Validation of Predictive Metabolic Syndrome Biomarkers of World Trade Center Lung Injury: A 16-Year Longitudinal Study

Abstract

Background: Metabolic syndrome (MetSyn) predicted future development of World Trade Center lung injury (WTC-LI) in a subgroup of firefighters who never smoked and were male. An intracohort validation of MetSyn as a predictor of WTC-LI is examined in the cohort exposed to the World Trade Center (WTC) that has been followed longitudinally for 16 years.

Methods: Results of pulmonary function tests (n = 98,221) in workers exposed to the WTC (n = 9,566) were evaluated. A baseline cohort of firefighters who had normal FEV₁ before 9/11 and who had had serum drawn before site closure on July 24, 2002 (n = 7,487) was investigated. Case subjects with WTC-LI (n = 1,208) were identified if they had at least two measured instances of FEV₁ less than the lower limit of normal (LLN). Cox proportional hazards modeled early MetSyn biomarker ability to predict development of FEV₁ less than the LLN.

Results: Case subjects were more likely to smoke, be highly exposed, and have MetSyn. There was a significant exposure dose response; the individuals most highly exposed had a 30.1% increased risk of developing WTC-LI, having MetSyn increased risk of developing WTC-LI by 55.7%, and smoking increased risk by 15.2%. There was significant interaction between smoking and exposure.

Conclusions: We validated the usefulness of MetSyn to predict future WTC-LI in a larger population of individuals who were exposed. MetSyn defined by dyslipidemia, insulin resistance, and cardiovascular disease suggests that systemic inflammation can contribute to future lung function loss.

Keywords: World Trade Center; lung injury; metabolic syndrome; validation.

Figure 1

Study design. Fire Department of New York rescue and recovery workers exposed to World Trade Center particulates. LLN = lower limit of normal; WTC = World Trade Center; WTC-LI = WTC lung injury.

Figure 2

MetSyn final model hazard ratios. The final model was adjusted for age at 9/11, smoking, and exposure. The final model had a significant exposure dose response (P = .007). There was also a significant increased risk associated with the number of MetSyn criteria met in a dose-response fashion (P < .001). MetSyn = metabolic syndrome. See Figure 1 legend for expansion of other abbreviation.

Figure 3

A, Kaplan-Meier curve shows MetSyn criteria stratified time to development of WTC-LI. Cumulative disease-free survival is expressed on the y-axis and time in years from their WTC exposure is on the x-axis. B, A 3-D density plot of hazard ratio and number of MetSyn criteria met demonstrates a large proportion of patients with zero MetSyn criteria with hazards < 1, in contrast to those with three or more MetSyn criteria who had more significant risk of developing WTC-LI. See Figure 1 and 2 legends for expansion of abbreviations.

Figure 4

Cumulative disease-free survival curves by individual metabolic syndrome biomarkers. Cumulative disease-free survival is expressed on the y-axis, and time in years from World Trade Center exposure is on the x-axis. A, High-density lipoprotein (HDL) (mg/dL). B, Triglycerides (Trig) (mg/dL). C, BMI (kg/m²). D, Systolic BP (mm Hg). E, Diastolic BP (mm Hg). F, Smoking status. G, Arrival time.