Tissue Disease-associated Interstitial Lung Disease Research Articles

Prognostic value of serum oncomarkers for patients hospitalized with acute exacerbation of interstitial lung disease.

Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear. To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes. Retrospective study. The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis. Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP. CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD.

Diagnostic Value of Serum KL-6 in Interstitial Lung Diseases.

To explore serum KL-6 level and investigate its diagnostic value in interstitial lung diseases (ILDs). Serum KL-6 level was measured using the chemiluminescent enzyme immunoassay. Statistical analysis was performed for determining the KL-6 concentration of each group. KL-6 level (U/mL) in the ILD group was 1388.321 ±1943.116, which was higher than that in the control group, showing a significant statistical difference. ROC curve analysis based on the receiver operating characteristic curve showed the optimal cut-off value of 402.5U/mL, sensitivity of 77.4%, specificity of 93.4%, and accuracy of 89.4%; through Chi-square test with the two groups, the positive rate of KL-6 in patients with ILD was proved to be significantly higher than that in the control group. KL-6 level was 1063.00±504.757 in the idiopathic pulmonary fibrosis (IPF) group, 1346.892 ±1827.252 in the connective tissue disease-associated interstitial lung disease (CTD-ILD) group, 467.889±288.859 in the organizing pneumonia (OP) group, 8252.333±6050.625 in the pulmonary alveolar proteinosis (PAP) group, and 359.200±392.707 in the sarcoidosis group. The rank sum test showed that the differences were statistically significant. KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group. Serum KL-6 level was confirmed to be highly sensitive, specific, and accurate in the diagnosis of ILD. Subgroup analysis showed that the KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.

Characteristics and risk factors of interstitial pneumonia with autoimmune features

BackgroundInterstitial pneumonia with autoimmune features (IPAF) has features of connective tissue disease-associated interstitial lung disease (CTD-ILD), but without meeting criteria for a specific CTD. We compared baseline characteristics, survival, and response to treatment of IPAF to both CTD-ILD and unclassifiable ILD. MethodsMeasurements were extracted from a prospective registry. Baseline features and survival were compared in IPAF against both CTD-ILD and unclassifiable ILD. Linear trajectory of lung function decline (%-predicted forced vital capacity [FVC%] and diffusion capacity of the lung for carbon monoxide [DLCO%]) before and after initiation of mycophenolate or azathioprine were compared in IPAF against both CTD-ILD and unclassifiable ILD using linear mixed models. ResultsCompared to CTD-ILD (n = 1240), patients with IPAF (n = 128) were older, more frequently male, and had greater smoking history. Compared to unclassifiable ILD (n = 665), patients with IPAF were younger, more frequently female, and had worse baseline lung function. IPAF had higher mortality compared to CTD-ILD and similar risk of mortality compared to unclassifiable ILD. Mycophenolate initiation was associated with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% in patients with IPAF, and azathioprine initiation with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% decline in IPAF and DLCO% decline in CTD-ILD. ConclusionPatients with IPAF had worse survival compared to those with CTD-ILD and similar mortality to unclassifiable ILD, with treatment being associated with stabilization in lung function in all three ILDs. It is uncertain whether IPAF should be considered a distinct ILD diagnostic subgroup.

Identification and functional prediction of long non-coding RNA and mRNA related to connective tissue disease-associated interstitial lung diseases.

Recently, the role of long non-coding RNA (lncRNA) in rheumatic immune diseases has attracted widespread attention. However, knowledge of lncRNA in connective tissue disease-associated interstitial lung disease (CTD-ILD) is limited. This study explored the expression profile and possible mechanisms of lncRNA and mRNA in peripheral blood mononuclear cells (PBMCs) of CTD-ILD patients, especially systemic sclerosis (SSc)-ILD and rheumatoid arthritis (RA)-ILD. LncRNA microarray analysis identified 240 diferentially expressed lncRNAs and 218 diferentially expressed mRNA in the CTD-ILD group and the connective tissue disease without associated interstitial lung disease (CTD-NILD) group. The bioinformatics analysis of diferential genes has identified several important biological processes and signal pathways, including nuclear factor kappa B (NF-kappa B) signaling pathway, interleukin 17 (IL-17) signaling pathway, B cell receptor signaling pathway. Relative expression levels of five diferentially expressed lncRNAs and one mRNA in 120 SSc and RA patients with or without ILD were detected by quantitative reverse-transcription (PCR). The ENST00000604692 expression level was significantly higher in the ILD than the without interstitial lung disease (NILD) group; T311354 and arginase-1 were significantly higher in SSc than RA group. These data suggest that the specific profile of lncRNA in PBMCs of CTD-ILD patients and the potential signal pathways related to the pathogenesis of CTD-ILD, which may provide newfound insights for the diagnosis and treatment of CTD-ILD patients.

