DOI

10.17077/etd.qf6k-fmqq

Document Type

Dissertation

Date of Degree

Fall 2018

Access Restrictions

Access restricted until 01/31/2020

Degree Name

PhD (Doctor of Philosophy)

Degree In

Occupational and Environmental Health

First Advisor

Thorne, Peter S.

First Committee Member

Chrischilles, Elizabeth A.

Second Committee Member

Field, R. William

Third Committee Member

McCray, Paul B.

Fourth Committee Member

Wang, Kai

Abstract

Background: Endotoxin is a lipopolysaccharide located on the outer membrane of the cell wall of Gram-negative bacteria that is widespread in the environment. Although domestic endotoxin has been found to be associated with asthma and wheeze, its association with chronic obstructive pulmonary disease (COPD) is unclear. It is also unknown how environmental exposures influence the relationship between endotoxin and asthma and very few studies have investigated the effectiveness of interventions in reducing endotoxin in the homes of people with asthma.

Goals: The goals of this dissertation were to examine 1) the association of house dust endotoxin with chronic bronchitis or emphysema, two phenotypes of COPD, 2) the influence on the relationship between endotoxin and asthma outcomes of environmental factors such as exposure to dog and cat in homes, climate regions, as well as co-exposure to ambient air pollution, and 3) the effectiveness of an environmental intervention in reducing home endotoxin and asthma symptoms in rural Iowa children with asthma.

Methods: For the first two goals of this dissertation, data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) was used. Dust sampled from the bedroom floor and bedding of 6,963 children and adult participants was evaluated for endotoxin at the University of Iowa Pulmonary Toxicology facility using a kinetic chromogenic Limulus amebocyte lysate assay. Data on asthma outcomes and chronic bronchitis or emphysema (CBE) was collected using questionnaires. Home exposure to dog and cat was considered by pet ownership and levels of dog (Canis familiaris 1) and cat (Feline domesticus 1) allergens in house dust. Annual average particulate matter ≤2.5 µm (PM2.5), ozone (O3), and nitrogen dioxide (NO2) concentrations at participants’ residential location were estimated using the Community Multiscale Air Quality (CMAQ) and Downscaler (DS) models.

In the third goal, data from the Louisa Environmental Intervention Project (LEIP) study which included schoolchildren 5-14 years-old with active asthma from Louisa and Keokuk counties in rural Iowa was analyzed. The households were block-randomized to receive extensive (education + professional cleaning) or educational intervention. Environmental sampling and questionnaire administration were done at baseline and during three follow-up visits.

Results: In the NHANES, the median concentration of endotoxin in house dust was 16.2 EU/mg. In adjusted analysis, house dust endotoxin (log10-endotoxin) was associated with increased odds of CBE diagnosis (OR: 1.27, 95% CI: 1.00-1.61) and chronic bronchitis symptoms (OR: 1.78, 95% CI: 1.01-3.12). Sensitization to inhalant allergens modified the relationship between log10-endotoxin and CBE diagnosis (P(interaction)=0.001), with stronger associations observed in sensitized participants (OR: 2.46, 95% CI: 1.72-3.50).

The association of endotoxin with asthma outcomes was different with climate regions of the U.S. Endotoxin was associated with higher prevalence of wheeze outcomes in the past 12 months in subarctic/very cold/cold regions (OR: 1.48, 95% CI:1.19-1.85) and in hot-humid regions (OR: 1.66, 95% CI:1.04-2.65). In hot-humid regions, endotoxin was positively associated with current asthma (OR: 1.56, 95% CI:1.11-2.18), but negatively with sensitization to any inhalant allergens (OR: 0.83, 95% CI:0.74-0.92). Exposure to dog and cat allergens enhanced endotoxin association with current asthma (OR: 2.00, 95% CI: 1.04-3.83, P(interaction)=0.012) and wheeze in the past 12 months (OR: 1.88, 95% CI: 1.32-2.66, P(interaction)=0.016). House dust endotoxin co-exposure with PM2.5 (CMAQ) was synergistically associated with emergency room visits for asthma in the past 12 months (OR: 5.01, 95% CI: 2.54-9.87) in general. In children, a synergistic association was found for co-exposure to house dust endotoxin and NO2 with the outcome (OR: 3.45, 95% CI: 1.65-7.18).

In LEIP, 104 asthmatic children from 89 homes were included in the study. In the main analysis, extensive compared to the educational intervention was associated with decreased endotoxin load in farm homes (P-value of main effect for intervention <0.0001) and with less frequent nighttime asthma symptoms (Intervention x visit interaction P-value = 0.044). In exploratory analysis, endotoxin load reduction from baseline was associated with less daytime wheeze (OR: 0.59, 95%CI: 0.38-0.91) and daytime cough (OR: 0.62, 95% CI: 0.40-0.97).

Conclusions: House dust endotoxin is associated with obstructive pulmonary diseases. The association of endotoxin with asthma outcomes is stronger in cold regions of the U.S. and is enhanced by exposure to pet allergens and co-exposure to ambient air pollutants such as PM2.5 and NO2 in children. The LEIP study demonstrated that extensive cleaning interventions can be effective at reducing endotoxin in the homes children with asthma and can alleviate their symptoms.

Keywords

Asthma, COPD, Endotoxin, Respiratory Diseases, Wheeze

Pages

xiii, 126 pages

Bibliography

Includes bibliographical references (pages 114-126).

Copyright

Copyright © 2018 Angelico Mendy

Available for download on Friday, January 31, 2020

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