Tissue Disease-related Interstitial Lung Disease Research Articles

Screening value of lung ultrasound and pleural shear wave elastography in connective tissue disease-related interstitial lung disease: a preliminary study.

To explore the diagnostic value of lung ultrasound (LUS) and pleural shear wave elastography (SWE) for connective tissue disease-interstitial lung disease (CTD-ILD). We selected 104 patients diagnosed with connective tissue disease (CTD) at our hospital. All patients underwent LUS, SWE, and high-resolution computed tomography (HRCT). With HRCT as the imaging gold standard for diagnosis, patients were categorized into CTD-ILD and CTD-non-ILD groups. We employed paired chi-square tests to compare the diagnostic differences between HRCT and LUS for ILD. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of pleural SWE for ILD. Correlation analysis was performed between pleural elasticity values and lung ultrasound scores. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of LUS for diagnosing CTD-ILD were 93.3%, 86.2%, 6.761, and 0.078, respectively. There was no statistically significant difference in the results between HRCT and LUS (P = 1.000), with a kappa value of 0.720 (P < 0.001). There was a statistically significant difference in the pleural elasticity in the bilateral lower back region between the case and control groups (P < 0.001). The area under the receiver operating characteristic (ROC) curve (AUC) for pleural SWE in diagnosing CTD-ILD was 0.685. In CTD-ILD patients, there was no significant correlation between pleural elasticity values and LUS scores (P > 0.05). The LUS can serve as an important imaging method for screening for CTD-ILD and assessing the severity of the disease. However, pleural SWE has been shown to demonstrate lower diagnostic efficacy for CTD-ILD, and its ability to assess disease severity is limited.

P129 Interdisciplinary collaboration in the care of patients with connective tissue disease-related interstitial lung disease in Wales: an interview study

Abstract Background/Aims Patients with connective tissue disease-related interstitial lung disease (CTD-ILD) often receive care from both rheumatologists and respiratory physicians to manage their conditions. As treatment options become increasingly complex with immunosuppressing and antifibrotic agents, there is a growing recognition of the importance of collaborative approaches to ensure accurate diagnosis, aid management decisions and deliver patient-centred care. However, there is currently no agreed optimal model for shared care, leading to significant practice variation. This study aimed to explore the perspectives of rheumatologists and respiratory physicians regarding the benefits and challenges of cross-speciality management in CTD-ILD. A better understanding of this will enhance the development of services and improve patient-centred care. Methods Semi-structured interviews, both face-to-face and virtual, were conducted with 11 respiratory physicians and nine rheumatologists working in Wales, ensuring representation from all health boards. Interview transcripts were analysed using thematic analysis to identify themes. Results Five main themes were identified: navigating complexity and uncertainty, reliance on clinical experience, prioritisation of efficiency, educational and training benefits, and inconsistent access to services for clinicians and patients. Conclusion The complexity of CTD-ILD care, combined with varying levels of physician expertise and a perceived lack of guidelines, presents significant challenges for clinicians. Cross-speciality collaboration is actively sought by physicians and is perceived to enhance patient care by improving efficiency, aiding confidence in decision-making and providing educational benefits to clinicians. However, resource limitations and geographical variations in service access hinder the implementation and development of shared care models. Physicians perceive that patients like being seen in joint clinics; future exploration of patient perspectives and experiences of joint care systems will be crucial to ensure the direction of clinical practice development remains patient-centred. In addition to implementing integrated cross-speciality clinical services, the development of joint respiratory and rheumatology guidelines as well as greater availability of training opportunities would assist physicians in delivering optimal care to patients with CTD-ILD. Disclosure P. Evans: None. K. Hett: None. N. Hutchinson: None. C. Beynon: None.

The Oral-Lung Microbiome Axis in Connective Tissue Disease-Related Interstitial Lung Disease.

