Our asthma research program involves both exposure assessment and prevention components, and focuses on the relationship between environmental exposures and asthma prevalence and morbidity. In collaboration with investigators at the CDC/NCHS, we developed and implemented an allergy/asthma focused component for the National Health and Nutrition Examination Survey (NHANES). This component, included in NHANES 2005-2006, queried on allergy and asthma prevalence and morbidity, measured levels of common indoor allergens and endotoxin in bedroom dust, and quantified total and allergen-specific IgE levels in serum of more than 9000 participants. Analysis of this large data set will allow us to 1) estimate nationwide prevalence of indoor allergen and endotoxin exposures, 2) estimate nationwide prevalence of allergic sensitization to indoor, outdoor and food allergens, 3) estimate nationwide prevalence of allergic diseases, including asthma, and 4) investigate the complex relationships between allergen and endotoxin exposures, allergic sensitization and allergic diseases. The new component not only tested a greater number of allergens across a wider age range than prior studies, but also provided quantitative information on the extent of allergic sensitization and exposures to indoor allergens and endotoxin. It established a second point-in-time estimate for evaluating allergen and endotoxin exposure trends in U.S. homes, the first being established in the National Survey of Lead and Allergens in Housing, which we completed in collaboration with the Department of Housing and Urban Development. NHANES showed that allergens were widespread, but highly variable in U.S. homes. The nations largest indoor allergen study to date demonstrated that more than 90 percent of homes had three or more detectable allergens, and 73 percent had at least one allergen at elevated levels. The presence of pets and pests had a major influence on high levels of indoor allergens, but housing characteristics also mattered; elevated exposure to multiple allergens was more likely in mobile homes, older homes, rental homes, and homes in rural areas. For individual allergens, exposure levels varied greatly with age, sex, race, ethnicity, and socioeconomic status. Differences were also found between geographic locations and climatic conditions. The findings provide beneficial information to a wide audience from allergy and asthma sufferers to clinicians, identifying factors that influence levels of exposure to individual and multiple allergens. To provide a more complete picture, we compared allergen exposures and previously reported sensitization patterns from this national survey. Differences and overlaps between exposure and sensitization patterns in the U.S. population highlight the complex nature of the relationships between allergen exposures, allergic sensitization and disease. Although endotoxin is a recognized cause of environmental lung disease, little is known whether the relationship between endotoxin and respiratory outcomes is influenced by climate. Our NHANES findings suggest that not only the associations with asthma and wheezing related outcomes but also predictors of exposure differ significantly across U.S. climate regions. Endotoxin was positively associated with wheeze or asthma in cold and hot-humid regions, but negatively with sensitization to inhalant allergens in hot-humid regions. Using the NHANES data, we also demonstrated that exposure to endotoxin as well as exposure and sensitization to dog and cat allergens were each independently associated with a higher prevalence of current asthma and/or wheeze in the past 12 months, especially in adults. The association of endotoxin with the respiratory outcomes was significantly altered by exposure to pet allergens and sensitization status. In participants not sensitized to dog, exposure to high levels of dog allergen enhanced the association of endotoxin with wheeze in the past 12 months, while in participants sensitized to cat, exposure to high levels of cat allergen heightened the odds of current asthma associated with endotoxin. The concurrent exposure to high levels of both dog and cat allergens augmented the association of endotoxin with both current asthma and wheeze in the past 12 months. Thus, measures aimed at decreasing the levels of endotoxin and dog and cat allergens in pet owners homes might reduce active asthma and wheeze in long-term. Our NHANES analysis revealed additional novel findings; we showed that exposure to endotoxin found in house dust at doses well below occupational levels was associated with higher odds of having chronic bronchitis symptoms and diagnosis of emphysema or chronic bronchitis in adults. Both chronic bronchitis and emphysema are phenotypes of chronic obstructive pulmonary disease (COPD), which affects more than 15 million Americans and is the third leading cause of death in the U.S. and worldwide. The finding is of public health interest given the ubiquity of endotoxin in our environment and the high