Post-infectious Olfactory Dysfunction Research Articles

Patient Experiences of Postinfectious Olfactory Dysfunction

Introduction: To highlight the importance of the need for new treatment modalities, this study aimed to characterise the experience of patients with postinfectious olfactory dysfunction (PIOD) in terms of the treatment they received. Methods: An online survey was hosted by the Norwich Clinical Trials Unit on the secure REDCap server. Members of the charity Fifth Sense (the UK charity that represents and supports people affected by smell and taste disorders) were invited to participate. Results: There were 149 respondents, of whom 127 had identified themselves as having (or had) PIOD. The age range of respondents to the survey was 28–85 years, with a mean of 58 ± 12 years, with the duration of their disorder <5 years in 63% of cases. Respondents reported experiencing variable treatment with oral and/or intranasal steroids given typically (28%), often with no benefit, but with 50% receiving no treatment whatsoever; only 3% reported undertaking olfactory training. Over two-thirds of patients experience parosmia and, up to 5 years from the onset of the problem, were still actively seeking a solution. Conclusion: There appears to be a need to encourage greater use of guidelines for olfactory disorders amongst medical practitioners and also to develop more effective treatments for patients with PIOD, where there is clearly an unmet need.

Prognostic value of olfactory evoked potentials in patients with post-infectious olfactory dysfunction

Prognostic assessment of patients with post-infectious olfactory dysfunction (PIOD) poses a challenge for clinicians. While there have been some studies on the prognostic factors of PIOD focusing on demographic factors, the aim of this study was to investigate whether event-related potentials (ERPs) could be used as a new predictor of olfactory recovery in PIOD. This was a retrospective study involving patients who underwent olfactory examinations using Sniffin' Sticks test before treatment and after 1year of follow-up. The responder group was defined by an increase of threshold-discrimination-identification (TDI) score of ≥ 6 points. All patients underwent ERP examination and the amplitude and latency of each wave of ERPs were recorded before treatment. A total of 61 patients (age 47.50 ± 11.04years, 27 males) were analyzed. The presence of olfactory ERPs (oERPs) was greater in the responder group than in the non-responder group (P = 0.007), while that of trigeminal ERPs (tERPs) did not differ between the two groups (P = 0.346). Logistic-regression analyses showed that factors associated with improvement of subjective olfactory function were duration (OR, 1.604; 95% CI, 1.062-2.423; P = 0.025), initial threshold (odds ratio [OR], 0.043; 95% confidence interval [CI], 0.004-0.439; P = 0.008), and latency of N1 in oERPs (OR, 1.007; 95% CI, 1.001-1.013; P = 0.021). Our study shows that duration of OD, initial threshold, and latency of N1 in oERPs were associated with olfactory improvement in PIOD patients, which may provide guidance for clinicians.

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.

Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction

Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin Adrops. Further research is needed to confirm the place of other therapeutic options.

Effects of Olfactory Training in Patients With Postinfectious Olfactory Dysfunction.

ObjectivesPostinfectious olfactory dysfunction (PIOD) is the most common etiology of olfactory dysfunction, and olfactory training (OT) is an accepted treatment modality for PIOD. Some studies have investigated OT in Korean patients, but they involved odorants unfamiliar to Koreans or had no control group. The aim of this study was to verify the efficacy of OT in PIOD patients, using odorants familiar to Koreans and including a control group.MethodsWe enrolled a total of 104 Korean patients with PIOD over the 3-year study period. All participants were assessed using endoscopy and an olfactory function test at the baseline assessment and 3 months after OT. The olfactory function test was performed using the Korean version of Sniffin’ stick (KVSS) II. Nasal and psychological function was evaluated using a visual analog scale and the Mini-Mental State Examination. OT was performed over a period of 3 months, using five odorants (rose, lemon, cinnamon, orange, and peach).ResultsOT improved olfactory function in approximately 40% of subjects over a period of 12 weeks compared to non-OT subjects. A comparison of changes between the initial and follow-up assessments demonstrated that the OT group had significantly better olfactory results for the total KVSS II, threshold, and identification scores than the non-OT group. The degree of olfactory improvement after OT was affected by the initial score.ConclusionThe effects of OT in patients with PIOD were demonstrated in this study. A meaningful contribution of this study is that Korean patients were tested using odors familiar to them in comparison with a control group.

Recovery Over Time and Prognostic Factors in Treated Patients with Post-Infectious Olfactory Dysfunction: A Retrospective Study.

