Effects of genetics on odor perception: Can a quick smell test effectively screen everyone?

SCENTinel, a rapid smell test designed to screen for olfactory disorders, including anosmia (no ability to smell an odor) and parosmia (distorted sense of smell), measures 4 components of olfactory function: detection, intensity, identification, and pleasantness. Each test card contains one of 9 odorant mixtures. Some people born with genetic insensitivities to specific odorants (i.e. specific anosmia) may fail the test if they cannot smell an odorant but otherwise have a normal sense of smell. However, using odorant mixtures has largely been found to prevent this from happening. To better understand whether genetic differences affect SCENTinel test results, we asked genetically informative adult participants (twins or triplets, N = 630; singletons, N = 370) to complete the SCENTinel test. A subset of twins (n = 304) also provided a saliva sample for genotyping. We examined data for differences between the 9 possible SCENTinel odors; effects of age, sex, and race on SCENTinel performance, test-retest variability; and heritability using both structured equation modeling and SNP-based statistical methods. None of these strategies provided evidence for specific anosmia for any of the odors, but ratings of pleasantness were, in part, genetically determined (h2 = 0.40) and were nominally associated with alleles of odorant receptors (e.g. OR2T33 and OR1G1; P < 0.001). These results provide evidence that using odorant mixtures protected against effects of specific anosmia for ratings of intensity but that ratings of pleasantness showed effects of inheritance, possibly informed by olfactory receptor genotypes.

Integrating the patient's voice into the research agenda for treatment of chemosensory disorders.

World-wide some 658 million people were infected with coronavirus disease 2019 (COVID-19) and millions suffer from chemosensory impairment associated with long COVID. Current treatments for taste and smell disorders are limited. Involving patients has the potential to catalyze the dynamic exchange and development of new ideas and approaches to facilitate biomedical research and therapeutics. We assessed patients' perceptions of the efficacy of treatments for chemosensory impairment using an online questionnaire completed by 5,815 people in the US Logistic regression determined variables predictive of reported treatment efficacy for patients aged 18 to 24, 25 to 39, 40 to 60, and 60+ yrs. who were treated with nasal steroids, oral steroids, zinc, nasal rinse, smell training, theophylline, platelet-rich plasma, and Omega 3. The most consistent predictor was age, with the majority of those 40 to 60 and 60+ reporting that nasal steroids, oral steroids, zinc, nasal rinse, and smell training were only slightly effective or not effective at all. Many of these treatment strategies target regeneration and immune response, processes compromised by age. Only those under 40 reported more than slight efficacy of steroids or smell training. Findings emphasize the need to include patients of all ages in clinical trials. Older adults with olfactory impairment are at increased risk for Alzheimer's disease (AD). We speculate that olfactory impairment associated with long COVID introduces the potential for a significant rise in AD. Long COVID-associated chemosensory impairment increases the urgency for translational and clinical research on novel treatment strategies. Suggestions for high-priority areas for epidemiological, basic, and clinical research on chemosensory impairment follow.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

More spice, less salt: How capsaicin affects liking for and perceived saltiness of foods in people with smell loss.

People who lose their sense of smell self-report consuming more salt to compensate for a lack of flavor and enhance eating enjoyment. However, this may contribute to excess sodium intake. Capsaicin may help increase salt taste intensity and eating enjoyment in people with smell loss, but this has not been studied in this population. The purpose of this study was to determine 1) whether salt intake in those with smell loss differs from population averages, 2) whether capsaicin increases flavor and salt taste intensity, and 3) if adding spice to foods increases liking in individuals with smell loss. Thirty-three participants 18-65 years old with confirmed smell loss for at least 12 weeks completed two sets of replicate test sessions (four total). In two sessions participants rated overall flavor intensity, taste qualities' intensities, spicy intensity, and liking for model tomato soups with low or regular sodium content and three levels of capsaicin (none, low, or moderate). In the other two sessions, participants rated the same sensory attributes for model food samples with three levels of added spice (none, low, or moderate). 24-hour urine samples were collected to determine sodium intake. Results indicate that although sodium intake is higher than recommended (<2300 mg/day) in those with smell loss (2893 ± 258 mg/day), they do not consume more sodium than population averages (3039 ± 100 mg/day; p = 0.3). Adding low and moderate amounts of capsaicin to a model tomato soup increased the intensity of overall flavor (p < 0.001) and saltiness (p = 0.004) compared to a model tomato soup without capsaicin. However, capsaicin's effect on liking differed by food type. Thus, capsaicin can improve flavor, salt taste intensity, and eating enjoyment in people with smell loss.

