Eicosanoids: mediators and therapeutic targets in fibrotic lung disease

2005 ◽  
Vol 108 (6) ◽  
pp. 479-491 ◽  
Author(s):  
Ryan P. CHARBENEAU ◽  
Marc PETERS-GOLDEN
Keyword(s):  
Prostaglandin E2 ◽  
Lung Disease ◽  
Lung Diseases ◽  
Lipid Mediators ◽  
Therapeutic Approaches ◽  
Chronic Lung Diseases ◽  
Fibrotic Lung Diseases ◽  
Fibrotic Lung Disease ◽  
End Stage

Fibrosis is a common end-stage sequella of a number of acute and chronic lung diseases. Current concepts of pathogenesis implicate dysregulated interactions between epithelial cells and mesenchymal cells. Although investigative efforts have documented important roles for cytokines and growth factors in the pathogenesis of fibrotic lung diseases, these observations have not as yet been translated into efficacious therapies, and there is a pressing need for new pathogenetic insights and therapeutic approaches for these devastating disorders. Eicosanoids are lipid mediators derived from arachidonic acid, the most studied of which are the prostaglandins and leukotrienes. Although they are primarily known for their roles in asthma, pain, fever and vascular responses, present evidence indicates that eicosanoids exert relevant effects on immune/inflammatory, as well as structural, cells pertinent to fibrogenesis. In general, leukotrienes promote, whereas prostaglandin E2 opposes, fibrogenic responses. An imbalance of eicosanoids also exists in pulmonary fibrosis, which favours the production of leukotrienes over prostaglandin E2. This review highlights the role of this imbalance in the evolution of fibrotic lung disease, discusses the mechanisms by which it may arise and considers approaches for therapeutic targeting of eicosanoids in these conditions.

scholarly journals The burden of Progressive Fibrotic Interstitial lung disease across the UK

2020 ◽  
Author(s):  
Thomas Simpson ◽  
Shaney L Barratt ◽  
Paul Beirne ◽  
Nazia Chaudhuri ◽  
Anjali Crawshaw ◽  
...  
Keyword(s):  
Lung Disease ◽  
Lung Diseases ◽  
Progressive Disease ◽  
Workforce Planning ◽  
Interstitial Lung Diseases ◽  
Specialist Centre ◽  
Patients At Risk ◽  
Fibrotic Lung Diseases ◽  
Fibrotic Lung Disease ◽  
The Uk

AbstractWhile Idiopathic pulmonary fibrosis (IPF) remains the exemplar progressive fibrotic lung disease, there remains a cohort of non-IPF fibrotic lung diseases (fILD) which adopt a similar clinical behaviour to IPF despite therap. This phenotypically related group of conditions, where progression of disease is similar to that seen in IPF, have recently been described as Progressive Fibrotic Interstitial Lung diseases (PF-ILD). Previous estimates suggest that between 18 to 40% of all fILD will develop progressive disease, however, the exact burden remains unknown. This retrospective, observational study therefore aimed to estimate the incidence of PF-ILD across England.All new referrals seen across nine UK centres for their first outpatient clinic appointment between 1st August 2017 and 31st January 2018 were assessed against the diagnostic criteria for PF-ILD laid out in the INBUILD trial. A total of 1749 patients with fILD were assessed. In this cohort of patients at risk of developing PF-ILD the INBUILD criteria were met in 14.5% (253/1749) of all new non-IPF fILD referrals. The average time from referral to specialist centre to diagnosis of progressive phenotype was 311 days. Of the progression events the majority were driven by a measured drop in FVC, with more than half of patients experiencing a drop of 10%. Almost one quarter of patients (24.1%) were diagnosed with progressive disease on the basis of radiological and symptomatic progression alone without a spirometric deterioration.This study represents a fair and balanced approach to assessing the incidence of objectively measurable and treatable PF-ILDs in the UK. A rate of 14.5% of new referrals with non-IPF ILD is less than that reported in previous studies however our methodology is likely to give a more accurate result than estimates based on extrapolation from general disease statistics, from physician-reported estimates prone to significant biases, or insurance claim processes also substantially prone to bias. This information has implication for workforce planning and the funding of anti-fibrotic therapy in the UK and beyond.

