Tissue Disease-associated Interstitial Lung Disease Research Articles

Quantitative evaluation of disease severity in connective tissue disease-associated interstitial lung disease by dual-energy computed tomography

BackgroundHigh-resolution computed tomography (HRCT) is recommended diagnosing and monitoring connective tissue disease-associated interstitial lung disease (CTD-ILD). Quantitative computed tomography has the potential to precisely assess the radiological severity of CTD-ILD, but has still been under study.ObjectiveTo investigate whether dual-energy computed tomography (DECT), a novel quantitative technique, can be used for quantitative severity assessment in CTD-ILD.MethodsThis cross sectional study recruited adult CTD-ILD patients who underwent DECT scans from the ICE study between October 2019 and November 2021. DECT parameters, including effective atomic number (Zeff), lung (lobe) volume, and monochromatic CT number (MCTN) of each lung lobe, were evaluated. CTD-ILD was classified into extensive CTD-ILD and limited CTD-ILD by staging algorithm using combined forced vital capacity (FVC)%predicted and total extent of ILD (TEI) on CT. Dyspnea, cough, and life quality were scored by Borg dyspnea score, Leicester cough questionnaire (LCQ), and short-form 36 health survey questionnaire (SF-36), respectively.ResultsThere was a total of 147 patients with DECT scans enrolled. Higher Zeff value (3.104 vs 2.256, p < 0.001), higher MCTN (− 722.87 HU vs − 802.20 HU, p < 0.001), and lower lung volume (2309.51cm3 vs 3475.21cm3, p < 0.001) were found in extensive CTD-ILD compared with limited CTD-ILD. DECT parameters had significant moderate correlations with FVC%predicted (|r|= 0.542–0.667, p < 0.01), DLCO%predicted (|r|= 0.371–0.427, p < 0.01), and TEI (|r|= 0.485–0.742, p < 0.01). Receiver operating characteristic (ROC) analysis indicated MCTN averaged over the whole lung had the best performance for extensive CTD-ILD discrimination (AUC = 0.901, cut-off: − 762.30 HU, p < 0.001), with a sensitivity of 82.1% and a specificity of 85.4%. The Zeff value was the independent risk factor for dyspnea (OR = 3.644, 95% CI: 1.846–7.192, p < 0.001) and cough (OR = 3.101, 95% CI: 1.528–6.294, p = 0.002), and lung volume significantly contributed to the mental component summary (MCS) in SF-36 (standardized β = 0.198, p < 0.05).ConclusionsDECT can be applied to evaluate the severity of CTD-ILD.

Serum IL-36 cytokines levels in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung diseases

BackgroundInterleukin-36 (IL-36) family is associated with several fibrosis-related disorders and connective tissue diseases. However, their expression in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-interstitial lung disease (CTD-ILD) is unknown. MethodsWe included 19 CTD-ILD patients, 16 IPF patients, and 27 healthy control subjects. Determination of serum concentrations of IL-36α, IL-36γ and IL-36 receptor antagonist (IL-36Ra) was performed by ELISA. The value of biomarkers for the diagnosis and assessment of ILD was assessed by lung function tests and high-resolution computed tomography. ResultsSerum concentrations of IL-36α and IL-36γ in patients with CTD-ILD and IPF were significantly higher than that in healthy controls, whereas serum IL-36Ra concentrations were not significantly different between the 3 groups. Increased IL-36 levels correlated with disease severity in IPF patients. ROC curve analysis showed that the AUC was 0.9931 for IL-36α and 0.8194 for IL-36γ in IPF group. In CTD-ILD group, the AUC was 0.9825 for IL-36α and 0.7973 for IL-36γ. ConclusionsWe demonstrated an imbalance in the agonist and antagonist profiles of IL-36 cytokines in ILD. IL-36 cytokines may be a new diagnostic or therapeutic target in ILD, especially in IPF.

