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https://www.readbyqxmd.com/read/29458107/wnt-receptor-signalling-in-lung-physiology-and-pathology
#1
REVIEW
Wioletta Skronska-Wasek, Reinoud Gosens, Melanie Königshoff, Hoeke Abele Baarsma
The WNT signalling cascades have emerged as critical regulators of a wide variety of biological aspects involved in lung development as well as in physiological and pathophysiological processes in the adult lung. WNTs (secreted glycoproteins) interact with various transmembrane receptors and co-receptors to activate signalling pathways that regulate transcriptional as well as non-transcriptional responses within cells. In physiological conditions, the majority of WNT receptors and co-receptors can be detected in the adult lung...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29453386/anti-fibrotic-effects-of-cxcr4-targeting-i-body-ad-114-in-preclinical-models-of-pulmonary-fibrosis
#2
K Griffiths, D M Habiel, J Jaffar, U Binder, W G Darby, C G Hosking, A Skerra, G P Westall, C M Hogaboam, M Foley
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3-5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4 + fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444413/involvement-of-alveolar-epithelial-cell-necroptosis-in-ipf-pathogenesis
#3
Ji-Min Lee, Masahiro Yoshida, Mi-So Kim, June-Hyuk Lee, Ae-Rin Baek, An Soo Jang, Do Jin Kim, Shunsuke Minagawa, Su Sie Chin, Choon-Sik Park, Jun Araya, Kazuyoshi Kuwano, Sung Woo Park
RATIONALE: Alveolar epithelial cell (AEC) injury leading to cell death is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF). Among regulated/programmed cell death, the excessive apoptosis of AECs has been widely implicated in IPF pathogenesis. Necroptosis is a type of regulated/programmed necrosis. A multiprotein complex composed of receptor-interacting protein kinase-1 and -3 (RIPK1/3) plays a key regulatory role in initiating necroptosis. Although necroptosis participates in disease pathogeneses through the release of damage-associated molecular patterns (DAMPs), its association with IPF progression remains elusive...
February 14, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29440315/jak2-mediates-lung-fibrosis-pulmonary-vascular-remodelling-and-hypertension-in-idiopathic-pulmonary-fibrosis-an-experimental-study
#4
Javier Milara, Beatriz Ballester, Anselm Morell, José L Ortiz, Juan Escrivá, Estrella Fernández, Francisco Perez-Vizcaino, Angel Cogolludo, Enrique Pastor, Enrique Artigues, Esteban Morcillo, Julio Cortijo
BACKGROUND: Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation ( V )/perfusion ( Q ) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. OBJECTIVE: The study of JAK2 as potential target to treat PH in IPF...
February 10, 2018: Thorax
https://www.readbyqxmd.com/read/29438171/analysis-of-the-histologic-features-associated-with-interobserver-variation-in-idiopathic-pulmonary-fibrosis
#5
Kati Mäkelä, Ulla Hodgson, Anneli Piilonen, Katariina Kelloniemi, Risto Bloigu, Eva Sutinen, Kaisa Salmenkivi, Mikko Rönty, Elisa Lappi-Blanco, Marjukka Myllärniemi, Riitta Kaarteenaho
The histologic manifestation of idiopathic pulmonary fibrosis (IPF) is usual interstitial pneumonia (UIP), which is a good prognostic determinant of survival compared with other histologic interstitial lung disease patterns. According to the current international guidelines, the histologic features of suspected IPF/UIP are divided into 4 categories: UIP, probable UIP, possible UIP, and not UIP pattern. Four pulmonary pathologists who were blinded to clinicoradiologic information reevaluated 50 surgical lung biopsies (83...
February 12, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29436402/best-supportive-care-for-idiopathic-pulmonary-fibrosis-current-gaps-and-future-directions
#6
REVIEW
Giovanni Ferrara, Fabrizio Luppi, Surinder S Birring, Stefania Cerri, Antonella Caminati, Magnus Sköld, Michael Kreuter
Best supportive care (BSC) is generally defined as all the interventions and the multiprofessional approach aimed to improve and optimise quality of life (QoL) in patients affected by progressive diseases. In this sense, it excludes and might be complementary to other interventions directly targeting the disease. BSC improves survival in patients with different types of cancer. Patients with idiopathic pulmonary fibrosis (IPF) experience a vast range of symptoms during the natural history of the disease and might have a beneficial effect of BSC interventions...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/29426911/hypoxia-induces-pulmonary-fibroblast-proliferation-through-nfat-signaling
#7
Lakmini Kumari Senavirathna, Chaoqun Huang, Xiaoyun Yang, Maria Cristina Munteanu, Roshini Sathiaseelan, Dao Xu, Craig A Henke, Lin Liu
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and typically fatal lung disease with a very low survival rate. Excess accumulation of fibroblasts, myofibroblasts and extracellular matrix creates hypoxic conditions within the lungs, causing asphyxiation. Hypoxia is, therefore, one of the prominent features of IPF. However, there have been few studies concerning the effects of hypoxia on pulmonary fibroblasts. In this study, we investigated the molecular mechanisms of hypoxia-induced lung fibroblast proliferation...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29424490/effects-of-2%C3%A2-years-of-caloric-restriction-on-oxidative-status-assessed-by-urinary-f2-isoprostanes-the-calerie-2-randomized-clinical-trial
#8
Dora Il'yasova, Luigi Fontana, Manjushri Bhapkar, Carl F Pieper, Ivan Spasojevic, Leanne M Redman, Sai Krupa Das, Kim M Huffman, William E Kraus
Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two-year randomized controlled trial. Healthy volunteers (n = 218) were randomized to prescribed 25% CR (n = 143) or ad libitum control (AL, n = 75) stratifying the randomization schedule by site, sex, and BMI. F2-isoprostanes were quantified using LC-MS/MS in morning, fasted urine specimens at baseline, at 12 and 24 months...
