Faculty Bibliography

RATIONALE: On September 11, 2001, the World Trade Center collapse created an enormous urban disaster site with high levels of airborne pollutants. First responders, rescue and recovery workers, and residents have since reported respiratory symptoms and developed pulmonary function abnormalities. OBJECTIVES: To quantify respiratory health effects of World Trade Center exposure in the New York City Fire Department. MEASUREMENTS: Longitudinal study of pulmonary function in 12,079 New York City Fire Department rescue workers employed on or before 09/11/2001. Between 01/01/1997 and 09/11/2002, 31,994 spirometries were obtained and the FEV(1) and FVC were analyzed for differences according to estimated World Trade Center exposure intensity. Adjusted average FEV(1) during the first year after 09/11/2001 was compared with the 5 yr before 09/11/2001. Median time between 09/11/2001 and a worker's first spirometry afterwards was 3 mo; 90% were assessed within 5 mo. MAIN RESULTS: World Trade Center-exposed workers experienced a substantial reduction in adjusted average FEV(1) during the year after 09/11/2001 (372 ml; 95% confidence interval, 364-381 ml; p < 0.001) This exposure-related FEV(1) decrement equaled 12 yr of aging-related FEV(1) decline. Moreover, exposure intensity assessed by initial arrival time at the World Trade Center site correlated linearly with FEV(1) reduction in an exposure intensity-response gradient (p = 0.048). Respiratory symptoms also predicted a further FEV(1) decrease (p < 0.001). Similar findings were observed for adjusted average FVC. CONCLUSIONS: World Trade Center exposure produced a substantial reduction in pulmonary function in New York City Fire Department rescue workers during the first year after 09/11/2001

Pulmonary tuberculosis (TB) has been characterized by inflammation with increased pro- or anti-inflammatory cytokines produced by macrophages. We have reported that IFN produces inhibitory C/EBPbeta and represses transcription of the HIV-1 LTR in macrophages. STAT-1 and type I IFN receptor knockout mice have macrophages that are defective in IFN signaling, yet LPS stimulation induces inhibitory C/EBPbeta, demonstrating that other cytokines can induce this repressor. LPS or Mycobacterium tuberculosis-derived lipoarabinomannan induce the anti-inflammatory cytokine interleukin (IL)-10, which represses the HIV-1 LTR in differentiated THP-1 macrophages by inducing inhibitory C/EBPbeta. In contrast, in undifferentiated THP-1 monocytes, IL-10 did not inhibit HIV-1 replication or induce C/EBPbeta. IL-10 signal transduction uses STAT-3, and macrophages from STAT-3-/- mice fail to produce inhibitory C/EBPbeta after LPS or IL-10 stimulation. Transfection of STAT-3 into THP-1 cells enhances C/EBPbeta promoter activity. THP-1 differentiation also increases STAT-3 protein, but not STAT-3 gene transcription, and induces a translational regulator, CUG-binding protein, that was essential for production of C/EBPbeta. Differentiation induced post-transcriptional regulation is required to produce inhibitory C/EBPbeta in response to IL-10. Only macrophages are able to repress HIV-1 LTR promoter activity and inhibit viral replication in response to IL-10 or type I IFN

BACKGROUND: The collapse of the World Trade Center (WTC) on September 11, 2001 created a large-scale disaster site in a dense urban environment. In the days and months thereafter, thousands of rescue/recovery workers, volunteers, and residents were exposed to a complex mixture of airborne pollutants. METHODS: We review current knowledge of aerodigestive inhalation lung injuries resulting from this complex exposure and present new data on the persistence of nonspecific bronchial hyperreactivity (methacholine PC20 < or =8 mg/mL) in a representative sample of 179 Fire Department of the City of New York (FDNY) rescue workers stratified by exposure intensity (according to arrival time) who underwent challenge testing at 1, 3, 6, and 12 months post-collapse. RESULTS: Aerodigestive tract inflammatory injuries, such as declines in pulmonary function, reactive airways dysfunction syndrome (RADS), asthma, reactive upper airways dysfunction syndrome (RUDS), gastroesophageal reflux disease (GERD), and rare cases of inflammatory pulmonary parenchymal diseases, have been documented in WTC rescue/recovery workers and volunteers. In FDNY rescue workers, we found persistent hyperreactivity associated with exposure intensity, independent of airflow obstruction. One year post-collapse, 23% of highly exposed subjects were hyperreactive as compared with only 11% of moderately exposed and 4% of controls. At 1 yr, 16% met the criteria for RADS. CONCLUSIONS: While it is too early to ascertain all of the long-term effects of WTC exposures, continued medical monitoring and treatment is needed to help those exposed and to improve our prevention, diagnosis, and treatment protocols for future disasters