scholarly journals Predictors of long-term prognosis in rheumatoid arthritis-related interstitial lung disease

2021 ◽  
Author(s):  
Juan Chen ◽  
Yaqiong Chen ◽  
Dehao Liu ◽  
Yihua Lin ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Serum Protein ◽  
Serum Proteins ◽  
Pulmonary Function Tests ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Binary Logistic Regression Model ◽  
Longitudinal Outcome ◽  
Over Time

Abstract The aim of the study was to identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease（RA-ILD). 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on changes in Quantitative Modified HRCT scores and PFTs over time. Specific serum protein biomarkers were assessed in serum samples at baseline and Year 5 by Multiplex enzyme-linked immunosorbent assays (ELISAs). At Year 5, 32% of patients demonstrated progressive RA-ILD, 35% were stable, and 33% improved. Baseline age and rheumatoid factor (RF) were significantly different between RA-ILD outcomes of progression vs. no-progression (p< 0.05). Changes in levels of CXCL11/I-TAC and MMP13 over 5 years also distinguished pulmonary outcomes (p< 0.05). A final binary logistic regression model revealed that baseline age and changes in serum MMP13 were associated with RA-ILD progression at Year 5 (p< 0.05), with an AUC of 0.7569. Collectively, these analyses demonstrated that baseline clinical variables (age, RF) and shifts in levels of selected serum proteins (CXCL11/I-TAC, MMP13) were strongly linked to RA-ILD outcome over time.

scholarly journals Predictors of Long-term Prognosis in Rheumatoid Arthritis-related Interstitial Lung Disease

2021 ◽  
Author(s):  
juan chen ◽  
Yaqiong Chen ◽  
Dehao Liu ◽  
Yihua Lin ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Serum Protein ◽  
Multivariate Analyses ◽  
Pulmonary Function Tests ◽  
Operating Characteristics ◽  
Protein Biomarkers ◽  
Longitudinal Outcome ◽  
Long Term Prognosis

Abstract Objective. To identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease（RA-ILD).Methods. 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on the changes in Quantitative Modified HRCT scores and PFTs over time. Specific serum protein biomarkers were assessed in serum samples at baseline and Year 5 by Multiplex enzyme-linked immunosorbent assays (ELISAs).Results. Based on changes of Quantitative Modified HRCT scores, 32% of patients demonstrated progressive RA-ILD, 35% were stable, and 33% improved. Baseline age and rheumatoid factor (RF) were significantly different between RA-ILD outcomes of progression versus no-progression (p=0.002 and 0.027, respectively). In multivariate analyses, changes in the serum levels of CXCL11/I-TAC and MMP13 from Year 0 to Year 5 (log Year 5-log Year 0) also distinguished RA-ILD outcomes (p< 0.05). A final binary logistic regression model revealed that baseline age and changes of MMP13 were associated with RA-ILD progression (Yes vs. No) at Year 5 (p< 0.05). Receiver Operating Characteristics analysis indicated that these variables predicted progression with an AUC of 0.7569.Conclusion. While baseline age and RF predicted RA-ILD outcomes of progression versus no-progression, changed levels of CXCL11/I-TAC and MMP-13 over 5 years were also correlated with long-term prognosis of RA-ILD. In multivariate analyses, baseline age and changed levels of MMP-13 were associated with the risk of progression of RA-ILD.Trial registrationNo

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

Chest wall muscle atrophy as a contributory factor for forced vital capacity decline in systemic sclerosis-associated interstitial lung disease

Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 250-255
Author(s):  
Takashi Nawata ◽  
Yuichiro Shirai ◽  
Mikito Suzuki ◽  
Masataka Kuwana
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Chest Wall ◽  
Muscle Atrophy ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Pulmonary Function Tests ◽  
Potential Contribution ◽  
Muscle Area ◽  
Chest Wall Muscle

Abstract Objective To investigate the potential contribution of accessory respiratory muscle atrophy to the decline of forced vital capacity (FVC) in patients with SSc-associated interstitial lung disease (ILD). Methods This single-centre, retrospective study enrolled 36 patients with SSc-ILD who underwent serial pulmonary function tests and chest high-resolution CT (HRCT) simultaneously at an interval of 1–3 years. The total extent of ILD and chest wall muscle area at the level of the ninth thoracic vertebra on CT images were evaluated by two independent evaluators blinded to the patient information. Changes in the FVC, ILD extent, and chest wall muscle area between the two measurements were assessed in terms of their correlations. Multiple regression analysis was conducted to identify the independent contributors to FVC decline. Results Interval changes in FVC and total ILD extent were variable among patients, whereas chest wall muscle area decreased significantly with time (P=0.0008). The FVC change was negatively correlated with the change in ILD extent (r=−0.48, P=0.003) and was positively correlated with the change in the chest wall muscle area (r = 0.53, P=0.001). Multivariate analysis revealed that changes in total ILD extent and chest wall muscle area were independent contributors to FVC decline. Conclusion In patients with SSc-ILD, FVC decline is attributable not only to the progression of ILD but also to the atrophy of accessory respiratory muscles. Our findings call attention to the interpretation of FVC changes in patients with SSc-ILD.

