ORCID Profile
0000-0001-9039-0302
Current Organisation
University of Tasmania
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Publisher: Public Library of Science (PLoS)
Date: 14-11-2014
Publisher: American Physiological Society
Date: 03-2020
DOI: 10.1152/AJPLUNG.00492.2019
Abstract: Both overdistension and atelectasis contribute to lung injury and mortality during mechanical ventilation. It has been proposed that combinations of tidal volume and end-expiratory lung volume exist that minimize lung injury linked to mechanical ventilation. The aim of this study was to examine this at the regional level in the healthy and endotoxemic lung. Adult female BALB/c mice were injected intraperitoneally with 10 mg/kg lipopolysaccharide (LPS) in saline or with saline alone. Four hours later, mice were mechanically ventilated for 2 h. Regional specific end-expiratory volume (sEEV) and tidal volume (sVt) were measured at baseline and after 2 h of ventilation using dynamic high-resolution four-dimensional computed tomography images. The regional expression of inflammatory genes was quantified by quantitative PCR. There was a heterogenous response in regional sEEV whereby endotoxemia increased gas trapping at end-expiration in some lung regions. Within the healthy group, there was a relationship between sEEV, sVt, and the expression of Tnfa, where high Vt in combination with high EEV or very low EEV was associated with an increase in gene expression. In endotoxemia there was an association between low sEEV, particularly when this was combined with moderate sVt, and high expression of IL6. Our data suggest that preexisting systemic inflammation modifies the relationship between regional lung volumes and inflammation and that although optimum EEV-Vt combinations to minimize injury exist, further studies are required to identify the critical inflammatory mediators to assess and the effect of different injury types on the response.
Publisher: European Respiratory Society (ERS)
Date: 09-03-2012
DOI: 10.1183/09031936.00204311
Abstract: In healthy in iduals, deep inspirations (DIs) taken prior to a bronchial challenge reduce the bronchoconstrictor response, which is termed "bronchoprotection". The mechanism(s) of DI-induced bronchoprotection is unclear. The forced oscillation technique was used to assess the effect of prior DI on subsequent bronchoconstriction to methacholine (MCh) in BALB/c mice. We assessed likely mechanisms for the bronchoprotective effects of DI including reduced airway narrowing (from changes in airway resistance) and/or closure (changes in tissue elastance) and enhanced bronchodilation to a subsequent DI (% reversal in airway narrowing). DI prior to MCh challenge: 1) did not reduce but instead enhanced airway narrowing (p<0.05) 2) increased ventilation heterogeneity (p<0.05) 3) enhanced the subsequent bronchodilatory response to DI (p<0.05) and 4) reduced tissue elastance (p<0.05), suggesting opening of closed airways or alveoli units. Our findings suggest that DI prior to MCh challenge may elicit a series of changes, some of which are beneficial to respiratory function (enhanced bronchodilation), while others place greater load on the system (enhanced bronchoconstriction and ventilation heterogeneity). It is proposed that the relative magnitudes of these opposing physiological and mechanical effects will determine the net effect on respiratory function in health and disease.
Publisher: American Physiological Society
Date: 10-2023
DOI: 10.1152/JAPPLPHYSIOL.00693.2022
Abstract: How the heterogeneous distribution of lung volumes changes in response to different mechanical ventilation (MV) strategies is unclear. Using our well-developed four-dimensional computed tomography (4DCT) high resolution imaging technique, we aimed to assess the effect of different MV strategies on the distribution and heterogeneity of regional lung volumes. Healthy adult female BALB/c mice received either 2h of "injurious" MV (n=6, HPZP) with a peak inspiratory pressure (PIP) of 20cmH 2 O and zero positive end-expiratory pressure (PEEP), or 2h of "protective" MV (n=8, LPP) with PIP=12cmH 2 O and PEEP=2cmH 2 O. 4DCT images were obtained at baseline (0h) and after 2h of MV. Tidal volume (Vt) and end-expiratory lung volume (EEV) were measured throughout the whole lung on a voxel-by-voxel basis. Heterogeneity of ventilation was determined by the coefficient of variation (COV) of Vt and EEV. Our data showed that MV had minimal impact on global Vt but decreased EEV in the HPZP group ( p .05). Both ventilation modes decreased the COV of Vt (39.4% for HPZP and 9.7% for LPP) but increased the COV in EEV (36.4% for HPZP and 29.2% for LPP). This was consistent with the redistribution index which was significantly higher in the HVZP group than the LPP group ( p .001). We concluded that regional assessment of the change in EEV showed different patterns in progression between LPP and HPZP strategies. Both ventilation strategies decreased heterogeneity in Vt after 2h of MV but increased heterogeneity in EEV. Further work is required to determine the link between these effects and ventilator induced lung injury.
Publisher: Springer Science and Business Media LLC
Date: 14-04-2021
DOI: 10.1038/S41598-021-87517-Z
Abstract: There has been an increase in the identification of cases of coal workers’ pneumoconiosis (CWP) in recent years around the world. While there are a range of possible explanations for this, studies have implicated the pyrite content of coal as a key determinant of CWP risk. However, experimental studies to support this link are limited. The aim of this study was to assess the association between the pyrite content, and subsequent release of bioavailable iron, in coal particles and the response of lung cells involved in the pathogenesis of CWP (epithelial cells, macrophages and fibroblasts). Using real-world Australian coal s les, we found no evidence of an association between the pyrite content of the coal and the magnitude of the detrimental cell response. We did find evidence of an increase in IL-8 production by epithelial cells with increasing bioavailable iron (p = 0.01), however, this was not linked to the pyrite content of the coal (p = 0.75) and we did not see any evidence of a positive association in the other cell types. Given the lack of association between the pyrite content of real-world coal particles and lung cell cytotoxicity (epithelial cells and macrophages), inflammatory cytokine production (epithelial cells, macrophages and fibroblasts), and cell proliferation (fibroblasts) our data do not support the use of coal pyrite content as a predictor of CWP risk.
Publisher: American Thoracic Society
Date: 11-2015
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.BBR.2015.03.008
Abstract: Prenatal exposure to vitamin D is thought to be critical for optimal fetal neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of pregnant women. The aim of this study was to determine whether a mouse model of vitamin D-deficiency alters fetal neurodevelopment. Female BALB/c mice were placed on either a vitamin D control (2,195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks prior to and during pregnancy. Fetal brains were collected at embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy reduced fetal crown-rump length and head size. Moreover, lateral ventricle volume was reduced in vitamin D-deficient foetuses. Expression of neurotrophin genes brain-derived neurotrophic factor (Bdnf) and transforming growth factor-β1 (Tgf-β1) was altered, with Bdnf reduced at E14.5 and increased at E17.5 following vitamin D deficiency. Brain expression of forkhead box protein P2 (Foxp2), a gene known to be important in human speech and language, was also altered. Importantly, Foxp2 immunoreactive cells in the developing cortex were reduced in vitamin D-deficient female foetuses. At E17.5, brain tyrosine hydroxylase (TH) gene expression was reduced in females, as was TH protein localization (to identify dopamine neurons) in the substantia nigra of vitamin D-deficient female foetuses. Overall, we show that prenatal vitamin D-deficiency leads to alterations in fetal mouse brain morphology and genes related to neuronal survival, speech and language development, and dopamine synthesis. Vitamin D appears to play an important role in mouse neurodevelopment.
Publisher: Environmental Health Perspectives
Date: 02-2013
DOI: 10.1289/EHP.1205590
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-06-2020
DOI: 10.1097/SHK.0000000000001591
Abstract: Lung - recruited Ly6C hi monocytes had been shown to be involved in ventilator-induced lung injury (VILI). Our present study aimed to investigate whether the cyclooxygenase-2 (COX-2) inhibition modulates the function of lung - recruited Ly6C hi monocytes in a mouse model of VILI. Mice were exposed to lipopolysaccharide (LPS 20 ng) intraperitoneally prior to injurious mechanical ventilation (Vt = 30 mL/kg, PEEP = 0 cmH 2 O). A subgroup of mice was treated with intravenous parecoxib (30 mg/kg), a COX-2 inhibitor, 1 h prior to ventilation. Control mice received saline and were not ventilated. At the end of the experiment, blood gas analysis was performed and lung tissue was collected for histological assessment. Flow cytometry was employed to quantify the different populations of lung monocytes/macrophages and their function. Isolated Ly6C hi cells were used to measure the intracellular concentrations of reactive oxygen species (ROS) and nitric oxide (NO) by fluorescent probes, and cytokine production by cytometric bead array. Exposure to LPS and injurious ventilation was associated with severe lung histological damage, oxygenation impairment, and pulmonary edema all of which were largely attenuated following the treatment of parecoxib. Furthermore, flow cytometry analysis revealed that parecoxib caused a reduction in the number of the lung-recruited CD11b lo Ly6C hi monocytes while there was no effect on tissue-resident CD64 + alveolar macrophages. In addition, the production of oxidative stress products (ROS, NO), MHC-II expression, and inflammatory cytokines in response to LPS and VILI in CD11b lo Ly6C hi monocytes was ameliorated by parecoxib. Parecoxib-induced alleviation of oxidative stress and inflammation in lung-recruited Ly6C hi monocytes may partly explain the beneficial action of COX-2 inhibition in VILI.
Publisher: American Physiological Society
Date: 2011
DOI: 10.1152/AJPLUNG.00158.2010
Abstract: Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.
Publisher: Wiley
Date: 21-09-2013
DOI: 10.1111/IRV.12012
Publisher: American Physiological Society
Date: 03-2017
DOI: 10.1152/JAPPLPHYSIOL.00476.2016
Abstract: Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo. NEW & NOTEWORTHY Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.
Publisher: The Endocrine Society
Date: 07-08-2015
DOI: 10.1210/EN.2015-1377
Abstract: The prevalence of vitamin D deficiency in pregnancy is increasing and implicated in adverse consequences for the health of offspring in later life. The aim of this study was to determine whether vitamin D deficiency increases fetal exposure to glucocorticoids, which are known to alter fetal development and result in adverse adult health outcomes. Female BALB/c mice were placed on either a vitamin D control (2195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks before and during pregnancy. Maternal serum, placentas and fetal brains were collected at embryonic day 14.5 or 17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy increased maternal corticosterone concentrations and reduced placental weight. Maternal vitamin D deficiency decreased placental expression of 11β-hydroxysteroid dehydrogenase type II, which inactivates glucocorticoids thereby protecting the fetus from inappropriate glucocorticoid exposure. There was a corresponding increase in placental and fetal expression of the highly glucocorticoid-sensitive factor glucocorticoid-induced leucine zipper. Furthermore, placental expression of the angiogenic factor vascular endothelial growth factor-A was reduced in vitamin D-deficient pregnancies, with a corresponding decline in fetal capillary volume within the placenta. Overall, we show that prenatal vitamin D deficiency leads to an increase in maternal corticosterone, alterations in genes indicative of increased fetal glucocorticoid exposure and impairment in placental vascular development. Thus, the long-term adverse health consequences of vitamin D deficiency during early development may not just be due to alteration in direct vitamin D-related pathways but also altered fetal glucocorticoid exposure.
