Connective Tissue Disease-related Interstitial Lung 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.

Hospitalization Rates in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Registry.

Little is known about hospitalization in other types of interstitial lung disease (ILD) besides idiopathic pulmonary fibrosis (IPF). We sought to determine the frequency of hospitalizations in various types of ILD and elucidate the association of hospitalization with outcomes. An analysis of the Pulmonary Fibrosis Foundation Patient Registry data was performed. Inpatient hospitalization rates and survival following hospitalization were compared for various types of ILD. Hospitalization rates were similar across ILD types (40.6% of IPF participants, 42.8% of connective tissue disease related ILD (CTD-ILD), 44.9% of non-IPF idiopathic interstitial pneumonia (IIPs), 46.5% of chronic hypersensitivity pneumonitis (CHP) participants, and 53.3% of "other" ILD participants). All-cause hospitalization was not associated with decreased transplant-free survival (adjusted hazard ratio (AHR) 1.20, 95% CI: 0.98, 1.46, p=0.0759) after adjusting for co-morbidities and severity of illness; however respiratory-related hospitalization was (AHR 1.53, 95% CI: 1.23, 1.90, p=0.0001). CTD-ILD (HR 0.43, 95% CI: 0.25, 0.75, p=0.0031) and non-IPF IIP (HR 0.3, 95% CI: 0.15, 0.58, p=0.005) had a lower risk of death following hospitalization compared to IPF while CHP (HR 0.67, 95% CI: 0.37, 1.20, p=0.1747) and "other-ILD" (HR 0.54, 95% CI: 0.19, 1.54, p=0.25) had a comparable risk to IPF. Rates of hospitalization are similar across ILD subtypes. The risk of death or transplant following hospitalization is lower in CTD-ILD, CHP and non-IPF IIP compared to IPF participants. In a mixed population of ILD participants, all-cause hospitalizations were not associated with decreased transplant-free survival; however respiratory-related hospitalizations were.

Connective tissue disease related interstitial lung disease: a single center experience

Objectives: We aimed to determine the clinical features of the patients followed by our hospital with the diagnosis of connective tissue disease related interstitial lung disease (CTD-ILD). Methods: The study included 113 patients who were followed up with the diagnosis of CTD-ILD, admitted to Kahramanmaraş Sütçü İmam University, Faculty of Medicine, Rheumatology Department between January 2019 and December 2020. Demographic characteristics, laboratory data and high-resolution computed tomography (HRCT) patterns of the patients were recorded retrospectively. Results: Of 113 patients diagnosed with CTD-ILD; 90 were female, 23 were male. When the distribution of connective tissue disease (CTD) evaluated; 50 were rheumatoid arthritis, 41 were systemic sclerosis, 8 were sjogren's syndrome, 4 were systemic lupus erythematosus, 7 were overlap syndrome and 3 were undifferentiated connective tissue disease. There was no statistically significant difference between laboratory parameters. In the HRCT evaluation, 86 patients had nonspecific interstitial pneumonia (NSIP), 25 patients had usual interstitial pneumonia (UIP), and 2 patients had lymphocytic interstitial pneumonia (LIP) pattern. The most common pattern, including rheumatoid arthritis, was NSIP. Conclusions: In our study, as inconsistent with the literature the most common pattern in RA patients was found to be NSIP.

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.

Alveolar nitric oxide concentration has a potential value in the diagnosis and differential diagnosis of interstitial lung diseases