The aims of the present study were to clarify the time-course of olfactory recovery and the prognostic factors in PIOD patients treated with Toki-shakuyaku-san (TSS). A retrospective cohort study of patients with PIOD was conducted by reviewing patients' medical records. This study included patients who received TSS or a combination of TSS and zinc sulfate. Olfactory function was examined by T&T olfactometer at each 3-monthly follow-up visit. Patients with normal and mild olfactory dysfunction were excluded. Gender, age, treatment, duration of disease until the first visit and olfactory function scores of the T&T olfactometer at the first visit were analyzed as candidate clinical predictors of recovery. A total of 82 PIOD patients with ages ranging from 16 to 79 years were included. The mean duration of follow-up was 14.5 months (range 3-45 months). The number of patients with olfactory recovery increased for 24 months and the cumulative recovery rate was 77.3%. In about 60% of patients, olfactory recovery occurred within 6 months. Multivariate analysis showed that younger age (<65 years) and residual olfactory function were significantly associated with good olfactory recovery. We revealed recovery rates over time in patients with PIOD. The recovery of olfactory function often occurred during the early period (≤6 months). However, the number of patients with olfactory recovery increased for a long-term of 24 months after the first visit. Residual olfactory function and younger age were prognostic factors exactly. TSS may be a useful therapeutic agent for patients with PIOD. We believe that these results provide important information that is useful for counseling patients with PIOD.

Olfactory training ball improves adherence and olfactory outcomes in post-infectious olfactory dysfunction.

In an effort to make olfactory training (OT) simpler, we designed an 'olfactory training ball' (OTB)-a baseball-size ball with four odor-containing tubes to use in OT. The study aimed to investigate the effects of OT with the OTB in comparison to classical OT with special attention to the effects of adherence to OT on olfactory outcome measures. Sixty patients with olfactory dysfunction following infections of the upper respiratory tract received OT either with classical methods-sniffing odors from jars (COT)-or the OTB for 12weeks. Patients exposed themselves to the odors for 5min twice daily. Adherence was measured with a modified version of the Morisky scale. Before and after OT, all patients underwent extensive olfactory testing using the Sniffin' Sticks test. At the end of the 12weeks of OT, TDI composite score (22.1 ± 2.8 vs. 19.9 ± 4.7, P = 0.044) and odor discrimination subtest scores (9.1 ± 1.8 vs.7.6 ± 2.5, P = 0.013) of the OTB group were significantly higher than that of the COT group. Adequate adherence to OT was significantly higher in patients receiving OTB when compared to those receiving COT (63% vs. 30%, P = 0.019). The present study shows that a novel OT device, the OTB, provides better adherence to the training process compared to COT. Moreover, findings of the current study show that better adherence to the OT process is associated with better olfactory outcomes.

Efficacy and associated factors of olfactory training in the treatment of olfactory dysfunction

Objective: To explore the clinical effects and the influence factors of olfactory training in the treatment of olfactory dysfunction. Methods: A total of 86 patients with olfactory dysfunction (49 post-infectious and 37 post-traumatic) in Beijing Anzhen Hospital during Dec 2016 to May 2017 were recruited in this prospective study. The clinical data of patients were analyzed, including gender, age, body mass index (BMI), course of disease, smoking history, drinking history, diabetes history, hypertension history, hyperlipidemia history, and anxiety visual analogue score (VAS). All patients were treated with olfactory training for 16 weeks, and all of them underwent Sniffin' Sticks olfactory test before and after treatment, which was evaluated by composite threshold-discrimination-identification score (TDI). SPSS 23.0 software, paired t test and univariate and multivariate Logistic regression analysis were used to analyze the data. Results: Eighty patients received treatment, including 46 post-infectious olfactory dysfunction and 34 post-traumatic olfactory dysfunction. After olfactory training, the total scores of TDI increased with statistically significant (18.3±8.6 vs 13.6±7.4, t=-6.158, P<0.05). The overall efficacy was 40% (32/80). The effective rate were 45.7% (21/46) in post-infectious olfactory dysfunction and 32.4% (11/34) in post-traumatic olfactory dysfunction respectively, with no statistically significant difference (χ(2)=1.441, P=0.230). Logistic regression analysis showed that the course of disease was an influence factor in the clinical curative effect (OR=0.881, 95%CI: 0.799-0.973, P=0.012). In patients with less than a year of olfactory dysfunction, the olfactory function improved obviously with the efficiency of 50.9% (29/57). Conclusion: Sixteen weeks of olfactory training provides a significant therapeutic effect on the post-infectious and post-traumatic olfactory dysfunction, and the olfactory training can achieve better therapeutic effects at the early stage.

