Abstract Rationale The effect of traffic related air pollution (TRAP) on the transcriptomic response to respiratory viral and bacterial infection (RVI and RBI, respectively) is an active area of research. Methods From a prospective cohort study developing a predictive classifier for differentiating bacterial from viral respiratory infection in adults, 360 patients who had transcriptional profiling of peripheral whole blood were enrolled. A panel of three infectious disease specialists and one pulmonary and critical care specialist adjudicated patients with RVI, RBI or no infection (controls) by using clinical histories, imaging, serum biomarkers, and microbiological samples. Using the LIMMA package for R we estimated the log2 fold change in genes within a targeted collection of infection-specific gene pathways associated with each interquartile range (IQR) increase in TRAP. Specifically we modelled IQR increases in particulate matter ≤ 2.5µm (PM2.5), black carbon, ultrafine particles (UFP; 100nm), nitrogen dioxide (NO2) and additional pollutants in the previous 1 (lag days 0-6), 2 (lag days 7-13), 3 (lag days 14-20), and 4 weeks (lag days 21-27), adjusting for batch, sex, age, area deprivation index, and relative humidity. Results For patients with RVI, we observed significant upregulation and log2 fold change 0.5 in 85 genes involved in both immune and inflammatory responses, including chemokines (CCL2, CCL8, CXCL11), interferon stimulated genes (ISIG15, IFIT1, OAS2/OAS3) and downregulation in cell adhesion (ITGB4) (Figure 1A). Specifically, increased NO2 concentrations in the 21-28 days prior to admission were associated with the largest statistically significant increase in the expression of CCL2 (3.3-fold), with a smaller increase at the 14-20 lag day period for NO2. For patients with RBI, only one gene related to tissue repair and immune cell migration (VCAN) was significantly upregulated associated with an increase in UFP (Figure 1B). In the non-infected control population, only eight genes were significantly upregulated, including a 2-fold increase in ISG15 associated with increased UFP concentrations at the 14-20 lag days. There were few significant associations were observed in the 0-14 lag days for any infection group. Conclusions The link between TRAP and the transcriptomic response to respiratory infection appeared strongest in RVI in the 3-4 weeks prior to infection, with upregulation of a wide variety of immune and inflammatory genes. The transcriptomic response to TRAP in patients with RBI appeared similar to that observed in non-infected controls. Further research is needed to understand how the observed transcriptomic changes correspond to the risk of hospitalization for RVI. This abstract is funded by: NIEHS Research Career Development Award K23 ES032459 and NIH/NIAID R01AI137364. Additionally NIH P30 ES001247
Croft et al. (Fri,) studied this question.