Qualitative Olfactory Dysfunction Research Articles

Functional connectivity patterns in parosmia

ObjectiveParosmia is a qualitative olfactory dysfunction presenting as “distorted odor perception” in presence of an odor source. Aim of this study was to use resting state functional connectivity to gain more information on the alteration of olfactory processing at the level of the central nervous system level.MethodsA cross sectional study was performed in 145 patients with parosmia (age range 20–76 years; 90 women). Presence and degree of parosmia was diagnosed on the basis of standardized questionnaires. Participants also received olfactory testing using the “Sniffin’ Sticks”. Then they underwent resting state scans using a 3 T magnetic resonance imaging scanner while fixating on a cross.ResultsWhole brain analyses revealed reduced functional connectivity in salience as well as executive control networks. Region of interest-based analyses also supported reduced functional connectivity measures between primary and secondary olfactory eloquent areas (temporal pole, supramarginal gyrus and right orbitofrontal cortex; dorso-lateral pre-frontal cortex and the right piriform cortex).ConclusionsParticipants with parosmia exhibited a reduced information flow between memory, decision making centers, and primary and secondary olfactory areas.

Subjective Perception of Recovery and Measured Olfactory Function in COVID-19 Patients.

This cross-sectional study aimed to investigate self-rated olfactory dysfunction in relation to measured olfactory function after partial or complete subjective recovery in individuals with a history of coronavirus disease 2019 (COVID-19) infection. A total of 186 individuals (aged 5-62 years) with a history of COVID-19 infection were included. Visual analogue scale (VAS) ratings for olfactory function (before, during, and after infection) and age-appropriate psychophysical olfactory test scores (odor threshold and odor identification: "Sniffin' Sticks" for adults and both "Sniffin' Sticks" and "U-Sniff" for children) were determined. Participants were assigned to four "age groups" and three "recovery classes" (incomplete recovery, complete recovery, no smell loss). Surprisingly, there were no significant differences in odor threshold and adult identification scores between the "recovery classes". However, children with "incomplete recovery" had lower identification scores than those with "complete recovery" (p = 0.033) and those with "no smell loss" (p = 0.022). The pediatric age groups had significantly higher VAS ratings during and after COVID-19 compared to older participants. Older individuals experienced greater magnitude of changes in their sense of smell after COVID-19 infection, but those with parosmia were 3.5 times more likely to report "incomplete recovery" of olfaction after COVID-19. The general prognosis for olfactory recovery after COVID-19 is good but appears to be particularly confounded by the presence of parosmia, leading patients to subjectively report incomplete olfactory recovery. Although it is of high significance to monitor recovery using validated psychophysical olfactory tests, subjective measures of olfaction help provide specific insight, especially for qualitative olfactory dysfunction.

Clinical characteristics and associated factors of qualitative olfactory dysfunction.

Although interest in qualitative olfactory dysfunction (OD), including parosmia and phantosmia, has been increasing since the COVID-19 pandemic, little is known about the clinical characteristics and associated factors of qualitative OD. Adult patients with subjective smell disturbance who underwent both the olfactory questionnaire and psychophysical olfactory function test were retrospectively enrolled. Demographic and clinical characteristics were analysed according to the presence or absence of parosmia or phantosmia. Among a total of 753 patients with self-reported OD, 60 (8%) and 167 (22.2%) patients reported parosmia and phantosmia, respectively. Younger age and female sex were related to both parosmia and phantosmia. The frequency of parosmia was significantly higher in patients with post-viral OD (17.9%) than in patients with the sinonasal disease (5.5%), whereas that of phantosmia was not different according to aetiologies of OD. Patients with COVID-19 had significantly younger ages and higher TDI scores than those with other viral infections. Remarkably, patients with parosmia or phantosmia had significantly higher TDI scores than those without but experienced more disruption in daily life. In the multivariate analysis, younger age and higher TDI score were identified as independent factors associated with both parosmia and phantosmia, while the viral infection was associated with parosmia but not with phantosmia. Patients with OD who have parosmia or phantosmia have higher odour sensitivity than those who do not, but experience more deterioration in the quality of life. Viral infection is a risk factor for parosmia but not for phantosmia.

Impairment of quality of life due to COVID-19-induced long-term olfactory dysfunction.

