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A feasibility study of metabolic phenotyping of dried blood spot specimens in rural Chinese women exposed to household air pollution

Journal of Exposure Science & Environmental Epidemiology volume 31, pages 328–344 (2021)Cite this article

Abstract

Background

Exposure–response studies and policy evaluations of household air pollution (HAP) are limited by current methods of exposure assessment which are expensive and burdensome to participants.

Methods

We collected 152 dried blood spot (DBS) specimens during the heating and non-heating seasons from 53 women who regularly used biomass-burning stoves for cooking and heating. Participants were enrolled in a longitudinal study in China. Untargeted metabolic phenotyping of DBS were generated using ultra-high performance liquid chromatography coupled with mass spectrometry to exemplify measurement precision and assessment for feasibility to detect exposure to HAP, evaluated by season (high pollution vs. low pollution) and measured personal exposure to fine particulate matter <2.5 μm diameters (PM2.5) and black carbon (BC) in the 48-h prior to collecting the DBS specimen.

Results

Metabolites e.g., amino acids, acyl-carnitines, lyso-phosphorylcholines, sphinganine, and choline were detected in the DBS specimens. Our approach is capable of detecting the differences in personal exposure to HAP whilst showing high analytical reproducibility, coefficient of variance (CV) <15%, meeting the U.S. Food and Drug Administration criteria.

Conclusions

Our results provide a proof of principle that high-resolution metabolic phenotypic data can be generated using a simple DBS extraction method thus suitable for exposure studies in remote, low-resource settings where the collection of serum and plasma is logistically challenging or infeasible. The analytical run time (19 min/specimen) is similar to most global phenotyping methods and therefore suitable for large-scale application.

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Fig. 1: Relative peak intensities together with the error bars indicate standard deviation based on three replicates of dry blood spot (DBS) extracts for various metabolites and following treatments with tissuelyser and sonication.
Fig. 2: High-quality and reproducible untargeted dry blood spot (DBS) phenotypes can be obtained using ultra-high performance liquid chromatography hyphenated with time-of-flight mass spectrometry (UHPLC-qTOF-MS).
Fig. 3: Discriminatory metabolites found to be differentiated the high-pollution seasons and high personal exposures to air pollution.

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Acknowledgements

This work was supported by the Pump-Priming Project Grant from the MRC Centre for Environment and Health, which was funded by the Medical Research Council and Public Health England [MR/L01341X/1, 2009–2019] and is currently funded by the Medical Research Council [MR/S019669/1] and Environmental Protection Agency, US [EPA-STAR #83542201]. RLL acknowledges support from Chinese Academy of Sciences President’s International Fellowship Initiative (2018VBB0001). QWL and HT acknowledge financial supports from National Key R&D Program of China (2017YFC0906800) and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) and the National Natural Science Foundation of China (81590953, 31821002 and 21405020). QC acknowledges support from Wellcome Trust, UK [Strategic Award 100693/Z/12/Z]. JB acknowledges support from the Canadian Institutes for Health Research [244383]. EC acknowledges support from the Burroughs Wellcome Fund Collaborative Research Travel Grant [1018789]. RLL is supported by the Western Australian Government through the Premier’s Science Fellowship Program.

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Authors and Affiliations

  1. Centre for Computational and Systems Medicine, Institute of Health Futures, Murdoch University, Perth, WA, Australia

    Ruey Leng Loo

  2. Australian National Phenome Centre, Murdoch University, Perth, WA, Australia

    Ruey Leng Loo

  3. State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Fudan University, Shanghai, China

    Qinwei Lu, Si Liu & Huiru Tang

  4. Department of Civil and Environmental Engineering, Colorado State University, Fort Collins, CO, USA

    Ellison M. Carter

  5. CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (CAS), Wuhan, China

    Si Liu & Huiru Tang

  6. Institute for Health and Social Policy and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada

    Sierra Clark & Jill Baumgartner

  7. Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, Singapore, Singapore

    Yulan Wang

  8. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    Queenie Chan

  9. MRC Centre for Environment and Health, Imperial College London, London, UK

    Queenie Chan

Authors
  1. Ruey Leng Loo
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  2. Qinwei Lu
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  3. Ellison M. Carter
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  4. Si Liu
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  5. Sierra Clark
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  6. Yulan Wang
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  7. Jill Baumgartner
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  8. Huiru Tang
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  9. Queenie Chan
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Contributions

JB, QC, and YW conceived and designed experiments; EC and SC collected data; SL performed the experiments; RLL, and QWL analyzed data; RLL and HT interpreted the results and wrote the paper; and YW, JB, EC, and QC contributed to the writing of the paper. All authors reviewed and approved the submission; and RLL and QWL contributed equally to this work.

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Correspondence to Huiru Tang or Queenie Chan.

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Loo, R.L., Lu, Q., Carter, E.M. et al. A feasibility study of metabolic phenotyping of dried blood spot specimens in rural Chinese women exposed to household air pollution. J Expo Sci Environ Epidemiol 31, 328–344 (2021). https://doi.org/10.1038/s41370-020-0252-0

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