Connective tissue disease-related interstitial lung disease (CTD-ILD) is a frequent and serious complication of CTD, leading to high morbidity and mortality. Unfortunately, its pathogenesis remains poorly understood; however, one intriguing contributing factor may be the microbiome of the mouth and lungs. The oral microbiome, which is a major source of the lung microbiome through recurrent microaspiration, is altered in ILD patients. Moreover, in recent years, several lines of evidence suggest that changes in the oral and lung microbiota modulate the pulmonary immune response and thus may play a role in the pathogenesis of ILDs, including CTD-ILD. Here, we review the existing data demonstrating oral and lung microbiota dysbiosis and possible contributions to the development of CTD-ILD in rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus. We identify several areas of opportunity for future investigations into the role of the oral and lung microbiota in CTD-ILD.

A Medical Record-based Pilot Study on the Diffusing Capacity of the Lungs for Carbon Monoxide versus Nailfold Capillaroscopy as an Early Marker for Lung Involvement in Connective Tissue Disease-related Interstitial Lung Diseases

Abstract Background: Connective tissue disease (CTD)-related interstitial lung diseases (ILDs) are one of the most common ILDs which affect relatively younger populations and can lead to extensive lung damage and fibrosis. Early detection and initiation of anti-inflammatory therapy can curtail the extent of lung damage. The diffusing capacity of the lungs for carbon monoxide (DLCO) is a well-established early marker of ILD. While most of the studies have shown specific nailfold capillaroscopy (NFC) findings in patients with CTD-ILD, none of them has evaluated the relation between diffusion impairment and nailfold capillary changes. The present study was carried out to evaluate the relationship between DLCO and NFC as markers for lung involvement in CTD-ILDs. Materials and Methods: This was a medical record-based observational study wherein the medical records of 100 diagnosed patients of CTD-ILD attending the pulmonology and rheumatology outpatient department were screened. Data concerning NFC, spirometry, and DLCO were collected and analyzed. Results: In our study of 100 patients, the minimum age was 29 years, and the maximum age was 78 years. A majority of patients in the study were found to be males (58%) and were suffering from CTD-ILD for a duration ranging from 2 to 5 years (58%). Eighty-nine percentage had a functional impairment on spirometry in the form of reduced forced vital capacity, and 61% had impaired DLCO. Nailfold capillary abnormalities were observed in all but one patient. The most common abnormal finding was a loss of capillary density (95% of patients) and a decrease in the intercapillary distance (94% of patients). A significant correlation was seen between diffusion impairment and abnormal nailfold capillary length. However, there was no significant correlation between DLCO and overall nailfold capillary abnormalities. Conclusion: The study concludes that NFC cannot be used as a tool to monitor diffusion impairment of the lungs in CTD-ILD. DLCO is a better assessment method compared to NFC changes as an indicator of lung involvement in CTD-ILD.

Radiologic approach and progressive exploration of connective tissue disease-related interstitial lung disease: meeting the curiosity of rheumatologists.

Interstitial lung disease (ILD) is often observed in connective tissue diseases (CTDs), frequently in rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and inflammatory myositis. Early detection of ILDs secondary to rheumatic diseases is important as timely initiation of proper management affects the prognosis. Among many imaging modalities, high-resuloution computed tomography (HRCT) serves the gold standard for finding early lung inflammatory and fibrotic changes as well as monitoring afterwards because of its superior spatial resolution. Additionally, lung ultrasound (LUS) and magnetic resonance imaging (MRI) are the rising free-radiation imaging tools that can get images of lungs of CTD-ILD. In this review article, we present the subtypes of ILD images found in each CTD acquired by HRCT as well as some images taken by LUS and MRI with comparative HRCT scans. It is expected that this discussion would be helpful in discussing recent advances in imaging modalities for CTD-ILD and raising critical points for diagnosis and tracing of the images from the perspective of rheumatologists.

Imaging Features of Idiopathic Interstitial Lung Diseases.

Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unclear etiology and are distinguished from diffuse parenchymal lung diseases of known cause, such as connective tissue disease-related interstitial lung diseases or hypersensitivity pneumonitis by history, physical exam, imaging, serologic testing, and, when necessary, histopathology. The 2013 American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines are the most widely accepted classification of IIPs and include the following diagnoses: idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, idiopathic lymphocytic interstitial pneumonia, idiopathic pleuro-parenchymal fibroelastosis, respiratory bronchiolitis-interstitial lung disease, and desquamative interstitial pneumonia. The gold standard for diagnosis of IIP involves multidisciplinary discussion among pulmonologists, radiologists, and pathologists. The focus of this review will be to discuss the imaging features of the most common IIPs and the role of multidisciplinary discussion as the gold standard for diagnosis.

Real world experience with nintedanib in connective tissue disease-related interstitial lung disease: a retrospective cohort study.

Various connective tissue diseases tend to affect specific organs, lungs being the organ with the most serious repercussions and consequences. The diagnosis of interstitial lung disease makes the treatment more difficult and worsens long-term prognosis and overall survival. Positive results from the registration studies of nintedanib led to approval of the drug for the treatment of idiopathic pulmonary fibrosis and chronic fibrosing interstitial lung diseases in connective tissue diseases. After registration, real-world data on the use of nintedanib are being collected in everyday clinical practise.The objective of the study was to collect and analyse real world experience gathered after the registration of nintedanib for the treatment of CTD-ILD and to show if the positive results collected from a homogeneous and "representative" study population can be applied to everyday clinical practice.We are presenting a retrospective observational case-series study of patients treated with nintedanib from the three largest Croatian centers specialised in the treatment of connective tissue diseases with interstitial lung diseases.Stabilisation or improved of lung function tests was reported in 68% of patients when changes in predicted FVC were observed and in 72% of patients when changes in DLco were analysed. Almost all of the reported patients (98%) were treated with nintedanib as an add-on drug to immunosuppressants. The most common side-effects were gastrointestinal symptoms and abnormal liver function tests in less extent.Our real-world data confirm the tolerability, efficacy and similar side-effects of nintedanib as reported in pivotal trials. Key Points • Interstitial lung disease is a common manifestation of several connective tissue diseases and its progressive fibrosing phenotype contributes to high mortality rate and many unmet needs regarding the treatment remain. • Registration studies of nintedanib obtained sufficient data and positive results to support approval of the drug. • Real-world evidence from our CTD-ILD centres confirm the clinical trial data regarding efficacy, tolerability and safety of nintedanib.

Monitoring small airway dysfunction in connective tissue disease-related interstitial lung disease: a retrospective and prospective study

BackgroundSmall airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored.MethodsWe conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment.ResultsCTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 ± 18.3 vs. 80.0 ± 20.9, p < 0.001) and lower diffusion capacity (% predicted DLCO, 58.8 ± 19.7 vs. 63.8 ± 22.1, p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 ± 1.53, p < 0.001 in patients with SAD; 5.13 ± 1.53, p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters.ConclusionIn our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.

Factors for progressive pulmonary fibrosis in connective tissue disease-related interstitial lung disease.

Progressive fibrosis can occur in connective tissue disease (CTD)-related interstitial lung disease (ILD) and make the prognosis worse. This study aimed to investigate factors related to progressive pulmonary fibrosis (PPF) phenotype in CTD-ILDs. Medical records of patients diagnosed as CTD and ILD at a single, tertiary hospital in South Korea were retrospectively reviewed. Patients whose lung functions were followed up for more than a year were included in analysis. PPF was defined as forced vital capacity (FVC) declined ⩾10% or diffusion capacity of carbon monoxide (DLco) ⩾15%. Of 110 patients with CTD-ILD, 24.5% progressed into PPF. Rheumatoid arthritis (RA) and Sjogren's disease accounted for more than 63% of PPF. Compositions of CTD type were similar between PPF and non-PPF. Clinical characteristics and proportion of usual interstitial pneumonia (UIP) pattern on chest images were also similar between PPF and non-PPF. Approximately 10% of patients in both groups were treated with anti-fibrotic agents. Use of systemic steroids and/or other immunomodulating agents lowered the risk of developing PPF in CTD-ILD patients after adjusting for gender-age-physiology score and smoking status (adjusted odds ratio: 0.25, 95% confidence interval: 0.07-0.85). About a quarter of CTD-ILD progressed into PPF. The use of immunomodulating agents lowered the risk of developing PPF. To improve outcomes of patients, future studies need to detect patients at higher risk for PPF earlier and set up clinical guidelines for treatment strategies in the process of PPF.

Clinical and HRCT features of amyopathic dermatomyositis associated with interstitial lung disease: A retrospective study of 128 patients with connective tissue disease-related interstitial lung disease

BackgroundThis study retrospectively analyzed the laboratory data and chest images of patients with amyopathic dermatomyositis associated with interstitial lung disease (ADM-ILD) and patients with other connective tissue disease-related ILDs (CTD-ILDs) to find a characteristic index for the early recognition of ADM-ILD and help clinicians consider the possibility of ADM-ILD as soon as possible. MethodsIn our cohort study, the records of 128 Chinese patients with CTD-ILD, including 33 ADM-ILD patients, 37 rheumatoid arthritis (RA)-ILD patients, 33 primary Sjogren's syndrome (pSS)-ILD patients, 14 systemic sclerosis (SSc)-ILD patients and 11 systemic lupus erythematosus (SLE)-ILD patients. The patients’ clinical features, laboratory parameters, and chest HRCT findings were analyzed. ResultsADM-ILD patients generally had significantly higher LDH (333.52±160.21 U/L), AST (66.21±83.66 U/L), and CK-MB (18.23±8.28 U/L) levels than other CTD-ILD patients. A total of 90.91% (30/33) of ADM-ILD patients had elevated LDH. Patients with ADM-ILD were more prone to organizing pneumonia radiologic patterns on chest HRCT scans than patients with other CTD-ILDs (χ2=37.39, p < 0.001) and were found in 18 of 33 ADM-ILD patients. Anti-MDA5 (45.45%) was the most commonly detected autoantibody in ADM-ILD patients, followed by anti-PL-7 (21.21%), anti-Jo-1 (12.12%), and anti-PL-12 (9.09%), and levels of ALT (96.93±119.79 vs. 17.50±6.218 U/L), AST (113.00±106.13 vs. 23.56±6.91 U/L), LDH (415.00±198.51 vs. 261.94±67.75 U/L) and CK-MB (22.57±5.91 vs. 14.61±8.36 U/L) were significantly higher in anti-MDA5-positive patients, but these patients had significantly lower WBC counts (4.82±2.61 vs. 7.14±3.00 × 109/L), lymphocyte counts (0.72±0.20 vs. 1.23±0.53 × 109/L), and ALB levels (31.90±4.76 vs. 35.49±4.71 g/L). ConclusionsADM-ILD patients have higher serum LDH, AST and CK-MB levels, especially serum LDH levels, and are more prone to organizing pneumonia radiologic patterns on chest HRCT scans than other CTD-ILD patients. A high level of serum LDH with ILD may be a useful characteristic index for recognizing ADM-ILD.

Connective tissue disease-related interstitial lung disease is alleviated by tripterine through inhibition of the PI3K/Akt, apoptosis, and TNF-α signalling pathways.

