scholarly journals SAT0304 TOFACITINIB INHIBITS TGF-Β1-INDUCED ACTIVATED CELL FUNCTIONS OF MYOFIBROBLAST IN HUMAN LUNG FIBROBLAST POPULATIONS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1097.1-1097
Author(s):  
F. Zhu ◽  
X. Zhang
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Diseases ◽  
Human Lung ◽  
Interstitial Lung Diseases ◽  
Migration And Invasion ◽  
Control Group ◽  
Tgf Β1 ◽  
Invasion Assays

Background:Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a class of refractory diseases.Non-specific treatment with hormone and immunosuppressive agents is mostly used at present, but the effect is limited and the long-term survival rate is not improved [1],while anti-fibrosis treatments (such as Pirfenidone and Nintedanib) have only recently been approved, the long-term efficacy is still unknown.Tofacitinib(TOFA), a JAK inhibitor, has recently been used to treat patients with severe dermatomyositis related interstitial pulmonary disease, with significantly improved survival rate [2-4].A basic study showed that TOFA improved interstitial pulmonary disease in mice by promoting the proliferation of myelogenic inhibitory cells [5].However, whether TOFA can affect the migration and invasion of human lung fibroblasts and further research to reveal the mechanism of its inhibition of pulmonary fibrosis has not been reported.Objectives:To investigate the anti - fibrosis effect of TOFA in CTD-ILD.Methods:Cell migration and invasion AssaysHLFs were incubated with TOFA for 72h, followed by TGF- β1 for 24h.DMEM serum-free medium was used to determine the cell density to 5. 0 × 107/L, 600 uL medium containing 10% fetal bovine serum was added to the lower compartment of Transwell chamber, and 200 uL cell suspension was added to the upper compartment.Incubate in incubator for 12 h.After fixation, staining and sealing, the cells were observed and counted under a microscope. At least 5 random field transmembrane cells were counted in each hole, and the mean value was taken.For the invasion assays, Transwell chamber coated with matrigel was used, and the cell incubation time was 16 h.Results:1. Effect of TOFA on HLFs migration function (Figure 1)Figure 1.Effect of TOFA on HLFs migration function(×200).Mean ± SEM. n = 5.The number of cells passing through the biofilm in the three groups was counted.It can be seen that TGF-β1 group significantly increased compared with control group (*P < 0.0001), and TOFA group significantly decreased compared with TGF- β1 group (#P < 0.0001), suggesting that TOFA can significantly inhibit TGF-β1- induced HLFs migration.2. Effect of TOFA on HLFs invasion function (Figure 2)Figure 2.Effect of TOFA on HLFs invasion function(×200).Mean ± SEM. n = 5.The number of cells passing through the matrigel in the three groups was counted.It can be seen that TGF-β1 group was significantly higher than the control group (*P < 0.0001), and TOFA group was significantly lower than TGF-β1 group(#P < 0.001), suggesting that TOFA can significantly inhibit the invasion function of HLFs induced by TGF-β1.Conclusion:TOFA can effectively inhibit the function of HLFs migration and invasion. Although further studies are needed to elucidate the mechanism by which TOFA inhibit the function of HLFs migration and invasion, our study suggests that TOFA has a potential therapeutic effect for CTD-ILD.References:[1]Aparicio, I.J. and J.S. Lee, Connective Tissue Disease-Associated Interstitial Lung Diseases: Unresolved Issues. Semin Respir Crit Care Med, 2016. 37(3): p. 468-76.[2]Kato, M., et al., Successful Treatment for Refractory Interstitial Lung Disease and Pneumomediastinum With Multidisciplinary Therapy Including Tofacitinib in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis. J Clin Rheumatol, 2019.[3]Kurasawa, K., et al., Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford), 2018. 57(12): p. 2114-2119.[4]Chen, Z., X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis-Associated Interstitial Lung Disease. N Engl J Med, 2019. 381(3): p. 291-293.[5]Sendo, S., et al., Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice. Arthritis Res Ther, 2019. 21(1): p. 184Disclosure of Interests:None declared

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.

