Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment: A longitudinal cohort study.

Objectives: Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD. Methods: We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available. Results: Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004). Conclusions: OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.

Subjective versus Psychophysical Measures of Chemosensory Alterations following COVID-19.

INTRODUCTION: Olfactory dysfunction is a common symptom of COVID-19. However, subjective perception of olfactory function does not always correlate well with more objective measures. This study seeks to clarify associations between subjective and psychophysical measures of olfaction and gustation in patients with subjective chemosensory dysfunction following COVID-19. METHODS: Adults with persistent COVID-19-associated chemosensory disturbance were recruited for a prospective, longitudinal cohort study at a tertiary care institution. Participants provided subjective measures of olfactory and gustatory function and underwent psychophysical assessment using Sniffin' Sticks olfactory and Monell gustatory tests. RESULTS: Data analysis (n = 65) showed a statistically significant association between subjective and psychophysical measures of olfaction (p < 0.001). For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p < 0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p < 0.001) point and 0.05 (95% CI: 0.03, 0.07; p < 0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. CONCLUSION: Subjective olfaction shows a mild to moderate association with psychophysical measures, but it fails to comprehensively assess persistent COVID-19-associated chemosensory deficits. The lack of significant association between subjective olfaction and threshold limits the utility of subjective olfaction in tracking recovery. These findings support the push for more widespread psychophysical chemosensory testing.

Endoscopic treatment of subglottic stenosis with flexible bronchoscopy via laryngeal mask airway.

OBJECTIVE: To evaluate the safety and efficacy of endoscopic treatment of subglottic stenosis with flexible bronchoscopy via laryngeal mask airway (LMA) approach. METHODS: The records of all patients who underwent endoscopic surgery for subglottic stenosis (SGS) from November 2019 to January 2023 at an academic medical center were reviewed with attention to demographics, patient comorbidities, airway stenosis characteristics, operative time details, surgical complications, and post-operative course. All patients, >18 years old, with one or more surgeries for SGS using (LMA) for intraoperative airway management were included. Surgeries with suspension microlaryngoscopy were excluded. Patients with glottic stenosis or tracheotomy were excluded. RESULTS: Thirty-five patients underwent 52 procedures meeting inclusion criteria. Mean age was 55 years (range 31-78, SD 13.3) and 33 patients (94%) were female. Mean BMI was 30.9 (range 18.4-60.5, SD 8.8). The most common etiology of stenosis was intubation injury in 17 patients (49%), followed by idiopathic in 13 patients (37%). Cotton-Meyer grade 3 (71-99% narrowing) was seen in 25 patients (71%). Mean anesthesia and surgical operative times were 75.9 min (SD 13.5 min) and 39.7 min (SD 11.0 min), respectively. Mean SpO2 nadir was 94.5% (SD 6.3%). No patients required intraoperative change to rigid laryngoscopy, intubation, or tracheotomy. There were no post-operative complications. Mean surgery-free interval was 12.2 months (SD 6.3). CONCLUSION: Endoscopic treatment of subglottic stenosis with flexible bronchoscopy and spontaneous ventilation via LMA approach is a safe and effective option, especially in patients with limitations for rigid laryngoscopy and elevated BMI. LEVEL OF EVIDENCE: Level Four (case series) Laryngoscope, 2023.

BMI Increases in Individuals with COVID-19-Associated Olfactory Dysfunction.

(1) Background: Reports suggest COVID-19-associated olfactory dysfunction (OD) may result in alterations in dietary behaviors and perceived weight change, but few studies using psychophysical evaluation of post-COVID-19-associated chemosensory dysfunction and body mass index (BMI) exist. The purpose of this study is to assess the impact of both quantitative and qualitative features of COVID-19-associated OD on BMI; (2) Methods: Recruitment of thirty-one participants with self-reported OD in the form of quantitative loss with and without qualitative features. Surveys with questions specific to qualitative olfactory function, Sniffin' Sticks tests, and BMI measures were completed at two visits, one year apart. Group differences were assessed with Wilcoxon signed-rank tests and the Holm-Bonferroni method; (3) Results: Individuals with persistent quantitative OD (n = 15) and self-reported parosmia (n = 19) showed statistically significant increases in BMI after 1 year (p = 0.004, adjusted α = 0.0125; p = 0.011, adjusted α = 0.0167). Controls with transient quantitative OD (n = 16) and participants without self-reported parosmia (n = 12) showed no statistically significant changes in BMI over the same time period (p = 0.079, adjusted α = 0.05; p = 0.028, adjusted α = 0.025); (4) Conclusions: This study shows an association between COVID-19-associated OD and BMI, suggesting olfaction may play a role in altering dietary habits and nutrition in this population. Larger study cohorts are needed to further evaluate this relationship.

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

BACKGROUND: Nearly 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: While 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.