Publisher: Wiley
Date: 30-11-2022
DOI: 10.1111/JACE.18902
Abstract: Due to their great performance and ease of installation, refractory castables are common ground materials to enable high‐temperature processes. However, their fully operational condition is slowed down by the gradual drying stage required. Therefore, better understanding of the moisture transport is essential to improve their efficiency and reduce the likelihood of explosive spalling events due to vapor pressurization. Neutron tomography provides a relevant inner view of the moisture distribution across a s le and its evolution over time. In this work, the effect of the heating rate on moisture clog was investigated and compared with available laboratory and industrial observations. It was found out that higher heating rates resulted in a faster and longer lasting water accumulation ahead of the drying front, in agreement with other macroscopic studies and explaining the common reasoning behind using slower heating rates and safer industrial operations. This study highlights the potential of neutron imaging for the ongoing effort to maximize the efficiency of the refractory castables drying process by controlling the moisture accumulation without exclusively relying on slower heating rates.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2022
DOI: 10.1186/S12931-022-01958-2
Abstract: Lung inhomogeneity plays a pivotal role in the development of ventilator-induced lung injury (VILI), particularly in the context of pre-existing lung injury. The mechanisms that underlie this interaction are poorly understood. We aimed to elucidate the regional transcriptomic response to mechanical ventilation (MV), with or without pre-existing lung injury, and link this to the regional lung volume response to MV. Adult female BALB/c mice were randomly assigned into one of four groups: Saline, MV, lipopolysaccharide (LPS) or LPS/MV. Lung volumes (tidal volume, Vt end-expiratory volume, EEV) were measured at baseline or after 2 h of ventilation using four-dimensional computed tomography (4DCT). Regional lung tissue s les corresponding to specific imaging regions were analysed for the transcriptome response by RNA-Seq. Bioinformatics analyses were conducted and the regional expression of dysregulated gene clusters was then correlated with the lung volume response. MV in the absence of pre-existing lung injury was associated with regional variations in tidal stretch. The addition of LPS also caused regional increases in EEV. We identified 345, 141 and 184 region-specific differentially expressed genes in response to MV, LPS and LPS/MV, respectively. Amongst these candidate genes, up-regulation of genes related to immune responses were positively correlated with increased regional tidal stretch in the MV group, while dysregulation of genes associated with endothelial barrier related pathways were associated with increased regional EEV and Vt when MV was combined with LPS. Further protein–protein interaction analysis led to the identification of two protein clusters representing the PI3K/Akt and MEK/ERK signalling hubs which may explain the interaction between MV and LPS exposure. The biological pathways associated with lung volume inhomogeneity during MV, and MV in the presence of pre-existing inflammation, differed. MV related tidal stretch induced up-regulation of immune response genes, while LPS combined with MV disrupted PI3K/Akt and MEK/ERK signalling.
Publisher: American Thoracic Society
Date: 15-09-2016
Publisher: Hindawi Limited
Date: 23-06-2019
DOI: 10.1111/JCPT.13000
Abstract: Fever, one of the most common symptoms of illness experienced by children, often creates undue parental anxiety about the consequences of fever, which can lead to overtreatment. The full extent of this problem in Australia is not known. This study aimed to describe parents' knowledge, beliefs and perceptions about childhood fever and its management, and identify any predictors of the burden on parents when children are febrile. This was a cross-sectional web-based survey of parents living in Australia. Parents with at least 1 child <6 years were recruited via Facebook. Demographic information, parental fever knowledge and beliefs and responses to the Parent Fever Management Scale, a measure of parental burden, were collected and analysed. Of the 12 179 parents who completed the survey, 42.0% knew that a temperature above 38°C constitutes a fever, with 33.4% underestimating the temperature of a fever. Parents believed that there were many harms associated with untreated fever, namely seizures (71.8%), dehydration (63.6%), serious illness (43.0%) and brain damage (36.8%). Phobic beliefs were more common among parents who underestimated the temperature of a fever. Identification of health professionals as a main information source about fever did not significantly improve knowledge or reduce fears. Up to 65.0% of respondents indicated that they practice non-evidence-based strategies to reduce temperature. The belief that 'every child with a fever should be treated with medication to lower temperature' was the strongest predictor of parental burden (ß = 0.245, P < 0.001). Poor parental knowledge and misconceptions surrounding fever and its management are still common among parents throughout Australia. Large-scale, sustainable educational interventions are needed to dispel misconceptions and concerns about fever, encourage appropriate and safe care of febrile children.
Publisher: Springer Science and Business Media LLC
Date: 23-09-2004
Publisher: Public Library of Science (PLoS)
Date: 12-11-2014
Publisher: American Thoracic Society
Date: 15-05-2011
Publisher: Elsevier BV
Date: 04-2020
Publisher: Wiley
Date: 13-01-2022
DOI: 10.1111/JACE.18297
Abstract: Structural failure of concrete buildings on fire and complete destruction of the monolithic refractory lining during their drying stage are dangerous ex les of the effect of explosive spalling on partially saturated porous media. Several observations in both cases indicated the presence of moisture accumulation ahead of the drying front, which are in tune with the most common theories on the explosive spalling of concrete. Previous studies have shown evidence of the existence of this phenomenon, however, they were biased by artifacts and experimental limitations (such as the beam hardening effect and changes in the microstructure of the material due to the presence of pressure and temperature sensors). In the current work, rapid neutron tomography was used to investigate the in‐operando drying behavior of a high‐alumina refractory castable, proposing a novel experimental layout aimed at a truly one‐dimensional drying front. This setup provided more realistic boundary conditions, such as the behavior of a larger wall heated from one of its sides, while also preventing some nonphysical artifacts (notably beam hardening). By eliminating these aspects, a direct proof that moisture accumulates ahead of the drying front was obtained. This work also lays the basis for further studies focusing on the response sensitivity analysis to boundary conditions and other parameters (e.g., heating rates and properties of the s le related to the moisture clog formation), as well as useful data for the validation and characterization stages of numerical models of partially saturated porous media.
Publisher: Wiley
Date: 23-12-2013
DOI: 10.1111/RESP.12150
Abstract: Particulate matter <10 μm (PM10 ) is well recognized as being an important driver of respiratory health however, the impact of PM10 of geogenic origin on inflammatory responses in the lung is poorly understood. This study aimed to assess the lung inflammatory response to community s led geogenic PM10 . This was achieved by collecting earth material from two regional communities in Western Australia (Kalgoorlie-Boulder and Newman), extracting the PM10 fraction and exposing mice by intranasal instillation to these particles. The physicochemical characteristics of the particles were assessed and lung inflammatory responses were compared to control particles. The primary outcomes were cellular influx and cytokine production in the lungs of the exposed mice. The physical and chemical characteristics of the PM10 from Kalgoorlie and Newman differed with the latter having a higher concentration of Fe and a larger median diameter. Control particles (2.5 μm polystyrene) caused a significant influx of inflammatory cells (neutrophils) with little production of proinflammatory cytokines. In contrast, the geogenic particles induced the production of MIP-2, IL-6 and a significant influx of neutrophils. Qualitatively, the response following exposure to particles from Kalgoorlie and Newman were consistent however, the magnitude of the response was substantially higher in the mice exposed to particles from Newman. The unique physicochemical characteristics of geogenic particles induced a proinflammatory response in the lung. These data suggest that particle composition should be considered when setting community standards for PM exposure, particularly in areas exposed to high geogenic particulate loads.
Publisher: Environmental Health Perspectives
Date: 10-2013
DOI: 10.1289/EHP.1306748
Publisher: Springer Science and Business Media LLC
Date: 12-2005
Abstract: To characterise the acute physiological and inflammatory changes induced by low-dose RSV infection in mice. BALB/c mice were infected as adults (8 wk) or weanlings (3 wk) with 1 × 10 5 pfu of RSV A2 or vehicle (intranasal, 30 μl). Inflammation, cytokines and inflammatory markers in bronchoalveolar lavage fluid (BALF) and airway and tissue responses to inhaled methacholine (MCh 0.001 – 30 mg/ml) were measured 5, 7, 10 and 21 days post infection. Responsiveness to iv MCh (6 – 96 μg/min/kg) in vivo and to electrical field stimulation (EFS) and MCh in vitro were measured at 7 d. Epithelial permeability was measured by Evans Blue dye leakage into BALF at 7 d. Respiratory mechanics were measured using low frequency forced oscillation in tracheostomised and ventilated (450 bpm, f lexiVent) mice. Low frequency impedance spectra were calculated (0.5 – 20 Hz) and a model, consisting of an airway compartment [airway resistance (Raw) and inertance (Iaw)] and a constant-phase tissue compartment [coefficients of tissue d ing (G) and elastance (H)] was fitted to the data. Inflammation in adult mouse BALF peaked at 7 d (RSV 15.6 (4.7 SE) vs. control 3.7 (0.7) × 10 4 cells/ml p 0.001), resolving by 21 d, with no increase in weanlings at any timepoint. RSV-infected mice were hyperresponsive to aerosolised MCh at 5 and 7 d (PC 200 Raw adults: RSV 0.02 (0.005) vs. control 1.1 (0.41) mg/ml p = 0.003) (PC 200 Raw weanlings: RSV 0.19 (0.12) vs. control 10.2 (6.0) mg/ml MCh p = 0.001). Increased responsiveness to aerosolised MCh was matched by elevated levels of cysLT at 5 d and elevated VEGF and PGE 2 at 7 d in BALF from both adult and weanling mice. Responsiveness was not increased in response to iv MCh in vivo or EFS or MCh challenge in vitro. Increased epithelial permeability was not detected at 7 d. Infection with 1 × 10 5 pfu RSV induced extreme hyperresponsiveness to aerosolised MCh during the acute phase of infection in adult and weanling mice. The route-specificity of hyperresponsiveness suggests that epithelial mechanisms were important in determining the physiological effects. Inflammatory changes were dissociated from physiological changes, particularly in weanling mice.
