Circulating Plasma Biomarkers of Progressive Interstitial Lung Disease.
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ABSTRACT:
SUBMITTER: Alqalyoobi S
PROVIDER: S-EPMC6961741 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed.
| S-EPMC3439977 | biostudies-literature
Project description:BackgroundThe progressive fibrosing (PF) phenotype of interstitial lung disease (ILD) is characterised by worsening respiratory symptoms, lung function, and extent of fibrosis on high-resolution computed tomography. We aimed to investigate the prevalence and clinical outcomes of PF-ILD in a real-world cohort and assess the prognostic significance of the PF-ILD diagnostic criteria.MethodsClinical data of patients with fibrosing ILD other than idiopathic pulmonary fibrosis (IPF) consecutively diagnosed at a single centre were retrospectively reviewed. A PF phenotype was defined based on the criteria used in the INBUILD trial.ResultsThe median follow-up duration was 62.7 months. Of the total of 396 patients, the mean age was 58.1 years, 39.9% were men, and rheumatoid arthritis-ILD was the most common (42.4%). A PF phenotype was identified in 135 patients (34.1%). The PF-ILD group showed lower forced vital capacity and total lung capacity (TLC) than the non-PF-ILD group. The PF-ILD group also showed poorer survival (median survival, 91.2 months vs. not reached; P < 0.001) than the non-PF-ILD group. In multivariable Cox analysis adjusted for age, DLCO, HRCT pattern, and specific diagnosis, PF phenotype was independent prognostic factor (hazard ratio, 3.053; P < 0.001) in patients with fibrosing ILD. Each criterion of PF-ILD showed similar survival outcomes.ConclusionsOur results showed that approximately 34% of patients with non-IPF fibrosing ILD showed a progressive phenotype and a poor outcome similar to that of IPF, regardless of the diagnostic criteria used.
| S-EPMC8559348 | biostudies-literature
Project description:Interstitial lung disease (ILD) is frequently a complication of rheumatoid arthritis (RA) as an extra-articular manifestation which has a poor prognosis. Acute-onset diffuse ILD (AoDILD) occasionally occurs in RA and includes acute exacerbation of ILD, drug-induced ILD, and Pneumocystis pneumonia. AoDILD also confers a poor prognosis in RA. Previously-established biomarkers for ILD include Krebs von den lungen-6 and surfactant protein-D originally defined in patients with idiopathic pulmonary fibrosis; the sensitivity of these markers for RA-associated ILD (RA-ILD) is low. Although many studies on ILD markers have been performed in idiopathic pulmonary fibrosis, only a few validation studies in RA-ILD or AoDILD have been reported. Biomarkers for RA-ILD and AoDILD are thus still required. Recently, genomic, cytokine, antibody, and metabolomic profiles of RA-ILD or AoDILD have been investigated with the aim of improving biomarkers. In this review, we summarize current preliminary data on these potential biomarkers for RA-ILD or AoDILD. The development of biomarkers on RA-ILD has only just begun. When validated, such candidate biomarkers will provide valuable information on pathogenesis, prognosis, and drug responses in RA-ILD in future.
| S-EPMC8216360 | 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:In patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking.We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010-2017) were examined retrospectively for pre-defined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses.In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were female. Baseline mean forced vital capacity (FVC) was 74±22% predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p<0.05), age ≥50 years (p<0.01) and diagnosis subgroup (p<0.01).In this cohort of patients with PF-ILD not receiving antifibrotic therapy, the disease followed a course characterised by continued decline in lung function, which predicted mortality.
| S-EPMC8411897 | biostudies-literature
Project description:The aim is to evaluate the published evidence on whether methotrexate (MTX) use causes progressive fibrotic interstitial lung disease (fILD). This PRISMA-compliant systematic review has been registered electronically with PROSPERO 2018 ID CRD42018087838, Centre of review and dissemination at the University of York. A total of 29 articles met the inclusion criteria. Thirteen articles were found to support the claim that MTX causes fILD. They all had a low Downs and Black quality score (< 6/27). Their 'risk of bias' assessment scores indicated serious to critical risk of bias. The 16 articles rejecting the claim that MTX causes fILD were of higher quality as indicated by their Downs and Black score. Their 'risk of bias' assessment scores suggested only a low to moderate risk of bias. This systematic literature review supports the finding that MTX does not cause fILD in humans. Three studies suggest that MTX treatment may actually improve outcomes in patients with rheumatoid arthritis (RA) associated fILD by slowing down ILD progression.
| S-EPMC8079289 | biostudies-literature
Project description:IntroductionThe term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour.MethodsUsing the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients' quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data.ResultsPhysicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease.ConclusionsProgression in fibrosing ILD causes a significant impact on QoL and HCRU and costs. These survey data underline the need for safe and effective therapies to slow the disease progression.
| S-EPMC7467418 | biostudies-literature
Project description:BACKGROUND:Inflammation and pulmonary diseases, including interstitial lung diseases, are associated with increased lung cancer risk. Circulating levels of surfactant protein-D (SP-D) and Krebs von Lungren-6 (KL-6) are elevated in interstitial lung disease patients and may be useful markers of processes contributing to lung cancer. METHODS:We conducted a nested case-control study, including 532 lung cancer cases, 582 matched controls, and 150 additional controls with chest X-ray (CXR) evidence of pulmonary scarring, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serum SP-D and KL-6 levels were measured using enzyme immunoassay. Logistic regression was used to estimate the associations of SP-D and KL-6 with lung cancer and CXR scarring. RESULTS:Cases had higher levels than controls for SP-D (median 118.7 vs. 105.4 ng/mL, P = 0.008) and KL-6 (372.0 vs. 325.8 ?g/mL, P = 0.001). Lung cancer risk increased with SP-D (P(trend) = 0.0003) and KL-6 levels (P(trend) = 0.005). Compared with the lowest quartile, lung cancer risk was elevated among those with the highest quartiles of SP-D (OR = 1.87, 95% CI: 1.32-2.64) or KL-6 (OR = 1.58, 95% CI: 1.11-2.25). Among controls, participants with CXR scarring were more likely than those without scarring to have elevated levels of SP-D (quartile 4 vs. quartile 1: OR = 1.67, 95% CI: 1.04-2.70, P(trend) = 0.05) but not of KL-6 (OR = 1.04, 95% CI: 0.64-1.68, P(trend) = 0.99). CONCLUSION:Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk. IMPACT:Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed.
| S-EPMC3189337 | biostudies-literature
Project description:Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included. The pooled sensitivity, specificity, and area under the curve (AUC) values of anti-MDA5 antibody for DM-ILD were 0.47 (95% CI: 0.37-0.57), 0.96 (95% CI, 0.92-0.97), and 0.90 (95% CI: 0.88-0.93), respectively, with a low sensitivity value. The pooled sensitivity, specificity, and AUC values were 0.83 (95% CI: 0.77-0.88), 0.86 (95% CI: 0.80-0.91), and 0.87 (95% CI: 0.84-0.90) for DM with RPILD versus without RPILD with good sensitivity and specificity values. Trial sequential analysis showed sufficient evidence to support that anti-MDA5 antibody was associated with DM-ILD and DM-RPILD. The statistical power of this study calculated using G*Power version 3.1.9.2 was more than 99% (? = 0.05). Taken together, these findings suggest that anti-MDA5 antibody has a potential useful ability as a noninvasive biomarker in the diagnosis of RPILD in patients with DM.
| S-EPMC5652692 | biostudies-literature
Project description: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.
| S-EPMC8197477 | biostudies-literature