagnosed with post-viral anosmia with a significant decrease in quality of life according to the QOD-NS questionnaire. An MRI scan of the brain revealed bilateral atrophy of the olfactory bulbs. Given the ineffectiveness of drug treatment, the patient underwent a 6-month course of olfactory training using virtual reality technology. A control assessment of the sense of smell after a course of training using subjective and objective research methods shows the restoration of the sense of smell to normosmia, an increase in the size of olfactory bulbs and confirms a clinically significant decrease in the negative impact of olfactory dysfunction on the patient’s quality of life.
... The outcome of olfactory training was not assessed through psychophysical tests, hence patients reporting persisting dysfunction may have qualitative rather than quantitative impairment. The effectiveness of olfactory training is probably depending on training duration and aetiology of chemosensory impairment 31 , hence the outcome in patients with COVID-related smell dysfunction needs to be assessed in large cohort studies 32 . ...
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COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training’s outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment.
... While there is no definitive cure, several therapeutic strategies have shown promise. These include intranasal corticosteroids to reduce inflammation [12], olfactory training to promote neuroplasticity and recovery [13] and supportive supplementation including omega-3 fatty acids, alpha-lipoic acid and zinc sulfate [5]. In addition, Intranasal vitamin A, in the form of retinoic acid, is also involved in the management to aid in the olfactory dysfunction treatment [14]. ...
Article
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Purpose Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen. Methods The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the “Sniffin’ Sticks” test, measuring threshold, discrimination and identification scores before and after treatment. Results Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores. Conclusion This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19. Trial registration DFM-IRB00012367-23-10-001.
... After the initial assessment (HT0), each patient underwent a 12-week olfactory training program (HT1), which involved daily exposure to four intense odors: phenyl ethyl alcohol (rose), eucalyptol (eucalyptus), citronellal (lemon), and eugenol (cloves) [21,19]During the olfactory training, each olfactory stimulus lasted for 10 consecutive seconds, using one substance at a time, with a 45-second break before the next odorant presentation. This routine was repeated three times, twice daily, resulting in a 10-minute complete session each time. ...
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Background: This longitudinal prospective study aims to investigate the potential of circulating calprotectin (cCLP) as a biomarker in persistent olfactory dysfunctions following COVID-19 infection. Methods: Thirty-six patients with persistent hyposmia or anosmia post COVID-19 were enrolled (HT0) and re-evaluated after three months of olfactory training (HT1). Two control groups included 18 subjects without ol-factory defects post COVID-19 (CG1) and 18 healthy individuals (CG2). Nasal brushing of the olfactory cleft and blood collection were performed to assess circulating calprotectin levels. Results: Higher calprotectin levels were observed in serum and nasal supernatant of hyposmic patients (HT0) compared to control groups (CG1 and CG2). Post-olfactory training (HT1), olfactory function improved significantly , paralleled by decreased calprotectin levels in serum and nasal samples. Circulating calprotectin holds potential as a biomarker in persistent olfactory dysfunctions after COVID-19.
... In a study comparing interventions for parosmia, while SGBs had the lowest utilization in comparison to oral steroids and smell training, it had the highest reported percentage improvement among participants with maintained benefit (60). The classic protocol as designed by Hummel et al. for smell training, or olfactory training, involves patients sniffing four odors for at least 10 s, twice daily, for at least 3 months (66,67). ...
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Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.
... Olfactory training (OT) has emerged as a first-line therapeutic approach to the management of olfactory dysfunction arising from various causes, particularly viral infection or head trauma. 1 This nonpharmacological rehabilitative treatment involves exposing patients to odorants at home in a set of four jars, each of which contains one aromatic compound (rose, eucalyptus, lemon, or cloves), twice daily for at least 3 months. 2 A number of studies and meta-analyses have corroborated the efficacy of conventional OT (COT) [3][4][5][6] ; however, inconsistencies in the results have prompted efforts to refine the OT protocol. ...
Article
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Objectives Olfactory training (OT) has emerged as a first‐line therapeutic approach to the management of olfactory dysfunction. Conventional OT (COT) involves the systematic home‐based exposure to four distinct odors. Previous research has demonstrated that immersive OT (IOT) involving full‐body exposure to dozens of distinct odors could also improve overall olfactory function. This study compared IOT and COT in terms of efficacy. Methods A total of 60 patients were enrolled and assigned to three groups. The IOT group (n = 25) underwent immersive exposure to 64 odors once daily in a specialized theater. COT participants (n = 17) sniffed four typical odors in a set of four jars twice daily at home. A control group (n = 18) underwent passive observation. Olfactory function was assessed before and after training. Results Significant improvements in composite threshold‐discrimination‐identification (TDI) scores were observed after training in both the IOT (mean difference = 2.5 ± 1.1. p = .030) and COT (mean difference = 4.2 ± 1.3, p = .002) groups. No changes were observed in the control group. A significantly higher proportion of patients in the COT group (41%) presented improvements of clinical importance (TDI ≥5.5) compared to the controls (p = .018). The improvements attained in the IOT group (20%) were less pronounced (p = .38). Conclusion While IOT did not exhibit the same efficacy as COT in restoring olfactory function, it still demonstrated promising outcomes. Future efforts to advance olfactory recovery should focus on cross‐modal integration. Level of Evidence Level 3.
... Those who received mometasone furoate nasal spray were instructed to administer two puffs (100 μg) once daily. The method and duration of intervention were proven to show improvement of olfactory function in cases of PVOD [21]. ...
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Introduction Persistent olfactory dysfunction was seen in many patients upon coronavirus disease 2019 (COVID-19) infection recovery. However, research on its management was very limited, especially among the Southeast Asian population. Objectives We aim to investigate the role of olfactory rehabilitation and topical corticosteroids among post-COVID-19 olfactory dysfunction patients in Malaysia, and at the same time to determine factors leading to olfactory recovery post-COVID-19 infection. Methods Adult Malaysians with persistent olfactory dysfunction one month post-COVID-19 recovery were recruited. Thirty-one patients were randomly assigned into three groups with 10 patients being given olfactory training (Group 1), another 10 being given mometasone furoate nasal spray/olfactory training (Group 2), and 11 patients being assigned to the control group (Group 3). All groups were followed up for an average duration of six months. Olfactory function was evaluated by Top International Biotech Smell Identification Test (TIBSIT) scores and Olfactory Disorder Questionnaire (eODQ) prior to randomization, at three and six months after recruitment. Results The baseline characteristics of patients were similar in all groups. Generally, patients of all three groups showed a statistically significant improvement in the TIBSIT scores after six months. The TIBSIT scores for Group 2 were statistically significantly higher than the control at three months but not at six months. As for Group 1, no statistically significant differences in TIBSIT scores at both three and six months were noted when compared to control. Statistically significant improvements were seen in the eODQ scores in all three groups. Conclusion No superiority of intervention for post-COVID-19 olfactory dysfunction was seen compared to control.
... So, the increase in olfactory sensitivity occurs not only in the olfactory epithelium, but also in the level of olfactory bulb and central processing of olfaction. 16 In some studies, olfactory dysfunction has been reported as the only symptom of disease. 17 In a similar randomized clinical trial by Choi et al., 104 Korean patients with olfactory dysfunctions following COVID-19 infection evaluated. ...
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Objectives The new corona virus infection, has a wide range of clinical manifestations. Fever and cough are the most common symptoms. The olfactory function may be also affected with COVID-19. In this randomized clinical trial, we wanted to evaluate the therapeutic effect of olfactory training with and without oral vitamin A for COVID-19-related olfactory dysfunction. Methods Patients answered to the standard Persian version of anosmia reporting tool and performed the quick smell test before and after 12 weeks and at the end of the 12 months follow up. The patients were randomly allocated to three groups; Group A treatment with olfactory training, Group B treatment with oral vitamin A and olfactory training, and Group C as control group which only underwent nasal irrigation twice a day. Patients were treated for 3 months and followed up for 12 months. Results Totally 90 patients were included in three groups. After interventions, 76.9% of patients in Group A, 86.7% of patients in Group B, and 26.7% of patients in Group C completely improved. The average intervention time was statistically significant in relationship with the final olfactory status of the patients in the 12 months follow-up. The olfactory training has significantly improved the smell alteration at the end of 3- and 12- months follow-up in A and B groups. Conclusion A three-months olfactory training is effective for improvement of COVID-19-related olfactory dysfunction. Adding daily oral vitamin A to olfactory training did not lead to better results in improving olfactory dysfunction. Level of evidence Step 2 (Level 2*): Randomized trial.
