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Environmental and personal risk factors for Sarcoidosis: a case-control study

Britton, Rachel N. (2017) Environmental and personal risk factors for Sarcoidosis: a case-control study. Master Essay, University of Pittsburgh.

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Abstract

Rationale
Sarcoidosis is a life threatening systemic disease characterized by granulomatous inflammation in affected organs. There is significant clinical heterogeneity in both manifestation and disease course. Sarcoidosis is seen worldwide, however, there is tremendous difference in the prevalence of sarcoidosis between different racial groups and the sexes. In the U.S., sarcoidosis affects 8.8 people out of 100,000 yearly; however, incidence rates vary widely between the races with 8.1 per 100,000 white individuals affected by sarcoidosis compared to 17.8 per 100,000. Females have a higher age-adjusted incidence rate (6.3 per 100,000) than males (5.9 per 100,000). Populations with exposure to specific environmental exposures have higher incidence rates of sarcoidosis as well. Although recent research has provided increased understanding of immunological pathways involved in sarcoidosis, determinants of the clinical course and manifestations as well as the etiologic processes remain uncertain. The human microbiome is increasingly recognized as a critical determinant of health and disease. The role of the microbiome in the pathobiology of immunologic diseases is as of yet unexplored. The microbiome may be responsible for the differences in clinical outcomes in sarcoidosis.
Objective
The analysis presented here aims to describe the epidemiology of sarcoidosis and risk factors using a subset of cases with sarcoidosis and a comparison group of individuals with a diagnosis of Alpha-1 Antitrypsin Deficiency (AATD). The objective of this analysis is to examine differences in residential, occupational, chemical and personal exposures and to characterize the gut fungal microbiome, the mycobiome, of participants with both disease types. In studying the mycobiome of sarcoidosis cases, the objective is to determine if distinct patterns in the microbiome are characteristic of sarcoidosis phenotypes.
Methods
A subpopulation of 96 participants from the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study were included in an analysis that compared environmental exposures and personal risk factors between those with sarcoidosis (cases) and those with AATD (controls). Mycobiome analysis was performed on stool samples from participants with sarcoidosis. Comparisons between abundance of fungi were made between clinical phenotype groups.
Results
A significant negative association was found between some environmental exposures including exposure to animal droppings (OR: 0.41, CI:0.17-0.96, p=0.04) and use of an air conditioner (OR:0.19, CI: 0.05-0.71, p=0.014). A significant association was made between exposure to parakeets and sarcoidosis (OR: 0.23, CI:0.08-0.66, p=0.006). No significant association was found between sarcoidosis and industrial exposures including metallurgic, organic and inorganic exposures. Differences were found in the abundance of fungi in the stool of phenotypically different participants with sarcoidosis, with differences in both the Saccharomyceales and Nectriaceae families.
Conclusion
Sarcoidosis is a life-threatening disease that can cause significant disability in affected individuals. The etiology and heterogeneity in clinical outcomes remains unclear. However, understanding role of microbial and environmental exposure in activation of inflammatory pathways in sarcoidosis may elucidate the etiological mystery. Discerning biological signatures specific to clinical phenotypes would provide for predictive biomarkers for disease outcomes. The potential therapeutic advances such a biomarker would allow for represent a significant advance in precision medicine and the potential for significant public health efforts toward prevention and awareness. The understanding the clinical determinants and risk factors would allow for the development of public health programs targeting those in at-risk occupations or populations for possible prevention activities and additional screening.


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Details

Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Britton, Rachel N.rnb20@pitt.edurnb20000-0001-9420-9718
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairTalbott, Evelyneot1@pitt.eduUNSPECIFIEDUNSPECIFIED
Committee MemberMorris, Alisonmorisa@upmc.eduUNSPECIFIEDUNSPECIFIED
Committee MemberAdibi, Jennieradibij@pitt.eduUNSPECIFIEDUNSPECIFIED
Date: 15 December 2017
Date Type: Submission
Submission Date: 27 November 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 142
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: Sarcoidosis Microbiome
Date Deposited: 16 Jul 2018 21:09
Last Modified: 01 Jan 2021 06:15
URI: http://d-scholarship.pitt.edu/id/eprint/33645

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