Comparing and Validating Dried Blood Spots with Plasma for Cytokine Assessments in Environmental Exposure Settings Open Access

Qian, Yuchen (2015)

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Introduction: Traffic air pollution has been linked with many adverse health effects including asthma and acute systemic inflammation. Measuring biomarker levels has been widely utilized in environmental research settings to examine systemic inflammation after exposure to traffic air pollutants. However, the traditional venipuncture sampling method is invasive and requires clinical settings for sample collection, which limits its use among research studies in large population. A new sampling method, Dried Blood Spots (DBS), has been introduced to be a promising alternative to venipuncture, while few studies addressed its application in environmental research settings. This study is aimed to compare and validate DBS with plasma for cytokine assessments in environmental exposure settings.

Methods: Each subject in the study conducted a highway commute and was randomly and equally assigned a surface street commute or indoor clinic exposure as a comparison. DBS and plasma samples were collected at the same time from two separate time points (baseline and 8 hours after commute) for each commute and cytokine (IL-1β, IL-6, IL-8 and TNF-α) concentrations were analyzed using the same technology. Correlation analysis was conducted to examine the association between cytokine concentrations in the two matrices. Mixed effect linear regression modeling was then used to further assess influence from subject factors including health status, gender, race, age and BMI, while controlling for within-subject correlation due to the repeated measure structure of the dataset.

Results: IL-8 showed significant linear associations between DBS and plasma samples, where associations involving the other three measured cytokines were not significant. In asthmatic subjects, exclusively, significant, positive correlations were shown in the association between TNF-α in DBS and plasma. For non-asthmatics subjects, IL-6 in the two matrices was also significantly correlated.

Conclusion: DBS may be a promising alternative to plasma in measuring IL-8 concentrations in environmental research settings. To obtain absolute concentrations for concentration agreement analysis, validation tests should be performed for each cytokine on each matrix to yield standard sample handling and treatment process for the study.

Table of Contents

Introduction 1

Methods 4

Subject Demographics 5

Biomarker Measurements or Cytokines Measurements 5

Data Analysis 7

Results 8

Discussion 12

References 17

Tables and Figures 21

Table 1. Baseline characteristics of study population by health status 21

Table 2. Descriptive statistics for cytokine concentrations in two matrices by health status 22

Table 3. Pearson correlation coefficients (p-value) among cytokines, measured in DBS and plasma, by health status 23

Figure 1. Correlation scatter plots between DBS and plasma among cytokines 24

A.IL-1β 24

B.IL-6 25

C.IL-8 26

D. TNF-α 27

Table 4. Linear mixed effect models among cytokines examining strength of linear association between levels quantitated in DBS and plasma 28

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