scholarly journals Association of circulating cell-free double-stranded DNA and metabolic derangements in idiopathic pulmonary fibrosis

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217315
Author(s):  
William Whalen ◽  
Mustafa Buyukozkan ◽  
Bethany Moore ◽  
Jong-Seok Moon ◽  
Charles S Dela Cruz ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Rapid Progression ◽  
Healthy Controls ◽  
Double Stranded Dna ◽  
Slow Progressors ◽  
Progression Of Disease

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with unclear aetiology and poorly understood pathophysiology. Although plasma levels of circulating cell-free DNA (ccf-DNA) and metabolomic changes have been reported in IPF, the associations between ccf-DNA levels and metabolic derangements in lung fibrosis are unclear. Here, we demonstrate that ccf-double-stranded DNA (dsDNA) is increased in patients with IPF with rapid progression of disease compared with slow progressors and healthy controls and that ccf-dsDNA associates with amino acid metabolism, energy metabolism and lipid metabolism pathways in patients with IPF.

scholarly journals Acute worsening of native lung fibrosis after single lung transplantation for pulmonary fibrosis: two case reports

2022 ◽  
Vol 16 (1) ◽  
Author(s):  
Tiphaine Goletto ◽  
Sixtine Decaux ◽  
Vincent Bunel ◽  
Gaëlle Weisenburger ◽  
Jonathan Messika ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Transplantation ◽  
Viral Infection ◽  
Lung Fibrosis ◽  
Case Reports ◽  
Rapid Progression ◽  
Single Lung Transplantation ◽  
Native Lung

Abstract Background In patients receiving single lung transplantation for idiopathic pulmonary fibrosis, worsening of fibrosis of the native lung is usually progressive over time, with no significant effects on gas exchange. Case presentation Here, we describe the cases of two Caucasian male recipients of single lung transplants for idiopathic pulmonary fibrosis, 65 and 62 years of age, who exhibited acute worsening of lung fibrosis after an episode of serious viral infection (cytomegalovirus primo-infection in one case and COVID-19 in the other). In both cases, along with opacification of the native lung over several days, the patients presented acute respiratory failure that required the use of high-flow nasal oxygen therapy. Eventually, hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung. Conclusion We conclude that acute worsening of fibrosis on the native lung secondary to a severe viral infection should be added to the list of potential complications developing on the native lung after single lung transplantation for idiopathic pulmonary fibrosis.

scholarly journals Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis

Respirology ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 437-444 ◽  
Author(s):  
Martin Thomas Gaugg ◽  
Anna Engler ◽  
Lukas Bregy ◽  
Yvonne Nussbaumer‐Ochsner ◽  
Lara Eiffert ◽  
...  
Keyword(s):  
Amino Acid ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Breath Analysis

scholarly journals SAT0098 TREATMENT OF A COHORT OF PATIENTS WITH INTERSTITIAL LUNG DISEASE AND RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 982.2-982
Author(s):  
C. Aguilera Cros ◽  
M. Gomez Vargas ◽  
R. J. Gil Velez ◽  
J. A. Rodriguez Portal
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Latin American ◽  
Usual Interstitial Pneumonia ◽  
Specific Treatment ◽  
American Thoracic Society ◽  
Rapid Progression

Background:There is no specific treatment for interstitial lung disease (ILD) secondary to Rheumatoid Arthritis (RA) other than the treatment of RA without extra-articular involvement. Current regimens usually include corticosteroid therapy with or without immunosuppressants (IS), there is no consensus for the treatment.Objectives:To analyze the different treatment regimens in a cohort of patients with ILD and RA in our clinical practice.Methods:Descriptive study of 57 patients treated in our Hospital (1/1/2018 until 12/31/2019) with a diagnosis of RA (ACR 2010 criteria) and secondary ILD.The most recent American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines define three HRCT (High Resolution Computed Tomography) patterns of fibrosing lung disease in the setting of idiopathic pulmonary fibrosis (IPF): definite Usual Interstitial pneumonia (UIP) (traction bronchiectasis and honeycombing), possible UIP and inconsistent with UIP. The distinction between definite UIP and possible UIP in these to the presence or absence of honeycombing. Approved by the Ethics Committee.Quantitative variables are expressed as mean (SD) and dichotomous variables as percentages (%). Statistical analysis with SPSS version 21.Results:21 men and 36 women were included, with a mean age of 69 ± 10 years (mean ± SD), history of smoking (smokers 14%, non-smokers 43%, former smokers 42%). Clinical ILD at diagnosis (dyspnea 61%, dry cough 56%, crackling 70%, acropachy 7%). 84% were positive rheumatoid factor and 70% positive anticitrullinated protein antibody.Diagnosis of ILD by HRCT in 100% of patients with different patterns: defined UIP 26 (45%), probable UIP 2 (3%) and not UIP 29 (50%). The diagnosis of ILD was confirmed by biopsy in 12 patients.79% underwent (T) treatment prior to the diagnosis of ILD with glucocorticoids and disease-modifying drugs (DMARD). Among the traditional DMARDs used were: Methotrexate 68% (there were no cases of MTX pneumonitis), Leflunomide 47%, Hydroxychloroquine 26% and Sulfasalazine 21%. Biological therapy in 15 patients: Etanercept 19%, Adalimumab 5%, Infliximab 3% and Certolizumab 2%. Two patients presented an exacerbation and rapid progression of the ILD during the T with Etanercept with the final result of death.T with IS after the diagnosis of ILD in 80% of patients (Azathioprine 15, Rituximab 14, Abatacept 10, Tocilizumab 4, Sarilumab 1, Mofetil mycophenolate 1 and Cyclophosphamide 1).Two patients with defined UIP perform T with antifibrotic: 1st Nintedanib (INBUILD Trial, This article was published on September 29, 2019, at NEJM.org) 2nd Pirfenidone (initial diagnosis of IPF Idiopathic Pulmonary Fibrosis and subsequent of seropositive RA with UIP). Both improved greater than 10% in forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) in the 6 months after onset of T.Conclusion:Our results, in general, agree with what is published in the literature. Prospective, multicentre and larger sample studies are necessary to better define which patients would benefit more from IS T or antifibrotic T (or if the antifibrotic should be added to the previous IS).Disclosure of Interests:None declared

