A5065792744- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Occupational and environmental lung diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Sarcoidosis and Beryllium Toxicity Research
- Microbial metabolism and enzyme function
- Advanced Fluorescence Microscopy Techniques
- Medical Imaging and Pathology Studies
- Pulmonary Hypertension Research and Treatments
- Eosinophilic Disorders and Syndromes
- Near-Field Optical Microscopy
- Photoacoustic and Ultrasonic Imaging
- Pleural and Pulmonary Diseases
- Respiratory viral infections research
- Bone and Dental Protein Studies
- Connective tissue disorders research
- Ultrasound in Clinical Applications
- Cellular Mechanics and Interactions
- Heme Oxygenase-1 and Carbon Monoxide
- Optical Coherence Tomography Applications
- Pharmacological Effects and Assays
- Streptococcal Infections and Treatments
- Galectins and Cancer Biology
- Eicosanoids and Hypertension Pharmacology
- Asthma and respiratory diseases
- Atherosclerosis and Cardiovascular Diseases
NIHR Southampton Biomedical Research Centre
2018-2024
University Hospital Southampton NHS Foundation Trust
2018-2024
University of Southampton
2018-2024
NIHR Leicester Biomedical Research Centre
2024
University of Leicester
2024
Wollongong Hospital
2023
University of Wollongong
2023
National Institute for Health Research
2022
Yale University
2022
NIHR Cambridge Biomedical Research Centre
2021
Abstract Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries an ageing, susceptible alveolar epithelium. Ageing risk factor for IPF and incidence has been demonstrated increase with age. Decreased (macro)autophagy age reported extensively in variety systems diseases, including IPF. However, it undetermined whether role faulty autophagy causal or coincidental context Here, we report...
Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however, pathologic changes extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are not defined human disease. By integrated multiscale biomechanical and biological analyses idiopathic pulmonary fibrosis lung tissue, we identify increased tissue stiffness a function dysregulated post-translational collagen cross-linking rather than any concentration...
Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture a key determinant pathogenetic ECM structure-function human fibrosis (Jones et al., 2018). Here, through tissue, bioinformatic and ex vivo studies we provide evidence hypoxia-inducible factor (HIF) pathway critical for this process regardless the oxygen status (pseudohypoxia). Whilst TGFβ increased rate...
Pyogenic vertebral osteomyelitis (PVO) is rising in incidence, but optimal methods of investigation and duration antibiotic therapy remain controversial.We conducted a single-center retrospective cohort study PVO at an Australian teaching hospital. We included all adults with first episode between 2006 2015. was defined based on the presence prespecified clinical radiological criteria. The main exposures interest were strategy treatment. outcome measures hospital admission, mortality during...
Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range measurement variation (5.0%-9.9%). We examined whether change in visual CT variables could help confirm marginal FVC declines represented genuine clinical deterioration rather than noise.In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs radiologists scored...
Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic scarring disease in which aging, environmental exposure(s) and genetic susceptibility have been implicated pathogenesis, however, the causes mechanisms of progressive fibrotic cascade are still poorly understood. As epithelial–mesenchymal interactions essential for normal wound healing, through human 2D 3D vitro studies, we tested hypothesis that IPF fibroblasts (IPFFs) dysregulate alveolar epithelial homeostasis. Conditioned media...
Superresolution (SR) optical microscopy has allowed the investigation of many biological structures below diffraction limit; however, most techniques are hampered by need for fluorescent labels. Nonlinear label-free such as second-harmonic generation (SHG) provide structurally specific contrast without addition exogenous labels, allowing observation unperturbed systems. We use photonic nanojet (PNJ) phenomena to achieve SR-SHG. A resolution <mml:math...
Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined and emphysema (CPFE) may associate reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality functional measures of disease progression in two cohorts.
Nintedanib, a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF), reduces annual forced vital capacity (FVC) decline in these patients by ∼50% with combined analysis data from clinical trials showing trend towards reduction mortality [1–3]. Nintedanib prescription criteria IPF vary between countries and 2016, National Institute Health Care Excellence nintedanib England Wales an FVC 50% 80% predicted [4]. Prior to this approval, was available through...
