One airway: Biomarkers of protection from upper and lower airway injury after World Trade Center exposure

Abstract

Firefighters exposed to World Trade Center (WTC) dust have developed chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1s(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. 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. 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 multivariable 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. 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.