Clinical features and risk factors for primary Sjögren's syndrome combined with interstitial lung disease: a retrospective study.

Objective: To analyze the clinical characteristics of primary Sjögren's syndrome (pSS) combined with interstitial lung disease (ILD), so as to provide a theoretical basis for the early diagnosis, treatment and prevention of PSS-ILD. Methods: From October 2017 to January 2022, patients with pSS who were admitted to the Department of Rheumatology at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine were included in this retrospective study. Patients were divided into the pSS-ILD (102 cases) and pSS-non-ILD groups (154 cases) based on the presence or absence of ILD on high-resolution computed tomography (HRCT). Demographics information, clinical symptoms, laboratory indicators and HRCT features were compared, and the logistic regression analysis was utilized to identify the risk factors. Results: A total of 256 patients were included. Patients with pSS-ILD were more often female, and their age and disease duration were significantly higher than those in the pSS-non-ILD group (p < 0.05). The HRCT imaging classification included ground glass-like shadow (78.4%) and patchy solid shadow (17.6%), and Non-specific interstitial pneumonitis (NSIP) (72.5%) was the predominant typology. Regarding the laboratory indexes, the positive rates of erythrocyte sedimentation rate, C-reactive protein, white blood cell count, neutrophil/lymphocyte ratio, triglycerides, total cholesterol, and anti-SS-A52 antibodies were significantly higher in the pSS-ILD patients than in the pSS-non-ILD group, while the positive rates of anti-synaptic antibodies were lower than in the pSS-non-ILD group, and the differences between two groups were statistically significant (p < 0.05). Logistic regression showed that age >60 years, longer duration of disease, higher triglycerides, and cholesterol were risk factors for pSS-ILD patients. Conclusion: The clinical features of pSS-ILD patients were xerophthalmia, cough and shortness of breath, and HRCT can help to diagnose the disease at an early stage. Age over 60 years, chronic course of disease, and elevated lipid levels are risk factors for ILD in pSS patients, and the relationship between autoimmune antibody levels and the occurrence of ILD needs to be further confirmed in follow-up studies with large sample sizes. These findings have the potential to provide useful information for early diagnosis, treatment, and prevention of the development of pSS-ILD.

Scoping review of exposure questionnaires and surveys in interstitial lung disease.

BACKGROUND: Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown. OBJECTIVES: This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire. METHODS: A scoping review based on Arksey and O'Malley's methodological framework was conducted. ELIGIBILITY CRITERIA: Any questionnaire that elicited exposures specific to ILD was included. A modified COSMIN Risk of Bias Framework was used to assess quality. SOURCES OF EVIDENCE: Relevant articles were identified from MEDLINE and EMBASE up to 23 July 2023. RESULTS: 22 exposure questionnaires were identified, including 15 generally pertaining to ILD, along with several disease-specific questionnaires for hypersensitivity pneumonitis (n=4), chronic beryllium disease, sarcoidosis and silicosis (1 questionnaire each). For most questionnaires, quality was low, whereby the methods used to determine exposure inclusion and questionnaire validation were not reported or not performed. Collectively the questionnaires covered 158 unique exposures and at-risk occupations, most commonly birds, mould/water damage, wood dust, asbestos, farming, automotive mechanic and miners. Only five questionnaires also provided free-text fields, and 13 queried qualifiers such as temporality or respiratory protection. CONCLUSIONS: Designing a robust ILD-specific questionnaire should include an evidence-based and relevance-based approach to exposure derivation, with clinicians and patients involved in its development and tested to ensure relevance and feasibility.

Multidimensional biomarker approach integrating tumor markers, inflammatory indicators, and disease activity indicators may improve prediction of rheumatoid arthritis-associated interstitial lung disease.

INTRODUCTION: Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). METHODS: Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. RESULTS: The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. CONCLUSION: The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes.

Review of Pulmonary Manifestations in Antisynthetase Syndrome.

Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be diverse. Additional common symptoms experienced by patients with ASyS include Raynaud's phenomenon, mechanic's hand, and fever. Although there is a significant overlap with polymyositis and dermatomyositis, the key distinction lies in the presence of antisynthetase antibodies (ASAs). Up to 10 ASAs have been identified to correlate with a presentation of ASyS, each having manifestations that may slightly differ from others. Despite the proposal of three classification criteria to aid diagnosis, the heterogeneous nature of patient presentations poses challenges. ILD confers a significant burden in patients with ASyS, sometimes manifesting in isolation. Notably, ILD is also often the initial presentation of ASyS, requiring pulmonologists to remain vigilant for an accurate diagnosis. This article will comprehensively review the various aspects of ASyS, including disease presentation, diagnosis, management, and clinical course, with a primary focus on its pulmonary manifestations.