Interstitial lung disease

2018 ◽  
Author(s):  
Patrick Davey ◽  
Sherif Gonem ◽  
David Sprigings
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Diseases ◽  
Lung Parenchyma ◽  
Interstitial Lung Diseases ◽  
Broad Group ◽  
Diffuse Parenchymal Lung Diseases ◽  
Parenchymal Lung

The interstitial lung diseases, also known as the diffuse or diffuse parenchymal lung diseases, are a broad group of pulmonary disorders which mainly affect the lung parenchyma as opposed to the airways. By convention, infectious and malignant conditions are excluded from this definition. Thus, the interstitial lung diseases comprise a group of conditions characterized by variable degrees of inflammation and fibrosis, centred on the lung interstitium and alveolar airspaces.

scholarly journals Comparison of Characteristics of Connective Tissue Disease-Associated Interstitial Lung Diseases, Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Diseases, and Idiopathic Pulmonary Fibrosis in Chinese Han Population: A Retrospective Study

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lin Pan ◽  
Yuan Liu ◽  
Rongfei Sun ◽  
Mingyu Fan ◽  
Guixiu Shi
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Western China ◽  
Undifferentiated Connective Tissue Disease

Our study compared the prevalence and characteristics of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD), or idiopathic pulmonary fibrosis (IPF) between January 2009 and December 2012 in West China Hospital, western China. Patients who met the criteria for ILD were included and were assigned to CTD-ILD, UCTD-ILD, or IPF group when they met the criteria for CTD, UCTD, or IPF, respectively. Clinical characteristics, laboratory tests, and high-resolution CT images were analyzed and compared among three groups. 203 patients were included, and all were Han nationality. CTD-ILD was identified in 31%, UCTD-ILD in 32%, and IPF in 37%. Gender and age differed among groups. Pulmonary symptoms were more common in IPF, while extrapulmonary symptoms were more common in CTD-ILD and UCTD-ILD group. Patients with CTD-ILD had more abnormal antibody tests than those of UCTD-ILD and IPF. Little significance was seen in HRCT images among three groups. A systematic evaluation of symptoms and serologic tests in patients with ILD can identify CTD-ILD, UCTD-ILD, and IPF.

Chronic fibrosing progressing interstitial lung disease: a decision of Multidisciplinary Expert Board

2021 ◽  
Vol 31 (4) ◽  
pp. 505-510
Author(s):  
S. N. Avdeev ◽  
S. Yu. Chikina ◽  
I. E. Tyurin ◽  
A. S. Belevskiy ◽  
S. A. Terpigorev ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Russian Federation ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Diagnosis And Treatment ◽  
Antifibrotic Therapy

Introduction. The natural course of some interstitial lung diseases (ILD) is characterized by progressive fibrosing phenotype resembling idiopathic pulmonary fibrosis (IPF). Until recently, the antifibrotic drug nintedanib was approved for treatment of the only fibrosing ILD which was IPF. A new indication for this drug which has been registered in Russian Federation in 2021 includes other fibrosing ILDs with progressive phenotype (PF-ILDs) and ILD associated with systemic scleroderma (SS-ILD).The aim of this publication is to describe general considerations of the decision of Multidisciplinary Expert Board on diagnosis and treatment of PF-ILDs including SS-ILD.Results. According to the extension in nintedanib use mentioned above, the Expert Board created an algorithm for diagnosis and treatment of patients with PF-ILDs and criteria for nuntedanib administration in PF-ILDs.Conclusion. Antifibrotic therapy is needed for patients with PF-ILDs with the failure of the stanrard therapy. In those patients antifibrotic treatment should be initiated as early as possible to better preserve the lung function.

scholarly journals Radiological diagnosis of interstitial lung diseases

2013 ◽  
Vol 66 (suppl. 1) ◽  
pp. 29-33
Author(s):  
Ruza Stevic ◽  
Vucinic Mihailovic ◽  
Dragana Jovanovic ◽  
Nada Vasic
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Lung Diseases ◽  
Usual Interstitial Pneumonia ◽  
Interstitial Lung Diseases ◽  
Ground Glass ◽  
Cryptogenic Organizing Pneumonia ◽  
Acute Interstitial Pneumonia ◽  
Nonspecific Interstitial Pneumonia

Introduction. Interstitial lung diseases include the entities of idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. Recent introduction of high-resolution computed tomography has made the diagnosis of interstitial lung disease much easier. Usual interstitial pneumonia A predominantly subpleural reticulation and honeycombing at the basal posterior part of the lung with a progression to anterior and superior parts are characteristic of usual interstitial pneumonia/ idiopathic pulmonary fibrosis. Nonspecific interstitial pneumonia Typical findings of nonspecific interstitial pneumonia are bilateral, relatively symmetrical subpleural ground glass opacifications and irregular linear opacities. Desquamative interstitial pneumonia is characterized by diffuse symmetrical ground glass opacifications. Respiratory bronchiolitisassociated interstitial lung disease Centrilobular nodules and irregular ground glass opacifications are present. Cryptogenic organizing pneumonia Subpleural and peribronchial consolidations are prominent findings that are not present in other idiopathic interstitial pneumonias. Acute interstitial pneumonia. Bilateral ground-glass opacifications are present and areas of peripheral consolidations may also be seen in acute interstitial pneumonia. Lymphocytic interstitial pneumonia. Diffuse or patchy areas of ground glass opacification with centrilobular nodules and occasionally well-defined cysts are seen. Conclusion. Imaging plays a crucial role in identifying interstitial lung diseases but precise diagnosis requires a dynamic interdisciplinary approach that correlates clinical, radiological and pathologic features.