Background: Interstitial lung disease (ILD) is the major cause of morbidity and mortality in patients with various rheumatic diseases. However, more interventions need to be sought. Tripterine, an extract of Tripterygium wilfordii Hook. F, has been widely studied for its powerful anti-inflammatory effect. However, its mechanism of action in treating connective tissue disease-related (CTD)-ILD remains unclear. Purpose: To investigate the mechanism of tripterine in CTD-ILD treatment by combining network pharmacology and an in vivo experiment. Methods: The related targets of tripterine were obtained after searching the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform, Comparative Toxicogenomics Database, GeneCards, Search Tool for Interacting Chemicals database, and SymMap database. Following this, Online Mendelian Inheritance in Man, GeneCards, Genebank, and DrugBank were used to screen the targets of CTD-ILD. A target-signalling pathway network was constructed using Cytoscape. Additionally, topological analysis was performed. Protein interaction analysis was performed using the STRING online analysis platform. Following this, Gene Ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) signalling pathway enrichment analyses were performed. Subsequently, the molecular docking between tripterine and the core targets was verified. Finally, experimental verification was performed in bleomycin-induced model mice. Results: A total of 134 common targets and 10 core targets of tripterine, including signal transducer and activator of transcription 3, tumour necrosis factor (TNF), v-rel avian reticuloendotheliosis viral oncogene homolog A, protein kinase B (Akt) α (Akt1), mitogen-activated protein kinase (MAPK) 1, Jun transcription factor family, tumour protein 53, MAPK3, nuclear factor kappa B subunit 1, and caspase 8, were obtained. GO enrichment analysis revealed that, while treating CTD-ILD, tripterine was mainly involved in cytokine receptor binding, receptor-ligand activity, signal receptor activation, cytokine activity, protein ubiquitination, deoxyribonucleic acid transcriptase activity, etc. The KEGG pathway enrichment analysis revealed that the most significant signalling pathways were multiple viral infections and the phosphatidylinositol-3-kinase (PI3K)/Akt, TNF, and apoptosis signalling pathways. Molecular docking results revealed that tripterine had good docking activity with the core targets. Experimental studies also demonstrated that tripterine could inhibit the activation of PI3K/Akt, apoptosis, and TNF-α signalling pathways in lung tissue and significantly improve lung pathology and collagen deposition in the model mice. Conclusions: This study preliminarily revealed the potential molecular biological mechanism of tripterine while treating CTD-ILD might be related to inhibiting the PI3K/Akt, apoptosis, and TNF-α signalling pathways. Tripterygium wilfordii Hook. F. and its extract could be used clinically for treating CTD-ILD.

Scorpion venom polypeptide governs alveolar macrophage M1/M2 polarization to alleviate pulmonary fibrosis

The onset of connective tissue disease-related interstitial lung disease (CTD-ILD) is generally insidious and progressive, with pulmonary fibrosis in the middle stage, and eventually respiratory failure and death. This study aimed to explore the role of scorpion venom polypeptide (SVP), the primary active constituent of the entire scorpion, in alveolar macrophages and pulmonary fibrosis. Pulmonary fibrosis mouse models were established, and then SVP and JAK inhibitor (tofacitinib) was used to treat models. Alveolar macrophages were isolated and the impacts of SVP on M1/M2 polarization and the JAK/STAT6 pathway in vitro were assessed. H&E and Masson staining revealed that SVP and tofacitinib treatment alleviated lung damage and fibrosis. They also hindered the M2-polarization of macrophages in lung tissue and declined cytokine levels associated with M2 polarization (IL-4, IL-13) and fibrosis drivers (TGF-β, VEGF) in mice. Consistent with the trend presented by tofacitinib treatment, SVP suppressed the phosphorylation of proteins in the JAK/STAT6 pathway. In addition, the in vitro treatment of SVP on the isolated macrophages represented consistent results with in vivo experiments. The findings of the present study indicated that SVP suppressed the JAK/STAT6 signaling pathway, hindered alveolar macrophage M2-type polarization, and possessed the potential to ameliorate pulmonary fibrosis.

