Background Attempts at gene therapy for the pulmonary manifestations of Cystic Fibrosis have relied mainly on airway delivery. However the efficiency of gene transfer and expression in the airway epithelia has not reached therapeutic levels. Access to epithelial cells is not homogenous for a number of reasons and the submucosal glands cannot be reached via the airways. Presentation We propose to inject gene delivery vectors directly into bronchial arteries combined with pre-delivery of vascular endothelial growth factor to increase vascular endothelial permeability and post-delivery flow reduction by balloon occlusion. Thus it may be possible to reach mucous secreting cells of the bronchial luminal epithelium and the submucosal glands in an increased and homogenous fashion. Testing This combination of techniques to the best of our knowledge has not previously been investigated, and may enable us to overcome some of the current limitations to gene therapy for Cystic Fibrosis.

Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. We hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4-hour exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 hours. After each time point, we assessed, circulating stress hormones and cytokines, lung gene expression, and live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, Th and Tc) in blood, thymus and spleen using flow cytometry. This dataset is associated with the following publication: Henriquez, A., W. Williams, S. Snow, M.C. Schladweiler, C. Fisher, M. Hargrove, D. Alewel, C. Colonna, S. Gavett, C. Miller, and U. Kodavanti. The Dynamicity of Acute Ozone-Induced Systemic Leukocyte Trafficking and Adrenal-Derived Stress Hormones. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 458(152823): 1, (2021).

Exposure of the airways to cigarette smoke (CS) is the primary risk factor for developing several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). CS consists of a complex mixture of over 6000 chemicals including the highly reactive α,β-unsaturated aldehyde acrolein. Acrolein is thought to be responsible for a large proportion of the non-cancer disease risk associated with smoking. Emerging evidence suggest a key role for CS-induced abnormalities in mitochondrial morphology and function in airway epithelial cells in COPD pathogenesis. Although in vitro studies suggest acrolein-induced mitochondrial dysfunction in airway epithelial cells, it is unknown if in vivo inhalation of acrolein affects mitochondrial content or the pathways controlling this. In this study, rats were acutely exposed to acrolein by inhalation (nose-only; 0-4 ppm), 4 hours/day for 1 or 2 consecutive days (n=6/group). Subsequently, the activity and abundance of key constituents of mitochondrial metabolic pathways as well as expression of critical proteins and genes controlling mitochondrial biogenesis and mitophagy were investigated in lung homogenates. A transient decreasing response in protein and transcript abundance of subunits of the electron transport chain complexes was observed following acrolein inhalation. Moreover, acrolein inhalation caused a decreased abundance of key regulators associated with mitochondrial biogenesis, respectively a differential response on day 1 versus day 2. Abundance of components of the mitophagy machinery was in general unaltered in response to acrolein exposure in rat lung. Collectively, this study demonstrates that acrolein inhalation acutely and dose-dependently disrupts the molecular regulation of mitochondrial metabolism in rat lung. Hence, understanding the effect of acrolein on mitochondrial function will provide a scientifically supported reasoning to shortlist aldehydes regulation in tobacco smoke. This dataset is not publicly accessible because: EPA does not own the data and therefore EPA does not have right to publish the data. It can be accessed through the following means: Data can be obtained from corresponding author of the paper. Format: The data in this paper are collected from lung tissue that were isolated from air or acrolein-exposed Wistar Kyoto rats. All data are derived from lung tissue assessment of many biological markers associated with mitochondrial homeostasis. For these data n=8 animals were used for each group of samples. This dataset is associated with the following publication: Tulen, C., S. Snow , P. Leermakers, U. Kodavanti, F. van Schooten, A. Opperhuizen, and A. Remels. Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 469(153129): 1, (2022).

