Faculty Bibliography

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.

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.