New funding for analyses of novel inflammatory, surfactant disfunction, oxidative stress,and fibrosis biomarkers within these exhaled breath condensate (EBC) samples could synergistically advanceour understanding of oxidative lung injury with relatively modest financial investment. We will synergize existingvirtual consortia (parent R01 & an ionizing radiation (IR) exposure cohorts) by adding two new trans-disciplinary laboratory-focused investigators from the host institutions (Sullivan & Kondrashova). Svendsen willlead the resulting joint epidemiological analyses. Our immediate goal is to identify reliable biomarkers ofoxidative lung injury that are reproducible, have reference values and provide information on the underlyingoxidative processes. Our long-term goal is to develop new translational countermeasures of latent adverselung effects of oxidative hazard exposures (e.g. Cl2, IR) within disaster populations. We believe that pulmonarysurfactant alterations may be a feasible option for further biomarker study and potential countermeasuredevelopment. We will test the overall hypothesis that inactivation of surfactant is the primary mechanismassociated with the observed oxidative lung injury that best explains the lung function changes rather thanfibrotic mechanisms. In two oxidative lung injury cohorts, we will assess novel biomarkers in archived EBCsamples from previous health screenings in 2005 and 2008-2010. This will position us to compete for newfunds for analysis of the parent R01 EBC samples where we can study additional potential progressive diseasemechanisms and oxidative stress biomarkers observed 7-10 years after the first EBC collection and relatethem to new comprehensive pulmonary diagnostic testing data (diffusing capacity, impulse oscillometry,plethesmography, 6-minute walk, eNO, spirometry, pre/post bronchodilator spirometry, EBC pH). This willexpand the impact of the parent R01 dramatically by allowing us to link the functional measures with theirpotential corresponding mechanisms. We will contrast the same EBC biomarkers between two oxidative lunginjury cohorts: one in the USA led by Dr. Sullivan (Cl2) while the other in Ukraine led by Dr. Kondrashova (137Csionizing radiation). Results from each parallel set of studies will advance the science of both chlorine andionizing radiation-induced lung injury independently. By performing such studies synergistically with identicalprotocols we can contrast disease mechanisms across exposures, and generate broader knowledge of lunginjury mechanisms and biomarkers. If our overall hypothesis is true, then our research will have a large impacton the understanding of oxidative lung injury. Unlike fibrotic mechanisms, mitigation of surfactant disfunctionmay be possible with additional pharmacological development. This study could help expedite development ofnovel countermeasures and subsequent public health interventions for those thousands currently suffering.

Public Health Relevance

We will synergize existing virtual consortia (parent R01 & an ionizing radiation (IR)exposure cohorts) by adding two new trans-disciplinary laboratory-focused investigators from the hostinstitutions (Sullivan & Kondrashova). In two oxidative lung injury cohorts; we will assess novel biomarkers inarchived EBC samples from previous health screenings in 2005 and 2008-2010. This will expand the impact ofthe parent R01 dramatically by allowing us to link the functional measures with their potential correspondingmechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
7R01ES015532-06
Application #
9110626
Study Section
Special Emphasis Panel (ZRG1-PSE-E (02))
Program Officer
Joubert, Bonnie
Project Start
2015-07-15
Project End
2015-11-30
Budget Start
2015-07-15
Budget End
2015-11-30
Support Year
6
Fiscal Year
2014
Total Cost
$40,320
Indirect Cost
$8,320
Name
Medical University of South Carolina
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
Summerhill, Eleanor M; Hoyle, Gary W; Jordt, Sven-Eric et al. (2017) An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness. Ann Am Thorac Soc 14:1060-1072
Carlisle, Matthew; Lam, Adam; Svendsen, Erik R et al. (2016) Chlorine-induced cardiopulmonary injury. Ann N Y Acad Sci 1374:159-67
Rothenberg, Craig; Achanta, Satyanarayana; Svendsen, Erik R et al. (2016) Tear gas: an epidemiological and mechanistic reassessment. Ann N Y Acad Sci 1378:96-107
Jani, Dev D; Reed, David; Feigley, Charles E et al. (2016) Modeling an irritant gas plume for epidemiologic study. Int J Environ Health Res 26:58-74
Clark, Kathleen A; Karmaus, Wilfried J J; Mohr, Lawrence C et al. (2016) Lung Function before and after a Large Chlorine Gas Release in Graniteville, South Carolina. Ann Am Thorac Soc 13:356-63
Hoyle, Gary W; Svendsen, Erik R (2016) Persistent effects of chlorine inhalation on respiratory health. Ann N Y Acad Sci 1378:33-40
Abara, Winston; Wilson, Sacoby; Vena, John et al. (2014) Engaging a chemical disaster community: lessons from Graniteville. Int J Environ Res Public Health 11:5684-97
Culley, Joan M; Svendsen, Erik (2014) A review of the literature on the validity of mass casualty triage systems with a focus on chemical exposures. Am J Disaster Med 9:137-50
Mackie, Emily; Svendsen, Erik; Grant, Stephen et al. (2014) Management of chlorine gas-related injuries from the Graniteville, South Carolina, train derailment. Disaster Med Public Health Prep 8:411-6
Clark, Kathleen A; Chanda, Debjani; Balte, Pallavi et al. (2013) Respiratory symptoms and lung function 8-10 months after community exposure to chlorine gas: a public health intervention and cross-sectional analysis. BMC Public Health 13:945

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