[Cu]Cu-PEG-FUD peptide for noninvasive and sensitive detection of murine pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease resulting in irreversible scarring within the lungs. However, the lack of biomarkers that enable real-time assessment of disease activity remains a challenge in providing efficient clinical decision-making and optimal patient care in IPF. Fibronectin (FN) is highly expressed in fibroblastic foci of the IPF lung where active extracellular matrix (ECM) deposition occurs.

Implementation of a prospective screening strategy to identify adults with a telomere biology disorder among those undergoing lung transplant evaluation for interstitial lung disease.

Introduction: Patients with interstitial lung disease (ILD) secondary to telomere biology disorders (TBD) experience increased morbidity after lung transplantation. Identifying patients with TBD may allow for personalized management to facilitate better outcomes. However, establishing a TBD diagnosis in adults is challenging.

Functional xenon-129 magnetic resonance imaging response to antifibrotic treatment in idiopathic pulmonary fibrosis.

https://bit.ly/3ZXipzD.

Cardiovascular and Pulmonary Responses to Acute Use of Electronic Nicotine Delivery Systems and Combustible Cigarettes in Long-Term Users.

Background: The acute cardiovascular and pulmonary effects of contemporary electronic nicotine delivery systems (ENDS) in long-term users are not known.

Research Question: What are the cardiovascular and pulmonary responses to an acute 15-min product use challenge with ENDS and combustible cigarettes in regular nicotine-containing product users compared with control participants who do not use tobacco or vape?

Study Design And Methods: Observational challenge study before and after nicotine-containing product use of 395 individuals who used ENDS exclusively (n = 164; exhaled carbon monoxide level, < 5 parts per million [ppm]; positive urine NicCheck I [Mossman Associates] results, 82%; fourth-generation ENDS), participants who smoked cigarettes exclusively (n = 117; carbon monoxide level, > 5 ppm; positive urine NicCheck I results), and control participants (n = 114; carbon monoxide level, < 5 ppm; negative urine NicCheck I results).

Results: During the 15-min product challenge, cigarette users took a median of 14.

An open microfluidic coculture model of fibroblasts and eosinophils to investigate mechanisms of airway inflammation.

Interactions between fibroblasts and immune cells play an important role in tissue inflammation. Previous studies have found that eosinophils activated with interleukin-3 (IL-3) degranulate on aggregated immunoglobulin G (IgG) and release mediators that activate fibroblasts in the lung. However, these studies were done with eosinophil-conditioned media that have the capacity to investigate only one-way signaling from eosinophils to fibroblasts.

Hyperpolarized Xe MR Spectroscopy in the Lung Shows 1-year Reduced Function in Idiopathic Pulmonary Fibrosis.

Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 (Xe) MRI measures of ventilation and gas transfer in IPF generally and as an early signature of future IPF progression.

Selective Inhibition of Bromodomain-Containing Protein 4 Reduces Myofibroblast Transdifferentiation and Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a lethal disease driven by myofibroblast expansion. Currently no therapies exist that target the epigenetic mechanisms controlling myofibroblast transdifferentiation, which is responsible for unregulated extracellular matrix (ECM) production. We have recently shown that bromodomain-containing protein 4 (BRD4), an epigenetic regulator that forms a scaffold for nuclear activators and transcription factors, is essential for TGFβ-induced myofibroblast transdifferentiation.

Autophagy Protects against Eosinophil Cytolysis and Release of DNA.

The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG.

[ Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity.

Purpose: The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis.

Methods: Pulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice.

Dynamic contrast enhanced MRI for the evaluation of lung perfusion in idiopathic pulmonary fibrosis.

Background: The objective of this work was to apply quantitative and semiquantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate lung perfusion in idiopathic pulmonary fibrosis (IPF).

Methods: In this prospective trial 41 subjects, including healthy control and IPF subjects, were studied using DCE-MRI at baseline. IPF subjects were then followed for 1 year; progressive IPF (IPF) subjects were distinguished from stable IPF (IPF) subjects based on a decline in percent predicted forced vital capacity (FVC % pred) or diffusing capacity of the lung for carbon monoxide ( % pred) measured during follow-up visits.

Derivation and validation of a prediction model for histopathologic fibrotic hypersensitivity pneumonitis.

Background: Clinical differentiation of fibrotic hypersensitivity pneumonitis (f-HP) remains challenging given variable and overlapping presentations with other fibrotic interstitial lung disease (f-ILD).

Objective: We derived a multivariable model for predicting histopathologic f-HP to better inform multidisciplinary team discussion (MDD) diagnosis, particularly when biopsy may be unsafe or cannot be achieved.

Methods: Patients with histopathologically-defined f-HP and other overlapping f-ILD were reviewed for distinguishing clinical and radiological variables.