scholarly journals Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mouhamad Nasser ◽  
Sophie Larrieu ◽  
Loic Boussel ◽  
Salim Si-Mohamed ◽  
Fabienne Bazin ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Healthcare Resource ◽  
Pulmonary Function Tests ◽  
Healthcare Services ◽  
Resource Utilisation ◽  
High Resolution Computed Tomography ◽  
Healthcare Database ◽  
Healthcare Resource Utilisation ◽  
Kaplan Meier

Abstract Background There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database. Methods The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD. Results We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan–Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622–54,287) and the median annual cost per patient was €18,362 (6856–52,026), of which €11,784 (3003–42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests. Conclusions This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842

scholarly journals Serum Metabolomic Profiles of Rheumatoid Arthritis Patients With Acute-Onset Diffuse Interstitial Lung Disease

2019 ◽  
Vol 14 ◽  
pp. 117727191987047 ◽  
Author(s):  
Hiroshi Furukawa ◽  
Shomi Oka ◽  
Kota Shimada ◽  
Atsushi Hashimoto ◽  
Akiko Komiya ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Stable State ◽  
Area Under The Curve ◽  
Stable Condition ◽  
Hierarchical Cluster ◽  
Acute Onset ◽  
Serum Samples ◽  
Drug Induced

Objective: Acute-onset diffuse interstitial lung disease (AoDILD) includes acute exacerbation of interstitial lung disease (ILD), drug-induced ILD, and Pneumocystis pneumonia, and frequently occurs in patients with rheumatoid arthritis (RA). Since AoDILD causes a poor prognosis in RA, biomarkers for AoDILD were eagerly desired. Metabolomic analyses were extensively performed in cancer patients and successfully generated better diagnostic biomarkers. In the present study, serum metabolomic profiles of AoDILD in RA were investigated to generate better potential metabolomic biomarkers. Methods: Serum samples of 10 RA patients with AoDILD were collected on admission and in a stable state, more than 3 months before the admission. Serum metabolomic analyses were conducted on the samples from these RA patients with AoDILD. Results: Apparently distinct serum metabolomic profiles in AoDILD were not observed in univariate or hierarchical cluster analyses. Partial least squares-discriminant analysis (PLS-DA) was performed to select candidate metabolites based on variable importance in projection (VIP) scores. The PLS-DA model generated from the four metabolites with VIP scores more than 2.25 (mannosamine, alliin, kynurenine, and 2-hydroxybutyric acid) could successfully discriminate AoDILD from the stable condition (area under the curve: 0.962, 95% confidence interval: 0.778–1.000). Conclusion: It was demonstrated that metabolomic profiling was useful to generate better biomarkers in AoDILD.

FRI0576 IDENTIFICATION OF SERUM PROTEIN BIOMARKERS ASSOCIATED WITH RA DISEASE SEVERITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 891-892
Author(s):  
D. Galbraith ◽  
M. Caliskan ◽  
O. Jabado ◽  
S. Hu ◽  
R. Fleischmann ◽  
...  
Keyword(s):  
Disease Severity ◽  
Serum Protein ◽  
Dynamic Range ◽  
Serum Proteins ◽  
Differentially Expressed ◽  
Protein Abundance ◽  
Healthy Individuals ◽  
Protein Biomarkers ◽  
Research Support ◽  
Baseline Serum

