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Article: Health effects following exposure to dust from the World Trade Center disaster: An update

Mears, Matthew J. / Aslaner, David M. / Barson, Chad T. / Cohen, Mitchell D. / Gorr, Matthew W. / Wold, Loren E.

Life sciences. 2022 Jan. 15, v. 289

2022

Abstract: Exposure to dust, smoke, and fumes containing volatile chemicals and particulate matter (PM) from the World Trade Center (WTC) towers' collapse impacted thousands of citizens and first responders (FR; firefighters, medicals staff, police officers) of New ...

Abstract	Exposure to dust, smoke, and fumes containing volatile chemicals and particulate matter (PM) from the World Trade Center (WTC) towers' collapse impacted thousands of citizens and first responders (FR; firefighters, medicals staff, police officers) of New York City. Surviving FR and recovery workers are increasingly prone to age-related diseases that their prior WTC dust exposures might expedite or make worse. This review provides an overview of published WTC studies concerning FR/recovery workers' exposure and causal mechanisms of age-related disease susceptibility, specifically those involving the cardiopulmonary and neurological systems. This review also highlights the recent findings of the major health effects of cardiovascular, pulmonary, and neurological health sequelae from WTC dust exposure. To better treat those that risked their lives during and after the disaster of September 11, 2001, the deleterious mechanisms that WTC dust exposure exerted and continue to exert on the heart, lungs, and brain of FR must be better understood.
Keywords	brain ; complications (disease) ; disease susceptibility ; dust ; heart ; international trade ; particulates ; police ; smoke ; New York
Language	English
Dates of publication	2022-0115
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.120147
Database	NAL-Catalogue (AGRICOLA)

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Article: Bacterial host resistance models in the evaluation of immunotoxicity.

Cohen, Mitchell D

Methods (San Diego, Calif.)

2007 Volume 41, Issue 1, Page(s) 20–30

Abstract: To assess potential immunomodulatory effects of a drug, pollutant, or natural product, an analysis of an exposed host's ability to resist challenge with a viable bacteria is one of the best gauges. Many factors govern whether a host exposed to a test ... ...

Abstract	To assess potential immunomodulatory effects of a drug, pollutant, or natural product, an analysis of an exposed host's ability to resist challenge with a viable bacteria is one of the best gauges. Many factors govern whether a host exposed to a test agent and then infected becomes ill or dies at rates greater than infected control counterparts. Beyond the status of the host's immunocompetence, a bacterium's route of entry into the host and its inherent virulence are important variables determining how (and rate at which) an infection resolves. A pre-determination of endpoint(s) to be defined is critical during planning of resistance assays. If a study is to determine overall changes in immunocompetence due to exposure (regardless of regimen or dosage of test agent), then assessing shifts in morbidity/mortality at a defined lethal dose [LD(x)] value for the chosen route of infection would suffice. However, if a study is to define extent of immunomodulation in a particular body organ/cavity--or specific alterations in particular aspects of the humoral or cell-mediated immune responses--then careful selection of the pathogen, dose of the inoculum, means of infection of target site, and extent of the post-infection period to be examined, need to be made prior to host exposure to the test toxicant. This review will provide the Reader with background information about bacterial infections and how endpoint selection could be approached when designing resistance assays. An overview of protocols involved in the assays (e.g., bacterial preparation, host infection, post-infection endpoint analyses) and information about three bacteria that are among the most commonly employed in resistance assays is provided as well.
MeSH term(s)	Animals ; Bacterial Infections/immunology ; Disease Models, Animal ; Immune System/immunology ; Immune System/microbiology ; Immunocompetence/immunology ; Immunologic Factors/immunology ; Immunologic Factors/toxicity
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2007-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2006.08.010
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Article ; Online: Health effects following exposure to dust from the World Trade Center disaster: An update.

Mears, Matthew J / Aslaner, David M / Barson, Chad T / Cohen, Mitchell D / Gorr, Matthew W / Wold, Loren E

