The current possibilities of diagnosing and therapies for olfactory disorders.

INTRODUCTION: Olfactory disorders significantly affect individuals, diminishing their capacity to detect dangers, appreciate flavors, and engage socially. Despite their considerable impact on quality of life, these disorders often receive less attention compared to other sensory impairments. This review emphasizes the importance of olfactory function and explores both traditional and innovative diagnostic and therapeutic approaches. AREAS COVERED: This review comprehensively covers the pathophysiology, diagnostic challenges, and treatment options for olfactory disorders. It delves into the nuances of different disorders, such as anosmia and parosmia, and discusses the array of diagnostic tools from traditional sniff tests to advanced imaging techniques. The review also evaluates therapeutic strategies, from pharmacological treatments to emerging therapies like electrical stimulation and regenerative medicine, highlighting recent advances in the field. EXPERT OPINION: Current insights suggest a growing recognition of the significance of olfactory disorders, driven by recent pandemics and advances in diagnostic and therapeutic technologies. Future perspectives indicate a promising direction toward more personalized medicine approaches and enhanced regenerative therapies. Continuous research and improved clinical awareness are critical for evolving the management strategies of olfactory impairments, potentially leading to better patient outcomes and quality of life enhancements.

Effects of Frequency-Controlled Ear Acupuncture on COVID-19- related Refractory Olfactory Dysfunction: a Randomized Clinical Trial.

Background: Olfactory dysfunction is a common COVID-19 symptom, posing treatment challenges. Objectives: We aimed to investigate the efficacy of frequency-controlled ear acupuncture in treating COVID-19-related olfactory dysfunction. Methods: A randomized, participant-blind clinical trial occurred at the Rasoul Akram Hospital (IRCT20210311050671N1). Forty patients were recruited, and 20 patients were randomly assigned to either the experimental or control group. The primary outcome was the improvement in patients' quality of smell. The olfactory dysfunction was confirmed using the Smell Identification Test. The intervention group received two sessions of acupuncture treatment according to auricular frequency treatment, with a one-week interval, while the control group received an equal number of switched-off laser sessions. Both groups were instructed to use nasal betamethasone drops. The patients were asked to rank their ability to smell before and after each intervention on a 10-point visual analog scale. Secondary outcomes were related side effects. Results: Covariance analysis revealed a significant difference in adjusted scores between the groups (F [37, 1] = 37.463; p = 0.000, Eta2 = 0.503). The smell quality improved from 2.80 ± 1.76 to 5.22 ± 3.40 after treatment in the intervention group (p = 0.007), while the control group showed no significant change (p = 0.184). Three patients reported short and transient side effects, such as nausea, headache, and dizziness, in the first hours after the intervention. Conclusion: Frequency-controlled ear acupuncture is an effective option for treating COVID-19-related olfactory dysfunction. The study highlights the potential of alternative therapies in the treatment of this condition, and further research is warranted to investigate its long-term effects.

The effect of smell training on COVID-19 induced smell loss.

OBJECTIVE: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss. METHODS: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores. RESULTS: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function. CONCLUSION: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.

Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.

PURPOSE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment. METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia. RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated. CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.

Effect of Different Therapeutic Strategies on Olfactory Outcomes in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review.

INTRODUCTION: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile evidence on the impact of medical, surgical, and biological treatment on olfactory outcomes in patients with CRSwNP. METHODS: This review was conducted by 2 reviewers according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence of all the studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP). RESULTS: Forty-four studies were included in the qualitative synthesis. These assessed sinonasal surgery (n=23), biologics (n=15), and conventional medical treatment (n=6). The methodological quality was moderate-to-high in most. Overall, significant improvements in the sense of smell were detected with all the interventions analyzed and measured using an objective tool, a subjective tool, or both. However, most studies used different outcome measures, thus hindering comparisons between interventions, and data on clinically relevant changes were missing. CONCLUSION: Oral corticosteroids, biologics, and sinonasal surgery improve the olfactory impairment associated with CRSwNP. However, the heterogeneous nature of existing studies does not allow accurate comparisons.