morbidity of COPD in the United States. While peripheral white blood cell (WBC) count is well-known in clinical medicine to rise acutely during infection, tissue injury, and certain toxic/occupational exposures, there is much less information available regarding chronic environmental exposures that determine WBC levels in healthy human populations. We used the national survey data to demonstrate for the first time that house endotoxin is positively associated with peripheral WBC count and serum C-reactive protein (CRP). The endotoxin-WBC association was also observed in a cohort of adult farmers and their spouses, with possible effect modification by a TLR4 polymorphism. Taken together with the existing literature on experimental human endotoxin inhalation, these findings suggest the provocative postulate that leukocyte number and systemic inflammatory state in healthy human subjects may be measurably influenced by real-world residential exposure to endotoxin in diverse settings. In collaboration with several federal agencies and national asthma experts, we developed and implemented a supplemental questionnaire for the National Ambulatory Medical Care Survey (NAMCS), an ongoing nationally representative survey that covers visits to office-based physicians and clinicians in community health centers (CHCs). The one-time supplemental questionnaire in the NAMCS 2012 was designed to assess clinician agreement, self-efficacy and self-reported adherence with the asthma guidelines at the national level. Findings from this study demonstrated notable differences in guideline agreement, adherence, and implementation among asthma care clinicians. Agreement and adherence to the asthma guidelines were higher for specialists than primary care clinicians but are low for both groups for several key recommendations. An understanding of clinician attitudes, beliefs and practices relative to guideline adherence is important and can inform new guidelines and future studies. The study findings may help to identify areas and approaches for future research and implementation strategies, including those that are clinician group-specific and those that focus on recommendations that are currently not embraced by either clinician group. Since the NHANES data set allows for the investigation of many interesting relationships, we continue to study the complex relationships between allergen exposure, allergic sensitization, and disease in more detail. Our research will lead to a better understanding of the characteristics of residential indoor allergen and endotoxin exposures and their role in allergic disorders, which in turn provides insights into development of effective environmental intervention approaches for the management of allergic diseases such as asthma.

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21
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2018
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U.S. National Inst of Environ Hlth Scis
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Mendy, Angelico; Wilkerson, Jesse; Salo, Päivi M et al. (2018) Exposure and Sensitization to Pets Modify Endotoxin Association with Asthma and Wheeze. J Allergy Clin Immunol Pract :
Salo, Päivi M; Wilkerson, Jesse; Rose, Kathryn M et al. (2018) Bedroom allergen exposures in US households. J Allergy Clin Immunol 141:1870-1879.e14
Cloutier, Michelle M; Salo, Paivi M; Akinbami, Lara J et al. (2018) Clinician Agreement, Self-Efficacy, and Adherence with the Guidelines for the Diagnosis and Management of Asthma. J Allergy Clin Immunol Pract 6:886-894.e4
Mendy, Angelico; Salo, Päivi M; Cohn, Richard D et al. (2018) House Dust Endotoxin Association with Chronic Bronchitis and Emphysema. Environ Health Perspect 126:037007
Mendy, Angelico; Wilkerson, Jesse; Salo, P?ivi M et al. (2018) Endotoxin predictors and associated respiratory outcomes differ with climate regions in the U.S. Environ Int 112:218-226
Gergen, Peter J; Mitchell, Herman E; Calatroni, Agustin et al. (2018) Sensitization and Exposure to Pets: The Effect on Asthma Morbidity in the US Population. J Allergy Clin Immunol Pract 6:101-107.e2
Salo, Päivi M; Zeldin, Darryl C (2018) Mite-impermeable bedding casings and severe asthma exacerbations. J Pediatr 192:266-269
Gold, Diane R; Adamkiewicz, Gary; Arshad, Syed Hasan et al. (2017) NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and childhood asthma-implications for home environmental intervention in asthma prevention and management. J Allergy Clin Immunol 140:933-949
Fessler, Michael B; Carnes, Megan U; Salo, Päivi M et al. (2017) House Dust Endotoxin and Peripheral Leukocyte Counts: Results from Two Large Epidemiologic Studies. Environ Health Perspect 125:057010
McGowan, Emily C; Matsui, Elizabeth C; Peng, Roger et al. (2016) Racial/ethnic and socioeconomic differences in self-reported food allergy among food-sensitized children in National Health and Nutrition Examination Survey III. Ann Allergy Asthma Immunol 117:570-572.e3

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