Faculty Bibliography

Microaspiration is a common phenomenon in healthy subjects, but its frequency is increased in chronic inflammatory airway diseases, and its role in inflammatory and immune phenotypes is unclear. We have previously demonstrated that acellular bronchoalveolar lavage samples from half of the healthy people examined are enriched with oral taxa (here called pneumotypeSPT) and this finding is associated with increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage. Here, we have characterized the inflammatory phenotype using a multi-omic approach. By evaluating both upper airway and acellular bronchoalveolar lavage samples from 49 subjects from three cohorts without known pulmonary disease, we observed that pneumotypeSPT was associated with a distinct metabolic profile, enhanced expression of inflammatory cytokines, a pro-inflammatory phenotype characterized by elevated Th-17 lymphocytes and, conversely, a blunted alveolar macrophage TLR4 response. The cellular immune responses observed in the lower airways of humans with pneumotypeSPT indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.

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.

PURPOSE: An increased incidence of sarcoidosis has been demonstrated in firefighters, supporting the concern that occupational/environmental exposure may pose an etiologic risk factor. This incidence increased further after September 11, 2001 following exposure to World Trade Center (WTC) dust and gases. We review computed tomography (CT) features in this population, comparing the range of findings and physiological correlates with those typically reported in unexposed individuals with pulmonary sarcoidosis. MATERIALS AND METHODS: With CT imaging we retrospectively identified 46 patients with WTC-related sarcoidosis, between March 18, 2002 and April 5, 2014. Scans were independently reviewed by 2 dedicated thoracic radiologists and assessed for disease patterns and correlation with pulmonary functions. RESULTS: The majority (37/46; 80%) had symmetric mediastinal and hilar lymphadenopathy. Similarly, most (38/46; 83%) had perilymphatic nodules. Foci of ill-defined ground glass attenuation were present in 6 (13%). Coalescent nodularity was present in 15 (33%). Only 3 (7%) had parenchymal reticulation. A mixed pattern of lung findings was present in 21 (46%). When all forms of parenchymal disease were scored by zonal distribution, 21 (46%) had parenchymal disease predominantly involving mid and upper lungs; 11/46 (24%) had a random distribution without zonal predominance; 6/46 (13%) demonstrated atypical lower zone predominance. Whereas 15/46 (33%) had obstructive airways disease on pulmonary function tests, there were no CT findings that were predictive of obstructive airways disease. CONCLUSIONS: The majority of cases of WTC-related sarcoidosis demonstrated typical radiographic appearances of sarcoidosis, with symmetric hilar and mediastinal lymphadenopathy and mid to upper lung perilymphatic nodules; these findings were consistent with other previously reported cases of sarcoid-like granulomatous disease in association with various alternate underlying etiologies. There was no correlation between disease patterns or extent on CT and pulmonary function testing, likely at least in part due to the overall mild extent of disease in this population.

BACKGROUND: World Trade Center (WTC)-exposed Fire Department of the City of New York firefighters lost, on average, 10% of lung function after September 11, 2011, and >10% developed new obstructive airways disease. There was little recovery (on average) over the first 6 years. Follow-up into the next decade allowed us to determine the longer-term exposure effects and the roles of cigarette smoking and cessation on lung function trajectories. METHODS: We examined serial measurements of FEV1 from March 11, 2000, to September 10, 2014, among 10,641 WTC-exposed Fire Department of the City of New York firefighters with known smoking and body weight histories. RESULTS: The median number of FEV1 measurements during follow-up was 9; 15% of firefighters arrived at the WTC during the morning of September 11, 2001; and 65% never smoked. Firefighters arriving the morning of September 11, 2001 averaged lower lung function than did lesser exposed firefighters; this difference remained significant during most of follow-up (P < .05). Never smokers had significantly better lung function than current smokers; former smokers fell in between, depending upon their cessation date. Those arriving the morning of September 11, 2001 were more likely to have an FEV1 < lower limits of normal compared with those arriving between September 13, 2001, and September 24, 2001 (OR = 1.70, P < .01). Current smokers were more likely to have an FEV1 < lower limits of normal compared with never smokers (OR = 2.06, P < .01), former smokers who quit before September 11, 2001 (OR = 1.96, P < .01), or those who quit between September 11, 2001 and March 10, 2008 (OR = 1.49, P < .01). CONCLUSIONS: Thirteen years after September 11, 2001, most firefighters continued to show a lack of lung function recovery, with the trajectory of decline differing by WTC exposure and smoking status. Unlike the immutable effect of WTC exposure, we demonstrated the benefit on lung function of smoking cessation in this unique occupational/environmental cohort.

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.