Factors associated with rapid progression in fibrotic interstitial lung disease

BackgroundEarly identification of fibrotic interstitial lung disease (F-ILD) patients with high risk of progression will help initiate early therapeutic intervention and potential improvement of outcomes. This study was designed to assess the predictors of progression in patients with F-ILD. MethodsPatients with F-ILD in Shanghai Pulmonary Hospital between January 1, 2019 and July 31, 2021 were retrospectively analyzed. The patients enrolled were divided into progressive group and non-progressive group according to the specified criteria. Baseline characteristics were collected and a multivariate regression was conducted to identify independent predictors of progression. ResultsOf the 177 F-ILD cases, 87 were enrolled in the progressive group and 90 were in the non-progressive group. The cohort included 11 types of F-ILD, primarily were connective tissue disease-associated interstitial lung disease (CTD-ILD) (43, 24.3 %), idiopathic pulmonary fibrosis (IPF) (39, 22.0 %), interstitial pneumonia with autoimmune features (IPAF) (32, 18.1 %), and unclassifiable (23, 13.0 %). The highest proportion of progression was seen in nonspecific interstitial pneumonia (NSIP) subgroup (66.7 %), followed by IPF (59.0 %) and HP (57.1 %). After adjusting for gender and age, a course of disease longer than 9.5 months (OR: 2.633; 95 % CI: 1.190–5.826, P = 0.017), lymphocyte in peripheral blood more than 2.24 (109/L) (OR: 2.670; 95 % CI: 1.095–6.510, P = 0.031), and emphysema in high-resolution computed tomography (HRCT) (OR: 2.387; 95 % CI: 1.017–5.640, P = 0.046) were independent predictors of progression in F-ILD patients. ConclusionsThis study suggested that in patients with F-ILD, long course of disease, elevated blood lymphocyte and emphysema on HRCT were independent predictors of progression, which may suggest utility in early therapeutic intervention.

Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis.

The decision for definitive therapy for the treatment of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) is difficult. Patients with CTD-ILD received 0.5 g twice a day of mycophenolate mofetil for 2 years (MMF cohort, n = 105) or cyclophosphamide 50 mg once every other day, and the cumulative dose of cyclophosphamide should not exceed 10 g (CYC cohort, n = 140). After complete of treatment (EL), % forced vital capacity (FVC) and % diffusing capacity of the lungs for carbon monoxide were increased in both the MMF and CYC cohorts as compared to before treatment (p < 0.001 for all). There were higher changes in % FVC values and a greater number of patients with significant change in % FVC (>10% change) in the CYC cohort than in the MMF cohort (p < 0.0001 for both) at EL. Patients in the CYC cohort had higher rates of leukopenia, thrombocytopenia, serious adverse effects related to treatment(s), and death than those in the MMF cohort (p < 0.05 for all). Cyclophosphamide plus prednisolone superiorly improved % FVC compared to mycophenolate mofetil plus prednisolone. Mycophenolate mofetil and cyclophosphamide improved pulmonary function. Mycophenolate mofetil is less toxic and increased patient survival.