Publisher: American Physiological Society
Date: 09-2010
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.CHEMOSPHERE.2019.03.088
Abstract: Little is known about the effect of pregnancy on the response to particulate matter. The aim of this study was to determine if pregnancy increases the susceptibility to PM from different sources using a mouse model. Pregnant, eight-week-old C57BL/6J mice were exposed intranasally to 50 μg of diesel exhaust particles (DEP), iron oxide (Fe Exposure to silica caused an influx of lymphocytes, eosinophils and neutrophils into the lung. The magnitude of this response was suppressed by pregnancy. Pregnancy also enhanced the production of CD4 Collectively, our data suggest that pregnancy reduces the inflammatory response to silica and alters the immune response to DEP. These responses were accompanied by pregnancy related changes including increased IL-4 production, reduced IL-8 production and an increase in the proportion of CD4
Publisher: Wiley
Date: 13-10-2020
DOI: 10.1111/RESP.13952
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.ENVPOL.2019.113340
Abstract: Evidence of health effects following early life exposure to short-to-medium duration of high pollution levels is extremely limited. We aimed to evaluate the associations between: 1. intrauterine exposure to fine particulate matter (PM All participants were recruited from the Latrobe Valley of Victoria, Australia. Participants' 24-h average and hourly peak mine fire-specific PM We included 286 of 311 children whose parents consented to be linked, comprising 77 with no exposure, 88 with intrauterine exposure and 121 with exposure in infancy. 10- and 100- μg m Exposure to coal mine fire emissions during infancy was associated with increased dispensing of antibiotics. This could reflect increased childhood infections or increased prescriptions of antibiotics in the year following the fire.
Publisher: Wiley
Date: 05-10-2020
DOI: 10.1111/RESP.13951
Publisher: Wiley
Date: 20-03-2022
DOI: 10.1111/RESP.14246
Abstract: Coal mine dust has a complex and heterogeneous chemical composition. It has been suggested that coal particle chemistry plays a critical role in determining the pathogenesis of coal workers' pneumoconiosis (CWP). In this study, we aimed to establish the association between the detrimental cellular response and the chemical composition of coal particles. We sourced 19 real‐world coal s les. S les were crushed prior to use to minimize the impact of particle size on the response and to ensure the particles were respirable. Key chemical components and inorganic compounds were quantified in the coal s les. The cytotoxic, inflammatory and pro‐fibrotic responses in epithelial cells, macrophages and fibroblasts were assessed following 24 h of exposure to coal particles. Principal component analysis (PCA) and stepwise regression were used to determine which chemical components of the coal particles were associated with the cell response. The cytotoxic, inflammatory and pro‐fibrotic response varied considerably between coal s les. There was a high level of collinearity in the cell responses and between the chemical compounds within the coal s les. PCA identified three factors that explained 75% of the variance in the cell response. Stepwise multiple regression analysis identified K 2 O ( p .001) and Fe 2 O 3 ( p = 0.011) as significant predictors of cytotoxicity and cytokine production, respectively. Our data clearly demonstrate that the detrimental cellular effects of exposure to coal mine dusts are highly dependent on particle chemistry. This has implications for understanding the pathogenesis of CWP.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.RESP.2008.06.011
Abstract: This study aimed to determine whether the route of administration of methacholine (MCh) influenced the pattern of airway hyper-responsiveness (AHR) in mice. BALB/c mice were inoculated with a 50-microL volume containing 10(4.5)-pfu Influenza virus A/Mem/1/71(H3N1) or media. MCh responsiveness in vivo [inhaled (0.01-30 mg/mL), i.v. MCh (6-48 microg/min/kg)] and in vitro were measured at day 4 post-infection (D4) during acute lower respiratory infection (LRI) and following resolution of infection at day 20 (D20) using a low-frequency, forced oscillation technique. Inflammation was assessed in bronchoalveolar lavage fluid. Infected mice had pulmonary inflammation and heightened responsiveness to both inhaled (p<0.03) and intravenous (p<0.02) MCh on D4, but not on D20. In vitro responsiveness was not altered at either time point. Influenza A LRI results in AHR during acute infection associated with a marked inflammatory response and increased permeability of the alveolar-capillary barrier. These data suggest that intrinsic muscle properties are not altered but MCh has greater access to airway smooth muscle during acute infection.
Publisher: Walter de Gruyter GmbH
Date: 2011
Abstract: This review provides a snapshot of some key environmental health issues that will provide ongoing challenges for the Pacific Basin region in the coming decades. It is clear that climate change as well as the rapidly increasing production of environmental pollutants are significant emerging environmental health issues. To date, research in these areas is limited, and the consequences of potential changes in disease vector distribution, disease outbreaks associated with climate change-induced severe weather events, and the consequences of chronic exposure to engineered nanoparticles and persistent organic pollutants (POPs), particularly in children, remain to be determined. Clearly, any progress in (i) predicting the outcomes of potential environmental health issues in the future, (ii) identifying subpopulations (at local, national, and international levels) that are at risk, and (iii) establishing measures to limit the impact of these issues in terms of public health, will require a coordinated effort from scientists, epidemiologists, monitoring agencies, governments, and aid agencies.
Publisher: MDPI AG
Date: 09-01-2023
Abstract: Emerging evidence suggests that inhalation of particulate matter (PM) can have direct adverse effects on liver function. Early life is a time of particular vulnerability to the effects of air pollution. On that basis, we tested whether in utero exposure to residential PM has an impact on the developing liver. Pregnant mice (C57BL/6J) were intranasally administered 100 µg of PM s led from residential roof spaces (~5 mg/kg) on gestational days 13.5, 15.5, and 17.5. The pups were euthanized at two weeks of age, and liver tissue was collected to analyse hepatic metabolism (glycogen storage and lipid level), cellular responses (oxidative stress, inflammation, and fibrosis), and genotoxicity using a range of biochemical assays, histological staining, ELISA, and qPCR. We did not observe pronounced effects of environmentally s led PM on the developing liver when examining hepatic metabolism and cellular response. However, we did find evidence of liver genomic DNA damage in response to in utero exposure to PM. This effect varied depending on the PM s le. These data suggest that in utero exposure to real-world PM during mid-late pregnancy has limited impacts on post-natal liver development.
Publisher: Public Library of Science (PLoS)
Date: 24-06-2013
Publisher: IOP Publishing
Date: 20-04-2018
Abstract: We have developed an x-ray imaging system for in vivo four-dimensional computed tomography (4DCT) of small animals for pre-clinical lung investigations. Our customized laboratory facility is capable of high resolution in vivo imaging at high frame rates. Characterization using phantoms demonstrate a spatial resolution of slightly below 50 μm at imaging rates of 30 Hz, and the ability to quantify material density differences of at least 3%. We benchmark our system against existing small animal pre-clinical CT scanners using a quality factor that combines spatial resolution, image noise, dose and scan time. In vivo 4DCT images obtained on our system demonstrate resolution of important features such as blood vessels and small airways, of which the smallest discernible were measured as 55-60 μm in cross section. Quantitative analysis of the images demonstrate regional differences in ventilation between injured and healthy lungs.
Publisher: Springer Science and Business Media LLC
Date: 06-2003
DOI: 10.1007/S00360-003-0335-Y
Abstract: This study investigated the pattern of autonomic innervation of the heart of the fat-tailed dunnart (Sminthopsis crassicaudata) using isolated cardiac preparations. While the pattern of autonomic innervation of the atria was consistent with that found in other mammals, the ventricles displayed an unusual pattern of mammalian cardiac innervation. Transmural stimulation of the intramural nerves of isolated right ventricular preparations caused a decrease in the force of contraction of 46.8+/-3.2% followed by a rebound increase in the force of contraction beyond basal levels of 40.9+/-6.9%. These responses could be blocked independently by the application of the muscarinic receptor antagonist hyoscine and beta-adrenoreceptor antagonist propranolol respectively and could also be mimicked by the application of the agonists acetylcholine (Ach) and noradrenaline (NA). These findings indicated the presence of a functional cholinergic innervation of the ventricles that was capable of reducing the force of contraction below basal levels. This pattern of innervation has only been found previously in one other mammal, the bent-winged bat (Miniopterus schreibersii). Given that both of these species are heterotherms, it is possible that such a pattern of innervation may relate to the control of cardiac output during torpor. These findings are the first that demonstrate the homogeneity of a physiological control mechanism in a so-called 'shallow, daily torpidator' (S. crassicaudata) and a 'deep hibernator' (M. schreibersii) that is absent in mammalian homeotherms. These findings are consistent with recent work suggesting that there may be little difference between these types of heterothermy.
Publisher: Wiley
Date: 02-08-2021
DOI: 10.1111/RESP.14117
Abstract: The link between respiratory and vascular health is well documented in adult populations. Impaired lung function is consistently associated with thicker arteries and higher incidence of cardiovascular disease. However, there are limited data on this relationship in young children and the studies that exist have focussed on populations at high risk of cardiorespiratory morbidity. We determined if an association exists between respiratory and cardiovascular function in young children and, if so, whether it is confounded by known cardiorespiratory risk factors. Respiratory and vascular data from a prospective cohort study established to evaluate the health implications 3 years after coal mine fire smoke exposure in children aged 3–5 years were used. Respiratory function was measured using the forced oscillation technique and included resistance at 5 Hz ( R 5 ), reactance at 5 Hz ( X 5 ) and area under the reactance curve (AX). Vascular health was measured by carotid intima‐media thickness (ultrasound) and pulse wave velocity (arterial tonometry). Regression analyses were used to examine the relationship between the respiratory Z ‐scores and cardiovascular measures. Subsequent analyses were adjusted for potential confounding by maternal smoking during pregnancy, maternal education and exposure to fine particulate matter .5 μm in aerodynamic diameter (PM 2.5 ). Peripheral lung function ( X 5 and AX), but not respiratory system resistance ( R 5 ), was associated with vascular function. Adjustment for maternal smoking, maternal education and early life exposure to PM 2.5 had minimal effect on these associations. These observations suggest that peripheral lung stiffness is associated with vascular stiffness and that this relationship is established early in life.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.ENVRES.2018.03.029
Abstract: In utero exposure to particulate matter (PM) from a range of sources is associated with adverse post-natal health however, the effect of maternal exposure to community-s led PM on early post-natal lung and immune development is poorly understood. Using a mouse model, we aimed to determine whether in utero exposure to PM alters early post-natal lung function and immune cell populations. We used PM collected from ceiling voids in suburban houses as a proxy for community PM exposure. Pregnant C57BL/6 mice were intranasally exposed to ceiling derived PM, or saline alone, at gestational day (E) 13.5, 15.5, and 17.5. When mice were two weeks old, we assessed lung function by the forced oscillation technique, and enumerated T and B cell populations in the spleen and thymus by flow cytometry. Maternal exposure to PM impaired somatic growth of male offspring resulting in reduced lung volume and deficits in lung function. There was no effect on thymic T cell populations in dams and their male offspring but PM decreased the CD4 +CD25 + T cell population in the female offspring. In contrast, maternal exposure to PM increased splenic CD3 +CD4 + and CD3 +CD8 + T cells in dams, and there was some evidence to suggest inhibition of splenic T cell maturation in male but not female offspring. Our findings suggested that maternal exposure to ceiling void PM has the capacity to impair early somatic growth and alter early life immune development in a sex specific manner.
