Biomarkers for interstitial lung disease and acute-onset diffuse interstitial lung disease in rheumatoid arthritis.
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ABSTRACT:
SUBMITTER: Furukawa H
PROVIDER: S-EPMC8216360 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveAcute-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.MethodsSerum 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.ResultsApparently 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).ConclusionIt was demonstrated that metabolomic profiling was useful to generate better biomarkers in AoDILD.
| S-EPMC6709435 | biostudies-literature
Project description:ObjectiveInterstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication.MethodsPatients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA-no ILD, RA-mild ILD, or RA-advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest.ResultsMMP-7 and interferon-γ-inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA-no ILD, 41 RA-ILD, 42 RA-indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA-no ILD, 49 RA-ILD, 15 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses.ConclusionLevels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.
| S-EPMC4624107 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a common systemic autoimmune disease whose fibro-inflammatory manifestations may affect a number of tissues and organs, including the lungs. In fact, interstitial lung disease (ILD) is a leading cause of mortality among patients with RA. RA-related interstitial lung disease (RA-ILD) most often presents in an injury pattern called usual interstitial pneumonia (UIP), which portends a relatively worse prognosis than other less commonly occurring patterns of RA-ILD, like non-specific interstitial pneumonia (NSIP). Biomarkers from serum or bronchoalveolar lavage fluid could aid in the identification of patients at risk for RA-ILD, the detection of patients most likely to develop the UIP pattern of RA-ILD, and the prediction of disease behaviour over time. Notably, the use of highly sensitive serologic biomarkers, including rheumatoid factor (RF) and antibodies targeting cyclic citrullinated peptides, while somewhat specific for RA joint disease, have only limited utility as biomarkers for RA-ILD. Candidate biomarkers for RA-ILD include these and other autoantibodies as well as certain genes and molecules that hold promise as biomarkers in other forms of ILD. In this manuscript, we summarize the state of knowledge on biomarkers for the development and progression of RA-ILD.
| S-EPMC6800546 | biostudies-literature
Project description:BackgroundInterstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases.MethodsA solid-phase antibody array was used for screening 274 biomarkers in pooled sera from collagen disease patients in the AoDILD state and in the stable state. Biomarkers in individual sera were detected without pooling by bead-based immunoassay.ResultsThe serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinase (TIMP)-1, osteopontin, interleukin (IL)-2 receptor ? (IL-2R?), and IL-1 receptor antagonist were significantly increased in AoDILD, but TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state. This tendency was also observed in RA patients with AoDILD. Moreover, serum IL-6 level was significantly increased in the AoDILD state in patients with acute exacerbation of ILD (AE-ILD). Serum TIMP-1 and IL-2R? levels were significantly increased in the AoDILD state in patients with drug-induced ILD (DI-ILD), whereas TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients with DI-ILD. The serum TIMP-3, MMP-9, osteopontin, IL-2R?, MMP-1, and MMP-8 levels were significantly increased in the AoDILD state in patients who subsequently died, whereas TIMP-2 and MMP-3 levels were decreased in those who survived. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients who died, but not in those who survived.ConclusionsSerum biomarker profiles could represent prognosis markers for AoDILD in collagen diseases.
| S-EPMC3598392 | biostudies-literature
Project description:Question addressed by the studyMethotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.MethodsThrough a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.ResultsAnalysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001).Answer to the questionOur results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.
| S-EPMC8212188 | biostudies-literature
Project description:Interstitial lung disease (ILD) is the most common extra-articular manifestations of rheumatoid arthritis (RA) in the lung. This study aimed to identify clinical features of RA-associated ILD (RA-ILD). Patients with RA were retrospectively enrolled and sub-classified as RA-ILD or RA without ILD based on high-resolution computed tomography imaging. Pulmonary function testing parameters and levels of RA-related biomarkers, tumour markers, and acute-phase proteins were compared between the two groups. Logistic regression model was used to assess the strength of association between RA-ILD and clinical features of interest. Receiver operating characteristic analysis was performed to assess potential predictive value of clinical features for detecting RA-ILD. Comparison analysis indicated that the percentage of predicted value of total lung capacity, inspiratory capacity, and diffusion capacity of the lung for carbon monoxide (DLCO) were reduced in patients with RA-ILD. Tumour markers CA15-3 and CA125 were increased in patients with RA-ILD. Logistic regression analysis revealed that decreased DLCO was related to the increased likelihood of RA-ILD (OR = 0.94, 95%CI = [0.91, 0.98]). The cut-off point at 52.95 percent of predicted value could sensitively discriminate RA patients with or without ILD. Our study suggested that DLCO value could be a useful tool for detecting ILD in patients with RA.