SCENTinel 1.0: Development of a Rapid Test to Screen for Smell Loss.

Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening.

Exploring the science, safety, and benefits of air care products: perspectives from the inaugural air care summit.

Seventy-one percent of US households purchase air care products. Air care products span a diverse range of forms, including scented aerosol sprays, pump sprays, diffusers, gels, candles, and plug-ins. These products are used to eliminate indoor malodors and to provide pleasant scent experiences. The use of air care products can lead to significant benefits as studies have shown that indoor malodor can cause adverse effects, negatively impacting quality of life, hygiene, and the monetary value of homes and cars, while disproportionately affecting lower income populations. Additionally, studies have also shown that scent can have positive benefits related to mood, stress reduction, and memory enhancement among others. Despite the positive benefits associated with air care products, negative consumer perceptions regarding the safety of air care products can be a barrier to their use. During the inaugural Air Care Summit, held on 18 May 2018 in the Washington, DC, metropolitan area, multidisciplinary experts including industry stakeholders, academics, and scientific and medical experts were invited to share and assess the existing data related to air care products, focusing on ingredient and product safety and the benefits of malodor removal and scent. At the Summit's completion, a panel of independent experts representing the fields of pulmonary medicine, medical and clinical toxicology, pediatric toxicology, basic science toxicology, occupational dermatology and experimental psychology convened to review the data presented, identify potential knowledge gaps, and suggest future research directions to further assess the safety and benefits of air care products.

Nasal Structural and Aerodynamic Features That May Benefit Normal Olfactory Sensitivity.

Nasal airflow that effectively transports ambient odors to the olfactory receptors is important for human olfaction. Yet, the impact of nasal anatomical variations on airflow pattern and olfactory function is not fully understood. In this study, 22 healthy volunteers were recruited and underwent computed tomographic scans for computational simulations of nasal airflow patterns. Unilateral odor detection thresholds (ODT) to l-carvone, phenylethyl alcohol (PEA) and d-limonene were also obtained for all participants. Significant normative variations in both nasal anatomy and aerodynamics were found. The most prominent was the formation of an anterior dorsal airflow vortex in some but not all subjects, with the vortex size being significantly correlated with ODT of l-carvone (r = 0.31, P < 0.05). The formation of the vortex is likely the result of anterior nasal morphology, with the vortex size varying significantly with the nasal index (ratio of the width and height of external nose, r = -0.59, P < 0.001) and nasal vestibule "notch" index (r = 0.76, P < 0.001). The "notch" is a narrowing of the upper nasal vestibule cartilage region. The degree of the notch also significantly correlates with ODT for PEA (r = 0.32, P < 0.05) and l-carvone (r = 0.33, P < 0.05). ODT of d-limonene, a low mucosal soluble odor, does not correlate with any of the anatomical or aerodynamic variables. The current study revealed that nasal anatomy and aerodynamics might have a significant impact on normal olfactory sensitivity, with greater airflow vortex and a narrower vestibule region likely intensifying the airflow vortex toward the olfactory region and resulting in greater olfactory sensitivity to high mucosal soluble odors.

Lack of respiratory and ocular effects following acute propylene glycol exposure in healthy humans.