Interstitial Lung Disease Associated with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by a tripod combining vasculopathy, fibrosis, and immune-mediated inflammatory processes. The prevalence of interstitial lung disease (ILD) in SSc varies according to the methods used to detect it, ranging from 25 to 95%. The fibrotic and vascular pulmonary manifestations of SSc, particularly ILD, are the main causes of morbidity and mortality, contributing to 35% of deaths. Although early trials were conducted with cyclophosphamide, more recent randomized controlled trials have been performed to assess the efficacy and tolerability of several medications, mostly mycophenolate, rituximab, tocilizumab, and nintedanib. Although many uncertainties remain, expert consensus is emerging to optimize the therapeutic management and to provide clinicians with evidence-based clinical practice guidelines for patients with SSc-ILD. This article provides an overview, in the light of the latest advances, of the available evidence for the diagnosis and management of SSc-ILD.

Current pharmacotherapies for advanced lung cancer with pre-existing interstitial lung disease : A literature review and future perspectives.

Patients with interstitial lung disease (ILD), especially those with idiopathic pulmonary fibrosis, are at increased risk of developing lung cancer (LC). Pharmacotherapy for advanced LC has dramatically progressed in recent years;however, management of LC with pre-existing ILD (LC-ILD) is challenging due to serious concerns about the risk of acute exacerbation of ILD (AE-ILD). As patients with LC-ILD have been excluded from most prospective clinical trials of advanced LC, optimal pharmacotherapy remains to be elucidated. Although the antitumor activity of first-line platinum-based cytotoxic chemotherapy appears to be similar in advanced LC patients with or without ILD, its impact on the survival of patients with LC-ILD is limited. Immune checkpoint inhibitors may hold promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Further understanding the predictive factors for AE-ILD after receiving pharmacotherapy in LC-ILD may lead to appropriate patient selection and lower treatment risk. The aim of this review was to summarize the current evidence related to pharmacotherapy for advanced LC-ILD and discuss emerging areas of research. J. Med. Invest. 71 : 9-22, February, 2024.

Novel Therapeutic Approaches in Connective Tissue Disease-Associated Interstitial Lung Disease.

Connective tissue diseases (CTD) comprise a group of autoimmune diseases that can affect multiple organs in the body including the lungs. The most common form of pulmonary involvement is interstitial lung disease (ILD). CTD-associated ILD (CTD-ILD) can take one of several courses including nonprogressive, chronically progressive, or rapidly progressive. Chronically and rapidly progressive patterns are associated with increased mortality. Limited randomized controlled trial data are available for treatment of CTD-ILD, with most data coming from systemic sclerosis-related ILD. The current first-line treatment for all CTD-ILD is immunosuppression with consideration of antifibrotics, stem cell transplant, and lung transplant in progressive disease. In this article, we review data for ILD treatment options in systemic sclerosis, rheumatoid arthritis, myositis, and primary Sjögren's syndrome-related ILDs.

Dysregulation of TNF-induced protein 3 and CCAAT/enhancer-binding protein ß in alveolar macrophages: Implications for systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: This study investigates the role of TNF-induced protein 3 (TNFAIP3) and CCAAT/enhancer-binding protein ß (C/EBPß) in alveolar macrophages (AMs) of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) and their influence on pulmonary fibrosis. METHODS: Transfection of HEK293T cells and AMs with plasmids carrying TNFAIP3 and C/EBPß was performed, followed by co-culturing AMs with pulmonary fibroblasts. Immunoblotting analysis was then utilized to assess the expression of TNFAIP3, C/EBPß, and collagen type 1 (Col1). Quantitative PCR analysis was conducted to quantify the mRNA levels of C/EBPß, IL-10, and TGF-ß1. STRING database analysis, and immunoprecipitation assays were employed to investigate the interactions between TNFAIP3 and C/EBPß. RESULTS: TNFAIP3 expression was significantly reduced in SSc-ILD AMs, correlating with increased Col1 production in fibroblasts. Overexpression of TNFAIP3 inhibited this pro-fibrotic activity. Conversely, C/EBPß expression was elevated in SSc-ILD AMs, and its reduction through TNFAIP3 restoration decreased pro-fibrotic cytokines IL-10 and TGFß1 levels. Protein-protein interaction studies confirmed the regulatory relationship between TNFAIP3 and C/EBPß. CONCLUSIONS: This study highlights the important role of TNFAIP3 in regulating pulmonary fibrosis in SSc-ILD by modulating C/EBPß expression in AMs. These findings suggest that targeting TNFAIP3 could be a potential therapeutic strategy for managing SSc-ILD patients.