Publisher: Informa UK Limited
Date: 03-07-2017
DOI: 10.1080/08958378.2017.1367054
Abstract: Inhalation of particulate matter less than 10 µm in diameter (PM
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.RESP.2008.04.010
Abstract: Infant mice were ventilated with either high tidal volume (V(T)) with zero end-expiratory pressure (HVZ), high V(T) with positive end-expiratory pressure (PEEP) (HVP), or low V(T) with PEEP. Thoracic gas volume (TGV) was determined plethysmographically and low-frequency forced oscillations were used to measure the input impedance of the respiratory system. Inflammatory cells, total protein, and cytokines in bronchoalveolar lavage fluid (BALF) and interleukin-6 (IL-6) in serum were measured as markers of pulmonary and systemic inflammatory response, respectively. Coefficients of tissue d ing and tissue elastance increased in all ventilated mice, with the largest rise seen in the HVZ group where TGV rapidly decreased. BALF protein levels increased in the HVP group, whereas serum IL-6 rose in the HVZ group. PEEP keeps the lungs open, but provides high volumes to the entire lungs and induces lung injury. Compared to studies in adult and non-neonatal rodents, infant mice demonstrate a different response to similar ventilation strategies underscoring the need for age-specific animal models.
Publisher: American Physiological Society
Date: 11-2009
DOI: 10.1152/JAPPLPHYSIOL.00393.2009
Abstract: The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10 4.5 plaque-forming units of influenza A/Mem/1/71 in 50 μl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue d ing and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue d ing, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage s le was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-α, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.
Publisher: Wiley
Date: 21-03-2011
Publisher: Elsevier BV
Date: 07-2020
Publisher: American Physiological Society
Date: 08-2009
DOI: 10.1152/AJPLUNG.00053.2009
Abstract: It is widely accepted that atopic asthma depends on an allergic response in the airway, yet the immune mechanisms that underlie the development of airway hyperresponsiveness (AHR) are poorly understood. Mouse models of asthma have been developed to study the pathobiology of this disease, but there is considerable strain variation in the induction of allergic disease and AHR. The aim of this study was to compare the development of AHR in BALB/c, 129/Sv, and C57BL/6 mice after sensitization and challenge with ovalbumin (OVA). AHR to methacholine was measured using a modification of the forced oscillation technique in anesthetized, tracheostomized mice to distinguish between airway and parenchymal responses. Whereas all strains showed signs of allergic sensitization, BALB/c was the only strain to develop AHR, which was associated with the highest number of activated (CD69 + ) CD4 + T cells in the airway wall and the highest levels of circulating OVA-specific IgG 1 . AHR did not correlate with total or antigen-specific IgE. We assessed the relative contribution of CD4 + T cells and specific IgG 1 to the development of AHR in BALB/c mice using adoptive transfer of OVA-specific CD4 + T cells from DO11.10 mice. AHR developed in these mice in a progressive fashion following multiple OVA challenges. There was no evidence that antigen-specific antibody had a synergistic effect in this model, and we concluded that the number of antigen-specific T cells activated and recruited to the airway wall was crucial for development of AHR.
Publisher: American Physiological Society
Date: 08-2006
DOI: 10.1152/JAPPLPHYSIOL.00011.2006
Abstract: Electrical stimulation of intercostal muscles was employed to measure thoracic gas volume (TGV) during airway occlusion in the absence of respiratory effort at different levels of lung inflation. In 15 tracheostomized and mechanically ventilated CBA/Ca mice, the value of TGV obtained from the spontaneous breathing effort available in the early phase of the experiments (TGVsp) was compared with those resulting from muscle stimulation (TGVst) at transrespiratory pressures of 0, 10, and 20 cmH 2 O. A very strong correlation ( r 2 = 0.97) was found, although with a systematically (∼16%) higher estimation of TGVst relative to TGVsp, attributable to the different durations of the stimulated (∼50 ms) and spontaneous (∼200 ms) contractions. Measurements of TGVst before and after injections of 0.2, 0.4, and 0.6 ml of nitrogen into the lungs in six mice resulted in good agreement between the change in TGVst and the injected volume ( r 2 = 0.98). In four mice, TGVsp and TGVst were compared at end expiration with air or a helium-oxygen mixture to confirm the validity of isothermal compression in the alveolar gas. The TGVst values measured at zero transrespiratory pressure in all CBA/Ca mice [0.29 ± 0.05 (SD) ml] and in C57BL/6 ( N = 6 0.34 ± 0.08 ml) and BALB/c ( N = 6 0.28 ± 0.06 ml) mice were in agreement with functional residual capacity values from previous studies in which different techniques were used. This method is particularly useful when TGV is to be determined in the absence of breathing activity, when it must be known at any level of lung inflation or under non-steady-state conditions, such as during pharmaceutical interventions.
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.RESP.2008.10.006
Abstract: The aim of the present study was to determine the short-term effects of hyperoxia on respiratory mechanics in mechanically ventilated infant and adult mice. Eight and two week old BALB/c mice were exposed to inspired oxygen fractions [Formula: see text] of 0.21, 0.3, 0.6, and 1.0, respectively, during 120 min of mechanical ventilation. Respiratory system mechanics and inflammatory responses were measured. Using the low-frequency forced oscillation technique no differences were found in airway resistance between different [Formula: see text] groups when corrected for changes in gas viscosity. Coefficients of lung tissue d ing and elastance were not different between groups and showed similar changes over time in both age groups. Inflammatory responses did not differ between groups at either age. Hyperoxia had no impact on respiratory mechanics during mechanical ventilation with low tidal volume and positive end-expiratory pressure. Hence, supplemental oxygen can safely be applied during short-term mechanical ventilation strategies in infant and adult mice.
Publisher: Springer Science and Business Media LLC
Date: 14-02-2019
DOI: 10.1007/S00408-019-00200-Z
Abstract: Our understanding of the respiratory health consequences of geogenic (earth-derived) particulate matter (PM) is limited. Recent in vivo evidence suggests that the concentration of iron is associated with the magnitude of the respiratory response to geogenic PM. We investigated the inflammatory and cytotoxic potential of silica and iron oxide particles alone, and in combination, on lung epithelial cells. Bronchial epithelial cells (BEAS-2B) were exposed to silica (quartz, cristobalite) and/or iron oxide (hematite, magnetite) particles. Cytotoxicity and cytokine production (IL-6, IL-8, IL-1β and TNF-α) were assessed by LDH assay and ELISA, respectively. In subsequent experiments, the cytotoxic and inflammatory potential of the particles was assessed using alveolar epithelial cells (A549). After 24 h of exposure, iron oxide did not cause significant cytotoxicity or production of cytokines, nor did it augment the response of silica in the BEAS2-B cells. In contrast, while the silica response was not augmented in the A549 cells by the addition of iron oxide, iron oxide particles alone were sufficient to induce IL-8 production in these cells. There was no response detected for any of the outcomes at the 4 h time point, nor was there any evidence of IL-1β or TNF-α production. While previous studies have suggested that iron may augment silica-induced inflammation, we saw no evidence of this in human epithelial cells. We found that alveolar epithelial cells produce pro-inflammatory cytokines in response to iron oxide particles, suggesting that previous in vivo observations are due to the alveolar response to these particles.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.ENVINT.2019.105187
Abstract: Cities are home to over half the global population that proportion is expected to rise to 70% by mid-century. The urban environment differs greatly from that in which humans evolved, with potentially important consequences for health. Rates for allergic, inflammatory and auto-immune diseases appear to rise with urbanization and be higher in the more urbanized nations of the world which has led some to suggest that cities promote the occurrence of these diseases. However, there are no syntheses outlining what urban-associated diseases are and what characteristics of cities promote their occurrence. To synthesize the current understanding of "urban-associated diseases", and discover the common, potentially modifiable features of cities that may be driving these associations. We focus on any diseases that have been associated with cities or are particularly prominent in today's urban societies. We draw on expertise across erse health fields to examine the evidence for urban connections and drivers. We found evidence for urban associations across allergic, auto-immune, inflammatory, lifestyle and infectious disease categories. Some conditions (e.g. obesity and diabetes) have complex relationships with cities that have been insufficiently explored. Other conditions (e.g. allergies and asthma) have more evidence demonstrating their relationship with cities and the mechanisms driving that association. Unsurprisingly, air pollution was the characteristic of cities most frequently associated with disease. Other identified urban risk factors are not as widely known: altered microbial exposure and a disconnect from environmental microbiomes, vitamin D deficiency, noise and light pollution, and a transient, over-crowded, impoverished population. However, many complexities and caveats to these relationships beg clarification we highlight the current knowledge gaps and outline ways to fill those gaps. Identifying urban-associated diseases and their drivers will allow us to prepare for the urban-disease burden of the future and create healthy cities that mitigate that disease burden.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2020
DOI: 10.1007/S10653-019-00492-3
Abstract: Australian Aboriginal populations have unacceptably high rates of bronchiectasis. This disease burden is associated with high rates of detection of pathogenic bacteria, particularly non-typeable Haemophilus influenzae (NTHi). While there is evidence to suggest that exposure to inorganic particulate matter (PM) is associated with worse respiratory infections, no studies have considered the direct effect of this PM on bacterial growth. Nine clinical isolates of pathogenic NTHi were used for this study. Isolates were exposed to two common iron oxides, haematite (Fe
Publisher: MDPI AG
Date: 26-07-2013
DOI: 10.3390/NU5082880
Publisher: Wiley
Date: 26-07-2007
DOI: 10.1111/J.1365-2222.2007.02750.X
Abstract: Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV-induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV-induced effects. To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen-induced airway immunity in a murine asthma model, and to examine the mechanisms involved. BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway-associated, asthma-like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA-specific proliferative responses and cytokine production by cells from the lung-draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB-induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA-sensitized mice were adoptively transferred into naïve BALB/c mice that were subsequently sensitized and challenged with OVA, or a non-specific antigen. UVB irradiation of skin significantly suppressed AHR to methacholine and OVA-specific responses in the LDLN and in the lung compartment. Reduced OVA-specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 x 10(6) LDLN cells from UVB irradiated, but not from non-irradiated, OVA-sensitized mice suggested that UVB-induced regulatory cells are responsible for many of the asthma-reducing effects of dorsal UVB exposure. UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.RESP.2006.11.009
Abstract: Epidemiological data suggests lower respiratory infections (LRI) with respiratory syncytial virus (RSV) are capable of causing long-term abnormalities in airway function. To directly test the effects of RSV LRI, we infected adult and weanling BALB/c mice with RSV (A2) or vehicle. Respiratory system impedance was used to assess baseline airway function and responses to iv methacholine (MCh) at 4, 8, 24 and 34 weeks post infection. In vitro airway responses were measured 24 weeks post infection using electrical field stimulation and MCh. Mice infected as adults showed no alterations in airway function. Mice infected as weanlings had increased MCh responses 24 weeks post infection. However, the increased response was not present 34 weeks post infection nor accompanied by alterations in in vitro responses or airway morphometry. This study did not detect long-lasting changes in airway function following RSV infection in mice. These data do not provide support for alterations in airway structure or function being responsible for the observed relationship between RSV infection in infants and asthma in later life.
