https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50840 Wed 28 Feb 2024 16:33:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29719 4 weeks) is associated with increased morbidity and reduced quality of life. One common cause of childhood chronic cough is protracted bacterial bronchitis (PBB), especially in children aged <6 years. PBB is characterized by a chronic wet or productive cough without signs of an alternative cause and responds to 2 weeks of appropriate antibiotics, such as amoxicillin-clavulanate. Most children with PBB are unable to expectorate sputum. If bronchoscopy and bronchoalveolar lavage are performed, evidence of bronchitis and purulent endobronchial secretions are seen. Bronchoalveolar lavage specimens typically reveal marked neutrophil infiltration and culture large numbers of respiratory bacterial pathogens, especially Haemophilus influenzae. Although regarded as having a good prognosis, recurrences are common and if these are frequent or do not respond to antibiotic treatments of up to 4-weeks duration, the child should be investigated for other causes of chronic wet cough, such as bronchiectasis. The contribution of airway malacia and pathobiologic mechanisms of PBB remain uncertain and, other than reduced alveolar phagocytosis, evidence of systemic, or local immune deficiency is lacking. Instead, pulmonary defenses show activated innate immunity and increased gene expression of the interleukin-1ß signalling pathway. Whether these changes in local inflammatory responses are cause or effect remains to be determined. It is likely that PBB and bronchiectasis are at the opposite ends of the same disease spectrum, so children with chronic wet cough require close monitoring.]]> Wed 23 Feb 2022 16:05:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51839 Wed 20 Sep 2023 16:12:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34787 Wed 19 Jan 2022 15:18:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26012 Wed 11 Apr 2018 14:44:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27569 Wed 11 Apr 2018 11:56:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24115 Wed 11 Apr 2018 11:19:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34558 Wed 10 Nov 2021 15:14:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26090 Wed 02 Mar 2022 14:26:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52880 Tue 31 Oct 2023 10:44:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37078 Tue 29 Sep 2020 11:48:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54220 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. Discussion: There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.]]> Tue 13 Feb 2024 12:02:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47085 Tue 13 Dec 2022 16:35:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33751 Tue 08 Jan 2019 15:37:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39063 Tue 03 May 2022 11:38:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54560 Thu 29 Feb 2024 10:27:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36051 Thu 28 Oct 2021 13:04:53 AEDT ]]> 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:24324 Tropheryma whipplei and Haemophilus influenzae in sputum. Adults with neutrophilic asthma had reduced bacterial diversity and species richness. Tropheryma was identified and confirmed with real-time PCR in 12 (40%) participants. Haemophilus occurred most often in a group of younger atopic males with an increased proportion of neutrophils. PCR confirmed the presence of H. influenzae in 35 (76%) participants with poorly controlled asthma. There are phenotype-specific alterations to the airway microbiome in asthma. Reduced bacterial diversity combined with a high prevalence of H. influenzae was observed in neutrophilic asthma, whereas eosinophilic asthma had abundant T. whipplei.]]> Thu 28 Oct 2021 13:02:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34913 Thu 27 Jan 2022 15:59:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29360 Thu 27 Jan 2022 15:58:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39023 Thu 21 Apr 2022 09:51:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49460 1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.]]> Thu 18 May 2023 12:40:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24852 Thu 17 Feb 2022 09:28:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49306 Thu 11 May 2023 14:32:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47850 Thu 02 Feb 2023 16:46:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12440 Sat 24 Mar 2018 08:15:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20295 Sat 24 Mar 2018 07:55:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23340 Sat 24 Mar 2018 07:13:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23311 Sat 24 Mar 2018 07:13:31 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40572 Mon 08 Aug 2022 15:11:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35554 Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Conclusions: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.]]> Fri 31 Jan 2020 16:15:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33089 Fri 24 Aug 2018 16:46:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40118 Fri 22 Jul 2022 13:48:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46066 Fri 11 Nov 2022 14:45:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37892 Fri 01 Apr 2022 09:25:28 AEDT ]]>