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Idiopathic pulmonary fibrosis

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https://www.readbyqxmd.com/read/28430774/is-nintedanib-effective-for-idiopathic-pulmonary-fibrosis
#1
Alejandro Jeldres, Gonzalo Labarca
Idiopathic pulmonary fibrosis has poor prognosis and effective therapies are scarce. In the search for treatments that can modify the course of the disease, nintedanib (BIBF 1120), a tyrosine kinase inhibitor, has emerged as an alternative. However, its role is still unclear. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple sources of information. We identified seven systematic reviews including seven randomized trials overall. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach...
April 10, 2017: Medwave
https://www.readbyqxmd.com/read/28430622/serious-adverse-events-of-cell-therapy-for-respiratory-diseases-a-systematic-review-and-meta-analysis
#2
REVIEW
Runzhen Zhao, Zhenlei Su, Jing Wu, Hong-Long Ji
BACKGROUND: Cell therapy holds the most promising for acute and chronic deleterious respiratory diseases. However, the safety and tolerance for lung disorders are controversy. METHODS: We undertook a systematic review and meta-analyses of all 23 clinical studies of cell therapy. The outcomes were odds ratio (OR), risk difference (RD), Peto OR, relative risk, and mean difference of serious adverse events. RESULTS: 342 systemic infusions and 57 bronchial instillations (204 recipients) of cells were analyzed for acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia, pulmonary arterial hypertension, silicosis, sarcoidosis, extensively drug-resistant tuberculosis, chronic obstructive pulmonary diseases (COPD), and idiopathic pulmonary fibrosis...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427556/pirfenidone-for-acute-exacerbation-of-idiopathic-pulmonary-fibrosis-a%C3%A2-retrospective-study
#3
Kenta Furuya, Susumu Sakamoto, Hiroshige Shimizu, Muneyuki Sekiya, Arisa Kinoshita, Takuma Isshiki, Keishi Sugino, Keiko Matsumoto, Sakae Homma
BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a rapid and ultimately fatal condition, and no effective treatment has been established. Pirfenidone has antifibrotic effects in IPF; however, its efficacy for AE-IPF is unclear. OBJECTIVES: To evaluate the efficacy of pirfenidone for AE-IPF. METHODS: We retrospectively reviewed the medical records of 135 IPF patients treated during the period from April 2008 to April 2015 and identified and extracted 47 AE-IPF patients (42 men, 5 women; mean age, 73...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28427553/familial-pulmonary-fibrosis-clinical-and-radiological-characteristics-and-progression-analysis-in-different-high-resolution-ct-patterns
#4
David Bennett, Maria Antonietta Mazzei, Nevada Cioffi Squitieri, Elena Bargagli, Rosa Metella Refini, Antonella Fossi, Luca Volterrani, Paola Rottoli
BACKGROUND: Familial pulmonary fibrosis (FPF) is defined as an idiopathic diffuse parenchymal lung disease affecting two or more members of the same primary biological family. The aim of the present study was to contribute to the clinical, functional and radiological characterisation of FPF with particular regards to disease progression and survival. METHODS: Baseline clinical, functional and radiological data of a FPF population (n = 46 patients) were retrospectively collected and analysed according to the 2011 IPF guidelines HRCT classification...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28424250/unifying-mechanism-for-different-fibrotic-diseases
#5
Gerlinde Wernig, Shih-Yu Chen, Lu Cui, Camille Van Neste, Jonathan M Tsai, Neeraja Kambham, Hannes Vogel, Yaso Natkunam, D Gary Gilliland, Garry Nolan, Irving L Weissman
Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts...
April 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28422760/cannabinoid-cb1-receptor-overactivity-contributes-to-the-pathogenesis-of-idiopathic-pulmonary-fibrosis
#6
Resat Cinar, Bernadette R Gochuico, Malliga R Iyer, Tony Jourdan, Tadafumi Yokoyama, Joshua K Park, Nathan J Coffey, Hadass Pri-Chen, Gergő Szanda, Ziyi Liu, Ken Mackie, William A Gahl, George Kunos
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without effective treatment, highlighting the need for identifying new targets and treatment modalities. The pathogenesis of IPF is complex, and engaging multiple targets simultaneously might improve therapeutic efficacy. To assess the role of the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF and its interaction with inducible nitric oxide synthase (iNOS) as dual therapeutic targets, we analyzed lung fibrosis and the status of the endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF, as well as controls...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420366/pirfenidone-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice-by-regulating-nrf2-bach1-equilibrium
#7
Yuan Liu, Fuai Lu, Lirong Kang, Zhihua Wang, Yongfu Wang
BACKGROUND: Oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the expression level of antioxidant factors, further regulating the function of oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for IPF therapy approved drugs...