Is conventional transbronchial lung biopsy out: The evaluation of clinical value in diffuse parenchymal lung disease

IntroductionTransbronchial lung biopsy (TBLB) is a relatively safe technique routinely employed by pulmonologists for the diagnosis of diffuse parenchymal lung disease (DPLD). Cryobiopsy is associated with higher diagnostic yield and a favorable risk/benefit ratio. Nevertheless, TBLB remains the representative method for definite diagnosis in developing countries.ObjectivesThis study aimed to evaluate whether the results obtained from TBLB had clinical value to pulmonologists in the management of DPLD.MethodsWe performed a retrospective analysis of patients who underwent conventional TBLB for the diagnosis of DPLD from May 1, 2017, to April 30, 2019, at the Beijing Chao‐yang Hospital, Capital Medical University. The clinical value of TBLB was defined as leading to a specific histopathological diagnosis or being consistent with the clinical and radiological data.ResultsSeven hundred and forty‐three patients with suspected DPLD were recruited. Conventional TBLB was considered clinically valuable in 439 procedures (59.1%), including 360 cases provided with definitive histopathological diagnoses, and 79 cases that were consistent with the working diagnoses. Among the 439 cases of clinically valuable TBLBs, 88 (20.0%), 37, 77 (10.7%), and 61 (13.9%) cases were diagnosed as connective tissue disease‐related interstitial lung disease, definite histopathological diagnoses, malignancies, and nonspecific interstitial pneumonia, respectively.ConclusionsConventional TBLB served as a key determinant or provided supplementary information in the final diagnosis of non‐infectious DPLDs. TBLB decision‐making should therefore be based on clinical and radiological data.

Evaluation of connective tissue disease-related interstitial lung disease using ultrasound elastography: a preliminary study.

Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD), which can lead to shortened survival. This article explores the ability of shear wave elastography (SWE) to assess lung surface elastic properties and to distinguish healthy lungs from diseased lungs with connective tissue disease-related interstitial lung disease (CTD-ILD). We aimed to determine whether SWE can be used to assess the severity of CTD-ILD. A total of 65 CTD-ILD patients and 60 healthy volunteers were included for the case group and the control group, respectively. All participants underwent lung ultrasound (count of B-line and measurement of pleural line thickness) and SWE [measurement of Young's modulus (Emean) and shear wave velocity (SMV) (Cmean)] examinations at 50 lung sites. All participants also underwent an examination with high-resolution computed tomography (HRCT) and a pulmonary function test (PFT). For SWE assessment, the Q-box was set to its minimum size (1 mm) and manually placed on the pleural line, rather than inside the lung, to measure the stiffness of the lung surface. The intra- and inter-reliability of SWE measurements of healthy controls (HC), the receiver operating characteristic (ROC) curve for SWE for CTD-ILD, and correlations between different assessment methods were analyzed. Excellent intra- and inter-reliability of SWE measurements on the mid-anterior lung site of HCs (correlation coefficient >0.97; P<0.01) were found. The results of the lung ultrasound of case group participants were significantly higher than those of HCs at each site (P<0.001). The SWE results revealed a significant increase in both Emean and Cmean in CTD-ILD patients (P<0.001) compared with HCs at certain sites (P<0.001). The areas under the curve (AUC) of Emean and Cmean for CTD-ILD were 0.646 and 0.647 (P<0.05), respectively, and the cutoff values for Emean and Cmean to distinguish CTD-ILD from healthy lungs were 15.81 kPa and 2.31 m/s, respectively. There was no significant correlation between the SWE measured values and the number of B-lines, or the HRCT and PFT results, respectively (P>0.05). As a noninvasive ultrasound elastography (UE) technique, SWE may provide a novel method to differentiate CTD-ILD-affected lungs and healthy lungs. It is a reliable way to measure the stiffness of a healthy lung surface in the supine position. However, the ability of SWE to evaluate the severity of CTD-ILD may be limited.

