TY - JOUR
T1 - Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters:
T2 - a multicentre study
AU - Wu, Chao-Chien
AU - Wang, Chin Chou
AU - Chung, Wen-Yu
AU - Sheu, Chau-Chyun
AU - Yang, Yi-Hsin
AU - Cheng, Ming-Yen
AU - Lai, Ruay-Sheng
AU - Leung, Sum-Yee
AU - Lin, Chi-Cheng
AU - Wei, Yu-Feng
AU - Lin, Ching-Hsiung
AU - Lin, Sheng-Hao
AU - Hsu, Jeng-Yuan
AU - Huang, Wei-Chang
AU - Tseng, Chia-Cheng
AU - Lai, Yung-Fa
AU - Cheng, Meng-Hsuan
AU - Chen, Huang-Chi
AU - Yang, Chih-Jen
AU - Hsu, Shih-Chang
AU - Su, Chian-Heng
AU - Wang, Chien-Jen
AU - Liu, Huei-Ju
AU - Chen, Hua-Ling
AU - Hsu, Yuan-Ting
AU - Hung, Chih-Hsing
AU - Lee, Chon-Lin
AU - Huang, Ming-Shyan
AU - Huang, Shau-Ku
N1 - Funding Information:
Funding This work was supported, in part, by grants from National Health Research Institutes, Taiwan (EOPP10-014, EOSP07-014 and NHRI-102A1-PDCO-03010201) and Ministry of Health and Welfare, Taiwan (EODOH01), National Science Council (NSC 102-2314-B-037-052), Ministry of Science and Technology (MOST 103-2320-B-110–001) and Academia Sinica (BM-102021170), Taiwan.
Publisher Copyright:
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - Asthma
UR - http://www.scopus.com/inward/record.url?scp=85132831615&partnerID=8YFLogxK
U2 - 10.1136/thoraxjnl-2021-218396
DO - 10.1136/thoraxjnl-2021-218396
M3 - Journal article
SN - 0040-6376
VL - 78
SP - 225
EP - 232
JO - Thorax
JF - Thorax
IS - 3
ER -