April 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28417017/galectin-1-inhibition-attenuates-profibrotic-signaling-in-hypoxia-induced-pulmonary-fibrosis
#8
Jaymin J Kathiriya, Niyati Nakra, Jenna Nixon, Puja S Patel, Vijay Vaghasiya, Ahmed Alhassani, Zhi Tian, Diane Allen-Gipson, Vrushank Davé
Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising from epithelial injury, aberrant fibroblast growth, and excessive deposition of extracellular matrix. Repeated epithelial injury elicits abnormal wound repair and lung remodeling, often associated with alveolar collapse and edema, leading to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult that contributes to pulmonary fibrosis (PF) and define its molecular roles in profibrotic activation of lung epithelial cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28416592/-wnt-er-is-coming-wnt-signalling-in-chronic-lung-diseases
#9
H A Baarsma, M Königshoff
Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD...
April 17, 2017: Thorax
https://www.readbyqxmd.com/read/28415591/the-purinergic-receptor-subtype-p2y2-mediates-chemotaxis-of-neutrophils-and-fibroblasts-in-fibrotic-lung-disease
#10
Tobias Müller, Susanne Fay, Rodolfo Paula Vieira, Harry Karmouty-Quintana, Sanja Cicko, Korcan Ayata, Gernot Zissel, Torsten Goldmann, Giuseppe Lungarella, Davide Ferrari, Francesco Di Virgilio, Bernard Robaye, Jean-Marie Boeynaems, Michael R Blackburn, Marco Idzko
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases.The concentration of different nucleotides was measured in the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals with bleomycin-induced pulmonary fibrosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414923/determining-the-true-selectivity-profile-of-%C3%AE-v-integrin-ligands-using-radioligand-binding-applying-an-old-solution-to-a-new-problem
#11
James E Rowedder, Steve B Ludbrook, Robert J Slack
The arginyl-glycinyl-aspartic acid (RGD) integrin subfamily contains five members that partner with the αv subunit: αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8. Within the αv integrins, the epithelially restricted αvβ6 has been identified as playing a key role in the activation of transforming growth factor β that is hypothesized to be pivotal in the development of idiopathic pulmonary fibrosis (IPF). As part of a drug discovery program to identify a selective αvβ6 RGD mimetic for IPF, cell adhesion and radioligand binding assays were investigated to screen compounds to determine affinity and αv integrin selectivity...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28414242/discovery-of-2-2-ethyl-6-4-2-3-hydroxyazetidin-1-yl-2-oxo-ethyl-piperazin-1-yl-8-methyl-imidazo-1-2-a-pyridin-3-yl-methyl-amino-4-4-fluorophenyl-thiazole-5-carbonitrile-glpg1690-a-first-in-class-autotaxin-inhibitor-undergoing-clinical-evaluation-for-the-treatment
#12
Nicolas Desroy, Christopher Housseman, Xavier Bock, Agnès Joncour, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Emilie Rondet, Christophe Peixoto, Jean-Marie Joël Grassot, Olivier Picolet, Denis Annoot, Nicolas Triballeau, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, Roland Blanque, Celine Cottereaux, Nele Vandervoort, Thierry Christophe, Patrick Mollat, Marieke B A C Lamers, Marielle Auberval, Boska Hrvacic, Jovica Ralic, Line Oste, Ellen Van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin is a circulating enzyme with a major role in the production of lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has been suggested in many disease areas including pulmonary fibrosis. Structural modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition and improve pharmacokinetic properties, led to the identification of clinical candidate GLPG1690 (11). Compound 11 was able to cause a sustained reduction of LPA levels in plasma in vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis model in mice, and in reducing extra-cellular matrix deposition in the lung whilst also reducing LPA 18:2 content in bronchoalveolar lavage fluid...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28404649/the-microbiome-in-respiratory-medicine-current-challenges-and-future-perspectives
#13
REVIEW
Rosa Faner, Oriol Sibila, Alvar Agustí, Eric Bernasconi, James D Chalmers, Gary B Huffnagle, Chaysavanh Manichanh, Philip L Molyneaux, Roger Paredes, Vicente Pérez Brocal, Julia Ponomarenko, Sanjay Sethi, Jordi Dorca, Eduard Monsó
The healthy lung has previously been considered to be a sterile organ because standard microbiological culture techniques consistently yield negative results. However, culture-independent techniques report that large numbers of microorganisms coexist in the lung. There are many unknown aspects in the field, but available reports show that the lower respiratory tract microbiota: 1) is similar in healthy subjects to the oropharyngeal microbiota and dominated by members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows changes in smokers and well-defined differences in chronic respiratory diseases, although the temporal and spatial kinetics of these changes are only partially known; and 3) shows relatively abundant non-cultivable bacteria in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and bronchiectasis, with specific patterns for each disease...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28400116/the-role-of-infection-in-interstitial-lung-diseases-a-review
#14
REVIEW
Natalya Azadeh, Andrew H Limper, Eva M Carmona, Jay H Ryu
Interstitial lung diseases (ILD) comprise an array of heterogeneous parenchymal lung diseases that are associated with a spectrum of pathologic, radiologic and clinical manifestations. There are ILDs with known etiologies and those that are idiopathic, making treatment strategies challenging. Prognosis can vary according to the type of ILD but many exhibit gradual progression with an unpredictable clinical course in individual patients as seen in idiopathic pulmonary fibrosis and the phenomenon of "acute exacerbation"(AE)...
