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.

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.

Odours and incontinence: What does the nose know?

The fear of producing malodours that can be detected by others is a daily cause of anxiety for millions of people with incontinence. For many, the risk-whether real or imagined-that leaked waste products will be detectable by odour is sufficiently concerning to result in limitations on many types of activities. However, worry about personal odours can sensitise our olfactory system and cause us to be more aware of odours that may otherwise not be perceptible. In addition, heightened olfactory attention can often lead to odour misattributions, such as when we erroneously identify our body as the source of an odour that may simply be present in the environment. Odours produced by our bodies (endogenous odours) do enjoy a greater access to emotional brain centers and are processed faster than general odours. Here we provide examples from both everyday life and laboratory studies to explain how and why the olfactory system is unique among our sensory systems and how this knowledge can provide insights to our concerns about smell and incontinence and inform the development of products and solutions for incontinence.

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.

Chemosignals of stress influence social judgments.

Human body odors have important communicative functions regarding genetic identity, immune fitness and general health, but an expanding body of research suggests they can also communicate information about an individual's emotional state. In the current study, we tested whether axillary odors obtained from women experiencing psychosocial stress could negatively influence personality judgments of warmth and competence made about other women depicted in video scenarios. 44 female donors provided three types of sweat samples: untreated exercise sweat, untreated stress sweat and treated stress sweat. After a 'washout' period, a commercial unscented anti-perspirant product was applied to the left axilla only to evaluate whether 'blocking' the stress signal would improve the social evaluations. A separate group of male and female evaluators (n = 120) rated the women in the videos while smelling one of the three types of sweat samples. Women in the video scenes were rated as being more stressed by both men and women when smelling the untreated vs. treated stress sweat. For men only, the women in the videos were rated as less confident, trustworthy and competent when smelling both the untreated stress and exercise sweat in contrast to the treated stress sweat. Women's social judgments were unaffected by sniffing the pads. The results have implications for influencing multiple types of professional and personal social interactions and impression management and extend our understanding of the social communicative function of body odors.

Olfactory assessment using the NIH Toolbox.

The human olfactory system provides us with information about our environment that is critical to our physical and psychological well-being. Individuals can vary widely in their ability to detect, recognize, and identify odors, but still be within the range of normal function. Although several standardized tests of odor identification are available, few specifically address the issues in testing very young children, most of whom are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select among choices. Based on the format of the San Diego Odor Identification Test and the delivery system of the University of Pennsylvania Smell Identification Test, we developed 2 versions of an odor identification test using standardized odor stimuli in a scratch-and-sniff format in which participants match 5 (children) or 9 (adults) odors to pictures representing the odor source. Results from normative testing and validation showed that for most participants, the test could be completed in 5 minutes or less and that the poorer performance among the youngest children and the elderly was consistent with data from tests with larger numbers of items. Expanding on the pediatric version of the test with adult-specific and public health-relevant odors increased the ecological validity of the test and facilitated comparisons of intraindividual performance across developmental stages.

Development of a test to evaluate olfactory function in a pediatric population.

OBJECTIVES/HYPOTHESIS: This study evaluated two versions of a test for olfactory function to determine suitability for use in a pediatric population. STUDY DESIGN: Cross-sectional cohort study. METHODS: In phase 1, 369 children (ages 3-17 years) and 277 adults (parents) were tested. Children began with identification and familiarity judgments to pictures representing target odors and distractors. Odors were administered via a six-item scratch and sniff test. Each answer sheet contained the correct odor source and three distractors. In phase 2, 50 children (ages 3-4 years) and 43 adults were given a revised version with eight odors judged more representative of the source and familiar to children. RESULTS: Both completion time and identification accuracy in phase 1 improved with age. Accuracy of children 5 years old and above equaled adults for two of the three best odors. In phase 2, adults' accuracy significantly improved relative to phase 1 (92% vs. 68%), and exceeded that of 4 year olds for four of eight odors and 3 year olds for seven of eight odors. CONCLUSIONS: Children as young as 3 years of age can perform olfactory testing, but take longer than do older children and adults (7.44 vs. 5.66 vs. 3.71 minutes). Identification accuracy also increases as a function of age. The current six-item National Institutes of Health Toolbox Odor Identification Test is a brief, easily conducted test for evaluating olfactory ability. Collection of normative data for children of all ages and adults is needed to determine the clinical utility of the test and its interpretations for pathological conditions.

Chemosensory loss: functional consequences of the world trade center disaster.

BACKGROUND: Individuals involved in rescue, recovery, demolition, and cleanup at the World Trade Center (WTC) site were exposed to a complex mixture of airborne smoke, dust, combustion gases, acid mists, and metal fumes. Such exposures have the potential to impair nasal chemosensory (olfactory and trigeminal) function. OBJECTIVE: The goal of this study was to evaluate the prevalence of chemosensory dysfunction and nasal inflammation among these individuals. METHODS: We studied 102 individuals who worked or volunteered at the WTC site in the days and weeks during and after 11 September 2001 (9/11) and a comparison group with no WTC exposure matched to each participant on age, sex, and job title. Participants were comprehensively evaluated for chemosensory function and nasal inflammation in a single session. Individual exposure history was obtained from self-reported questionnaires. RESULTS: The prevalence of olfactory and trigeminal nerve sensitivity loss was significantly greater in the WTC-exposed group relative to the comparison group [prevalence ratios (95% confidence intervals) = 1.96 (1.2-3.3) and 3.28 (2.7-3.9) for odor and irritation thresholds, respectively]. Among the WTC responders, however, individuals caught in the dust cloud from the collapse on 9/11 exhibited the most profound trigeminal loss. Analysis of the nasal lavage samples supported the clinical findings of chronic nasal inflammation among the WTC-exposed cohort. CONCLUSIONS: The prevalence of significant chemosensory impairment in the WTC-exposed group more than 2 years after their exposure raises concerns for these individuals when the ability to detect airborne odors or irritants is a critical safety factor. RELEVANCE TO CLINICAL PRACTICE: This outcome highlights the need for chemosensory evaluations among individuals with exposure to acute high or chronic levels of airborne pollutants.