Publisher: Wiley
Date: 15-09-2023
DOI: 10.1111/RESP.14593
Publisher: Elsevier BV
Date: 10-2019
Publisher: American Thoracic Society
Date: 05-2014
Publisher: MDPI AG
Date: 13-07-2021
Abstract: Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.
Publisher: The American Association of Immunologists
Date: 11-2007
DOI: 10.4049/JIMMUNOL.179.9.5748
Abstract: Airway mucosal dendritic cells (AMDC) and other airway APCs continuously s le inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy in iduals. This homeostasis is thought to be disrupted in allergic respiratory disorders such as allergic asthma, such that a potentially damaging Th2-biased, CD4+ T cell-mediated inflammatory response develops against intrinsically nonpathogenic allergens. Using a mouse model of experimental allergic airways disease (EAAD), we have investigated the functional changes occurring in AMDC and other airway APC populations during disease onset. Onset of EAAD was characterized by early and transient activation of airway CD4+ T cells coinciding with up-regulation of CD40 expression exclusively on CD11b− AMDC. Concurrent enhanced allergen uptake and processing occurred within all airway APC populations, including B cells, macrophages, and both CD11b+ and CD11b− AMDC subsets. Immune serum transfer into naive animals recapitulated the enhanced allergen uptake observed in airway APC populations and mediated activation of naive allergen-specific, airway CD4+ T cells following inhaled allergen challenge. These data suggest that the onset of EAAD is initiated by enhanced allergen capture and processing by a number of airway APC populations and that allergen-specific Igs play a role in the conversion of normally quiescent AMDC subsets into those capable of inducing airway CD4+ T cell activation.
Publisher: Elsevier BV
Date: 2003
Abstract: We investigated the effect of parasympathetic antagonism on the patterns of heart rate during torpor in the western pygmy possum Cercatetus concinnus (Marsupialia: Burramyidae). This is the first study to examine the influence of the autonomic nervous system on cardiac function in a metatherian hibernator. During torpor, antagonism of the parasympathetic nervous system eliminated the ventilatory tachycardia, variability in instantaneous heart rate, and increased the overall heart rate. These findings are consistent with previous studies on other mammalian heterotherms, which have shown that the parasympathetic nervous system is responsible for these patterns in heart rate. During extended bouts of torpor (2 to 3 days) the ventilatory tachycardia persisted throughout each bout, which indicates that the parasympathetic nervous system remained functional during that time. It has been suggested that the progressive removal of autonomic tone is characteristic of deep steady-state hibernation. There is no evidence to suggest that such a state was going to be reached in the possums in this study. To date there is little evidence that clearly demonstrates a physiological basis for the distinction between shallow, daily torpor and deep hibernation.
Publisher: MDPI AG
Date: 16-08-2021
DOI: 10.3390/IJMS22168790
Abstract: In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue d ing and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized in iduals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function.
Publisher: Hogrefe Publishing Group
Date: 2006
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.CHEMOSPHERE.2018.03.052
Abstract: Adverse health effects of particulate matter (PM) vary with chemical composition however, evidence regarding which elements are the most detrimental is limited. The roof space area provides an open and stable environment for outdoor PM to settle and deposit. Therefore, this study used roof space PM s les as a proxy of residential cumulative exposure to outdoor air pollution to investigate their pro-inflammatory effects on human lung cells and the contribution of the endotoxin and chemical content. Roof space PM s les of 36 different homes were collected and analysed using standardised techniques. We evaluated cytotoxicity and cytokine production of BEAS-2B cells after PM exposure using MTS and ELISA, respectively. Principle component analysis (PCA) and linear regression analyses were employed to assess the associations between cytokine production and the PM components. PM caused significant time- and dose-dependent increases in cellular cytokine production (p < 0.05). PCA identified four factors that explained 68.33% of the variance in the chemical composition. An increase in Factor 1 (+Fe, +Al, +Mn) score and a decrease in Factor 2 (-Ca, +Pb, +PAH) score were associated with increased interleukin (IL)-6 (Factor 1 p = 0.010 Factor 2 p = 0.006) and IL-8 (Factor 1 p = 0.003 Factor 2 p = 0.020) production, however, only the association with Factor 1 was evident after correcting for endotoxin and particle size. Our study provides novel insight into the positive associations between pro-inflammatory effects of roof space PM s les with Fe, Al and Mn levels.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.SCITOTENV.2015.07.001
Abstract: Particulate matter (PM) exposure has been linked epidemiologically to exacerbations of lung disease, including respiratory infections. We investigated the effects of geogenic (earth-derived) PM10 (PM<10 μm diameter) on the response to a respiratory viral infection. Geogenic dust was s led from four communities in arid environments in Western Australia. Adult female BALB/c mice were intranasally exposed to chronic doses of PM10 (10 μg/day for 10 days), and/or infected with influenza (A/Mem/1/71) virus. Inflammation (cells, IL-6, IFN-γ) was measured in bronchoalveolar lavage. Lung mechanics were measured using the forced oscillation technique. Geogenic PM10 induced lung inflammation (neutrophils, macrophages) with additive effects in mice also infected with influenza. PM10 also modified the influenza-induced IL-6 and IFN-γ responses. Geogenic PM10 increased airway resistance, and increased hysteresivity in those exposed to both insults. Viral titres were significantly higher after PM10 exposure. Iron concentration was inversely associated with IFN-γ and positively associated with viral titre and hysteresivity. Geogenic PM10 exposure increases inflammation, impairs lung function and increases viral load, exacerbating the response to respiratory viral infection. Iron in the particles may be a driver of these responses. This has important implications for respiratory health in communities exposed to high geogenic PM10, such as those in arid environments.
Publisher: Microbiology Society
Date: 10-2014
Abstract: The aim of the study was to investigate the association between the presence of altered penicillin-binding protein 3 (PBP3) in non-typable Haemophilus influenzae (NTHi) and an increased capacity to invade bronchial epithelial cells in vitro . A collection of 40 clinical isolates of NTHi comprised of 20 with normal PBP3 and 20 with altered PBP3 (defined by an N526K substitution) was established. The isolates were tested for the ability to invade bronchial epithelial cells in vitro using a 4 h gentamicin survival assay. Invasion was measured as the percentage of intracellular organisms relative to the initial inoculum. The mean invasion rate was 0.00–14.79 % in the normal PBP3 isolates and 0.02–36.69 % in the altered PBP3 isolates. The altered PBP3 isolates had a higher ( P = 0.003) mean invasion rate (6.86 %, n = 20) than the normal PBP3 isolates (1.31 %, n = 20). Subsequently, two variants of altered PBP3 (transformant 1, N526K transformant 2, M377I, S385T, L389F and N526K) were cloned into three of the initial isolates (parents) with normal PBP3 and relatively low invasive ability, and the parents and transformants tested for invasion as above. There was no difference ( P = 0.89) in the mean invasion rates for the parents (0.81 %, n = 3), transformants 1 (0.90 %, n = 3) and transformants 2 (1.38 %, n = 3). There was an association between the presence of altered PBP3 in NTHi and an increased capacity to invade BEAS-2B cells in vitro , but cloning experiments suggested that the altered PBP3 was not involved directly in enhanced invasion.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.RESP.2008.01.009
Abstract: Basal airway smooth muscle (ASM) tone has not been demonstrated in mice in vivo. To determine whether basal ASM tone is present in mouse airways we measured respiratory system impedance (Zrs) before and after either atropine or bilateral vagotomy. Zrs was measured using forced oscillations delivered via a wave-tube during slow ( approximately 35s) inflation-deflation maneuvers between transrespiratory pressures (Prs) of 0 and 20 cm H2O. A constant-phase tissue model was applied to the Zrs to calculate airway resistance (R aw), tissue d ing (G) and elastance (H). Thoracic gas volume (TGV) was determined plethysmographically at Prs=0 cm H2O and by integration of the inspiratory flow. The relationship between conductance (G aw=1/R aw) and TGV during inflation was also examined. Neither atropine nor vagotomy produced any change in R aw, H, eta (=G/H), TGV or the slope of G aw vs. TGV that was different to that observed in the relevant control groups. These data show that BALB/c mice do not have cholinergic ASM tone in vivo.
Publisher: Wiley
Date: 23-06-2019
DOI: 10.1111/RESP.13617
Abstract: Long-term respiratory risks following exposure to relatively short periods of poor air quality early in life are unknown. We aimed to evaluate the association between exposure to a 6-week episode of air pollution from a coal mine fire in children aged <2 years, and their lung function 3 years after the fire. We conducted a prospective cohort study. In idual exposure to 24-h average and peak concentrations of particulate matter with an aerodynamic diameter <2.5 μm in diameter (PM Of the 203 infants originally recruited, 84 aged 4.3 ± 0.5 years completed FOT testing. Median (interquartile range, IQR) for average and peak PM Infant exposure to coal mine fire emissions could be associated with long-term impairment of lung reactance.
Publisher: Public Library of Science (PLoS)
Date: 14-03-2014
Publisher: American Thoracic Society
Date: 05-2019
Publisher: Wiley
Date: 20-02-2018
DOI: 10.1111/CEA.13097
Abstract: Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AECs) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children. Primary AECs were obtained from children with and without asthma, differentiated into air-liquid interface (ALI) cultures and infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1 (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER R Basal TJ gene expression of claudin-1 and occludin was significantly upregulated in asthmatic children compared to non-asthmatics however, no difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1 protein expression was significantly reduced in AEC of asthmatic children compared to non-asthmatic controls suggesting possible post-transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non-asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction in TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed. This study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma.
