Spatial lung imaging in clinical and translational settings.

For many severe lung diseases, non-invasive biomarkers from imaging could improve early detection of lung injury or disease onset, establish a diagnosis, or help follow-up disease progression and treatment strategies. Imaging of the thorax and lung is challenging due to its size, respiration movement, transferred cardiac pulsation, vast density range and gravitation sensitivity. However, there is extensive ongoing research in this fast-evolving field.

Utilizing MRI, [F]FDG-PET and [Zr]Zr-DFO-28H1 FAP-PET tracer to assess inflammation and fibrogenesis in a reproducible lung injury rat model: a multimodal imaging study.

Objective: Accurate imaging biomarkers that indicate disease progression at an early stage are highly important to enable timely mitigation of symptoms in progressive lung disease. In this context, reproducible experimental models and readouts are key. Here, we aim to show reproducibility of a lung injury rat model by inducing disease and assessing disease progression by multi-modal non-invasive imaging techniques at two different research sites.

Contrast enhanced longitudinal changes observed in an experimental bleomycin-induced lung fibrosis rat model by radial DCE-MRI at 9.4T.

Identifying biomarkers in fibrotic lung disease is key for early anti-fibrotic intervention. Dynamic contrast-enhanced (DCE) MRI offers valuable perfusion-related insights in fibrosis but adapting human MRI methods to rodents poses challenges. Here, we explored these translational challenges for the inflammatory and fibrotic phase of a bleomycin lung injury model in rats.

MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin.

Unlabelled: Drug-induced interstitial lung disease (ILD) is crucial to detect early to achieve the best treatment outcome. Optimally, non-invasive imaging biomarkers can be used for early detection of disease progression and treatment follow-up. Therefore, reliable models are warranted in new imaging biomarker development to accelerate better-targeted treatment options.

C57Bl/6N mice have an attenuated lung inflammatory response to dsRNA compared to C57Bl/6J and BALB/c mice.

Background: Lower respiratory infections caused by ssRNA viruses are a major health burden globally. Translational mouse models are a valuable tool for medical research, including research on respiratory viral infections. In in vivo mouse models, synthetic dsRNA can be used as a surrogate for ssRNA virus replication.

NFκB1 Dichotomously Regulates Pro-Inflammatory and Antiviral Responses in Asthma.

Asthma exacerbations are commonly triggered by rhinovirus infections. Viruses can activate the NFκB pathway resulting in airway inflammation and increased Th2 cytokine expression. NFκB signaling is also involved in early activation of IFNβ, which is a central mediator of antiviral responses to rhinovirus infection.

Early Career Members at the ERS Lung Science Conference 2020: metabolic alterations in lung ageing and disease.

https://bit.ly/2XZ5YGQ.

Imaging Biomarkers in Animal Models of Drug-Induced Lung Injury: A Systematic Review.

For drug-induced interstitial lung disease (DIILD) translational imaging biomarkers are needed to improve detection and management of lung injury and drug-toxicity. Literature was reviewed on animal models in which in vivo imaging was used to detect and assess lung lesions that resembled pathological changes found in DIILD, such as inflammation and fibrosis. A systematic search was carried out using three databases with key words "Animal models", "Imaging", "Lung disease", and "Drugs".

Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model.

Non-invasive imaging biomarkers (IBs) are warranted to enable improved diagnostics and follow-up monitoring of interstitial lung disease (ILD) including drug-induced ILD (DIILD). Of special interest are IB, which can characterize and differentiate acute inflammation from fibrosis. The aim of the present study was to evaluate a PET-tracer specific for Collagen-I, combined with multi-echo MRI, in a rat model of DIILD.

Early Career Members at the Lung Science Conference and the Sleep and Breathing Conference 2019.

http://bit.ly/2XNX6V6.

Early Career Members at the ERS Lung Science Conference: cell-matrix interactions in lung disease and regeneration: Early career forum.

http://ow.ly/6hjS30jB6P9.

Interferon-β deficiency at asthma exacerbation promotes MLKL mediated necroptosis.

Defective production of antiviral interferon (IFN)-β is thought to contribute to rhinovirus-induced asthma exacerbations. These exacerbations are associated with elevated lung levels of lactate dehydrogenase (LDH), indicating occurrence of cell necrosis. We thus hypothesized that reduced lung IFN-β could contribute to necrotic cell death in a model of asthma exacerbations.

IL-1β mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation.

Background: Viral-induced asthma exacerbations, which exhibit both Th1-type neutrophilia and Th2-type inflammation, associate with secretion of Interleukin (IL)-1β. IL-1β induces neutrophilic inflammation. It may also increase Th2-type cytokine expression.

Increased expression of upstream TH2-cytokines in a mouse model of viral-induced asthma exacerbation.

Background: Exacerbations of asthma caused by respiratory viral infections are serious conditions in need of novel treatment. To this end animal models of asthma exacerbations are warranted. We have shown that dsRNA challenges or rhinoviral infection produce exacerbation effects in mice with ovalbumin (OVA)-induced allergic asthma.

Selective inhibition by simvastatin of IRF3 phosphorylation and TSLP production in dsRNA-challenged bronchial epithelial cells from COPD donors.

Background And Purpose: Statin treatment may ameliorate viral infection-induced exacerbations of chronic obstructive pulmonary disease (COPD), which exhibit Th2-type bronchial inflammation. Thymic stromal lymphopoietin (TSLP), a hub cytokine switching on Th2 inflammation, is overproduced in viral and dsRNA-stimulated bronchial epithelial cells from COPD donors. Hence, TSLP may be causally involved in exacerbations.

Capacity of capsazepinoids to relax human small airways and inhibit TLR3-induced TSLP and IFNβ production in diseased bronchial epithelial cells.

Thymic stromal lymphopoietin (TSLP), an immunomodulating potentially disease-inducing cytokine, is overproduced in TLR3-stimulated bronchial epithelial cells from asthmatic donors whereas production of antiviral IFNβ is deficient. It is of therapeutic interest that capsazepine inhibits epithelial TSLP and relaxes human small airways with similar potencies. However, it is not known if other capsazepine-like compounds share such dual actions.