To investigate the value of exhaled nitric oxide (eNO) in the diagnosis and differential diagnosis of interstitial lung disease (ILD). This study was conducted among 45 patients with interstitial lung disease, including 18 with connective tissue disease-related ILD (CTD-ILD) and 27 with non-CTD-ILD, with 68 healthy subjects as the control group. According to European Respiratory Association Guidelines, alveolar nitric oxide (CaNO) concentration and fractional exhaled nitric oxide (FeNO) level were measured at the flow rates of 50 and 200 mL/s. The predictive level of CaNO was analyzed using receiver-operating characteristic curve (ROC), and the correlations between CaNO and pulmonary function indicators were examined in the patients with ILD. CaNO, FeNO50, and FeNO200 levels were significantly higher in patients with ILD than in the healthy controls. Logistic regression analysis showed that lowered levels of CaNO and FeNO200 were risk factors for ILD. ROC curve analysis showed that the area under the curve (AUC) of CaNO combined with FeNO200 was 0.829 (95% CI: 0.752-0.906) for the diagnosis of ILD. In patients with ILD, CaNO levels were negatively correlated with DLCO%pred (r=-0.471, P < 0.05). Subgroup comparison showed a significantly higher CaNO level in CTD-ILD group than in non-CTD-ILD group. The AUC for CaNO to discriminate CTD-ILD from non-CTD-ILD was 0.725 (95% CI: 0.576 to 0.875). CaNO has a potential value in the diagnosis of ILD and differential diagnosis of CTD-ILD.

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.

Diagnostic Value of Connective Tissue Disease Related CT Signs in Usual Interstitial Pneumonia Pattern of Interstitial Lung Disease.

Purpose Usual interstitial pneumonia (UIP) pattern of interstitial lung disease (ILD) can have varied etiology, with connective tissue disease (CTD) being a common known cause. The anterior upper lobe (AUL) sign, exuberant honeycombing (EHC), and straight edge (SE) sign are recently described computed tomography (CT) signs in CTD-related UIP. We test the diagnostic value of these CT signs for CTD in patients with UIP and compare the incidence of these signs between CTD-related UIP and non-CTD-related UIP. We also evaluated the interobserver agreement in detection of these CT signs. Methods Retrospective study of all patients who had UIP pattern of ILD on CT thorax done from January 1, 2016 to January 31, 2019, was grouped into two: non-CTD-related UIP or CTD-related UIP. CT thorax was reviewed for the presence of these signs-AUL, SE, and EHC. The diagnostic values of these signs in diagnosing CTD-related UIP was assessed. For assessment of interobserver agreement, another radiologist reviewed a subset of 30 randomly selected cases and looked for the presence of these signs. Results Of the 156 patients included, 76 had CTD. The incidence of CT signs were significantly higher in CTD-related UIP. The specificities of AUL, EHC, and SE were 82.5, 75, and 85%, respectively. The EHC sign had highest sensitivity of 48.7%. Inclusion of more than one sign increased the specificity of diagnosis of CTD-related UIP; however, the sensitivity decreases. There was excellent interobserver agreement (0.81-0.87) for each of these signs. Conclusion The presence of SE, AUL, and EHC signs in cases with UIP pattern are specific imaging markers to diagnose underlying CTD; however, due to its low sensitivity, the absence of these signs cannot exclude the same. Because of its excellent interobserver agreement, these signs are reliable in the evaluation of CTD-related ILD.

Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease.