| S-EPMC4595674 | biostudies-other
Project description:ObjectivesTo explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD).MethodsThe Korean Rheumatoid Arthritis-Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories.ResultsThis study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were 'improving' [n = 11 (7.9%)], 'stable' [n = 68 (38.4%)], 'slowly declining' [n = 54 (48.6%)] and 'rapidly declining' [n = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)].ConclusionMost patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.
| S-EPMC10473227 | biostudies-literature
Project description:Purpose of reviewSummarize recent evidence on the identification and management of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Recent findingsClinical and subclinical interstitial lung disease (ILD) are frequent extra-articular manifestations of rheumatoid arthritis (RA). Better means of identifying and treating RA-ILD are needed to improve the prognosis, with a median survival of only 3-7 years after diagnosis. Several serum biomarkers are currently being evaluated for their ability to detect RA-ILD. Thorough evaluation and multidisciplinary discussion remains the gold standard for establishing the diagnosis of RA-ILD. Management is challenging with most RA disease-modifying antirheumatic drugs (DMARDs) linked to pneumonitis. Methotrexate is typically avoided in clinically significant ILD, although alternative therapies including leflunomide and biologic DMARDs also carry risks in RA-ILD. Antifibrotics appear to slow the progression of ILD, and a large phase II trial exclusively in RA-ILD is underway. In addition, smoking cessation, pulmonary rehabilitation, oxygen therapy, managing comorbidities, and lung transplantation evaluation are vital to improving patient outcomes in RA-ILD.SummaryWith little high-quality evidence to guide the management of RA-ILD, multidisciplinary teams with expertise in RA-ILD are highly valuable for diagnosing and treating RA-ILD. Clinical and translational research in RA-ILD is needed to fill the many evidence gaps.
| S-EPMC7331796 | biostudies-literature
Project description:BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) featuring dense fibrosis of the visceral pleura and subpleural parenchyma, mostly in the upper lobes. PPFE can present in other ILDs, including rheumatoid arthritis-associated ILD (RA-ILD). The aim of this retrospective study was to investigate the prevalence and clinical implications of coexistent PPFE in RA-ILD.MethodsOverall, 477 patients with RA-ILD were recruited from two cohorts; their clinical data and HRCT images were analysed. The criteria for diagnosing PPFE were (1) pleural thickening with bilateral subpleural dense fibrosis in the upper lobes, (2) evidence of disease progression, and (3) absence of other identifiable aetiologies.ResultsThe median follow-up duration was 3.3 years. The mean age of the patients was 63.4 years, and 60.0% were women. PPFE was identified in 31 patients (6.5%). The PPFE group showed significantly lower body mass index and forced vital capacity (FVC) and more frequent usual interstitial pneumonia (UIP)-like pattern on HRCT than no-PPFE group. The risk factors for all-cause mortality were older age, lower FVC, and the presence of UIP-like pattern on HRCT; PPFE was not significantly associated with mortality in both all patients and a subgroup with a UIP-like pattern. The presence of PPFE was associated with a significantly increased risk of pneumothorax and greater decline in diffusing capacity.ConclusionsPPFE was not rare in patients with RA-ILD and was significantly associated with an increased risk of pneumothorax and greater lung function decline, though we found no significant association with mortality.
| S-EPMC9161503 | biostudies-literature
Project description:ObjectivesTo investigate the risk factors and prognosis associated with acute exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).DesignA retrospective case-control study.SettingA single academic hospital.Participants51 consecutive patients diagnosed with RA-ILD between 1995 and 2012. All patients fulfilled the diagnostic criteria of the American College of Rheumatology for RA. ILD was diagnosed on the basis of clinical presentation, pulmonary function tests, high-resolution CT (HRCT) findings and lung biopsy findings.Main outcome measuresOverall survival and cumulative AE incidence were analysed using Kaplan-Meier method. Cox hazards analysis was used to determine significant variables associated with AE occurrence and survival status.ResultsA total of 11 patients (22%) developed AE, with an overall 1-year incidence of 2.8%. Univariate analysis revealed that older age at ILD diagnosis (HR 1.11; 95% CI 1.02 to 1.21; p=0.01), usual interstitial pneumonia (UIP) pattern on HRCT (HR 1.95; 95% CI 1.07 to 3.63; p=0.03) and methotrexate usage (HR 3.04; 95% CI 1.62 to 6.02; p=0.001) were associated with AE. Of 11 patients who developed AE during observation period, 7 (64%) died of initial AE. In survival, AE was a prognostic factor for poor outcome (HR 2.47; 95% CI 1.39 to 4.56; p=0.003).ConclusionsIn patients with RA-ILD, older age at ILD diagnosis, UIP pattern on HRCT and methotrexate usage are associated with the development of AE. Furthermore, AE has a serious impact on their survival.
| S-EPMC3773638 | biostudies-literature