OBJECTIVE: Propylene glycol (PG) is a widely used solvent, chemical intermediate and carrier substance for foods, pharmaceutical and cosmetic products. Professional and occupational exposure to PG aerosol and vapor may occur from theatrical smoke generators and during application of deicing products to airplanes. While PG is considered to have low toxicity, the results of one study suggested that brief (1-min) exposure to PG mist elicited ocular and respiratory effects in humans. Because the high concentrations and brief exposure duration in that study were not representative of most occupational exposures, a controlled experimental exposure study was conducted to clarify or confirm the earlier findings. MATERIALS AND METHODS: Ten males and 10 females were exposed to PG aerosol for 4 hrs at 20 and 100 mg/m3 and 30 min at 200 mg/m3. Total PG exposure concentrations (droplets plus gas phase) were 95.6, 442.4 and 871 mg/m3 for the three conditions, respectively. Participants rode a stationary bicycle to simulate physical effort at regular intervals during exposure. Objective measures evaluated in this study included ocular irritation via eye blink task and eye photography and pulmonary function via spirometry, while subjective measures included health symptoms ratings, irritation and dryness ratings of eyes, nose, throat and mouth. RESULTS: Objective measures of pulmonary function and ocular irritation did not reveal any exposure-related changes. Exposure-related changes in symptom reporting were observed; however, the highest symptom ratings did not exceed "slight" on the scale. CONCLUSIONS: The results indicate at the concentrations and acute durations tested, PG does not affect human respiratory function or produce ocular irritation.

Formaldehyde Induces Rho-Associated Kinase Activity to Evoke Airway Hyperresponsiveness.

Formaldehyde, a common indoor air pollutant, exacerbates asthma and synergizes with allergen to induce airway hyperresponsiveness (AHR) in animal models. The mechanisms mediating formaldehyde-induced AHR remain poorly understood. We posit that formaldehyde modulates agonist-induced contractile response of human airway smooth muscle (HASM) cells to elicit AHR. HASM cells were exposed to formaldehyde or vehicle and agonist-induced intracellular Ca2+ ([Ca2+]i) and myosin light-chain phosphatase (MYPT1) phosphorylation were determined. Air-liquid interface-differentiated human bronchial epithelial (HBE) cells were exposed to formaldehyde or vehicle and cocultured with HASM cells. Agonist-induced [Ca2+]i and MYPT1 phosphorylation were determined in the cocultured HASM cells. Precision-cut human lung slices were exposed to PBS or varying concentrations of formaldehyde, and then carbachol-induced airway narrowing was determined 24 hours after exposure. HASM cells were transfected with nontargeting or nuclear factor erythroid-derived 2, like 2 (Nrf-2)-targeting small interfering RNA and exposed to formaldehyde or vehicle, followed by determination of antioxidant response (quinone oxido-reductase 1 and thioredoxin 1) and basal and agonist-induced MYPT1 phosphorylation. Formaldehyde enhanced the basal Rho-kinase activity and MYPT1 phosphorylation with little effect on agonist-induced [Ca2+]i in HASM cells. Formaldehyde induced Nrf-2-dependent antioxidant response in HASM cells, although the MYPT1 phosphorylation was independent of Nrf-2 induction. Although HBE cells exposed to formaldehyde had little effect on agonist-induced [Ca2+]i or MYPT1 phosphorylation in cocultured HASM cells, formaldehyde enhanced carbachol-induced airway responsiveness in precision-cut human lung slices. In conclusion, formaldehyde induces phosphorylation of the regulatory subunit of MYPT1, independent of formaldehyde-induced Nrf-2 activation in HASM cells. The findings suggest that the Rho kinase-dependent Ca2+ sensitization pathway plays a role in formaldehyde-induced AHR.

Effect of taste sensation on cough reflex sensitivity.

Cough is among the most common symptoms with which people present for medical attention, but evidence-based treatments remain limited. One issue compromising interpretation of clinical trials of cough preparations is that control formulations often are nearly as effective as those that contain active ingredients. This observation has caused some researchers to propose that one or more nominally inactive ingredients may have some physiological effects. For example, most liquid cough preparations are highly sweetened, and it has been suggested that sweet taste might modulate cough sensitivity. The fact that honey has been used for thousands of years as a cough remedy is consistent with this idea. However, empirical evidence for modulation of cough sensitivity by taste was lacking. Evidence is still sparse, but relevant experiments have now been published: rinsing the mouth with a sweet sucrose solution increased cough thresholds in a single-inhalation capsaicin challenge. Furthermore, rinsing the mouth with a bitter solution did not affect thresholds, an important demonstration of specificity. The underlying mechanisms of cough suppression by sweet taste are still unclear. However, extant data suggest that modulation of cough sensitivity by taste is a promising area for further investigation. Such work may lead to greater understanding of apparent placebo effects in clinical trials and provide empirical support for therapies based on stimulation of taste nerves.

