Faculty Bibliography

INTRODUCTION/BACKGROUND:Use of alternative nicotine delivery systems, such as electronic cigarettes and hookahs, has increased dramatically in the USA, but limited research has been conducted on the secondhand effects of these products, especially in children. The objective of this study is to assess the cardiopulmonary effects of e-cigarette and hookah use in vaping and smoking adults, and in non-smoking/non-vaping adults and children exposed to secondhand particles and gases. METHODS AND ANALYSIS/UNASSIGNED:This study uses a pre/post design, with four groups: two control groups (non-smoking/non-vaping and cigarette smoking) and two test groups (hookah smoking and e-cigarette vaping). Participants will be recruited by household, so that each home includes one smoking or vaping adult and one non-smoking/non-vaping adult and/or child (5-18 years). Non-smoking/non-vaping homes include an adult and child who do not smoke or vape and do not live with individuals who do. Air quality measures will be completed during a household smoking or vaping session (ambient air for non-smoking/non-vaping group), while cardiopulmonary measures and biological samples will be taken directly before and after the smoking/vaping session, and again 24 hours later, for all participants. Air quality measures include carbon monoxide, black carbon, particulate matter, trace elements, nicotine and carbonyls; cardiopulmonary measures include heart rate variability, blood pressure, pulmonary function and exhaled carbon monoxide; biological samples will assess cotinine, inflammatory cytokines and biomarkers in urine, saliva and nasal mucosa. ETHICS AND DISSEMINATION/UNASSIGNED:This study was approved by the Institutional Review Board at New York University School of Medicine (s16-02226 and s17-01143). Special attention was given to the inclusion of children, who are likely significantly impacted by the use of these products at home, and thus should be included in research. Results of the study will be distributed at conferences, in peer-reviewed journals and to relevant public health authorities for use in developing policy.

BACKGROUND:With the number of annual global travelers reaching 1.2 billion, many individuals encounter greater levels of air pollution when they travel abroad to megacities around the world. This study's objective was to determine if visits to cities abroad with greater levels of air pollution adversely impacts cardiopulmonary health. METHODS:Thirty-four non-smoking, adult, healthy participants who traveled abroad to selected cities from the NYC metropolitan area were pre-trained to measure lung function, blood pressure, heart rate/variability, and record symptoms before, during, and after traveling abroad. Outdoor PM2.5 concentrations were obtained from central monitors in each city. Associations between PM exposure concentrations and cardiopulmonary health endpoints were analyzed using a mixed effects statistical design. RESULTS:East and South Asian cities had significantly higher PM2.5 concentrations compared to pre-travel NYC PM2.5 levels, with maximum concentrations reaching 503 μg/m3. PM exposure-related associations for lung function were statistically significant and strongest between evening FEV1 and same day morning PM2.5 concentrations: a 10 μg/m3 increase in outdoor PM2.5 was associated with a mean decrease of 7 ml. Travel to a highly polluted city (PM2.5 > 100 μg/m3) was associated with a 209 ml reduction in evening FEV1 compared to a low polluted city (PM2.5 < 35 μg/m3). In general, participants who traveled to East and South Asian cities experienced increased respiratory symptoms/scores and changes in heart rate and heart rate variability. CONCLUSIONS:Exposure to increased levels of PM2.5 in cities abroad caused small but statistically significant acute changes in cardiopulmonary function and respiratory symptoms in healthy young adults. These data suggest that travel-related exposure to increased PM2.5 adversely impacts cardiopulmonary health, which may be particularly important for travelers with pre-existing respiratory or cardiac disease.

Annual increases in global travel have resulted in more individuals being exposed to varying environmental conditions abroad and, thereby, subject to air pollution related health risks. Individuals who travel abroad may be exposed to varying levels of air pollution within a matter of hours. We wish to consider whether exposure to air pollution could be a significant contributor to the risk of illness and death in travelers, particularly those who travel to highly polluted cities. We report the findings of a study in which the peak expiratory flow (PEF) of a traveler decreased in Shanghai relative to baseline in New York City; the decline in PEF correlated to concentration of particulate matter (PM2.5). We discuss the health implication of these results on global travel.

