Assessment of Left Lung Remodeling With Magnetic Resonance Imaging in a Murine Model Following Exposure to Douglas Fir Smoke.

Wildland firefighters (WLFFs) experience lung function decline due to occupational exposure to fire smoke. WLFFs typically do not wear respiratory personal protective equipment, and if they do, it is a simple bandana, which is not effective at filtering smoke. To pinpoint the biological underpinnings of abnormal respiratory function following 3-7 years of WLFF service, we exposed mice to Douglas fir smoke (DFS) over 8 weeks. Following exposure, we assessed changes in lung structure through Magnetic Resonance Imaging (MRI) and histological analysis, which was supported by immunohistochemistry staining. With MRI, we found that the signal decay time, T2*, from ultrashort echo time (UTE) images was significantly shorter in mice exposed to DFS compared to air controls. In addition, the variation in T2* was more heterogeneously distributed throughout the left lung in DFS-exposed mice, compared to air controls. As confirmed by histological analysis, shorter T2* was caused by larger parenchyma airspace sizes and not fibrotic remodeling. Destruction of the alveolar spaces was likely due to inflammation, as measured by an influx of CD68+ macrophages and destruction due to enhanced neutrophil elastase. In addition, measurements of airspace dimensions from histology were more heterogeneously distributed throughout the lung, corroborating the enhanced relative dispersion of T2*. Findings from this study suggest that the decline in lung function observed in WLFFs may be due to emphysema-like changes in the lung, which can be quantified with MRI.

Respiratory mechanics following chronic cigarette smoke exposure in the Apoe[Formula: see text] mouse model.

Even though cigarette smoking (CS) has been on the decline over the past 50 years, it is still the leading cause of preventable premature death in the United States. Preclinical models have investigated the cardiopulmonary effects of CS exposure (CSE), but the structure-function relationship in the respiratory system has not yet been fully explored. To evaluate these relationships, we exposed female apolipoprotein E-deficient (Apoe[Formula: see text]) mice to mainstream CS ([Formula: see text]) for 5 days/week over 24 weeks with room air as a control (AE, [Formula: see text]). To contextualize the impact of CSE, we also assessed the natural aging effects over 24 weeks of air exposure (baseline, [Formula: see text]). Functional assessments were performed on a small animal mechanical ventilator (flexiVent, SCIREQ), where pressure-volume curves and impedance data at four levels of positive end-expiratory pressure ([Formula: see text]) and with increasing doses of methacholine were collected. Constant phase model parameters ([Formula: see text]: Newtonian resistance, H: coefficient of tissue elastance, and G: coefficient of tissue resistance) were calculated from the impedance data. Perfusion fixed-left lung tissue was utilized for quantification of parenchyma airspace size and tissue thickness, airway wall thickness, and measurements of elastin, cytoplasm + nucleus, fibrin, and collagen content for the parenchyma and airways. Aging caused the lung to become more compliant, with an upward-leftward shift of the pressure-volume curve and a reduction in all constant phase model parameters. This was supported by larger parenchyma airspace sizes, with a reduction in cell cytoplasm + nucleus area. Airway walls became thinner, even though low-density collagen content increased. In contrast, CSE caused a downward-rightward shift of the pressure-volume curve along with an increase in H, G, and hysteresivity ([Formula: see text]). Organ stiffening was accompanied by enhanced airway hyper-responsiveness following methacholine challenge. Structurally, parenchyma airspaces enlarged, as indicated by an increase in equivalent airspace diameter ([Formula: see text]), and the septum thickened with significant deposition of low-density collagen along with an influx of cells. Airway walls thickened due to deposition of both high and low-density collagen, infiltration of cells, and epithelial cell elongation. In all, our data suggest that CSE in female Apoe[Formula: see text] mice reduces respiratory functionality and causes morphological alterations in both central and peripheral airways that results in lung stiffening, compared to AE controls.

Prolonged smoldering Douglas fir smoke inhalation augments respiratory resistances, stiffens the aorta, and curbs ejection fraction in hypercholesterolemic mice.

