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Background: Firefighters exposed to World Trade Center (WTC) dust have developed chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1 s (FEV1).Overlapping but distinct immune responses may be responsible for the clinical manifestations of upper and lower airway injury. We investigated whether a panel of inflammatory cytokines, either associated or not associated with WTC-LI, can predict future chronic rhinosinusitis disease and its severity. Methods: Serum obtained within six months of 9/11/2001 from 179 WTC exposed firefighters presenting for subspecialty evaluation prior to 3/2008 was assayed for 39 cytokines. The main outcomes were medically managed CRS (N = 62) and more severe CRS cases requiring sinus surgery (N = 14). We tested biomarker-CRS severity association using ordinal logistic regression analysis. Results: Increasing serum IL-6, IL-8, GRO and neutrophil concentration reduced the risk of CRS progression. Conversely, increasing TNF-α increased the risk of progression. In a multi- a variable model adjusted for exposure intensity, increasing IL-6, TNF-α and neutrophil concentration remained significant predictors of progression. Elevated IL-6 levels and neutrophil counts also reduced the risk of abnormal FEV1 but in contrast to CRS, increased TNF-α did not increase the risk of abnormal FEV1. Conclusions: Our study demonstrates both independent and overlapping biomarker associations with upper and lower respiratory injury, and suggests that the innate immune response may play a protective role against CRS and abnormal lung function in those with WTC exposure. [ABSTRACT FROM AUTHOR]

Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome predict loss of lung function in World Trade Center (WTC) lung injury (LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI. This nested case-cohort study used 801 never-smoker, WTC-exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. A representative subcohort of 124 out of 801 subjects with serum drawn within 6 months of 9/11 defined CVD biomarker distribution. Post-9/11 forced expiratory volume in 1 s (FEV1) at defined cases were as follows: susceptible WTC-LI cases with FEV1 ≤77% predicted (66 out of 801) and resistant WTC-LI cases with FEV1 ≥107% predicted (68 out of 801). All models were adjusted for WTC exposure intensity, body mass index at SPE, age on 9/11 and pre-9/11 FEV1. Susceptible WTC-LI cases had higher levels of apolipoprotein-AII, C-reactive protein and macrophage inflammatory protein-4 with significant relative risks (RRs) of 3.85, 3.93 and 0.26, respectively, with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher soluble vascular cell adhesion molecule and lower myeloperoxidase, with RRs of 2.24 and 2.89, respectively (AUC 0.830). Biomarkers of CVD in serum 6 months post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways either producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure.