Pamela Dalton, Ph.D, MPH - US grants

DESCRIPTION: The first aim of this application is to determine if perceptual responses to odors can be influenced by labels provided by the experimenter or by a subject's implicit beliefs about the health benefits or hazards of the stimulus. In Experiment 1, subjects will rate the intensity of a suprathreshold concentration of an ambient odorant and clean air. Pre and -1-A second aim of the project will be to determine the ability of attention or arousal to influence the perceptual responses to odors previously classified as "hazardous." Experiment 3 will use the psychophysical tests described in Experiment 1 except that subjects will be given a task that either has high or low demands on attention during the odor exposure period. High demand subjects will rate intensity every minute whereas low demand subjects will rate the intensity only at the beginning and end of the exposure period. In Experiment 4, the subjects will be presented with continuous 85 dB white noise (high arousal) or 60 dB white noise (non-arousal) delivered through headphones during the odor exposure period.

The overall goal of this proposal is to understand how an individual's experience of chemical exposure is related on the one hand to the sensory and physiological signals resulting from exposures to volatile compounds and on the other hand to psychological processes involved in perception, memory, and judgment. The proposed research pursue this goal by using an information-processing analysis of chemosensory perception as a unifying framework. Such an analysis seeks to describe how individuals process, combine, and interpret both the primary (sensory) and secondary (physiological) signals from chemosensory exposure and to understand how certain variables, such as personality factors, attentional and memory-retrieval strategies, and attributional tendencies, produce variations in the response. The three specific aims of the proposed research are: (1) to examine the role of selected antecedent, subject-based factors in producing variations in response to volatile organic compound (VOC) exposure, specifically, the roles of pre-existing dispositional factors such as negative affectivity and of pre-existing processing structures or mental models; (2) to examine the role of situational factors in producing variations in response to VOC exposures, specifically, the roles of instructional manipulation, multi- task processing, and social cues that guide the content and direction of attention during exposure to a volatile compound; and, (3) to examine the role of attributions (and misattributions) pertaining to arousal in producing variations in response to VOC exposure, specifically, the degree to which diffuse arousal tends to be prejudicially attributed to VOC exposure. The research will increase our understanding of the variation in human chemosensory perception. It has important implications for efforts to alleviate people's adverse responses to volatile compounds in indoor and outdoor air, and it may be of particular utility for addressing the higher incidence among women of adverse responses to low-level chemical exposures. The results can also provide information needed to evaluate the locus of responses (i.e., sensory, physiological, psychological) to volatiles that are currently advocated as alternative therapies.

The overall goal of this project is to describe the variation in the dynamics of olfactory adaptation and recovery, and to relate the contribution of per-receptor mechanisms involved in odorant transport and clearance to this variation. The proposed research will pursue this goal through experimental and clinical studies aimed at elucidating the range and sources of variation in adaptation, and by developing a mathematical model of olfactory adaptation to serve as a unifying framework. The three specific aims of the proposed research are: (1) to evaluate the extent to which peri-receptor processes involved in odorant transport and clearance can modulate the time-course of adaptation and recovery, (2) to characterize the variation in the dynamic response of a challenged olfactory system as a function and clinical etiology and age, especially among clinic patients who report rapid and prolonged adaptation to ambient and food-mediated odors, and (3) to develop a mathematical transport model of olfactory adaptation capable of simulating the odorant transport, accumulation and clearance in the nasal/olfactory region, and if appropriate, the time-course of receptor adaptation and recovery (as measured in Project 1). This project will increase our understanding of the role of peri-receptor events in the development of both short- and long-term adaptation and recovery. Moreover, through interactions with Project 4 in this CCRC we will obtain a better understanding of the relationship between receptor and peri-receptor events in adaptation. The project has important implications for efforts to remediate dynamic olfactory loss in real world situations. Although rapid adaptation is frequently reported in clinical evaluations, current clinical assessments of olfactory dysfunction do not include tests that measure rates of adaptation and recovery. However, abnormal rates of adaptation or recovery could significantly diminish olfactory sensitivity, as well as render individuals more vulnerable to hazards such as gas leaks, fires and spoiled food. Aberrant adaptation and/or recovery could also contribute to nutritional problems by reducing the perception and enjoyment of food. Peri-receptor mechanisms that contribute significantly to dynamic olfactory loss may be amenable to therapeutic interventions for restoring certain aspects of olfactory function.