Intravenous olfactory test latency correlates with improvement in post-infectious olfactory dysfunction

Conclusion: This cohort study showed that onset latency in the intravenous olfactory test (IVO) may help predict when olfaction in patients with post-infectious olfactory dysfunction (PIOD) improves.Objectives: To identify factors that predict the olfactory improvement period in patients with PIOD.Methodology/Principal: All consecutive patients presenting with PIOD in 1994–2014 who were followed up for 2 years were identified retrospectively. The ability of demographic/clinical factors (age, sex, body mass index, presence/absence of allergic rhinitis, treatment/non-treatment with herbal medicines, patient dependence on herbal medicine treatment, presence/absence of diabetes mellitus, and smoking status) and olfactory test factors (response/no response and onset latency and duration in the IVO test, and detection and recognition scores on the T&T olfactory test) to predict the olfactory improvement period (defined respectively as the time from PIOD onset or olfactory testing to the first self-report of olfaction improvement) was analyzed by univariate and multivariate regression.Results: Of the 187 PIOD patients, the prognostic ability of demographic/clinical factors was analyzed in 65. None predicted the olfactory improvement period. Of the 65 patients, 20 did not respond in the IVO test. In the remaining 45 patients, onset latency (but not the other olfactory test factors) was a significant prognosticator of olfactory improvement period (R2=0.24, p = 0.003).

Long term effects of olfactory training in patients with post-infectious olfactory loss

There is evidence of the effectiveness of repeated exposure to odours on short-term olfactory function. The aim of this study was to assess the long-term effects of olfactory training. We conducted a prospective study of 111 patients with post-infectious olfactory dysfunction. Two groups of patients performed olfactory training for 16 and 56 weeks, respectively, and were compared with a control group. The training was performed twice daily using four odours (phenyl ethyl alcohol, eucalyptol, citronellal, eugenol). Olfactory testing was performed by means of the Sniffin Sticks test as a baseline assessment and then every 8 weeks for 56 weeks. Subjective ratings were performed using a visual analogue scale (0-100). Both training groups presented significantly higher scores than the controls. The long-term group had better results than the short-term group. Short-term training patients sustained their improvement within the follow-up period. Subsets analysis showed that training patients mainly increased identification and discrimination. Subjective ratings were in accordance with the olfactory test results. Long-term olfactory training seems to be associated with better results in patients with post-infectious olfactory loss than a short-term scheme. Short-term training provides sustainable results at 56 weeks follow-up assessment.

Machine-learned pattern identification in olfactory subtest results.

The human sense of smell is often analyzed as being composed of three main components comprising olfactory threshold, odor discrimination and the ability to identify odors. A relevant distinction of the three components and their differential changes in distinct disorders remains a research focus. The present data-driven analysis aimed at establishing a cluster structure in the pattern of olfactory subtest results. Therefore, unsupervised machine-learning was applied onto olfactory subtest results acquired in 10,714 subjects with nine different olfactory pathologies. Using the U-matrix, Emergent Self-organizing feature maps (ESOM) identified three different clusters characterized by (i) low threshold and good discrimination and identification, (ii) very high threshold associated with absent to poor discrimination and identification ability, or (iii) medium threshold, i.e., in the mid-range of possible thresholds, associated with reduced discrimination and identification ability. Specific etiologies of olfactory (dys)function were unequally represented in the clusters (p < 2.2 · 10−16). Patients with congenital anosmia were overrepresented in the second cluster while subjects with postinfectious olfactory dysfunction belonged frequently to the third cluster. However, the clusters provided no clear separation between etiologies. Hence, the present verification of a distinct cluster structure encourages continued scientific efforts at olfactory test pattern recognition.

Long term effects of olfactory training in patients with post-infectious olfactory loss.

There is evidence of the effectiveness of repeated exposure to odours on short-term olfactory function. The aim of this study was to assess the long-term effects of olfactory training. We conducted a prospective study of 111 patients with post-infectious olfactory dysfunction. Two groups of patients performed olfactory training for 16 and 56 weeks, respectively, and were compared with a control group. The training was performed twice daily using four odours (phenyl ethyl alcohol, eucalyptol, citronellal, eugenol). Olfactory testing was performed by means of the Sniffin Sticks test as a baseline assessment and then every 8 weeks for 56 weeks. Subjective ratings were performed using a visual analogue scale (0-100). Both training groups presented significantly higher scores than the controls. The long-term group had better results than the short-term group. Short-term training patients sustained their improvement within the follow-up period. Subsets analysis showed that training patients mainly increased identification and discrimination. Subjective ratings were in accordance with the olfactory test results. Long-term olfactory training seems to be associated with better results in patients with post-infectious olfactory loss than a short-term scheme. Short-term training provides sustainable results at 56 weeks follow-up assessment.

Modified olfactory training in patients with postinfectious olfactory loss.

