Lung Disease In Rheumatoid Arthritis Research Articles

Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound. A Diagnostic Test Accuracy study.

The Objective was to determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. Individuals with RA visiting Rheumatological outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnoea, cough, recurrent pneumonia, prior severe pneumonia or a chest X-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high-resolution CT (HRCT) <12 months or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if ≥10 B-lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV). An ILD-specialised thoracic radiologist assessed HRCT, followed by a multi-disciplinary team discussion, which was the reference standard. The accepted window of HRCT was <30 days after TUS was performed. 77 participants received HRCT <30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% CI: 61.2% to 95.0%) and a specificity of 51.9% (95% CI: 37.8% to 65.7%), corresponding to a PPV of 42.2% (95%CI 27.7% to 57.8%) and an NPV of 87.5% (95% CI 71.0% to 96.5%). To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA.

Interstitial lung disease in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder mainly involving joints but almost 50% of the patients develop extra-articular manifestation, one of the most common being lung involvement. While essentially any of the lung compartments can be involved, interstitial lung disease (ILD) is associated with significant morbidity and mortality. In this review, we discuss main current concepts in the screening, diagnostic and monitoring strategies of RA-ILD as well as therapeutic recommendations.

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan–Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p &lt; 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p &lt; 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients.

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35-3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients.

Is JAK inhibition an option in the treatment of interstitial lung disease in rheumatoid arthritis?

A69-year-old male patient with seropositive erosive rheumatoid arthritis (RA) presented to our clinic due to progressive dyspnea. High-resolution computed tomography (HRCT) and immunological bronchioalveolar lavage revealed ground-glass opacities and alymphocytic alveolitis caused by interstitial lung disease (ILD) in RA. Considering previous forms of treatment, disease-modifying antirheumatic drug (DMARD) treatment was switched to tofacitinib. Tofacitinib treatment demonstrated a33% reduction in ground-glass opacities by artificial intelligence-based quantification of pulmonary HRCT over the course of 6 months, which was associated with an improvement in dyspnea symptoms. In conclusion, tofacitinib represents an effective anti-inflammatory therapeutic option in the treatment of RA-ILD.

Serum alarmins and the risk of incident interstitial lung disease in rheumatoid arthritis.

To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Using serum collected at enrolment, three alarmins (interleukin [IL]-33, thymic stromal lymphopoietin [TSLP], and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score, and anti-cyclic citrullinated antibody positivity. Of 2,835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (HR 0.73 per log-fold increase; 95% CI 0.57-0.95; p= 0.018) and adjusted (HR 0.77; 95% CI 0.59-1.00, p= 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA.

Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis.

Interstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD. A total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1. Among the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR. Our findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.

Patient-level factors predictive of interstitial lung disease in rheumatoid arthritis: a systematic review

Objective Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients with RA are at the highest...

Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020

ObjectiveTo investigate prevalence, incidence and medication of interstitial lung disease (ILD) among German individuals with rheumatoid arthritis (RA).MethodsNationwide BARMER claims data from 2007 to 2020 were used. RA-ILD was identified...

Progressive fibrosing interstitial lung disease in rheumatoid arthritis: A retrospective study.

Rheumatoid arthritis associated-interstitial lung disease (RA-ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA) and an important cause of mortality. In patients suffering from interstitial lung diseases (ILD) from different etiologies (including RA-ILD), a significant proportion is exhibiting a fibrotic progression despite immunosuppressive therapies, defined as progressive fibrosing interstitial lung disease (PF-ILD). Here, we report the frequency of RA-ILD and PF-ILD in all RA patients' cohort at University Hospital of Liège and compare their characteristics and outcomes. Patients were retrospectively recruited from 2010 to 2020. PF-ILD was defined based on functional, clinical and/or iconographic progression criteria within 24 months despite specific anti-RA treatment. Out of 1,500 RA patients, about one third had high-resolution computed tomography (HRCT) performed, 89 showed RA-ILD and 48 PF-ILD. RA-ILD patients were significantly older than other RA patients (71 old of median age vs. 65, p < 0.0001), with a greater proportion of men (46.1 vs. 27.7%, p < 0.0001) and of smoking history. Non-specific interstitial pneumonia pattern was more frequent than usual interstitial pneumonia among RA-ILD (60.7 vs. 27.0%) and PF-ILD groups (60.4 vs. 31.2%). The risk of death was 2 times higher in RA-ILD patients [hazard ratio 2.03 (95% confidence interval 1.15-3.57), p < 0.01] compared to RA. We identified a prevalence of PF-ILD of 3% in a general RA population. The PF-ILD cohort did not seem to be different in terms of demographic characteristics and mortality compared to RA-ILD patients who did not exhibit the progressive phenotype yet.