scholarly journals Role of extracellular vesicles in chronic lung disease

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216370
Author(s):  
Anne Trappe ◽  
Seamas C Donnelly ◽  
Paul McNally ◽  
Judith A Coppinger
Keyword(s):  
Lung Disease ◽  
Extracellular Vesicles ◽  
Chronic Lung Disease ◽  
Lung Diseases ◽  
Drug Carriers ◽  
Chronic Obstructive ◽  
Sources Of Information ◽  
Chronic Obstructive Pulmonary Disorder ◽  
Chronic Lung Diseases

To explore the role of extracellular vesicles (EVs) in chronic lung diseases.EVs are emerging as mediators of intercellular communication and possible diagnostic markers of disease. EVs harbour cargo molecules including RNA, lipids and proteins that they transfer to recipient cells. EVs are intercellular communicators within the lung microenvironment. Due to their disease-specific cargoes, EVs have the promise to be all-in-one complex multimodal biomarkers. EVs also have potential as drug carriers in chronic lung disease.Descriptive discussion of key studies of EVs as contributors to disease pathology, as biomarkers and as potential therapies with a focus on chronic obstructive pulmonary disorder (COPD), cystic fibrosis (CF), asthma, idiopathic pulmonary fibrosis and lung cancer.We provide a broad overview of the roles of EV in chronic respiratory disease. Recent advances in profiling EVs have shown their potential as biomarker candidates. Further studies have provided insight into their disease pathology, particularly in inflammatory processes across a spectrum of lung diseases. EVs are on the horizon as new modes of drug delivery and as therapies themselves in cell-based therapeutics.EVs are relatively untapped sources of information in the clinic that can help further detail the full translational nature of chronic lung disorders.

scholarly journals Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD

2021 ◽  
Vol 10 (11) ◽  
pp. 2285
Author(s):  
John N. Shumar ◽  
Abhimanyu Chandel ◽  
Christopher S. King
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Treatment Pathway ◽  
Antifibrotic Therapy ◽  
New Treatment ◽  
Fibrotic Lung Diseases

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.

scholarly journals Specialized Pro-Resolving Lipid Mediators in Neonatal Cardiovascular Physiology and Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 933
Author(s):  
Andrea Gila-Diaz ◽  
Gloria Herranz Carrillo ◽  
Pratibha Singh ◽  
David Ramiro-Cortijo
Keyword(s):  
Tissue Repair ◽  
Cardiovascular Health ◽  
Critical Role ◽  
Potential Effect ◽  
Lipid Mediators ◽  
Physiological Effects ◽  
Therapeutic Approaches ◽  
The Impact ◽  
Long Chain

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.

The role of pulmonary rehabilitation in the prevention of exacerbations of chronic lung diseases

2017 ◽  
pp. 224-246
Author(s):  
Fernanda M. Rodrigues ◽  
Matthias Loeckx ◽  
Thierry Troosters ◽  
Wim Janssens
Keyword(s):  
Pulmonary Rehabilitation ◽  
Lung Diseases ◽  
Chronic Lung Diseases

scholarly journals Prescription Patterns for Pulmonary Vasodilators in the Treatment of Pulmonary Hypertension Associated With Chronic Lung Diseases: Insights From a Clinician Survey

2021 ◽  
Vol 8 ◽  
Author(s):  
Christopher A. Thomas ◽  
Justin Lee ◽  
Roberto J. Bernardo ◽  
Ryan J. Anderson ◽  
Vladimir Glinskii ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Targeted Therapy ◽  
Lung Disease ◽  
Lung Diseases ◽  
Online Survey ◽  
Treatment Approach ◽  
Initial Therapy ◽  
Triple Combination Therapy ◽  
Management Guidelines ◽  
Chronic Lung Diseases