Mass spectrometry-based autoimmune profiling reveals predictive autoantigens in idiopathic pulmonary fibrosis

Autoimmunity plays a role in certain types of lung fibrosis, notably connective tissue disease-associated interstitial lung disease (CTD-ILD). In idiopathic pulmonary fibrosis (IPF), an incurable and fatal lung disease, diagnosis typically requires clinical exclusion of autoimmunity. However, autoantibodies of unknown significance have been detected in IPF patients. We conducted computational analysis of B cell transcriptomes in published transcriptomics datasets and developed a proteomic Differential Antigen Capture (DAC) assay that captures plasma antibodies followed by affinity purification of lung proteins coupled to mass spectrometry. We analyzed antibody capture in two independent cohorts of IPF and CTL-ILD patients over two disease progression time points. Our findings revealed significant upregulation of specific immunoglobulins with V-segment bias in IPF across multiple cohorts. We identified a predictive autoimmune signature linked to reduced transplant-free survival in IPF, persisting over time. Notably, autoantibodies against thrombospondin-1 were associated with decreased survival, suggesting their potential as predictive biomarkers.

Plasma LTBP2 as a potential biomarker in differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis: a pilot study.

Few biomarkers distinguish connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF). Latent transforming growth factor-β binding protein-2 (LTBP2), a secreted extracellular matrix protein, is involved in pulmonary fibrosis. However, the role of LTBP2 in differentially diagnosing CTD-ILD and IPF is unclear. In this study, enzyme-linked immunosorbent assays quantified plasma LTBP2 concentrations in 200 individuals (35 healthy controls, 42 CTD patients without ILD, 89 CTD-ILD patients, and 34 IPF patients). CTD-ILD and IPF were further classified based on chest imaging pattern and pulmonary function test results. Plasma LTBP2 levels were significantly elevated in the IPF group compared with the CTD-ILD group. ROC analysis further suggested the possible value of LTBP2 in differentially diagnosing CTD-ILD and IPF. Additionally, CTD-ILD patients with progressive lung fibrosis had higher plasma LTBP2 concentrations than those who did not. Similarly, patients with IPF developing acute exacerbation showed higher plasma LTBP2 levels than those with stable IPF. This is the first study showing that LTBP2 was closely associated with the usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated ILD (RA-ILD). Moreover, the optimal cutoff values of LTBP2 for distinguishing IPF from CTD-UIP/RA-UIP were 33.75 and 38.33ng/mL with an AUC of 0.682 and 0.681, respectively. Our findings suggest that plasma LTBP2 levels may differentially diagnose CTD-ILD and IPF, and assess their fibrotic activity. Additionally, clinical LTBP2 evaluation may be a great aid to identifying the presence of the UIP pattern in RA-ILD and to discriminating IPF from CTD-UIP, particularly RA-UIP.

Clinical effect of progressive pulmonary fibrosis on patients with connective tissue disease-associated interstitial lung disease: a single center retrospective cohort study

The concept of progressive pulmonary fibrosis (PPF) has been introduced to predict the diverse prognosis of interstitial lung disease (ILD). However, the incidence and effect of PPF on outcomes in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) need to be elucidated. This study reviewed 197 patients with CTD-ILD. Symptomatic worsening, pulmonary function decline, and radiological deterioration were investigated to assess the fulfillment of PPF diagnostic criteria. Clinical outcomes, including mortality, were compared based on the presence or absence of PPF. The median follow-up duration was 17.4 months. The mean age of the patients was 64.0 years, and 60.9% were female. Among the underlying CTDs, rheumatoid arthritis (42.1%), inflammatory myositis (19.8%), and systemic sclerosis (13.2%) were the most common. Of the 197 patients, 37 (18.8%) met the diagnostic criteria for PPF during the follow-up period. Even after adjusting for other significant risk factors, PPF was independently associated with mortality [hazard ratio (HR) 3.856; 95% confidence interval (CI) 1.387–10.715; P = 0.010] and baseline albumin was marginally significantly associated with mortality (HR 0.549; CI 0.298–1.010; P = 0.054). The median survival was also significantly shorter in the PPF group than in the non-PPF group (72.3 ± 12.9 vs. 126.8 ± 15.5 months, P < 0.001). Baseline KL-6 ≥ 1000 (U/mL) was a significant risk factor for PPF (HR 2.885; CI 1.165–7.144; P = 0.022). In addition to increased mortality, the PPF group had significantly higher rates of respiratory-related hospitalizations, pneumonia, acute exacerbations, and weight loss than the non-PPF group. PPF is a significant prognostic indicator in patients with CTD-ILD. Thus, healthcare professionals should know that patients with CTD-ILD are at risk of PPF.

Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease.

It is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system. Patients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis. A total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827-0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816-0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720-0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness. The CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages.

Clinical significance of interleukin-6, total bilirubin, CD3 + CD4 + T cells counts in the acute exacerbation of connective tissue disease-associated interstitial lung disease: a cross-sectional study

ObjectiveInterstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease.MethodsThis study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables.ResultsElevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = − 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = − 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker.ConclusionsElevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better.

The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area.

A computed tomography-based radiomics nomogram for predicting overall survival in patients with connective tissue disease-associated interstitial lung disease

ObjectivesAccurate prognostic prediction is beneficial for the management of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The purpose of the present study was to develop and validate a nomogram using clinical features and computed tomography (CT) based radiomics features to predict overall survival (OS) in patients with CTD-ILD, and to assess the incremental prognostic value the radiomics might add to clinical risk factors. Materials & methodsPatients from two clinical centers with CTD-ILD were enrolled in the present retrospective study. A radiomics signature, a clinical model and a combined nomogram were developed and assessed in the cohorts. The incremental value of radiomics signature to the clinical independent risk factors in survival prediction was evaluated. The models were externally validated to evaluate the model generalization ability. ResultsA total of 215 patients (mean age, 53 years ± 14 [standard deviation], 45 men) were evaluated. Patients with higher radiomics scores had higher mortality risk than those with lower radiomics scores (Hazard ratio, 12.396; 95% CI, 3.364–45.680; P < 0.001). The combined nomogram showed better predictive capability than the clinical model did with higher C-indices (0.800, 0.738, 0.742 vs. 0.747, 0.631, 0.587 in the training, internal- and external-validation cohort, respectively), time-AUCs and overall net-benefit. ConclusionThe radiomics signature is a potential prognostic biomarker of CTD-ILD and add incremental value to the clinical independent risk factors. The combined nomogram can provide a more accurate estimation of OS than the clinical model for CTD-ILD patients. Clinical relevance statementThe developed combined nomogram showed accurate prognostic prediction performance, which is beneficial for the management of CTD-ILD patients. It also proved radiomics could extract prognostic information from CT images.

Computed Tomography-Based Deep Learning Model for Assessing the Severity of Patients With Connective Tissue Disease-Associated Interstitial Lung Disease.

This study aimed to develop a computed tomography (CT)-based deep learning model for assessing the severity of patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD). The retrospective study included 298 CTD-ILD patients between January 2018 and May 2022. A deep learning-based RDNet model was established (1610 fully annotated CT images for training and 402 images for validation). The model was used to automatically classify and quantify 3 radiologic features (ground glass opacities [GGOs], reticulation, and honeycombing), along with a volumetric sum of 3 areas (ILD%). As a control, we used 4 previously defined CT threshold methods to calculate the ILD assessment index. The Spearman rank correlation coefficient ( r ) evaluated the correlation between various indicators and the lung function index in the remaining 184 CTD-ILD patients who were staged according to the gender-age-physiology (GAP) system. The RDNet model accurately identified GGOs, reticulation, and honeycombing, with corresponding Dice indexes of 0.784, 0.782, and 0.747, respectively. A total of 137 patients were at GAP1 (73.9%), 36 patients at GAP2 (19.6%), and 11 patients at GAP3 (6.0%). The percentages of reticulation and honeycombing at GAP2 and GAP3 were markedly elevated compared with those at GAP1 ( P < 0.001). The percentage of GGOs was not significantly different among the GAP stages ( P = 0.62). As the GAP stage increased, all lung function indicators tended to decrease, and the composite physiologic index (CPI) indicated an upward tendency. The percentage of honeycombs moderately correlated with the percentage of diffusing capacity of the lung for carbon monoxide (DLco%) ( r = -0.58, P < 0.001) and CPI ( r = 0.63, P < 0.001). The ILD assessment index calculated by the CT threshold method (-260 to -600 Hounsfield units) had a low correlation with DLco% and CPI (DLco%: r = -0.42, P < 0.001; CPI: r = 0.45, P < 0.001). The RDNet model can quantify GGOs, reticulation, and honeycombing of chest CT images in CTD-ILD patients, among which honeycombing had the most significant effect on lung function indicators. In addition, this model provided good clinical utility for evaluating the severity of CTD-ILD.