Background:RA is a systemic autoimmune disease with heterogeneous manifestation. Recent advances in serum proteomics, such as the SomaScan®platform (SomaLogic, Inc., Boulder, USA), allow for a deeper exploration of the protein biomarkers associated with RA and a better understanding of the molecular aetiology of the disease.Objectives:To characterise the differences in baseline serum proteome of patients with RA (enrolled in the Phase IIIb Abatacept vs adaliMumab comParison in bioLogic-naïvERA subjects with background MTX [AMPLE] study)1compared with a healthy population, and to identify serum protein biomarkers associated with disease severity and radiographic progression.Methods:Patients in the AMPLE study had an inadequate response to MTX and were naïve to biologic DMARDs. Protein abundance was assessed in baseline serum samples from 440 AMPLE study patients and 123 healthy individuals with matching demographics using the SomaScan®platform, with 5000+ slow off-rate modified aptamers and up to 8 log of dynamic range.2Differential abundance testing was performed using linear models to identify differences in protein abundance in patients with RA vs healthy individuals. A separate analysis using a linear model was conducted in only the patients with RA to identify the proteins associated with DAS28 (CRP) and TSS. Pathway analyses were performed for proteins significantly (false discovery rate-adjusted p value <0.05) associated with RA and the disease severity measurements to identify over-representation of the molecular pathways.Results:Compared with healthy individuals, >2000 serum proteins were significantly differentially expressed in patients with RA, including many proteins that have been associated with RA (e.g. serum amyloid A [SAA], CRP) and complement. Most of the protein expression differences were of small magnitude (fold change <2). Proteins that were differentially expressed between patients with RA and healthy individuals were enriched in interleukin signalling, neutrophil degranulation, platelet activation/degranulation and extracellular matrix organisation pathways. DAS28 (CRP) was significantly associated with several biomarkers, including SAA, fibrinogen and CRP; in general, proteins associated with DAS28 (CRP) were most strongly enriched in the platelet activation/degranulation pathways (Figure 1), also seen in patients with RA vs healthy individuals. Additionally, many proteins were significantly associated with TSS, including SAA, matrix metalloproteinase-3 and cartilage acidic protein 1. Here, the proteins were most strongly enriched in the extracellular matrix remodelling pathways (Figure 2).Conclusion:Our study revealed that thousands of serum proteins are differentially expressed and several pathways are dysregulated between patients with RA and healthy individuals. Additional pathways were identified that reflect disease severity, including joint damage, distinct from those pathways associated with the disease. The SomaScan®platform provides a unique proteomic tool with a wide dynamic range for the identification of serum protein biomarkers associated with RA and disease severity. Proteomic signatures should be considered in clinical trials to better understand disease pathogenesis and predict risk in response to treatment.References:[1]Schiff M, et al.Ann Rheum Dis2014;73:86–94.[2]Gold L, et al.PLoS One2010;5:e15004.Acknowledgments:Rachel Rankin (medical writing, Caudex; funding: Bristol-Myers Squibb)Disclosure of Interests:David Galbraith Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Minal Caliskan Employee of: Bristol-Myers Squibb, Omar Jabado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sarah Hu Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Michael Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo, Lily, Sanofi/Regeneron, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo, Gilead, Horizon, Lily, Pfizer, Roche, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Michael A Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sheng Gao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

scholarly journals Lung ultrasound B-lines and serum KL-6 correlate with the severity of idiopathic inflammatory myositis-associated interstitial lung disease

Rheumatology ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 2024-2029 ◽  
Author(s):  
Yukai Wang ◽  
Shaoqi Chen ◽  
Jianqun Lin ◽  
Xuezhen Xie ◽  
Shijian Hu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Lung Ultrasound ◽  
Pulmonary Function Tests ◽  
Forced Expiratory Volume ◽  
Inflammatory Myositis ◽  
Idiopathic Inflammatory Myositis ◽  
Function Tests ◽  
B Lines

Abstract Objective Idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) significantly increases morbidity and mortality. Lung ultrasound B-lines and Krebs von den Lungen-6 (KL-6) are identified as new sonographic and serum markers of ILD, respectively. The aim of our work was to assess the role of B-lines and KL-6 as markers of the severity of IIM-ILD. For this purpose, the correlation among B-lines score, serum KL-6 levels, high-resolution CT (HRCT) score, and pulmonary function tests were investigated in IIM-ILD patients. Methods Thirty-eight patients with IIM-ILD underwent chest HRCT scans, lung ultrasound and pulmonary function tests (independently performed within 1 week) examination. To assess severity and extent of ILD at HRCT, the Warrick score was used. The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 50 scanning sites. Serum KL-6 levels (U/ml) was measured by chemiluminescent enzyme immunoassay. Results A significant correlation was found between the B-lines score and serum KL-6 levels (r = 0.43, P &lt; 0.01), and between the Warrick score and serum KL-6 levels (r = 0.45, P &lt; 0.01). A positive correlation between B-lines score and the Warrick score (r = 0.87, P &lt; 0.0001) was also confirmed. Both B-lines score and KL-6 levels inversely correlated to diffusion capacity for carbon monoxide (r = −0.77, P &lt; 0.0001 and r = −0.42, P &lt; 0.05, respectively) and total lung capacity (r = −0.73, P &lt; 0.0001 and r = −0.36, P &lt; 0.05, respectively). Moreover, B-lines correlated inversely with forced vital capacity (r = −0.73, P &lt; 0.0001), forced expiratory volume in 1 s (r = −0.69, P &lt; 0.0001). Conclusion B-lines score and serum KL-6 levels correlate with HRCT findings and pulmonary function tests, supporting their use as measures of IIM-ILD severity.