scholarly journals Evaluation of Regional Pulmonary Ventilation in Spontaneously Breathing Patients with Idiopathic Pulmonary Fibrosis (IPF) Employing Electrical Impedance Tomography (EIT): A Pilot Study from the European IPF Registry (eurIPFreg)

2021 ◽  
Vol 10 (2) ◽  
pp. 192
Author(s):  
Ekaterina Krauss ◽  
Daniel van der Beck ◽  
Isabel Schmalz ◽  
Jochen Wilhelm ◽  
Silke Tello ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Electrical Impedance Tomography ◽  
Spontaneous Breathing ◽  
Electrical Impedance ◽  
Statistical Significance ◽  
Pulmonary Ventilation ◽  
Healthy Controls ◽  
Impedance Tomography ◽  
Spontaneously Breathing

Objectives: In idiopathic pulmonary fibrosis (IPF), alterations in the pulmonary surfactant system result in an increased alveolar surface tension and favor repetitive alveolar collapse. This study aimed to assess the usefulness of electrical impedance tomography (EIT) in characterization of regional ventilation in IPF. Materials and methods: We investigated 17 patients with IPF and 15 healthy controls from the University of Giessen and Marburg Lung Center (UGMLC), Germany, for differences in the following EIT parameters: distribution of ventilation (TID), global inhomogeneity index (GI), regional impedance differences through the delta of end-expiratory lung impedance (dEELI), differences in surface of ventilated area (SURF), as well as center of ventilation (CG) and intratidal gas distribution (ITV). These parameters were assessed under spontaneous breathing and following a predefined escalation protocol of the positive end-expiratory pressure (PEEP), applied through a face mask by an intensive care respirator (EVITA, Draeger, Germany). Results: Individual slopes of dEELI over the PEEP increment protocol were found to be highly significantly increased in both groups (p < 0.001) but were not found to be significantly different between groups. Similarly, dTID slopes were increasing in response to PEEP, but this did not reach statistical significance within or between groups. Individual breathing patterns were very heterogeneous. There were no relevant differences of SURF, GI or CGVD over the PEEP escalation range. A correlation of dEELI to FVC, BMI, age, or weight did not forward significant results. Conclusions: In this study, we did see a significant increase in dEELI and a non-significant increase in dTID in IPF patients as well as in healthy controls in response to an increase of PEEP under spontaneous breathing. We propose the combined measurements of EIT and lung function to assess regional lung ventilation in spontaneously breathing subjects.

scholarly journals Idiopathic pulmonary fibrosis: unmasking cryptogenic environmental factors

2019 ◽  
Vol 53 (2) ◽  
pp. 1801699 ◽  
Author(s):  
Coralynn Sack ◽  
Ganesh Raghu
Keyword(s):  
Environmental Factors ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Treatment Modality ◽  
Unknown Origin ◽  
Clinical Implications ◽  
High Morbidity ◽  
Novel Treatment ◽  
Progression Of Disease ◽  
Fibrotic Lung Disease

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown origin that is associated with high morbidity and mortality. In this perspective, we briefly review the current understanding of the pathophysiology of IPF and the importance of environmental triggers as a precipitant of disease. We discuss occult intrinsic and extrinsic environmental factors that affect the lung microenvironment and may contribute to the development and progression of disease. The clinical implications of this framework need to be further elucidated, because prompt identification and elimination of occult exposures may represent a novel treatment modality.

scholarly journals Effects of Nintedanib on Quantitative Lung Fibrosis Score in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 14 (1) ◽  
pp. 22-31
Author(s):  
Lisa Lancaster ◽  
Jonathan Goldin ◽  
Matthias Trampisch ◽  
Grace Hyun Kim ◽  
Jonathan Ilowite ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Lung Fibrosis ◽  
Open Label ◽  
High Resolution Computed Tomography ◽  
Double Blind ◽  
Phase Iiib ◽  
Exploratory Data ◽  
Relative Change

Background: Nintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied. Objective: We conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF. Methods: 113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory. Results: Adjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: −9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: −1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were −14.2 mL and −83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: −8.7, 146.8]). Conclusion: Exploratory data suggest that in patients with IPF, 6 months’ treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.

Effect of nintedanib on hyaluronic acid metabolism in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis

2015 ◽  
Author(s):  
Katrin Hostettler ◽  
Eleni Papakonstantinou ◽  
Ioannis Klagas ◽  
Ioannis Bonovolias ◽  
Michael Tamm ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Acid Metabolism ◽  
Lung Fibroblasts

scholarly journals Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Kosuke Hamai ◽  
Hiroshi Iwamoto ◽  
Nobuhisa Ishikawa ◽  
Yasushi Horimasu ◽  
Takeshi Masuda ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Bacterial Pneumonia ◽  
Protein A ◽  
Survival Rates ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Survival Prediction ◽  
Healthy Controls ◽  
Disease Markers

Background.Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D.Methods.The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF.Results.The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic.Conclusions.The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF.

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