While mounting evidence suggests that wildland fire smoke (WFS) inhalation may increase the burden of cardiopulmonary disease, the occupational risk of repeated exposure during wildland firefighting remains unknown. To address this concern, we evaluated the cardiopulmonary function in mice following a cumulative exposure to lab-scale WFS equivalent to a mid-length wildland firefighter (WLFF) career. Dosimetry analysis indicated that 80 exposure hours at a particulate concentration of 22 mg/m3 yield in mice the same cumulative deposited mass per unit of lung surface area as 3600 h of wildland firefighting. To satisfy this condition, male Apoe-/- mice were whole-body exposed to either air or smoldering Douglas fir smoke (DFS) for 2 h/day, 5 days/week, over 8 consecutive weeks. Particulate size in DFS fell within the respirable range for both mice and humans, with a count median diameter of 110 ± 20 nm. Expiratory breath hold in mice exposed to DFS significantly reduced their minute volume (DFS: 27 ± 4; Air: 122 ± 8 mL/min). By the end of the exposure time frame, mice in the DFS group exhibited a thicker (DFS: 109 ± 3; Air: 98 ± 3 µm) and less distensible (DFS: 23 ± 1; Air: 28 ± 1 MPa-1) aorta with reduced diastolic blood augmentation capacity (DFS: 53 ± 2; Air: 63 ± 2 kPa). Cardiac magnetic resonance imaging further revealed larger end-systolic volume (DFS: 14.6 ± 1.1; Air: 9.9 ± 0.9 µL) and reduced ejection-fraction (DFS: 64.7 ± 1.0; Air: 75.3 ± 0.9 %) in mice exposed to DFS. Consistent with increased airway epithelium thickness (DFS: 10.4 ± 0.8; Air: 7.6 ± 0.3 µm), airway Newtonian resistance was larger following DFS exposure (DFS: 0.23 ± 0.03; Air: 0.20 ± 0.03 cmH2O-s/mL). Furthermore, parenchyma mean linear intercept (DFS: 36.3 ± 0.8; Air: 33.3 ± 0.8 µm) and tissue thickness (DFS: 10.1 ± 0.5; Air: 7.4 ± 0.7 µm) were larger in DFS mice. Collectively, mice exposed to DFS manifested early signs of cardiopulmonary dysfunction aligned with self-reported events in mid-career WLFFs.

Pharmacological and physiological response in Apoe-/- mice exposed to cigarette smoke or e-cigarette aerosols.

OBJECTIVE: Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe-/- mice exposed to tank/box-mod e-cig (e-cigtank), pod e-cig (e-cigpod), or cig smoke. MATERIALS AND METHODS: Reproducible puff profiles were generated for each aerosol and delivered to Apoe-/- mice via a nose-only exposure system. Serum cotinine levels were quantified at various time points through ELISA and utilized to model cotinine pharmacokinetics. In addition, particle size measurements and mouse respiratory function were characterized to calculate particle dosimetry. RESULTS AND DISCUSSION: Cig and e-cigtank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cigtank: 200 ± 34nm), while e-cigpod particles were bimodally distributed and smaller (116 ± 13 and 13.3 ± 0.4 nm). Minute volumes decreased with cig exposure (5.4 ± 2.7 mL/min) compared to baseline (90.8 ± 11.6 mL/min), and less so with e-cigtank (45.2 ± 9.2 mL/min) and e-cigpod exposures (58.6 ± 6.8 mL/min), due to periods of apnea in the cig exposed groups. Cotinine was absorbed and eliminated most rapidly in the e-cigpod group (tmax = 14.5; t1/2' = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cigtank: 40.1 min) and eliminated (cig: 104.6, e-cigtank: 94.1 min) similarly in the cig and e-cigtank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cigtank) and 4.6× (e-cigpod) more nicotine deposited in e-cig compared to cig exposed mice. CONCLUSIONS: This study provides a basis for incorporating cotinine pharmacokinetics into preclinical exposure studies, allowing for longitudinal studies of structural and functional changes due to exposure.

This study highlights that pod e-cigs deliver smaller particles than tank/box-mode e-cigs and cig smoke. Minute volumes were substantially reduced in cig smoke-exposed mice, due to periods of apnea, whereas only expiration times increased in the e-cig-exposed groups. More particles deposit in e-cig exposed mice, compared to the cig group, for equivalent daily area under the cotinine concentration curve.

