https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32992 Haemophilus influenzae (NTHi), and expression of genes involved in various inflammatory pathways was assessed. Result: NTHi induced production of large amounts of IL-1ß, IL-6, and IL-8 in adult-control BAL cells, ho wever BAL cells from PBB airways appeared refractory to NTHi stimulation. BAL cells from PBB and bronchiectasis showed differential expression of several genes relative to control cells, including CCL20, MARCO, CCL24, IL-10, PPAR-¿, CD200R, TREM2, RelB. Expression of genes involved in resolution of inflammation and anti-inflammation response, such as CD200R and IL-10, was associated with the number of pathogenic bacteria found in the airways. Conclusion: In summary, we have shown that the expression of genes related to macrophage function and resolution of inflammation are similar in PBB and bronchiectasis. Lung immune cell dysfunction in PBB and bronchiectasis may contribute to poor bacterial clearance and prolonged resolution of inflammation.]]> Thu 28 Oct 2021 13:03:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4767 Sat 24 Mar 2018 07:20:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32658 Mon 23 Sep 2019 11:23:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46104 adj = 9.6, 95% CI: 1.8–50.1) and the presence of Haemophilus influenzae in the BAL (OR_adj = 5.1, 95% CI: 1.4–19.1). Clinician-diagnosed asthma at final follow-up was present in 27.1% of children with PBB. A significant BDR (FEV₁ improvement >12%) was obtained in 63.5% of the children who underwent reversibility testing. Positive allergen-specific IgE (OR_adj = 14.8, 95% CI: 2.2–100.8) at baseline and bronchomalacia (OR_adj = 5.9, 95% CI: 1.2–29.7) were significant predictors of asthma diagnosis. Spirometry parameters were in the normal range. Conclusion: As a significant proportion of children with PBB have ongoing symptoms at 5 years, and outcomes include bronchiectasis and asthma, they should be carefully followed up clinically. Defining biomarkers, endotypes and mechanistic studies elucidating the different outcomes are now required.]]> Mon 21 Nov 2022 09:17:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32993 Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1ß axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14⁺ monocytes contributed to 95% of total IL-1ß-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1ß expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL-1ß secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1ß. NTHi stimulation induced formation of specks of cleaved IL-1ß, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1ß-dominated inflammation in PBB.]]> Mon 08 Jul 2019 11:29:52 AEST ]]>