Prediction of long-term mortality by using machine learning models in Chinese patients with connective tissue disease-associated interstitial lung disease

BackgroundThe exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. In the present study, we develop a nomogram to predict 3‑ and 5-year mortality by using machine learning approach and test the ILD-GAP model in Chinese CTD-ILD patients.MethodsCTD-ILD patients who were diagnosed and treated at the First Affiliated Hospital of Zhengzhou University were enrolled based on a prior well-designed criterion between February 2011 and July 2018. Cox regression with the least absolute shrinkage and selection operator (LASSO) was used to screen out the predictors and generate a nomogram. Internal validation was performed using bootstrap resampling. Then, the nomogram and ILD-GAP model were assessed via likelihood ratio testing, Harrell’s C index, integrated discrimination improvement (IDI), the net reclassification improvement (NRI) and decision curve analysis.ResultsA total of 675 consecutive CTD-ILD patients were enrolled in this study, during the median follow-up period of 50 (interquartile range, 38–65) months, 158 patients died (mortality rate 23.4%). After feature selection, 9 variables were identified: age, rheumatoid arthritis, lung diffusing capacity for carbon monoxide, right ventricular diameter, right atrial area, honeycombing, immunosuppressive agents, aspartate transaminase and albumin. A predictive nomogram was generated by integrating these variables, which provided better mortality estimates than ILD-GAP model based on the likelihood ratio testing, Harrell’s C index (0.767 and 0.652 respectively) and calibration plots. Application of the nomogram resulted in an improved IDI (3- and 5-year, 0.137 and 0.136 respectively) and NRI (3- and 5-year, 0.294 and 0.325 respectively) compared with ILD-GAP model. In addition, the nomogram was more clinically useful revealed by decision curve analysis.ConclusionsThe results from our study prove that the ILD-GAP model may exhibit an inapplicable role in predicting mortality risk in Chinese CTD-ILD patients. The nomogram we developed performed well in predicting 3‑ and 5-year mortality risk of Chinese CTD-ILD patients, but further studies and external validation will be required to determine the clinical usefulness of the nomogram.

Prognostic Value of Human Epididymis Protein 4 in Connective Tissue Disease-Associated Interstitial Lung Disease with a Usual Interstitial Pneumonia Phenotype

Prognostic Value of Human Epididymis Protein 4 in Connective Tissue Disease-Associated Interstitial Lung Disease with a Usual Interstitial Pneumonia Phenotype

Review: Serum Biomarkers of Lung Fibrosis in Interstitial Pneumonia with Autoimmune Features—What Do We Already Know?

Interstitial pneumonia with autoimmune features (IPAF) belongs to a group of diseases called interstitial lung diseases (ILDs), which are disorders of a varied prognosis and course. Finding sufficiently specific and sensitive biomarkers would enable the progression to be predicted, the natural history to be monitored and patients to be stratified according to their treatment. To assess the significance of pulmonary fibrosis biomarkers studied thus far, we searched the PubMed, Medline and Cochrane Library databases for papers published between January 2015 and June 2021. We focused on circulating biomarkers. A primary review of the databases identified 38 articles of potential interest. Overall, seven articles fulfilled the inclusion criteria. This review aims to assess the diagnostic and prognostic value of molecules such as KL-6, SP-A, SP-D, circulating fibrocytes, CCL2, CXCL13, CXCL9, CXCL10 and CXCL11. All of these biomarkers have previously been studied in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPAF is a disorder of a heterogeneous nature. It explains the lack of coherent observations in terms of correlations with functional parameters. There is still no meta-analysis of pulmonary fibrosis biomarkers in IPAF. This is mainly due to the heterogeneity of the methodology and groups analysed in the research. More research in this area is needed.

Antitussive Effect of a Chest Band in Patients with Interstitial Lung Disease: The Preliminary Results from a Pre-post Intervention Study.

Objective Evidence supporting the efficiency of clinically administered therapies against interstitial lung disease (ILD)-related cough is limited. Thus, we conducted a study to evaluate the efficacy of short-term use of chest bands on cough in patients with ILD. Methods This pre-post intervention study was performed at two university hospitals between April 2017 and August 2020. Scores of the visual analog scale (VAS) for cough severity (in terms of frequency and intensity), Leicester Cough Questionnaire (LCQ)-acute, and frequency scale for symptoms of gastroesophageal reflux disease (FSSG) were assessed before and after the use of the chest band (24/48 hours). Patients The study included patients with idiopathic interstitial pneumonias (IIPs) or connective tissue disease-associated interstitial lung disease (CTD-ILD). Results Four patients with IIPs and seven with CTD-ILD were included in the analysis. The cough intensity and LCQ-acute total score improved significantly after the use of the chest band (p=0.007 and p=0.005, respectively), although the cough frequency showed no significant reduction (p=0.074). Furthermore, the FSSG total and acid-reflux symptom scores improved (p=0.018 and p=0.027, respectively), and a negative correlation between the change in LCQ-acute total score and that in FSSG score for acid-reflux symptoms was observed (Spearman rho =-0.841, p=0.001). Conclusion The results of the current study suggest that chest bands might be useful for treating chronic refractory cough in patients with ILD and gastroesophageal reflux disease. However, these results should be interpreted with caution due to methodological limitations associated with this study.