scholarly journals A contemporary practical approach to the multidisciplinary management of unclassifiable interstitial lung disease

2021 ◽  
pp. 2100276
Author(s):  
Christopher J. Ryerson ◽  
Tamera J. Corte ◽  
Jeffrey L. Myers ◽  
Simon L. F. Walsh ◽  
Sabina A. Guler
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Practical Approach ◽  
Multidisciplinary Management ◽  
Management Decisions ◽  
Histopathological Features ◽  
Radiological Features ◽  
Immunomodulatory Therapies

Fibrotic interstitial lung diseases (ILDs) frequently have nonspecific and overlapping clinical and radiological features, resulting in approximately 10–20% of patients with ILD lacking a clear diagnosis and thus being labelled with unclassifiable ILD. The objective of this review is to describe how patients with unclassifiable ILD should be evaluated and what impact specific clinical, radiological, and histopathological features may have on management decisions, focusing on patients with a predominantly fibrotic phenotype. We highlight recent data that have suggested an increasing role for antifibrotic medications in a variety of fibrotic ILDs, but justify the ongoing importance of making an accurate ILD diagnosis given the benefit of immunomodulatory therapies in many patient populations. We provide a practical approach to support management decisions that can be used by clinicians and tested by clinical researchers, and further identify the need for additional research to support a rational and standardised approach to the management of patients with unclassifiable ILD.

scholarly journals Management of patients with fibrosing interstitial lung diseases

2021 ◽  
Author(s):  
Lee E Morrow ◽  
Daniel Hilleman ◽  
Mark A Malesker
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Underlying Disease ◽  
Interstitial Lung Diseases ◽  
Interstitial Space ◽  
Fda Approval ◽  
Antifibrotic Agents

Abstract Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone. Summary The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature—infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis–associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, pulmonary vasodilators) lack efficacy or cause harm. Conclusion With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients.

scholarly journals Chronic interstitial lung disease in children

2018 ◽  
Vol 27 (147) ◽  
pp. 170100 ◽  
Author(s):  
Matthias Griese
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Diseases ◽  
Transmembrane Protein ◽  
Case Reports ◽  
Genetic Disorders ◽  
The United States ◽  
Interstitial Lung Diseases ◽  
European Respiratory Society ◽  
Increased Risk

Children's interstitial lung diseases (chILD) are increasingly recognised and contain many lung developmental and genetic disorders not yet identified in adult pneumology. Worldwide, several registers have been established. The Australasian Registry Network for Orphan Lung Disease (ARNOLD) has identified problems in estimating rare disease prevalence; focusing on chILD in immunocompetent patients, a period prevalence of 1.5 cases per million children and a mortality rate of 7% were determined. The chILD-EU register highlighted the workload to be covered per patient included and provided protocols for diagnosis and initial treatment, similar to the United States chILD network. Whereas case reports may be useful for young physicians to practise writing articles, cohorts of patients can catapult progress, as demonstrated by recent studies on persistent tachypnoea of infancy, hypersensitivity pneumonitis in children and interstitial lung disease related to interferonopathies from mutations in transmembrane protein 173. Translational research has linked heterozygous mutations in the ABCA3 transporter to an increased risk of interstitial lung diseases, not only in neonates, but also in older children and adults. For surfactant dysfunction disorders in infancy and early childhood, lung transplantation was reported to be as successful as in adult patients. Mutual potentiation of paediatric and adult pneumologists is mandatory in this rapidly extending field for successful future development.This brief review highlights publications in the field of paediatric interstitial lung disease as reviewed during the Clinical Year in Review session presented at the 2017 European Respiratory Society (ERS) Annual Congress in Milan, Italy. It was commissioned by the ERS and critically presents progress made as well as drawbacks.

