title: House Dust Endotoxin Levels Are Associated with Adult Asthma in a U.S. Farming Population.
abstract: BACKGROUND
  Endotoxin initiates a proinflammatory response from the innate immune system. Studies in children suggest that endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations.
  
  
  OBJECTIVE
  To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population.
  
  
  METHODS
  Dust was collected from the bedrooms (n = 2,485) of participants enrolled in a case-control study of current asthma (927 cases) nested within the Agricultural Health Study. Dust endotoxin was measured by Limulus amebocyte lysate assay. Outcomes were measured by questionnaire, spirometry, and blood draw. We evaluated associations using linear and logistic regression.
  
  
  RESULTS
  Endotoxin was significantly associated with current asthma (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.14-1.47), and this relationship was modified by early-life farm exposure (born on a farm: OR, 1.18; 95% CI, 1.02-1.37; not born on a farm: OR, 1.67; 95% CI, 1.26-2.20; Interaction P = 0.05). Significant positive associations were seen with both atopic and nonatopic asthma. Endotoxin was not related to either atopy or wheeze. Higher endotoxin was related to lower FEV1/FVC in asthma cases only (Interaction P = 0.01). For asthma, there was suggestive evidence of a gene-by-environment interaction for the CD14 variant rs2569190 (Interaction P = 0.16) but not for the TLR4 variants rs4986790 and rs4986791.
  
  
  CONCLUSIONS
  House dust endotoxin was associated with current atopic and nonatopic asthma in a U.S. farming population. The degree of the association with asthma depended on early-life farm exposures. Furthermore, endotoxin was associated with lower pulmonary function in patients with asthma.
authors.affiliation: 1 Epidemiology Branch and.
authors.forename: Megan Ulmer
authors.initials: MU
authors.lastname: Carnes
authors.affiliation: 2 Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hoppin
authors.affiliation: 3 Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa.
authors.forename: Nervana
authors.initials: N
authors.lastname: Metwali
authors.affiliation: 1 Epidemiology Branch and.
authors.forename: Annah B
authors.initials: AB
authors.lastname: Wyss
authors.affiliation: 4 Hankinson Consulting, Inc., Athens, Georgia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hankinson
authors.affiliation: 5 Social & Scientific Systems, Inc., Durham, North Carolina.
authors.forename: Elizabeth Long
authors.initials: EL
authors.lastname: O'Connell
authors.affiliation: 6 Westat, Durham, North Carolina.
authors.forename: Marie
authors.initials: M
authors.lastname: Richards
authors.affiliation: 6 Westat, Durham, North Carolina.
authors.forename: Stuart
authors.initials: S
authors.lastname: Long
authors.affiliation: 7 Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland; and.
authors.forename: Laura E Beane
authors.initials: LE
authors.lastname: Freeman
authors.affiliation: 1 Epidemiology Branch and.
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.affiliation: 8 Respiratory Health Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Department of Health and Human Services, Morgantown, West Virginia.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Henneberger
authors.affiliation: 5 Social & Scientific Systems, Inc., Durham, North Carolina.
authors.forename: Christie
authors.initials: C
authors.lastname: Barker-Cummings
authors.affiliation: 9 Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
authors.forename: David M
authors.initials: DM
authors.lastname: Umbach
authors.affiliation: 3 Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.affiliation: 1 Epidemiology Branch and.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
mesh_terms: D000368:Aged; D000383:Agriculture / Q000706:statistics & numerical data*; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D004391:Dust / Q000032:analysis*; D004731:Endotoxins / Q000032:analysis*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012135:Respiratory Sounds; D011795:Surveys and Questionnaires; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: D004391:Dust; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: CD14; TLR4; atopy; pulmonary function; wheeze