Dynamic Metabolic Risk Profiling of World Trade Center Lung Disease: A Longitudinal Cohort Study

Rationale: Metabolic syndrome (MetSyn) increases the risk of World Trade Center (WTC) lung injury (LI). However, the temporal relationship of MetSyn, exposure intensity, and lung dysfunction is not well understood. Objective: To model the association of longitudinal MetSyn characteristics with WTC lung disease to define modifiable risk. Methods: Firefighters, for whom consent was obtained (N = 5,738), were active duty on September 11, 2001 (9/11). WTCLI (n = 1,475; FEV1% predicted,lower limit of normal [LLN]) and non-WTC-LI (n= 4,263; FEV1% predicted >= LLN at all exams) was the primary outcome, and FVC% predicted < LLN and FEV1/FVC < 0.70 were secondary outcomes. We assessed 1) the effect of concurrent MetSyn on longitudinal lung function by linear mixed models, 2) the temporal effect of MetSyn and exposure by Weibull proportional hazards, 3) the effects of MetSyn's rate of change by two-stage models, and 4) the nonlinear joint effect of longitudinal MetSyn components by a partially linear single-index model (PLSI). Measurements and Main Results: WTC-LI cases were more often ever-smokers, arrived in the morning (9/11), and had MetSyn. Body mass index >30 kg/m(2) and high-density lipoprotein,40 mg/dl were most contributory to concurrent loss of FEV1% predicted and FVC% predicted while conserving FEV1/FVC. Body mass index >30 kg/m(2) and dyslipidemia significantly predicted WTC-LI, FVC% predicted <LLN in a Weibull proportional hazards model. Dynamic risk assessment of WTCLI on the basis of MetSyn and exposure showed how reduction of MetSyn factors further reduces WTC-LI likelihood in susceptible populations. PLSI demonstrates that MetSyn has a nonlinear relationship with WTC lung disease, and increases in cumulative MetSyn risk factors exponentially increase WTC-LI risk. An interactive metabolic-risk modeling application was developed to simplify PLSI interpretation. Conclusions: MetSyn and WTC exposure contribute to the development of lung disease. Dynamic risk assessment may be used to encourage treatment of MetSyn in susceptible populations. Future studies will focus on dietary intervention as a disease modifier.