Mortality and survival of patients with rheumatoid arthritis and symptomatic diffuse interstitial lung disease

Introduction: In Spain, few data have been reported on mortality and survival in rheumatoid arthritis with diffuse interstitial lung disease. Objectives: To estimate mortality and survival for patients with symptomatic diffuse interstitial lung disease and rheumatoid arthritis and to analyze the effect of clinical factors. Methods: We performed an observational study between 2007 and 2018 at the Interdisciplinary Rheumatology and Pulmonology Clinic, from a tertiary Hospital. Patients with rheumatoid arthritis and symptomatic of diffuse interstitial lung disease confirmed by high-resolution computed tomography were included. Causes of death and clinical factors were reported. Results: We identified 90 patients with rheumatoid arthritis and symptomatic interstitial lung disease. Twenty-six patients died and diffuse interstitial lung disease was the most frequent cause (50%). The overall mortality rate was 19.7 per 1000 patient-years (95% CI: 13.4 - 29). The multivariate model revealed the predictors of mortality to be a long time between diagnosis of rheumatoid arthritis and lung involvement (HR = 1.17; p = 0.003) and low forced vital capacity (HR = 0.02; p = 0.018). The probability of survival was 50% at 10.2 years from diagnosis of interstitial lung disease. Comparison of survival did not reveal significant differences by type of radiologic pattern (p = 0.823). Conclusions: The fact that almost one-third of patients died and that survival is 50% at 10 years highlights the important role of diffuse interstitial lung disease in rheumatoid arthritis. The radiologic pattern does not seem to be as important for survival as forced vital capacity at diagnosis and the time between diagnosis of rheumatoid arthritis and lung involvement. Key points 1. DILD is associated with shorter survival in patients with RA. 2. The radiologic pattern does not seem to influence the survival in patients with RA and DILD. 3. The FVC at diagnosis is an important factor that influences the prognosis of patients with RA and DILD.

Suppressed paraoxonase-1 activity associates with elevated oxylipins and the presence of small airways disease in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA)-associated lung disease (LD) associates with significantly increased morbidity and mortality. Although oxidative stress plays an important role in the inflammatory responses in other forms of lung disease, minimal work has evaluated its role in RA-LD. The current work examines the relationship between the anti-oxidant HDL-associated enzyme paraoxonase-1 (PON1), the PON1 Q192R polymorphism, and a targeted oxylipin panel with RA-LD.MethodsThis study was conducted as a retrospective chart review of a longitudinal single-center cohort of 250 RA patients. CT scans of the chest were reviewed by the interpreting radiologist and classified as small airways disease (SAD), interstitial lung disease (ILD), and bronchiectasis. PON1 activity was measured by its lactonase, arylesterase, and paraoxonase functions. The PON1 Q192R polymorphism and a targeted lipidomics panel were performed as previously reported.Results43.2% of the 250 RA patient cohort (n = 108) had available CT scans, including 48 patients (44.4%) with SAD, 27 patients (25.0%) with bronchiectasis, and 16 patients (14.8%) with ILD. Patients with SAD had significantly lower baseline PON1 activity by its arylesterase, and lactonase functions, as well as higher 15-HETE, LTB4, and PGE2 levels compared to those without SAD. These predictors of SAD remained significant after multivariate analysis including known risk factors for RA-LD. Suppressed PON1 activity also correlated with higher levels of 15-HETE and 12-HETE.ConclusionIn a single-center RA cohort, suppressed baseline PON1 activity and elevation in the oxylipins 15-HETE, LTB4, and PGE2 predicted the presence of RA-SAD in longitudinal follow-up.Key Points• Small airways disease (SAD) was present in 44.4% of this rheumatoid arthritis (RA) cohort.• Patients with SAD had significantly lower baseline PON1 activity, as well as higher levels of the oxylipins 15-HETE, LTB4, and PGE2 levels compared to those without SAD.• Further work is warranted to confirm these findings and further define the role of PON1 and lipid oxidation in RA lung disease.

