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*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

7 Citations (Scopus)


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 languageEnglish
Pages (from-to)225-232
Number of pages8
Issue number3
Early online date16 Jun 2022
Publication statusPublished - Mar 2023

Scopus Subject Areas

  • Pulmonary and Respiratory Medicine

User-Defined Keywords

  • Asthma


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