Characterization of e-cigarette users according to device type, use behaviors, and self-reported health outcomes: Findings from the EMIT study.

INTRODUCTION: Electronic cigarettes (e-cigarettes) rapidly evolved from large modifiable (MOD) devices, to small and affordable 'POD' devices. Detailed information on user demographics and preferences according to device type, which can inform potential chemical exposure and policy recommendations, is currently limited. The goal of this study is to describe user demographics, use behaviors and preferences, as well as self-reported health outcomes according to the e-cigarette device type used. METHODS: From April 2019 to March 2020, 91 participants from Maryland (18 MOD users, 26 POD users, 16 dual users (use of both combustible and e-cigarettes), and 31 non-users (never e-cigarette users and never smokers or >6 months former use) were recruited. A comprehensive questionnaire collected sociodemographic characteristics, e-cigarette/tobacco use behaviors, self-reported health outcomes, device characteristics and preferences. Chi-squared tests for categorical variables, ANOVA for continuous variables, qualitative thematic analysis, linear and logistic regressions were used to assess relationships between variables and groups. RESULTS: POD users were younger (average 22.5 years) than MOD users (30.8 years) or dual users (34.3 years) (p<0.001). MOD users reported more puffs per day (mean ± SD: 373 ± 125 puffs) compared to POD users (123.0 ± 172.5). E-cigarette users who were former smokers used 1.16 mg/mL lower nicotine concentrations compared to lifetime exclusive e-cigarette users (p=0.03) in linear models. Exclusive POD users self-reported more coughing than exclusive MOD or dual users (p=0.02). E-cigarette users reported more shortness of breath, headaches, and fatigue from their e-cigarette use compared to non-users. CONCLUSIONS: We found significant differences between user demographics, e-cigarette preferences, device characteristics, and use behaviors by user group. This information can help explain exposure to chemicals from e-cigarettes, including compounds with known toxic effects (e.g. metals, formaldehyde), and help inform the design of prevention and intervention strategies and policy decisions.

The relationship between the use of electronic nicotine delivery systems (ENDS) and effects on pulmonary immune responses-a literature review.

INTRODUCTION: The use of electronic nicotine delivery systems (ENDS), or vaping, is a relatively recent phenomenon, and there are various gaps in our current knowledge regarding the specific effects of e-cigarettes, such as their immunological effects. The importance of this question became even more relevant in light of the COVID-19 pandemic. OBJECTIVE: This literature review examines the relationship between the use of electronic nicotine delivery systems (ENDS) and immunological effects to examine available information and identify gaps in the current knowledge. Our search strategy included studies focusing on the effects of ENDS on the immune response during infectious respiratory diseases such as COVID-19 and pneumonia. METHODS: Peer-reviewed studies presenting quantitative data published from 2007, the year that e-cigarettes were introduced to the US market until 2022 have been included. All studies were indexed in PubMed. We excluded papers on THC and EVALI (E-cigarette, or Vaping Product, Use Associated Lung Injury) as we wanted to focus on the effects of nicotine devices. RESULTS: Among the 21 articles that assessed the relationship between ENDS and immunological health effects, we found eight studies based on cell models, two articles based on both cell and mouse models, five articles based on mouse models, and six studies of human populations. Most of the articles identified in our review demonstrated a potential association between vaping and adverse immunological health effects. DISCUSSION: Overall, the evidence from the cell and animal studies indicates that there is a positive, statistically significant association between vaping and adverse immune response during infectious respiratory diseases. The evidence from human studies is not conclusive.

Assessing variability of aerosols generated from e-Cigarettes.

While some in vitro and in vivo experiments have studied the toxic effects of e-cigarette (e-cig) components, the typical aerosol properties released from e-cigarettes have not been well characterized. In the present study, we characterized the variability in mass concentration and particle size distribution associated with the aerosol generation of different devices and e-liquid compositions in an experimental setup. The findings of this study indicate a large inter-day variability in the experiments, likely due to poor quality control in some e-cig devices, pointing to the need for a better understanding of all the factors affecting exposures in in vitro and in vivo experiments, and the development of standardized protocols for generation and measurement of e-cig aerosols.

Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles.

Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.

An optimised spectrophotometric assay for convenient and accurate quantitation of intracellular iron from iron oxide nanoparticles.

We report the development and optimisation of an assay for quantitating iron from iron oxide nanoparticles in biological matrices by using ferene-s, a chromogenic compound. The method is accurate, reliable and can be performed with basic equipment common to many laboratories making it convenient and inexpensive. The assay we have developed is suited for quantitation of iron in cell culture studies with iron oxide nanoparticles, which tend to manifest low levels of iron. The assay was validated with standard reference materials and with inductively coupled plasma-mass spectrometry (ICP-MS) to accurately measure iron concentrations ∼1 × 10-6 g in about 1 × 106 cells (∼1 × 10-12 g Fe per cell). The assay requires preparation and use of a working solution to which samples can be directly added without further processing. After overnight incubation, the absorbance can be measured with a standard UV/Vis spectrophotometer to provide iron concentration. Alternatively, for expedited processing, samples can be digested with concentrated nitric acid before addition to the working solution. Optimization studies demonstrated significant deviations accompany variable digestion times, highlighting the importance to ensure complete iron ion liberation from the nanoparticle or sample matrix to avoid underestimating iron concentration. When performed correctly, this method yields reliable iron ion concentration measurements to ∼2 × 10-6 M (1 × 10-7 g/ml sample).