Stellate ganglion block for treating post-COVID-19 parosmia.

BACKGROUND: Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD). METHODS: Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts. RESULTS: Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05). CONCLUSION: SGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

OBJECTIVE: The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. STUDY DESIGN: Prospective case series. SETTING: Quaternary Care Academic Medical Center. METHODS: In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). RESULTS: Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. CONCLUSION: Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.

Olfactory training in normosmic individuals: a randomised controlled trial.

BACKGROUND: Even if olfactory training (OT) is a well-established treatment for individuals with olfactory dysfunction, the effect on individuals with normosmia remains uncertain. In this randomised controlled trial, we explore how OT with different exposure lengths affect olfactory function in individuals with normosmia. METHODOLOGY: Two hundred normosmic individuals were randomly assigned to one of two intervention groups performing OT with different exposure lengths or to a control group. The OT groups did OT twice daily for three months, g four different odours (eucalyptus, lavender, mint, and lemon) for 10 seconds per bottle during either a total of 40 seconds (standard OT) or 4 minutes (extended OT), while the control group did not perform any OT. Olfactory function was assessed using a 48-item Sniffin Sticks test at baseline, after the intervention, and after one year. RESULTS: We found no significant effect of OT in either of the intervention groups on any aspect of olfaction after intervention or at follow-up. There was no association between sex, age, allergic rhinitis, education or olfactory scores at baseline, and changes in olfactory function after OT. The extended OT group performed significantly fewer training sessions compared to those in the standard OT group. CONCLUSIONS: OT had a limited effect on olfactory function in individuals with normosmia. Further, the superiority of a more extended OT is not supported by this study, and shorter training sessions seem to improve compliance with OT.

Olfactory dysfunction and training in children with COVID-19 infection: A prospective study Post-COVID pediatric olfactory training.

OBJECTIVE: Postviral olfactory dysfunction (OD) including corona 2019 viral disease (COVID-19) OD occurs in both adults and children. Despite limited reports of efficacy in treating adult postviral including COVID-19 OD with olfactory training (OT), its effects on children in general, and post-COVID-19 in specific, is unknown. The study aimed at evaluating the effects of OT in a COVID-19 OD pediatric cohort. METHODS: A single-arm prospective study of pediatric COVID-19 OD subjects confirmed by the University of Pennsylvania Smell Identification Test (UPSIT), was conducted. All subjects underwent OT by sniffing 4 odorants (lavender, orange, peppermint, and eucalyptus) for 1 min twice a day for 3 months. Subjects underwent an odorant identification test (OIT) of the 4 odorants each visit. A repeat UPSIT was administered at the 4th visit. RESULTS: The study enrolled a total of 37 subjects [11 males/26 females with mean age/standard deviation (std) of 15.6(2.1) years]. The time interval between COVID-19 and entry was 5.3(2.4) months. The mean pre/post study UPSIT score improvement was 2.3(4.7), p = .09. OIT scores between entry and 3 subsequent visits showed a mean improvement of 1.8(1.5), 1.8(1.9) and 2.3(1.9) odorants, respectively, with P < .001 for all 3 comparisons. CONCLUSIONS: OT subjects were predominantly female teens with substantial OD lasting greater than 5 months. OT did not affect OD as measured by UPSIT but OIT scores improved during OT. We postulate that OT likely has a role in pediatric post-COVID OD recovery, but UPSIT likely is too rigid to detect disparate odorant improvement.

Effectiveness of Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Controlled Study.