Remote olfactory assessment using the NIH Toolbox Odor Identification test and the brain health registry.

BACKGROUND: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting. AIM: The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test). MATERIALS AND METHODS: Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting. RESULTS: We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41. CONCLUSION: These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

Topical platelet-rich plasma as a possible treatment for olfactory dysfunction-A randomized controlled trial.

BACKGROUND: Olfactory dysfunction (OD) affects many survivors of COVID-19. Prior studies have investigated the use of platelet-rich plasma (PRP) injections for OD. We describe the first randomized controlled trial investigating topical PRP for OD treatment and contribute to existing literature illustrating PRP as an emerging therapeutic. METHODS: This is a single-blinded, randomized controlled trial conducted from July 2022 to December 2023. Adult patients with OD ≥6 months secondary to COVID-19 with Brief Smell Identification Test (BSIT) scores of ≤8/12 or SCENTinel odor intensity of ≤40/100 were included. Patients were randomized to three, monthly PRP or placebo-impregnated Surgifoam treatments into bilateral olfactory clefts. The BSIT, SCENTinel, and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) were completed monthly through month 12. RESULTS: Of 104 patients screened, 83 participated. No significant differences in age, OD duration, BSIT, SCENTinel, or QOD-NS scores were found between PRP (n = 42) and placebo (n = 41) patients at baseline. PRP patients experienced a statistically significant increase in BSIT scores from baseline at months 5‒9, 11, and 12, while placebo patients did not (p < 0.05). However, total BSIT scores were similar between the two groups throughout the study. Neither the SCENTinel odor intensity scores nor the change from baseline were significantly different between the treatment groups. At month 12, PRP patients experienced minor improvement in OD-related quality-of-life compared with placebo. CONCLUSIONS: This study is the first to describe topical PRP as a safe, experimental treatment for OD in humans. PRP may impact odor identification in post-COVID-19 OD patients, although the lack of difference in total BSIT scores highlights the need for further study.

Using SCENTinel® to predict SARS-CoV-2 infection: insights from a community sample during dominance of Delta and Omicron variants.

Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.

Mind over age--stereotype activation and olfactory function.

Given that context affects olfaction and the elderly exhibit olfactory deficits, the current study tested whether a subtle change in internal context, evoked by priming the elderly stereotype, would affect performance in a variety of olfactory tasks including odor sensitivity, discrimination, and identification (Experiment 1), as well as perceived odor intensity, pleasantness and familiarity, and an odor reaction time task (Experiment 2). Such internalization of the elderly stereotype has been demonstrated with slower walking speeds and fewer words recalled in a memory task. In the current study, 76 participants first listened to a presentation about age-related declines in olfaction and then participated in 3 language tasks which, unbeknownst to them, served as the elderly stereotype priming manipulation. This priming manipulation was effective at decreasing walking speed and word recall, confirming the findings of previous researchers; however, olfaction was not affected. Whether olfaction is resistant to stereotype priming is discussed.

More spice, less salt: how capsaicin affects liking for and perceived saltiness of foods in people with smell loss.