Magnetic resonance imaging contrast of iron oxide nanoparticles developed for hyperthermia is dominated by iron content.

PURPOSE: Magnetic iron oxide nanoparticles (MNPs) are used as contrast agents for magnetic resonance imaging (MRI) and hyperthermia for cancer treatment. The relationship between MRI signal intensity and cellular iron concentration for many new formulations, particularly MNPs having magnetic properties designed for heating in hyperthermia, is lacking. In this study, we examine the correlation between MRI T2 relaxation time and iron content in cancer cells loaded with various MNP formulations. MATERIALS AND METHODS: Human prostate carcinoma DU-145 cells were loaded with starch-coated bionised nanoferrite (BNF), iron oxide (Nanomag® D-SPIO), Feridex™, and dextran-coated Johns Hopkins University (JHU) particles at a target concentration of 50 pg Fe/cell using poly-D-lysine transfection reagent. T2-weighted MRI of serial dilutions of these labelled cells was performed at 9.4 T and iron content quantification was performed using inductively coupled plasma mass spectrometry (ICP-MS). Clonogenic assay was used to characterise cytotoxicity. RESULTS: No cytotoxicity was observed at twice the target intracellular iron concentration (∼100 pg Fe/cell). ICP-MS revealed highest iron uptake efficiency with BNF and JHU particles, followed by Feridex and Nanomag-D-SPIO, respectively. Imaging data showed a linear correlation between increased intracellular iron concentration and decreased T2 times, with no apparent correlation among MNP magnetic properties. CONCLUSIONS: This study demonstrates that for the range of nanoparticle concentrations internalised by cancer cells the signal intensity of T2-weighted MRI correlates closely with absolute iron concentration associated with the cells. This correlation may benefit applications for cell-based cancer imaging and therapy including nanoparticle-mediated drug delivery and hyperthermia.

Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease.

OBJECT: The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure. METHODS: A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee. RESULTS: Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction. CONCLUSIONS: Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.

The effect of cell cluster size on intracellular nanoparticle-mediated hyperthermia: is it possible to treat microscopic tumors?

AIM: To compare the measured surface temperature of variable size ensembles of cells heated by intracellular magnetic fluid hyperthermia with heat diffusion model predictions. MATERIALS & METHODS: Starch-coated Bionized NanoFerrite (Micromod Partikeltechnologie GmbH, Rostock, Germany) iron oxide magnetic nanoparticles were loaded into cultured DU145 prostate cancer cells. Cell pellets of variable size were treated with alternating magnetic fields. The surface temperature of the pellets was measured in situ and the associated cytotoxicity was determined by clonogenic survival assay. RESULTS & CONCLUSION: For a given intracellular nanoparticle concentration, a critical minimum number of cells was required for cytotoxic hyperthermia. Above this threshold, cytotoxicity increased with increasing cell number. The measured surface temperatures were consistent with those predicted by a heat diffusion model that ignores intercellular thermal barriers. These results suggest a minimum tumor volume threshold of approximately 1 mm(3), below which nanoparticle-mediated heating is unlikely to be effective as the sole cytotoxic agent.

Preliminary study of injury from heating systemically delivered, nontargeted dextran-superparamagnetic iron oxide nanoparticles in mice.

AIM: To assess the potential for injury to normal tissues in mice due to heating systemically delivered magnetic nanoparticles in an alternating magnetic field (AMF). MATERIALS & METHODS: Twenty three male nude mice received intravenous injections of dextran-superparamagnetic iron oxide nanoparticles on days 1-3. On day 6, they were exposed to AMF. On day 7, blood, liver and spleen were harvested and analyzed. RESULTS: Iron deposits were detected in the liver and spleen. Mice that had received a high-particle dose and a high AMF experienced increased mortality, elevated liver enzymes and significant liver and spleen necrosis. Mice treated with low-dose superparamagnetic iron oxide nanoparticles and a low AMF survived, but had elevated enzyme levels and local necrosis in the spleen. CONCLUSION: Magnetic nanoparticles producing only modest heat output can cause damage, and even death, when sequestered in sufficient concentrations. Dextran-superparamagnetic iron oxide nanoparticles are deposited in the liver and spleen, making these the sites of potential toxicity. Original submitted 16 August 2011; Revised submitted 21 March 2012; Published online 26 July 2012.