OBJECTIVE: To investigate the effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of coronavirus disease 2019 (COVID-19) patients with persistent olfactory dysfunction (OD). STUDY DESIGN: Controlled study. SETTING: Multicenter study. METHODS: From March 2022 to November 2022, COVID-19 patients with persistent OD were recruited from three European hospitals to undergo PRP injections into the olfactory clefts. Olfactory function was evaluated at baseline and 10 weeks postinjection with the Olfactory Disorder Questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. Data were compared with a control group of untreated patients. RESULTS: Eighty-one patients who underwent PRP injection and 78 controls were included. Sixty-five PRP patients (80.3%) experienced subjective smell improvement after a mean duration of 3.4 ± 1.9 weeks. The parosmia, life quality statement, and ODQ sub- and total scores significantly decreased from pre- to 10-week postinjection in the PRP group. The TDI sub- and total scores significantly increased 10 weeks postinjection. In controls, the ODQ score did not change over time, while the discrimination, identification, and total TDI scores significantly increase after 10 weeks of follow-up. The 10-week TDI and ODQ scores were significantly better in the PRP group compared with the controls. CONCLUSION: Patients who underwent PRP injection reported better 10-week subjective and objective smell outcomes than controls. Future randomized-controlled studies using saline injection into the olfactory cleft of controls are needed to determine the superiority of PRP over placebo.

Hyperbaric oxygen therapy for treatment of COVID-19-related parosmia: a case report.

Parosmia is a qualitative olfactory dysfunction characterized by distortion of odor perception. Traditional treatments for parosmia include olfactory training and steroids. Some patients infected with COVID-19 have developed chronic parosmia as a result of their infection. Here, we present the case of a patient who developed parosmia after a COVID-19 infection that was not improved by traditional treatments but found significant improvement after hyperbaric oxygen therapy[A1].

Effectiveness of platelet-rich plasma on post-COVID chronic olfactory dysfunction.

OBJECTIVE: The aim of this study was to investigate the efficacy of platelet-rich plasma injection on the olfactory cleft of patients with post-COVID olfactory dysfunction lasting over 1 year, who were unresponsive to common treatments. METHODS: Patients over 18 years of age with post-COVID olfactory dysfunction over 1 year whose complaints did not improve with intranasal steroids and D-panthenol/vitamin A combination nasal sprays with olfactory rehabilitation training for 1 month were prospectively collected and randomized into two groups: intranasal platelet-rich plasma group and control group. At the end of 1 month, Connecticut Chemosensory Clinical Research Center olfaction test scores of smell detection threshold and smell identification test were compared accordingly. RESULTS: A total of 25 patients were randomized into platelet-rich plasma (n=12) and control (n=13) groups. In the platelet-rich plasma group, the mean smell detection threshold score increased from 5.63 (SD 0.68) to 6.46 (SD 0.45), and the mean smell identification test score increased from 11.42 (SD 1.17) to 15.17 (SD 0.39). In the control group, the mean smell detection threshold score changed from 5.69 (SD 0.66) to 5.77 (SD 0.70), and the mean smell identification test score changed from 11.20 (SD 1.12) to 11.85 (SD 1.57). Post-hoc analysis revealed that similar mean smell detection threshold (mean difference 0.07; p=0.994) and smell identification test (mean difference -0.50; p=0.703) scores were transformed into a significant difference between groups (smell detection threshold mean difference 0.69; p=0.037; smell identification test mean difference 3.32; p<0.001). CONCLUSION: At the end of the first month, there was a significant improvement in olfactory threshold values in the platelet-rich plasma group compared to the control group. No side effect or adverse event related to platelet-rich plasma injection was observed.

Mechanism and treatment of olfactory dysfunction caused by coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the start of the pandemic, olfactory dysfunction (OD) has been reported as a common symptom of COVID-19. In some asymptomatic carriers, OD is often the first and even the only symptom. At the same time, persistent OD is also a long-term sequela seen after COVID-19 that can have a serious impact on the quality of life of patients. However, the pathogenesis of post-COVID-19 OD is still unclear, and there is no specific treatment for its patients. The aim of this paper was to review the research on OD caused by SARS-CoV-2 infection and to summarize the mechanism of action, the pathogenesis, and current treatments.

[Diagnostics and treatment of olfactory disorders]. / Reukstoornissen in de klinische praktijk.