... Repeated, systematic, bi-daily exposure to odours (i.e., olfactory training; OT) has been introduced to the otorhinolaryngological practice as a tool to rehabilitate the sense of smell in people with olfactory dysfunction (Hummel et al., 2009;Pieniak et al., 2022). OT has improved the sense of smell in patients with various olfactory dysfunction aetiologies (Konstantinidis et al., 2013;Oleszkiewicz et al., 2018a;Poletti et al., 2017). ...
... This programme should consist of cycling or walking at an intensity of 55%-80% of VO2 max or 60%-80% of maximal heart rate. This programme should be repeated 2-3 times a week, as these parameters safely improve immune function without causing exhaustion in the study by Hummel et al., 22 neurological rehabilitation in patients with olfactory loss consisted of daily exposure to 4 odours (phenylethyl alcohol, eucalyptol, citronella and eugenol) over a period of 12 weeks, and Sheen F et al. 23 conducted a taste rehabilitation study in which post-COVID-19 patients received small amounts of powders selected to represent four prototypical tastes: "sweet" (table sugar), "salty" (table salt), "bitter" (granulated table salt, coffee powder) and "sour" (lime powder) for 28 days. ...
Article
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Background COVID-19 demonstrated the possibility of neurological complications such as loss of sense of smell and taste, together with respiratory problems. Respiratory training and rehabilitation of neurological sequelae are essential to improve respiratory function and thus quality of life, and the aim of this study is to evaluate the efficacy of a pulmonary and neurological rehabilitation program. Objectives To apply a treatment to reduce dyspnea, increase exertional capacity, increase vital capacity and respiratory muscle strength, together with an increase in olfactory and gustatory sensitivity in post-SARS-CoV-2 patients. Methods A randomised controlled experimental study was conducted in 220 patients with a medical diagnosis of COVID-19 and more than 5 months of evolution, dyspnoea or perceived fatigue, including olfactory and gustatory perception problems, of whom 200 patients completed the study. 100 patients were randomly assigned to the intervention group, consisting of an inspiratory training treatment plan (Powerbreathe Plus®) combined with aerobic exercise and olfactory gustatory treatment for 31 days, and 100 patients to the control group, for 31 days without any type of therapy. Results The study was conducted in post-Covid-19 patients for 5 months. Two hundred patients were divided into an intervention group (n = 100) and a control group (n = 100). The comparison between the groups showed significant differences in spirometric variables; forced vital capacity (p < .001; Eta2 (0.439); Mean: 0,6135), the ratio between both FEV1/FVC (p < 0.01; Eta2 (0.728); Mean:9,313), peak inspiratory pressure (p < 0.01; Eta2 (0.906); Mean:4,526); changes were observed in dyspnoea measured with the modified Borg scale (p < 0.01; Eta2 (0.811); Mean:1,481) and the modified Medical Research Council scale (p < 0.01; Eta2 (0.881); Mean: 0.777); finally, changes were found in neurological variables, in the questions of the Singapore Smell and Taste Questionnaire, How was your sense of smell after treatment? (p < 0.01; Eta2 (0.813); Mean: 1,721) and How is your sense of taste after treatment? (p < 0.01; Eta2 (0.898); Mean: 1,088). Conclusion The implementation of a respiratory rehabilitation treatment plan with the Powerbreathe Plus® device, aerobic exercise and neurorehabilitation with olfactory and gustatory training, is a therapeutic option against respiratory and neurological sequelae in patients who have suffered such sequelae due to the SARS-CoV-2 virus. Clinicaltrials.gov: NCT05195099. First posted 18/01/2022; Last Update Posted 29/06/2022.
... In patients suffering from post-viral, post-traumatic, or idiopathic OD, 12 weeks of OT improved olfactory function in 30% of patients [128]. Another study took into consideration the same causes of OD, adding 12 patients with sino-nasal diseases. ...
Article
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Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.
... Olfactory tests, including the phenylethanol threshold, odor recognition test, and odor recognition test, were conducted using "olfactory sticks" before and after the training period. Results indicate that structured, short-term exposure to specific odors can enhance olfactory sensitivity [81]. ...
Article
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The prevalence of COVID-19 has drawn increasing attention to olfactory dysfunction among researchers. Olfactory dysfunction manifests in various clinical types, influenced by numerous pathogenic factors. Despite this diversity, the underlying pathogenesis remains largely elusive, contributing to a lack of standardized treatment approaches. However, the potential regeneration of olfactory neurons within the nasal cavity presents a promising avenue for addressing olfactory dysfunction effectively. Our review aims to delve into the current research landscape and treatment modalities concerning olfactory dysfunction, emphasizing etiology, pathogenesis, clinical interventions, and the role of stem cells in regenerating olfactory nerves. Through this comprehensive examination, we aim to provide valuable insights into understanding the onset, progression, and treatment of olfactory dysfunction diseases.
... If needed, workers can be referred to an otolaryngologist for smell or taste testing and olfactory training. 109 Olfactory training was associated with improved smell scores for approximately half of COVID-19 patients in 3 weeks, which was not further improved by the addition of intranasal steroids. 110 In a clinical trial, gabapentin was also found not to be effective. ...
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Persistent symptoms are common after acute COVID-19, often referred to as long COVID. Long COVID may affect the ability to perform activities of daily living, including work. Long COVID occurs more frequently in those with severe acute COVID-19. This guidance statement reviews the pathophysiology of severe acute COVID-19 and long COVID and provides pragmatic approaches to long COVID symptoms, syndromes, and conditions in the occupational setting. Disability laws and workers’ compensation are also addressed.
... 39,50,51 Originally developed in an effort to treat sensorineural olfactory impairments from multiple etiologies including postviral, posthead trauma, or presbyosmia, this has been examined extensively. 52 Individual reports, as well as a meta-analysis, suggest that in certain groups there is evidence for slight improvement in odor TDI. 53 The groups most likely to exhibit improvements, however, are generally those that are likely to spontaneously recover function, such as younger subjects with milder loss of shorter duration. ...
Article
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An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus in the early phases of the COVID‐19 pandemic. In most COVID‐19 patients, olfaction recovers over the course of a few weeks. However, a lasting partial or complete loss of smell, often associated with distorted olfactory perceptions termed parosmia, has emerged as a widespread problem impacting at least 5%–10% of those who experience anosmia due to COVID‐19. Our inability to offer effective therapies to this hyposmic or anosmic population, comprising millions of patients, highlights an enormous unmet need for the medical system. Here, we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS‐CoV‐2 infection, focusing on how the virus interacts with the peripheral olfactory system, a major site of viral infection. We also explore the problem of long‐COVID olfactory dysfunction, which may accompany other persistent systemic disorders collectively termed postacute sequelae of COVID‐19. Specifically, we discuss an emerging model focused on unresolved immune cell activity driving ongoing dysfunction. Finally, we review current and future therapeutic approaches aimed at restoring olfactory function.
... Motnje voha se lahko zdravijo farmakološko in kirurško, a obstajajo dokazi, da tudi s pomočjo izpostavljenosti različnim vonjavam (vrtnici, evkaliptusu, limoni, nageljnovim žbicam) oziroma z vohalnim treningom voh lahko povrnemo v prvotno obliko. Regeneracija voha traja zelo različno, a dokazano je, da kratkoročna izpostavljenost omenjenim vonjavam poveča vohalno občutljivost (Hummel et al., 2009). Glede na preteklo obdobje okužb z virusom SARS-CoV-2 Niedenthal & Nilsson (2021) menita, da je prav pandemija povzročila povečano potrebo po spremljanju in ocenjevanju voha, saj je bil pri koronavirusni bolezni (covid-19) pogost začetni simptom prav izguba slednjega. ...
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Uvod: Motnje voha so pogoste pri okužbah dihal in vplivajo na kakovost življenja, saj imajo nekateri pacienti lahko moten voh vse življenje. Kot pomoč pri rehabilitaciji voha obstaja vohalni trening, ki je nefarmakološka, nekirurška in stroškovno učinkovita metoda zdravljenja pacientov z motnjami voha zaradi različnih indikacij. Namen raziskave je raziskati, kakšni so učinki vohalnega treninga pri pacientih z vohalno disfunkcijo.Metode: Uporabljen je bil pregled strokovne in znanstvene literature. Iskanje literature je potekalo po podatkovnih bazah Web of Science, CINAHL in Pubmed. Vključena je bila literatura med letoma 2019 in 2022. Pri iskanju so bile uporabljene kombinacije ključnih besed: voh, motnje voha, anozmija. Potek iskanja in izbor raziskav smo prikazali s pomočjo diagrama PRISMA. Tematska analiza je potekala na način kodiranja rezultatov.Rezultati: Iz celotnega niza smo pridobili 253 zadetkov, med katerimi smo v končno analizo uvrstili šest kvantitativnih raziskav, ki so opisovale uporabo ter učinke vohalnega treninga za zdravljenje vohalne disfunkcije. Rezultati iskanja literature so bili kritično ovrednoteni z orodji JBI (JBI, 2020). Glavni izpostavljeni vsebinski področji sta bili: izidi vohalnega treninga in lastnosti vohalnega treninga.Diskusija in zaključek: Vohalni trening pomembno vpliva na vračanje in izboljšanje vonjanja. Gre za učinkovito podporo pri rehabilitaciji voha. Za prihodnje raziskovanje področja se predlaga raziskava predvsem na področjih razločevanja in zaznavanja voha po uporabi vohalnega treninga.