People who lose their sense of smell self-report consuming more salt to compensate for a lack of flavor and enhance eating enjoyment. However, this can contribute to excess sodium intake and a poor diet. Capsaicin may help increase salt taste intensity and eating enjoyment in this population, but this has not been studied. The purpose of this study was to determine 1) whether salt intake in those with smell loss differs from population averages, 2) whether capsaicin increases flavor and salt taste intensity, and 3) if adding spice to foods increases food liking in individuals with smell loss. Participants 18-65 years old with confirmed partial or total smell loss for at least 12 weeks completed two sets of replicate test sessions (four total). In two sessions participants rated overall flavor intensity, taste qualities' intensities, spicy intensity, and liking for model tomato soups with low or regular sodium content and three levels of capsaicin (none, low, or moderate). In the other two sessions, participants rated the same sensory attributes for model food samples with three levels of added spice (none, low, or moderate). 24-hour urine samples were also collected to determine sodium intake. Results indicate that although sodium intake is higher than recommended in those with smell loss (2893 ± 258 mg/day), they do not consume more sodium than population averages. Adding low and moderate amounts of capsaicin to a model tomato soup increased the intensity of overall flavor and saltiness compared to a model tomato soup without capsaicin. However, the effect of capsaicin on liking differed by food type. In conclusion, the addition of capsaicin can improve flavor, salt taste intensity, and eating enjoyment in people with smell loss.

Characterization of Ethyl Butyrate-Induced Cough Before and After Breath Control Techniques in Healthy Adults.

PURPOSE: Methods for cough elicitation frequently involve aerosolized tussive agents. Here, we sought to determine whether healthy individuals demonstrate a quantifiable cough response after inhaling a volatile ester and if breath control techniques modify this chemically induced cough response. METHOD: Sixty adult male and female participants inhaled prepared liquid dilutions of ethyl butyrate dissolved in paraffin oil at 20%, 40%, and 60% v/v concentrations in triplicate, with presentation order randomized. We delivered stimuli through a face mask connected to an olfactometer and respiratory pneumotachograph. Participants rated sensations of their urge to cough and pleasantness of the odor while cough airflow was measured. Following baseline testing, participants were randomized to implement pursed-lip breathing or slow-paced breathing after inhaling ethyl butyrate to determine the effects of breath control on cough measures. RESULTS: Inhaled ethyl butyrate elicited cough in 70% of participants. Higher concentrations of ethyl butyrate resulted in significantly greater sensation of the urge to cough, F(2, 80) = 10.72, p < .001, and significantly more generated coughs, F(2, 63) = 13.14, p < .001. Compared to baseline, participants rated significantly decreased urge to cough during breath control techniques, F(1, 40) = 11.01, p = .0019. No significant changes were observed in the number of generated coughs between baseline and breath control techniques, F(1, 31) = 7.23, p = .01. CONCLUSIONS: Airborne ethyl butyrate is a tussigenic agent in humans. Our findings provide opportunities for future research directions in normal and disordered cough responses to volatile compounds.

Examining the Influence of Chemosensation on Laryngeal Health and Disorders.

Inhaled airborne stimuli are associated with laryngeal disorders affecting respiration. Clinically, several themes emerged from the literature that point to specific gaps in the understanding and management of these disorders. There is wide variation in the types of airborne stimuli that trigger symptoms, lack of standardization in provocation challenge testing using airborne stimuli, and vague reporting of laryngeal symptoms. Scientifically, evidence exists outside the field of voice science that could prove useful to implement among patients with impaired laryngeal-respiration. To expand this area of expertise, here we provide a thematic overview of relevant evidence and methodological tools from the discipline of chemosensory sciences. This review provides distinctions across the three chemosensory systems of olfaction, trigeminal chemesthesis, and gustation, guidance on selecting and delivering common chemosensory stimuli for clinical testing, and methods of quantifying sensory experiences using principles of human psychophysics. Investigating the science of chemosensation reveals that laryngeal responses to inhaled airborne stimuli have explanations involving physiological mechanisms as well as higher cognitive processing. Fortunately, these findings are consistent with current pharmacological and nonpharmacological interventions for impaired laryngeal-respiration. Based on the close relationships among inhaled airborne stimuli, respiration, and laryngeal function, we propose that new perspectives from chemosensory sciences offer opportunities to improve patient care and target areas of future research.

Environmental chamber studies of eye and respiratory irritation from use of a peracetic acid-based hospital surface disinfectant.