Life sciences

2021 Volume 289, Page(s) 120147

Abstract	Exposure to dust, smoke, and fumes containing volatile chemicals and particulate matter (PM) from the World Trade Center (WTC) towers' collapse impacted thousands of citizens and first responders (FR; firefighters, medicals staff, police officers) of New York City. Surviving FR and recovery workers are increasingly prone to age-related diseases that their prior WTC dust exposures might expedite or make worse. This review provides an overview of published WTC studies concerning FR/recovery workers' exposure and causal mechanisms of age-related disease susceptibility, specifically those involving the cardiopulmonary and neurological systems. This review also highlights the recent findings of the major health effects of cardiovascular, pulmonary, and neurological health sequelae from WTC dust exposure. To better treat those that risked their lives during and after the disaster of September 11, 2001, the deleterious mechanisms that WTC dust exposure exerted and continue to exert on the heart, lungs, and brain of FR must be better understood.
MeSH term(s)	Cardiovascular Diseases/chemically induced ; Cardiovascular Diseases/epidemiology ; Humans ; Lung Diseases/chemically induced ; Lung Diseases/epidemiology ; Nervous System Diseases/chemically induced ; Nervous System Diseases/epidemiology ; New York City/epidemiology ; Particulate Matter/toxicity ; September 11 Terrorist Attacks
Chemical Substances	Particulate Matter
Language	English
Publishing date	2021-11-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.120147
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Article ; Online: Health effects of World Trade Center (WTC) Dust: An unprecedented disaster's inadequate risk management.

Lippmann, Morton / Cohen, Mitchell D / Chen, Lung-Chi

Critical reviews in toxicology

2015 Volume 45, Issue 6, Page(s) 492–530

Abstract: The World Trade Center (WTC) twin towers in New York City collapsed on 9/11/2001, converting much of the buildings' huge masses into dense dust clouds of particles that settled on the streets and within buildings throughout Lower Manhattan. About 80-90% ... ...

Abstract	The World Trade Center (WTC) twin towers in New York City collapsed on 9/11/2001, converting much of the buildings' huge masses into dense dust clouds of particles that settled on the streets and within buildings throughout Lower Manhattan. About 80-90% of the settled WTC Dust, ranging in particle size from ∼2.5 μm upward, was a highly alkaline mixture of crushed concrete, gypsum, and synthetic vitreous fibers (SVFs) that was readily resuspendable by physical disturbance and low-velocity air currents. High concentrations of coarse and supercoarse WTC Dust were inhaled and deposited in the conductive airways in the head and lungs, and subsequently swallowed, causing both physical and chemical irritation to the respiratory and gastroesophageal epithelia. There were both acute and chronic adverse health effects in rescue/recovery workers; cleanup workers; residents; and office workers, especially in those lacking effective personal respiratory protective equipment. The numerous health effects in these people were not those associated with the monitored PM2.5 toxicants, which were present at low concentrations, that is, asbestos fibers, transition and heavy metals, polyaromatic hydrocarbons or PAHs, and dioxins. Attention was never directed at the very high concentrations of the larger-sized and highly alkaline WTC Dust particles that, in retrospect, contained the more likely causal toxicants. Unfortunately, the initial focus of the air quality monitoring and guidance on exposure prevention programs on low-concentration components was never revised. Public agencies need to be better prepared to provide reliable guidance to the public on more appropriate means of exposure assessment, risk assessment, and preventive measures.
MeSH term(s)	Air Pollutants/analysis ; Animals ; Disasters ; Dust/analysis ; Environmental Exposure/analysis ; Humans ; New York City ; Particle Size ; Risk Assessment/methods ; Risk Management/methods
Chemical Substances	Air Pollutants ; Dust
Language	English
Publishing date	2015-06-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	1097071-x
ISSN	1547-6898 ; 1040-8444
ISSN (online)	1547-6898
ISSN	1040-8444
DOI	10.3109/10408444.2015.1044601
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Article ; Online: Preface.

Cohen, Mitchell D

Journal of immunotoxicology

2004 Volume 1, Issue 1, Page(s) 1

Language	English
Publishing date	2004-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2205064-4
ISSN	1547-6901 ; 1547-691X
ISSN (online)	1547-6901
ISSN	1547-691X
DOI	10.1080/15476910490444552
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Article ; Online: Pulmonary immunotoxicology of select metals: aluminum, arsenic, cadmium, chromium, copper, manganese, nickel, vanadium, and zinc.

Cohen, Mitchell D

Journal of immunotoxicology

2004 Volume 1, Issue 1, Page(s) 39–69

Language	English
Publishing date	2004-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2205064-4
ISSN	1547-6901 ; 1547-691X
ISSN (online)	1547-6901
ISSN	1547-691X
DOI	10.1080/15476910490438360
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Article ; Online: Impact on rats from acute intratracheal inhalation exposures to WTC dusts.