scholarly journals Serum metabolites as biomarkers in systemic sclerosis-associated interstitial lung disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
C. Meier ◽  
K. Freiburghaus ◽  
C. Bovet ◽  
J. Schniering ◽  
Y. Allanore ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Clinical Care ◽  
Adenosine Monophosphate ◽  
Serum Samples ◽  
Serum Metabolites ◽  
Routine Clinical Care ◽  
Individual Profiles ◽  
Prognosis Score

AbstractSystemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death. While targeted therapies are emerging, biomarkers for sub-stratifying patients based on individual profiles are lacking. Herein, we investigated how levels of serum metabolites correlated with different stages of SSc and SSc-ILD. Serum samples of patients with SSc without ILD, stable and progressive SSc-ILD as well as of healthy controls (HC) were analysed using liquid targeted tandem mass spectrometry. The best discriminating profile consisted of 4 amino acids (AA) and 3 purine metabolites. l-tyrosine, l-tryptophan, and 1-methyl-adenosine distinguished HC from SSc patients. l-leucine, l-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. In SSc-ILD, both, l-leucine and xanthosine negatively correlated with changes in FVC% predicted. Additionally, xanthosine was negatively correlated with changes in DLco% predicted and positively with the prognostic GAP index. Validation of l-leucine and l-isoleucine by an enzymatic assay confirmed both the sub-stratification of SSc-ILD patients and correlation with lung function and prognosis score. Serum metabolites may have potential as biomarkers for discriminating SSc patients based on the presence and severity of ILD. Confirmation in larger cohorts will be needed to appreciate their value for routine clinical care.

scholarly journals EP29 An evaluation of the use of baseline pulmonary function tests in the detection of interstitial lung disease in patients newly diagnosed with rheumatoid arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Ashraful Haque ◽  
Rachael Kilding ◽  
Ruth Smith ◽  
Sameena Khalid ◽  
Robert Sandler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Newly Diagnosed ◽  
Tertiary Centre ◽  
Function Tests ◽  
Low Sensitivity ◽  
New Diagnosis

Abstract Background Interstitial lung disease (ILD) is a serious extra-articular manifestation of rheumatoid arthritis (RA). Risk factors include smoking, the presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (CCP). Pulmonary function tests (PFT) show reduced carbon monoxide diffusion capacity (DLCO) early and reduced forced vital capacity (FVC) later in disease. HRCT is the gold standard diagnostic test while chest X-ray (CXR) has low sensitivity. PFT are routinely performed in the majority of RA patients at baseline at our tertiary centre. The aim of this study was to evaluate the frequency of abnormal PFT, specificity for ILD and influence on subsequent decision-making in patients newly diagnosed with RA. Methods A retrospective analysis was undertaken of patients with a new diagnosis of RA between January 2016 and December 2017. Patients meeting the ACR (2010) criteria for RA, with baseline PFT data available were included. Clinic letters and the hospital electronic records were used to obtain the data. Results 139 patients were included in the data analysis (Table 1). 23 patients had DLCO &lt;70% predicted, while 7 patients had an FVC &lt;80% predicted. Patients with abnormal PFT were more likely to be older, female, seropositive and to have smoked. Of the patients with DLCO &lt;70%, CXR was abnormal in 6 patients with changes suggesting ILD in 2 patients. 13 patients had HRCT and 7/13 patients had evidence of ILD and 6/13 patients had significant emphysema on CXR or HRCT. 1 patient with DLCO of 82% had changes of ILD on a CT scan organised for another reason. Methotrexate was commenced in 19/23 patients with DLCO&lt;70% and discontinued in 2 patients for respiratory reasons. Conclusion This evaluation suggests baseline PFT are more sensitive than baseline CXR in detecting ILD but that a DLCO &lt;70% is not specific for this diagnosis. The abnormal PFT lead to HRCT being requested in 13/24 patients, of whom 7 had ILD which had not been identified by CXR in 5 patients. Baseline PFT are also useful as a reference point in patients who go on to develop respiratory symptoms at a later point in their illness. Disclosures A. Haque None. R. Kilding None. R. Smith None. S. Khalid None. R. Sandler None. M. Cox None. T. Hendry None. A. Flores-martin None. K. Lindop None. J. Maxwell None.

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