Patients with olfactory dysfunction benefit from repeated exposure to odors, so-called olfactory training (OT). This does not mean occasional smelling but the structured sniffing of a defined set of odors, twice daily, for a period of 4 months or longer. In this prospective study, we investigated whether the effect of OT might increase through the use of more odors and extension of the training period. This study shows OT results when performed with four or 12 odors for 36 weeks in patients with postinfectious olfactory dysfunction. A total of 85 subjects participated (mean age 45.6 ± 10.5 years, range 24-68 years). Three groups were formed: 1) In the modified olfactory training (MOT) group, patients used three sets of four different odors sequentially. 2) Participants in the classical odor training (COT) group used four odors. 3) Participants in the control group did not perform OT. All groups were matched for age and sex distribution of participants. Both participants in the COT and MOT groups reached better scores than controls in terms of odor discrimination and odor identification. Continuing OT with four different odors after the 12th and 24th weeks produced better results in terms of odor discrimination and odor identification scores as compared to using the same four odors throughout the entire study. This study confirmed the effectiveness of OT. Increasing the duration of OT and changing the odors enhances the success rate of this therapy. 2b. Laryngoscope, 125:1763-1766, 2015.

Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients

Introduction and aimThere is a high prevalence of olfactory dysfunction in the general population. Several causes of olfactory dysfunction have been reported and this disorder is classically divided into sinonasal and non-sinonasal-related olfactory dysfunction. The aims of this study were firstly, to evaluate the frequency of the various aetiologies of olfactory dysfunction in a population of patients with non-sinonasal-related olfactory dysfunction and secondly, to evaluate the degree of olfactory impairment associated with these various aetiologies. Material and methodsWe retrospectively reviewed a cohort of 496 patients with non-sinonasal-related olfactory dysfunction. The aetiology of the olfactory dysfunction was recorded for each patient. The aetiology was determined by a complete clinical assessment, including medical history, complete otorhinolaryngological examination, psychophysical testing of olfactory function, recording of olfactory event-related potentials and brain magnetic resonance imaging. Six groups of patients were defined on the basis of the aetiology of the disease and orthonasal and retronasal psychophysical olfactory performances were evaluated in each group. ResultsPost-infectious and post-traumatic aetiologies were the most common causes, representing 37.9% and 33.1% of patients, respectively, followed by idiopathic (16.3%), congenital (5.9%), toxic (3.4%) and neurological (3.4%) olfactory dysfunction. Anosmia was significantly more frequent in congenital (93.1%) and post-traumatic (62.8%) olfactory dysfunction, whereas hyposmia was more frequent in the post-infectious group (59.6%). Orthonasal and retronasal olfactory function tests were significantly correlated in all groups except for the congenital group. ConclusionsThe data of this study confirm that the most common causes of non-sinonasal-related olfactory dysfunction are post-infectious and post-traumatic. Post-infectious olfactory dysfunction is mainly observed in middle-aged women and is mainly associated with hyposmia, whereas post-traumatic olfactory dysfunction is mainly observed in young men and is associated with a high rate of anosmia.

Use of olfactory training in post‐traumatic and postinfectious olfactory dysfunction

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.

Olfactory training is helpful in postinfectious olfactory loss: A randomized, controlled, multicenter study

The aim of this study was to evaluate the effects of olfactory training (OT) on olfactory function in patients with persistent postinfectious olfactory dysfunction (PIOD). Randomized, single-blind, controlled, multicenter crossover study. Twelve tertiary university medical centers participated. Investigations were performed at three visits (baseline, after 18 weeks, and after 36 weeks), including only subjects with PIOD of <24-months duration. At each visit, participants received detailed assessment of olfactory function. Seventy subjects trained with high concentrations of four 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 <12 months, olfactory function improved in 15/24 participants (63%) of the high-training group and in 6/31 participants (19%) of the low-training group (P = .03). OT improves PIOD, and the use of odors at higher concentrations is beneficial to improvement. OT is a safe procedure and appears to be particularly useful in patients who start OT within 12 months after the onset of the disorder. OT is the first successful therapy regime in patients with PIOD. 1b.

Treatment of postinfectious olfactory disorders with minocycline: A double‐blind, placebo‐controlled study

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.

Reduced olfactory bulb volume in post-traumatic and post-infectious olfactory dysfunction

The olfactory bulb is a highly plastic structure the volume of which partly reflects the degree of afferent neural activity. In this study, 22 patients with post-infectious olfactory deficit, nine participants with post-traumatic olfactory deficit, and 17 healthy controls underwent magnetic resonance volumetry of the olfactory bulb. Patients presented with significantly smaller olfactory bulb volumes than controls; significant correlations between olfactory function and bulb volume were observed. Patients with parosmia exhibited smaller olfactory bulb volumes than those without parosmia. Findings indicate that smell deficits leading to a reduced sensory input to the olfactory bulb result in structural changes at the level of the bulb. Reduced olfactory bulb volumes may also be considered to be characteristic of parosmia.