Cohen, Mitchell D / Prophete, Colette / Horton, Lori / Sisco, Maureen / Park, Sung-Hyun / Lee, Hyun-Wook / Zelikoff, Judith / Chen, Lung-Chi

Inhalation toxicology

2020 Volume 32, Issue 5, Page(s) 218–230

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Administration, Inhalation ; Air Pollutants/toxicity ; Animals ; Blood Proteins/metabolism ; Chemokine CCL2/metabolism ; Chemokine CCL5/metabolism ; Dust ; Galectin 3/metabolism ; Leukocyte Count ; Male ; Matrix Metalloproteinase 9/metabolism ; Rats, Inbred SHR ; Receptor for Advanced Glycation End Products/metabolism ; September 11 Terrorist Attacks
Chemical Substances	Ager protein, rat ; Air Pollutants ; Blood Proteins ; Ccl2 protein, rat ; Chemokine CCL2 ; Chemokine CCL5 ; Dust ; Galectin 3 ; Lgals3 protein, rat ; Receptor for Advanced Glycation End Products ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Mmp9 protein, rat (EC 3.4.24.35)
Language	English
Publishing date	2020-05-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1038809-6
ISSN	1091-7691 ; 0895-8378
ISSN (online)	1091-7691
ISSN	0895-8378
DOI	10.1080/08958378.2020.1768322
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Article ; Online: Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.

Park, Sung-Hyun / Lu, Yuting / Shao, Yongzhao / Prophete, Colette / Horton, Lori / Sisco, Maureen / Lee, Hyun-Wook / Kluz, Thomas / Sun, Hong / Costa, Max / Zelikoff, Judith / Chen, Lung-Chi / Cohen, Mitchell D

PloS one

2021 Volume 16, Issue 10, Page(s) e0257241

Abstract: Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, ... ...

Abstract	Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.
MeSH term(s)	Anesthetics, Inhalation/administration & dosage ; Anesthetics, Inhalation/adverse effects ; Animals ; Heart/drug effects ; Inhalation Exposure/adverse effects ; Isoflurane/administration & dosage ; Isoflurane/adverse effects ; Male ; Rats ; Rats, Inbred SHR ; Transcriptome/drug effects
Chemical Substances	Anesthetics, Inhalation ; Isoflurane (CYS9AKD70P)
Language	English
Publishing date	2021-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0257241
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Longitudinal Impact of WTC Dust Inhalation on Rat Cardiac Tissue Transcriptomic Profiles.

International journal of environmental research and public health

2022 Volume 19, Issue 2

Abstract: First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative ... ...

Abstract	First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.
MeSH term(s)	Administration, Inhalation ; Animals ; Dust/analysis ; Emergency Responders ; Humans ; New York City ; Rats ; September 11 Terrorist Attacks ; Transcriptome
Chemical Substances	Dust
Language	English
Publishing date	2022-01-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19020919
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Article: Disruption of iron homeostasis as a mechanism of biologic effect by ambient air pollution particles.

Ghio, Andrew J / Cohen, Mitchell D

Inhalation toxicology

2005 Volume 17, Issue 13, Page(s) 709–716

Abstract: Several features of the clinical presentation and changes in physiology and pathology following exposure to many diverse ambient air pollution particles are comparable, suggesting a common mechanism for their biological effect. We propose that a ... ...

Abstract	Several features of the clinical presentation and changes in physiology and pathology following exposure to many diverse ambient air pollution particles are comparable, suggesting a common mechanism for their biological effect. We propose that a mechanism of biological effect common to many ambient air pollution particles is a disruption of iron homeostasis in cells and tissues. Among traits shared by every particle-related lung injury is the introduction of a solid-liquid interface into the respiratory tract. All surfaces of particulate matter have some concentration of oxygen-containing functional groups. As a result of its electropositivity, Fe(3+) has a high affinity for oxygen-donor ligands and will react with these groups at the particle surface. Retained particles accumulate metal from available sources in a cell and tissue, and this complexed iron mediates oxidant generation. In addition to complexation onto the solid-liquid interface provided by the surface of particulate matter (PM), there are several alternative pathways by which metal homeostasis in the lower respiratory tract can be disrupted following exposure to ambient air pollution particles to affect an oxidative stress. Evidence suggests that disruption in iron homeostasis following exposures to ambient air pollution particles is an initial event in their biological effect. An association between metal equilibrium in the lower respiratory tract and biological effect in the lung could explain the observed differential toxicity of ultrafine, fine, and coarse particles and disparities in host susceptibility.
MeSH term(s)	Air Pollutants/toxicity ; Homeostasis ; Humans ; Iron/metabolism ; Lung/chemistry ; Lung/physiology ; Particle Size
Chemical Substances	Air Pollutants ; Iron (E1UOL152H7)
Language	English
Publishing date	2005-09-15
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1038809-6
ISSN	1091-7691 ; 0895-8378
ISSN (online)	1091-7691
ISSN	0895-8378
DOI	10.1080/08958370500224482
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