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High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster

Jasra, Sakshi; Giricz, Orsi; Zeig-Owens, Rachel; Pradhan, Kith; Goldfarb, David G; Barreto-Galvez, Angelica; Silver, Alexander J; Chen, Jiahao; Sahu, Srabani; Gordon-Mitchell, Shanisha; Choudhary, Gaurav S; Aluri, Srinivas; Bhagat, Tushar D; Shastri, Aditi; Bejan, Cosmin A; Stockton, Shannon S; Spaulding, Travis P; Thiruthuvanathan, Victor; Goto, Hiroki; Gerhardt, Jeannine; Haider, Syed Hissam; Veerappan, Arul; Bartenstein, Matthias; Nwankwo, George; Landgren, Ola; Weiden, Michael D; Lekostaj, Jacqueline; Bender, Ryan; Fletcher, Frederick; Greenberger, Lee; Ebert, Benjamin L; Steidl, Ulrich; Will, Britta; Nolan, Anna; Madireddy, Advaitha; Savona, Michael R; Prezant, David J; Verma, Amit
The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.7%; 17 out of 255; odds ratio, 3.14; 95% confidence interval, 1.64-6.03; P = 0.0006) after controlling for age, sex and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A, TET2 and other CH-associated genes. Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. In summary, the high burden of CH in WTC-exposed first responders provides a rationale for enhanced screening and preventative efforts in this population.
PMID: 35256801
ISSN: 1546-170x
CID: 5180942

A Pandemic's Lifecycle: A Longitudinal Validation of Predictors in 26,249 Severe COVID-19 NYC Admissions [Meeting Abstract]

Crowley, G; Kwon, S; Kim, J; Liu, M; Nolan, A
ORIGINAL:0015551
ISSN: 1535-4970
CID: 5203472

Critically Ill Unrepresented Patients Phenotypic Characteristics: A [Meeting Abstract]

Walsh, BC; Nolan, A
ORIGINAL:0015552
ISSN: 1535-4970
CID: 5203482

Alveolar Macrophages and Epithelial Cells Express RAGE in a Murine [Meeting Abstract]

Veerappan, A; Sunseri, M; Young, IR; Nolan, A
ORIGINAL:0015553
ISSN: 1535-4970
CID: 5203492

The Microbiome of Inflammation and Nutrition: World Trade Center [Meeting Abstract]

Kim, J; Lam, R; Phillips, W; Kwon, S; Crowley, G; Prezant, DJ; Nolan, A
ORIGINAL:0015554
ISSN: 1535-4970
CID: 5203502

A Bloody Drowning: an Uncommon EVALI Presentation Complicated by [Meeting Abstract]

Forster, M; Demirci, T; Benes, L; Carlucci, PM; Palmares, F; Hache-Marliere, M; Nolan, A
ORIGINAL:0015555
ISSN: 1535-4970
CID: 5203512

A Prospective Longitudinal Assessment of Nutrition in the FDNY World [Meeting Abstract]

Lam, R; Kwon, S; Crowley, G; Zeig-Owens, R; Mueller, A; Prezant, DJ; Nolan, A
ORIGINAL:0015556
ISSN: 1535-4970
CID: 5203522

World Trade Center Particulate Matter-Induced Cardiorespiratory and [Meeting Abstract]

Kwon, S; Crowley, G; Liu, M; Zeig-Owens, R; Mueller, A; Presant, DJ; Nolan, A
ORIGINAL:0015557
ISSN: 1535-4970
CID: 5203532

Twenty-Year Reflection on the Impact of World Trade Center Exposure on Pulmonary Outcomes in Fire Department of the City of New York (FDNY) Rescue and Recovery Workers

Cleven, Krystal L; Rosenzvit, Carla; Nolan, Anna; Zeig-Owens, Rachel; Kwon, Sophia; Weiden, Michael D; Skerker, Molly; Halpren, Allison; Prezant, David J
After the terrorist attacks on September 11, 2001 (9/11), many rescue/recovery workers developed respiratory symptoms and pulmonary diseases due to their extensive World Trade Center (WTC) dust cloud exposure. Nearly all Fire Department of the City of New York (FDNY) workers were present within 48 h of 9/11 and for the next several months. Since the FDNY had a well-established occupational health service for its firefighters and Emergency Medical Services workers prior to 9/11, the FDNY was able to immediately start a rigorous monitoring and treatment program for its WTC-exposed workers. As a result, respiratory symptoms and diseases were identified soon after 9/11. This focused review summarizes the WTC-related respiratory diseases that developed in the FDNY cohort after 9/11, including WTC cough syndrome, obstructive airways disease, accelerated lung function decline, airway hyperreactivity, sarcoidosis, and obstructive sleep apnea. Additionally, an extensive array of biomarkers has been identified as associated with WTC-related respiratory disease. Future research efforts will not only focus on further phenotyping/treating WTC-related respiratory disease but also on additional diseases associated with WTC exposure, especially those that take decades to develop, such as cardiovascular disease, cancer, and interstitial lung disease.
PMCID:8583580
PMID: 34766209
ISSN: 1432-1750
CID: 5050772

Dynamic Metabolic Risk Profiling of World Trade Center-Lung Disease: A Longitudinal Cohort Study

Kwon, Sophia; Lee, Myeonggyun; Crowley, George; Schwartz, Theresa; Zeig-Owens, Rachel; Prezant, David J; Liu, Mengling; Nolan, Anna
PMID: 34473012
ISSN: 1535-4970
CID: 4995692