Study on short term treatment response of connective tissue disease related interstitial lung disease

Background: Interstitial lung disease is a major cause of morbidity and mortality in patients suffering from connective tissue diseases. Early detection and prompt recognition of symptoms with appropriate treatment is necessary for effective control of the disease and for better prognosis and long-term survival. Aim: To study the short-term treatment response of patients with connective tissue disease-related interstitial lung disease. Objectives: The purpose of this study was to evaluate the treatment response of connective tissue disease-related interstitial lung disease patients treated with intravenous pulses of cyclophosphamide (CYP) based on improvements in lung function: forced vital capacity (FVC)% predicted, forced expiratory volume in the first second (FEV1)% predicted, dyspnea Borg scale and 6-minute walk test. To determine the factors affecting the treatment outcomes like age, sex, duration of the connective tissue disease, type of connective tissue disease, HRCT type, and presence of PAH. Methods: A cohort study was conducted in the Department of General Medicine, Rheumatology, and Pulmonology at the Amala Institute of Medical Sciences, Thrissur, and Kerala from November 2015 to June 2017 that evaluated 74 patients having connective tissue disease-related ILD. A detailed history and a thorough clinical examination were done.

The mechanism of triptolide in the treatment of connective tissue disease-related interstitial lung disease based on network pharmacology and molecular docking

Background Interstitial lung disease (ILD) is associated with substantial morbidity and mortality, which is one of the key systematic manifestations of connective tissue disease (CTD). Tripterygium wilfordii, known as Leigongteng in Chinese, has been applied to treat connective tissue disease-related interstitial lung disease (CTD-ILD) for many years. Triptolide is a key effective component from Tripterygium wilfordii. But the molecular mechanism of Triptolide for treating CTD-ILD is not yet clear. Methods Gaining insight into the molecular mechanism of Triptolide intervention CTD-ILD, we used the method of network pharmacology. And then we conducted drug-target networks to analyse the potential protein targets between Triptolide and CTD-ILD. Finally, AutoDock Vina was selected for molecular docking. Results By analysing the interaction genes between Triptolide and CTD-ILD, 242 genes were obtained. The top 10 targets of the highest enrichment scores were STAT3, AKT1, MAPK1, IL6, TP53, MAPK3, RELA, TNF, JUN, JAK2. GO and KEGG enrichment analysis exhibited that multiple signalling pathways were involved. PI3K-Akt, multiple virus infections, cancer signalling, chemokine, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. And it is related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. Molecular docking shows Triptolide can bind with its target protein in a good bond by intermolecular force. Conclusions This study preliminarily reveals the internal molecular mechanism of Triptolide interfere with CTD-ILD through multiple targets, multiple access, validated through molecular docking. KEY MESSAGES Triptolide intervention CTD-ILD, which are related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. PI3K-Akt, multiple virus infections, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. Triptolide can bind with related target protein in a good bond by Intermolecular force, exhibiting a good docking activity.

Covid-19 Course in Connective Tissue Disease-Related Interstitial Lung Disease Patients

Covid-19 Course in Connective Tissue Disease-Related Interstitial Lung Disease Patients

Medication-induced Pulmonary Injury: A Scenario- and Pattern-based Approach to a Perplexing Problem.

Medication-induced pulmonary injury (MIPI) is a complex medical condition that has become increasingly common yet remains stubbornly difficult to diagnose. Diagnosis can be aided by combining knowledge of the most common imaging patterns caused by MIPI with awareness of which medications a patient may be exposed to in specific clinical settings. The authors describe six imaging patterns commonly associated with MIPI: sarcoidosis-like, diffuse ground-glass opacities, organizing pneumonia, centrilobular ground-glass nodules, linear-septal, and fibrotic. Subsequently, the occurrence of these patterns is discussed in the context of five different clinical scenarios and the medications and medication classes typically used in those scenarios. These scenarios and medication classes include the rheumatology or gastrointestinal clinic (disease-modifying antirheumatic agents), cardiology clinic (antiarrhythmics), hematology clinic (cytotoxic agents, tyrosine kinase inhibitors, retinoids), oncology clinic (immune modulators, tyrosine kinase inhibitors, monoclonal antibodies), and inpatient service (antibiotics, blood products). Additionally, the article draws comparisons between the appearance of MIPI and the alternative causes of lung disease typically seen in those clinical scenarios (eg, connective tissue disease-related interstitial lung disease in the rheumatology clinic and hydrostatic pulmonary edema in the cardiology clinic). Familiarity with the most common imaging patterns associated with frequently administered medications can help insert MIPI into the differential diagnosis of acquired lung disease in these scenarios. However, confident diagnosis is often thwarted by absence of specific diagnostic tests for MIPI. Instead, a working diagnosis typically relies on multidisciplinary consensus. ©RSNA, 2021.