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Alzheimer’s disease and other dementias pose significant challenges to global economies and healthcare systems, exacerbated by an aging population. This results in substantial economic burdens due to the high costs of long-term care and loss of productivity. Despite extensive research, effective treatments to slow disease progression and recover cognitive function remain elusive. This review explores Environmental Enrichment (EE) as a treatment strategy for Alzheimer’s and other dementias. Decades of neuroscience research on EE have yielded significant findings, including hippocampal neurogenesis instrumental in memory and cognition, improved mood and behavior, cognitive enhancements, and modulation of neuro-inflammation, all without adverse effects. These findings suggest a promising new direction for Alzheimer’s Disease treatment. We present evidence of major health benefits observed in animal models of dementia following EE exposure as well as research on neurological disorders in human populations and recommend a large-scale study to verify these findings in human subjects with Alzheimer’s. Clinical experiences with severe autism, Huntington’s disease, and stroke provide additional context for applying EE in human populations. EE is a cost-effective potential strategy for enhancing the quality of life, mood and cognitive functions in Alzheimer’s patients. Given its affordability, ease of implementation, and straightforward metrics for tracking improvement, EE represents a promising approach that warrants rigorous investigation.
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Some individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience anosmia, or loss of smell. Although the prevalence of anosmia has decreased with the emergence of the Omicron variant, it remains a significant concern. This review examines the potential role of polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs, in treating COVID-19-induced anosmia by focusing on the underlying mechanisms of the condition. Omega-3 PUFAs are known for their anti-inflammatory, neuroprotective, and neurotransmission-enhancing properties, which could potentially aid in olfactory recovery. However, study findings are inconsistent. For instance, a placebo-controlled randomized clinical trial found no significant effect of omega-3 PUFA supplementation on olfactory recovery in patients with COVID-19-induced anosmia. These mixed results highlight the limitations of existing research, including small sample sizes, lack of placebo controls, short follow-up periods, and combined treatments. Therefore, more rigorous, large-scale studies are urgently needed to definitively assess the therapeutic potential of omega-3 PUFAs for olfactory dysfunction. Further research is also crucial to explore the broader role of PUFAs in managing viral infections and promoting sensory recovery.
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Introduction While olfactory function decreases with age, it is unknown how age affects olfactory training (OT) efficacy. This study compared OT in two cohorts of subjects: aged ≤50 (younger cohort) and aged 51+ (older cohort) with olfactory dysfunction (OD) primarily from COVID‐19 infection. Methods Subjects with OD primarily secondary to COVID‐19 infection were prospectively recruited and enrolled into an OT registry. Baseline data were collected and they were provided with a training kit and asked to complete OT at home twice daily for 6 months. Participants were asked to follow‐up at 3 and 6 months during training for olfactory testing and quality‐of‐life surveys (Sino‐Nasal Outcomes Test‐22 [SNOT‐22] and Questionnaire of Olfactory Disorders Negative Statements [QoD‐NS]). Results Fifty‐six participants completed OT (younger cohort: n = 26, older cohort: n = 30). There were no significant differences between cohorts’ Affordable Rapid Olfactory Measurement Array (AROMA), QoD‐NS, or SNOT‐22 scores at any time point. Both cohorts showed significant AROMA score improvement of more than 16 points from baseline to 3 months (younger cohort: p = 0.001; older cohort: p = 0.008). The younger cohort had significant improvements in QoD‐NS ( p = 0.008) and SNOT‐22 ( p = 0.042) between baseline and 3 months while the older cohort improved from 3 to 6 months (QoD‐NS: p = 0.027, SNOT‐22: p = 0.049). Conclusion Both cohorts demonstrated similar significant improvement in olfactory function after 3 months of OT. The timeline of subjective improvement was different between cohorts, with younger patients experiencing earlier improvement.
Chapter
Two essential elements primarily impact the sensory perception of food: flavor and aroma. Flavor can be defined as the entire range of sensations encountered during food or beverage consumption. It includes the subjective perception of taste, scent, and other physical characteristics connected with a substance. Historically, the extraction of taste and fragrance compounds has mostly relied on sourcing them from plant and animal origins. The current way of life and the ever-growing worldwide population have led to increased demands and challenges for the food processing industry. Today, the food processing industry is incorporating synthetic chemicals to effectively address the increased demand and costs associated with a diverse array of products. The emerging trend in innovation emphasizes health and utility, placing a stronger emphasis on offering food products that provide health benefits and serve practical purposes for consumers. Food makers have incorporated substances that effectively improve mood, energy, and relaxation, inspired by customers’ use of food and drinks for these purposes. Companies have a distinct chance to investigate ingredient innovation to meet the growing customer need for functional food and beverage products. These goods not only offer health benefits but also deliver enjoyable taste sensations, enabling them to effectively cater to both functional and flavor preferences. The current way of life and the ever-growing worldwide population have led to increased demands and challenges for the food processing industry. Changes in people’s dietary habits are currently causing a significant upheaval in the food industry. Consequently, we anticipate that various factors will impact the substantial usage of flavors and fragrances due to the increasing demand driven by certain key trends. The factors driving this phenomenon include a rise in gross national income, accelerated urbanization, global population expansion, improved living standards, heightened demand for packaged food, and an increase in the aging population. We anticipate that the increasing recognition of sustainability in society will drive research and development efforts in the field of sustainable manufacturing or green industrialization, which includes the food sector. This chapter examines the latest developments in the flavor business and explores the necessary adjustments in flavor production methods to effectively fulfill the requirements of these developing trends in flavor manufacture.
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Purpose Olfactory training (OT) is an effective and affordable option in the treatment of olfactory dysfunction. Despite significant progress in the field in recent years, some factors influencing OT participation remain unclear. Methods Based on an anonymous online survey orchestrated by AbScent.org the present study enrolled 450 participants and divided them into OT (n = 161) and No OT (n = 289) groups based on their OT participation. Participants also provided information on demographics, medical history, quality of life, OT duration for those who engaged in OT, and the reasons for non-participation in OT among those who did not. Results Patients who had greater loss of quality of life participated more in OT. Similarly, more participation was observed in patients who noticed an improvement in their ability to smell. Notably, most of the sample engaged in OT trained less than four weeks (73%). In the No OT group, the primary barrier to OT participation was the unawareness of OT treatment (37%) and these barriers differed by age, where older people expressed interest but were unaware of OT treatment, while younger individuals exhibited more cautiousness about its effectiveness. Conclusion Lower quality of life drives active OT participation. Limited training periods and unawareness of OT serve as potential barriers to olfactory recovery. Clinicians should actively promote the background of OT and underscore the significance of adhering to the “prescribed” training regimen.
Article
Objective] Herein, we report a case of a remarkably effective combination of acupuncture and daily olfactory training for treating postinfectious olfactory dysfunction that had not improved for years.[Case] A 45-year-old woman complained of decreased sense of smell and inability to smell properly. She had postinfectious olfactory dysfunction four years ago, which resulted in olfactory deglutition. She continued taking zinc preparations prescribed by the hospital; however, they showed no therapeutic response. She discontinued a yearlong hospital visit and received approximately 10 acupuncture sessions. Her odor problems gradually recovered to some extent after the acupuncture treatment, but dysphoria appeared. Her symptoms showed no significant changes over the next 3 years.[Results] The pretreatment olfactory VAS score was 38mm and the self-administered odor questionnaire score was 30%. Acupuncture treatment was focused on the facial area; thus, she was instructed to perform daily olfactory training by smelling various odors. Consequently, the olfactory VAS score improved to 97mm and the self-administered odor questionnaire score improved to 97.5% after 18 acupuncture sessions for 18 months.[Conclusion] The results indicated that the combination of acupuncture and daily olfactory training could improve postinfectious olfactory dysfunction that had not improved over the years.
