Translational Program in Rhinology Research

The goals of our research agenda are:
1) to improve knowledge of basic nasal physiology
2) to develop and test novel treatments for chemosensory and upper airway diseases
3) to utilize immunologic methods to understand sinonasal inflammation
4) to determine factors that underlie susceptibility to olfactory and sinonasal disease using genetic and population approaches

Diseases of Interest

Chronic Rhinosinusitis
Sinusitis is an important public health problem in the US, with a substantial impact. Although its true incidence and prevalence is unknown, sinusitis was the most frequently reported chronic disease in the 1998 National Health Interview Survey, with about 16.3% of respondents affected. This disease is responsible for 18-22 million physician office visits, 29,000 hospital discharges, and 170,000 sinus surgeries, 73 million days of restricted activity, and an estimated $5.8 billion expenditure annually. Most importantly, chronic rhinosinusitis causes a significant impact on quality of life with resultant functional and emotional impairment.

The hallmark of CRS is extensive sinus mucosal inflammation. Understanding how the dysregulation of mucosal immune responses leads to a chronic inflammatory state in the sinuses coupled with the ability to manipulate these responses would provide a major advance in the field and remains our goal.

Age-Related Olfactory Decline
Olfactory decline in aging affects up to 24.5% of persons over age 53 and rising to 62.5% in those over age 80. Approximately 14 million Americans over age 55 are estimated to have chronic olfactory impairment. The impact of this special sensory impairment leads to more than 200,000 physician visits to each year for chemosensory complaints. Olfactory dysfunction can cause major problems for the older persons. The sense of smell plays an important role in pleasure, including the palatability and flavor of food, and can even modify dietary behavior and nutrition. Patients with impaired olfaction have a decreased ability to detect hazards in the environment, including smoke, spoiled food, toxins, and gas leaks. Olfaction influences mood, cognition, and behavior. Thus, olfactory sensory loss is related to a number of health and social factors critical to the physical and social function and quality of life in older adults. Unfortunately, physicians have little prognostic information and few diagnostic tests or therapeutic options for the vast majority of patients with olfactory dysfunction.

Therapeutic options for olfactory impairment are empiric and severely limited by the currently poor understanding of the pathophysiology of impaired olfaction. Understanding which factors predispose to olfactory loss would provide advances in clinical care as well as important contributions to the basic understanding of the olfactory system and how it changes with age in humans.

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Projects

Genetics of Age-Related Olfactory Decline
In collaboration with Carole Ober in Human Genetics, we are employing genome wide association studies in a founder population to identify genetic variation that underlies age-related olfactory loss using quantitative traits. We have recently published the first successful linkage study for an olfactory trait in humans. Findings will be replicated in a well characterized aging cohort (NSHAP—see below).

Genetics of Chronic Rhinosinusitis
Again in collaboration with Carole Ober, we have identified subjects with chronic rhinosinusitis and performed the first linkage study for this complex trait. With an expanded sample of newly phenotyped subjects, we plan new linkage analyses with high density markers to further refine our previous work. We are also recruiting subjects in Chicago for further case-control studies of variation in relevant candidate genes.

Regulatory T cells in Chronic Rhinosinusitis
To investigate the role of the regulatory T cells in chronic rhinosinusitis and nasal polyposis, we are examining the presence and function of these cells in the nose and periphery. Immunologic phenotyping is performed using gene expression, flow cytometry, immunohistochemistry, and cytokine production in subjects with disease and controls.

Treatment of Olfactory Dysfunction in Seasonal Allergic Rhinitis
This is a clinical trial to determine if intranasal steroids can improve olfactory dysfunction in seasonal allergic rhinitis in humans.

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Interdisciplinary Collaborations

Demographic Factors in Age-Related Olfactory Decline
In collaboration with Linda Waite in Sociology, we are employing the National Social Life, Health, and Aging Project (NSHAP) data set to study the demographic and other non-genetic factors that are associated with olfactory decline in aging. This data set will also serve as a replication sample for genetic studies described above and complements that work. Other collaborators on this project include Martha McClintock in Psychology and William Dale in Geriatric and Palliative Medicine.

Effects of Pollution on Respiratory Disease
In collaboration with Argonne National Laboratory and Edward Naureckas and Fuad Baroody, we are studying the effects of pollution on upper and lower airway inflammatory disease.

Immersive simulation and airway management
In collaboration with Stephen Small in Anesthesiology and Elizabeth Blair, we are using high fidelity immersive simulation in an innovative project to measure and improve professionalism in resident education using emergency airway management as a topic. Ethical issues are addressed in partnership with Peter Angelos in General Surgery.

Olfaction and Psychiatric Disease
In collaboration with Royce Lee and Kristen Jacobsen in Psychiatry, we are examining translational studies relating the olfactory and central nervous system as it relates to psychiatric disease. This work includes gene expression studies in olfactory epithelium in conjunction with Yoav Gilad in Human Genetics.

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Jayant Pinto, MD

Pinto Group Links

Translational Program in Rhinology Research

Diseases of Interest

Projects

Interdisciplinary Collaborations