Assessing the role for nailfold videocapillaroscopy in interstitial lung disease classfication: a systematic review and meta-analysis.

The nailfold videocapillaroscopy (NVC) has been known to assist with interstitial lung disease (ILD) classification. However, evidence on its diagnostic efficacy is limited, particularly in some connective tissue disease-related interstitial lung diseases (CTD-ILD), and in interstitial pneumonia with autoimmune features (IPAF). This study aimed to address this limitation by conducting a meta-analysis on the efficacy of the NVC in ILD subgroups of CTD-ILD, IPAF and idiopathic pulmonary fibrosis (IPF). MEDLINE, EMBASE, CENTRAL were screened from inception to December 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that report prevalence of nailfold abnormalities (NVC+) in CTD-ILD, IPAF and IPF cohorts were included. Data were presented as prevalence ratio (PR) with 95% CI using a random-effects model. Quality of evidence was assessed using GRADE criteria. Twenty-one studies were eligible. Prevalence of NVC+ was highest in CTD-ILD; PR (95 CI%) 80.4% (74.3%, 85.3%), followed by IPAF; 27.4% (10.9%, 53.7%), and IPF; 13.8% (5.7%, 29.9%). Late scleroderma pattern was the most prevalent nailfold pattern; 40.4% (28.1%, 54.1%) in our CTD-ILD cohort. Quality of evidence was low for CTD-ILD, IPAF and IPF cohorts, moderate for the late scleroderma pattern cohort. NVC can increase the diagnostic accuracy of ILD when used in a multi-disciplinary setting, and appears to have greatest utility in CTD-ILD, followed by IPAF and IPF. The Late Scleroderma Pattern was the most frequent nailfold capillary pattern in SSc-ILD. Future research will allow for greater understanding of the prognostic value of the NVC in ILD.

Predictive Factors for Pneumomediastinum During Management of Connective Tissue Disease-related Interstitial Lung Disease: A Retrospective Study.

Objective To identify factors associated with pneumomediastinum during management of connective tissue disease (CTD)-related interstitial lung disease (ILD). Methods Patients diagnosed with pneumomediastinum after the initiation of corticosteroid therapy for their CTD-ILD were enrolled. The baseline characteristics of patients who developed pneumomediastinum after the initiation of corticosteroid therapy (n=13, all occurring within 120 days) were compared to those of patients who did not develop pneumomediastinum (n=49). A multivariate logistic regression analysis was performed to identify factors associated with pneumomediastinum. A receiver operating characteristic (ROC) curve analysis was also performed to assess the predictive performance. Results The body mass index (BMI) [odds ratio (OR) (95% confidence interval (CI)) 0.482 (0.272-0.853)] and serum lactate dehydrogenase (LDH) [OR (95% CI) 1.013 (1-1.025)] levels at baseline were identified as independent factors associated with pneumomediastinum after corticosteroid initiation. The optimal cut-off points of the BMI and LDH levels for predicting pneumomediastinum development, as estimated by the Youden index, were 20.2 kg/m2 and 378 U/L, respectively. LDH showed a sensitivity of 61.5% and the highest specificity of 87.8%. Importantly, combining these markers resulted in the highest sensitivity of 100% and a specificity of 71.4%. Conclusion A low BMI and high serum LDH levels at baseline are useful predictive factors for pneumomediastinum development in CTD-ILD patients.