Can transbronchial lung cryobiopsy benefit adaptive treatment strategies in connective tissue disease-associated interstitial lung disease?

BackgroundSome patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) progress to pulmonary fibrosis over their disease course despite initial improvement, potentially indicating a poor prognosis. Transbronchial lung cryobiopsy (TBLC) is a new bioptic approach used in diffuse parenchymal lung diseases. This study of CTD-ILD assessed the utility of TBLC in determining therapeutic decision-making strategies.MethodsWe analyzed medical records of 31 consecutive CTD-ILD patients who underwent TBLC focusing on radio-pathological correlation and disease course. A TBLC-based usual interstitial pneumonia (UIP) score was used that assessed three morphologic descriptors: i) patchy fibrosis, ii) fibroblastic foci, and iii) honeycombing.ResultsAmong the patients with CTD-ILD, 3 had rheumatoid arthritis, 2 systemic sclerosis, 5 polymyositis/dermatomyositis, 8 anti-synthetase syndrome, 6 Sjögren’s syndrome, and 5 had microscopic polyangiitis. Pulmonary function test results showed a mean %FVC of 82.4% and %DLCO of 67.7%. Among the 10 CTD patients and TBLC-proven pathological UIP, 3 patients had prominent inflammatory cells in addition to a framework of UIP, and pulmonary function of most patients improved with anti-inflammatory agents. Six (40%) of 15 patients with TBLC-based UIP score ≥ 1 had a progressive disease course during follow-up, of whom 4 patients received anti-fibrotic agents.ConclusionsTBLC in patients with CTD-ILD can help determine an appropriate medication strategy, particularly when UIP-like lesions are present. TBLC may be useful when judging which agents to prioritize, anti-inflammatory or anti-fibrotic, is difficult. Moreover, additional information from TBLC may be beneficial when considering early intervention with anti-fibrotic agents in clinical practice.

Recent advances in the treatment of systemic sclerosis associated interstitial lung disease.

Connective tissue diseases (CTDs) are a heterogenous group of systemic inflammatory disorders. The development of connective tissue disease-associated interstitial lung disease (CTD-ILD) is a key complication associated with significant morbidity and mortality. The aim of this review is to explore the pathogenesis of CTD-ILD and summarize the recent evidence from clinical trials for novel treatment options, including the role of antifibrotics and immunomodulatory therapies with a focus on systemic sclerosis associated ILD. Further clinical trials are ongoing to explore combination therapies and more targeted therapeutic options. Clinicians remain faced with the difficult challenge of appropriately selecting patients who will benefit from the available therapies and timing the start of therapy at the most suitable part of the disease course.

Profile of COVID-19 Patients with Persistent Respiratory Symptoms

Background and objective: COVID pandemic struck the entire world causing high mortality and morbidity. After-effects of the infection were manifested in various clinical forms for the varying duration. As the pandemic waxes and wanes, COVID has become one of the differential diagnoses for various clinical and radiological pictures and triggers for respiratory diseases. While COVID sequelae are still much to explore, this study aimed to assess the clinicoradiological profile of COVID-19 patients who have persistent symptoms pertaining to the respiratory system. Materials and methods: This prospective study was conducted for 1 year from December 2020 to December 2021. COVID-19 patients aged between 10 and 85 years with persistent respiratory symptoms were included in this study. Results: There were a total of 90 patients. The mean age was 50.79 years. Forty-eight (53.3%) patients were males and 42 (46.7%) were females. Among these patients, eight patients (8.9%) had an asymptomatic or minimal symptomatic gap of at least 2 weeks from the date of positivity to the development of full-blown symptoms. The maximum duration of symptoms reported was more than 1 year and continuing. Dyspnea on exertion was the predominant symptom, in 59 patients (65.6%). Hypoxia at rest was seen in 35 (38.9%) patients, whereas seven patients with normal oxygen saturation showed exertional desaturation. Out of the 33 patients with post-COVID changes in computed tomography (CT) of the thorax, ground-glass opacities were seen in all 33 patients (100%), consolidation in 18 patients (54.5%), septal thickening in 18 patients (54.5%), and fibrosis in 15 patients (45.4%). Predominant CT finding was that of organizing pneumonia, but a few had fibrotic picture similar to usual interstitial pneumonia (UIP) or fibrotic nonspecific interstitial pneumonia (fibrotic NSIP). Hypoxia severity was significantly associated with diabetes (p = 0.028), hypertension (p = 0.028), chronic kidney disease (p = 0.027), chronic obstructive pulmonary disease (p = 0.001), obesity (p = 0.000), and smoking (p = 0.004). CT severity scoring was significantly associated with hypoxia severity. Conclusion: After the initial weeks, COVID patients can present with varying respiratory symptoms. They can present with respiratory failure as late as 1 month after the test positivity. Although CT picture was predominantly that of organizing pneumonia, COVID lung sequelae can masquerade as UIP or fibrotic NSIP as in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease, whereas atypical infections and malignancy can masquerade as COVID lung. Irreversible changes like honeycombing can occur as early as 2nd month after COVID.