Effect of moisture content and fuel type on emissions from vegetation using a steady state combustion apparatus.

Emission measurements are available in the literature for a wide variety of field burns and laboratory experiments, although previous studies do not always isolate the effect of individual features such as fuel moisture content (FMC). This study explores the effect of FMC on gaseous and particulate emissions from flaming and smouldering combustion of four different wildland fuels found across the United States. A custom linear tube-heater apparatus was built to steadily produce emissions in different combustion modes over a wide range of FMC. Results showed that when compared with flaming combustion, smouldering combustion showed increased emissions of CO, particulate matter and unburned hydrocarbons, corroborating trends in the literature. CO and particulate matter emissions in the flaming mode were also significantly correlated with FMC, which had little influence on emissions for smouldering mode combustion, when taking into account the dry mass of fuel burned. These variations occurred for some vegetative fuel species but not others, indicating that the type of fuel plays an important role. This may be due to the chemical makeup of moist and recently live fuels, which is discussed and compared with previous measurements in the literature.

Simulated Wildfire Smoke Significantly Alters Sperm DNA Methylation Patterns in a Murine Model.

Wildfires are now a common feature of the western US, increasing in both intensity and number of acres burned over the last three decades. The effects of this changing wildfire and smoke landscape are a critical public and occupational health issue. While respiratory morbidity due to smoke exposure is a priority, evaluating the molecular underpinnings that explain recent extrapulmonary observations is necessary. Here, we use an Apoe-/- mouse model to investigate the epigenetic impact of paternal exposure to simulated wildfire smoke. We demonstrate that 40 days of exposure to smoke from Douglas fir needles induces sperm DNA methylation changes in adult mice. DNA methylation was measured by reduced representation bisulfite sequencing and varied significantly in 3353 differentially methylated regions, which were subsequently annotated to 2117 genes. The differentially methylated regions were broadly distributed across the mouse genome, but the vast majority (nearly 80%) were hypermethylated. Pathway analyses, using gene-derived and differentially methylated region-derived gene ontology terms, point to a number of developmental processes that may warrant future investigation. Overall, this study of simulated wildfire smoke exposure suggests paternal reproductive risks are possible with prolonged exposure.

Structural and functional remodeling of the female Apoe-/- mouse aorta due to chronic cigarette smoke exposure.

Despite a decline in popularity over the past several decades, cigarette smoking remains a leading cause of cardiovascular morbidity and mortality. Yet, the effects of cigarette smoking on vascular structure and function are largely unknown. To evaluate changes in the mechanical properties of the aorta that occur with chronic smoking, we exposed female apolipoprotein E-deficient mice to mainstream cigarette smoke daily for 24 wk, with room air as control. By the time of euthanasia, cigarette-exposed mice had lower body mass but experienced larger systolic/diastolic blood pressure when compared with controls. Smoking was associated with significant wall thickening, reduced axial stretch, and circumferential material softening of the aorta. Although this contributed to maintaining intrinsic tissue stiffness at control levels despite larger pressure loads, the structural stiffness became significantly larger. Furthermore, the aorta from cigarette-exposed mice exhibited decreased ability to store elastic energy and augment diastolic blood flow. Histological analysis revealed a region-dependent increase in the cross-sectional area due to smoking. Increased smooth muscle and extracellular matrix content led to medial thickening in the ascending aorta, whereas collagen deposition increased the thickness of the descending thoracic and abdominal aorta. Atherosclerotic lesions were larger in exposed vessels and featured a necrotic core overlaid by a thinned fibrous cap and macrophage infiltration, consistent with a vulnerable phenotype. Collectively, our data indicate that cigarette smoking decreases the mechanical functionality of the aorta, inflicts morphometric alterations to distinct segments of the aorta, and accelerates the progression of atherosclerosis.NEW & NOTEWORTHY We studied the effects of chronic cigarette smoking on the structure and function of the aorta in a mouse model of nose-only aerosol inhalation. Our data indicated that exposure to cigarette smoke impairs vascular function by reducing the ability of the aorta to store elastic energy and by decreasing aortic distensibility. Combined with a more vulnerable atherosclerotic phenotype, these findings reveal the biomechanical mechanisms that support the development of cardiovascular disease due to cigarette smoking.