Chapter
Aging is associated with a gradual deterioration of sensory function, including hearing and smell with a prevalence of 80% and 40% in those over 80 years of age, respectively. Both are significant sources of disability, and both have a significant impact on the quality of life. Age-related disturbances of sensory function are in part genetic, but are to a significant extent influenced by lifetime exposures and modifiable risk factors. Given their significant impact on the quality of life, it is not surprising that both hearing and smell losses have been associated with increased risk of cognitive decline. Preventive and rehabilitation strategies generally involve control of risk factors and continued stimulation of both sensory systems to preserve and strengthen neural connections between sensory cells and the central nervous system.
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The recommended treatment for hyposmia (clinically reduced sense of smell) is olfactory training using odors in containers that the patients smell twice a day for several weeks. Adherence to the olfactory training regimen is, however, generally low. We aimed to investigate if a new form of olfactory delivery via scented nasal inserts could enhance olfactory training adherence by allowing participants to be mobile while performing the training and thereby lower perceived intrusion in their everyday life, using a randomized controlled parallel-group design. Two groups of individuals with hyposmia underwent 8 weeks of olfactory training. One group (n=60) performed olfactory training using scented nasal inserts (nasal plugs that retain nasal patency) and one group (n=56) performed the standard care regiment currently recommended by the Swedish healthcare system. We assessed objective and subjective olfactory ability before and after olfactory training as well as adherence to training. While both groups significantly improved their objective and subjective olfactory abilities, training with nasal insert produced similar improvement as standard care in overall treatment outcome. However, there was a significantly greater increase in discrimination performance and lower dropout rate (6.7%) in the nasal insert compared to the standard care group (23.2%). Critically, the nasal insert group had a significantly higher adherence to the training regimen, i.e. fewer missed training sessions. In addition, they reported overall greater satisfaction with their treatment. These data suggest that olfactory training with nasal inserts could serve as a more effective form of treatment for hyposmia, due to patients improved adherence to protocol and increased tendency to finish their treatment regimen.
Article
Olfactory sensory neurons (OSNs) are one of a few neuron types that are generated continuously throughout life in mammals. The persistence of olfactory sensory neurogenesis beyond early development has long been thought to function simply to replace neurons that are lost or damaged through exposure to environmental insults. The possibility that olfactory sensory neurogenesis may also serve an adaptive function has received relatively little consideration, largely due to the assumption that the generation of new OSNs is stochastic with respect to OSN subtype, as defined by the single odorant receptor gene that each neural precursor stochastically chooses for expression out of hundreds of possibilities. Accordingly, the relative birthrates of different OSN subtypes are predicted to be constant and impervious to olfactory experience. This assumption has been called into question, however, by evidence that the birthrates of specific OSN subtypes can be selectively altered by manipulating olfactory experience through olfactory deprivation, enrichment, and conditioning paradigms. Moreover, studies of recovery of the OSN population following injury provide further evidence that olfactory sensory neurogenesis may not be strictly stochastic with respect to subtype. Here we review this evidence and consider mechanistic and functional implications of the prospect that specific olfactory experiences can regulate olfactory sensory neurogenesis rates in a subtype‐selective manner.
Article
Background and Objectives Decreased olfactory function commonly occurs alongside the aging process. Research suggests olfactory training (OT) has the potential to improve olfactory and cognitive function in individuals with and without olfactory dysfunction. The degree to which these benefits extend into older age and among those with cognitive impairment (i.e., people with dementia and mild cognitive impairment) is less clear. The purpose of the current review was to investigate the extent to which OT affects olfactory function, cognition, and well-being among older people. Research Design and Methods A scoping review of the literature was conducted in PubMed, Embase, EbscoHost, and SCOPUS. Articles were considered eligible for original research studies with human populations, included adults aged 55 and older, performed any type of OT, and included a form of olfactory testing. The data from the included studies were synthesized and presented narratively. Results A total of 23 studies were included. The results suggest that OT provides multiple benefits to older adults, including those with cognitive impairment. Particularly, OT was associated with measurable changes in olfactory function, improved cognitive function, specifically semantic verbal fluency and working memory, reduced depressive symptoms, and protection from cognitive decline. Discussion and Implications The findings suggest that benefits from OT extend beyond changes in olfactory function and include improved cognitive function, amelioration of depressive symptoms, and protection from cognitive decline. Future research is needed across specific participant groups, including those with differentiated types of dementia, to investigate the olfactory and cognitive benefits of OT.
Article
Introduction: The prevalence of post-viral olfactory dysfunction has increased significantly during the COVID-19 pandemic, posing a major challenge for patients and practitioners. While olfactory training (OT) is a common approach to therapy, there has been increasing interest in supplementing therapy with a combination of palmitoylethanolamide (PEA) and luteolin (LUT), which are known for their anti-inflammatory properties. In this study, their efficacy in the treatment of patients with olfactory loss following upper respiratory tract infections, mainly COVID-19, was investigated in an outpatient clinic. Methods: Fifty patients with persistent olfactory dysfunction were randomized to two groups: one receiving OT and PEA-LUT, the other OT alone. Olfactory function was evaluated before and after treatment. Results: The study group showed significant improvements in odor discrimination and overall olfactory function (TDI score) after treatment with PEA-LUT and OT, while the control group did not. However, when clinically meaningful improvements were considered, there was no significant difference between the groups. Conclusion: The present study suggests that while PEA-LUT may have the potential to improve olfactory function in post-viral dysfunction, the additional benefit over OT alone may be limited. These results contrast with some previous studies.
Article
Background Olfactory dysfunction (OD) affects many survivors of COVID‐19. Prior studies have investigated the use of platelet‐rich plasma (PRP) injections for OD. We describe the first randomized controlled trial investigating topical PRP for OD treatment and contribute to existing literature illustrating PRP as an emerging therapeutic. Methods This is a single‐blinded, randomized controlled trial conducted from July 2022 to December 2023. Adult patients with OD ≥6 months secondary to COVID‐19 with Brief Smell Identification Test (BSIT) scores of ≤8/12 or SCENTinel odor intensity of ≤40/100 were included. Patients were randomized to three, monthly PRP or placebo‐impregnated Surgifoam treatments into bilateral olfactory clefts. The BSIT, SCENTinel, and Questionnaire of Olfactory Disorders—Negative Statements (QOD‐NS) were completed monthly through month 12. Results Of 104 patients screened, 83 participated. No significant differences in age, OD duration, BSIT, SCENTinel, or QOD‐NS scores were found between PRP ( n = 42) and placebo ( n = 41) patients at baseline. PRP patients experienced a statistically significant increase in BSIT scores from baseline at months 5‒9, 11, and 12, while placebo patients did not ( p < 0.05). However, total BSIT scores were similar between the two groups throughout the study. Neither the SCENTinel odor intensity scores nor the change from baseline were significantly different between the treatment groups. At month 12, PRP patients experienced minor improvement in OD‐related quality‐of‐life compared with placebo. Conclusions This study is the first to describe topical PRP as a safe, experimental treatment for OD in humans. PRP may impact odor identification in post‐COVID‐19 OD patients, although the lack of difference in total BSIT scores highlights the need for further study.
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Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson's disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.
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Alzheimer’s disease (AD) is the leading cause of dementia, with over 45 million patients worldwide, and poses significant economic and emotional burdens to both patients and caregivers, significantly raising the number of those affected. Unfortunately, much of the existing research on the disease only addresses a small subset of associated symptomologies and pathologies. In this review, we propose to target the earliest stages of the disease, when symptomology first arises. In these stages, before the onset of hallmark symptoms of AD such as cognitive impairments and memory loss, circadian and olfactory disruptions arise and are detectable. Functional similarities between circadian and olfactory systems provide a basis upon which to seek out common mechanisms in AD which may target them early on in the disease. Existing studies of interactions between these systems, while intriguing, leave open the question of the neural substrates underlying them. Potential substrates for such interactions are proposed in this review, such as indirect projections that may functionally connect the two systems and dopaminergic signaling. These substrates may have significant implications for mechanisms underlying disruptions to circadian and olfactory function in early stages of AD. In this review, we propose early detection of AD using a combination of circadian and olfactory deficits and subsequent early treatment of these deficits may provide profound benefits to both patients and caregivers. Additionally, we suggest that targeting research toward the intersection of these two systems in AD could uncover mechanisms underlying the broader set of symptoms and pathologies that currently elude researchers.
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Repeated exposure to odors modifies olfactory function. Consequently, “olfactory training” plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19–43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the “Sniffin‘ Sticks” test battery. OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.