Computed Tomography Radiomics-based Prediction Model for Gender–Age–Physiology Staging of Connective Tissue Disease-associated Interstitial Lung Disease

To analyze the feasibility of predicting gender-age-physiology (GAP) staging in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) by radiomics based on computed tomography (CT) of the chest. Chest CT images of 184 patients with CTD-ILD were retrospectively analyzed. GAP staging was performed on the basis of gender, age, and pulmonary function test results. GAP I, II, and III have 137, 36, and 11 cases, respectively. The cases in GAP Ⅱ and Ⅲ were then combined into one group, and the two groups of patients were randomly divided into the training and testing groups with a 7:3 ratio. The radiomics features were extracted using AK software. Multivariate logistic regression analysis was then conducted to establish a radiomics model. A nomogram model was established on the basis of Rad-score and clinical factors (age and gender). For the radiomics model, four significant radiomics features were selected to construct the model and showed excellent ability to differentiate GAP I from GAP Ⅱ and Ⅲ in both the training group (the area under the curve [AUC]=0.803, 95% confidence interval [CI]: 0.724-0.874) and testing group (AUC=0.801, 95% CI:0.663-0.912). The nomogram model that combined clinical factors and radiomics features improved higher accuracy of both training (88.4% vs. 82.1%) and testing (83.3% vs. 79.2%). The disease severity assessment of patients with CTD-ILD can be evaluated by applying the radiomics method based on CT images. The nomogram model demonstrates better performance for predicting the GAP staging.

Prognostication of progressive pulmonary fibrosis in connective tissue disease-associated interstitial lung diseases: A cohort study.

Connective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice. This is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort. A total of 230 patients with CTD-ILD were included and the median follow-up period was six (3-9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO (adjusted HR 0.97, p = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts. Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication.

Assessing prognostic factors correlating with response to nintedanib for connective tissue disease-associated interstitial lung disease: A real-world single-center study.

For patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), early medical intervention would be desirable. This study analyzed the real-world, single-center use of nintedanib for CTD-ILD patients. Patients with CTD who received nintedanib from January 2020 to July 2022 were enrolled. Medical records review and stratified analyses of the collected data were conducted. Reduction in the percentage of predicted forced vital capacity (%FVC) was seen in the elderly group (>70 years; P=.210), males (P=.027), the late group who started nintedanib >80 months after confirmation of an ILD disease activity (P=.03), the severe %DLco (diffusing capacity for carbon monoxide as a percentage of predicted) group (<40%; P=.20), the group who had extensive pulmonary fibrosis at the beginning of nintedanib (pulmonary fibrosis score >35%), and the low-dose group (nintedanib 50-100 mg/d; P=.40). %FVC did not decrease by >5% in the young group (<55 years), the early group who started nintedanib within 10months after confirmation of an ILD disease activity, and the group whose pulmonary fibrosis score at the beginning of nintedanib was <35%. It is important to diagnose ILD early and start antifibrotic drugs with proper timing for cases in need. It is better to start nintedanib early, especially for patients at risk (>70 years old, male, <40% DLco, and >35% areas of pulmonary fibrosis).