https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50942 Wed 28 Feb 2024 16:05:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48595 Wed 22 Mar 2023 08:46:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48068 Wed 22 Feb 2023 16:37:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31003 Wed 19 Jan 2022 15:18:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22098 Wed 19 Apr 2023 16:41:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52419 Wed 11 Oct 2023 12:06:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23630 Wed 11 Apr 2018 17:16:57 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17148 Wed 11 Apr 2018 17:15:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31124 Wed 11 Apr 2018 16:45:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13589 Wed 11 Apr 2018 16:34:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14698 Wed 11 Apr 2018 16:15:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16827 Wed 11 Apr 2018 16:01:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22120 Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.]]> Wed 11 Apr 2018 15:36:56 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18585 Wed 11 Apr 2018 15:35:46 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15696 Wed 11 Apr 2018 13:53:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15127 Wed 11 Apr 2018 12:25:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25730 Wed 11 Apr 2018 10:14:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15055 Wed 11 Apr 2018 09:51:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34714 Wed 10 Nov 2021 15:05:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24433 Wed 09 Feb 2022 15:59:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36077 Haemophilus influenzae is the most commonly identified bacteria. Haemophilus influenzae is divided into typeable and nontypeable (NTHi) strains based on the presence or absence of a polysaccharide capsule. While NTHi is a common commensal in the human nasopharynx, it is associated with considerable inflammation when it is present in the lower airways of COPD patients, resulting in morbidity due to worsening symptoms and increased frequency of COPD exacerbations. Treatment of lower airway NTHi infection with antibiotics, though successful in the short term, does not offer long-term protection against reinfection, nor does it change the course of the disease. Hence, there has been much interest in the development of an effective NTHi vaccine. This review will summarize the current literature concerning the role of NTHi infections in COPD patients and the consequences of using prophylactic antibiotics in patients with COPD. There is particular focus on the rationale, findings of clinical studies and possible future directions of NTHi vaccines in patients with COPD.]]> Wed 09 Feb 2022 15:54:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50855 Wed 09 Aug 2023 09:52:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49859 Wed 07 Jun 2023 10:25:30 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35918 Wed 07 Jul 2021 12:41:58 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30800 Wed 02 Mar 2022 14:24:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47835 Wed 01 Feb 2023 14:10:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:56082 Tue 30 Jul 2024 14:37:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51997 Tue 26 Sep 2023 11:07:44 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17834 Tue 26 Jun 2018 11:21:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42445 1% predicted) and consumption of fried fish (OR -0.12, 95% CI -0.22, -0.01, P = 0.026) but not fish prepared by other cooking methods or estimated intakes of PUFA. There was no association between fish or PUFA intakes and COPD risk. Compared to age and sex matched controls, cases had poorer lung function and a higher rate of smoking prevalence but did not differ in their intakes of fish or PUFA or their PUFA levels in plasma phospholipids. In this sub-population, we found a marginally significant association between COPD risk and total long chain n-3PUFA levels in plasma phospholipids (OR 1.22 95% CI 1.00-1.49, P = 0.046). Given the relatively small number of cases in this analysis, this finding should be interpreted with caution, especially given the lack of association with other markers of n-3PUFA intake or status. Taken together, our data suggest that n-3PUFA intake and status are not determinants of improved lung function in this regional Australian population.]]> Tue 23 Aug 2022 10:54:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35330 Tue 16 Jul 2019 12:26:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46351 n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.]]> Tue 15 Nov 2022 15:15:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19901 Tue 09 Jun 2020 09:48:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45554 Muc5ac-deficient (Muc5ac^–/–) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.]]> Tue 01 Nov 2022 11:18:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36424 61% or >162x10⁴ cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database. In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses. Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients.]]> Thu 30 Apr 2020 12:50:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30656 Thu 28 Oct 2021 13:03:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41166 Thu 28 Jul 2022 09:55:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45336 Thu 27 Oct 2022 10:50:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45028 Zfp36 gene is an anti‐inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD. Methods: Here, we identify a novel protective role for TTP in CS‐induced experimental COPD using Zfp36^aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNA‐destabilising factor. TTP wild‐type (Zfp36^+/+) and Zfp36^aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed. Results: After four days of CS exposure, Zfp36^aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild‐type controls. After eight weeks, Zfp36^aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema‐like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL_(S), and the proteasome inhibitor, bortezomib) to promote the activation and stabilisation of TTP and show that hallmark features of CS‐induced experimental COPD were ameliorated. Conclusion: Collectively, our study provides the first evidence for the therapeutic potential of inducing TTP as a treatment for COPD.]]