DESCRIPTION (provided by applicant): Variation in the perception of environmental health risks and adverse response to airborne chemical exposures constitutes a complex public health challenge for policy makers, the medical profession and the public. The goal of this project is to develop a comprehensive map of factors that determine how the subjective experience from an airborne chemical exposure is related to (1) the sensory and physiological effects that are directly elicited by the chemical and (2) the psychological processes involved in perception, memory and judgment that can indirectly mediate health effects from chemical exposures. Our findings to date continue to support the perspective that among healthy individuals, expectancies related to the chemical or the exposure situation, modulated by factors such as exposure history or personality type, lead to significant variation in an individual's response to a chemical exposure. These factors are likely to be enhanced and consequently have a greater public health impact for individuals with pre-existing respiratory disease, such as asthma. The current proposal will extend our understanding of the interaction between cognitive beliefs, expectancies and physiological responses to odors and irritants by studying those of asthmatics, for whom there is both greater perceived and actual health risk from chemical exposures. This effort will lead to better identification of the respiratory health impact of exposure to a range of odorous chemicals for nearly 17 million Americans, and may possibly identify therapies via autonomic regulation and feedback that may be particularly useful for ameliorating the adverse response of these individuals to a range of airborne chemical exposures.

Olfactory dysfunction increases susceptibility to the hazards of fire, ingestion of spoiled food and exposure to chemical toxins, and it can lead to nutritional problems and reduce the quality of life. These risks are heightened in the workplace. Yet, more than 10% of the U.S. workforce approximately 14 million people) has daily occupational exposure to chemicals or particulates and as many as 40% of these individuals report symptoms of chronic nasal inflammation or rhinitis that are known precursors of olfactory loss. Despite this, the evaluation of olfactory function in susceptible occupational cohorts is rarely performed and consequently, little is known about the prevalence of and mechanisms underlying chemical-induced olfactory dysfunction in humans. Because the mechanisms of olfactory dysfunction secondary to chemical exposure are likely to be multi-factorial, including anatomical changes (e.g., congestion, polyposis), changes in mucociliary transport and direct effects of inflammatory mediators on the olfactory neuroepithelium, this proposal takes a multi-pronged approach to provide a comprehensive, longitudinal clinical evaluation of the chemosensory function, nasal inflammatory processes and airflow patterns among individuals with prospective and ongoing chemical exposures. Using techniques developed in the current funding period and advances in our ability to numerically model olfactory transport and deposition in individualized patient models, we propose to study three cohorts with exposure to putative olfactory toxicants. We will evaluate chemosensory function at multiple timepoints before, during and after exposure (Aim 1) and develop profiles of the physical and biochemical inflammatory changes that occur in the noses of exposed individuals (Aim 2). In addition to the clinical cohorts, we will develop a database of olfactory function based on job type by screening individuals with chemical exposures who are referred to the University of Pennsylvania Occupational Medicine Clinic. In Aim 3, we will use our computational model to evaluate the impact of inflammatory changes in nasal airflow which are responsible for olfactory toss secondary to chemical exposures and nasal-sinus disease (in Project 1). Results of these studies will provide an important resource for predicting and mitigating the effects from occupational chemical exposure on chemosensory function. These findings will inform policies and practices to protect the sensory function and health of both young adults and the elderly, for whom chemical exposure appears to increase the severity of age-related sensory declines. Through evaluation of a wide range of relevant characteristics, the outcome will also support reasoned predictions about risk factors that may mitigate or exacerbate the functional chemosensory impact of inflammatory processes, which are prevalent in the general population from a variety of chronic health and exposure conditions.

