@article{ef72f5c5b27c462e8bcba215e314e97e,
title = "Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: A multicentre study",
abstract = "Background: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. Methods: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. Findings: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nϵ-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. Interpretation: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.",
keywords = "Asthma",
author = "Wu, {Chao Chien} and Wang, {Chin Chou} and Chung, {Wen Yu} and Sheu, {Chau Chyun} and Yang, {Yi Hsin} and Cheng, {Ming Yen} and Lai, {Ruay Sheng} and Leung, {Sum Yee} and Lin, {Chi Cheng} and Wei, {Yu Feng} and Lin, {Ching Hsiung} and Lin, {Sheng Hao} and Hsu, {Jeng Yuan} and Huang, {Wei Chang} and Tseng, {Chia Cheng} and Lai, {Yung Fa} and Cheng, {Meng Hsuan} and Chen, {Huang Chi} and Yang, {Chih Jen} and Hsu, {Shih Chang} and Su, {Chian Heng} and Wang, {Chien Jen} and Liu, {Huei Ju} and Chen, {Hua Ling} and Hsu, {Yuan Ting} and Hung, {Chih Hsing} and Lee, {Chon Lin} and Huang, {Ming Shyan} and Huang, {Shau Ku}",
note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2022",
doi = "10.1136/thoraxjnl-2021-218396",
language = "English",
volume = "78",
pages = "225--232",
journal = "Thorax",
issn = "0040-6376",
publisher = "BMJ Publishing Group",
number = "3",
}