> Thu 22 Aug 2024 13:33:30 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48885 10 years: 65% vs. 33%, p < 0.002). QoL was impaired in both groups, but there were no significant differences between severe asthma and COPD carers in either of the SF-12 component scores. The HADS scores revealed no difference between groups. Compared to severe asthma carers, COPD carers had significantly greater needs for: ‘having time for self’ (33% vs. 13%, p = 0.006), ‘equipment to help care for relative’ (33% vs. 13%, p = 0.006), ‘practical help in the home’ (35% vs. 18%, p = 0.006) and ‘getting a break from caring overnight’ (21% vs. 6%, p = 0.023). Conclusion: QoL is impaired in carers of people with severe asthma to a similar degree of COPD carers and other debilitating diseases like cancer. These novel data highlight the support needs of severe asthma carers and identifies areas where tailored support is needed to reduce their substantial carer burden.]]> Thu 20 Apr 2023 09:27:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36371 Thu 17 Feb 2022 09:31:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29745 9/L vs 0.15×10⁹/L; P<0.0001). Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67–0.84; P<0.0001). At a threshold of ≥0.3×10/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of ≥0.4×10⁹/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, ≥0.2×10⁹/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia. There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66–0.88; P<0.0001). Conclusion: Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy.]]> Thu 17 Feb 2022 09:29:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31150 Thu 17 Feb 2022 09:28:47 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53654 Thu 14 Dec 2023 14:34:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33298 Thu 04 Oct 2018 09:48:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36651 Haemophilus influenzae (NTHi) preparation was demonstrated in the mid-1980s. Subsequently, studies aiming to validate clinical efficacy of this oral treatment were complicated by a number of factors, including the modification of clinical definitions, the implications of which were not recognized at that time. The objective of this review is to integrate our pre-clinical and clinical research in this field conducted over the past 30 years to demonstrate the evolution of the idea of communication between mucosal surfaces through the common mucosal immune system and the development of an effective oral NTHi immunotherapy. Our earliest studies recruited subjects with chronic sputum production and high levels of culture-positive sputum for Gram-negative bacteria but by 2000, the clinical diagnostic focus had switched from "chronic bronchitis" to "chronic obstructive pulmonary disease" (COPD), which was functionally defined using spirometry. This change led to variable clinical trial results, confirming the importance of chronic sputum production and culture-positive sputum. Additional conditioning factors such as patient age and gender were influential in study populations with low culture-positive sputum production. Through this period, studies in human and in rodent models provided new insights into airway protection mechanisms and the pathogenesis of airway inflammation. Key findings were the importance of a dysbiosis within the airway microbiome, and the critical role of an interdependence between the bronchus and the gut, with a Peyer's patch-dependent extra-bronchus "loop" controlling the composition of the bronchus microbiome. Within this context, intercurrent virus infections initiate a microbiome-dependant hypersensitivity reaction involving Peyer's patch-derived Th17 cells. We conclude that whole-cell killed NTHi immunotherapy has consistent and significant benefits when examined in the context of changing clinical disease definitions, age and gender, and has the potential to change the natural history of chronic airway disease.]]> Thu 04 Nov 2021 10:39:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49088 Thu 04 May 2023 13:43:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31327 Thu 03 Feb 2022 12:22:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33159 in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. Measurements and Main Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. Conclusions: We highlight a role for miR-218-5p in the pathogenesis of COPD.]]> Thu 03 Feb 2022 12:18:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7725 Sat 24 Mar 2018 10:48:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31553 Sat 24 Mar 2018 08:44:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31233 Sat 24 Mar 2018 08:43:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7532 Sat 24 Mar 2018 08:38:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13806 Sat 24 Mar 2018 08:22:47 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16017 Sat 24 Mar 2018 08:19:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14652 Sat 24 Mar 2018 08:19:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12772 Sat 24 Mar 2018 08:18:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12974 Sat 24 Mar 2018 08:16:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10877 Sat 24 Mar 2018 08:14:28 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16896 Sat 24 Mar 2018 07:58:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19878 Sat 24 Mar 2018 07:57:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19120 Sat 24 Mar 2018 07:55:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19123 55 