Project Abstract: The Monell Chemical Senses Center Institutional (T32) Postdoctoral Training Program provides a unique opportunity for postdoctoral fellows to obtain training at the world?s foremost center for research into the chemical senses?taste and smell. Twenty-three faculty members have diverse scientific and international backgrounds and conduct collaborative, multidisciplinary research using specialized methods derived from disciplines such as electrophysiology, molecular biology, genetics, analytical chemistry, and psychophysics. Many applicants to the training program have little background in chemosensation but are given the opportunity to apply skills learned elsewhere to chemical senses research. In addition to specialized hands-on research training provided by faculty mentors, fellows attend instructional courses, workshops, and journal clubs; they have opportunities for small-group review of data, one-on-one assistance with clear scientific communication, and instruction on academic ethics tailored to their stage of professional development. A three-person mentoring committee helps formulate an individual training plan for each fellow?s unique career path and then tracks the fellow?s progress, helps set practical scientific goals, suggests skill development opportunities (e.g., learning new statistical or wet-lab techniques), and provides written feedback every six months. There is emphasis on learning the skills to prepare results for publication and to write successful research grants. During the previous funding period, Monell?s T32 program supported nine postdoctoral fellows; four are still in training, and five now have positions in academic institutions or elsewhere in the biomedical research workforce. All the trainees have published papers in appropriate peer-reviewed journals, attended national and/or international conferences, sought specialized training in courses and workshops, and become familiar with new standards for the responsible conduct of research (including rigor and reproducibility). Four trainees have won awards for excellence in research; others have won competitive research grants, including three Individual Research Training Grants (F32s) and one similar governmental award. The long-term goal of Monell?s Postdoctoral Training Program is to train independent scientists in taste and smell biology, part of NIH?s mission to improve the nation?s health.

PROJECT SUMMARY Smell loss is a predominant symptom of COVID-19, and initial evidence based on self-reports suggests that chemosensory loss is a sensitive predictor of COVID-19 in the general population, more so than fever. However, given the natural lack of awareness of chemosensory changes, self-reports underestimate the true prevalence of smell loss in patients with COVID-19 by 20% compared to an objective test. Therefore, we propose testing and deploying a rapid and objective measure of smell ability, the SCENTinel test, inspired by the NIH Toolbox® Odor Identification Test that our team previously developed. SCENTinel is an inexpensive, and convenient smell test for COVID-19 surveillance of the population that quickly and easily assesses three smell loss factors: odor detection, odor intensity, and odor identification. It is designed for practical use in several contexts, including high-density areas such as community medical sites, universities, subacute care facilities, and both industrial and nonindustrial workplaces. Our multi-disciplinary team has expertise in understanding taste and smell, developing and validating chemosensory tests, as well as studying the broad symptomatology of COVID-19. The group is led by MPI Dalton from the Monell Chemical Senses Center, an expert in human olfaction and designing olfactory tests; MPI Parma from Temple University is an expert in COVID-19 smell loss, is the Chair of the Global Consortium for Chemosensory Research, and has expertise in conducting research in rapidly changing situations; Dr. Schalet and his team at Northwestern University and Dr. Chun and his team at Yale University, among the other established and interested partners (Fox subacute nursing homes, Hormel Food). Our team also includes the Director of Technology Transfer at the Monell Center, Dr. O?Leary, to explore potential partners and expand SCENTinel deployment nationwide. Dr. Reed from the Monell Chemical Senses Center will work directly with the Data Coordination Center, drawing on her experience in managing large shared NIH datasets. All will work closely with the NIH Project Scientist. This proposal aims to a) fine-tune SCENTinel?s ability to predict a positive COVID-19 diagnostic test; b) examine marginal smell loss as a sign of the earliest phases of COVID-19, before a positive diagnostic test; and c) assess the test?s psychometric validity with test-retest reliability measures and validation against the NIH Toolbox® Odor Identification Test. Together, these aims will establish a standardized protocol for use of SCENTinel as a rapid and objective smell test that can easily be incorporated into onsite COVID-19 testing centers, schools, and workplaces nationwide. Furthermore, it will provide key insights into early-onset chemosensory symptoms in relation to a confirmed COVID-19 diagnosis, providing a crucially needed means to contain the spread of COVID-19.