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Olfactory training consisting of daily suprathreshold odor exposure over 12 weeks seems to improve olfactory function. It is unknown if a longer period of training might be more effective. A prospective non-randomized clinical study was performed including 39 patients with olfactory loss after an upper respiratory tract infection (URTI) of less than 24 months duration. Patients exposed themselves with suprathreshold concentrations of four odors (rose, eucalyptus, lemon, cloves) applied in ''Sniffin' Sticks'' felt-tip pens over 32 weeks. Olfactory function was performed before (T1), after 16 weeks (T2), and 32 weeks of training (T3) using the 'the Sniffin' Sticks test kit calculating the TDI score (Threshold, Discrimination, Identification). The mean TDI score showed a non-significant trend of improvement at T2, and was significantly increased at T3 (p = 0.021). Overall, 31 patients (79 %) showed an increased TDI score at T3. The increase of TDI from T1 to T3 was 4.6 ± 5.1. Age, gender, duration and initial severity of olfactory loss had no influence on the improvement (all p > 0.05). Only patients with a D score lower than the median value of 8 showed a significantly higher increase of the D score at T3 (p = 0.004). The present study confirmed that olfactory training improves olfactory function in patients with olfactory loss after URTI. A longer duration of training over 32 weeks seems to increase the effectiveness in comparison to a 12-week period. This was tested in a completed German multicenter trial to be published soon containing a control group to include the effect of a spontaneous recovery after URTI.
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The purpose of this study was to determine cognitive correlates of olfactory performance across three different tasks. A total of 170 men and women (30-87 years of age) were assessed in olfactory sensitivity, discrimination, and identification. Also, participants were tested in a range of cognitive tests covering executive functioning, semantic memory, and episodic memory. Hierarchical regression analyses showed that proficiency in executive functioning and semantic memory contributed significantly to odor discrimination and identification performance, whereas all of the cognitive factors proved unrelated to performance in the odor threshold test. This pattern of outcome suggests that an individual's cognitive profile exerts a reliable influence on performance in higher order olfactory tasks.
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Selective adaptation has been used to evaluate receptor specificity in olfaction on the assumption that exposure to 1 stimulus will inhibit or cross-adapt the olfactory system to similar stimuli. It is theoretically possible that a stimulus could also facilitate or enhance the sensitivity to another stimulus, although this has not been demonstrated. Evidence for such facilitation in odor detection measured as a change in the human neonate's respiration is shown. It is hypothesized that facilitation may be explained in terms of the solubility of the odorants. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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This study examined whether a previously established (D. G. Laing & G. W. Francis, 1989) limited capacity to discriminate and identify the components of olfactory mixtures resulted from the participants' lack of familiarity with the task, training designed to optimize cognitive and perceptual performance, or professional experience in odor discrimination. The participants were a trained panel of 10 women (23-43 years old), and an expert panel of 8 male professional perfumers and flavorists (25-55 years old). The individual chemical stimuli were 7 common dissimilar odorants of equal moderate intensity. An air dilution olfactometer delivered a single odorant or a mixture containing up to 5 odorants. The results indicated that for both panels only 3 or 4 components of a complex mixture could be discriminated and identified and that this capacity could not be increased by training. Therefore, the limit may be imposed physiologically or by processing constraints.
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"Sniffin' Sticks" is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score--i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject's age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using "Sniffin' Sticks."
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Induction of olfactory sensitivity in humans was first illustrated when men and women who were initially unable to smell the volatile steroid androstenone (5alpha-androst-16-en-3-one) developed that ability after repeated, brief exposures. Because this finding has not been replicated with other compounds in humans, it has been assumed that olfactory induction is a narrowly constrained phenomenon, occurring only in individuals with specific anosmias, perhaps only to androstenone (compare ref. 2). Here we show that induction of enhanced olfactory sensitivity seems to be a more general phenomenon, with marked changes in olfactory acuity occurring during repeated test exposures to several odorants among people with average baseline sensitivity to these compounds. This increased sensitivity (averaging five orders of magnitude) was observed only among females of reproductive age. These observations provide convincing evidence that female olfactory acuity to a variety of odorants can vastly improve with repeated test exposures. They also suggest a sensory basis for the anecdotal observation of greater olfactory sensitivities among females and raise the possibility that the olfactory-induction process may be associated with female reproductive behaviors such as pair bonding and kin recognition.
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To estimate the prevalence of isolated self-reported allergic and non-allergic rhinitis symptoms in an adult population and to explore the relations to age, gender, olfaction and smoking habits. Self-judged health and environmental exposures were investigated by means of a questionnaire survey administered to a stratified random sample of 15,000 adults in Stockholm County. A total of 10,670 individuals were included in the analysis, corresponding to a response rate of 73%. The results revealed a high prevalence of self-reported non-allergic rhinitis, 19%, almost as high as the prevalence of self-reported allergic rhinoconjunctivitis, 24%. In contrast to current clinical opinion, we did not find a significant increase in the prevalence of non-allergic symptoms with increased age. There were no statistically significant gender differences in the prevalence of either allergic or non-allergic symptoms. A reduced sense of smell was twice as common in the non-allergic group, 23%, as in the healthy population. The prevalence of rhinitis symptoms differed according to smoking habits. Both self-reported allergic rhinitis symptoms and non-allergic nasal symptoms are frequent in the population sample. Self-reported non-allergic nasal symptoms seem to occur independent of age and reduced olfactory sense is a common complaint among these subjects. The prevalence of self-reported allergic and non-allergic nasal symptoms did not differ much between men and women or between individuals with different smoking habits.
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Age-associated loss of olfactory function, or presbyosmia, has been described in many studies of olfactory ability. Presbyosmia has been ascribed to idiopathic causes despite recognition that many neurodegenerative diseases also induce loss of olfactory function and increase in incidence in the aged population. Often this olfactory loss is unnoticed or unreported by affected individuals. More effective olfactory function in women compared with men is another common feature of many studies of olfactory function. Here we report on normative data from an Australian population study (n = 942) that has been divided into 2 subpopulations and reassessed as (included) a population of healthy, nonmedicated, nonsmokers with no history of nasal problems (n = 485) and (excluded) a population of participants who were either medicated, smokers or had a history of nasal problems (n = 457). The "included" data set shows a strong relationship between self-reporting of olfactory sensitivity and olfactory function score. The included data set shows a small but significant decline in olfactory ability after 65 years of age and better olfactory function in females compared with males. Data from the excluded population show a marked decline in olfactory ability after 65 years of age, no difference between males and females, and a weak relationship between self-reporting of olfactory function and actual olfactory function. The power of this approach is that it provides a normative data set against which many factors such as medication schedules and pathological conditions can be compared.
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"Sniffin' Sticks" is a test of nasal chemosensory function that is based on pen-like odor dispensing devices, introduced some 10 years ago by Kobal and co-workers. It consists of tests for odor threshold, discrimination, and identification. Previous work established its test-retest reliability and validity. Results of the test are presented as "TDI score", the sum of results obtained for threshold, discrimination, and identification measures. While normative data have been established they are based on a relatively small number of subjects, especially with regard to subjects older than 55 years where data from only 30 healthy subjects have been used. The present study aimed to remedy this situation. Now data are available from 3,282 subjects as compared to data from 738 subjects published previously. Disregarding sex-related differences, the TDI score at the tenth percentile was 24.9 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6 for subjects older than 55 years. Because the tenth percentile has been defined to separate hyposmia from normosmia, these data can be used as a guide to estimate individual olfactory ability in relation to subject's age. Absolute hyposmia was defined as the tenth percentile score of 16-35 year old subjects. Other than previous reports the present norms are also sex-differentiated with women outperforming men in the three olfactory tests. Further, the present data suggest specific changes of individual olfactory functions in relation to age, with odor thresholds declining most dramatically compared to odor discrimination and odor identification.
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Olfactory disorders are common and affect about one-fifth of the general population. The main causes of olfactory loss are post viral upper respiratory infection, nasal/sinus disease, and head trauma and are therefore very frequent among patients in ear, nose, and throat clinics. We have systematically reviewed the impact of quantitative, qualitative, and congenital olfactory disorders on daily life domains as well as on general quality of life and depression. From the extensive body of literature, it can be concluded that loss of the sense of smell leads to disturbances in important areas, mainly in food enjoyment, detecting harmful food and smoke, and to some extent in social situations and working life. Most patients seem to deal well and manage those restrictions. However, a smaller proportion has considerable problems and expresses a noticeable reduction in general quality of life and enhanced depression. The impact of coping strategies is discussed.
