C-reactive protein from dried blood spots: Application to household air pollution field studies.

Household air pollution (HAP) is estimated to be an important risk factor for cardiovascular disease, but little clinical evidence exists and collecting biomarkers of disease risk is difficult in low-resource settings. Among 54 Nicaraguan women with woodburning cookstoves, we evaluated cross-sectional associations between 48-hour measures of HAP (eg, fine particulate matter, PM2.5 ) and C-reactive protein (CRP) via dried blood spots; secondary analyses included seven additional biomarkers of systemic injury and inflammation. We conducted sub-studies to calculate the intraclass correlation coefficient (ICC) in biomarkers collected over four consecutive days in Nicaragua and to assess the validity of measuring biomarkers in dried blood by calculating the correlation with paired venous-drawn samples in Colorado. Measures of HAP were associated with CRP (eg, a 25% increase in indoor PM2.5 was associated with a 7.4% increase in CRP [95% confidence interval: 0.7, 14.5]). Most of the variability in CRP concentrations over the 4-day period was between-person (ICC: 0.88), and CRP concentrations were highly correlated between paired dried blood and venous-drawn serum (Spearman ρ = .96). Results for secondary biomarkers were primarily consistent with null associations, and the sub-study ICCs and correlations were lower. Assessing CRP via dried blood spots provides a feasible approach to elucidate the association between HAP and cardiovascular disease risk.

Association of Toll-like receptor 4 alleles with symptoms and sensitization to laboratory animals.

BACKGROUND: Researchers and technicians working with laboratory animals (LAs) are exposed to animal allergen and endotoxin, which can interact to potentiate or inhibit symptoms or allergic responses. We hypothesized that functional genetic variants of Toll-like receptor 4 (TLR4), a key surface receptor for endotoxin, interface between worker and workplace and affect animal sensitization, symptoms, or both. OBJECTIVE: We sought to determine whether TLR4/8551 variants alter the risk for LA sensitization, symptoms, or both. METHODS: Three hundred thirty-five researchers, 195 of whom worked with animals, completed questions on workplace practices and symptoms and underwent skin prick tests or RASTs to common and animal allergens. Real-time PCR assessed TLR4/8551 and TLR4/8851 variants. Nominal logistic regression was used to analyze the contribution of demographic, exposure, and genetic variables to outcomes of interest. RESULTS: Twenty-one percent of workers were LA sensitized, and 29% reported 1 or more symptoms to LAs. The TLR4/8551 G variant, which is less responsive to endotoxin, was detected in 9% and in linkage disequilibrium with the TLR4/8851 T allele. The G variant significantly associated with atopy and LA sensitization. Workers with the G variant spent significantly longer hours in high endotoxin/animal allergen tasks compared with those with the AA variant, which is perhaps less affected by endotoxin exposures. In multivariate analyses the G variant and longer animal research hours increased the risk of LA sensitization. Job tasks and LA sensitization, but not TLR4 variants, were predictors of LA-induced symptoms. CONCLUSION: Workers with TLR4 variants that reduce responsiveness to endotoxin have higher risks for LA and other allergen sensitization but spend longer hours in tasks with high endotoxin and animal allergen exposures.