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

Author(s):  
juan chen ◽  
Yaqiong Chen ◽  
Dehao Liu ◽  
Yihua Lin ◽  
Lei Zhu ◽  
...  

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

2021 ◽  
Author(s):  
Juan Chen ◽  
Yaqiong Chen ◽  
Dehao Liu ◽  
Yihua Lin ◽  
Lei Zhu ◽  
...  

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.


2020 ◽  
Vol 72 (3) ◽  
pp. 409-419 ◽  
Author(s):  
Daniel J. Kass ◽  
Mehdi Nouraie ◽  
Marilyn K. Glassberg ◽  
Nitya Ramreddy ◽  
Karen Fernandez ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
pp. 00235-2020
Author(s):  
Anna-Maria Hoffmann-Vold ◽  
Toby M. Maher ◽  
Edward E. Philpot ◽  
Ali Ashrafzadeh ◽  
Oliver Distler

This systematic review summarises current evidence to help guide treatment decisions for patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD). A systematic search of the literature (January 2012 to April 2018), including grey literature (searched between 1992 and 2011), was conducted using multiple electronic databases. Guidelines, meta-analyses, randomised controlled trials and observational studies reporting on risk stratification, screening, diagnosis, treatment and management outcomes for patients with SSc-ILD were included. A quality assessment of the included evidence was undertaken.In total, 2464 publications were identified and 280 included. Multiple independent risk factors for ILD in patients with SSc were identified, including older age, male sex and baseline pulmonary function. High-resolution computed tomography (HRCT) has been used for characterising ILD in patients with SSc, and pulmonary function tests are a key adjunctive component in the diagnostic and monitoring pathway. The clinical value of biomarkers relating to SSc-ILD diagnosis or assessment for disease progression is unknown at present. Immunosuppressive therapy (monotherapy or combined therapy) is the current standard of care for SSc-ILD; long-term evidence for effective and safe treatment of SSc-ILD is limited.Identification of patients at risk for SSc-ILD remains challenging. HRCT and pulmonary function tests are key to diagnosing and monitoring for disease progression. Although immunosuppressive therapy is considered current first-line treatment, it is partly associated with adverse effects and long-term follow-up evidence is limited. Novel therapies and biomarkers should be further explored in well-controlled clinical studies.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1097.1-1097
Author(s):  
F. Zhu ◽  
X. Zhang

Background:Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a class of refractory diseases.Non-specific treatment with hormone and immunosuppressive agents is mostly used at present, but the effect is limited and the long-term survival rate is not improved [1],while anti-fibrosis treatments (such as Pirfenidone and Nintedanib) have only recently been approved, the long-term efficacy is still unknown.Tofacitinib(TOFA), a JAK inhibitor, has recently been used to treat patients with severe dermatomyositis related interstitial pulmonary disease, with significantly improved survival rate [2-4].A basic study showed that TOFA improved interstitial pulmonary disease in mice by promoting the proliferation of myelogenic inhibitory cells [5].However, whether TOFA can affect the migration and invasion of human lung fibroblasts and further research to reveal the mechanism of its inhibition of pulmonary fibrosis has not been reported.Objectives:To investigate the anti - fibrosis effect of TOFA in CTD-ILD.Methods:Cell migration and invasion AssaysHLFs were incubated with TOFA for 72h, followed by TGF- β1 for 24h.DMEM serum-free medium was used to determine the cell density to 5. 0 × 107/L, 600 uL medium containing 10% fetal bovine serum was added to the lower compartment of Transwell chamber, and 200 uL cell suspension was added to the upper compartment.Incubate in incubator for 12 h.After fixation, staining and sealing, the cells were observed and counted under a microscope. At least 5 random field transmembrane cells were counted in each hole, and the mean value was taken.For the invasion assays, Transwell chamber coated with matrigel was used, and the cell incubation time was 16 h.Results:1. Effect of TOFA on HLFs migration function (Figure 1)Figure 1.Effect of TOFA on HLFs migration function(×200).Mean ± SEM. n = 5.The number of cells passing through the biofilm in the three groups was counted.It can be seen that TGF-β1 group significantly increased compared with control group (*P < 0.0001), and TOFA group significantly decreased compared with TGF- β1 group (#P < 0.0001), suggesting that TOFA can significantly inhibit TGF-β1- induced HLFs migration.2. Effect of TOFA on HLFs invasion function (Figure 2)Figure 2.Effect of TOFA on HLFs invasion function(×200).Mean ± SEM. n = 5.The number of cells passing through the matrigel in the three groups was counted.It can be seen that TGF-β1 group was significantly higher than the control group (*P < 0.0001), and TOFA group was significantly lower than TGF-β1 group(#P < 0.001), suggesting that TOFA can significantly inhibit the invasion function of HLFs induced by TGF-β1.Conclusion:TOFA can effectively inhibit the function of HLFs migration and invasion. Although further studies are needed to elucidate the mechanism by which TOFA inhibit the function of HLFs migration and invasion, our study suggests that TOFA has a potential therapeutic effect for CTD-ILD.References:[1]Aparicio, I.J. and J.S. Lee, Connective Tissue Disease-Associated Interstitial Lung Diseases: Unresolved Issues. Semin Respir Crit Care Med, 2016. 37(3): p. 468-76.[2]Kato, M., et al., Successful Treatment for Refractory Interstitial Lung Disease and Pneumomediastinum With Multidisciplinary Therapy Including Tofacitinib in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis. J Clin Rheumatol, 2019.[3]Kurasawa, K., et al., Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford), 2018. 57(12): p. 2114-2119.[4]Chen, Z., X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis-Associated Interstitial Lung Disease. N Engl J Med, 2019. 381(3): p. 291-293.[5]Sendo, S., et al., Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice. Arthritis Res Ther, 2019. 21(1): p. 184Disclosure of Interests:None declared


Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 347
Author(s):  
Tomoyuki Fujisawa

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies’ status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.


Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 250-255
Author(s):  
Takashi Nawata ◽  
Yuichiro Shirai ◽  
Mikito Suzuki ◽  
Masataka Kuwana

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.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mouhamad Nasser ◽  
Sophie Larrieu ◽  
Loic Boussel ◽  
Salim Si-Mohamed ◽  
Fabienne Bazin ◽  
...  

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


Respiration ◽  
2018 ◽  
Vol 96 (3) ◽  
pp. 210-221 ◽  
Author(s):  
Hideaki Yamakawa ◽  
Eri Hagiwara ◽  
Hideya Kitamura ◽  
Tae Iwasawa ◽  
Ryota Otoshi ◽  
...  

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