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There is evidence that the olfactory system can be modulated by repeated exposure to odors, a procedure called olfactory training. The aim of this study was to assess the effectiveness of olfactory training in patients with postinfectious and post-traumatic olfactory dysfunction. Prospective study of 119 patients with postinfectious and post-traumatic olfactory dysfunction. Two groups of patients (postinfectious and post-traumatic) performed the olfactory training (n = 49 and n = 23, respectively) over a period of 16 weeks and were compared with two control groups of the same etiology (n = 32 and n = 15). Patients with sinunasal, neurologic, or idiopathic disease were excluded. Training was performed twice daily with the use of four odors (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon], and eugenol [cloves]). Olfactory testing was performed by means of the Sniffin' Sticks test battery (threshold, discrimination, identification) at the time of diagnosis, and 8 and 16 weeks later. All patients evaluated their olfactory function by means of a visual analogue scale (0-100). Compared to controls, training patients in both groups presented significantly higher scores of olfactory function as measured by the Sniffin' Sticks test. This increase was measured in 67.8% of postinfectious and 33.2% of post-traumatic patients. Subjective ratings were in accordance with the olfactory test results. Subset analysis showed that olfactory function mainly increased olfactory identification followed by discrimination in both training groups. The present study suggests that a 16-week short-term exposure to specific odors may increase olfactory sensitivity in patients with postinfectious and post-traumatic olfactory dysfunction. 3b. Laryngoscope, 2013.
Article
The aim of this study was to evaluate the effects of olfactory training (OT) on olfactory function in patients with persistent post-infectious olfactory dysfunction (PIOD). Randomized, single-blind, controlled multicenter cross-over study. 1b SETTING: Twelve tertiary University medical centers participated. Investigations were performed at three visits (baseline; after 18 and 36 weeks), including only subjects with PIOD of less than 24 months duration. At each visit, participants received detailled assessment of olfactory function. Seventy subjects trained with high concentrations of 4 odors for 18 weeks, the other half (n=74) trained with low concentrations of odors; for the following 18 weeks this regimen was switched. After 18 weeks olfactory function improved in the high-training-group in 18 of 70 participants (26%), whereas only 11/74 improved in the low-training group (15%). In subjects with a duration of olfactory dysfunction of less than 12 months olfactory function improved in 15/24 (63%) of the high-training-group and in 6/31 participants (19%) of the low-training-group (p=0.03). OT improves PIOD; use of odors at higher concentrations is beneficial to that. OT is a safe procedure; it seems particularly useful in patients who start OT within 12 months after onset of the disorder. OT is the first successful therapy regime in patients with PIOD. Laryngoscope, 2013.
Article
Introduction Olfactory dysfunction has been reported to affect more than 200,000 patients a year in the USA. The aim of this survey was to obtain comparable epidemiological data and treatment information on olfactory dysfunction in German speaking countries. Methods Questionnaires were sent to all otorhinolaryngology departments in Germany, Austria and Switzerland; 52% of hospitals completed the survey. Results An average of 46 patients with olfactory dysfunction were treated per hospital every month. Hyp- and anosmia were most commonly caused by inflammatory diseases of the nose/paranasal sinuses (53%), respiratory dysfunction (19%), or postviral conditions (11%). Steroids were used most frequently for pharmacological treatment (topically 82%; orally 65%). Approximately one third of the clinics used B vitamins, or zinc; 80% of the hospitals performed surgery to treat underlying diseases. Acupuncture and smell training was used by approximately 20%. Conclusion A total of 79,000 patients per year are treated for olfactory dysfunction in German hospitals. The vast majority of these disorders (72%) is caused by sinunasal diseases. The quality control of therapeutic strategies is urgently needed.
Article
In den USA erkranken pro Jahr ca. 200.000 Patienten neu an Riechstörungen. Epidemiologische Daten liegen für den deutschsprachigen Raum nicht vor.Erhebung von Prävalenzen, Ursachen und Therapiekonzepten von/bei Riechstörungen im deutschsprachigen Raum.Ein Fragebogen zu Riechstörungen und deren Therapie wurde an alle HNO-Kliniken in Deutschland, Österreich und der Schweiz verschickt (Rücklaufquote 52%). Im Mittel werden pro Klinik 46 Patienten mit Riechstörungen im Monat behandelt. Häufigste Ursachen sind Entzündungen der Nase/Nebenhöhlen (53%), gefolgt von respiratorischen (19%) und postviralen Riechstörungen (11%). Bei der pharmakologischen Therapie finden Steroide die breiteste Anwendung (topisch: 82%; systemisch: 65%), über 40% verwenden Vitamin-Komplexe und Zink. Chirurgische Maßnahmen werden von 80% zur Behandlung der Grunderkrankung eingesetzt (meist NNH-OPs; Septumplastiken).Basierend auf den hier erhobenen Daten werden pro Jahr mehr als 79.000 Patienten mit Riechstörungen (meist sinunasaler Ätiologie) alleine an deutschen HNO-Kliniken behandelt. Die Behandlungskonzepte bei Riechstörungen sind regional sehr unterschiedlich, ebenso die Indikationsstellung für eine Therapie unter Berücksichtigung der Ätiologie. Maßnahmen zur Qualitätssicherung der Therapie von Riechstörungen sind daher dringend erforderlich.
Article
Background: Although widely used in healthy subjects and patients with olfactory loss, the significance of changes of scores from validated olfactory tests is unknown. Aim and methods: The aim of the present study was to relate the self-assigned changes of olfactory function in terms of "better," "unchanged," and "worse" in patients with smell disorders with the results from olfactory testing by means of a validated test set. Olfactory function of 83 anosmic or hyposmic patients (40 women, 43 men; age 12-84 yr) was tested on two occasions (mean interval 136 days, minimum 7 days, maximum 6.7 yr). Olfactory function was assessed using a validated technique ("Sniffin' Sticks"). This test consists of three subtests, one for odor threshold (T), odor discrimination (D), and odor identification (I), with possible results ranging up to 16 points each. From the sum of the results from the three subtests a composite "TDI" score was obtained. Results: Forty-four patients indicated an improvement of olfactory function, whereas 39 patients reported no change. No subject reported deterioration of olfactory sensitivity. Subjects assigned to group BETTER had higher TDI scores in the second olfactory tests than subjects assigned to the group UNCHANGED, both in absolute terms and as compared with the first olfactory test (effect "test occasion" by "self-assessed improvement," P < .001). There was no significant difference between groups with respect to age and sex (P = .99 and .84, respectively). Logistic regression showed that more than 60% of the subjects reported an improvement of olfactory sensitivity when the TDI score increased by 5.5 points. Conclusion: We show that there is a statistically significant relation between measured and perceived improvement of olfactory function in patients who first presented with the diagnosis of anosmia or hyposmia. The results indicate that improved olfactory function in patients with olfactory deficiency is perceived as such in everyday life and is quantitatively related to an improvement in the composite TDI score of the "Sniffin' Sticks" olfactory test battery. This is the basis for the application of a specific therapy for olfactory loss because of a possible gain in quality of life for the patients.
Article
Infection of the upper respiratory tract is one of the most common causes of olfactory loss. One of the possible underlying pathologic pathways is an increase of apoptosis of olfactory receptor neurons. Therefore, treatment with the antibiotic minocycline, which has been shown to act as an antiapoptotic agent, is thought to accelerate improvement of olfactory function. To investigate this idea, 55 patients with postinfectious olfactory dysfunction were tested for their olfactory ability. Randomized, prospective, double-blind, placebo-controlled. Olfactory function was examined by means of a standardized psychophysical method (Sniffin' Sticks) before and 7 months after a 3-week treatment with either minocycline (2 × 50 mg/d) or a placebo. Statistical analyses did not reveal any influence of the treatment on the progress of olfactory function, possibly indicating that pathologic changes other than apoptosis contribute to postinfectious olfactory loss, either on a peripheral level (e.g., scarring/reorganization of the olfactory epithelium) or on a central nervous level. In conclusion, the present results indicate that minocycline in the given dosage has little or no effect on the recovery of human olfactory function following postinfectious olfactory loss. However, spontaneous recovery is found in approximately 20% of the patients over an observation period of 7 months.
Article
This paper is a review of progress in the ‘specific anosmia’ approach to the classification of odors. We have developed a suggestion by Guillot that the study of specific chemical defects in olfactory perception might reveal the fundamental or primary odors of the human sense of smell. Six varieties of specific anosmia have been mapped out in chemical detail. The maximum anosmic defects were observed with the following primary odorants: isovaleric acid, l-pyrroline, trimethylamine, isobutyraldehyde, 5α-androst-16-en-3-one and ω-pentadecalactone. We have named the corresponding primary odors: sweaty, spermous, fishy, malty, urinous and musky. There is evidence that other mammals may possess many of the same primary odor sensitivities. These primary odors appear to be well adapted for perceiving food and body odors, thereby conveying nutritional information and pheromonal signals in animals and man. Evidence from the known varieties of specific anosmia suggests that the total number of human primary odors is at least 32.