Impact of Race, Ethnicity, and Socioeconomic Status on Nasopharyngeal Carcinoma Disease-Specific and Conditional Survival.

Introduction Race, ethnicity, and socioeconomic status (SES) are complex, interconnected social determinants of health outcomes. This study uses multivariable analysis on a combination of large national datasets to examine the effects of these factors on 5-year disease-specific survival (DSS) and conditional DSS (CDSS) for nasopharyngeal carcinoma (NPC). Methods A retrospective study of adults with NPC between 2000 and 2017 from the Surveillance, Epidemiology, End Results (SEER) registry was performed, using the National Cancer Institute Yost Index, a census tract-level composite score of SES to categorize patients. Kaplan-Meier analysis and Cox's regression for DSS and CDSS were stratified by SES. Logistic regression was conducted to identify risk factors for advanced cancer stage at time of diagnosis and receiving multimodal therapy. Results Our analysis included 5,632 patients. DSS was significantly associated with race and SES ( p < 0.01). Asian/Pacific Islander patients exhibited increased survival when controlling for other variables (hazard ratio [HR] = 0.73, p < 0.01). Although Black patients were more likely to be diagnosed with advanced disease (Black odds ratio [OR] = 1.47, p < 0.01), Black patients were also less likely to receive multimodal therapy; however, this relationship lost statistical significance once SES was incorporated into the multivariable analysis. DSS was decreased among the lowest (first) and middle (second) tertiles of SES (first HR = 1.34, p < 0.01; second HR = 1.20, p < 0.01) compared with the highest (third). Conclusion Our results indicate that race, ethnicity, and SES significantly affect survival, stage at diagnosis, and treatment of NPC. An interplay of tumor biology and inequalities in access to care likely drives these disparities.

Grizzlies and gazelles: Duty factor is an effective measure for categorizing running style in English Premier League soccer players.

English Premier League soccer players run at multiple speeds throughout a game. The aim of this study was to assess how well the duty factor, a dimensionless ratio based on temporal variables, described running styles in professional soccer players. A total of 25 players ran on an instrumented treadmill at 12, 16, and 20 km/h. Spatiotemporal and ground reaction force data were recorded for 30 s at each speed; video data (500 Hz) were collected to determine footstrike patterns. In addition to correlation analysis amongst the 25 players, two groups (both N = 9) of high and low duty factors were compared. The duty factor was negatively correlated with peak vertical force, center of mass (CM) vertical displacement, and leg stiffness (k leg) at all speeds (r ≥ -0.51, p ≤ 0.009). The low duty factor group had shorter contact times, longer flight times, higher peak vertical forces, greater CM vertical displacement, and higher k leg (p < 0.01). Among the high DF group players, eight were rearfoot strikers at all speeds, compared with three in the low group. The duty factor is an effective measure for categorizing soccer players as being on a continuum from terrestrial (high duty factor) to aerial (low duty factor) running styles, which we metaphorically refer to as "grizzlies" and "gazelles," respectively. Because the duty factor distinguishes running style, there are implications for the training regimens of grizzlies and gazelles in soccer, and exercises to improve performance should be developed based on the biomechanical advantages of each spontaneous running style.

Time-domain and frequency-domain effects of tensor tympani contraction on middle ear sound transmission in gerbil.

The middle ear is a high-fidelity, broadband impedance transformer that transmits acoustic stimuli at the eardrum to the inner ear. It is home to the two smallest muscles in mammalian species, which modulate middle ear transmission. Of this pair, the function of the tensor tympani muscle (TTM) has remained obscure. We investigated the acoustic effects of this muscle in young adult gerbils. We measured changes in middle ear vibration produced by pulse-train-elicited TTM contraction - in the time-domain with a click stimulus and in the frequency-domain with multitone zwuis stimuli. In our click experiments, there was generally a small reduction in the primary peak of the response and a slight increase in the subsequent ringing, but there was essentially no change in the delay of the click response at the umbo (less than 1 µs change). In our multitone experiments, there were consistent patterns of attenuation and enhancement in the velocity responses at the umbo and ossicles. TTM contraction produced a narrow band of enhancement around 6 kHz (maximally ~5 dB) that can be modeled with an increased stiffness of an overdamped spring-mass resonance. At frequencies below 2 kHz and above 35 kHz, TTM contraction attenuated middle ear vibrations by as much as fivefold.

Fuel Use during Exercise at Altitude in Women with Glucose-Fructose Ingestion.

PURPOSE: This study compared the coingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women. METHOD: Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to HA (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. RESULTS: The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (effect size [ES] > 0.99, P < 0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6% ± 6.1% vs 36.0% ± 6.1%, ES = 0.56, P = 0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2% ± 1.2% vs 3.1% ± 0.8%, ES = 0.09, P = 0.635 and 5.1 ± 1.8 vs 5.4 ± 1.7 g, ES = 0.19, P = 0.217), and muscle glycogen (14.4% ± 12.2% vs 15.8% ± 9.3%, ES = 0.11, P = 0.934 and 23.1 ± 19.0 vs 28.7 ± 17.8 g, ES = 0.30, P = 0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3 ± 21.4 vs 59.6 ± 7.7 g, ES = 0.32, P = 0.557). CONCLUSIONS: In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity.