Publisher: Hong Kong STM Publishing Co., Ltd.
Date: 2013
DOI: 10.7178/JEIT.18
Publisher: Wiley
Date: 19-04-2010
DOI: 10.1111/J.1365-2222.2010.03469.X
Abstract: In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4(+) effector cells at the airway mucosa orchestrate, and CD4(+)CD25(+) regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma-like responses in respiratory tissues. To determine whether UV-induced changes in CD11c(+) cells, CD4(+)CD25(+) effector cells or CD4(+)CD25(+) regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease. The phenotype and function of CD11c(+) cells and CD4(+)CD25(+) cells in the trachea and ADLNs of UV- and non-irradiated, OVA-sensitized mice was examined 24 h after a single exposure to aerosolized OVA. No changes in the function of CD11c(+) cells from UV-irradiated mice were observed. CD4(+)CD25(+) cells from UV-irradiated, OVA-sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA-sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV-irradiated, OVA-sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE-loaded, OVA-TCR-specific CD4(+) cells adoptively transferred into UV- and non-irradiated, OVA-sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL-10, TGF-beta mRNA). To examine effector T cells, ADLN cells from UV-irradiated, OVA-sensitized and -challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4(+)CD25(+) cells, and reduced proliferation in the absence of the regulatory cytokine, IL-10. Reduced allergic airways disease in UV-irradiated mice is due to fewer effector CD4(+)CD25(+) cells in the trachea and ADLNs, and not due to UV-induced regulatory cells.
Publisher: International Union of Crystallography (IUCr)
Date: 2016
DOI: 10.1107/S1600577515021700
Abstract: This work utilized synchrotron imaging to achieve a regional assessment of the lung's response to imparted oscillations. The forced oscillation technique is increasingly being used in clinical and research settings for the measurement of lung function. During the forced oscillation technique, pressure oscillations are imparted to the lungs via the subjects' airway opening and the response is measured. This provides information about the mechanical properties of the airways and lung tissue. The quality of measurements is dependent upon the input signal penetrating uniformly throughout the lung. However, the penetration of these signals is not well understood. The development and use of a novel image-processing technique in conjunction with synchrotron-based imaging was able to regionally assess the lungs' response to input pressure oscillation signals in anaesthetized mice. The imaging-based technique was able to quantify both the power and distribution of lung tissue oscillations during forced oscillations of the lungs. It was observed that under forced oscillations the apices had limited lung tissue expansion relative to the base. This technique could be used to optimize input signals used for the forced oscillation technique or potentially as a diagnostic tool itself.
Publisher: MDPI AG
Date: 28-12-2020
Abstract: Exposure to geogenic (earth-derived) particulate matter (PM) is linked to severe bacterial infections in Australian Aboriginal communities. Experimental studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of silica and iron oxide on the inflammatory response and bacterial phagocytosis in macrophages. THP-1 and peripheral blood mononuclear cell-derived macrophages were exposed to iron oxide (haematite or magnetite) or silica PM with or without exposure to lipopolysaccharide. Cytotoxicity and inflammation were assessed by LDH assay and ELISA respectively. The uptake of non-typeable Haemophilus influenzae by macrophages was quantified by flow cytometry. Iron oxide increased IL-8 production while silica also induced significant production of IL-1β. Both iron oxide and silica enhanced LPS-induced production of TNF-α, IL-1β, IL-6 and IL-8 in THP-1 cells with most of these responses replicated in PBMCs. While silica had no effect on NTHi phagocytosis, iron oxide significantly impaired this response. These data suggest that geogenic particles, particularly iron oxide PM, cause inflammatory cytokine production in macrophages and impair bacterial phagocytosis. These responses do not appear to be linked. This provides a possible mechanism for the link between exposure to these particles and severe bacterial infection.
Publisher: Wiley
Date: 03-2014
DOI: 10.1002/PHY2.276
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.RESP.2010.08.003
Abstract: Previous studies have suggested that in vitro modulation of neutrophil chemokines and inflammatory cytokines by neutrophil elastase (NE) does not translate to the in vivo setting. We aimed to test the role of NE in the recruitment of neutrophils, cytokine production and lung function responses to respiratory viral infection. To address this, we inoculated neutrophil elastase (NE(-/-)) deficient and wild-type (WT) 129Sv mice with 50μL of 10(4.5)pfu Influenza A/Mem71 (H3N1) or a control preparation. Mice were subjected to methacholine (MCh) challenge at 3-4 days post-infection during the peak of cellular inflammation. Inflammation, protein content and cytokines (TNF-α and MIP-2) were assessed in bronchoalveolar lavage fluid. Influenza-infected mice had a heightened responsiveness to MCh, increased cellular inflammation, increased protein leak and altered cytokine production, none of which were influenced by the absence of NE. These data demonstrate that NE does not modulate neutrophil recruitment, cytokine production, epithelial permeability or responsiveness to bronchoconstricting agents during acute influenza infection in mice.
Publisher: SAGE Publications
Date: 23-08-2018
Abstract: Recent observational studies have reported that patients with low circulating levels of vitamin D experience larger infarct volumes and worse functional outcomes after ischemic stroke compared to those with sufficient levels. However, it is unknown whether a causal relationship exists between low vitamin D levels and poor stroke outcome. This study aimed to assess the effect of vitamin D deficiency on acute outcomes post-stroke. Male C57Bl6 mice (six week old) were assigned to either a control or vitamin D deficient diet for four weeks prior to stroke. Stroke was induced by 1 h middle cerebral artery occlusion (MCAO) with reperfusion. At 24 h, we assessed functional outcomes, infarct volume, quantified immune cells in the brain by immunofluorescence and examined susceptibility to lung infection. ELISAs showed that the plasma level of hydroxyvitamin D 3 was 85% lower in mice fed the vitamin D-deficient diet compared with the control group. Despite this, vitamin D deficiency had no impact on functional outcomes or infarct volume after stroke. Further, there were no differences in the numbers of infiltrating immune cells or bacterial load within the lungs. These data suggest that diet-induced vitamin D deficiency has no effect on acute post-stroke outcomes.
Publisher: European Respiratory Society (ERS)
Date: 10-02-2011
DOI: 10.1183/09031936.00156910
Abstract: The aim of this study was to assess whether in utero tobacco smoke exposure alone affects early-life lung growth and development. Pregnant BALB/c mice were exposed to cigarette smoke from six cigarettes per day, or air, from day 8 to 20 of gestation. At 2 weeks of age, pups were weighed and had their lung volumes and lung mechanics measured. Pups born from mothers exposed to cigarette smoke (CS pups n=17) were significantly lighter (6.76 ± 0.76 versus 7.72 ± 0.68 g) and had lower lung volumes (0.123 ± 0.02 versus 0.149 ± 0.02 mL) than control pups (n=20). Respiratory mechanics were adversely impacted by cigarette smoke exposure. CS pups had higher baseline airway resistance, tissue d ing and tissue elastance. These differences were largely due to lower lung volumes. Both tissue d ing and elastance were increased excessively in CS pups at high transrespiratory pressures, while other parameters were not affected. There were no histological differences between groups. In utero tobacco smoke exposure significantly affects growth and development in BALB/c mice. These impacts may partially explain the susceptibility of infants born to smoking mothers to early respiratory disease and chronic respiratory disease as adults.
Publisher: American Academy of Pediatrics (AAP)
Date: 2015
Abstract: Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life. It is uncertain to what extent maternal vitamin D status influences fetal development. Using an unselected community-based cohort of 901 mother-offspring pairs (the Western Australian Pregnancy Cohort [Raine] Study), we examined the relationship between maternal vitamin D deficiency at 18 weeks’ pregnancy and long-term health outcomes of offspring who were born in Perth, Western Australia (32° South), in 1989–1991. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] & nmol/L) was present in 36% (323 of 901) of the pregnant women. After adjusting for relevant covariates, maternal vitamin D deficiency during pregnancy was associated with impaired lung development in 6-year-old offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at 20 years. In summary, vitamin D may have an important, multifaceted role in the development of fetal lungs, brain, and bone. Experimental animal studies support an active contribution of vitamin D to organ development. Randomized controlled trials of vitamin D supplementation in pregnant women with long-term follow-up of offspring are urgently required to examine whether the correction of vitamin D deficiency in pregnant women is beneficial for their offspring and to determine the optimal level of maternal serum 25(OH)D for fetal development.
Publisher: American Physiological Society
Date: 08-2008
DOI: 10.1152/JAPPLPHYSIOL.90328.2008
Abstract: The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H 2 O transrespiratory pressure (P rs ) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated. Thoracic gas volume was calculated using plethysmography and electrical stimulation of the intercostal muscles. Lung mechanics were tracked during inflation-deflation maneuvers using a modification of the forced oscillation technique. Inflation beyond 20 cm H 2 O caused a shift in subsequent PV curves with an increase in slope of the inflation limb and an increase in lung volume at 20 cm H 2 O. There was an overall decrease in tissue elastance and a fundamental change in its volume dependence. This apparent “softening” of the lung could be recovered by partial degassing of the lung or applying a negative transrespiratory pressure such that lung volume decreased below functional residual capacity. Allowing the lung to spontaneously recover revealed that the lung required ∼1 h of mechanical ventilation to return to the original state. We propose a number of possible mechanisms for these observations and suggest that they are most likely explained by the unfolding of alveolar septa and the subsequent redistribution of the fluid lining the alveoli at high transrespiratory pressure.
Publisher: Wiley
Date: 11-2016
DOI: 10.14814/PHY2.13021
Publisher: Springer Science and Business Media LLC
Date: 23-02-2018
Publisher: MDPI AG
Date: 07-09-2017
DOI: 10.3390/NU9090985
Abstract: Both dietary fat and vitamin D deficiency have been linked with increased incidence of non-alcoholic fatty liver disease and insulin resistance. While sex differences in disease prevalence and severity are well known, the impact on disease pathogenesis remains unclear. To further explore the effect of these exposures on metabolic function, C57BL/6 male and female mice were weaned onto one of four diets low fat vitamin D replete, low fat vitamin D deficient, or two high fat diets, one vitamin D replete and one deficient. Visceral fat, hepatic adiposity, and insulin resistance were measured after five and a half weeks. Vitamin D deficiency, independent of dietary fat, increased hepatic fat accumulation in both sexes (p = 0.003), although did not increase hepatic expression of interleukin-6 (p = 0.92) or tumor necrosis factor-α (p = 0.78). Males were observed to have greater insulin resistance (glucose area under the curve: p 0.001, homeostatic model assessment for insulin resistance: p = 0.046), and have greater visceral adiposity (p 0.001), while female mice had greater hepatic fat accumulation (p 0.001). This study is the first to demonstrate vitamin D deficiency alone can cause hepatic accumulation while also being the first to observe higher liver fat percentages in female mice.
