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One airway: Biomarkers of protection from upper and lower airway injury after World Trade Center exposure
Cho, Soo Jung; Echevarria, Ghislaine C; Kwon, Sophia; Naveed, Bushra; Schenck, Edward J; Tsukiji, Jun; Rom, William N; Prezant, David J; Nolan, Anna; Weiden, Michael D
BACKGROUND: Firefighters exposed to World Trade Center (WTC) dust have developed chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1 s (FEV1). Overlapping but distinct immune responses may be responsible for the clinical manifestations of upper and lower airway injury. We investigated whether a panel of inflammatory cytokines, either associated or not associated with WTC-LI, can predict future chronic rhinosinusitis disease and its severity. METHODS: Serum obtained within six months of 9/11/2001 from 179 WTC exposed firefighters presenting for subspecialty evaluation prior to 3/2008 was assayed for 39 cytokines. The main outcomes were medically managed CRS (N = 62) and more severe CRS cases requiring sinus surgery (N = 14). We tested biomarker-CRS severity association using ordinal logistic regression analysis. RESULTS: Increasing serum IL-6, IL-8, GRO and neutrophil concentration reduced the risk of CRS progression. Conversely, increasing TNF-alpha increased the risk of progression. In a multivariable model adjusted for exposure intensity, increasing IL-6, TNF-alpha and neutrophil concentration remained significant predictors of progression. Elevated IL-6 levels and neutrophil counts also reduced the risk of abnormal FEV1 but in contrast to CRS, increased TNF-alpha did not increase the risk of abnormal FEV1. CONCLUSIONS: Our study demonstrates both independent and overlapping biomarker associations with upper and lower respiratory injury, and suggests that the innate immune response may play a protective role against CRS and abnormal lung function in those with WTC exposure.
PMCID:3946892
PMID: 24290899
ISSN: 0954-6111
CID: 665952
Paradoxical Hypotension Associated With Fluid Resuscitation In Early Sepsis Management [Meeting Abstract]
Lee, YI; Smith, RL; Cho, SJ; Gartshteyn, Y; Rom, WN; Nolan, A
ORIGINAL:0009142
ISSN: 1073-449x
CID: 1082562
YKL-40 is a Protective Biomarker for Fatty Liver in World Trade Center Particulate Matter-Exposed Firefighters
Cho, Soo Jung; Echevarria, Ghislaine C; Lee, Young Im; Kwon, Sophia; Park, Kwan Yong; Tsukiji, Jun; Rom, William N; Prezant, David J; Nolan, Anna; Weiden, Michael D
BACKGROUND: Serum biomarkers of metabolic syndrome predict abnormal lung function in World Trade Center particulate matter (WTC-PM)-exposed Fire Department of New York (FDNY) rescue workers. In animal models, exposure to ambient PM induces non-alcoholic fatty liver disease (NAFLD), a well-known comorbidity of metabolic syndrome. YKL-40 is an inflammatory biomarker for both liver and lung disease. We tested if YKL-40 is a biomarker for NAFLD in this dust-exposed cohort. METHODS: Using a nested case-control design, we studied 131 FDNY personnel who had Computer Tomography performed within 5 years post 9/11. NAFLD was defined by a liver/spleen attenuation ratio of =1. Serum biomarkers, lipid panel and liver function were measured in serum that had been drawn within 6 months of September 11, 2001. YKL-40 and chitotriosidase were assayed by ELISA. We tested biomarker and NAFLD association using logistic regression adjusted for age, BMI, and post-911 lung function. RESULTS: NAFLD was present in 29/131 (22%) of the cohort. In a multivariable model increasing YKL-40 was protective while increasing triglyceride and alkaline phosphatase were risk factors for NAFLD. CONCLUSIONS: Increased YKL-40 is a protective biomarker in non-alcoholic fatty liver disease. Further studies may reveal a link between PM-induced lung and liver diseases.
PMCID:4337810
PMID: 25717419
ISSN: 2155-9929
CID: 1473982
Inflamamatory Myositis-Increased Incidence In Fire Department Of New York Firefighters After World Trade Center Exposure [Meeting Abstract]
Qayyum, Basit ; Glaser, Michelle S. ; Jaber, Nadia ; Zeig-Owens, Rachel ; Webber, Mayris P. ; Nolan, Anna ; Kelly, Kerry J. ; Prezant, David J.