Objective: To characterize personal exposures and measures of eye and respiratory tract irritation in controlled environmental chamber studies of 44 healthy adult volunteers simulating upper-bound use of peracetic acid (PAA)-based surface disinfectant for terminal cleaning of hospital patient rooms. Design: Experimental, within-subject, double-blinded cross-over design. Methods: Objective and subjective exposure effects were assessed for PAA and its components: acetic acid (AA) and hydrogen peroxide (HP). Deionized water was included as a control. Breathing-zone concentrations of PAA, AA, and HP were assessed for 8 female multiday volunteers (5 consecutive days) and 36 single-day volunteers (32 females and 4 males). Wetted cloths were used to wipe high-touch surfaces for 20 minutes per trial. Also, 15 objective measures of tissue injury or inflammation and 4 subjective odor or irritation scores were assessed. Results: Disinfectant trials showed 95th percentile breathing zone concentrations of 101 ppb PAA, 500 ppb AA, and 667 ppb HP. None of the volunteers observed over 75 test days exhibited significant increases in IgE or objective measures of eye and respiratory tract inflammation. Subjective ratings for disinfectant and AA-only trials showed similar increases for odor intensity and nose irritation, with lower ratings for eye and throat irritation. Females were 2.5-fold more likely than males to assign moderate + irritation ratings. Conclusions: Simulated upper-bound hospital use of PAA-based disinfectant led to no significant increases in objective markers of tissue injury, inflammation, or allergic sensitization, and no frank signs of eye or respiratory tract irritation.

Exploring Olfactory Dysfunction as a Marker of Frailty and Postoperative Outcomes in Head and Neck Cancer.

Importance: Olfactory dysfunction (OD) is increasingly recognized as a robust marker of frailty and mortality. Despite broad recognition of frailty as a critical component of head and neck cancer (HNC) care, there is no standardized frailty assessment. Objective: To assess the prevalence of OD and its association with frailty and postoperative outcomes in HNC. Design, Setting, and Participants: In this prospective cohort study with enrollment between February 17, 2021, to September 29, 2021, at a tertiary academic medical center, 85 eligible adult patients with primary, treatment-naive HNC of mucosal or cutaneous origin were included. Patients with a history of COVID-19, neurocognitive, or primary smell/taste disorders were excluded. Exposures: Prospective olfactory assessments (self-reported, visual analog scale [VAS] and psychophysical, University of Pennsylvania Smell Identification Test [UPSIT]) with concurrent frailty assessment (Risk Analysis Index [RAI]) were used. Olfactory-specific quality of life (QOL) was examined with brief Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). Main Outcome(s) and Measure(s): The primary outcome was the prevalence of OD as assessed by VAS (0-10, no to normal smell) and UPSIT (0-40, higher scores reflect better olfaction) and its association with frailty (RAI, 0-81, higher scores indicate greater frailty). For surgical patients, secondary outcomes were associations between OD and postoperative length of stay (LOS), 30-day postoperative outcomes, and QOD-NS (0-21, higher scores indicate worse QOL). Results: Among 51 patients with HNC (mean [SD] age, 63 [10] years; 39 [77%] male participants; 41 [80%] White participants), 24 (47%) were frail, and 4 (8%) were very frail. Despite median (IQR) self-reported olfaction by VAS of 9 (8-10), 30 (59%) patients demonstrated measured OD with psychophysical testing. No meaningful association was found between self-reported and psychophysical testing (Hodges-Lehmann, <0.001; 95% CI, -2 to 1); a total of 46 (90%) patients did not report decreased olfaction-specific QOL. Median UPSIT scores were lower in frail patients (Hodges-Lehmann, 6; 95% CI, 2-12). Multivariate modeling demonstrated severe microsmia/anosmia was associated with 1.75 (95% CI, 1.09-2.80) times odds of being frail/very frail and approximately 3 days increased LOS (ß, 2.96; 95% CI, 0.29-5.62). Conclusions and Relevance: Although patients with HNC are unaware of olfactory changes, OD is common and may serve as a bellwether of frailty. In this prospective cohort study, a dose-dependent association was demonstrated between increasing degrees of OD and frailty, and the potential utility of olfaction was highlighted as a touchstone in the assessment of HNC frailty.