Asthma and lower airway diseaseInhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation
Section snippets
Study demographics
Seventeen white participants (see Tables I and II) were recruited to the Air Pollution Exposure Laboratory in Vancouver, British Columbia, Canada. Written consent was obtained from all subjects, and the protocols were approved by the institutional review board for human studies at the University of British Columbia. Participants were 20 to 46 years old (median = 27, SD = 7.8), all nonsmokers, and 47% had asthma (Table I). We excluded individuals with any of the following: (1)
Study cohort and samples
To evaluate the effects of allergen and DE exposure on DNA methylation in the human lung, we performed a rigorous randomized crossover-controlled exposure study. Specifically, 17 individuals were randomized into 2 study groups (group I and group II), defined by whether FA or DE was inhaled first (Fig 1, A). Following inhalation of FA or DE, allergen was instilled into one lung and saline into the other. The process was repeated approximately 4 weeks later with opposite exposures. This resulted
Discussion
The molecular mechanisms regulating the interaction between air pollution and allergic disease are poorly understood. Defining these mechanisms is critical for creating strategies to reduce susceptibility and severity of airways disease,8 especially given dynamics associated with both air pollution and allergens associated with global climate change.35 DNA methylation may be one of the mechanisms by which environmental exposures, including DE, can exert lasting effects on gene expression, cell
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Cited by (0)
This project was supported by funding from the Canadian Institutes for Health Research (MOP 123319), WorkSafe BC (RG2011-OG07), AllerGen NCE (GxE2; GxE4), the European Respiratory Society (ERS) and the Canadian Thoracic Surgery (CTS)/Canadian Lung Association, joint ERS/CTS Long-Term Research Fellowship LTRF 2013 (to R.L.C.), and a Mining for Miracles postdoctoral fellowship (to M.J.J.). C.C. is the Canada Research Chair in Occupational and Environmental Lung Disease. M.S.K. is the Canada Research Chair in Social Epigenetics and a Senior Fellow of the Canadian Institute for Advanced Research (CIFAR). S.M. is the Canada Research Chair in Computational Biology and a Fellow of CIFAR. The funding bodies had no involvement in the study design; collection, analysis, or interpretation of the data; the writing of the report; or the decision to submit the article for publication.
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
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Rachel L. Clifford, PhD, is currently affiliated with the Department of Respiratory Medicine and Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom.
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These authors contributed equally to this work as senior authors.