Article
Differentiation of progenitor cells into neurons in the olfactory bulb depends on olfactory stimulation that can lead to an increase in olfactory bulb volume. In this study, we investigated whether the human olfactory bulb volume increases with increasing olfactory function due to treatment of chronic rhinosinusitis. Nineteen patients with chronic rhinosinusitis were investigated before and after treatment. For comparison, additional measurements were performed in 18 healthy volunteers. Volumetric measurements of the olfactory bulb were based on planimetric manual contouring of magnetic resonance scans. Olfactory function was evaluated separately for each nostril using tests for odour threshold, odour discrimination and odour identification. Measurements were performed on two occasions, 3 months apart. In healthy controls, the olfactory bulb volume did not change significantly between the two measurements. In contrast, the olfactory bulb volume in patients increased significantly from the initial 64.5 +/- 3.2 to 70.0 +/- 3.5 mm(3) on the left side (P = 0.02) and from 60.9 +/- 3.5 to 72.4 +/- 2.8 mm(3) on the right side (P < 0.001). The increase in olfactory bulb volume correlated significantly with an increase in odour thresholds (r = 0.60, P = 0.006, left side; r = 0.49, P = 0.03, right side), but not with changes in odour discrimination or odour identification. Results of this study support the idea that stimulation of olfactory receptor neurons impacts on the cell death in the olfactory bulb, not only in rodents but also in humans. To our knowledge, this is the first longitudinal study that describes an enlargement of the human olfactory bulb due to improvement of peripheral olfactory function.
Article
The aim of this study was to evaluate the effect of smoking on taste and smell impairment in a large population- based study. Cross-sectional survey in Dortmund, Germany. The population sample was randomly drawn from the city's central registration office. Following a standardized interview, validated taste and smell tests were performed. Descriptive statistics and logistic regression was used in the analysis. Among the 1312 study participants, 3.6 % were functionally anosmic, and 18 % had olfactory dysfunction. Approximately 20 % recognized only three or less of the four tastes when presented at suprathreshold concentrations, indicating signs of taste impairment. Current smoking in general increased the risk for impairment of olfactory function (odds ratio 1.71, 95 % CI 1.19-2.47), but not the risk for taste impairment. Heavy smokers of 20 or more cigarettes/day had significant increased risks for impairment in both senses. Our results reveal that both olfactory and gustatory function are compromised in a significant proportion of the general population. Smoking increases significantly the risk of impairment of olfactory function. Our findings add an important detail to the large body of evidence that describes adverse health effects of smoking.
Article
Otolaryngologists, neurologists and other medical practitioners are often not well equipped for assessing olfactory (dys)function. They either use no or inadequate olfactory tests. This problem of inadequate olfactory testing was systematically attacked by American psychologists in the early 80's and led to the construction of odour identification tests which are easy to administer. Combining the advantages of two of these American tests we developed a Dutch odour identification test (GITU), consisting of two subsets of 18 natural odourants and applicable in two ways: one for use in the ENT clinic, the other for industrial purposes. The first results of this test indicate that the incidence of serious olfactory disorder among adults in the Netherlands may be conservatively estimated at about 1%. The GITU readily discriminates between patients and controls and is sensitive to variables known to affect olfaction (gender, age). The recognition of olfactory dysfunction as a major problem has led in the U.S.A. to the establishment of clinical research centers for the study of human chemoreception. Evaluation results of four of those clinics together with data of three more case series--with a total number of patients of 4000--show that two thirds of all patients fall into three etiological categories: 1. Nasal disease and/or paranasal sinus disease. 2. Viral infection of the upper respiratory pathway. 3. Head trauma. For each of the three categories the literature is reviewed in order to arrive at a clearer picture of the olfactory patient with respect to age, gender, degree of olfactory deficit, spontaneous recovery, effectiveness of therapy and localization of the defect along the olfactory pathway. Finally an appeal is made to clinicians with interest in the subject to exchange more information with research scientists in olfaction. Such exchange is considered essential to making progress in this field.
Article
The olfactory test administered to patients at the Connecticut Chemosensory Clinical Research Center combines stability of outcome with sensitivity to variables known to affect olfaction (age, sex). The test, which pairs an odor threshold component with an odor identification component, readily resolves differences in function between patients and controls. It reveals differences in the distribution of functioning for various probable causes (nasal/sinus disease, postupper respiratory infection, and head trauma), proves sensitive to improvements in function caused by therapeutic intervention (ethmoidectomy, steroid administration for nasal/sinus disease), and correlates with objective signs of nasal/sinus disease (visual exam, x-ray). The two components of the test agree well, though the odor identification component seems somewhat more sensitive than the threshold component as currently designed.
Article
To determine the extent to which olfactory function can improve after loss induced by head trauma or a previous upper respiratory tract infection (URI) and the time for this improvement for more effective patient counseling. Patients initially evaluated at the University of Cincinnati (Ohio) Taste and Smell Center were reevaluated for olfactory loss with the University of Pennsylvania (Philadelphia) Smell Identification Test 1 to 5 years after initial testing. Changes in score on this test were used to indicate improvement in sensory function. Subjective information on olfactory ability and olfactory symptoms was also collected. University-based tertiary care center. Forty-one patients with olfactory loss induced by head trauma (20) or previous URI (21). Seven (35%) of 20 patients with head trauma improved on the smell test by 4 points or more. Fourteen of 21 (67%) patients with a previous URI had improved scores of this magnitude or more. A statistically significant correlation was noted between the amounts of improvement and length of follow-up for URI patients. Thirteen of these patients also reported improved olfactory function. These findings for patients with head trauma are consistent with other reports of recovery of (or improvement in) olfactory function after trauma-induced loss. For patients with previous URI, these data indicate that improvement in olfactory function occurs, but the improvement may take several years.
Article
Previous studies have demonstrated that there are intrinsic spatial patterns of odorant sensitivity across the rat olfactory mucosa. The question of how these patterns are determined and whether they are modifiable with experience remains open. Therefore, the present study examined whether the odorant-induced spatial activity patterns which are characteristic of different odorants would be altered by experience. Odorant exposure was achieved as a consequence of training and testing on a five odorant identification task in which rats were trained to differentially report (i.e. identify) the odorants propanol, ehtylacetoacetate, carvone, citral, and propyl acetate. At the completion of testing, each animal was sacrificed and their mucosal activity patterns recorded using optical techniques and a voltage-sensitive dye. Using the dye, di-4-ANEPPS, we monitored the fluorescence changes at 100 contiguous sites with a 10 x 10 photodiode array on the olfactory mucosa of each rat's septum and medial surface of the turbinates in response to the same five odorants. The recorded spatial activity patterns of trained animals were compared to those of age-matched controls. For the trained animals, both mucosal surfaces showed a significant increase in the average response magnitude. Furthermore, for the septal mucosa only, there was a significant increase in the distinctiveness of an odorant's characteristic 'hot spot'.
Article
Repeated exposure to olfactory ligands (odorants) increased peripheral olfactory sensitivity in mice. For two unrelated ligands, androstenone and isovaleric acid, induction of olfactory sensitivity was odorant-specific and occurred only in inbred strains that initially had low sensitivity to the exposure odorant. These data demonstrate stimulus-induced plasticity in a sensory receptor cell, suggesting a form of stimulus-controlled gene expression. Induction with two unrelated odorants implies that olfactory induction is a general phenomenon that may occur in a large fraction of the human population.
Article
In the first of three studies, children (aged 8 to 14 years) were found to perform worse than young and middle-aged adults in unprompted identification of doors, with average performance much like that of elderly adults. Comparisons on other tasks, specifically odor threshold, prompted odor identification, and object naming (Boston Naming Test), across the life span (five groups) revealed that children have the same excellent olfactory sensitivity as young adults and merely lack odor-specific knowledge that accumulates slowly through life. Such knowledge apparently accumulates so slowly that age-associated discriminative losses, measurable by early middle age, begin to wear away gains obtained through experience before odors can become overlearned. In the second study, a novel adaptive psychophysical method, the step procedure, confirmed the equivalent sensitivity of children and young adults. In the third study, a paired-associate task illustrated the sluggish course of odor learning. Young adults outperformed children, though the youngest group, first graders, made up ground relatively fast. For children and adults, common odors facilitated performance relative to novel odors. The outcome highlighted the relevance of semantic factors in odor learning irrespective of age.
