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House Dust Endotoxin and Peripheral Leukocyte Counts: Results from Two Large Epidemiologic Studies

Michael B. Fessler, Megan U. Carnes, Päivi M. Salo, Jesse Wilkerson, Richard D. Cohn, Debra King, Jane A. Hoppin, Dale P. Sandler, Greg Travlos, Stephanie J. London, Peter S. Thorne, and Darryl C. Zeldin.
Environmental Health Perspectives (2017). DOI: https://doi.org/10.1289/EHP661 PMID: 28599265

Publication

Abstract

BACKGROUND: The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood.

OBJECTIVES: We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects.

METHODS: The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (TLR4), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term.

RESULTS: There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×103/μL (95% CI: 0.070, 0.301×103/μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15).

CONCLUSIONS: This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings.

Figures

Figure 1. Weighted penalized B-spline of white blood cell (WBC) count.

Weighted penalized B-spline of white blood cell (WBC) count through the full range of household dust endotoxin concentration in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 study population.

Tables

Table 1. Linear regression of the change in white blood cells and serum C-reactive protein.

Linear regression of the change in white blood cells and serum C-reactive protein associated with a 10-fold increase in house dust endotoxin concentration, in the overall NHANES 2005–2006 study population and within disease/symptom strata.

Table 2. Linear regression of the change in absolute count of WBC subtypes.

Linear regression of the change in absolute count of WBC subtypes associated with a 10-fold increase in house dust endotoxin concentration in the NHANES 2005–2006 study population.

Table 3. Linear regression of the change in count of leukocyte subtypes.

Linear regression of the change in count of leukocyte subtypes in NHANES 2005–2006 study population associated with a 10-fold increase in house dust endotoxin concentration within strata of smoking status and serum cotinine.

Table 4. Linear regression of the change in absolute count of total WBC and WBC subtypes.

Linear regression of the change in absolute count of total WBC and WBC subtypes associated with a 10-fold increase in house dust endotoxin concentration in the ALHS.

Table 5. Gene by environment interaction analysis of WBC count and log10 house dust endotoxin.

Gene by environment interaction analysis of WBC count and log10 house dust endotoxin in the ALHS study population.

Supplemental Materials

Supplemental Material