February 9, 2018: Aging Cell
https://www.readbyqxmd.com/read/29422061/n-acetylcysteine-exposure-is-associated-with-improved-survival-in-anti-nuclear-antibody-seropositive-patients-with-usual-interstitial-pneumonia
#9
Justin M Oldham, Leah J Witt, Ayodeji Adegunsoye, Jonathan H Chung, Cathryn Lee, Scully Hsu, Lena W Chen, Aliya Husain, Steven Montner, Rekha Vij, Mary E Strek, Imre Noth
BACKGROUND: Mortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients...
February 8, 2018: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29420550/spectrum-of-interstitial-lung-diseases-at-a-tertiary-center-in-a-developing-country-a-study-of-803-subjects
#10
Sahajal Dhooria, Ritesh Agarwal, Inderpaul Singh Sehgal, Kuruswamy Thurai Prasad, Mandeep Garg, Amanjit Bal, Ashutosh Nath Aggarwal, Digambar Behera
BACKGROUND: The spectrum of interstitial lung diseases (ILDs) have mainly been reported from the developed countries; data from developing countries is sparse and conflicting. The aim of this study is to describe the distribution of various ILDs from a developing country. METHODS: This is an analysis of prospectively collected clinical, radiological and histological data of consecutive subjects (age >12 years) with ILDs from a single tertiary care medical center...
2018: PloS One
https://www.readbyqxmd.com/read/29420051/loss-of-cdkn2b-promotes-fibrosis-via-increased-fibroblast-differentiation-rather-than-proliferation
#11
Anne M Scruggs, Hailey B Koh, Priya Tripathi, Nicholas J Leeper, Eric S White, Steven K Huang
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease characterized by excessive scarring and fibroblast activation. We previously showed that fibroblasts from patients with IPF are hypermethylated at the CDKN2B gene locus resulting in decreased CDKN2B expression. Here, we examine how diminished CDKN2B expression in normal and IPF fibroblasts affect fibroblast function and how loss of CDKN2B contributes to IPF pathogenesis. We first confirmed that protein expression of CDKN2B was diminished in IPF lungs in situ...
February 8, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29416456/evaluation-of-safety-and-efficacy-of-regional-anesthesia-compared-with-general-anesthesia-in-thoracoscopic-lung-biopsy-procedure-on-patient-with-idiopathic-pulmonary-fibrosis
#12
Waseem M Hajjar, Sami A Al-Nassar, Ghaida S Al-Sugair, Alaa Al-Oqail, Shahd Al-Mansour, Rand Al-Haweel, Adnan W Hajjar
Background: Interstitial lung diseases are diseases that need histology diagnosis or obtaining a lung biopsy to establish the diagnosis. Surgical biopsies are performed usually using the thoracoscopy technique under general anesthesia (GA) although this procedure is still associated with morbidity rate. The aim of this study is to determine the effectiveness and safety of regional anesthesia (RA) compared with GA in thoracoscopic lung biopsy procedures done on patients with idiopathic pulmonary fibrosis (IPF)...
January 2018: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/29415439/inhibiting-skp2-e3-ligase-suppresses-bleomycin-induced-pulmonary-fibrosis
#13
Masashi Mikamo, Kyoko Kitagawa, Satoshi Sakai, Chiharu Uchida, Tatsuya Ohhata, Koji Nishimoto, Hiroyuki Niida, Sayuri Suzuki, Keiichi I Nakayama, Naoki Inui, Takafumi Suda, Masatoshi Kitagawa
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and no curative therapies. SCF-Skp2 E3 ligase is a target for cancer therapy, but there have been no reports about Skp2 as a target for IPF. Here we demonstrate that Skp2 is a promising therapeutic target for IPF. We examined whether disrupting Skp2 suppressed pulmonary fibrosis in a bleomycin (BLM)-induced mouse model and found that pulmonary fibrosis was significantly suppressed in Skp2-deficient mice compared with controls. The pulmonary accumulation of fibrotic markers such as collagen type 1 and fibronectin in BLM-infused mice was decreased in Skp2-deficient mice...
February 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29414827/statin-therapy-and-outcomes-in-trials-of-nintedanib-in-idiopathic-pulmonary-fibrosis
#14
Michael Kreuter, Ulrich Costabel, Luca Richeldi, Vincent Cottin, Marlies Wijsenbeek, Francesco Bonella, Elisabeth Bendstrup, Toby M Maher, Daniel Wachtlin, Susanne Stowasser, Martin Kolb
BACKGROUND: Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. OBJECTIVES: We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. METHODS: Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials...