Article
Ten tests of olfactory function (including tests of odor identification, detection, discrimination, memory, and suprathreshold odor intensity and pleasantness perception) were administered on two test occasions to 57 subjects ranging in age from 18 to 83 years. The stability of the average test scores was determined across the two test sessions for 14 measures derived from these 10 tests and for subcomponents of the Japanese T&T olfactometer threshold test. In addition, the test-retest reliability (Pearson r) of each test measure was established. With the exception of a response bias measure, the average test scores did not differ significantly across the two test sessions. Statistically, the reliability coefficients of the primary test measures fell into three general classes bound by the following r values: 0.43-0.53; 0.67-0.71; 0.76-0.90. Detection threshold values were more reliable than recognition threshold values; those based upon a single ascending presentation series were much less reliable than those based upon a staircase procedure. The relationship between test length and reliability was examined for several of the tests and mathematically modeled. For example, within the staircase series incorporating the odorant phenyl ethyl alcohol, reliability was related (R2 = 0.984) to the number of reversals included in the threshold estimate by a function derived from the Spearman-Brown formula; namely, reliability = 0.455* # reversals/[1 + 0.455 (# reversals - 1)]. Reversal location, per se, had little influence on reliability. Overall, this study suggests that (i) considerable variation is present in the reliability of olfactory tests, (ii) reliability is a function of test length, and (iii) caution is warranted in comparing results from nominally different olfactory tests in applied settings since the findings may, in some instances, simply reflect the differential reliability of the tests.
Article
'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.
Article
The high dimensionality and unpredictability of the chemical world makes it difficult for the olfactory system to anticipate relevant stimuli and construct neural filters accordingly. A developmental solution to this problem would be to alter the sensory surface according to environmental conditions so as to enhance sensitivity to molecules of particular relevance. Evidence for this has been obtained in the rabbit. By feeding pregnant does aromatic juniper berries, it could be shown that newborn, weanling and even adult animals demonstrate a preference for juniper odor without subsequent postnatal experience, and that this is associated with enhanced peripheral sensitivity for juniper odor as measured by electro-olfactogram (EOG). This is consistent with the report that in young salmon olfactory imprinting is associated with enhanced, odor-specific sensitivity of receptor cells as measured by patch clamp. The mechanisms underlying such changes are unknown, including the extent to which they are a particular feature of developing systems.
Article
We used the inhalation of methyl bromide gas to produce a near-complete destruction of the rat olfactory epithelium and analyzed the reinnervation of the bulb during reconstitution of the epithelium. The degeneration of olfactory axons elicits a transient up-regulation of glial cell proliferation and glial fibrillary acidic protein expression in the olfactory nerve and olfactory nerve layer of the bulb. Anterograde transport after intranasal infusion of wheat germ agglutinin conjugated horseradish peroxidase demonstrates that the first nascent axons reach the bulb within the first week after lesion. Subsequently, a massive wave of fibers arrives at the bulb between 1 and 2 weeks postlesion, and enters the glomeruli between 2 and 3 weeks postlesion. However, the olfactory projection does not stabilize until 8 weeks after lesion judging from the return in growth associated protein-43 expression to control levels. The extent of reinnervation after lesion is correlated with the completeness with which the epithelium reconstitutes itself. In rats that are lesioned while fed ad libitum, there is near-complete reconstitution of the neuronal population, and the projection onto the bulb fills the glomerular layer in its entirety. However, in rats that are lesioned while food restricted, a significant fraction of olfactory epithelium becomes respiratory during its reconstitution, and the population of reinnervating fibers is less. As a consequence, the posterior half of the bulb remains hypoinnervated overall and denervated at its caudal margin. The preferential reinnervation of the anterior bulb in the food-restricted, methyl bromide gas-lesioned animals indicates that the mechanisms that guide the growth of the olfactory axons and restore receptotopy do not operate with the same precision in this setting as they do during development or during the lower level of turnover associated with the "normal" laboratory existence. Accordingly, we hypothesize that the persistence of a significant population of pre-existing neurons is needed to preserve receptotopy during reinnervation. In addition, the results suggest that in the face of massive turnover and a reduced afferent population, there is a tendency for reinnervating axons to fill available synaptic space.
Article
The olfactory test battery "Sniffin'Sticks" comprises a perception threshold test, an odour discrimination test and an odour identification test. The purpose of this study was to examine the suitability of the Sniffin'Sticks for use in everyday practice and to obtain (at least provisional) normal values. Thirty normosmic and 15 anosmic volunteers were examined with the Sniffin'Sticks and the "University of Pennsylvania Smell Identification Test" (UPSIT). All three Sniffin'Sticks tests distinguish between normosmics and anosmics in a highly significant manner. The good correlation of the individual tests with each other and with the results of the UPSIT documents the reliability of the test results. Critical mention must be made of the overly complex determination of the olfactory threshold. In conclusion, the Sniffin'Sticks test battery provides a validated instrument adapted to European conditions for the examination of olfactory disorders. It has proven successful in everyday clinical practice and constitutes a major aid for compiling medical certificates.
Article
Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. To determine the prevalence of olfactory impairment in older adults. A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.
Article
The study aimed to investigate the potential therapeutic effects of alpha-lipoic acid in olfactory loss following infections of the upper respiratory tract. Possible mechanisms of actions include the release of nerve growth factor and antioxidative effects, both of which may be helpful in the regeneration of olfactory receptor neurons. Unblinded, prospective clinical trial. A total of 23 patients participated (13 women, 10 men; mean age 57 y, age range 22-79 y; mean duration of olfactory loss, 14 mo; range, 4 to 33 mo); 19 of them were hyposmic and 4 had functional anosmia. Alpha-lipoic acid was used orally at a dose of 600 mg/day; it was prescribed for an average period of 4.5 months. Olfactory function was assessed using olfactory tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. Seven patients (30%) showed no change in olfactory function. Two patients (9%) exhibited a moderate decrease in olfactory function; in contrast, six patients (26%) showed moderate and eight patients (35%) remarkable increase in olfactory function. Two of the 4 patients with functional anosmia reached hyposmia; 5 of 19 hyposmic patients became normosmic. Overall, this resulted in a significant improvement in olfactory function following treatment (P =.002). At the end of treatment parosmias were less frequent (22%) than at the beginning of therapy (48%). Interestingly, recovery of olfactory function appeared to be more pronounced in younger patients than in patients above the age of 60 years (P =.018). The results indicate that alpha-lipoic acid may be helpful in patients with olfactory loss after upper respiratory tract infection. However, to judge the true potential of this treatment, the outcome of double-blind, placebo-controlled studies in large groups of patients must be awaited, especially when considering the relatively high rate of spontaneous recovery in olfactory loss after upper respiratory tract infection.
Article
The treatment of non-conductive olfactory disorders is to a large extent an unsolved problem. This proof-of-concept study focused on possible effects of the N-methyl-D-aspartate (NMDA) antagonist caroverine. Potential mechanisms for the hypothesized effect included reduced feedback inhibition in the olfactory bulb as a consequence of NMDA antagonistic actions and antagonism of an excitotoxic action of glutamate. A total of 77 consecutive patients with non-conductive olfactory disorders were included in the study. Fifty-one patients received caroverine for 4 weeks (120 mg/day); 26 controls matched for age, gender and duration of olfactory loss were treated with zinc sulfate for the same length of time (400 mg/day). Olfactory sensitivity was evaluated before and after treatment. Testing included assessment of n-butanol odor threshold and odor identification. When compared to baseline, treatment with caroverine improved both odor thresholds (p = 0.005) and odor identification (p = 0.042) in anosmic patients. In hyposmic patients it significantly improved odor identification ability (p = 0.041). In contrast, zinc sulfate had no significant effect on olfactory function. These results indicate that caroverine appears to be effective for the treatment of non-conductive smell disorders.
Article
The aim of this study was to investigate the accuracy of self-reported ratings of olfactory function in 83 healthy subjects. Such ratings were compared with quantitative measures of olfactory function, as well as with ratings of nasal patency. In experiment 1 subjects rated olfactory function and nasal patency before olfactory testing, whereas in experiment 2 the reverse was the case. No feedback regarding test results were provided until after completion of the testing. The principal findings were: (i) when ratings preceded measurements of olfactory function, there was no significant correlation between the two parameters. However, ratings of olfactory function correlated significantly with ratings of nasal airway patency. (ii) In contrast, when measurements of olfactory function preceded the ratings, this constellation switched. Now ratings of olfactory function correlated significantly with measured olfactory function, whereas there was no significant correlation between ratings of nasal airway patency and ratings of olfactory function. In conclusion, these data suggest that ratings of olfactory function are unreliable in healthy, untrained subjects. The ratings seem to reflect changes of nasal airway patency to a larger degree than measurable olfactory function. The results further indicate that this is mainly due to the limited attention the sense of smell receives in daily life.