Clinical features of rheumatoid arthritis-associated interstitial lung disease.
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ABSTRACT:
SUBMITTER: Wang T
PROVIDER: S-EPMC4595674 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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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: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: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:Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.3 million adults in the United States. Approximately 10% of these individuals with RA have clinically evident interstitial lung disease (RA-ILD), and an additional one-third demonstrate subclinical ILD on chest CT scan. The risk of death for individuals with RA-ILD is three times higher than for patients with RA without ILD, with a median survival after ILD diagnosis of only 2.6 years. Despite the high prevalence and mortality of RA-ILD, little is known about its molecular features and its natural history. At present, we lack a standard validated approach to the definition, diagnosis, risk stratification, and management of RA-ILD. In this perspective, we discuss the importance of clinical and translational research and how ongoing research efforts can address important gaps in our knowledge over the next few years. Furthermore, recommendations are made to design multicenter collaborative studies that will expedite the development of clinical trials designed to decrease the significant morbidity and mortality associated with RA-ILD.
| S-EPMC3941243 | biostudies-other
Project description:PurposeTo determine the accuracy of computed tomography (CT) in identifying the histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Materials and methodsAll patients were enrolled into institutional review board-approved longitudinal cohorts at their respective institution, and informed consent was obtained at the time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n = 69) were collected from three tertiary care centers. Two experienced thoracic radiologists independently reviewed the CT scans. The CT pattern was categorized as definite UIP, possible UIP, or inconsistent with UIP in accordance with published criteria. Findings of biopsies were reviewed by an experienced lung pathologist. The sensitivity and specificity of definite CT UIP pattern to histopathologic UIP pattern were determined. The agreement between radiologists was assessed by calculating a ? score.ResultsThe histopathologic UIP pattern was present in 42 of 69 (61%) patients. Men were more likely than women to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69) had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96% (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95% CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement between radiologists for definite UIP pattern versus not was 87% (? = 0.67, P < .0001).ConclusionDefinite UIP pattern on a CT scan in RA-ILD is highly specific and moderately sensitive for histopathologic UIP pattern. CT can therefore help accurately identify the UIP pattern in RA-ILD.
| S-EPMC4228744 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5-1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor ? agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease.
| S-EPMC4637848 | biostudies-literature
Project description:Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA), and is designated RA-associated ILD (RA-ILD). RA-ILD has a large impact on the prognosis of RA. Here, we investigated the micro RNAs (miRNAs) profiles to determine whether they may be useful for diagnosing RA-ILD.RNA was isolated from plasma samples and cDNA was synthesized. Real-time RT-PCR analysis was performed to evaluate 752 miRNA expression profiles in plasma pools from RA patients with or without RA-ILD. Sixteen selected miRNA levels were analyzed in individual plasmas from 64 RA patients with or without RA-ILD.Expression levels of hsa-miR-214-5p (mean relative expression level?±?standard deviation, 8.1?±?28.2 in RA with ILD, 0.2?±?0.9 in RA without ILD, P?=?0.0156) and hsa-miR-7-5p (56.2?±?260.4 in RA with ILD, 4.7?±?11.8 in RA without ILD, P?=?0.0362) were higher in RA patients with RA-ILD than in those without. The values of miRNA index (214, 7) generated from hsa-miR-214-5p and hsa-miR-7-5p for ILD were significantly elevated in RA patients with RA-ILD compared with those without (0.122?±?0.332 in RA with ILD, 0.006?±?0.013 in RA without ILD, P?=?0.0010). The area under the curve value of the receiver operating characteristic curve for the miRNA index (214, 7) was 0.740.To the best of our knowledge, this is the first report of miRNA profiles in RA-ILD. The expression levels of hsa-miR-214-5p and hsa-miR-7-5p were increased in RA with ILD.
| S-EPMC5244611 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5-1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10-20% of mortality, with a mean survival of 5-8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.
| S-EPMC7230307 | biostudies-literature