Common and Distinct Transcriptome and Proteome Expression Patterns from Lungs in Idiopathic Pulmonary Fibrosis (IPF) and Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD)

2019 ◽  
Author(s):  
S. Matson ◽  
J.S. Lee ◽  
W. Ren ◽  
H.R. Collard ◽  
M.A. Matthay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Expression Patterns ◽  
Proteome Expression

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

Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 72 (3) ◽  
pp. 409-419 ◽  
Author(s):  
Daniel J. Kass ◽  
Mehdi Nouraie ◽  
Marilyn K. Glassberg ◽  
Nitya Ramreddy ◽  
Karen Fernandez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Serum Protein ◽  
Protein Biomarkers

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 Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease

2015 ◽  
Vol 9s1 ◽  
pp. CCRPM.S23289 ◽  
Author(s):  
Takafumi Suda
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Acute Exacerbation ◽  
Interstitial Pneumonia ◽  
Usual Interstitial Pneumonia ◽  
Cytotoxic Agents ◽  
Radiological Patterns

Pulmonary involvement is common in rheumatoid arthritis (RA) and affects all the components of the lung. Interstitial lung disease (ILD) is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP) pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.

scholarly journals SAT0040 RISK FACTORS FOR DEVELOPING AND MORTALITY FOR ACUTE EXACERBATION OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 950.2-951
Author(s):  
S. Izuka ◽  
H. Yamashita ◽  
Y. Takahashi ◽  
H. Kaneko
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Acute Exacerbation ◽  
Vascular Diseases ◽  
Collagen Vascular Diseases ◽  
Survivor Group

Background:Among collagen vascular diseases, rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is the most commonly associated with ILD with acute exacerbation (AE) [1]. One study reported that ILD diagnosis at an older age, the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and methotrexate (MTX) use were associated with AE in patients with RA-ILD [2]. However, because these studies included few patients, the risk factors and prognosis of AE in patients with RA-ILD remain unclear. Therefore, this study examined the characteristics of RA-ILD patients with AE, and the variables associated with mortality due to AE of RA-ILD.Objectives:To investigate the risk factors for AE and mortality of RA-ILD.Methods:We retrospectively collected the clinical data of 165 RA-ILD patients admitted to our hospital between July 2010 and October 2019. We compared clinical characteristics between patients who developed AE (AE group) and those who did not (non-AE group), and identified the variables significantly associated with AE occurrence. We also compared the admission characteristics of those who survived (survivor group) and those who died (non-survivor group) after admission for AE. AE was defined using previously proposed criteria [3], which were modified slightly for application to RA-ILD.Results:The mean patient age was 73.6 ± 9.7 years and 97 (71.9%) patients were female. Thirty (22.2%) patients developed AE, of whom thirteen (43.3%) died (mean follow-up, 64.9 months). In univariate analyses UIP pattern and MTX were not associated with AE. However, in multivariate analyses, UIP pattern was associated with AE (OR 2.68, 95% CI 1.10–6.52,p=0.03). Median age (70vs. 80 years,p=0.003), non-use of MTX (70.6%vs. 23.1%,p=0.025), and C reactive protein level (median 9.38vs. 18.12 mg/dL,p=0.02) on admission were significantly higher in patients who died of AE. In the Cox proportional hazard model, UIP pattern (HR 4.67, 95% CI 1.02–21.5,p=0.048) and non-use of MTX (HR 0.16, 95% CI 0.04–0.72,p=0.016) were associated with death.Conclusion:Our data suggest that the UIP pattern is related to AE, and non-use of MTX and UIP pattern are related to death due to AE of RA-ILD.References:[1] Suda T, Kaida Y, Nakamura Y et al. Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases.Respir Med2009;103:846-53.[2] Hozumi H, Nakamura Y, Johkoh T et al. Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study.BMJ Open2013;3:e003132.[3] Collard HR, Moore BB, Flaherty KR et al. Idiopathic pulmonary fibrosis clinical research network investigators. Acute exacerbations of idiopathic pulmonary fibrosis.Am J Respir Crit Care Med2007;176:636-43.Disclosure of Interests:None declared

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