Normosmic Patients Research Articles

Late olfactory bulb involvement in COVID19.

Transient or persistent hypo-anosmia is common in SARS‑CoV‑2 infection but olfactory pathway late-term morphometric changes are still under investigation. We evaluated late olfactory bulb (OB) imaging changes and their correlates with the olfactory function in otherwise neurologically asymptomatic COVID-19 patients. Eighty-three subjects (mean-age 43±14 years; 54 females; time-interval infection/MRI: 129±68 days) affected by asymptomatic to mild COVID19 in 2020 and 25 healthy controls (mean-age 40±13 years; 9 females) underwent 3T-MRI and olfactory function evaluation through anamnestic questionnaire and Sniffin' Sticks. Exclusion criteria were intensive care treatment or neurological involvement other than olfaction. Maximal OB area was measured blindly on high-resolution coronal T2w images by two observers. Patients were subdivided into: i) persistently hypo/anosmic, ii) recovered normosmic and iii) never complaining smell dysfunction with proven normal olfactory function. No significant differences were observed among patients' subgroups (p=0.76). Intra-observer and inter-observer reliability were high.(r=0.96 and 0.86). Former COVID19 patients had decreased mean maximal OB area than controls (6.52±1.11mm2 vs 7.26±1.17mm2, p=0.008) even when considering persistently hypo-anosmic (6.46±0.90, p=0.006) or normosmic patients at MRI (6.57±1.25, p=0.04). SARS-CoV-2 infection is associated with mid/late-term morphological changes on the olfactory bulbs, regardless of presence or persistence of olfactory dysfunction. The long-term consequences on olfactory aging need to be further investigated including possible links with neurodegenerative disorders.

Chemosensory assessment and impact on quality of life in neurosensorial cluster of the post COVID 19 syndrome

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.

Variety of genetic defects in GnRH and hypothalamic-pituitary signaling and development in normosmic patients with IHH.

Normosmic isolated hypogonadotropic hypogonadism (nIHH) is a clinically and genetically heterogeneous disorder. Deleterious variants in over 50 genes have been implicated in the etiology of IHH, which also indicates a possible role of digenicity and oligogenicity. Both classes of genes controlling GnRH neuron migration/development and hypothalamic/pituitary signaling and development are strongly implicated in nIHH pathogenesis. The study aimed to investigate the genetic background of nIHH and further expand the genotype-phenotype correlation. A total of 67 patients with nIHH were enrolled in the study. NGS technology and a 38-gene panel were applied. Causative defects regarded as at least one pathogenic/likely pathogenic (P/LP) variant were found in 23 patients (34%). For another 30 individuals, variants of unknown significance (VUS) or benign (B) were evidenced (45%). The most frequently mutated genes presenting P/LP alterations were GNRHR (n = 5), TACR3 (n = 3), and CHD7, FGFR1, NSMF, BMP4, and NROB1 (n = 2 each). Monogenic variants with solid clinical significance (P/LP) were observed in 15% of subjects, whereas oligogenic defects were detected in 19% of patients. Regarding recurrence, 17 novel pathogenic variants affecting 10 genes were identified for 17 patients. The most recurrent pathogenic change was GNRHR:p.Arg139His, detected in four unrelated subjects. Another interesting observation is that P/LP defects were found more often in genes related to hypothalamic-pituitary pathways than those related to GnRH. The growing importance of the neuroendocrine pathway and related genes is drawing increasing attention to nIHH. However, the underestimated potential of VUS variants in IHH etiology, particularly those presenting recurrence, should be further elucidated.

Mucosal antibody response and SARS-CoV-2 shedding in patients with COVID-19 related olfactory dysfunction.

Olfactory dysfunction (OD) was one of the most common symptom of infection with the Wuhan strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and could persist for several months after symptom onset. The pathogenesis of prolonged OD remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS-CoV-2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed coronavirus disease 2019 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS-CoV-2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS-CoV-2 specific nasal immunoglobulins (Ig) IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS-CoV-2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS-CoV-2 replication and thereby help in the control of persistent OD.

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.

Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3[IER3]) had an false discovery rate(FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL-4 and IL-13 signaling, IL-10 signaling, and rhodopsin-like receptors. RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL-10, rhodopsin-like receptors, and IER3 in the pathogenesis of olfactory dysfunction.

