Faculty Bibliography

RATIONALE: The World Trade Center (WTC) collapse generated caustic airborne particulates that caused chronic rhinosinusitis in exposed fire department of New York (FDNY) firefighters. Surgery was performed when symptoms remained uncontrolled despite medical management. OBJECTIVES: To identify predictors of surgical intervention for chronic rhinosinusitis in firefighters exposed to airborne irritants at the WTC collapse site. METHODS: We assessed in 8,227 firefighters with WTC-exposure between 9/11/2001 (9/11) and 9/25/2001, including WTC-site arrival time, months of rescue/recovery work, and eosinophil concentration measured between 9/11 and 3/10/2003. We assessed the association of serum cytokines and immunoglobulins with eosinophil concentration and surgery for rhinosinusitis in 112 surgical cases and 376 controls with serum available from the first 6 months after exposure to the WTC collapse site. MEASUREMENTS AND MAIN RESULTS: Between 9/11 and 3/10/2015, the surgery rate was 0.47 cases per 100 person years. In the first 18 months post 9/11, surgical patients had higher mean blood eosinophil levels than study cohort patients(219+/-155 vs. 191+/-134; P <0.0001). Increased surgery risk was associated with increasing blood eosinophil counts (HR 1.12 per 100 cells/uL; 95% CI 1.07 to1.17; P <0.001); arriving at the WTC site 9/11 or 9/12/2001 (HR 1.43; 95% CI 1.04 to 1.99; P=0.03); and working >/=6 months at the WTC-site (HR 1.48; 95% CI 1.14 to 1.93; P<0.01). Median blood eosinophil levels for surgery patients were above levels for the cohort in all 18-month intervals 3/11/2000 through 3/10/2015 using 51,163 measurements representing 97,733 person-years of observation. Increasing age, increasing IL-17A and low IgA in serum from 2001-2002 predicted blood eosinophil concentration in surgical patients but not in controls (R2=0.26, p<0.0001 vs. R2=0.008, p=0.56). CONCLUSIONS: Increasing blood eosinophil concentration predicts surgical intervention for chronic rhinosinusitis, particularly in those with intense acute and prolonged exposure to airborne irritants. WTC-exposed FDNY firefighters who underwent irritant-associated sinus surgery are immunologically different from the cohort. Surgical patients have a higher blood eosinophil levels that is associated with mediators of mucosal immunity.

BACKGROUND: Adverse respiratory effects of World Trade Center (WTC) exposure have been widely documented, but the length of time that exposure remains associated with disease is uncertain. We estimate the incidence of new cases of physician-diagnosed obstructive airway disease (OAD) as a function of time since 9/11/2001 in WTC-exposed firefighters. METHODS: Exposure was categorized by first WTC arrival time: high (9/11/2001 AM); moderate (9/11/2001 PM or 9/12/2001); or low (9/13-24/2001). We modeled relative rates (RR) and 95% confidence intervals (CI) of OAD incidence by exposure over the first 10 years post-9/11/2001, estimating the time(s) of change in the RR with change point models. We further examined the relationship between self-reported lower respiratory symptoms and physician diagnoses. RESULTS: Change points were observed at 15 and 84 months post-9/11/2001, with relative incidence rates for the high versus low exposure group of 4.02 (95% CI 2.62-6.16) prior to 15 months, 1.90 (95% CI 1.49-2.44) from months 16 to 84, and 1.20 (95% CI 0.92-1.56) thereafter. Incidence in all exposure groups increased after the WTC health program began to offer free coverage of OAD medications in month 63. Self-reported lower respiratory symptoms in the first 15 months had 80.6% sensitivity, but only 35.9% specificity, for eventual OAD diagnoses. CONCLUSIONS: New OAD diagnoses are associated with WTC exposure for at least seven years. Some portion of the extended duration of that association may be due to delayed diagnoses. Nevertheless, our results support recognizing OAD among rescue workers as WTC-related even when diagnosed years after exposure.

Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung's normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well-phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC-exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after WTC exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1 below the lower limit of normal known as WTC-Lung Injury (WTC-LI). We utilized a nested case-cohort control design of previously healthy never smokers who sought subspecialty pulmonary evaluation to explore predictive biomarkers of WTC-LI. We have identified biomarkers of inflammation, metabolic derangement, protease/antiprotease balance, and vascular injury expressed in serum within 6 months of WTC exposure that were predictive of their FEV1 up to 7 years after their WTC exposure. Predicting future risk of airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services.