Abstract Rationale Recent data from patients with chronic respiratory diseases suggest that air pollution influences airway microbial composition and the local immune tone. Traffic-related air pollution has been associated with pulmonary impairment, oxidative stress, and airway inflammation in patients with COPD. The impact of urban traffic exposure on individuals with bronchiectasis, who experience chronic infection, inflammation, and dilated airways is still not understood. We investigated how traffic related air pollution in New York City influences the lower airway microbiome and host transcriptome in bronchiectasis. Methods Outdoor air pollution exposure data was derived from the Chemical Speciation Network and was available on 96 patients in whom we also have lower airway samples. We separated the cohort into two groups based on the median Traffic score and labeled them “High-Traffic-Exposure” and “Low-Traffic-Exposure”. Chi-square tests were used for categorical variables, reported as frequency/percentage, while continuous variables were analyzed using the Mann-Whitney U test and reported as median/interquartile range. All samples underwent 16s rRNA, RNA metatranscriptome and host transcriptome sequencing. Differential gene expression between the two exposure groups was assessed using Ingenuity Pathway Analysis (IPA) to identify enriched molecular pathways associated with traffic exposure. Results 48/96(50%) of patients had “High Traffic Exposure” and the rest had “Low Traffic Exposure”. NTM positivity was 49%(47/96) in this cohort. Analysis of the microbial communities in the full cohort using 16SrRNA gene sequencing and metatranscriptome did not show any significant differences in the alpha or beta diversity between high/low traffic exposure. Across all patients EdgeR analysis of 16SrRNA and metatranscriptome sequencing showed enrichment with Achromobacter. Amongst NTM+ patients EdgeR analysis of 16SrRNA and metatranscriptome sequencing showed enrichment with Pseudomonas, Staphylococcus, and Bacillus. In contrast to NTM+, oral commensal ASV’s in NTM- subjects were infrequent (both on 16SrRNA and metatranscriptome)(Fig.1A and 1B). Analysis of the host transcriptome identified 2897 differentially enriched genes (DEGs) in the high-traffic group. IPA showed that this group had up-regulated canonical pathways related to platelet homeostasis, macrophage classical activation, MyD88 signaling, natural killer cell signaling, and phagosome formation(Fig 1C). Finally, we identified multiple DEGs in the NTM+ group with high-traffic exposure including up-regulation of IL-8, IL-12, macrophage classical activation pathway and Stat5 signaling(Fig. 1D). Conclusions Distinct environmental exposure profiles in bronchiectasis are associated with specific shifts in lower airway microbiome. These findings suggest the potential role of environmental air pollution on modulated the lower airway microbiome which could potential impact the pathogenesis of bronchiectasis. This abstract is funded by: American Thoracic Society, NIH
Atandi et al. (Fri,) studied this question.