Changes in balance and joint position sense during a 12-day high altitude trek: The British Services Dhaulagiri medical research expedition.

Postural control and joint position sense are essential for safely undertaking leisure and professional activities, particularly at high altitude. We tested whether exposure to a 12-day trek with a gradual ascent to high altitude impairs postural control and joint position sense. This was a repeated measures observational study of 12 military service personnel (28±4 years). Postural control (sway velocity measured by a portable force platform) during standing balance, a Sharpened Romberg Test and knee joint position sense were measured, in England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12-day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and Lake Louise scores were also recorded on the morning and evening of each trek day. Data were compared between altitudes and relationships between pulse oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior sway velocity during standing balance with eyes open was also significantly greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001, d = 1.9). Knee joint position sense was not altered at higher altitudes. There were no significant correlations between Lake Louise scores, pulse oximetry and postural sway. Despite a gradual ascent profile, exposure to 3619 m was associated with impairments in postural control without impairment in knee joint position sense. Importantly, these impairments did not worsen at higher altitudes of 4600 m or 5140 m. The present findings should be considered during future trekking expeditions when developing training strategies targeted to manage impairments in postural control that occur with increasing altitude.

Markers of physiological stress during exercise under conditions of normoxia, normobaric hypoxia, hypobaric hypoxia, and genuine high altitude.

PURPOSE: To investigate whether there is a differential response at rest and following exercise to conditions of genuine high altitude (GHA), normobaric hypoxia (NH), hypobaric hypoxia (HH), and normobaric normoxia (NN). METHOD: Markers of sympathoadrenal and adrenocortical function [plasma normetanephrine (PNORMET), metanephrine (PMET), cortisol], myocardial injury [highly sensitive cardiac troponin T (hscTnT)], and function [N-terminal brain natriuretic peptide (NT-proBNP)] were evaluated at rest and with exercise under NN, at 3375 m in the Alps (GHA) and at equivalent simulated altitude under NH and HH. Participants cycled for 2 h [15-min warm-up, 105 min at 55% Wmax (maximal workload)] with venous blood samples taken prior (T0), immediately following (T120) and 2-h post-exercise (T240). RESULTS: Exercise in the three hypoxic environments produced a similar pattern of response with the only difference between environments being in relation to PNORMET. Exercise in NN only induced a rise in PNORMET and PMET. CONCLUSION: Biochemical markers that reflect sympathoadrenal, adrenocortical, and myocardial responses to physiological stress demonstrate significant differences in the response to exercise under conditions of normoxia versus hypoxia, while NH and HH appear to induce broadly similar responses to GHA and may, therefore, be reasonable surrogates.

A comparison of substrate oxidation during prolonged exercise in men at terrestrial altitude and normobaric normoxia following the coingestion of 13C glucose and 13C fructose.

This study compared the effects of coingesting glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at altitude and sea level, in men. Seven male British military personnel completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to altitude (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min-1 of glucose (enriched with 13C glucose) and 0.6 g·min-1 of fructose (enriched with 13C fructose) directly before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. Total carbohydrate oxidation during the exercise period was lower at altitude (157.7 ± 56.3 g) than sea level (286.5 ± 56.2 g, P = 0.006, ES = 2.28), whereas fat oxidation was higher at altitude (75.5 ± 26.8 g) than sea level (42.5 ± 21.3 g, P = 0.024, ES = 1.23). Peak exogenous carbohydrate oxidation was lower at altitude (1.13 ± 0.2 g·min-1) than sea level (1.42 ± 0.16 g·min-1, P = 0.034, ES = 1.33). There were no differences in rates, or absolute and relative contributions of plasma or liver glucose oxidation between conditions during the second hour of exercise. However, absolute and relative contributions of muscle glycogen during the second hour were lower at altitude (29.3 ± 28.9 g, 16.6 ± 15.2%) than sea level (78.7 ± 5.2 g (P = 0.008, ES = 1.71), 37.7 ± 13.0% (P = 0.016, ES = 1.45). Acute exposure to altitude reduces the reliance on muscle glycogen and increases fat oxidation during prolonged cycling in men compared with sea level.

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude.

BACKGROUND: There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses. MATERIALS AND METHODS: This was a prospective observational study of 14 healthy subjects aged 22-35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375 m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA. RESULTS: All 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S', lateral S', tricuspid S' and A' velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A' was higher with GHA compared with NH at 15 minutes post exercise. CONCLUSIONS: GHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function.