scholarly journals MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

2017 ◽  
Vol 3 (1) ◽  
pp. 00074-2016 ◽  
Author(s):  
Yasmina Bauer ◽  
Eric S. White ◽  
Simon de Bernard ◽  
Peter Cornelisse ◽  
Isabelle Leconte ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Disease Progression ◽  
Therapeutic Interventions ◽  
Normal Lung ◽  
Type I ◽  
Objective Evidence ◽  
Baseline Levels

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease.Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF.In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4.MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

scholarly journals Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
H. Jessen ◽  
N. Hoyer ◽  
T. S. Prior ◽  
P. Frederiksen ◽  
M. A. Karsdal ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Real World ◽  
Progressive Disease ◽  
Type Iii Collagen ◽  
Type I ◽  
Collagen Turnover ◽  
Baseline Levels ◽  
Longitudinal Biomarker

Abstract Background Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. Methods Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not. Results Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. Conclusion Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

scholarly journals Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease

2019 ◽  
Vol 316 (3) ◽  
pp. L487-L497 ◽  
Author(s):  
Jie Zhang ◽  
Dan Wang ◽  
Lei Wang ◽  
Shaohua Wang ◽  
Anja C. Roden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
T Helper 17 ◽  
Direct Role ◽  
Lung Biopsies

Interleukin (IL)-17 is a T helper 17 cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, its role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA-associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with IPF and RA-ILD to determine IL-17A receptor (IL-17RA) expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17RA and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast transdifferentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on NF-κB-mediated signaling. In addition, inhibiting Janus activated kinase (JAK) 2 by either siRNA or a selective pharmacological inhibitor, AZD1480—but not a JAK1/JAK3 selective inhibitor, tofacitinib—also significantly reduced this IL-17A-induced fibrogenic response. Lung biopsies of RA-ILD patients demonstrate significantly higher IL-17RA expression in areas of fibroblast accumulation and fibrosis, compared with either IPF or normal lung tissue. These observations support a direct role for IL-17A in lung fibrosis that may be particularly relevant in the context of RA-ILD.

scholarly journals Disparate Interferon Signaling and Shared Aberrant Basaloid Cells in Single-Cell Profiling of Idiopathic Pulmonary Fibrosis and Systemic Sclerosis-Associated Interstitial Lung Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Eleanor Valenzi ◽  
Tracy Tabib ◽  
Anna Papazoglou ◽  
John Sembrat ◽  
Humberto E. Trejo Bittar ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Single Cell ◽  
Alveolar Type ◽  
Type I ◽  
Interferon Signaling ◽  
Mesenchymal Transition

Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) differ in the predominant demographics and identified genetic risk alleles of effected patients, however both diseases frequently progress to respiratory failure and death. Contrasting advanced SSc-ILD to IPF provides insight to the role dysregulated immunity may play in pulmonary fibrosis. To analyze cell-type specific transcriptome commonalities and differences between IPF and SSc-ILD, we compared single-cell RNA-sequencing (scRNA-seq) of 21 explanted lung tissue specimens from patients with advanced IPF, SSc-ILD, and organ donor controls. Comparison of IPF and SSc-ILD tissue identified divergent patterns of interferon signaling, with interferon-gamma signaling upregulated in the SPP1hi and FABP4hi macrophages, cytotoxic T cells, and natural kill cells of IPF, while type I interferon signaling and production was upregulated in the corresponding SSc-ILD populations. Plasmacytoid dendritic cells were found in diseased lungs only, and exhibited upregulated cellular stress pathways in SSc-ILD compared to IPF. Alveolar type I cells were dramatically decreased in both IPF and SSc-ILD, with a distinct transcriptome signature separating these cells by disease. KRT5-/KRT17+ aberrant basaloid cells exhibiting markers of cellular senescence and epithelial-mesenchymal transition were identified in SSc-ILD for the first time. In summary, our study utilizes the enriched capabilities of scRNA-seq to identify key divergent cell types and pathways between IPF and SSc-ILD, providing new insights into the shared and distinct mechanisms between idiopathic and autoimmune interstitial lung diseases.

