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Association Between Amyotrophic Lateral Sclerosis (ALS) and Environmental Exposures: A Case-Control Study

Wu, Fan (2023) Association Between Amyotrophic Lateral Sclerosis (ALS) and Environmental Exposures: A Case-Control Study. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Amyotrophic lateral sclerosis (ALS) is a rare, rapidly progressive, and fatal neurodegenerative disease, with an average age at onset of 51-66 years and a mean survival of 2-5 years. Few risk factors have been identified for ALS that include male sex, older age, and family history, especially for sporadic ALS which comprises 90-95% of all cases. However, environmental exposures and gene-environment interaction have been suspected as risk factors. Ambient air exposure, an important environmental exposure, has been associated with neurodegenerative diseases including dementia, Parkinson’s disease, and Alzheimer's disease. However, there have been only a limited number of studies on the association between ambient air toxic exposure, and in particular neurotoxic compounds, and ALS. To add evidence to the knowledge of ALS etiology, we conducted a case-control study involving 267 ALS patients from the Agency for Toxic Substances and Disease Registry (ATSDR)/Centers for Disease Control and Prevention (CDC) National ALS Registry and Biorepository and 267 population-based matched controls to investigate the association between residential exposure to air neurotoxicants and ALS. Levels of 34 air pollutants were estimated at study subjects’ residential ZIP code using census tract-level United States Environmental Protection Agency (USEPA) National Air Toxics Assessment (NATA) data for 2011. Additionally, using 2011 and 2014 NATA, this exposure assignment method was evaluated by comparison to the standard NATA-assignment method based on the street address of the controls. We found higher residential air exposure levels of 2,4-dinitrotoluene, carbon disulfide, vinyl chloride, cadmium, and cyanide were associated with elevated ALS risk, with the evidence strongest for 2,4-dinitrotoluene (Q4 vs. Q1: adjusted OR=5.45, 95% CI: 1.53-19.36) and cyanide (Q4 vs. Q1: adjusted OR=4.34, 95% CI: 1.52-12.43). We also found that residential exposure to higher levels of ambient organic/chlorinated solvents (Q4 vs. Q1: adjusted OR=2.62, 95% CI: 1.003-6.85) was associated with ALS. Evaluation of our exposure assignment method suggested that it provided reliable exposure estimation results overall, although noted differences particularly for volatile organics (styrene, toluene, and 1,1,1-trichloroethane) in urban residences. These findings show the value of use of such exposure databases in the ongoing surveillance of air toxics exposure for populations at risk.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Wu, Fanfaw19@pitt.edufaw190000-0002-8863-3026
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBarchowsky, Aaronaab20@pitt.eduaab20
Thesis AdvisorTalbott, Evelyneot1@pitt.edueot1
Committee MemberBuchanich, Jeaninejeanine@pitt.edujeanine
Committee MemberFabisiak, Jamesfabs@pitt.edufabs
Committee MemberSharma, Ravirks1946@pitt.edurks1946
Committee MemberArena, Vincentarena@pitt.eduarena
Committee MemberMalek, Angelamalek@musc.edumalek
Date: 28 June 2023
Date Type: Publication
Defense Date: 22 May 2023
Approval Date: 28 June 2023
Submission Date: 23 June 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 184
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Environmental and Occupational Health
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Amyotrophic lateral sclerosis, ALS, Air Toxicant, Risk Factor, National Air Toxics Assessment, NATA, Exposure Assignment
Date Deposited: 28 Jun 2023 15:33
Last Modified: 28 Jun 2023 15:33


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