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies.

Objectives: Interstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS). Methods: Here, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately. Results: Peripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/µL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/µL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS. Conclusions: Patients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD.

Smoking-Related Interstitial Lung Disease: Historical Perspective and Advances in the Twenty-first Century.

In the twenty- first century, there is widespread agreement that in addition to lung cancer, emphysema, and chronic bronchitis, cigarette smoking causes accumulation of pigmented macrophages, interstitial fibrosis, and Langerhans cell proliferation in various permutations. These histologic changes remain subclinical in some patients and produce clinical manifestations and imaging abnormalities in others. Debate surrounds terminology of these lesions, which are often grouped together under the umbrella of "smoking-related interstitial lung disease." This review summarizes modern concepts in our understanding of these abnormalities and explains how the recognition of smoking-related interstitial fibrosis has advanced the field.

Smoking-Related Interstitial Lung Disease and Emphysema.

Diagnosis and treatment of patients with smoking-related lung diseases often requires multidisciplinary contributions to optimize care. Imaging plays a key role in characterizing the underlying disease, quantifying its severity, identifying potential complications, and directing management. The primary goal of this article is to provide an overview of the imaging findings and distinguishing features of smoking-related lung diseases, specifically, emphysema/chronic obstructive pulmonary disease, respiratory bronchiolitis-interstitial lung disease, smoking-related interstitial fibrosis, desquamative interstitial pneumonitis, combined pulmonary fibrosis and emphysema, pulmonary Langerhans cell histiocytosis, and E-cigarette or vaping related lung injury.

The outcome of 12-week corticosteroid therapy in COVID-19-related diffuse interstitial lung abnormalities.

INTRODUCTION: The efficacy of long-course corticosteroid therapy in treating COVID-19-related diffuse interstitial lung abnormalities (DILA) needs to be better understood. We aimed to investigate the benefits of 12-week corticosteroid treatment in COVID-19-related DILA by evaluating computed tomography (CT) lung severity scores. MATERIALS AND METHODS: This retrospective, single-centre observational study included patients aged 18 years or older admitted with moderate to severe COVID-19 pneumonia who received 12 weeks of oral prednisolone between January 2021 and December 2021. We recorded clinical parameters, baseline CT scores and post-treatment, modified Medical Research Council (mMRC) dyspnoea scale and pulmonary function tests. RESULTS: A total of 330 patients were analysed. The mean (standard deviation, SD) age was 54.6 (14.2) years, and 43% were females. Three-point nine per cent (3.9%) require noninvasive ventilation (NIV), while 14.6% require mechanical ventilation (MV). On follow-up at 12 weeks, the CT patterns showed improvement in ground-glass opacities, perilobular density and consolidation. There was an improvement in the mean (SD) CT score before and after prednisolone therapy, with values of 17.3 (5.3) and 8.6 (5.5), respectively (p<0.001). The median mMRC was 1 (IQR 0-1), and 98.8% had a radiological response. The common side effects of prednisolone therapy were weight gain (13.9%), hyperglycaemia (1.8%) and cushingoid habitus (0.6%). CONCLUSION: A 12-week treatment with prednisolone showed significant improvement in CT scores with minimal residual dyspnoea and was relatively safe. Longer duration of steroids may be beneficial in moderate to severe COVID-19- related DILA.

Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.

OBJECTIVES: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. METHODS: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. RESULTS: A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. CONCLUSION: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Dynamic change in red cell distribution width as a predictor for short-time mortality in dermatomyositis-associated rapid progressive interstitial lung disease.