Reliability and validity of the Polish version of the Questionnaire of Olfactory Disorders.

The comprehensive counseling of patients with olfactory dysfunctions requires accurate diagnosis. The recommendations include subjective assessment. The Questionnaire of Olfactory Disorders (QOD) is a disease-specific questionnaire for the subjective evaluation of olfactory dysfunctions. The study included 54 patients with olfactory dysfunctions, who were recruited to the study group (SG). The other 47 patients without the history of olfactory dysfunction and nasal cavity pathology were voluntarily allocated to the control group (CG). The protocol of the study was introduced to each patient and included: olfactory testing with Sniffin' Stick test, fulfillment of the Polish version of World Health Organization Quality of Life brief questionnaire and completing of the Polish version of the QOD. All participants (101) were invited for refilling the QOD questionnaire after 2 weeks for the test-retest statistics. The Polish QOD statements were significantly correlated and met the requirement by having test-retest correlation larger than 0.7. We found that internal consistency of the test measured by Cronbach's alpha coefficient was very high. The mean scores of the QOD test in normosmic SG patients were compared with corresponding scores in normosmic CG patients using U Mann-Whitney test. The analysis revealed statistically significant differences on mean QOD scores for each domains except QOD-S between both groups. The Polish version of the QOD demonstrated high rate of the validity and the reliability. This instrument may be widely used in research projects and clinical practice concerning olfactory disorders in Polish patients. NA.

Comparison of prevalence and evolution of COVID-19 olfactory disorders in patients infected by D614 (wild) and B.1.1.7. Alpha variant: a brief report.

To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves. From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection. Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (rs = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes. Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus).

A multicenter real-life study to determine the efficacy of corticosteroids and olfactory training in improving persistent COVID-19-related olfactory dysfunction.

No definitive treatment exists to effectively restore function in patients with persistent post-infectious olfactory dysfunction (OD). Corticosteroids have been considered as a therapeutic option in post-infectious OD but their benefit in COVID-19-related OD remains unexplored. We aim to determine the role of the combination of corticosteroids plus olfactory training (OT) in improving persistent COVID-19-related OD. A multicenter real-life cohort study was conducted between December 2020 and April 2022 on patients with reported COVID-19-related OD. Only patients with confirmed OD at Sniffin' Sticks (S'S) and those who attended their 6-month follow-up were included. Patients were started on a combined treatment of corticosteroids and OT. Patients refusing corticosteroids or not doing any treatment formed the control groups. Visual analogue scale (VAS) for sense of smell and SNOT-22 were used to assess patients reported symptoms. Sixty-seven subjects with reported COVID-19-related OD were initially seen. Normosmic patients at S'S (n=14) and those not attending their follow-up (n=9) were excluded. Of the 44 patients included in the analysis, 19 patients had the combined treatment (group A), 16 patients refused to take corticosteroids and did the OT alone (group B) whereas 9 patients did not do any treatment (group C). An improvement of threshold + discrimination + identification (TDI) score (p=.01) and VAS for smell (p=.01) was found in group A whereas only the TDI score improved in group B (p=.04). Presence of comorbidities, age, sex (male), and length of OD negatively influenced olfactory recovery. Our study confirms the importance of OT in long-term OD suggesting that the addition of corticosteroids may give a benefit in terms of patient's perceived olfaction. 2b.

Comparison of Olfactory Tract Diffusion Measures Between Early Stage Parkinson's Disease Patients and Healthy Controls Using Ultra-High Field MRI.

MRI is a valuable method to assist in the diagnostic work-up of Parkinson's disease (PD). The olfactory tract (OT) has been proposed as a potential MRI biomarker for distinguishing PD patients from healthy controls. This study aims to further investigate whether diffusion measures of the OT differ between early stage PD patients and healthy controls. Twenty hyposmic/anosmic PD patients, 65 normosmic PD patients, and 36 normosmic healthy controls were evaluated and a 7T diffusion weighted image scan was acquired. Manual seed regions of interest were drawn in the OT region. Tractography of the OT was performed using a deterministic streamlines algorithm. Diffusion measures (fractional anisotropy and mean- radial- and axial diffusivity) of the generated streamlines were compared between groups. Diffusion measures did not differ between PD patients compared to healthy controls and between hyposmic/anosmic PD patients, normosmic PD patients, and normosmic healthy controls. A positive correlation was found between age and mean- and axial diffusivity within the hyposmic/anosmic PD subgroup, but not in the normosmic groups. A positive correlation was found between MDS-UPDRSIII scores and fractional anisotropy. This study showed that fiber tracking of the OT was feasible in both early stage PD and healthy controls using 7T diffusion weighted imaging data. However, 7T MRI diffusion measures of the OT are not useful as an early clinical biomarker for PD. Future work is needed to clarify the role of other OT measurements as a biomarker for PD and its different subgroups.

