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Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline
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    Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung's normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well-phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC-exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after WTC exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1 below the lower limit of normal known as WTC-Lung Injury (WTC-LI). We utilized a nested case-cohort control design of previously healthy never smokers who sought subspecialty pulmonary evaluation to explore predictive biomarkers of WTC-LI. We have identified biomarkers of inflammation, metabolic derangement, protease/antiprotease balance, and vascular injury expressed in serum within 6 months of WTC exposure that were predictive of their FEV1 up to 7 years after their WTC exposure. Predicting future risk of airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services.

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  • Funding:
    K23 HL084191/HL/NHLBI NIH HHS/United States
    K23HL084191/HL/NHLBI NIH HHS/United States
    K24 AI080298/AI/NIAID NIH HHS/United States
    K24A1080298/PHS HHS/United States
    R01 HL057879/HL/NHLBI NIH HHS/United States
    R01HL057879/HL/NHLBI NIH HHS/United States
    U10 OH008242/OH/NIOSH CDC HHS/United States
    U10 OH008243/OH/NIOSH CDC HHS/United States
    U10-OH008242/OH/NIOSH CDC HHS/United States
    U10-OH008243/OH/NIOSH CDC HHS/United States
    UL1 RR029893/RR/NCRR NIH HHS/United States
    UL1 TR000038/TR/NCATS NIH HHS/United States
    UL1 TR001445/TR/NCATS NIH HHS/United States
    UL1RR029893/RR/NCRR NIH HHS/United States
    UL1TR000038/TR/NCATS NIH HHS/United States
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