Evolution of Risk Factors for Sinusitis in WTC Exposed Firefighters

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DESCRIPTION (provided by applicant): World Trade Center (WTC) exposure resulted in upper and lower airway injury in all exposed cohorts. This collaboration between the FDNY, NYU and Mt. Sinai will study WTC-related upper airway injury. While cases of lower airway injury presented within weeks of 9/11/2001, it took years longer for the extent of upper airway injury such as chronic sinusitis to emerge. In the FDNY cohort, the incidence of chronic sinusitis has been rising. Since 9/11/2001, 1,821 cases of chronic sinusitis have been confirmed by sinus CT scans; 412 of these patients with the most severe disease have required surgery. Because of the urgent need for better predictive tools to risk stratify these patients, the NYU/FDNY team sought biomarkers of sinusitis severity. We recently reported that increasing neutrophil concentration in blood early after exposure reduced the risk of subsequent sinusitis and sinus surgery (Cho et al., 2013: One airway: Biomarkers of protection from upper and lower airway injury after World Trade Center exposure). The current proposal will test the hypothesis that leukocyte concentration in the Complete Blood Count (CBC) early after exposure predicts subsequent sinus polyps and need for sinus surgery. Because the CBC is a routine part of the WTC medical monitoring exam, the neutrophil and eosinophil concentrations are already components of the longitudinal data sets for all WTC exposed cohorts. As a result, the risk models developed by this proposal can be readily confirmed in and applied to all WTC exposed cohorts. AIM 1: We propose a retrospective cohort study using data from all 1,540 WTC- exposed FDNY firefighters who have had an early CBC and subsequent sinus CT scan. We will develop two logistic models with sinus surgery and sinus polyps as outcomes to confirm our preliminary data that early neutrophil and eosinophil concentrations predict these outcomes. AIM 2: We propose a prospective nested case control study. We will enroll patients who have not been diagnosed with chronic sinusitis but who do have persistent sinus symptoms on screening questionnaires. The outcome is sinus polyps because this is an objective surrogate for sinusitis severity in this undiagnosed but persistently symptomatic group. We will recruit 106 firefighters with low PMN concentration soon after WTC exposure who have high probability for sinus polyps (cases) and 106 firefighters with high PMN who have low probability for sinus polyps (controls). We will obtain sinus CT, nasal lavage, and an ENT evaluation. We will perform objective measures of sinusitis severity and inflammation and identify potential pathogens by culture-independent techniques. Relative to controls, we predict that cases will have more sinus polyps, inflammation, and pathogens. A better stratification of WTC patients with sinus symptoms using information from prior CBCs could point to more effective diagnostic and therapeutic approaches. Low risk patients could avoid expensive but unnecessary testing. Alternately, high risk patients could receive more intensive treatment in early in the course of this emerging and disabling WTC related disease.