ISI:000325359204474
ISSN: 0004-3591
CID: 656602
Chitotriosidase is a Biomarker for the Resistance to World Trade Center Lung Injury in New York City Firefighters
Cho, Soo Jung; Nolan, Anna; Echevarria, Ghislaine C; Kwon, Sophia; Naveed, Bushra; Schenck, Edward; Tsukiji, Jun; Prezant, David J; Rom, William N; Weiden, Michael D
PURPOSE: World Trade Center (WTC) exposure caused airflow obstruction years after exposure. Chitinases and IgE are innate and humoral mediators of obstructive airway disease. We investigated if serum expression of chitinases and IgE early after WTC exposure predicts subsequent obstruction. METHODS: With a nested case-control design, 251 FDNY personnel had chitotriosidase, YKL-40 and IgE measured in serum drawn within months of 9/11/2001. The main outcome was subsequent Forced Expiratory Volume after 1 second/Forced Vital Capacity (FEV1/FVC) less than the lower limit of normal (LLN). Cases (N = 125) had abnormal FEV1/FVC whereas controls had normal FEV1/FVC (N = 126). In a secondary analysis, resistant cases (N = 66) had FEV1 (>/=107 %) one standard deviation above the mean. Logistic regression adjusted for age, BMI, exposure intensity and post-exposure FEV1/FVC modeled the association between early biomarkers and later lung function. RESULTS: Cases and Controls initially lost lung function. Controls recovered to pre-9/11 FEV1 and FVC while cases continue to decline. Cases expressed lower serum chitotriosidase and higher IgE levels. Increase in IgE increased the odds of airflow obstruction and decreased the odds of above average FEV1. Alternately, increasing chitotriosidase decreased the odds of abnormal FEV1/FVC and increased the odds of FEV1 >/= 107 %. Serum YKL-40 was not associated with FEV1/FVC or FEV1 in this cohort. CONCLUSIONS: Increased serum chitotriosidase reduces the odds of developing obstruction after WTC-particulate matter exposure and is associated with recovery of lung function. Alternately, elevated IgE is a risk factor for airflow obstruction and progressive lung function decline.
PMCID:3722498
PMID: 23744081
ISSN: 0271-9142
CID: 366742
The respiratory pyramid: From symptoms to disease in World Trade Center exposed firefighters
Niles, Justin K; Webber, Mayris P; Cohen, Hillel W; Hall, Charles B; Zeig-Owens, Rachel; Ye, Fen; Glaser, Michelle S; Weakley, Jessica; Weiden, Michael D; Aldrich, Thomas K; Nolan, Anna; Glass, Lara; Kelly, Kerry J; Prezant, David J
BACKGROUND: This study utilizes a four-level pyramid framework to understand the relationship between symptom reports and/or abnormal pulmonary function and diagnoses of airway diseases (AD), including asthma, recurrent bronchitis and COPD/emphysema in WTC-exposed firefighters. We compare the distribution of pyramid levels at two time-points: by 9/11/2005 and by 9/11/2010. METHODS: We studied 6,931 WTC-exposed FDNY firefighters who completed a monitoring exam during the early period and at least two additional follow-up exams 9/11/2005-9/11/2010. RESULTS: By 9/11/2005 the pyramid structure was as follows: 4,039 (58.3%) in Level 1, no respiratory evaluation or treatment; 1,608 (23.2%) in Level 2, evaluation or treatment without AD diagnosis; 1,005 (14.5%) in Level 3, a single AD diagnosis (asthma, emphysema/COPD, or recurrent bronchitis); 279 (4.0%) in Level 4, asthma and another AD. By 9/11/2010, the pyramid distribution changed considerably, with Level 1 decreasing to 2,612 (37.7% of the cohort), and Levels 3 (N = 1,530) and 4 (N = 796) increasing to 22.1% and 11.5% of the cohort, respectively. Symptoms, spirometry measurements and healthcare utilization were associated with higher pyramid levels. CONCLUSIONS: Respiratory diagnoses, even four years after a major inhalation event, are not the only drivers of future healthcare utilization. Symptoms and abnormal FEV-1 values must also be considered if clinicians and healthcare administrators are to accurately anticipate future treatment needs, years after initial exposure. Am. J. Ind. Med. (c) 2013 Wiley Periodicals, Inc.