Expression of serum response factor in the lung mesenchyme is essential for development of pulmonary fibrosis.

Extracellular matrix deposition characterizes idiopathic pulmonary fibrosis (IPF) and is orchestrated by myofibroblasts. The lung mesenchyme is an essential source of myofibroblasts in pulmonary fibrosis. Although the transcription factor serum response factor (SRF) has shown to be critical in the process of myofibroblast differentiation, its role in development of pulmonary fibrosis has not been determined in vivo.

Interleukin-1α Is a Critical Mediator of the Response of Human Bronchial Fibroblasts to Eosinophilic Inflammation.

Eosinophils contribute to allergic inflammation in asthma in part via elaboration of a complex milieu of soluble mediators. Human bronchial fibroblasts (HBF) respond to stimulation by these mediators by acquiring a pro-inflammatory profile including induction of interleukin 6 (IL6) and IL8. This study sought to determine key component(s) of eosinophil soluble factors that mediate IL6 and IL8 induction in HBF.

Treatment of primary sjögren's syndrome-related interstitial lung disease: a retrospective cohort study.

Background: Interstitial lung disease (ILD) is a common complication of primary Sjögren's syndrome (pSS). Because there is a paucity of literature on the management of pSS-associated ILD (pSS-ILD), this retrospective cohort study assessed the efficacy of azathioprine and mycophenolate therapy in adult patients with pSS-ILD.

Methods: A retrospective cohort study was performed using electronic health records to identify adults meeting the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for pSS.

Probing ECM remodeling in idiopathic pulmonary fibrosis via second harmonic generation microscopy analysis of macro/supramolecular collagen structure.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis with short lifespan following diagnosis as patients have limited effective treatment options. A fundamental limitation is a lack of knowledge of the underlying collagen alterations in the disease, as this could lead to better diagnostics, prognostics, and measures of treatment efficacy. While the fibroses is the primary presentation of the disease, the collagen architecture has not been well studied beyond standard histology.

Analysis of fibroblast migration dynamics in idiopathic pulmonary fibrosis using image-based scaffolds of the lung extracellular matrix.

Idiopathic pulmonary fibrosis (IPF) is characterized by a profound remodeling of the collagen in the extracellular matrix (ECM), where the fibers become both denser and more highly aligned. However, it is unknown how this reconfiguration of the collagen matrix affects disease progression. Here, we investigate the role of specific alterations in collagen fiber organization on cell migration dynamics by using biomimetic image-based collagen scaffolds representing normal and fibrotic lung, where the designs are derived directly from high-resolution second harmonic generation microscopy images.

Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho-associated protein kinase signalling.

Background: The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Cell-free eosinophil granules are found in tissues in eosinophilic diseases, including asthma. This suggests that eosinophils have lysed and released cellular content, likely harming tissues.

Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform.

Mechanical forces have long been recognized as fundamental drivers in biological processes, such as embryogenesis, tissue formation and disease regulation. The collagen gel contraction (CGC) assay has served as a classic tool in the field of mechanobiology to study cell-induced contraction of extracellular matrix (ECM), which plays an important role in inflammation and wound healing. In a conventional CGC assay, cell-laden collagen is loaded into a cell culture vessel (typically a well plate) and forms a disk-shaped gel adhering to the bottom of the vessel.

Repeatability of regional pulmonary functional metrics of Hyperpolarized Xe dissolved-phase MRI.

Background: MRI of hyperpolarized Xenon (HP Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology.

Purpose: To quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase Xe imaging and their dependence on intervisit changes in lung inflation volume.

Matrix Metalloproteinase-9-Dependent Release of IL-1 by Human Eosinophils.

Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways. A concomitant type-2 and type-17 response has been reported in some individuals.

"Structure-Function Imaging of Lung Disease Using Ultrashort Echo Time MRI".

Rationale And Objectives: The purpose of this review is to acquaint the reader with recent advances in ultrashort echo time (UTE) magnetic resonance imaging (MRI) of the lung and its implications for pulmonary MRI when used in conjunction with functional MRI technique.

Materials And Methods: We provide an overview of recent technical advances of UTE and explore the advantages of combined structure-function pulmonary imaging in the context of restrictive and obstructive pulmonary diseases such as idiopathic pulmonary fibrosis (IPF) and cystic fibrosis (CF).

Results: UTE MRI clearly shows the lung parenchymal changes due to IPF and CF.

marks a cellular lineage with distinct contributions to myofibroblasts in lung maturation and injury response.

-expressing () cells have been implicated as progenitors in many mesenchymal tissues. To determine lineage potential, we generated knockin mice using CRISPR/Cas9. During lung maturation, counter to a prior study reporting that + cells give rise equally to myofibroblasts and lipofibroblasts, lineage tracing using mice indicated that ~95% of the lineaged cells are myofibroblasts.