Long-term quality-of-life impairment in patients with more than 1-year COVID-19-related olfactory dysfunction.

Long-term quality-of-life impairment in patients with more than 1-year COVID-19-related olfactory dysfunction.

Parosmia assessment with structured questions and its functional impact in patients with long-term COVID-19-related olfactory dysfunction.

Parosmia assessment with structured questions and its functional impact in patients with long-term COVID-19-related olfactory dysfunction.

Loss of smell in patients with aspirin-exacerbated respiratory disease impacts mental health and quality of life.

The impact of anosmia on quality-of-life (QoL) for patients with aspirin-exacerbated respiratory disease (AERD) is poorly understood. We aimed to investigate how the severity of smell loss and olfactory dysfunction (OD) in patients with AERD affects their QoL, mental health and physical well-being. Five validated QoL questionnaires (Sinonasal Outcome Test-22, Asthma Control Test, Healthy Days Core Module-4, Short Form-36 and Patient Health Questionnaire-4) and two newly developed questionnaires assessing severity and consequences of OD were electronically sent to all 2913 patients in the Brigham and Women's Hospital AERD registry. Responses were received from 853 participants for analysis. Overall, 85% of participants reported a present diminished sense of smell and/or taste, and 30% categorized their OD severity was, "as bad as it can be." There were significant relationships between the severity of self-reported OD and both psychological distress and general health scores, even after adjusting for asthma control. Additionally, incidence rates for physically and mentally unhealthy days in the prior month were higher for patients with moderate or severe OD than for normosmic patients. Patients with diminished smell responded that they could not identify spoiled food (86%), did not enjoy food (71%), felt unsafe (63%) and had encountered dangerous situations (51%) as consequences of their OD. Anosmia and hyposmia severely impact the physical, emotional and mental health of AERD patients, and lead to safety concerns in their daily lives. The importance of olfaction and the relevance of OD to patients' QoL should be acknowledged and evaluated by clinicians caring for these patients.

Covid-19 outbreak: does the use of a surgical mask impact the sense of smell?

Background The current context of Covid-19 pandemic has broadened mask use. Objectives Evaluate the impact of wearing a surgical mask on sense of smell by comparing the results of sniffin’ sticks test (SST) with and without a surgical mask and evaluate the feasibility of practicing SST with a mask. Material and methods A crossover prospective comparative study between two groups of volunteers. The results of SST with a mask were compared to the results without a mask: group 1 first performed SST with a surgical mask and then one week later performed SST without a mask, while group 2 started without a mask. Results Twenty volunteers were included. In group 1 and 2, all the subjects, except one, had a significantly better total score (TDI) without a mask. The average TDI difference score with and without a mask, was inferior to 5. 8/20 (40%) subjects had a TDI difference superior to 5 with and without mask, while 4/20 (20%) were normosmic without a mask, while being recategorized as hyposmic with a mask. Conclusions and significance Wearing a surgical mask may reduce the sense of smell, in a cohort of normosmic patients. Further larger studies must be conducted in hyposmic subjects.

Relationship between Olfactory Function and BMI in Normal Weight Healthy Subjects and Patients with Overweight or Obesity.

