title: Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of Distal Airway and Blood Biomarkers that Predict FEV₁ Decline.
abstract: 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.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weiden
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: Sophia
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: Erin
authors.initials: E
authors.lastname: Caraher
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: Joan
authors.initials: J
authors.lastname: Reibman
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.affiliation: Bureau of Health Services and Office of Medical Affairs, Fire Department of New York, Brooklyn, New York.
authors.forename: David J
authors.initials: DJ
authors.lastname: Prezant
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New York, New York.
authors.forename: Anna
authors.initials: A
authors.lastname: Nolan
mesh_terms: D000402:Airway Obstruction / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D061388:Firefighters; D005541:Forced Expiratory Volume; D006801:Humans; D055370:Lung Injury / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D009519:New York City; D016273:Occupational Exposure / Q000009:adverse effects*; D052638:Particulate Matter / Q000633:toxicity*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D052638:Particulate Matter