Olfactory dysfunction is one of many long-lasting symptoms associated with COVID-19, estimated to affect approximately 60% of individuals and often lasting several months after infection. The associated daily life problems can cause a decreased quality of life. Here, we assessed the association between perceived quality of life and both qualitative and quantitative olfactory function (distorted and weakened sense of smell, respectively) in 58 individuals who had undergone confirmed SARS-CoV-2 infection and who complained about olfactory dysfunction. Participants with large quantitative olfactory dysfunction experienced a greater reduction in their quality of life. Moreover, our participants had a high prevalence of qualitative olfactory dysfunction (81%) with a significant correlation between qualitative olfactory dysfunction and daily life impairment. Strong drivers of low quality of life assessments were lack of enjoyment of food as well as worries related to coping with long-term dysfunctions. These results stress the clinical importance of assessing qualitative olfactory dysfunction and the need to develop relevant interventions. Given the poor self-rated quality of life observed, healthcare systems should consider developing support structures, dietary advice, and guidelines adapted to individuals experiencing qualitative olfactory dysfunction.

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.

COVID-19-Related Quantitative and Qualitative Olfactory and Gustatory Dysfunction: Long-Term Prevalence and Recovery Rate

Introduction: No studies have reported data on 2-year prevalence and recovery rates of self-reported COVID-19-related quantitative and qualitative olfactory and gustatory dysfunction. The aim of the present study was to estimate the 2-year prevalence and recovery rate of self-reported COVID-19-related olfactory and gustatory dysfunction in a cohort of patients with antecedent mild-to-moderate disease. Methods: This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Trieste University Hospital, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020. Results: Overall, 174 (68.8%), 53 (20.9%), and 36 (14.2%) of 253 responders reported an altered sense of smell or taste (SNOT-22 >0) at baseline, 12 months, and 24 months, respectively. Among the 174 patients who have complained a COVID-19-associated olfactory or gustatory dysfunction at baseline, 138 (79.3%) reported complete resolution of smell or taste impairment with 17 subjects (9.8%) recovering after more than 1 year after the initial infection, 33 (19.0%) reported a decrease in the severity, and only 3 (1.7%) reported that the symptom was unchanged at the 24-month interview. Twenty subjects (7.9%) complained of at least one qualitative long-term symptom. Conclusion: Two years after the infection, most patients experience a favourable evolution of COVID-19-related olfactory or gustatory dysfunction. A late recovery was observed in 10% of subjects.

Assessment of postviral qualitative olfactory dysfunction using the short SSParoT in patients with and without parosmia.

PurposeTo examine if the short formed Sniffin Sticks Parosmia Test (SSParoT), a test for parosmia can distinguish cases with parosmia from cases without parosmia.MethodsIn this study, 63 patients with postviral olfactory dysfunction were investigated including both COVID and non-COVID cases. The age, symptom duration, degree of parosmia/phantosmia was collected. For olfactory function, the Sniffin Sticks olfactory score was obtained including scores for odor threshold, discrimination and identification. For assessment of parosmic changes, the short SSParoT was adopted and both hedonic range (HedRang) and direction (HedDir) was calculated.ResultsThe mean HedRang of patients with parosmia (2.35, standard deviation, SD = 1.40) and without parosmia (2.78, SD = 1.09) was smaller than that in controls (4.5, SD = 2.15). However, the mean HedDir of both parosmia (− 0.32, SD = 0.98) and non-parosmia patients (0.04, SD = 1.07) was similar to controls (− 0.1, SD = 1.55). When considering that the 10th percentile of the distribution of SSParoT score should distinguish between patients with and without parosmia, the sensitivity of the HedRang was 29% and specificity was 67%. For HedDir, the sensitivity was 6% and specificity was 100%. Only the odor identification score (r = 0.34, p = 0.01) discriminated parosmia and non-parosmia while other measures including HedRang and HedDir did not.ConclusionThe present study showed that the short SSParoT score could not distinguish patients with parosmia from patients without parosmia. Although the SSParoT represents an innovative approach to assess parosmia, and could be useful in the tracking of parosmic changes, the development of measures to diagnose parosmia in an objective way remains a challenge.

Qualitative Olfactory Dysfunction and COVID-19: An Evidence-Based Review with Recommendations for the Clinician.