Olfactory disorders are common and have consequences for the quality of life of patients. The main causes are post viral upper respiratory tract infections, head trauma and sinonasal disease. However, there are many more less frequent causes which we illustrate by showing three different rare cases. A distinguishment between qualitative and quantitative olfactory disorders is made which is mainly based on the patient's history and olfactory testing. It is important to diagnose the cause of an olfactory disorder because treatment options are dependent on it and it can be a symptom of a progressive disease. Olfactory training is a proven treatment for many perceptive olfactory disorders and is easily performed by most patients.

[Persistent olfactory impairment after COVID-19-recommendations of the Working Group on Olfactology and Gustology of the German Society of Oto-rhino-laryngology, Head and Neck Surgery]. / Persistierende Riechminderung nach COVID-19 ­ Empfehlungen der Arbeitsgemeinschaft Olfaktologie und Gustologie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

This article does not intend to comprehensively review the existing literature on coronavirus disease 2019 (COVID-19)-associated smell disorders, but aims to summarize scientific evidence for otorhinolaryngological practice and provide recommendations for diagnosis and treatment of persistent smell disorders following COVID-19.

Are YouTube videos on smell dysfunction a good source of information for patients seeking a cure for their illness?

OBJECTIVE: To conduct unbiased research into the quality and reliability of videos published on YouTube on the subject of smell dysfunction and treatment through two Ear, Nose, and Throat (ENT) specialists using three different tools. METHODS: The videos were separated into two groups (reliable: Group 1; non-reliable: Group 2) according to whether or not the content was scientifically reliable, proven, accurate, and useful, as determined by two ENT specialist physicians. The DISCERN reliability tool, Global quality scale (GQS), and JAMA scoring system were used as video scoring tools in the evaluations. RESULTS: Group 1 included 173 videos, and Group 2, 16 videos. The GQS (First ENT specialist) points were 3 (2-5) and GQS (Second ENT specialist) points were 3 (2-5) in Group 1, and 2 (2-3) and 2 (1-3) in Group 2, respectively (p = 0.0001). The points in the DISCERN and JAMA scoring systems were found to be higher in Group 1 than in Group 2 (p = 0.0001). CONCLUSION: Although the majority of videos on YouTube related to smell dysfunction are reliable, the number of unreliable videos is not inconsiderable. When videos related to medical information are accepted onto YouTube, weighting should be given to videos which include scientifically proven evidence uploaded by specialist professionals and institutions.

OBJETIVO: realizar una investigación imparcial sobre la calidad y la confiabilidad de los videos publicados en YouTube sobre el tema de la disfunción y el tratamiento del olfato, a través de dos especialistas en oído, nariz y garganta que utilizan tres herramientas diferentes. MÉTODOS: Los videos se separaron en dos grupos (confiables: Grupo 1; no confiables: Grupo 2) según si el contenido era o no científicamente confiable, probado, preciso y útil, según lo determinado por dos médicos especialistas en Otorrinolaringología. La herramienta de confiabilidad DISCERN, la escala de calidad global (GQS) y el sistema de puntuación JAMA se utilizaron como herramientas de puntuación de video en las evaluaciones. RESULTADOS: el Grupo 1 incluyó 173 videos y el Grupo 2, 16 videos. Los puntos GQS (Primer especialista en ORL) fueron 3 (2-5) y los puntos GQS (Segundo especialista en ORL) fueron 3 (2-5) en el Grupo 1, y 2 (2-3) y 2 (1-3) en el Grupo 2, respectivamente (p= 0.0001). Se encontró que los puntos en los sistemas de puntuación DISCERN y JAMA eran más altos en el Grupo 1 que en el Grupo 2 (p= 0.0001). CONCLUSIÓN: aunque la mayoría de los videos en YouTube relacionados con la disfunción del olfato son confiables, la cantidad de videos poco confiables no es despreciable. Cuando se aceptan videos relacionados con información médica en YouTube, se debe dar peso a los videos que incluyen evidencia científicamente probada y subidos por instituciones y profesionales especialistas.