Recent epidemiological data indicate that the popularity of electronic cigarettes (e-cigarettes), and consequently nicotine use, is rising in both adolescent and adult populations. As nicotine is a known developmental neurotoxin, these products present a potential threat for those exposed during early life stages. Despite this, few studies have evaluated the toxicity of e-cigarettes on the developing central nervous system (CNS). The goal of this study was to assess neurotoxicity resulting from early life exposure to electronic cigarette aerosols in an in vivo model. Specifically, studies here focused on neuro-parameters related to neuroinflammation and neurotrophins. To accomplish this, pregnant and neonatal C57BL/6 mice were exposed to aerosols produced from classic tobacco flavor e-cigarette cartridges (with [13 mg/ml] and without nicotine) during gestation ( approximately 3-wk) and lactation ( approximately 3-wk) via whole-body inhalation. Exposure to e-cigarette aerosols with and without nicotine caused significant reductions in hippocampal gene expression of Ngfr and Bdnf, as well as in serum levels of cytokines IL-1beta, IL-2 and IL-6. Exposure to e-cigarette aerosols without nicotine enhanced expression of Iba-1, a specific marker of microglia, in the CA1 region of the hippocampus. Overall, our novel results indicate that exposure to e-cigarette aerosols, with and without nicotine, poses a considerable risk to the developing CNS. Consequently, e-cigarettes should be considered a potential public health threat, especially early in life, requiring further research and policy considerations.

Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rodent studies indicate that AgNPs can cause lung inflammation and toxicity in a strain- and particle type-dependent manner, but mechanisms of susceptibility remain unclear. The aim of this study was to assess the variation in AgNP-induced lung inflammation and toxicity across multiple inbred mouse strains and to use genome-wide association (GWA) mapping to identify potential candidate susceptibility genes. Mice received doses of 0.25 mg/kg of either 20-nm citrate-coated AgNPs or citrate buffer using oropharyngeal aspiration. Neutrophils in bronchoalveolar lavage fluid (BALF) served as markers of inflammation. We found significant strain- and treatment-dependent variation in neutrophils in BALF. GWA mapping identified 10 significant single-nucleotide polymorphisms (false discovery rate, 15%) in 4 quantitative trait loci on mouse chromosomes 1, 4, 15, and 18, and Nedd4l (neural precursor cell expressed developmentally downregulated gene 4-like; chromosome 18), Ano6 (anocatmin 6; chromosome 15), and Rnf220 (Ring finger protein 220; chromosome 4) were considered candidate genes. Quantitative RT-PCR revealed significant inverse associations between mRNA levels of these genes and neutrophil influx. Nedd4l, Ano6, and Rnf220 are candidate susceptibility genes for AgNP-induced lung inflammation that warrant additional exploration in future studies.-Scoville, D. K., Botta, D., Galdanes, K., Schmuck, S. C., White, C. C., Stapleton, P. L., Bammler, T. K., MacDonald, J. W., Altemeier, W. A., Hernandez, M., Kleeberger, S. R., Chen, L.-C., Gordon, T., Kavanagh, T. J. Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice.

United States soldiers are returning from the Greater Middle East with respiratory illnesses ranging from new onset asthma to constrictive bronchiolitis. The etiology of the diseases is unknown. A study was conducted to determine the possible role of local mineral dust in the development of abnormal respiratory illnesses in soldiers during and after deployment in Iraq. A dust sample obtained in proximity to a burn pit in Camp Victory, Iraq, (CVD) was characterized both chemically and mineralogically. For comparison, a dust sample from Fort Irwin, California, (FID) was also collected. The ability of the dust samples to generate reactive oxygen species (ROS) was quantified, as well as their ability to generate an inflammatory stress response (ISR) in human lung epithelial cells. Both samples are comprised of common silicate and carbonate minerals and contain heavy metals with concentration ranges expected for mineral dust. The ISR generated by each sample was within the range of inert material with the minimal stress generated associated with the carbonate phases. The findings based on this one sample suggest that the origin of the disease is not driven by the particles ability to generate ROS. However it is likely that particle overload, and associated complications, or endotoxin contribute extensively to pathogenesis.

World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)>/=97pg/mL, CRP>/=2.4mg/L, and MMP-9