BackgroundNearly 40% of patients who experience smell loss during SARS-CoV-2 infection may develop qualitative olfactory dysfunction, most commonly parosmia. Our evidence-based review summarizes the evolving literature and offers recommendations for the clinician on the management of patients experiencing parosmia associated with COVID-19.MethodsWe performed a systematic search using independent queries in PubMed, Embase, Ovid, and Cochrane databases, then categorized articles according to themes that emerged regarding epidemiology, effect on quality of life, disease progression, prognosis, pathophysiology, diagnosis, and treatment of parosmia.ResultsWe identified 123 unique references meeting eligibility and performed title and abstract review with 2 independent reviewers, with 74 articles undergoing full-text review. An inductive approach to thematic development provided 7 central themes regarding qualitative olfactory dysfunction following COVID-19.ConclusionsWhile other respiratory viruses are known to cause qualitative olfactory disturbances, the incidence of parosmia following COVID-19 is notable, and correlates negatively with age. The presence of parosmia predicts persistent quantitative olfactory dysfunction. Onset can occur months after infection, and symptoms may persist for well over 7 months. Affected patients report increased anxiety and decreased quality of life. Structured olfactory training with essential oils is the preferred treatment, where parosmia predicts recovery of aspects of quantitative smell loss when undergoing training. There is limited evidence that nasal corticosteroids may accelerate recovery of olfactory function. Patients should be prepared for the possibility that symptoms may persist for years, and providers should guide them to resources for coping with their psychosocial burden.

Insights into the molecular triggers of parosmia based on gas chromatography olfactometry

BackgroundParosmia is a debilitating condition in which familiar smells become distorted and disgusting, with consequences for diet and mental health. It is a feature of post-infectious olfactory loss, particularly resulting from COVID-19. There is currently little understanding of its pathophysiology, and the prevailing hypothesis for the underlying mechanism is aberrant growth of regenerating olfactory sensory neurons after damage.MethodsWe use gas-chromatograph olfactometry to individually present components of a complex olfactory mixture as a rapid screening tool for assessment of both quantitative and qualitative olfactory dysfunction in those with and without parosmia. This allows them to report the associated sensory effects and to identify those molecules which are altered or parosmic in nature.ResultsHere we show 15 different molecular triggers of this symptom. These trigger molecules are common to many in the parosmic volunteer group and share certain characteristics such as extremely low olfactory threshold and common molecular structureConclusionsWe posit that specific highly odour-active molecules are the cause of the parosmic symptom in most cases and initiate the sense of disgust, suggesting that parosmia is, at least in part, a receptor-level phenomenon.

A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Patients’ Perspectives on Qualitative Olfactory Dysfunction: Thematic Analysis of Social Media Posts

BackgroundThe impact of qualitative olfactory disorders is underestimated. Parosmia, the distorted perception of familiar odors, and phantosmia, the experience of odors in the absence of a stimulus, can arise following postinfectious anosmia, and the incidences of both have increased substantially since the outbreak of COVID-19.ObjectiveThe aims of this study are to explore the symptoms and sequalae of postinfectious olfactory dysfunction syndrome using unstructured and unsolicited threads from social media, and to articulate the perspectives and concerns of patients affected by these debilitating olfactory disorders.MethodsA thematic analysis and content analysis of posts in the AbScent Parosmia and Phantosmia Support group on Facebook was conducted between June and December 2020.ResultsIn this paper, we identify a novel symptom, olfactory perseveration, which is a triggered, identifiable, and usually unpleasant olfactory percept that persists in the absence of an ongoing stimulus. We also observe fluctuations in the intensity and duration of symptoms of parosmia, phantosmia, and olfactory perseveration. In addition, we identify a group of the most common items (coffee, meat, onion, and toothpaste) that trigger distortions; however, people have difficulty describing these distortions, using words associated with disgust and revulsion. The emotional aspect of living with qualitative olfactory dysfunction was evident and highlighted the detrimental impact on mental health.ConclusionsQualitative and unsolicited data acquired from social media has provided useful insights into the patient experience of parosmia and phantosmia, which can inform rehabilitation strategies and ongoing research into understanding the molecular triggers associated with parosmic distortions and research into patient benefit.

Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients

ObjectivesWe have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. We also aimed to determine whether sodium citrate is beneficial in treating qualitative olfactory dysfunction.MethodsWe performed a prospective, controlled study. Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The left nasal cavity was untreated and, therefore, acted as an internal control. Monorhinal olfactory function was assessed using the “Sniffin’ Sticks” composite ‘TDI’ score, before and after treatment. The presence of parosmia and phantosmia was also assessed.ResultsOverall, there was a significant increase in TDI after treatment (using the best of right and left sides). Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. The proportion of patients reporting parosmia did not change significantly after treatment. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period.ConclusionsTreatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. It may, however, be beneficial in treating phantosmia, which should be further addressed in future work.