Interstitielle Lungenerkrankung bei rheumatischen Erkrankungen – neue Therapieansätze

2020 ◽  
Vol 145 (07) ◽  
pp. 470-473
Author(s):  
Anna Jakubczyc ◽  
Claus Neurohr
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Interstitielle Lungenerkrankung ◽  
Wird Eine ◽  
Antifibrotische Therapie ◽  
Allergische Alveolitis ◽  
Mycophenolat Mofetil

Was ist neu? Glukokortikosteroide und Immunsuppressiva In der Therapie der Lungengerüstveränderungen bei Patienten mit Kollagenose (connective tissue disease-associated interstitial lung disease, CTD-ILD) werden Kortikosteroide, Immunsuppressiva und auch Biologika angewendet. Im Vergleich zur Scleroderma-Lung-Study (SLS) I und II, die die Effektivität der Immunsuppressiva Cyclophosphamid (CYC) und Mycophenolat-Mofetil (MMF) bei pulmonaler Beteiligung der Sklerodermie (SSc-ILD) belegen, ist die Datenlage bezüglich der Therapie der anderen CTD-ILD unbefriedigend. Biologika In der Gruppe der Biologika nimmt Rituximab (RTX) an Bedeutung zu. Die aktuell erwarteten Studienergebnisse werden die Wirksamkeit von Immunsuppressiva (vor allem MMF und CYC) mit RTX bei verschiedenen CTD-ILD vergleichen. Zu den weiteren untersuchten Biologika gehören u. a. der monoklonale Anti-IL6-Rezeptor-Antikörper Tocilizumab bei SSc-ILD bzw. Abatacept (ein Fusionsprotein, das die T-Zell-Antworten inhibiert) bei pulmonaler Beteiligung bei rheumatoider Arthritis (RA-ILD). Autologe Stammzelltransplantation Die autologe Stammzelltransplantation ist eine potente, aber nebenwirkungsbehaftete Therapie bei schwerer Sklerodermie. Antifibrotische Therapie Für die Gruppe der Lungengerüstkrankheiten unterschiedlicher Genese inkl. CTD-ILD mit einem progredienten fibrosierenden Verlauf trotz adäquater Therapie (z. B. chronische exogen-allergische Alveolitis, RA, SSc) wurde der Begriff der fibrosierenden interstitiellen Lungenerkrankungen mit progressivem Phänotyp (progressive fibrosing interstitial lung diseases, PF-ILD) geprägt. In jüngster Zeit erschienen Arbeiten, die einen positiven Effekt der antifibrotischen Medikamente (Nintedanib, Pirfenidon) in einer solchen Situation nachweisen. Aktuell wird eine Reihe weiterer Ergebnisse bezüglich der Effektivität der Antifibrotika bei CTD-ILD erwartet. Die Studien auf diesem Gebiet haben das Potential der Erweiterung der Behandlungsmöglichkeiten bei CTD-ILD.

scholarly journals Metastatic cancer mimics interstitial lung disease. Cases when we need fast diagnosis and treatment

2019 ◽  
Vol 89 (2) ◽  
Author(s):  
Ana Hecimovic ◽  
Marko Jakopovic ◽  
Andrea Vukic Dugac ◽  
Feda Dzubur ◽  
Miroslav Samarzija
Keyword(s):  
Differential Diagnosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Diseases ◽  
Metastatic Cancer ◽  
Diagnostic Procedures ◽  
Interstitial Lung Diseases ◽  
Unknown Primary ◽  
Exertional Dyspnea ◽  
Lymphangitic Carcinomatosis

Interstitial lung diseases (ILD) are a heterogeneous group of diseases and one of the differential diagnosis which have to be excluded during diagnostic procedures are malignancies. We will present four patients who were referred to our Department because of suspicion of interstitial lung diseases according to radiology finding. In one case only, one of the radiologist’s differential diagnosis was pulmonary lymphangitic carcinomatosis. All four patients had exertional dyspnea and dry cough which are nonspecific and can be first manifestation of ILD or obstructive lung diseases. After diagnostic evaluation in three cases, diagnosis was pulmonary lymphangitic carcinomatosis due to metastatic lung adenocarcinoma and in one due to metastatic adenocarcinoma of unknown primary origin. Patients with lymphangitic carcinomatosis have poor prognosis without treatment and usually die because of respiratory failure. With these four cases we want to highlight importance of thinking about malignancies when we have patients with suspicion of interstitial lung disease especially when reticular pattern is present on chest X ray. We also wanted to show how important is radiology finding and multidisciplinary approach, and how radiologist’s differential diagnosis can be very helpful in making decisions in further investigations and way of clinicians thinking.

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