AIM: We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with idiopathic inflammatory myopathies (IIM). METHODS: A total of 1822 consecutive patients with IIM between 2009 and 2021 were evaluated retrospectively. All proven cases of naïve ILD with complete medical records were included. Red cell distribution width (RDW) values at the initial stage, 3 months and last follow-up were collected. The clinical characteristics and outcomes of the patients were recorded. RESULTS: We identified 532 patients with IIM with an average follow-up of 4 years. ILD prevalence was higher in patients of elevated RDW (p<0.001). The patients with ILD and elevated RDW had lower levels of PaO2/FiO2, FVC% and DLco% and a higher prevalence of RP-ILD than those with normal RDW (p<0.001). Prognostic analysis revealed that RDW was an independent risk factor for prognosis in patients with IIM-ILD (HR=2.9, p=0.03). Patients with dermatomyositis (DM) with RP-ILD with a change in RDW within 3 months (∆RDW-3) greater than 0 were more likely to die within 3 months. Moreover, the prevalence of ∆RDW-3>0 was higher in patients with RP-ILD and positive for anti-melanoma differentiation-associated gene 5 antibody who died within 3 months (87.5%) compared with those alive at 3 months (24.6%) (p<0.001). CONCLUSION: These findings suggest that repeated RDW assays could assist physicians in identifying patients with DM-ILD who were at a high risk of RP-ILD and death.

A Review of Antisynthetase Syndrome-Associated Interstitial Lung Disease.

Our objective in this review article is to present a clinical case of a patient with antisynthetase syndrome (ASyS) and provide an overview of the pathogenesis, classification criteria, antibody profiles, clinical features, and current knowledge of treatment options, focusing on interstitial lung disease (ILD). ASyS is an uncommon autoimmune disease with a heterogenous clinical presentation characterized by the presence of autoantibodies against an aminoacyl-tRNA synthetase and manifested by myositis, fever, inflammatory arthritis, Raynaud's phenomenon, mechanics hands, and ILD. ASyS-associated ILD (ASyS-ILD) is the most serious complication of ASyS, which may evolve to rapidly progressive ILD; therefore, it often requires thorough clinical and radiologic evaluation including recognition of a specific clinical phenotype associated with the antisynthetase antibodies (ASAbs) to guide therapeutic interventions.

The Value of Ultrasound for Detecting and Following Subclinical Interstitial Lung Disease in Systemic Sclerosis.

BACKGROUND: Interstitial lung disease (ILD) is a complication in patients with systemic sclerosis (SSc). Accurate strategies to identify its presence in early phases are essential. We conducted the study aiming to determine the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to ascertain its potential in determining the disease progression. METHODS: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), auscultation, chest radiographs, and respiratory function tests (RFT) were performed. A rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. The patients were followed every 12 weeks for 48 weeks. RESULTS: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p = 0.0001). Anti-centromere antibodies (p = 0.005) and RSS (p = 0.004) showed an association with ILD. A positive correlation was demonstrated between the US and HRCT findings (p = 0.001). The sensitivity and specificity of US in detecting ILD were 91.2% and 88.6%, respectively. In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. CONCLUSIONS: US showed a high prevalence of subclinical ILD in SSc patients. It proved to be a valid, reliable, and feasible tool to detect ILD in SSc and to monitor disease progression.

[Interstitial Lung Disease associated with Connective Tissue Diseases]. / Interstitielle Pneumopathien bei Konnektivitiden.

INTRODUCTION: Interstitial Lung Disease associated with Connective Tissue Diseases Abstract: Interstitial lung diseases (ILD) are in up to one-third of cases associated with connective tissue diseases (CTD). In systemic sclerosis, rheumatoid arthritis, polymyositis/dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease, an associated ILD significantly increases morbidity and mortality. The diagnostic workup for suspected CTD-ILD includes a range of functional, radiological, laboratory, and, if necessary, invasive tests. A thorough medical history and physical examination with targeted rheumatological diagnosis is particularly important. Also, patients with unclassified ILDs should be evaluated thoroughly for any underlying CTD. Pharmacological treatment options for CTD-ILD differ significantly from those for other ILDs. In addition to short-term glucocorticoids, antimetabolites and biological agents are often used. Antifibrotic drugs have also been successfully used in CTD-ILDs. The decision on whether and which immunosuppressive and/or antifibrotic therapy is indicated depends on the underlying disease, disease activity, extrapulmonary manifestations, severity of organ involvement, ILD progression, comorbidities, and patient preferences. Complex treatment decisions are ideally made in multidisciplinary expert teams.