February 7, 2018: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29414453/physiological-predictors-of-hypoxic-challenge-testing-hct-outcomes-in-interstitial-lung-disease-ild
#15
Shaney L Barratt, Jonathon Shaw, Rachel Jones, Anna Bibby, Huzaifa Adamali, Naveed Mustfa, Ian Cliff, Helen Stone, Nazia Chaudhuri
BACKGROUND: Pre-flight risk assessments are currently recommended for all Interstitial Lung Disease (ILD) patients. Hypoxic challenge testing (HCT) can inform regarding the need for supplemental in-flight oxygen but variables which might predict the outcome of HCT and thus guide referral for assessment, are unknown. METHODS: A retrospective analysis of ILD patients attending for HCT at three tertiary care ILD referral centres was undertaken to investigate the concordance between HCT and existing predictive equations for prediction of in-flight hypoxia...
February 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29414448/anti-parietal-cell-autoimmunity-is-associated-with-an-accelerated-decline-of-lung-function-in-ipf-patients
#16
Guillaume Beltramo, Gabriel Thabut, Nicolas Peron, Pascale Nicaise, Aurélie Cazes, Marie-Pierre Debray, Audrey Joannes, Yves Castier, Arnaud A Mailleux, Justine Frija, Pauline Pradère, Aurélien Justet, Raphaël Borie, Marie-Christine Dombret, Camille Taille, Michel Aubier, Bruno Crestani
BACKGROUND: Autoantibodies against lung epithelial antigens are often detected in patients with Idiopathic Pulmonary Fibrosis (IPF). Anti-Parietal Cell Antibodies (APCA) target the H+/K+ATPase (proton pump). APCA prevalence and lung H+/K+ATPase expression was never studied in IPF patients. METHODS: We retrospectively collected clinical, lung function and imaging data from APCA positive patients (APCA+IPF) and compared them with APCA negative IPF patients matched on the date of diagnostic assessment...
February 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29413500/evaluation-of-a-respiratory-symptom-diary-for-clinical-studies-of-idiopathic-pulmonary-fibrosis
#17
Elizabeth Dansie Bacci, Sean O'Quinn, Nancy Kline Leidy, Lindsey Murray, Margaret Vernon
BACKGROUND: There are no validated patient diaries for evaluating respiratory symptoms in idiopathic pulmonary fibrosis (IPF). PURPOSE: To evaluate the performance properties of the chronic obstructive pulmonary disease (COPD) Evaluating Respiratory Symptoms™ (E-RS™: COPD) measure in patients with IPF. METHODS: Concept elicitation and cognitive interviews were conducted with IPF patients to evaluate content validity, including comprehensiveness, relevance, and interpretability of E-RS™ items in this patient population...
January 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29413085/validation-of-multidisciplinary-diagnosis-in-ipf
#18
Diego Castillo, Simon Walsh, David M Hansell, Martina Vasakova, Vincent Cottin, Goksel Altinisik, Stefano Palmucci, Martina Sterclova, Sergio Harari, Luca Richeldi, Carlo Vancheri, Athol U Wells
No abstract text is available yet for this article.
February 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29413083/time-for-a-change-is-idiopathic-pulmonary-fibrosis-still-idiopathic-and-only-fibrotic
#19
Paul J Wolters, Timothy S Blackwell, Oliver Eickelberg, James E Loyd, Naftali Kaminski, Gisli Jenkins, Toby M Maher, Maria Molina-Molina, Paul W Noble, Ganesh Raghu, Luca Richeldi, Marvin I Schwarz, Moises Selman, Wim A Wuyts, David A Schwartz
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and typically fatal lung disease characterised by subpleural fibrosis, subepithelial fibroblast foci, and microscopic honeycombing. Although understanding of the pathogenic mechanisms continues to evolve, evidence indicates that distal airway and alveolar epithelial cells are central drivers of the disease. In this Viewpoint, we review the history of naming and classifications used to define the disease now referred to as IPF, in the context of understanding the clinical presentation, causes, and pathogenesis of the disease...
February 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29412521/longitudinal-outcomes-of-patients-enrolled-in-a-phase-ib-clinical-trial-of-the-adipose-derived-stromal-cells-stromal-vascular-fraction-in-idiopathic-pulmonary-fibrosis
#20
Paschalis Ntolios, Eleni Manoloudi, Argyris Tzouvelekis, Evangelos Bouros, Pachalis Steiropoulos, Stavros Anevlavis, Demosthenes Bouros, Marios E Froudarakis
BACKGROUND: Cell based therapies have been used for the management of several diseases, holding promising results. Few studies have evaluated their use in chronic lung diseases. Idiopathic Pulmonary Fibrosis (IPF) remains a lethal disease, although new therapies have emerged the recent years. We have recently published a phase I study of 14 patients receiving endobronchially Adipose-Derived Stem Cells (ADSCs). The aim of the current report is to assess the outcome for our patient population...
February 7, 2018: Clinical Respiratory Journal
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