This data set is an excel file pertaining to the study that examined ozone-induced systemic and pulmonary effects in rats that underwent SHAM surgery (control), adrenal demedullation or total bilateral adrenalectomy. Different pages of the spreadsheet shows individual animal data for markers of lung injury and inflammation, body weights, whole body plethysmography measurements, levels of circulating hormones and lipids, and circulating white blood cell count as well as platelet count. This dataset is associated with the following publication: Miller, D., S. Snow, M. Schladweiler , J. Richards , A. Ghio , A. Ledbetter , and U. Kodavanti. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#. TOXICOLOGICAL SCIENCES. Society of Toxicology, 150(2): 312-22, (2016).

This data set is broken up into 2 Excel files. In one file are all the data pertaining to the vascular and pulmonary effects of ozone exposure in rats fed either a normal diet or diet enriched with coconut oil, fish oil, or olive oil. The different tabs of the spreadsheet pertain to each figure or table found in the manuscript. This file was updated on 12/7/17 to reflect changes to Figure 3 in response to reviewers comments following submission to Toxicological Sciences. In the second file is all the data for Figure 8 pertaining to the global microRNA assessment. This dataset is associated with the following publication: Snow, S., W. Cheng, A. Henriquez, M. Hodge, V. Bass, G. Nelson, G. Carswell, J. Richards, M. Schladweiler, A. Ledbetter, B. Chorley, K. Gowdy, H. Tong, and U. Kodavanti. Ozone-Induced Vascular Contractility and Pulmonary Injury are Differentially Impacted by Diets Enriched with Coconut Oil, Fish Oil, and Olive Oil. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(1): 57-69, (2018).

This data set is broken up into 2 Excel files. In one file are all the data pertaining to the vascular and pulmonary effects of ozone exposure in rats fed either a normal diet or diet enriched with coconut oil, fish oil, or olive oil. The different tabs of the spreadsheet pertain to each figure or table found in the manuscript. This file was updated on 12/7/17 to reflect changes to Figure 3 in response to reviewers comments following submission to Toxicological Sciences. In the second file is all the data for Figure 8 pertaining to the global microRNA assessment. This dataset is associated with the following publication: Snow, S., W. Cheng, A. Henriquez, M. Hodge, V. Bass, G. Nelson, G. Carswell, J. Richards, M. Schladweiler, A. Ledbetter, B. Chorley, K. Gowdy, H. Tong, and U. Kodavanti. Ozone-Induced Vascular Contractility and Pulmonary Injury are Differentially Impacted by Diets Enriched with Coconut Oil, Fish Oil, and Olive Oil. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(1): 57-69, (2018).

Data include: trans-epithelial electrical resistance, FITC-dextran permeability, cell viability and gene expression (RNA and protein). This dataset is associated with the following publication: Faber, S., N. McNabb, P. Ariel, E. Aungst, and S. McCullough. Exposure Effects Beyond the Epithelial Barrier: Trans-Epithelial Induction of Oxidative Stress by Diesel Exhaust Particulates in Lung Fibroblasts in an Organotypic Human Airway Model. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 177(1): 140-155, (2020).

Data and code availability •The full proteomics mass spectrometry data were uploaded into the PRoteomics IDEntifications Database (PRIDE) and are publicly available as of the date of publication. (65) EV isolation methods and study logistics have been uploaded to the EV-Track knowledgebase (EV-TRACK ID: EV230971). (66) Cell viability, cell permeability, NTA, and proteomics data were also uploaded to the UNC Center for Environmental Medicine, Asthma and Lung Biology (UNC-CEMALB)-Dataverse. (67) The PRIDE project accession number, EV-TRACK ID, and accession link to UNC-CEMALB-Dataverse are listed in the key resources table. •Script used to analyze NTA and proteomics data were organized via the UNC-CEMALB Github website and is publicly available as of the date of publication. (68) •Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request. This dataset is associated with the following publication: Vitucci, E., C. Carberry, A. Payton, L. Herring, A. Mordant, S. McCullough, and J. Rager. Characterizing the Extracellular Vesicle Proteomic Landscape of the Human Airway using In vitro Organotypic Multi-Cellular Models. iScience. Elsevier B.V., Amsterdam, NETHERLANDS, 26(11): 108162, (2023).