Assessment of odor hedonic perception: the Sniffin\u2019 sticks parosmia test (SSParoT)

Qualitative olfactory dysfunction is characterized as distorted odor perception and can have a profound effect on quality of life of affected individuals. Parosmia and phantosmia represent the two main subgroups of qualitative impairment and are currently diagnosed based on patient history only. We have developed a test method which measures qualitative olfactory function based on the odors of the Sniffin’ Sticks Identification subtest. The newly developed test is called Sniffin’ Sticks Parosmia Test (SSParoT). SSParoT uses hedonic estimates of two oppositely valenced odors (pleasant and unpleasant) to assess hedonic range (HR) and hedonic direction (HD), which represent qualitative olfactory perception. HR is defined as the perceivable hedonic distance between two oppositely valenced odors, while HD serves as an indicator for overall hedonic perception of odors. This multicenter study enrolled a total of 162 normosmic subjects in four consecutive experiments. Cluster analysis was used to group odors from the 16-item Sniffin’ Sticks Identification test and 24-additional odors into clusters with distinct hedonic properties. Eleven odor pairs were found to be suitable for estimation of HR and HD. Analysis showed agreement between test–retest sessions for all odor pairs. SSparoT might emerge as a valuable tool to assess qualitative olfactory function in health and disease.

Diagnosis and treatment of qualitative olfactory dysfunction

Diagnosis and treatment of qualitative olfactory dysfunction

Phantom Smells: Prevalence and Correlates in a Population-Based Sample of Older Adults.

Loss of olfactory function is common in old age, but evidence regarding qualitative olfactory dysfunction in the general older population is scarce. The current study investigates the prevalence and correlates of phantom smell experiences (phantosmia) in a population-based study (Swedish National Study on Aging and Care in Kungsholmen [SNAC-K]) of Swedish adults (n = 2569) aged between 60 and 90 years. Phantosmia was assessed through a standardized interview and defined as reporting having experienced an odor percept in the absence of any stimuli in the surrounding environment that could emit the odor. The relationships between phantosmia and demographic, genetic, health-related, and behavioral variables were analyzed with hierarchical logistic regression analyses. The overall prevalence of phantom smells was 4.9%, and was associated with female gender, carrying the met allele of the BDNF gene, higher vascular risk burden, and reporting distorted smell sensations (parosmia). Olfactory dysfunction was, however, not related to phantosmia. The most frequently reported phantom smell was smoky/burnt. A novel finding was that some individuals reported phantom smells with an autobiographical connotation. The results from this study indicate that the prevalence of phantosmia in the general older population is not negligible and that some factors that are beneficial for preserved olfactory function, such as female gender and the BDNF met allele, are also associated with the occurrence of phantom smells.

A study on the prognostic significance of qualitative olfactory dysfunction

We investigated the frequency and prognostic significance of qualitative olfactory dysfunction (parosmia, phantosmia) in a retrospective patient based study. A total of 392 patients with impairment of olfaction were tested at least two times for their olfactory function using the "Sniffin' Sticks". The mean interval between the first and the last test was 11 months. At the first visit 34% of all patients reported parosmia. Parosmia was most frequent in patients with postinfectious olfactory loss (56%), and less frequent in idiopathic, posttraumatic, sinunasal disease with frequencies of 10, 14, and 28%, respectively. In contrast, only 12% of all patients had phantosmias, with no significant differences between the patient groups. Improvement of olfactory function was found in 23% of all patients (n = 90). Pre-existing parosmia or phantosmia had no significant effect on recovery rate. Regarding qualitative olfactory dysfunction, 29% of those patients reporting parosmia reported relief of this symptom after an average of 12 months, whereas 53% of phantosmic patients lost phantosmia during the observation period. Although it has been suggested that olfactory distortion s could be regarded as an indicator of early recovery of decreased olfactory sensitivity, the current data indicate that occurrence of parosmia or phantosmia has little prognostic value. Phantosmia disappears at a faster rate than parosmia. These insights into qualitative olfactory dysfunction are regarded to be significant in the counseling of patients with olfactory loss.

Prevalence and assessment of qualitative olfactory dysfunction in different age groups.

The prevalence of parosmia and phantosmia among 363 chemosensory and nasal/sinus patients was studied, as was the accuracy with which our clinical questionnaire could assess these dysfunctions. We then investigated whether patients with parosmia or phantosmia, matched for odor intensity, perform poorer on odor identification than do patients with no dysosmia. More than 40% of the study group evidenced either parosmia (18.7%) and/or phantosmia (25.6%), a finding that suggests that more attention should be paid by the medical practitioner in addressing qualitative olfactory dysfunction. Furthermore, it appears that assessment of these dysfunctions may aid in differential diagnosis, and that questionnaires can be used with reasonable validity irrespective of the patient's age. Finally, the results imply that parosmia may be reflected in a discrepancy between odor identification and detection.