Publisher: AMPCo
Date: 08-08-2020
DOI: 10.5694/MJA2.50719
Publisher: Wiley
Date: 14-03-2023
DOI: 10.1111/RESP.14490
Publisher: Informa UK Limited
Date: 07-06-2016
Publisher: Informa UK Limited
Date: 29-11-2011
DOI: 10.3109/08958378.2011.625454
Abstract: Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a sex-influenced dose-response relationship between acute PM exposure and respiratory health, similar data are lacking for DEP. Further, experimental evidence showing deleterious effects on respiratory health due to acute DEP exposure is sparse. To establish and characterize a mouse model of acute DEP exposure, comparing male and female mice and assessing the kinetics of the elemental carbon content of alveolar macrophages (AMs) to relate our model to human exposure. Adult BALB/c mice were intranasally inoculated with 0 (control), 10, 30 or 100 µg DEP in saline. Bronchoalveolar lavage cellular inflammation and cytokine levels were assessed 3, 6, 12, 24, 48 and 168 hours post exposure. Elemental carbon uptake by AMs was additionally assessed at 336 and 672 hours post DEP exposure. Thoracic gas volume and lung mechanics were measured 6 and 24 hours post exposure. DEP resulted in dose-dependent cellular inflammation and cytokine production in both sexes. Males and females responded differently with females having more severe and prolonged neutrophilia, monocyte chemoattractant protein-1 and developing greater abnormalities in lung function. The sexual dimorphism in response was not related to the capacity of AMs to phagocytise DEP. Our mouse model of acute diesel exhaust particle exposure shows a dose dependency and sexual dimorphism in response. Quantification of elemental carbon in AMs allows for comparison of the results of our study with human studies.
Publisher: Elsevier
Date: 2015
Publisher: Oxford University Press (OUP)
Date: 2018
DOI: 10.1093/BIOMETHODS/BPY010
Abstract: Nearly half of the world’s population uses biomass fuel for the purposes of cooking and heating. Smoke derived from biomass increases the risk of the development of lung diseases, including pneumonia, chronic obstructive pulmonary disease, airway tract infections, and lung cancer. Despite the evidence linking biomass smoke exposure to pulmonary disease, only a small number of experimental studies have been conducted on the impact of biomass smoke on airway epithelial cells. This is in part due to the lack of a standard and easily accessible procedure for the preparation of biomass smoke. Here, we describe a cost-effective and reproducible method for the generation of different smoke extracts, in particular, cow dung smoke extract (CDSE) and wood smoke extract (WSE) for use in a range of biological applications. We examined the effect of the biomass smoke extracts on human bronchial epithelial cell expression of a known responder to cigarette smoke exposure (CSE), the platelet-activating factor receptor (PAFR). Similar to the treatment with CSE, we observed a dose-dependent increase in PAFR expression on human airway epithelial cells that were exposed to CDSE and WSE. This method provides biomass smoke in a re-usable form for cell and molecular bioscience studies on the pathogenesis of chronic lung disease.
Publisher: MDPI AG
Date: 16-06-2022
Abstract: Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily in idualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%) wheeze/whistling chest (53%) and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.
Publisher: Wiley
Date: 07-12-2008
DOI: 10.1111/J.1365-2222.2007.02884.X
Abstract: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.
Publisher: Springer Science and Business Media LLC
Date: 02-07-2020
DOI: 10.1038/S41598-020-67633-Y
Abstract: To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung. However, X-ray velocimetry (XV) has recently been demonstrated to be a sophisticated and non-invasive lung function measurement tool that is able to display the full dynamics of airflow throughout the lung over the natural breathing cycle. In this study we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of cystic fibrosis (CF)-like disease in β-ENaC mice. Secondly, we present a technique for numerical quantification of CF-like disease in mice that can delineate between two major modes of disease symptoms. We propose this analytical model as a simple, easy-to-interpret approach, and one capable of being readily applied to large quantities of data generated in XV imaging. Together these advances show the power of XV for assessing local airflow changes. We propose that XV should be considered as a novel lung function measurement tool for lung therapeutics development in small animal models, for CF and for other muco-obstructive diseases.
Publisher: American Physiological Society
Date: 10-2020
DOI: 10.1152/JAPPLPHYSIOL.00097.2020
Abstract: This study provides novel insights into the regional response to mechanical ventilation in the setting of acid-induced lung injury and highlights the complex interaction between tidal stretch and low end-expiratory lung volumes both of which caused altered regulation of different injury pathways.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2017
DOI: 10.1038/SREP45172
Abstract: Vitamin D has a range of non-skeletal health effects and has been implicated in the response to respiratory infections. The aim of this study was to assess the effect of vitamin D on the response of epithelial cells, neutrophils and macrophages to lipopolysaccharide (LPS) stimulation. BEAS-2B cells (airway epithelial cell line) and primary neutrophils and macrophages isolated from blood s les were cultured and exposed to LPS with and without vitamin D (1,25(OH) 2 D). The production of IL-6, IL-8, IL-1β and TNF-α of all cells and the phagocytic capacity of neutrophils and macrophages to E. coli were assessed. Vitamin D had no effect on BEAS-2B cells but enhanced the production of IL-8 in neutrophils (p = 0.007) and IL-1β in macrophages (p = 0.007) in response to LPS. Both vitamin D (p = 0.019) and LPS (p 0.001) reduced the phagocytic capacity of macrophages. These data suggest that the impact of vitamin D on responses to infection are complex and that the net effect will depend on the cells that respond, the key response that is necessary for resolution of infection (cytokine production or phagocytosis) and whether there is pre-existing inflammation.
Publisher: Springer Science and Business Media LLC
Date: 02-2018
Publisher: American Physiological Society
Date: 09-2016
DOI: 10.1152/AJPLUNG.00026.2016
Abstract: Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung s les were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1039/C6PP00278A
Abstract: Epidemiological studies have demonstrated an association between maternal vitamin D deficiency and an increased risk of chronic lung disease in offspring. While vitamin D and UV induced non-vitamin D pathways have the capacity to modulate immune function, this relationship may also be explained by an effect on lung development which is an independent predictor of lung function and the risk of lung disease later in life. To date there are not sufficient data to support the role of non-vitamin D pathways in this association, while in vivo and in vitro data suggest that there is a causal relationship between vitamin D and lung development. However, equivocal results in recent high profile clinical trials have d ened enthusiasm for vitamin D as an important public health intervention for improving lung development. In this narrative review we summarise our current understanding of the link between UV exposure, vitamin D and lung development.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2020
Publisher: American Physiological Society
Date: 09-2017
DOI: 10.1152/JAPPLPHYSIOL.00903.2016
Abstract: Increased dead space is an important prognostic marker in early acute respiratory distress syndrome (ARDS) that correlates with mortality. The cause of increased dead space in ARDS has largely been attributed to increased alveolar dead space due to ventilation erfusion mismatching and shunt. We sought to determine whether anatomic dead space also increases in response to mechanical ventilation. Mice received intratracheal lipopolysaccharide (LPS) or saline and mechanical ventilation (MV). Four-dimensional computed tomography (4DCT) scans were performed at onset of MV and after 5 h of MV. Detailed measurements of airway volumes and lung tidal volumes were performed using image analysis software. The forced oscillation technique was used to obtain measures of airway resistance, tissue d ing, and tissue elastance. The ratio of airway volumes to total tidal volume increased significantly in response to 5 h of mechanical ventilation, regardless of LPS exposure, and airways demonstrated significant variation in volumes over the respiratory cycle. These findings were associated with an increase in tissue elastance (decreased lung compliance) but without changes in tidal volumes. Airway volumes increased over time with exposure to mechanical ventilation without a concomitant increase in tidal volumes. These findings suggest that anatomic dead space fraction increases progressively with exposure to positive pressure ventilation and may represent a pathological process. NEW & NOTEWORTHY We demonstrate that anatomic dead space ventilation increases significantly over time in mice in response to mechanical ventilation. The novel functional lung-imaging techniques applied here yield sensitive measures of airway volumes that may have wide applications.
Publisher: Springer Science and Business Media LLC
Date: 12-2002
DOI: 10.1007/S00360-002-0295-7
Abstract: This study investigated the effect of parasympathetic inhibition on the cardio-ventilatory interaction during torpor in the fat-tailed dunnart (Sminthopsis crassicaudata). Studies on the influence of the autonomic nervous system on cardiac function during torpor have focused on deep hibernation in eutherians. S. crassicaudata was used as a representative of the Metatheria that exhibits shallow, daily torpor as a comparison for the patterns of cardiac function found in other mammalian heterotherms. During torpor, parasympathetic inhibition removed the cardio-ventilatory interaction, eliminated heart rate variability and increased the overall heart rate these are responses that have been shown to be typical of eutherian hibernators under the same conditions. Similarly, there was evidence to suggest that as the bout of torpor progressed, the variation in instantaneous heart rate decreased as a result of the progressive removal of parasympathetic tone. It has been suggested that the ability to enter a "steady state" during torpor, which is characterised by a regular heart rate, is limited to deep hibernators. On the basis of this, and the results of previous physiological studies, it was proposed that there is little evidence to suggest that there is any physiological difference between shallow, daily torpor and deep hibernation.
Publisher: Wiley
Date: 08-11-2013
DOI: 10.1111/IRV.12034
Publisher: Wiley
Date: 18-06-2007
DOI: 10.1111/J.1365-2222.2007.02740.X
Abstract: Animal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.
