Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: A multicentre study

Chao Chien Wu; Chin Chou Wang; Wen Yu Chung; Chau Chyun Sheu; Yi Hsin Yang; Ming Yen Cheng; Ruay Sheng Lai; Sum Yee Leung; Chi Cheng Lin; Yu Feng Wei; Ching Hsiung Lin; Sheng Hao Lin; Jeng Yuan Hsu; Wei Chang Huang; Chia Cheng Tseng; Yung Fa Lai; Meng Hsuan Cheng; Huang Chi Chen; Chih Jen Yang; Shih Chang Hsu; Chian Heng Su; Chien Jen Wang; Huei Ju Liu; Hua Ling Chen; Yuan Ting Hsu; Chih Hsing Hung; Chon Lin Lee; Ming Shyan Huang; Shau Ku Huang

doi:10.1136/thoraxjnl-2021-218396

Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: A multicentre study

Chao Chien Wu, Chin Chou Wang, Wen Yu Chung, Chau Chyun Sheu, Yi Hsin Yang, Ming Yen Cheng, Ruay Sheng Lai, Sum Yee Leung, Chi Cheng Lin, Yu Feng Wei, Ching Hsiung Lin, Sheng Hao Lin, Jeng Yuan Hsu, Wei Chang Huang, Chia Cheng Tseng, Yung Fa Lai, Meng Hsuan Cheng, Huang Chi Chen, Chih Jen Yang, Shih Chang HsuChian Heng Su, Chien Jen Wang, Huei Ju Liu, Hua Ling Chen, Yuan Ting Hsu, Chih Hsing Hung, Chon Lin Lee, Ming Shyan Huang, Shau Ku Huang

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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.

Original language	English
Article number	218396
Pages (from-to)	225-232
Number of pages	8
Journal	Thorax
Volume	78
Issue number	3
DOIs	https://doi.org/10.1136/thoraxjnl-2021-218396
Publication status	Accepted/In press - 2022

Keywords

Asthma

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/thoraxjnl-2021-218396

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Wu, C. C., Wang, C. C., Chung, W. Y., Sheu, C. C., Yang, Y. H., Cheng, M. Y., Lai, R. S., Leung, S. Y., Lin, C. C., Wei, Y. F., Lin, C. H., Lin, S. H., Hsu, J. Y., Huang, W. C., Tseng, C. C., Lai, Y. F., Cheng, M. H., Chen, H. C., Yang, C. J., ... Huang, S. K. (Accepted/In press). Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: A multicentre study. Thorax, 78(3), 225-232. Article 218396. https://doi.org/10.1136/thoraxjnl-2021-218396

Wu, CC, Wang, CC, Chung, WY, Sheu, CC, Yang, YH, Cheng, MY, Lai, RS, Leung, SY, Lin, CC, Wei, YF, Lin, CH, Lin, SH, Hsu, JY, Huang, WC, Tseng, CC, Lai, YF, Cheng, MH, Chen, HC, Yang, CJ, Hsu, SC, Su, CH, Wang, CJ, Liu, HJ, Chen, HL, Hsu, YT, Hung, CH, Lee, CL, Huang, MS & Huang, SK 2022, 'Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: A multicentre study', Thorax, vol. 78, no. 3, 218396, pp. 225-232. https://doi.org/10.1136/thoraxjnl-2021-218396

@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",

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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

PY - 2022

Y1 - 2022

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

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U2 - 10.1136/thoraxjnl-2021-218396

DO - 10.1136/thoraxjnl-2021-218396

M3 - Article

C2 - 35710744

AN - SCOPUS:85132831615

SN - 0040-6376

VL - 78

SP - 225

EP - 232

JO - Thorax

JF - Thorax

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M1 - 218396

ER -

Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: A multicentre study

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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