Background: Pulmonary hypertension is a complication of chronic lung diseases (PH-CLD) associated with significant morbidity and mortality. Management guidelines for PH-CLD emphasize the treatment of the underlying lung disease, but the role of PH-targeted therapy remains controversial. We hypothesized that treatment approaches for PH-CLD would be variable across physicians depending on the type of CLD and the severity of PH.Methods and Results: Between May and July 2020, we conducted an online survey of PH experts asking for their preferred treatment approach in seven hypothetical cases of PH-CLD of varying severity. We assessed agreement amongst clinicians for initial therapy choice using Fleiss' kappa calculations. Over 90% of respondents agreed that they would treat cases of severe PH in the context of mild lung disease with some form of PH-targeted therapy. For cases of severe PH in the context of severe lung disease, over 70% of respondents agreed to use PH-targeted therapy. For mild PH and mild lung disease cases, <50% of respondents chose to start PH-specific therapy. There was overall poor agreement between respondents in the choice to use mono-, double or triple combination therapy with PH-specific agents in all cases.Conclusion: Although management guidelines discourage the routine use of PH-targeted therapies to treat PH-CLD patients, most physicians choose to treat patients with some form of PH-targeted therapy. The choice of therapy and treatment approach are variable and appear to be influenced by the severity of the PH and the underlying lung disease.

824 Case Series on the Use of Volume Assured Pressure Support in Patients with Chronic Pulmonary Disease and Progressive Hypercapnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A321-A322
Author(s):  
William LeMaster ◽  
Dale Jun ◽  
Sharon De Cruz ◽  
Michelle Zeidler ◽  
Rajan Saggar
Keyword(s):  
Respiratory Failure ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Lung Transplant ◽  
Pressure Support ◽  
Case Series ◽  
Chronic Obstructive ◽  
Hypoxemic Respiratory Failure ◽  
Chronic Lung Diseases

Abstract Introduction Chronic hypercapnia results from destruction of lung parenchyma which occurs in chronic lung diseases including interstitial lung disease (ILD), bronchiectasis, and chronic lung transplant rejection. Many patients with these diseases will experience progressive respiratory failure eventually requiring consideration of transplantation or re-transplantation. Due to physiologic changes in sleep including reduction in tidal volume, worsening air tapping, and REM atonia, hypoventilation can be exacerbated during the sleeping hours. We present four patients who were prescribed nocturnal Volume Assured Pressure Support VAPS for their progressive hypercapnia. Report of case(s) Subject 1 is a 72 year old female with severe bronchiectasis and restrictive lung disease due to TB pneumonia at a young age. Subject 2 is a 45 year old male with history of pulmonary cavitation due to extensive TB disease when he was younger. Subject 3 is a 45-year-old woman with rheumatoid arthritis related ILD with associated pulmonary arterial hypertension. Subject 4 is a 74 year old patient with a bilateral lung transplant for IPF complicated by bronchiolitis obliterans syndrome who presented with progressive dyspnea and hypercapnia. Despite optimal therapy, all of these patients were admitted for hypercapnic and hypoxemic respiratory failure requiring treatment with BPAP then transitioned to nocturnal VAPS on discharge. For all patients, dyspnea and pCO2 improved as outpatients although all patients did eventually experience an exacerbation of their lung disease requiring repeat admission. Conclusion Due to the physiologic changes that occur with sleep, patients with severe lung disease may experience worsening CO2 retention while sleeping. There is little data assessing the use of chronic nocturnal non-invasive ventilation (NIV) to treat the hypercapnia of chronic lung diseases other than chronic obstructive pulmonary disease, extra-thoracic restriction, and neuromuscular disease. In this case series, nocturnal VAPS stabilized and/or reduced pCO2 in patients with pulmonary parenchymal disease of various etiologies. Additional studies are needed to assess long term effects of VAPS in these patients, including exacerbations, symptoms, and overall mortality. Support (if any):

scholarly journals Exosomal miRNAs in Lung Diseases: From Biologic Function to Therapeutic Targets