Ultrasound evaluation of interstitial lung disease in rheumatoid arthritis and autoimmune diseases.

The interpretation of lung ultrasound (US) is the result of the analysis of artifacts, rather than exact representations of anatomical structures, which appear when changes in the physical properties of the lung occur. Its application to the study of interstitial lung disease (ILD) associated with autoimmune diseases has aroused great interest in the last 10 years, as evidenced by a growing number of publications studying its usefulness in the diagnostic process, as a prognostic marker, and as an aid in monitoring of patients. The main elements in lung US interpretation in ILD are the B lines and the changes in the pleural line. B lines are vertical artifacts that are generated when there is a partial decrease in the air content of the lung parenchyma and/or the volume of the interstitial area expands. Pleural line alterations that can be seen are irregularities, thickening, fragmentation, or subpleural nodules. Both the B lines and the changes in the pleural line have shown a significant positive correlation with the evidence on chest computed tomography (high-resolution computed tomography [HRCT]) of ILD associated with autoimmune diseases, with sensitivity and negative predictive values of up to 100%. These results, together with the safety, accessibility, and low cost of lung US, support this imaging technique as a promising screening method for optimizing the indication for HRCT. The role of lung US regarding sensitivity to change needs further investigation with multicenter prospective studies.

Serum rheumatoid factor IgA, anti-citrullinated peptide antibodies with secretory components, and anti-carbamylated protein antibodies associate with interstitial lung disease in rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD.MethodsSera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay.ResultsThe comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10− 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10− 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10− 11).ConclusionRF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis.

Background:Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities.Methods:The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities.Results:Based on experts’ consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities.Conclusions:These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.

Lymphoid Interstitial Pneumonitis In Rheumatoid Arthritis

Lymphoid Interstitial Pneumonitis (LIP) is a rare interstitial lung disease in rheumatoid arthritis (RA). LIP occurs in a patient with high titers of rheumatoid factor (RF), absence of inflammatory pain and limited joint damage, despite long-standing RA. In these patients, extra-articular manifestations occur even if joint disease activity is low. RA is an autoimmune disease which affects mostly the diarthrodial joints but can also have extra-articular manifestations such as lung disease. Interstitial lung disease (ILD) is frequently encountered in patients with RA. Patterns of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), lymphoid interstitial pneumonitis (LIP) and organizing pneumonia (OP) have been described on surgical lung biopsies in RA patients [1].

Fine particulate matter components and interstitial lung disease in rheumatoid arthritis.

Exposure to ambient fine particulate matter with an aerodynamic diameter <2.5 μg·m-3 (PM2.5) is a risk factor for pulmonary and systemic autoimmune diseases; however, evidence on which PM2.5 chemical components are more harmful is still scant. Our goal is to investigate potential associations between major PM2.5 components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA). New-onset RA subjects identified from a US healthcare insurance database (MarketScan) were followed for new onset of RA-associated ILD (RA-ILD) from 2011 to 2018. Annual concentrations of ambient PM2.5 chemical components (i.e. sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to 1 year before ILD onset or end of study were assigned to subjects based on their core-based statistical area or metropolitan division codes. A novel time-to-event quantile-based g (generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM2.5 chemical components adjusting for age, sex and prior chronic obstructive pulmonary disease (as a proxy for smoking). We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% CI 1.47-1.63) per every decile increase in all seven exposures. Ammonium, mineral dust and black carbon contributed more to ILD risk than the other PM2.5 components. Exposure to components of PM2.5, particularly ammonium, increases ILD risk in RA.

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

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).

Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in rheumatoid arthritis

BackgroundPrevious studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD.MethodsBlood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis.ResultsSerum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P = 0.01, r = − 0.354), total lung capacity (TLC%) (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689.ConclusionSerum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study.

Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.