Publisher: Rockefeller University Press
Date: 06-11-2006
DOI: 10.1084/JEM.20060155
Abstract: An important feature of atopic asthma is the T cell–driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4+ T helper memory cells. The study below extends these investigations to chronic aeroallergen exposure. We demonstrate that prevention of ensuing cycles of T cell activation and resultant AHR during chronic exposure of sensitized rats to allergen aerosols is mediated by CD4+CD25+Foxp3+LAG3+ CTLA+CD45RC+ T cells which appear in the airway mucosa and regional lymph nodes within 24 h of initiation of exposure, and inhibit subsequent Th-mediated upregulation of AMDC functions. These cells exhibit potent regulatory T (T reg) cell activity in both in vivo and ex vivo assay systems. The maintenance of protective T reg activity is absolutely dependent on continuing allergen stimulation, as interruption of exposure leads to waning of T reg activity and reemergence of sensitivity to aeroallergen exposure manifesting as AMDC/T cell upregulation and resurgence of T helper 2 cytokine expression, airways eosinophilia, and AHR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2019
Publisher: The American Association of Immunologists
Date: 11-2006
DOI: 10.4049/JIMMUNOL.177.9.5861
Abstract: An increase in the tempo of local dendritic cell (DC)-mediated immune surveillance is a recognized feature of the response to acute inflammation at airway mucosal surfaces, and transient up-regulation of the APC functions of these DC preceding their emigration to regional lymph nodes has recently been identified as an important trigger for T cell-mediated airway tissue damage in diseases such as asthma. In this study, using a rat model, we demonstrate that the kinetics of the airway mucosal DC (AMDC) response to challenge with heat-killed bacteria is considerably more rapid and as a consequence more effectively compartmentalized than that in recall responses to soluble Ag. Notably, Ag-bearing AMDC expressing full APC activity reach regional lymph nodes within 30 min of cessation of microbial exposure, and in contrast to recall responses to nonpathogenic Ags, there is no evidence of local expression of APC activity within the airway mucosa preceding DC emigration. We additionally demonstrate that, analogous to that reported in the gut, a subset of airway intraepithelial DC extend their processes into the airway lumen. This function is constitutively expressed within the AMDC population, providing a mechanism for continuous immune surveillance of the airway luminal surface in the absence of “danger” signals.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2016
Publisher: Elsevier BV
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 22-01-2018
Publisher: MDPI AG
Date: 24-07-2019
Abstract: Indigenous children have much higher rates of ear and lung disease than non-Indigenous children, which may be related to exposure to high levels of geogenic (earth-derived) particulate matter (PM). The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia (W.A.). Data were from a population-based s le of 1077 Indigenous children living in 66 remote communities of W.A. ( ,000,000 km2), with information on health outcomes derived from carer reports and hospitalisation records. Associations between dust levels and health outcomes were assessed by multivariate logistic regression in a multi-level framework. We assessed the effect of exposure to community s led PM on epithelial cell (NuLi-1) responses to non-typeable Haemophilus influenzae (NTHi) in vitro. High dust levels were associated with increased odds of hospitalisation for upper (OR 1.77 95% CI [1.02–3.06]) and lower (OR 1.99 95% CI [1.08–3.68]) respiratory tract infections and ear disease (OR 3.06 95% CI [1.20–7.80]). Exposure to PM enhanced NTHi adhesion and invasion of epithelial cells and impaired IL-8 production. Exposure to geogenic PM may be contributing to the poor respiratory health of disadvantaged communities in arid environments where geogenic PM levels are high.
Publisher: Wiley
Date: 06-06-2018
DOI: 10.1111/JPC.14071
Abstract: We investigated the presentations of children with unspecified fever to an Australian emergency department (ED): (i) to determine the proportion of these presentations that could be classified as potentially avoidable and (ii) to identify factors associated with an increased risk of hospital admission. This study retrospectively identified and described children aged <6 years who presented to the Royal Hobart Hospital (Tasmania, Australia) ED with unspecified fever (ICD-10-AM code R50.9) between January 2013 and December 2015, using data from the ED information system and digital medical records. The Australian Institute of Health and Welfare method was used to estimate the number of potentially avoidable general practitioner-type presentations. Predictors of hospital admission were determined using multivariate logistic regression. A total of 459 patients aged <6 years presented to the ED with a primary diagnosis description of unspecified fever. Of these, 30.7% were classed as potentially avoidable general practitioner-type presentations. Overall, 26.1% of presentations resulted in admission to hospital. Administration of intravenous fluids in the ED and a longer treat time were identified as significant predictors of a child with non-specific fever being admitted to hospital. Older age, administration of antipyretics in the ED and presentations triaged as semi-urgent and non-urgent significantly reduced the probability of admission. To our knowledge, this is the first Australian study that has assessed the impact of unspecified childhood fever on an Australian ED. Further investigation of presentations classified as potentially avoidable is warranted to investigate whether these could be managed in the primary care setting.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2017
DOI: 10.1038/S41598-017-15517-Z
Abstract: Vitamin D deficiency is increasing around the world and has been associated with the development of asthma. This study aims to evaluate the effect of dietary vitamin D deficiency at different life stages on lung function using a murine model of allergic airways disease. BALB/c mice were challenged intranasally with HDM or saline alone for 10 days. Twenty four hours after the last challenge, mice were anesthetized and lung function was measured using the forced oscillation technique (FOT). Mice were euthanized for assessment of inflammation in the bronchoalveolar lavage (BAL) and total collagen content in lung homogenates by ELISA. Vitamin D deficiency impaired lung function in both male and female mice, increasing tissue d ing and elastance, however had no effect on HDM induced inflammation. The impact of vitamin D deficiency was more evident in females. HDM also decreased airway distensibility, but only in females and this response was not altered by vitamin D deficiency. Our data suggest that vitamin D deficiency and HDM exposure have independent effects on lung mechanics and that females are more susceptible to these effects. Vitamin D deficiency may exacerbate lung function deficits by having a direct, but independent, effect on parenchymal mechanics.
Publisher: Wiley
Date: 06-2016
DOI: 10.5694/MJA16.00357
Abstract: Coal workers' pneumoconiosis (CWP) is an untreatable but preventable lung disease arising from chronic inhalation of coal dust. Recent reports of CWP in Queensland, along with international data, suggest that there is a resurgence in pneumoconiosis. The prevalence of CWP varies considerably between countries. In Australia, there is no mandatory reporting system and no national data on the prevalence of CWP. The symptoms and manifestations of CWP vary depending on the composition of the inhaled dust, duration of exposure, stage of disease and host-related factors. CWP may develop into progressive massive fibrosis (PMF), which can be fatal. Radiological assessment should be performed according to evidence-based standards using the ILO (International Labour Office) International Classification of Radiographs of Pneumoconioses. As preventing exposure to coal dust prevents CWP, it is important to implement and enforce appropriate standards limiting exposure. In Australia, these standards currently vary between states and are not in keeping with international understanding of the levels of coal dust that cause disease. Longitudinal screening programs are crucial for monitoring the health of coal workers to identify in iduals with early-stage disease and prevent progression from mild disease to PMF. We recommend: standardisation of coal dust exposure limits, with harmonisation to international regulations implementation of a national screening program for at-risk workers, with use of standardised questionnaires, imaging and lung function testing development of appropriate training materials to assist general practitioners in identifying pneumoconiosis and a system of mandatory reporting of CWP to a centralised occupational lung disease register.
Publisher: Informa UK Limited
Date: 08-08-2016
DOI: 10.1080/01902148.2016.1235237
Abstract: No studies have assessed the effects of human rhinovirus (HRV) infection on epithelial tight junctions (TJs) and resultant barrier function. To correlate viral infection with TJ disassembly, epithelial barrier integrity, and function. Human airway epithelial cells were infected with HRV minor serotype 1B (HRV-1B) at various 50% tissue culture infectivity doses (TCID HRV-1B infection affected viability that was both time and TCID HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via an antiviral response of IL-15.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2013
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.ENVRES.2018.02.025
Abstract: Exposure to environmental geogenic (or earth-derived) dust can lead to more frequent and severe infections in the human airway. Particulate matter < 10 µm (PM
Publisher: Public Library of Science (PLoS)
Date: 28-02-2014
Publisher: Springer Science and Business Media LLC
Date: 21-07-2017
DOI: 10.1007/S00360-016-1021-1
Abstract: Evidence for a functional ventricular parasympathetic innervation of the mammalian heart between and within taxa remains controversial. We have previously proposed that the presence of a functional parasympathetic innervation of the ventricle was indicative of heterothermy, and is essential for maintaining ventricular stability at low body temperature. However, it is possible that the presence of such an innervation is also representative of the primitive mammalian state. In this study, we aimed to determine whether a functional parasympathetic innervation of the ventricle, that is capable of actively reducing the force of contraction, is present across metatherian mammals. Using in vitro isolated cardiac preparations, we examined evidence for a functional ventricular parasympathetic innervation of the ventricle in two species of metatherian mammal, one heterotherm (Western pygmy possum Cercatetus concinnus) and one homeotherm (Golden bandicoot Isoodon auratus), from different families to complement existing data from a heterothermic dasyurid. Both C. concinnus and I. auratus had a potent biphasic response to transmural electrical stimulation in both atrial and ventricular preparations. Both the decrease and increase in the force of contraction in response to stimulation were almost entirely blocked by the cholinergic and adrenergic antagonists, atropine and propranolol, respectively. These observations provide clear evidence for a parasympathetic innervation of the ventricle that is capable of directly influencing the force of contraction across metatherian mammals with different thermoregulatory strategies. While this innervation may facilitate heterothermy, this suggests that the presence of such an innervation pattern is indicative of the primitive mammalian state.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.RESP.2009.09.012
Abstract: The study aim was to establish how recruitment maneuvers (RMs) influence lung mechanics and to determine whether RMs produce lung injury. Healthy BALB/c mice were allocated to receive positive end-expiratory pressure (PEEP) at 2 or 6 cmH(2)O and volume- (20 or 40 mL/kg) or pressure-controlled (25 cmH(2)O) RMs every 5 or 75 min for 150 min. The low-frequency forced oscillation technique was used to measure respiratory input impedance. Large RMs resulting in peak airway opening pressures (P(ao))>30 cmH(2)O did not increase inflammatory response or affect transcutaneous oxygen saturation but significantly lowered airway resistance, tissue d ing and tissue elastance the latter changes are likely associated with the bimodal pressure-volume behavior observed in mice. PEEP increase alone and application of RMs producing peak P(ao) below 25 cmH(2)O did not prevent or reverse changes in lung mechanics whereas frequent application of substantial RMs on top of elevated PEEP levels produced stable lung mechanics without signs of lung injury.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2016
DOI: 10.1038/SREP29438
Abstract: Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls identified locations of airway obstruction and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool.
Start Date: 2016
End Date: 2016
Funder: Centre for Air Quality and Health Research Evaluation
View Funded ActivityStart Date: 2017
End Date: 2021
Funder: National Health & Medical Research Council
View Funded ActivityStart Date: 2017
End Date: 2020
Funder: FightMND
View Funded ActivityStart Date: 2019
End Date: 2019
Funder: University of Tasmania
View Funded ActivityStart Date: 2013
End Date: 2016
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Donation via University of Tasmania Foundation
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Department of Industry, Innovation and Science
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Royal Hobart Hospital Research Foundation
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Marinova Pty Ltd
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: University of Tasmania
View Funded Activity