April 8, 2017: Chest
https://www.readbyqxmd.com/read/28399537/antacid-therapy-and-disease-progression-in-patients-with-idiopathic-pulmonary-fibrosis-who-received-pirfenidone
#15
Michael Kreuter, Paolo Spagnolo, Wim Wuyts, Elisabetta Renzoni, Dirk Koschel, Francesco Bonella, Toby M Maher, Martin Kolb, Derek Weycker, Klaus-Uwe Kirchgässler, Ulrich Costabel
BACKGROUND: Gastroesophageal reflux disease is a potential risk factor for idiopathic pulmonary fibrosis (IPF) progression; however, the impact of antacid therapy (AAT) is under debate. OBJECTIVE: To evaluate the effect of AAT on IPF progression in pirfenidone-treated patients. METHODS: This post hoc analysis included patients with IPF who received pirfenidone in 3 trials (CAPACITY [PIPF-004/PIPF-006] and ASCEND [PIPF-016]). Pulmonary function, exercise tolerance, survival, hospitalizations, and adverse events (AEs) over 52 weeks were analyzed by baseline AAT use...
April 12, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28395683/pulmonary-scar-carcinoma-in-south-africa
#16
N Jenkins, E M Irusen, C F N Koegelenberg
BACKGROUND: The association between lung scarring and the subsequent development of cancer remains controversial. South Africa has one of the highest incidences of tuberculosis in the world, and resultant scarring may predispose to malignancy. The country also carries a very high burden of smoking and smoking-related diseases that may be synergistic in malignant transformation. OBJECTIVE: To assess the frequency of pulmonary scarring in patients with lung cancer...
March 29, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28389561/tgf-beta-1-induced-cd44v6-nox4-signaling-in-pathogenesis-of-idiopathic-pulmonary-fibrosis
#17
Shibnath Ghatak, Vincent C Hascall, Roger R Markwald, Carol Feghali-Bostwick, Carol M Artlett, Monika Gooz, Galina S Bogatkevich, Ilia Atanelishvili, Richard M Silver, Jeanette Wood, Victor J Thannickal, Suniti Misra
Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of fatal outcome. The lack of information about the signaling pathways that sustain fibrosis and the myofibroblasts phenotype has prevented the development of targeted therapies for IPF. Our previous study (1) showed that isolated fibrogenic lung fibroblasts have high endogenous levels of the hyaluronan receptor, CD44v6 (CD44-variants containing exon-6), which enhances the TGF-beta-1 autocrine signaling and induces fibroblasts to transdifferentiate into myofibroblasts...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28388260/acute-exacerbation-and-decline-in-forced-vital-capacity-are-associated-with-increased-mortality-in-idiopathic-pulmonary-fibrosis
#18
Miya O Paterniti, Youwei Bi, Dinko Rekić, Yaning Wang, Banu A Karimi-Shah, Badrul A Chowdhury
RATIONALE: Exploration of forced vital capacity (FVC) as it relates to mortality in idiopathic pulmonary fibrosis (IPF), a chronic, progressive, and ultimately fatal parenchymal lung disease, is important both clinically and to the current drug development paradigm. We evaluated the association between FVC decline and mortality in the largest, well-characterized placebo cohort to date. Additionally, we sought to explore the risk of death from acute exacerbations and further validate previously identified baseline predictors of mortality...
April 7, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28386365/calpain-1-regulates-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells-via-pi3k-akt-signaling-pathway
#19
Wei-Jun Tan, Qiu-Yue Tan, Ting Wang, Min Lian, Li Zhang, Zhen-Shun Cheng
Cell proliferation, transformation, and epithelial-mesenchymal transition (EMT) are key processes involved in the development of idiopathic pulmonary fibrosis (IPF). This study investigated the regulatory factors and signaling pathways that mediate EMT in the human type II alveolar epithelial A549 cell line. A549 cells were cultured in RPMI-1640 medium and allocated to the following four groups: blank control group or treated with transforming growth factor-β1 (TGF-β1), TGF-β1 + PD 150606 (a calpain 1 inhibitor), or PD 150606...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386328/kallistatin-protects-against-bleomycin-induced-idiopathic-pulmonary-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#20
Xiaoping Huang, Xiao Wang, Xiaolan Xie, Shulan Zeng, Zhaofa Li, Xianxiang Xu, Huiyong Yang, Fei Qiu, Junsheng Lin, Yong Diao
Aberrant angiogenesis and vascular remodeling are the main features of idiopathic pulmonary fibrosis. Kallistatin is an anti-angiogenic peptide with known effects on endothelial cells. This study aimed to demonstrate that kallistatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in a rat model by inhibiting angiogenesis. Twenty-five rats were randomly divided into five experimental groups: (A) Saline only (SA)-as the negative control, (B) BLM only (BLM)-as the model group, (C) BLM and 0...
2017: American Journal of Translational Research
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