Abstract 10064: Pulmonary Hypertension in Patients with Connective Tissue Disease-associated Interstitial Lung Disease and Vascular Changes on Computed Tomography

Introduction: Pulmonary hypertension (PH) is a complication in patients with connective-tissue disease-associated interstitial lung disease (CTD-ILD) associated with mortality. In Idiopathic Pulmonary Fibrosis, increased vascular volume has been reported to be associated with poor outcomes. We sought to elicit whether similar changes could be observed in patients with CTD-ILD and pulmonary hypertension. Methods: We identified patients with a known diagnosis of CTD-ILD who had undergone chest CT, transthoracic echocardiography (TTE), and right heart catherization (RHC) using the Mass General Brigham Research Patient Data Repository (IRB #2018P000419). The electronic health records (EHR) were reviewed to confirm the diagnosis of CTD-ILD. A 3D reconstruction of the pulmonary vasculature using the Chest Imaging Platform ( www.chestimagingplatform.com ) to compute the total vascular volume was performed on thin sliced CT scans closest to the RHC. Vessels were separated into arterial and venous components using a deep learning approach. Statistical analysis was performed with R 4.01. Values are shown as medians and interquartile ranges and were compared using Wilcoxon Rank-Sum tests. Results: A total of 104 patients with CTD-ILD were identified: Pre-capillary PH (n=43), Isolated Post-capillary PH (n=9), Combined Pre- and Post-capillary PH (n=8), and PH Absent (n=44). There was no difference in patient age or lung volume by CT scan. On TTE, RVSP was elevated in PH (52 mmHg, IQR 41-64 mmHg vs 34 mm Hg, IQR 27-49 mmHg, p &lt; 0.0001), as was the arterial total vascular volume (118 mL, IQR 85-152 ml vs 100 mL, IQR 77-126 ml, p = 0.009) with no trend for significance for venous total vascular volume. Addition of total arterial volume remained a statistically significant predictor of presence of PH (p = 0.01) when added to logistic regression models predicting PH by TTE RVSP, with improvement in model AIC (106.1 to 97.9) and AUC (0.75 to 0.80) of the model. Conclusions: In this retrospective study of patients with CTD-ILD and available imaging and hemodynamics, patients with PH have increased arterial vascular volume compared to those without PH. Information derived from CT images routinely acquired in this population could be used to improve screening and phenotyping.

Predictors of Mortality in Progressive Fibrosing Interstitial Lung Diseases.

Background: Progressive fibrosing interstitial lung disease (PF-ILD) and idiopathic pulmonary fibrosis (IPF) share similar progression phenotype but with different pathophysiological mechanism. The purpose of this study was to assess clinical characteristics and outcomes of patients with PF-ILD in a single-center cohort. Methods: Patients with PF-ILD treated in Shanghai Pulmonary Hospital from Jan. 2013 to Dec. 2014 were retrospectively analyzed. Baseline characteristics and clinical outcomes were collected for survival analysis to identifying clinical predictors of mortality. Results: Among 608 patients with ILD, 132 patients met the diagnostic criteria for PF-ILD. In this single-center cohort, there were 51 (38.6%) cases with connective tissue disease-associated interstitial lung disease (CTD-ILD) and 45 (34.1%) with unclassifiable ILDs. During follow-up, 83 patients (62.9%) either died (N = 79, 59.8%) or underwent lung transplantations (N = 4, 3.0%) with a median duration follow-up time of 53.7 months. Kaplan-Meier survival curves revealed that the 1, 3 and 5-years survival of PF-ILD were 90.9, 58.8 and 48.1%, respectively. In addition, the prognosis of patients with PF-ILD was similar to those with IPF, while it was worse than non-PF-ILD ones. Multivariate Cox regression analysis demonstrated that high-resolution computed tomography (HRCT) scores (HR 1.684, 95% CI 1.017–2.788, p = 0.043) and systolic pulmonary artery pressure (SPAP) > 36.5 mmHg (HR 3.619, 95%CI 1.170–11.194, p = 0.026) were independent risk factors for the mortality of PF-ILD. Conclusion: Extent of fibrotic changes on HRCT and pulmonary hypertension were predictors of mortality in patients with PF-ILD.