PMCID:5719892
PMID: 23788055
ISSN: 0271-3586
CID: 402032
Elevated IP-10 and IL-6 from bronchoalveolar lavage cells are biomarkers of non-cavitary tuberculosis
Nolan, A; Condos, R; Huie, M L; Dawson, R; Dheda, K; Bateman, E; Rom, W N; Weiden, M D
BACKGROUND: Active TB disease can destroy lung parenchyma leading to cavities. Immune responses that predispose or protect individuals from lung damage during TB are poorly defined. OBJECTIVE: To sample lung immune cells and assay bronchoalveolar lavage (BAL) cell cytokine production. DESIGN: Enrolled subjects (n = 73) had bilateral infiltrates and underwent BAL. RESULTS: All had sputum culture demonstrating Mycobacterium tuberculosis and 22/73 (30%) had cavities on their chest radiograph. Those with cavities at presentation had a higher percentage of polymorphonuclear neutrophils (PMN) in BAL as well as lower inducible protein (IP) 10 (P < 0.01) and interleukin (IL) 6 (P = 0.013) in BAL cell supernatants compared to those without cavities. There was no correlation between cavities and other BAL or serum cytokines. IP-10 was negatively associated with BAL PMN. IP-10 and IL-6 expression above median reduces the odds of cavities by 79% and 78% in logistic regression models. IP-10 and IL-6 clustered with interferon-gamma and tumour necrosis factor-alpha in a principal component analysis, while IL-4 clustered with PMN. CONCLUSION: Increasing IP-10 and IL-6 production by BAL cells is associated with non-cavitary TB in patients who present with radiographically advanced TB. IP-10 and IL-6 may reflect an effective T-helper 1 immune control pathway for TB, attenuating tuberculous lung destruction.
PMCID:4050635
PMID: 23743311
ISSN: 1027-3719
CID: 366752
Acute Respiratory Failure Secondary to Achalasia
Adamson, Rosemary; Lee, Young Im; Berger, Kenneth I; Sutin, Kenneth; Nolan, Anna
PMCID:5475431
PMID: 23802830
ISSN: 2325-6621
CID: 402022
Cardiovascular disease biomarkers predict susceptibility or resistance to lung injury in World Trade Center dust exposed firefighters
Weiden, Michael D; Naveed, Bushra; Kwon, Sophia; Jung Cho, Soo; Comfort, Ashley L; Prezant, David J; Rom, William N; Nolan, Anna
Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome, predicts loss of lung function in World Trade Center Lung Injury(WTC-LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI.This nested case-cohort study used 801 never smoker, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March, 2008. A representative sub-cohort of 124/801 with serum drawn within six months of 9/11 defined CVD biomarker distribution. Post-9/11/01 FEV1 at subspecialty exam defined cases: susceptible WTC-LI cases with FEV1=77% predicted (66/801) and resistant WTC-LI cases with FEV1>/=107% (68/801). All models were adjusted for WTC exposure intensity, BMI at SPE, age at 9/11, and pre-9/11 FEV1.Susceptible WTC-LI cases had higher levels of Apo-AII, CRP, and MIP-4 with significant RRs of 3.85, 3.93, and 0.26 respectively with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher sVCAM and lower MPO with RRs of 2.24, and 2.89 respectively; AUC 0.830.Biomarkers of CVD in serum six-month post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure.
PMCID:3642231
PMID: 22903969
ISSN: 0903-1936
CID: 212242
Chitotriosidase And Immunoglobulin E Predict Airway Obstruction In World Trade Center Exposed New York City Firefighters [Meeting Abstract]
Cho, S; Echevarria, G; Kwon, S; Schenck, E; Tsukiji, J; Prezant, D.J.; Rom, WN ; Nolan, A; Weiden, M.D.
ORIGINAL:0008266
ISSN: 1752-8054
CID: 353042