Faculty Bibliography

BACKGROUND: World Trade Center (WTC)-exposed rescue/recovery workers endured massive respiratory insult from inhalation of particulate matter and gases, resulting in respiratory symptoms, loss of lung function, and, for many, bronchial hyperreactivity (BHR). The persistence of respiratory symptoms and lung function abnormalities has been well-documented, whereas persistence of BHR has not been investigated. METHODS: A total of 173 WTC-exposed firefighters with bronchial reactivity measured within 2 years after September 11, 2001 (9/11) (baseline methacholine challenge test), were reevaluated in 2013 and 2014 (follow-up methacholine challenge test). FEV1 measurements were obtained from the late pre-9/11, early post-9/11, and late post-9/11 periods. Respiratory symptoms and corticosteroid treatment were recorded. RESULTS: Bronchial reactivity remained stable (within 1 doubling dilution) for most (n = 101, 58%). Sixteen of 28 (57%) with BHR (provocative concentration of methacholine producing a 20% decline in FEV1 <8 mg/mL) at baseline had BHR at follow-up, and an additional 27 of the 145 (19%) without BHR at baseline had BHR at follow-up. In multivariable models, we found that BHR baseline was strongly associated with BHR follow-up (OR, 6.46) and that BHR at follow-up was associated with an estimated 15.4 mL/y greater FEV1 decline than experienced by those without BHR at follow-up. Annual FEV1 decline was moderated by corticosteroid use. CONCLUSIONS: Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease.

BACKGROUND: High rates of upper and lower airways disease have occurred in Fire Department of the City of New York (FDNY) workers exposed to the World Trade Center (WTC) disaster site. Most experienced acute declines in pulmonary function, and some continued to experience decline over 14 years of follow-up. Similarly, some with rhinosinusitis had symptoms requiring sinus surgery. AIM: To increase generalizability of biomarker investigation, we describe biomarkers of risk for upper and lower airway injury that do not require stored serum. METHODS: We review WTC biomarker literature. RESULTS: Cytokines expressed in stored serum from the first 6 months post-9/11 can identify individuals at higher risk for future abnormal pulmonary function. CONCLUSION: This research will help identify individuals at high risk of lung and sinus disease that develop after these, or future, irritant exposures for intensive monitoring and treatment. It may also identify targets for effective therapeutic interventions. Am. J. Ind. Med. 59:788-794, 2016. (c) 2016 Wiley Periodicals, Inc.

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: The study of sepsis is hindered by its heterogeneous time course and evolution. A subgroup of patients with severe sepsis develops shock soon after the initiation of treatment while others present hypotensive. We sought to determine the incidence of hypotension after the initiation of treatment for sepsis, and characterize their clinical features and course. METHODS: A retrospective review of electronic medical record of all septic patients (n = 542) that met the definition of septic shock within 24 hours of admission (2011 - 2012) at an urban Veteran Affairs Hospital was performed. Subjects either had 1) initial normotension (INT) with hypotension developing within 24 hours or 2) initial hypotension (IH). Logistic regression was used to model associated factors of INT/IH. RESULTS: INT occurred in 62 patients (11%) with average initial blood pressure of 120/71 mm Hg and developed hypotension to 79/48 mm Hg. IH was identified in 52 patients (10%) with average presenting blood pressure of 81/46 mm Hg. INT showed evidence of increased sympathetic tone with significantly higher heart rate, blood pressure and temperature. INT patients were younger, more frequently on alpha-blockers, and more likely septic from pneumonia compared to IH patients. INT and IH patients had similar timing of antibiotic initiation, amount of 24-hour fluid resuscitation, vasopressor use, organ dysfunction and mortality at 28 days. Using alpha-blockers, being Caucasian, and having higher temperatures were independent predictors of INT. CONCLUSION: INT is a distinctive presentation of septic shock characterized by rapid deterioration during early treatment. By further studying this subgroup, mediators of septic shock may be identified that clarify pathophysiology and provide timely targeted treatment.