Evaluating the prevalence of olfactory dysfunction in a pediatric population.

Although smell loss has several potential etiologies (e.g., head trauma, allergic rhinitis, and enlarged adenoids) that are common among children, studies evaluating the prevalence of olfactory dysfunction in the pediatric population are rare. Several challenges confront the clinician or researcher hoping to evaluate odor identification ability in young children. Children are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select from alternative choices, which is the typical adult response option. Consequently, specialized forms of olfactory tests must be developed for this population. Based on the format of the San Diego Odor Identification Test(1) and the delivery system of the Brief Smell Identification Test,(2) we are developing a short form odor identification test utilizing standardized odor stimuli in which participants match 6 odorants to pictures of the odor source. The pilot version of this test is being administered to children between the ages of 3-17 as part of the pre-surgical intake evaluation at the A.I. duPont Hospital for Children and as part of basic research studies at the Monell Center. The hospital study population is broad and includes children undergoing ear, nose, and throat surgery as well as controls subjects (children undergoing general surgery), with approximately 50 children per week eligible for evaluation. To improve correct interpretation of the results, stimulus familiarity is evaluated by having the child's parent/guardian also complete the test and answer a short questionnaire about the child's experience with the various odor stimuli. The challenges confronted in studying this clinical population as well as extrapolation to larger populations will be discussed.

The Use of Semantic Differential Scaling to Define the Multi-Dimensional Representation of Odors.

The mental representation elicited by smelling an odor often consists of multiple sensory and affective dimensions, yet, the richness of this elaboration is difficult to capture using methods to rate the intensity of these factors in isolation. Attempts to use language descriptors for olfactory experience have also been shown to be rather limited; among non-specialists, there is no universally accepted system for describing odors, leading to greater reliance on specific item associations. In this study we explored the utility of semantic differential scaling for illustrating the various dimensions of olfactory experience. 300 volunteers rated thirty distinct odorants using 50 SDS adjectives. Three factors emerged from the analysis (based on 17 adjective-pairs) accounting for 53% of the variance, and corresponding to the evaluation, potency and activity dimensions identified for other stimulus types. SD scaling appears to be a viable method for identifying the multiple dimensions of mental representation evoked when smelling an odorant and may prove a useful tool for both consumer and basic research alike. PRACTICAL APPLICATIONS: Although numerous methods of classifying odors have been developed, little agreement has been achieved on the dimensions that are useful to both basic and consumer research. The identification of a set of Semantic Differential adjectives which are relevant to olfactory experience can become a useful tool for classifying the qualitative and affective basis on which odorants differ.. In particular, the degree to which odorants evokes multi-dimensional representations from other sensory modalities (visual, auditory, somatosensory or gustatory), can be usefully applied in the arena of product development both within and across cultures.

Acute sensory irritation from exposure to isopropanol (2-propanol) at TLV in workers and controls: objective versus subjective effects.

OBJECTIVES: Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and naïve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using subjective health symptom reports and objective, physiological end-points; and (ii) differences in measured effects in relation to exposure history. METHODS: Before, during and after exposure subjects gave self-reports of health complaints. During exposure subjects rated the intensity of the odor, sensory irritation and annoyance. Objective end-points of ocular hyperemia, nasal congestion, nasal secretion and respiration were obtained at various times before, during and after exposure. Results were compared with exposure to phenylethyl alcohol (PEA), a negative control for irritation, and to clean air (CA), a negative control for odor and irritation, using a within-subjects design. RESULTS: Significantly higher intensity ratings of odor, irritation and annoyance were reported during the exposure to IPA, when compared with exposure to CA or PEA. Nevertheless, the overall level of reported sensory irritation to IPA was low and perceived as 'weak' on average. Health symptom ratings were not significantly elevated for IPA as compared with PEA or CA exposure. The only physiological end-point that showed a change exclusively in the IPA condition was respiration frequency: relative to baseline, respiration frequency increased in response to IPA in both groups. No differences were encountered between the occupationally exposed and the control groups. CONCLUSIONS: The increase in respiration frequency in response to IPA may reflect either a reflexive change due to sensory irritation (an autonomic event) or a voluntary change in breathing in response to perception of an unpleasant, solvent-like odor (a physiological event caused by cognitive mediation). Our findings on objective end-points, including nasal and ocular sensory irritation, did not confirm subjective irritation reports. Irritation reports and odor intensity decreased, rather than increased, over time, lending credence to the cognitive argument and suggesting that the elevated subjective responses to IPA may be mediated by responses to its odor.