Association of Red Blood Cell Distribution Width Levels with Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD).

Objective The aim of this study was to evaluate the diagnostic and prognostic value of red blood cell distribution width (RDW) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods We retrospectively reviewed 213 CTD-ILD patients and 97 CTD patients without ILD from February 2017 to February 2020. Hospital and office records were used as data sources. CTD-ILD patients were followed up. Results Patients with CTD-ILD had significantly higher RDW than those with CTD without ILD (p < 0.001). The area under the receiver operating characteristic curve (AUROC) of RDW for discriminating CTD-ILD from CTD without ILD was 0.64 (95% CI: 0.57-0.70, p < 0.001). The cutoff value of RDW for discriminating CTD-ILD from CTD without ILD was 13.95% with their corresponding specificity (55.9%) and sensitivity (70.1%). Correlation analyses showed that the increased RDW was significantly correlated with decreased DLCO%predicted (r = −0.211, p = 0.002). Cox multiple regression analysis indicated that RDW (HR = 1.495, p < 0.001) was an independent factor in the survival of CTD-ILD. The best cutoff value of RDW to predict the survival of patients with CTD-ILD was 14.05% (AUC = 0.78, 95% CI: 0.72-0.84, p < 0.001). The log-rank test showed a significant difference in survival between the two groups (RDW > 14.05% and RDW < 14.05%). Conclusion RDW was higher in CTD-ILD patients and had a negative correlation with DLCO%predicted. RDW may be an important serum biomarker for severity and prognosis of patients with CTD-ILD.

The Prediction and Prognosis of Fungal Infection in Lung Transplant Recipients-A Retrospective Cohort Study in South Korea.

(1) Background: Lung transplant recipients (LTRs) are at substantial risk of invasive fungal disease (IFD), although no consensus has been reached on the use of antifungal agents (AFAs) after lung transplantation (LTx). This study aimed to assess the risk factors and prognosis of fungal infection after LTx in a single tertiary center in South Korea. (2) Methods: The study population included all patients who underwent LTx between January 2012 and July 2019 at a tertiary hospital. It was a retrospective cohort study. Culture, bronchoscopy, and laboratory findings were reviewed during episodes of infection. (3) Results: Fungus-positive respiratory samples were predominant in the first 90 days and the overall cumulative incidence of Candida spp. was approximately three times higher than that of Aspergillus spp. In the setting of itraconazole administration for 6 months post-LTx, C. glabrata accounted for 36.5% of all Candida-positive respiratory samples. Underlying connective tissue disease-associated interstitial lung disease, use of AFAs before LTx, a longer length of hospital stay after LTx, and old age were associated with developing a fungal infection after LTx. IFD and fungal infection treatment failure significantly increased overall mortality. Host factors, antifungal drug resistance, and misdiagnosis of non-Aspergillus molds could attribute to the breakthrough fungal infections. (4) Conclusions: Careful bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are recommended during the first year after LTx.

Comparative analysis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis from a tertiary care centre in Pakistan.

To compare the characteristics of connective tissue disease-associated interstitial lung disease with idiopathic pulmonary fibrosis at a tertiary care hospital. The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised demographical, clinical and radiological data of patients with interstitial lung disease between October 2016 and October 2017 accessed through the outpatient data registry. Data was compared in terms of characteristics and key features of patients with connective tissue disease-associated interstitial lung disease with those of idiopathic pulmonary fibrosis. Statistical analysis was done using STATA 12. Of the 184 patients, 52(29.3%) had connective tissue disease-associated interstitial lung disease and 62(35%) had idiopathic pulmonary fibrosis. The most prevalent conditions among connective tissue disease-associated interstitial lung disease patients were rheumatoid arthritis 22(42.3%) and scleroderma 13(25%). Compared to patients with idiopathic pulmonary fibrosis, those with connective tissue disease-associated interstitial lung disease were predominantly younger (p<0.001) and female (p<0.001). History of gastroesophageal reflux disease was also significantly lower in connective tissue disease-associated interstitial lung disease (p=0.05). Connective tissue disease-associated interstitial lung disease patients were found to be younger and predominantly female compared to patients of idiopathic pulmonary fibrosis.

Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease.

Introduction: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. Results: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86–1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60–0.97). Conclusion: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.

Management of Patients with Connective Tissue Disease-associated Interstitial Lung Diseases During the COVID-19 Pandemic.

The novel coronavirus disease (COVID-19) is similar to connective tissue disease-associated interstitial lung diseases (CTD-ILD) in many aspects. However, patients with CTD-ILD have required particular attention during the pandemic since they are at high risk due to -immunosuppressive treatments. Thus, prompt decisions for diagnosis and treatment initiation have become more important than earlier for these patients during the pandemic. Radiological perspectives have become inevitable for the differential diagnosis of this group ¬during the pandemic, particularly to obtain rapid and accurate results that allow the physicians to start treatment immediately. However, in addition to radiological images, a definitive diagnosis also requires access to extensive information regarding patient history, including characteristics of comorbidities, and clinical and serological findings. Consequently, the differential diagnosis of COVID-19 and CTD-ILD can yield accurate treatment regimens that differ greatly between the 2 diseases, and also prevent the spread of the outbreak with COVID-19 patients treated under isolation.

Outcomes after lung transplantation among Chinese patients with connective tissue disease-associated interstitial lung disease and pulmonary hypertension: a retrospective cohort study.

The present study aimed to compare the post-lung transplant survival and complications of connective tissue disease (CTD)-related interstitial lung disease (ILD) and/or pulmonary arterial hypertension with idiopathic pulmonary fibrosis (IPF). The clinical data of patients with CTD-ILD or IPF who received lung transplantation between 2015 and 2020 were retrospectively reviewed. Cumulative survival rates after transplantation were estimated using the Kaplan-Meier method. The study included 31 patients with confirmed CTD-ILD and 98 with IPF. Patients with CTD-ILD were significantly younger (53.2 ± 13.7 vs. 62.3 ± 7.2 years, p=0.001) and more likely female (61.3% vs. 7.1%, p<0.001) than patients with IPF. No significant difference was noticed in the 1-year and 5-year survival rates between CTD-ILD and IPF patients (1-year, 73.2% vs 71.4%, p=0.76; 5-year, 69.1% vs. 39.5%, p=0.21). The incidence of primary graft dysfunction was significantly higher in CTD-ILD patients (90.3% vs. 70.4%, p=0.03), while there was no significant difference in primary graft dysfunction-related mortality (6.5% vs. 6.1%, p=0.95) between the two groups. There was no significant difference in post-lung transplant survival and complications between CTD-ILD and IPF.

Interstitial pneumonia with autoimmune features: from research classification to diagnosis

The term interstitial pneumonia with autoimmune features (IPAF) was first proposed by an international task force in 2015 as a research classification to standardise nomenclature regarding patients with idiopathic interstitial pneumonia and features of connective tissue disease. However, how the use of this term and its proposed definition translates to clinical practice remains uncertain. This review will provide a comprehensive overview of studies of IPAF cohorts to date, discuss the consideration of IPAF as a distinct diagnostic entity and outline a suggested approach to patient management. Considerable heterogeneity exists between published IPAF cohorts, with some cohorts exhibiting similarities to those with connective tissue disease-associated interstitial lung disease (CTD-ILD), and others more similar to idiopathic interstitial pneumonias including idiopathic pulmonary fibrosis (IPF). Little data exist to inform the management of patients who fulfil the IPAF criteria. Preliminary data supports pragmatic management of these patients as having a working clinical diagnosis of either idiopathic interstitial pneumonia or CTD-ILD. Future research studies into this approach are required. The term IPAF, and its definition, have been of fundamental benefit to facilitating research in this diverse patient group. However, to date, there remain many unanswered questions regarding their natural histories and response to treatment.

The other connective tissue disease-associated interstitial lung diseases: Sjogren's syndrome, mixed connective tissue disease, and systemic lupus erythematosus.