2019 ◽  
Vol 8 (9) ◽  
pp. 1345 ◽  
Author(s):  
Julien Guiot ◽  
Ingrid Struman ◽  
Edouard Louis ◽  
Renaud Louis ◽  
Michel Malaise ◽  
...  
Keyword(s):  
Lung Disease ◽  
Disease Progression ◽  
Lung Diseases ◽  
Potential Role ◽  
Protective Effects ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
Stress Signals ◽  
Therapeutic Tools

Increasing evidence suggests the potential role of extracellular vesicles (EVs) in many lung diseases. According to their subcellular origin, secretion mechanism, and size, EVs are currently classified into three subpopulations: exosomes, microvesicles, and apoptotic bodies. Exosomes are released in most biofluids, including airway fluids, and play a key role in intercellular communication via the delivery of their cargo (e.g., microRNAs (miRNAs)) to target cell. In a physiological context, lung exosomes present protective effects against stress signals which allow them to participate in the maintenance of lung homeostasis. The presence of air pollution alters the composition of lung exosomes (dysregulation of exosomal miRNAs) and their homeostatic property. Indeed, besides their potential as diagnostic biomarkers for lung diseases, lung exosomes are functional units capable of dysregulating numerous pathophysiological processes (including inflammation or fibrosis), resulting in the promotion of lung disease progression. Here, we review recent studies on the known and potential role of lung exosomes/exosomal miRNAs, in the maintaining of lung homeostasis on one hand, and in promoting lung disease progression on the other. We will also discuss using exosomes as prognostic/diagnostic biomarkers as well as therapeutic tools for lung diseases.

scholarly journals From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 636 ◽  
Author(s):  
Birger Tielemans ◽  
Kaat Dekoster ◽  
Stijn E. Verleden ◽  
Stefan Sawall ◽  
Bartosz Leszczyński ◽  
...  
Keyword(s):  
Lung Disease ◽  
Disease Progression ◽  
Lung Diseases ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Space Technology ◽  
Study Results ◽  
Life Threatening ◽  
End Stage

Lung diseases such as fibrosis, asthma, cystic fibrosis, infection and cancer are life-threatening conditions that slowly deteriorate quality of life and for which our diagnostic power is high, but our knowledge on etiology and/or effective treatment options still contains important gaps. In the context of day-to-day practice, clinical and preclinical studies, clinicians and basic researchers team up and continuously strive to increase insights into lung disease progression, diagnostic and treatment options. To unravel disease processes and to test novel therapeutic approaches, investigators typically rely on end-stage procedures such as serum analysis, cyto-/chemokine profiles and selective tissue histology from animal models. These techniques are useful but provide only a snapshot of disease processes that are essentially dynamic in time and space. Technology allowing evaluation of live animals repeatedly is indispensable to gain a better insight into the dynamics of lung disease progression and treatment effects. Computed tomography (CT) is a clinical diagnostic imaging technique that can have enormous benefits in a research context too. Yet, the implementation of imaging techniques in laboratories lags behind. In this review we want to showcase the integrated approaches and novel developments in imaging, lung functional testing and pathological techniques that are used to assess, diagnose, quantify and treat lung disease and that may be employed in research on patients and animals. Imaging approaches result in often novel anatomical and functional biomarkers, resulting in many advantages, such as better insight in disease progression and a reduction in the numbers of animals necessary. We here showcase integrated assessment of lung disease with imaging and histopathological technologies, applied to the example of lung fibrosis. Better integration of clinical and preclinical imaging technologies with pathology will ultimately result in improved clinical translation of (therapy) study results.

scholarly journals The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nurfatin Asyikhin Kamaruzaman ◽  
Egi Kardia ◽  
Nurulain ‘Atikah Kamaldin ◽  
Ahmad Zaeri Latahir ◽  
Badrul Hisham Yahaya
Keyword(s):  
Stem Cell ◽  
Lung Disease ◽  
Lung Diseases ◽  
Inflammatory Responses ◽  
Rabbit Model ◽  
Screening Tests ◽  
Cell Based Therapy ◽  
Chronic Lung Diseases ◽  
Reliable Model ◽  
Single Animal

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

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