Smell plays a critical role in food choice and intake by influencing energy balance and body weight. Malnutrition problems or modified eating behaviors have been associated with olfactory impairment or loss. The obesity epidemic is a serious health problem associated with an increased risk of mortality and major physical comorbidities. The etiopathogenesis of obesity is complex and multifactorial, and one of the main factors contributing to the rapid increase in its incidence is the environment in which we live, which encourages the overconsumption of foods rich in energy, such as saturated fats and sugars. By means of the “Sniffin’ Sticks” test, we measured the olfactory threshold, discrimination and identification score (TDI score) in patients of the Obesity Center of the University Hospital (OC; n = 70) and we compared them with that of healthy normal weight controls (HC; n = 65). OC patients demonstrated a significantly lower olfactory function than HC subjects both general and specific for the ability to discriminate and identify odors, even when they were considered separately as females and males. For OC patients, a negative correlation was found between body mass index (BMI) and olfactory scores obtained by each subject, both when they were divided according to gender and when they were considered all together. Besides, normosmic OC patients showed a significantly lower BMI than hyposmic ones. A reduced sense of smell may contribute to obesity involving the responses of the cephalic phase, with a delay in the achievement of satiety and an excessive intake of high-energy foods and drinks.

PLXNB1 mutations in the etiology of idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin-releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH, n=293 and Kallmann syndrome, n=43) from 290 independent families were included in the present study. Six PLXNB1 rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in PLXNA1. Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild-type. Our results provide clinical, genetic, molecular/cellular, and modeling evidence to implicate variants in PLXNB1 in the etiology of IHH.

Hippocampal volume is related to olfactory impairment in Parkinson's disease.

Recent evidence has suggested that hyposmia in patients with Parkinson's disease (PD) may be due to impaired central processing. Furthermore, the hippocampus has been regarded as a critical structure linking olfactory impairment and cognitive impairment in PD patients. This study aimed to identify significant structural alterations of the hippocampus in PD patients with hyposmia, and to determine whether these structural changes are significantly associated with olfactory impairment severity. Eighteen idiopathic PD patients with hyposmia and 18 age- and sex-matched PD patients without hyposmia were enrolled. Hippocampal volume and its subfields were measured using FreeSurfer software and compared between hyposmic and normosmic PD patients. We also compared hippocampal substructures' volumes and correlated the hippocampal volumes with hyposmia severity. PD patients with hyposmia had significantly smaller hippocampal volumes. Among the three components of the hippocampus, the hippocampal body showed a markedly lower volume, which correlated significantly with the cross-cultural smell identification test score that represents olfactory function status. Hippocampal subfield analysis showed that substructures (subiculum, molecular layer) that constitute the hippocampal body showed the most significant volume difference. We suggest that atrophy of the bilateral hippocampus implies underlying problems in the central olfaction process in PD patients. In particular, the hippocampus might not only play a critical role in olfaction but could also be important for elucidating possible mechanisms of broad nonmotor symptoms in PD patients.

Genetic Profiles and Three-year Follow-up Study of Chinese Males With Congenital Hypogonadotropic Hypogonadism

BackgroundThe correlation between long-term treatment outcomes with genotypes in congenital hypogonadotropic hypogonadism (CHH) males is rarely reported. AimTo investigate the correlations among genotypes, phenotypes, and treatment outcomes for CHH male patients. MethodsWhole exome sequencing was performed for 73 Chinese CHH males from one academic center. Patients self-selected one of the 4 treatments: pulsatile Gonadorelin pump (PGP), cyclical gonadotropins therapy (CGT), human menopausal gonadotropin monotherapy, or testosterone replacement treatment. Clinical assessments were performed every 3 months for 3 years. OutcomesThe pathogenicity of variants was determined. Baseline clinical features, spermatogenesis outcomes were analysed. Results62 variants were identified in 51 patients (69.9%), 17 of which were novel. Among these mutations, variants on FGFR1, PROKR2, CHD7, ANOS1 and NSMF gene were 16.1%, 16.1%, 11.3%, 8.1% and 8.1% respectively. 11 patients followed the oligogenic pattern (21.6%). All CHD7 patients had hearing impairment or structural deformities of external/inner ear, and were diagnosed as CHARGE syndrome. 24.7% of CHH patients manifested with ear/hearing anomalies. KS patients had higher rates of cryptorchidism history and ear/hearing anomalies than normosmic CHH subjects. Male patients with PROKR2 mutations showed relatively better testicular development, less dental deformity when compared with FGFR1 mutations. About 30% normosmic patients defined by simple olfactory assessment showed olfactory nerve center (ONC) dysplasia under nasal sinus MRI examination. Among the CHH males treated with CGT or PGP, 70.2% reached spermatogenesis within 3 years of treatment. Clinical ImplicationsNo direct correlation was observed between certain responsible genes and spermatogenic outcomes. When CHH patients were identified with CHD7 variants, ear/hearing evaluation should be carefully performed. The precise assessment of ONC development was advised for normosmic CHH subjects. Strengths & LimitationsThis study provided informative long-term treatment data of CHH male patients screened with whole exome sequencing. The limitations included small number of subgroups with multifaceted gene variants, clinical heterogeneity, and uncontrolled sperm-inducing treatment method. The seventeen novel mutations worth experimental validation in the future. ConclusionThe clinical severity is partially related with specific gene variants, and detailed individualized data and outcomes were provided. Ear/hearing anomalies were closely connected with CHD7 variants, and were common problems for CHH patients. Simple olfactory assessment underestimated the true olfactory deficit. L. Zhang, Y. Gao, Q. Du, et al. Genetic Profiles and Three-year Follow-up Study of Chinese Males With Congenital Hypogonadotropic Hypogonadism. J Sex Med 2021;18:1500–1510.

