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Event
Thu 9/19/2019 11:00AM - 12:00PM
EOH Journal Club
Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen EOH Journal Club
Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen
Thu 9/19/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Brandy Hill

Paper: Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study

Authors: Denise J. Wooding, Min Hyung Ryu, Anke Huls, Andrew D. Lee, David T. S. Lin, Christopher F. Rider, Agnes C. Y. Yuen, and Chris Carlsten

Abstract:
Rationale: Diesel exhaust (DE), an established model of trafficrelated
air pollution, contributes significantly to the global burden of
asthma and may augment the effects of allergen inhalation. Newer
diesel particulate-filtering technologies may increaseNO2 emissions,
raising questions regarding their effectiveness in reducing harm from
associated engine output.

Objectives: To assess the effects of DE and allergen coexposure on
lung function, airway responsiveness, and circulating leukocytes, and
determine whether DE particle depletion remediates these effects.

Methods: In this randomized, double-blind crossover study, 14
allergen-sensitized participants (9 with airway hyperresponsiveness)
underwent inhaled allergen challenge after 2-hour exposures to DE,
particle-depleted DE (PDDE), or filtered air. The control condition
was inhaled saline after filtered air. Blood sampling and spirometry
were performed before and up to 48 hours after exposures. Airway
responsiveness was evaluated at 24 hours.

Measurements and Main Results: PDDE plus allergen
coexposure impaired lung function more than DE plus allergen,
particularly in those genetically at risk. DE plus allergen and PDDE
plus allergen each increased airway responsiveness in normally
responsive participants.DEplus allergen increased blood neutrophils
and was associated with persistent eosinophilia at 48 hours. DE and
PDDE each increased total peripheral leukocyte counts in a manner
affected by participant genotypes. Changes in peripheral leukocytes
correlated with lung function decline.

Conclusions: Coexposure to DE and allergen impaired lung
function, which was worse after particle depletion (which increased
NO2). Thus, particulates are not necessarily the sole or main
culprit responsible for all harmful effects of DE. Policies and
technologies aimed at protecting public health should be scrutinized
in that regard.
Clinical trial registered with www.clinicaltrials.gov (NCT02017431).

Keywords: diesel exhaust; asthma; filter; genetic susceptibility


4140 Public Health, Young Seminar Room

Recent Events

EOH Journal Club

Maternal phthalate exposure promotes allergic airway inflammation over 2 generations

Thursday 3/28 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Nicole Shuangjia Xue

Paper: Maternal phthalate exposure promotes allergic airway inflammation over 2 generations through epigenetic modifications

Authors: Susanne Jahreis, PhD, Saskia Trump, PhD, Mario Bauer, MD, Tobias Bauer, PhD,c Loreen Th€urmann, MSc, Ralph Feltens, PhD, Qi Wang, PhD, Lei Gu, PhD, Konrad Gr€utzmann, PhD, Stefan R€oder, PhD, Marco Averbeck, MD, Dieter Weichenhan, PhD, Christoph Plass, PhD, Ulrich Sack, MD, Michael Borte, MD, Virginie Dubourg, MSc, Gerrit Sch€u€urmann, PhD, Jan C. Simon, MD, Martin von Bergen, PhD, J€org Hackerm€uller, PhD,h Roland Eils, PhD, Irina Lehmann, PhD, and Tobias Polte, PhD

Abstract:
Background: Prenatal and early postnatal exposures to environmental factors are considered responsible for the increasing prevalence of allergic diseases. Although there is some evidence for allergy-promoting effects in children because of exposure to plasticizers, such as phthalates, findings of previous studies are inconsistent and lack mechaistic information.

Objective: We investigated the effect of maternal phthalate exposure on asthma development in subsequent generations and their underlying mechanisms, including epigenetic alterations.

Methods: Phthalate metabolites were measured within the prospective mother-child cohort Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk (LINA) and correlated with asthma development in the children. A murine transgenerational asthma model was used to identify involved pathways.


Results: In LINA maternal urinary concentrations of mono-nbutyl phthalate, a metabolite of butyl benzyl phthalate (BBP), were associated with an increased asthma risk in the children. Using a murine transgenerational asthma model, we demonstrate a direct effect of BBP on asthma severity in the offspring with a persistently increased airway inflammation up to the F2 generation. This disease-promoting effect was mediated by BBP-induced global DNA hypermethylation in CD41 T cells of the offspring because treatment with a DNA-demethylating agent alleviated exacerbation of allergic
airway inflammation. Thirteen transcriptionally downregulated genes linked to promoter or enhancer hypermethylation were identified. Among these, the GATA-3 repressor zinc finger protein 1 (Zfpm1) emerged as a potential mediator of the enhanced susceptibility for TH2-driven allergic asthma.

Conclusion: These data provide strong evidence that maternal BBP exposure increases the risk for allergic airway inflammation in the offspring by modulating the expression of genes involved in TH2 differentiation through epigenetic alterations. (J Allergy Clin Immunol 2018;141:741-53.)

Click Here For Article

Last Updated On Tuesday, January 22, 2019 by Orbell, Adam W
Created On Tuesday, January 22, 2019

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