Association of Endogenous Secretory RAGE and World Trade Center Particulate Matter-Induced AHR and Lung Injury

Details

• Personal Author:
  Kwon S ; Lam R ; Liu M ; Nolan A ; Ostrofsky D ; Prezant DJ
• Description:
  RATIONALE. World Trade Center (WTC)-particulate matter (PM) exposed firefighters have developed airway hyperreactivity (WTC-AHR) and lung injury (WTC-LI). Risk factors of WTC-AHR/LI include metabolic syndrome (MetSyn) and serum soluble receptor of advanced glycation endproducts (RAGE). RAGE not only has many ligands but also has many biologically active isoforms which are mediators of MetSyn related disease. One isoform of interest is endogenously secreted RAGE (esRAGE), which has been inversely associated with body mass index (BMI) and MetSyn. Therefore, our objective was to quantity esRAGE in cases of WTC associated LI and AHR. METHODS. For our pilot study, we assayed serum samples of WTC-exposed male firefighters with either AHR, WTC-LI or normal pulmonary function from a randomly selected representative 10% cohort control(N=449/4,487). Cases of AHR (N=21) had positive methacholine and/or bronchodilator response, and FEV1>LLN al WTC-HP entry, whereas N=85 cases of WTC-LI had FEV1≤LLN at WTC-HP entry. Age and BMI-matched cohort controls (N=41) and WTC-LI (N=24) were selected in a 1:1:2 ratio (AHR: WTC-LI: control). Available serum aliquots drawn at WTC-HP entry were assayed tor esRAGE (B-Bridge International). AHR were compared to non-AHR/WTC-LI controls enriched with WTC-LI cases, whereas WTC-LI cases were compared to non-AHR/WTC-LI controls enriched with AHR cases. Fold change over mean concentration of control was calculated and compared by student t-test (SPSS 23). RESULTS. WTC-LI cases had significantly higher triglycerides compared to cohort controls (mean 197.0mg/dL v 163.4mg/dL respectively), whereas AHR cases were no different WTC-LI/AHR were not significantly different compared to cohort controls in smoking, exposure intensity, and FEV1%pred al WTC-HP entry by student t-test. WTC-LI/AHR cases were also not different in blood pressure, cholesterol, LDL, or HDL at WTC-HP entry. WTC-LI and AHR cases also expressed different patterns of esRAGE expression. WTC-LI cases had a decreased expression of esRAGE (0.7806: p<0.01) whereas AHR had increased relative expression (1.1195; (p<0.01) compared to cohort controls. CONCLUSIONS WTC-LI and AHR express different patterns of esRAGE. While esRAGE level is positively associated with AHR in our cohort, it is negatively associated with WTC-LI. This suggests that esRAGE could mediate different pathways of inflammation leading to lung disease. Future work will focus on validating our pilot study results in the cohort control. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Firefighters Immune System Lung Occupational Health Particulate Matter Respiratory System Safety September 11 Terrorist Attacks
• Keywords:
  Fire Fighters Immune Reaction Lung Function Metabolic Effects Particulates Respiratory Irritants World Trade Center WTC
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  201
• NIOSHTIC Number:
  nn:20066342
• Citation:
  Am J Respir Crit Care Med 2020 May; 201(Abstract Issue):A7128
• Email:
  dean.ostrotsky@nyumc.org
• Federal Fiscal Year:
  2020
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  False
• Start Date:
  20170701
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:679c39c7fc9926de1ab22e07ce3f5de33e311d8ec154c8bf0421230c6b8f5b694f20442f4d6bf7c0b647554281053e7c8f5edc614a30e645f221ce2d2e98c186
• Download URL:
  https://stacks.cdc.gov/view/cdc/212810/cdc_212810_DS1.pdf
• File Type:
  [PDF - 165.76 KB ]