Olfaction in patients with Parkinson\u2019s disease: a new threshold test analysis through turning points trajectories

Olfactory deficit is a widely documented non-motor symptom in Parkinson’s disease (PD). Abnormal turning points trajectories through olfactory threshold testing have been recently reported in patients with olfactory dysfunction, who seem to adapt faster to olfactory stimuli, but data on PD patients are lacking. The aim of this study is to perform olfactory threshold test and explore the turning points trajectories in PD patients in comparison to normal controls. We recruited 59 PD patients without dementia, and no conditions that could influence evaluation of olfaction and cognition. Sixty healthy subjects served as controls. Patients and controls underwent a comprehensive olfactory evaluation with the Sniffin’ Sticks extended test assessing threshold, discrimination and identification and a full neuropsychological evaluation. Besides, threshold test data were analyzed examining all the turning points trajectories. PD patients showed a different olfactory threshold test pattern, i.e., faster olfactory adaptation, than controls with no effect of age. Normosmic PD patients showed different olfactory threshold test pattern, i.e., better threshold score, than normosmic controls. Visuospatial dysfunction was the only factor that significantly influenced this pattern. Olfactory threshold trajectories suggested a possible adaptation phenomenon in PD patients. Our data offered some new insights on normosmic PD patients, which appear to be a subset with a specific psychophysical profile. The analysis of the turning points trajectories, through an olfactory threshold test, could offer additional information on olfactory function in PD patients. Future larger studies should confirm these preliminary findings.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult participants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of lower age and baseline olfactory function with improvements of overall OF. This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additionally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improvements after OT.

Epidemiological, otolaryngological, olfactory and gustatory outcomes according to the severity of COVID-19: a study of 2579 patients.

ObjectiveTo investigate prevalence and epidemiological and clinical factors associated with olfactory dysfunction (OD) and gustatory dysfunction (GD) in COVID-19 patients according to the disease severity. Study designCross-sectional study. MethodsA total of 2579 patients with a positive diagnosis of COVID-19 were identified between March 22 and June 3, 2020 from 18 European hospitals. Epidemiological and clinical data were extracted. Otolaryngological symptoms, including OD and GD, were collected through patient-reported outcome questionnaire and Sniffin’Sticks tests were carried out in a subset of patients. ResultsA total of 2579 patients were included, including 2166 mild (84.0%), 144 moderate (5.6%) and 269 severe-to-critical (10.4%) patients. Mild patients presented an otolaryngological picture of the disease with OD, GD, nasal obstruction, rhinorrhea and sore throat as the most prevalent symptoms. The prevalence of subjective OD and GD was 73.7 and 46.8%, and decreases with the severity of the disease. Females had higher prevalence of subjective OD and GD compared with males. Diabetes was associated with a higher risk to develop GD. Among the subset of patients who benefited from psychophysical olfactory evaluations, there were 75 anosmic, 43 hyposmic and 113 normosmic patients. The prevalence of anosmia significantly decreased with the severity of the disease. Anosmia or hyposmia were not associated with any nasal disorder, according to SNOT-22.ConclusionOD and GD are more prevalent in patients with mild COVID-19 compared with individuals with moderate, severe or critical diseases. Females might have a higher risk of developing OD and GD compared with males.