years) with OADs who underwent a multidimensional assessment at baseline and 4 years which involved spirometry, 6-min walk distance (6MWD), assessments of health status (Saint George's Respiratory Questionnaire, SGRQ), comorbidity, and serum and sputum biomarkers. All-cause mortality and respiratory hospitalisation during the follow-up period were recorded. Clinical outcomes were compared between basal and final visits, and changes in clinical outcomes were compared among asthma, COPD and asthma-COPD overlap groups. Associations between clinical parameters, biomarkers and prognosis were examined. Results: After a median follow-up of 4.2 years, outcome data were available for 75 (75.8%) patients. There were 16 (16.2%) deaths. The BODE index predicted all-cause mortality in older people with OADs. While spirometry, 6MWD and SGRQ deteriorated significantly over the 4 years, there was significant heterogeneity in the longitudinal changes in these clinical outcomes. Participants with COPD had a significant decline in FEV1 (p = 0.003), SGRQ (p = 0.030) and 6MWD [decline of 75.5 (93.4) m, p = 0.024]. The change in 6MWD was lower in the asthma-COPD overlap group. Airflow reversibility was associated with a reduced decline in 6MWD. Conclusion: COPD patients had a poor prognosis compared with asthma and asthma-COPD overlap patients. The BODE index is a useful prognostic indicator in older adults with OADs. Both airway disease diagnosis and BODE index warrant specific attention in clinical practice.]]> Sat 24 Mar 2018 07:55:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21333 Sat 24 Mar 2018 07:52:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28283 Sat 24 Mar 2018 07:41:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26603 Sat 24 Mar 2018 07:33:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27246 Sat 24 Mar 2018 07:29:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26966 Sat 24 Mar 2018 07:26:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30177 P _Trend < .001). Conclusions: COPD and PLOS are 2 of many factors that affect long-term mortality in postoperative CABG patients. Aggressive treatment strategies aimed at early weaning off of mechanical ventilation and prevention of reintubation among COPD patients must be considered carefully as a means to reduce length of stay after CABG. Our results also have important implications for the long-term management of these patients and strategies for containing costs over the life course of the patient.]]> Sat 24 Mar 2018 07:26:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22024 Sat 24 Mar 2018 07:15:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22085 Sat 24 Mar 2018 07:15:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22164 Sat 24 Mar 2018 07:14:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23782 Sat 24 Mar 2018 07:13:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22113 Sat 24 Mar 2018 07:13:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22677 Sat 24 Mar 2018 07:12:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42345 Mon 22 Aug 2022 13:54:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23403 Mon 19 Aug 2024 09:48:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49262 Mon 08 May 2023 11:02:56 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40012 Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa)to induce infection in both the respiratory and gastroin-testinal (GI) tracts. However, the importance and mechanism of HIF-1αin augmenting PAFR-dependent bacterial infections in COPD are poorly understood. Here, we review the evidence for the roles of local tissue hypoxia-induced inflammation, HIF-1α and PAFR in facilitating bacterial infections in COPD. Blocking PAFR may provide a novel antimicrobial approach to manage bacterial infections in COPD.]]> Fri 22 Jul 2022 13:06:35 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49505 Fri 19 May 2023 14:07:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41784 Fri 12 Aug 2022 12:10:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46080 Fri 11 Nov 2022 10:10:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38952 Haemophilus influenzae (NTHi), using immunofluorescence microscopy. In addition, expression of a known receptor of NTHi, platelet-activating factor receptor (PAFR), and two pro-inflammatory cytokines, interleukin 6 (IL-6) and interleukin-8 (IL-8), were determined using quantitative polymerase chain reaction. We observed a dose-dependent increase in NTHi adhesion to human bronchial epithelial cells following exposure to cow dung but not wood smoke extracts. Pre-treatment with PAFR antagonists, WEB-2086 and its analogue, C17, decreased adherence by NTHi to airway epithelial cells exposed to cow dung smoke. Both cow dung and wood smoke-induced expression of PAFR, as well as of IL-6 and IL-8, which was inhibited by WEB-2086 and C17. In conclusion, biomass smoke from combustion of cow dung and wood-induced expression of PAFR and airway inflammatory markers in human bronchial epithelial cells. Cow dung exposure, but not wood smoke exposure, mediated a measurable increase in NTHi adhesion to airway epithelial cells that was inhibited by PAFR antagonists. This work highlights the potential of PAFR as a therapeutic target for reducing the impact of hazardous biomass smoke exposure on respiratory health.]]> Fri 11 Mar 2022 14:48:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30102 Fri 11 Jun 2021 13:30:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25154 Fri 11 Jun 2021 13:29:59 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14158 Fri 09 Aug 2024 10:45:54 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14805 Fri 02 Nov 2018 14:20:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24513 Fri 01 Apr 2022 09:29:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31379 Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe-COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe-host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.]]> Fri 01 Apr 2022 09:22:01 AEDT ]]>