To investigate the role of serum B-cell activating factor (BAFF) and lung ultrasound (LUS) B-lines in connective tissue disease related interstitial lung disease (CTD-ILD), and their association with different ILD patterns on high resolution computed tomography (HRCT) of chest. We measured the levels of BAFF and KL-6 by ELISA in the sera of 63 CTD-ILD patients [26 with fibrotic ILD (F-ILD), 37 with non-fibrotic ILD (NF-ILD)], 30 CTD patients without ILD, and 26 healthy controls. All patients underwent chest HRCT and LUS examination. Serum BAFF levels were significantly higher in CTD patients compared to healthy subjects (617.6 ± 288.1 pg/ml vs. 269.0 ± 60.4 pg/ml, p < 0.01). BAFF concentrations were significantly different between ILD group and non-ILD group (698.3 ± 627.4 pg/ml vs. 448.3 ± 188.6 pg/ml, p < 0.01). In patients with ILD, BAFF concentrations were significantly correlated with B-lines number (r = 0.37, 95% CI 0.13-0.56, p < 0.01), KL-6 level (r = 0.26, 95% CI 0.01-0.48, p < 0.05), and Warrick score (r = 0.33, 95% CI 0.09-0.53, p < 0.01), although all correlations were only low to moderate. B-lines number correlated with Warrick score (r = 0.65, 95% CI 0.48-0.78, p < 0.01), and KL-6 levels (r = 0.43, 95% CI 0.21-0.61, p < 0.01). Patients with F-ILD had higher serum BAFF concentrations (957.5 ± 811.0 pg/ml vs. 516.1 ± 357.5 pg/ml, p < 0.05), KL-6 levels (750.7 ± 759.0 U/ml vs. 432.5 ± 277.5 U/ml, p < 0.05), B-lines numbers (174.1 ± 82 vs. 52.3 ± 57.5, p < 0.01), and Warrick score (19.9 ± 4.6 vs. 13.6 ± 3.4, p < 0.01) vs. NF-ILD patients. The best cut-off values to separate F-ILD from NF-ILD using ROC curves were 408 pg/ml for BAFF (AUC = 0.73, p < 0.01), 367 U/ml for KL-6 (AUC = 0.72, p < 0.05), 122 for B-lines number (AUC = 0.89, p < 0.01), and 14 for Warrick score (AUC = 0.87, p < 0.01) respectively. Serum BAFF levels and LUS B-lines number could be useful supportive biomarkers for detecting and evaluating the severity and/or subsets of CTD-ILD. If corroborated, combining imaging, serological, and sonographic biomarkers might be beneficial and comprehensive in management of CTD-ILD.

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.

Health-related quality of life in a multiracial Asian interstitial lung disease cohort.

Understanding health-related quality of life (HRQL) in patients with interstitial lung disease (ILD) provides insight into disease burden and treatment effects on patients' well-being. We examined HRQL in a multiracial Asian ILD cohort using the King's brief ILD (K-BILD) and EuroQol 5-dimension-3-level (EQ5D-3L) questionnaires and their associations with several clinical variables. This was a single-centre cross-sectional study of ILD patients in a university-affiliated tertiary public hospital in Singapore. All patients completed two self-administered HRQL questionnaires upon study entry, and their clinical information was retrieved from electronic medical records. Ninety-nine patients (56% male, 75% Chinese) were included. The median (interquartile range) age was 63 (54-72) years. The most common ILD diagnosis was connective tissue disease-related ILD (n=51, 52%), followed by idiopathic pulmonary fibrosis (n=27, 27%). The mean (standard deviation) scores for the EQ5D-3L utility value, EQ5D Visual Analogue Scale (VAS) and K-BILD total were 0.806 (0.284), 75.1 (12.8) and 63.9 (14.3), respectively. A moderate correlation was found between the EQ5D-3L and K-BILD total and domain scores. The HRQL scores also correlate moderately with the modified Medical Research Council dyspnoea scale (mMRC) scores. There was a weak-to-moderate correlation between HRQL and forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) and Charlson comorbidity index. Multiple linear regression showed a significant association of K-BILD total [beta coefficient 0.244, 95% confidence interval (CI): 0.075-0.414; P=0.005], K-BILD 'breathlessness and activities' (beta coefficient 0.448, 95% CI: 0.192-0.703; P=0.001), and the 'psychological' domain (beta coefficient 0.256, 95% CI: 0.024-0.488; P=0.031) with DLCO %pred after adjustment for age, sex, BMI, race, smoking history, comorbidities, FVC %pred and ILD diagnosis. Non-Chinese race was a predictor of better K-BILD 'psychological' domain (beta coefficient 8.680, 95% CI: 0.656-16.704; P=0.034) after adjustment. HRQL is significantly impaired in ILD patients, and low DLCO is a strong predictor of this impairment.

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.