Turnover of Type I and III Collagen Predicts Progression of Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Henrik Jessen ◽  
Nils Hoyer ◽  
Thomas Prior ◽  
Peder Frederiksen ◽  
Morten Karsdal ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Real World ◽  
Progressive Disease ◽  
Type Iii Collagen ◽  
Type I ◽  
Collagen Turnover ◽  
Baseline Levels ◽  
Longitudinal Biomarker

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. Methods: Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as >5% decline in forced vital capacity (FVC) and/or >10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not.Results: Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P=0.038) and PRO-C3 (P=0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. Conclusion: Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

scholarly journals Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging

2021 ◽  
Vol 10 (12) ◽  
pp. 2663
Author(s):  
Jonathan H. Chung ◽  
Ayodeji Adegunsoye ◽  
Brenna Cannon ◽  
Rekha Vij ◽  
Justin M. Oldham ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Quantitative Imaging ◽  
Multivariable Analysis ◽  
Normal Lung ◽  
Derivation Cohort

A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of this multicenter study was to assess whether quantitative imaging data differ between IPF and CTD-ILD in the setting of UIP. Patients evaluated at two medical centers with CTD-ILD or IPF and a UIP pattern on CT or pathology served as derivation and validation cohorts. Chest CT data were quantitatively analyzed including total volumes of honeycombing, reticulation, ground-glass opacity, normal lung, and vessel related structures (VRS). VRS was compared with forced vital capacity percent predicted (FVC%) and percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO%). There were 296 subjects in total, with 40 CTD-ILD and 85 IPF subjects in the derivation cohort, and 62 CTD-ILD and 109 IPF subjects in the validation cohort. VRS was greater in IPF across the cohorts on univariate (p < 0.001) and multivariable (p < 0.001–0.047) analyses. VRS was inversely correlated with DLCO% in both cohorts on univariate (p < 0.001) and in the derivation cohort on multivariable analysis (p = 0.003) but not FVC%. Total volume of normal lung was associated with DLCO% (p < 0.001) and FVC% (p < 0.001–0.009) on multivariable analysis in both cohorts. VRS appears to have promise in differentiating CTD-ILD from IPF. The underlying pathophysiological relationship between VRS and ILD is complex and is likely not explained solely by lung fibrosis.

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 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 Clinicoserological features of antisynthetase syndrome (ASyS)-associated interstitial lung disease presenting to respiratory services: comparison with idiopathic pulmonary fibrosis and ASyS diagnosed in rheumatology services

2021 ◽  
Vol 8 (1) ◽  
pp. e000829
Author(s):  
Shaney L Barratt ◽  
Havra H Adamali ◽  
Caroline Cotton ◽  
Ben Mulhearn ◽  
Hina Iftikhar ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Trna Synthetase ◽  
Musculoskeletal Symptoms ◽  
Antisynthetase Syndrome ◽  
Cytoplasmic Staining ◽  
Phenotypic Differences ◽  
Lung Physiology

IntroductionAntisynthetase syndrome (ASyS) is a rare autoimmune connective tissue disease (CTD), associated with autoantibodies targeting tRNA synthetase enzymes, that can present to respiratory (interstitial lung disease (ILD)) or rheumatology (myositis, inflammatory arthritis and systemic features) services. The therapeutic management of CTD-associated ILD and idiopathic pulmonary fibrosis (IPF) differs widely, thus accurate diagnosis is essential.MethodsWe undertook a retrospective, multicentre observational cohort study designed to (1) evaluate differences between ASyS-associated ILD with IPF, (2) phenotypic differences in patients with ASyS-ILD presenting to respiratory versus rheumatology services, (3) differences in outcomes between ASySassociated with Jo-1 versus non-Jo-1 autoantibodies and (4) compare long-term outcomes between these groups.ResultsWe identified 76 patients with ASyS-ILD and 78 with IPF. Patients with ASyS were younger at presentation (57 vs 77 years, p<0.001) with a female predominance (57% vs 33%, p=0.006) compared with IPF. Cytoplasmic staining on indirect immunofluorescence was a differentiating factor between ASyS and IPF (71% vs 0%, p<0.0001). Patients with ASyS presenting initially to respiratory services (n=52) had a higher prevalence of ASyS non-Jo-1 antibodies and significantly fewer musculoskeletal symptoms/biochemical evidence of myositis, compared with those presenting to rheumatology services (p<0.05), although lung physiology was similar in both groups. There were no differences in high-resolution CT appearances or outcomes in those with Jo-1 versus non-Jo-1 ASyS-ILD.ConclusionsExtended autoimmune serology is needed to evaluate for ASyS autoantibodies in patients presenting with ILD, particularly in younger female patients. Musculoskeletal involvement is common in ASyS (typically Jo-1 autoantibodies) presenting to rheumatology but the burden of ILD is similar to those presenting to respiratory medicine.

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