We review the clinical manifestations of three less common connective tissue disease (CTD)-associated interstitial lung diseases (ILDs): Sjogren's syndrome (SjS), mixed CTD (MCTD), and systemic lupus erythematosus (SLE). SjS is classically associated with lymphocytic interstitial pneumonia and cystic lung disease, but the most common type of ILD in Sjogren's patients is nonspecific interstitial pneumonia. ILD is prevalent in MCTD and associated with worse survival. SLE-associated ILD, while rare, is more common in those with CTD overlap syndromes. Regardless of underlying cause, a subset of patients with fibrotic CTD-associated ILD develop a progressive course for which antifibrotic agents and lung transplantation should be considered. An understanding of the characteristics of ILD in SjS, MCTD, and SLE is important for the pulmonary specialist. Future research should identify risk factors for progression and develop additional treatment modalities for both CTD-related autoimmune features and progressive ILD.

Efficacy and Safety of Tripterygium Wilfordii Hook. F for Connective Tissue Disease-Associated Interstitial Lung Disease:A Systematic Review and Meta-Analysis.

Background: Tripterygium wilfordii Hook. F (TwHF), a Chinese herbal medicine used to treat CTD-ILD patients in China, has been previously found to have immunoinhibitory, antifibrotic and anti inflammatory effects. It has also shown good results in treating autoimmune and inflammatory diseases. Objectives: This systematic review and meta-analysis aims to evaluate the efficacy and safety of TwHF for CTD-ILD. Methods: A systematic search was performed on PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, Scopus, CNKI, Wanfang, VIP, and CBM databases up to May 2021. Randomized controlled trials (RCTs) comparing TwHF plus conventional therapy versus conventional therapy alone were included. We followed the PRISMA checklist, and applied Cochrane handbook 5.1.0 and RevMan 5.3 for data analysis and quality evaluation of the included studies. Results: Based on Cochrane handbook 5.1.0, nine RCTs consisting 650 patients met the inclusion/exclusion criteria and were selected for further analysis. The obtained data showed significant improvement in lung function with TwHF plus conventional treatment compared with conventional treatment (post-treatment FVC% (MD= 8.68, 95%Cl (5.10, 12.26), p < 0.00001), FEV1% (MD = 11.24, 95%Cl (6.87, 15.61), p < 0.00001), TLC% (MD = 5.28, 95%Cl (0.69, 9.87), p = 0.02)], but no significant difference in the post-treatment DLCO% [(MD = 4.40, 95%Cl (−2.29, 11.09), p = 0.20)]. Moreover, the data showed that TwHF combined with conventional treatment significantly reduced the HRCT integral of patients [MD = -0.65, 95% (-1.01, -0.30), p = 0.0003], the level of erythrocyte sedimentation rate (MD = −9.52, 95%Cl (−11.55, −7.49), p < 0.00001), c-reactive protein (CRP) (MD = −8.42, 95%Cl (−12.47, −4.38), p < 0.0001), and rheumatoid factor (MD = −25.48, 95%Cl (−29.36, −21.60), p < 0.00001). Compared to conventional therapy, TwHF combined with conventional therapy significantly improved clinical effects (RR = 1.33, 95%Cl (1.17, 1.51), p < 0.0001), in five trials with 354 patients. In terms of improvement of symptoms and signs, the TwHF group showed a more significant improvement than the conventional treatment group (Cough (MD = −0.96, 95%Cl (−1.43, −0.50), p < 0.0001), velcro rales (MD = −0.32, 95%Cl (−0.44, −0.20), p < 0.00001), shortness of breath (MD = −1.11, 95%Cl (−1.67, −0.56), p < 0.0001)], but no statistical difference in dyspnea (MD = −0.66, 95%Cl (−1.35, 0.03), p = 0.06). There was no statistical significance in the incidence of adverse reactions. Conclusion: The performed meta-analysis indicated that TwHF combined with conventional treatment was more beneficial to patients for improving symptoms, lung function and laboratory indicators. As it included studies with relatively small sample size, the findings require confirmation by further rigorously well-designed RCTs.

Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis

Fibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05). The percentages of peripheral blood fibrocytes in the IPF group (4.2550 ± 0.3483%) and CTD-ILD group (4.7100 ± 0.4811%) were higher than that in the control group (1.6340 ± 0.2549%) (both P < 0.05). In vitro, PBMCs transfected with siRNA-CFL-1 showed lower expression of CFL-1, and the percentage of fibrocytes was lower than that of the control (P < 0.05). PBMCs transfected with Lv-CFL-1 to increase the expression of CFL-1 showed a higher percentage of fibrocytes than the control (P < 0.05). In mice with bleomycin-induced pulmonary fibrosis, the relative expression of CFL-1 was increased, and the percentage of fibrocytes was higher than that in the saline group (P < 0.05). In bleomycin-induced mice, interference with Lv-CFL-1 decreased the expression of CFL-1, the percentage of fibrocytes was lower, and the lung tissue showed less fibrosis (P < 0.05). The overexpression of CFL-1 is associated with pulmonary fibrogenesis. CFL-1 could promote the differentiation of fibrocytes from monocyte peripheral blood mononuclear cells and promote pulmonary fibrosis.

The Role of Lung Colonization in Connective Tissue Disease-Associated Interstitial Lung Disease.

Connective tissue diseases (CTDs) may frequently manifest with interstitial lung disease (ILD), which may severely impair quality and expectation of life. CTD-ILD generally has a chronic clinical course, with possible acute exacerbations. Although several lines of evidence indicate a relevant role of infections in the acute exacerbations of CTD-ILD, little information is available regarding the prevalence of infections in chronic CTD-ILD and their possible role in the clinical course. The aim of the present retrospective study was the identification of lung microbial colonization in broncho-alveolar lavage from patients affected by stable CTD-ILD with radiologically defined lung involvement. We demonstrated that 22.7% of patients with CTD-ILD display microbial colonization by Pseudomonas aeruginosa, Haemophilus influenzae, and non-tuberculous mycobacteria. Moreover, these patients display a major radiologic lung involvement, with higher impairment in lung function tests confirmed in a multivariate logistic regression analysis. Overall, the present study provides new information on lung colonization during CTD-ILD and its possible relationship with lung disease progression and severity.

Survival and outcomes after lung transplantation for connective tissue disease-associated interstitial lung diseases.

BackgroundLung transplantation (LTx) is the most important treatment for end-stage lung diseases. However, the treatment of connective tissue disease-associated interstitial lung diseases (CTD-ILD) using LTx is still controversial especially for polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD).MethodsPatients diagnosed with idiopathic pulmonary fibrosis (IPF) (n=180) and CTD-ILD (n= 36) from 1st January 2015 to 31st December 2019 were recruited into the study. We set polymyositis/dermatomyositis (PM/DM) as a single subgroup, and all the patients underwent LTx at the Wuxi People’s Hospital.ResultsWe found that patients with non-myositis connective tissue-related ILD (NM-CTLD) were younger (p=0.007) and had a higher percentage of females (p=0.000) than patients with IPF. PM/DM-ILD was associated with a higher incidence of primary graft dysfunction (PGD) (p=0.006) and a longer time in the intensive care unit (ICU) (p=0.000). The cumulative survival rates of patients with PM/DM-ILD were significantly lower than those with IPF (log rank, p=0.003). However, there were no significant differences when compared with the cumulative survival rates of patients with NM-CTLD and IPF (log rank, p=0.528). Age- and gender-adjusted Cox proportional hazard analyses indicated that post-LTx PGD (HR 1.498, 95% CI 1.227–1.828, p=0.000) and duration of ICU (HR 1.027, 95% CI 1.007–1.047, p=0.000) were the independent contributors of disease status to survival. Lung infection was the leading cause of post-LTx death in the groups, where the incidence was 65.3% (47/72) in IPF, 66.7% (8/12) in NM-CTLD, and 66.7% (4/6) in PM/DM-ILD.ConclusionsThis study found that patients with NM-CTLD had a similar survival outcome with IPF. However, patients with PM/DM-ILD-performed LTx had a lower survival rate than those with IPF. Key Points• Previous studies have shown that the myopathies associated ILD patients had similar post-LTx outcomes with IPF patients. However, our retrospective analysis indicated that patients with PM/DM-ILD-performed LTx had a lower survival rate than those with IPF.• Patients with NM-CTLD had a similar survival outcome with IPF.• We also found that PM/DM-ILD was associated with a higher incidence of PGD and a longer time in the ICU.