scholarly journals Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Liu Liang ◽  
Jiali Chen ◽  
Chun Di ◽  
Minghua Zhan ◽  
Huizhang Bao ◽  
...  

Objective: Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA).Methods: This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer.Results: The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080, p < 0.001).Conclusion: Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).

2018 ◽  
Vol 4 (2) ◽  
pp. 00124-2017 ◽  
Author(s):  
Simon Bax ◽  
Charlene Bredy ◽  
Aleksander Kempny ◽  
Konstantinos Dimopoulos ◽  
Anand Devaraj ◽  
...  

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs.Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used “additional PH signs” where RVSP was unavailable, using a bootstrapping technique.Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%).This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.


2015 ◽  
Vol 47 (2) ◽  
pp. 588-596 ◽  
Author(s):  
Joshua J. Solomon ◽  
Jonathan H. Chung ◽  
Gregory P. Cosgrove ◽  
M. Kristen Demoruelle ◽  
Evans R. Fernandez-Perez ◽  
...  

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a “definite” or “possible” usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.


Cureus ◽  
2020 ◽  
Author(s):  
Mahesh Gautam ◽  
Mah Jabeen Masood ◽  
Sadaf Arooj ◽  
Mufazzal-e-Haque Mahmud ◽  
Muhammad Umer Mukhtar

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 969.1-970
Author(s):  
M. DI Carlo ◽  
M. Tardella ◽  
E. Filippucci ◽  
F. Salaffi

Background:In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. LUS allows the detection of artifacts (B-lines) characteristic of ILD, without the need to use ionizing radiation. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD.Objectives:To determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods:A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS, chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of HRCT using a computer-aided method (CaM). The 10% of fibrosis, measured with this method, was considered as a cut-off for the presence of significant RA-ILD. The LUS was carried out in 14 defined intercostal spaces using a linear multifrequency probe 6-18 MHz (MyLab Class C, Esaote S.p.A., Genoa, Italy) and the number of B-lines present in each intercostal space was counted and summed up (Figure 1). The discriminating validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Figure 1.LUS B-line illustrative.Results:72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years), a mean ACPA titre of 327.6 (SD 633.3) U/ml and a rheumatoid factor of 324.6 (SD 748.7) U/ml. The mean estimate of pulmonary fibrosis using the CaM was 11.2% (SD 7.5) at HRCT, while at LUS the mean number of B-lines was 10.6 (SD 15.1). Pulmonary fibrosis of 10% as measured by the CaM at HRCT was detected in 25 patients (34.72%). Applying this HRCT cut-off point as an estimate of significant fibrosis, the presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant fibrosis with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4 (Figure 2).Figure 2.Area under the ROC curve to determine the number of B-lines at LUS to define a significant RA-ILD, applying the 10% of fibrosis at chest HRCT measured by OsiriX as external criterion.Conclusion:The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.References:[1] Tardella M, et al. Ultrasound B-lines in the evaluation of interstitial lung disease in patients with systemic sclerosis: Cut-off point definition for the presence of significant pulmonary fibrosis. Medicine (Baltimore). 2018;97(18):e0566.[2] Salaffi F, et al. High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities. Medicine (Baltimore). 2019;98(38):e17088.Disclosure of Interests:Marco Di Carlo: None declared, Marika Tardella: None declared, Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work., Fausto Salaffi: None declared


2020 ◽  
Vol 79 (5) ◽  
pp. 587-594 ◽  
Author(s):  
Raul Castellanos-Moreira ◽  
Sebastian Cruz Rodríguez-García ◽  
Maria Jose Gomara ◽  
Virginia Ruiz-Esquide ◽  
Andrea Cuervo ◽  
...  

ObjectiveTo analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.MethodsCross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies.ResultsWe enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample.ConclusionsAnti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 600.2-600
Author(s):  
C. Aguilera Cros ◽  
M. Gomez Vargas ◽  
R. J. Gil Velez ◽  
J. A. Rodriguez Portal

Background:Among the risk factors associated with the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) are: male sex, old age, erosive RA, rheumatoid nodules, smoking and high levels of rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA). The factors of poor prognosis include: HRCT (High Resolution Computed Tomography) pattern of usual interstitial pneumonia (NIU) with altered baseline functional tests (forced vital capacity FVC <60%, diffusion capacity of the lung for carbon monoxide DLCO<40%).RA associated UIP (RA-UIP) has an appearance that is identical to idiopathic UIP (idiopathic pulmonary fibrosis [IPF]) on HRCT.Objectives:To analyze different risk factors and poor prognosis in a cohort of patients with ILD-RA.To assess the degree of association between tobacco (smokers, ex-smokers and non-smokers) and altered baseline functional respiratory tests (FRT) (FVC <80% and DLCO <40%) with HRCT patterns.Methods:Descriptive study of 57 patients treated in our Hospital (1/1/2018 until 12/31/2019) with a diagnosis of RA (ACR 2010 criteria) and secondary ILD.The most recent American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines define three HRCT (High Resolution Computed Tomography) patterns of fibrosing lung disease in the setting of idiopathic pulmonary fibrosis (IPF): definite UIP (traction bronchiectasis and honeycombing), possible UIP and inconsistent with UIP. The distinction between definite UIP and possible UIP in these to the presence or absence of honeycombing. Approved by the Ethics Committee.Quantitative variables are expressed as mean (SD) and dichotomous variables as percentages (%). The association between tobacco-UIP and FVC-UIP was studied using two Chi-square tests and the DLCO-UIP relationship with an exact Fisher test. Statistical analysis with SPSS version 21.Results:21 men and 36 women were included, with a mean age of 69 ± 10 years (mean ± SD), history of smoking (smokers 14%, non-smokers 43%, ex-smokers 42%). 83% were positive RF and 70% positive ACPA. Regarding the HRCT findings: 29 (50%) had a inconsistent with UIP pattern and 28 (49%) had an UIP pattern (45% defined, 3% possible). Of the UIP patients, 14 (50%) had a smoking relationship (35% ex-smokers, 25% smokers) and 15 were male (53%). Of the sample analyzed, 8% (5 patients) have died, all ex-smoking men, the UIP pattern being the most frequent found (4 UIP, 1 inconsistent with UIP).No statistical association was observed between patients with exposure to tobacco and the UIP pattern (p = 0.438), nor among patients with baseline FVC <80% and UIP (p = 0.432) and also among patients with baseline DLCO <40% and UIP pattern (p = 0.459).Conclusion:Our results, in general, do not match what is published in the literature. Male sex, smoking exposure and fibrosing pattern (UIP) represent a worse prognosis for patients with ILD-RA. However, more studies are required to determine more precisely how these risk factors affect the disease.Disclosure of Interests:None declared


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