The care of patients with idiopathic pulmonary fibrosis (IPF) has been transformed by the widespread approval antifibrotic therapies [1]. Within primary care-based healthcare systems, diagnosis IPF and commencement therapy typically requires a patient referral from physician to respiratory in secondary care, then made specialist interstitial lung disease (ILD) centre [2]. Following ILD review multidisciplinary team (MDT) discussion, is may be commenced. For IPF, length time systems prior an...
Idiopathic pulmonary fibrosis (IPF) and pleuroparenchymal fibroelastosis (PPFE) are known to have poor outcomes but detailed examinations of prognostic significance an association between these morphologic processes lacking.Retrospective observational study independent derivation validation cohorts IPF populations. Upper-lobe PPFE extent was scored visually (vPPFE) as categories absent, moderate, marked. Computerised upper-zone (cPPFE) examined continuously using a threshold 2·5% pleural...
An acute exacerbation of idiopathic pulmonary fibrosis (AEIPF) is a potentially fatal complication an already debilitating disease. Management currently centred on delivering excellent supportive care and identifying reversible triggers. Despite growing international awareness collaboration, no effective therapies have been identified. Corticosteroids are often the mainstay treatment; however, evidence base for their use poor. Here, we review our current understanding disease process how to...
Background Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined associations longitudinal change computer-quantified PPFE-like lesions IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods Two CT scans 6–36 months apart were retrospectively one (n=414) FHP population (n=98). Annualised computerised upper-zone pleural surface area comprising...
<b>In patients with combined pulmonary fibrosis and emphysema, emphysema do not have a synergistic effect that results in worsened survival when compared to IPF without emphysema</b>https://bit.ly/35EJMo6
Significance: Idiopathic pulmonary fibrosis (IPF) patients have a poor prognosis with short lifespan following diagnosis as there are limited effective treatment options. Despite matrix stiffening being the hallmark of disease remains lack knowledge surrounding underlying collagen alterations in disease. Specifically, while increased crosslinking has been implicated, resulting effects on macro/supramolecular changes not explored. Aim: We sought to determine if second-harmonic generation...
Abstract Light sheet microscopy (LSM) has emerged as one of most profound three dimensional (3D) imaging tools in the life sciences over last decade. However, LSM is currently performed with fluorescence detection on one- or multi-photon excitation. Label-free approaches have been rather limited. Second Harmonic Generation (SHG) a label-free technique that enabled detailed investigation collagenous structures, including its distribution and remodelling cancers respiratory tissue, how these...
Pleural procedures are essential for the investigation and management of pleural disease can be associated with significant morbidity mortality. There is a lack procedure complication data in Australian New Zealand region.
<b>Background:</b> Altered collagen architecture, rather than quantity, is a key determinant of abnormal tissue structure-function in idiopathic pulmonary fibrosis (IPF), with the cross-linking enzymes lysyl hydroxylase 2 (LH2) and oxidase-like (LOXL2) promoting pathological bone-type crosslinking increased stiffness (Jones et al eLife. 2018;7:e36354). However, upstream mechanisms regulating this process remain unknown. <b>Objective:</b> To determine cellular provenance LOXL2 LH2 IPF...
Abstract Super-resolution (SR) optical microscopy has allowed the investigation of many biological structures below diffraction limit, however, most techniques are hampered by need for fluorescent labels. Non-linear label-free such as Second Harmonic Generation (SHG) provide structurally specific contrast without addition exogenous labels, allowing observation unperturbed systems. Here we achieve super-resolution SHG (SR-SHG) first time. We use photonic nanojet (PNJ) phenomena to a...
<b>Background:</b> Altered collagen architecture with increased “bone-type” pyridinoline cross-linking, rather than quantity, is a key determinant of abnormal tissue structure-function in Idiopathic Pulmonary Fibrosis (IPF). We recently identified that hypoxia inducible factor (HIF) pathway activation promotes induction the bone-type cross-linking enzymes lysyl hydroxylase 2 and oxidase-like 2, yet consequences this on lung fibrosis remain unknown. <b>Methods:</b> Using long term 3D <i>in...