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Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs
  1. Min Hyung Ryu1,
  2. Kevin Soon-Keen Lau1,
  3. Denise Jill Wooding1,
  4. Shuyu Fan1,
  5. Don D Sin2,
  6. Christopher Carlsten1
  1. 1Air Pollution Exposure Laboratory, Department of Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  2. 2Centre for Heart Lung Innovation, St. Paul's Hospital, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  1. Correspondence to Dr Christopher Carlsten, Air Pollution Exposure Laboratory, Department of Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia Faculty of Medicine, Vancouver, BC V5Z 1M9, Canada; carlsten{at}mail.ubc.ca

Abstract

Rationale Exposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways.

Methods Fourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators.

Results In human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p<0.005), eotaxin-3 (p<0.0001), interleukin 5 (IL-5; p<0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV1.

Conclusion Short-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion.

Trial registration number NCT02017431.

  • asthma
  • surfactant protein
  • innate immunity
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Footnotes

  • Contributors KS-KL and DJW contributed equally to the manuscript.

  • Funding This study was supported by Canadian Institutes of Health Research (CIHR) grant MOP 123319, WorkSafe BC grant RG2011-OG07, AllerGen National Centre for Excellence grant (GxE4). MHR was supported by WorkSafe BC Research Training Award RS2016-TG08 and NSERC Alexander Graham Bell Scholarship CGS-D. DJW was supported by CIHR scholarship CGS-M and WorkSafe BC Research Training Award (RS2017-TG05). CC was supported by Canada Research Chairs program.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by the University of British Columbia Research Ethics Board (H11-01831).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Deidentified participant data and statistical analysis code are available upon reasonable request to the corresponding author.

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