Tissue Disease-related Interstitial Lung Research Articles

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.

Comparison of the diagnostic criteria for progressive pulmonary fibrosis in connective tissue disease related interstitial lung disease

BackgroundProgressive pulmonary fibrosis (PPF) is possible among patients with connective tissue disease (CTD) related interstitial lung disease (ILD). Our aim herein was to compare the prevalence and clinical characteristics of patients with CTD-ILD, with and without PPF, according to the different diagnostic criteria currently used in practice. MethodsThis retrospective study included patients diagnosed with CTD-ILD, with a ≥1-year follow-up of their lung function, at a single tertiary hospital in South Korea. Diagnostic criteria from two clinical trials (RELIEF and TRAIL1) and from a recently updated guideline (ATS/ERS/JRS/ALAT) were applied. ResultsOf the 107 patients included, 80% tested positive for Sjogren's disease, rheumatoid arthritis, and systemic sclerosis. The prevalence of CTD-ILD with PPF for the different diagnostic criteria was as follows: RELIEF, 25.2%; TRAIL1, 20.6%; and ATS/ERS/JRS/ALAT, 38.3%. More previous history of pulmonary tuberculosis and less positivity for antinuclear antibodies were identified in the PPF group. The radiologic pattern of ILD did not differ between patients with and without PPF, with a usual interstitial pneumonia pattern identified in 34.6% of the patients. Systemic steroids and immunomodulatory agents were used in about 80% of patients with PPF and 50% without PPF, irrespective of the diagnostic criteria used. Antifibrotic therapy was used in a limited number of patients in both groups. ConclusionsThe proportion of patients with CTD-ILD and PPF was higher for the ATS/ERS/JRS/ALAT guideline criteria, without a between-group difference in clinical characteristics.

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.

Screening value of lung ultrasound in connective tissue disease related interstitial lung disease

BackgroundInterstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD) that can lead to poor quality of life and prognosis. ObjectivesTo explore the screening value of lung ultrasound (LUS) for connective tissue disease-associated interstitial lung disease (CTD-ILD). MethodsData of patients with CTD were collected, and each patient underwent LUS, high-resolution computed tomography (HRCT), and pulmonary function tests. Considering HRCT is the gold standard for diagnosing CTD-ILD, patients were divided into CTD-ILD and CTD-non-ILD groups. The LUS and HRCT results were assessed using semiquantitative and Warrick scores, respectively. Pulmonary function results were also collected. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of LUS diagnosis. Spearman correlation analysis was used to analyze the correlation between LUS, HRCT, and lung function indices. ResultsA total of 88 patients (65 with CTD-ILD and 23 with CTD-non-ILD) were included in this study. The sensitivity and specificity of LUS for the diagnosis of CTD-ILD were 86.60% and 82.60%, respectively, which was consistent with the HRCT results (P < 0.05). The LUS results (total number of B-lines, frequency of B-line, pleural thickness, and pleural-line irregularity) were positively correlated with the HRCT Warrick score (r = 0.77, 0.76, 0.65 and 0.71, P < 0.05). ConclusionsLUS may be a promising tool for screening patients with CTD-ILD.

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

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

Management of Connective Tissue Disease–related Interstitial Lung Disease

Purpose of ReviewThis review aims to collate current evidence on the screening, diagnosis, and treatment of various connective tissue disease (CTD)–associated interstitial lung diseases (CTD-ILD) and present a contemporary framework for the management of such patients. It also seeks to summarize treatment outcomes including efficacy and safety of immunosuppressants, anti-fibrotics, and stem cell transplantation in CTD-ILD.Recent FindingsScreening for ILD has been augmented by the use of artificial intelligence, ultra-low dose computerized tomography (CT) of the chest, and the use of chest ultrasound. Serum biomarkers have not found their way into clinical practice as yet. Identifying patients who need treatment and choosing the appropriate therapy is important to minimize the risk of therapy-related toxicity. The first-line drugs for systemic sclerosis (SSc) ILD include mycophenolate and cyclophosphamide. Nintedanib, an anti-fibrotic tyrosine kinase inhibitor, is approved for use in SSc-ILD. The US Food and Drug Administration (FDA) has recently approved tocilizumab subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD. Autologous stem cell transplantation may have a role in select cases of SSc-ILD.SummaryCTD-ILD is a challenging area with diverse entities and variable outcomes. High-resolution CT is the investigative modality of choice. Treatment decisions need to be individualized and are based on patient symptoms, lung function, radiologic abnormalities, and the risk of disease progression. Precision medicine may play an important role in determining the optimal therapy for an individual patient in the future.

Prevalence of airway reversibility in connective tissue disease-interstitial lung disease (CTD-ILD)

Background: Spirometry is the most reproducible and objective measurement of airflow limitation. Improvement in FEV1 and/or FVC by 12% or 200ml after using bronchodilator is definitive of reversible airway disease.[1] Several conditions like sarcoidosis predominantly involve the interstitium have nevertheless been associated with reversible airways obstruction. Connective tissue diseases (CTDs) form another important subgroup of interstitial lung disease(ILD). CTDs usually produce a restrictive pattern of lung involvement on spirometry, but might have unrecognized additional reversible airway obstruction. Seeking out and treating the latter components of disease may be crucial in optimizing lung function and alleviating the breathlessness that is common to the problem. Aim: The aim of this study is therefore to determine the post bronchodilator response in patients with connective tissue disease related interstitial lung disease (CTD-ILD) and thus potentially help improve quality of life by addressing the latter component by inhaled bronchodilator-steroid therapy. Methods: Consecutive patients with a confirmed diagnosis of CTD-ILD were identified in the out-patient clinics of our institute. CTD was diagnosed by a combination of clinical and serological parameters. ILD was confirmed by high resolution computed tomography (HRCT) images. &#x0D;

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations.

Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.

Transbronchial lung cryobiopsy for connective tissue disease-related interstitial lung disease and interstitial pneumonia with autoimmune features: a single center retrospective case series.

Transbronchial lung cryobiopsy (TBLC) has been recently introduced for diagnosing interstitial lung diseases. We aimed to assess the effectiveness and safety of TBLC by identifying the specific patterns of histology in the diagnosis of connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF). The clinical-radiological-pathological data from the Affiliated Hospital of Guilin Medical University between July 1, 2017, and October 31, 2020, of patients whose clinical-radiological or clinical-radiological-pathological diagnosis was CTD-ILD or IPAF and who underwent TBLC, transbronchial lung biopsy (TBLB), or surgical lung biopsy were retrospectively analyzed and summarized with review. The size of biopsy samples, complications, and diagnostic yield were compared. Fourteen patients met the inclusion criteria, of whom 12 underwent TBLC, 1 underwent TBLB, and 1 underwent each procedure at different times. Compared to the size of TBLB specimens (5.625 ± 0.479 mm2), the size of TBLC specimens (12.00 (12.00, 15.00) mm2) was much larger (Z = - 3.262, P = 0.001). The diagnostic yields of TBLC and TBLB were 100.00% (13/13) and 0.00% (2/2), respectively (P = 0.0095). The most frequent complication was mild bleeding. The risk of bleeding between TBLB (1/2, 50.00%) and TBLC (10/13, 76.92%) did not differ significantly (P = 0.469). TBLC can add extra diagnostic value by effectively identifying specific types of histology for patients with suspected CTD-ILD or IPAF, with a procedure that is safe from adverse events. Key Points • Transbronchial lung cryobiopsy has been introduced recently for diagnosing interstitial lung disease. • Transbronchial lung cryobiopsy was found to be effective and safe in the diagnosis for patients with suspected interstitial lung disease. It can be used as a preferred method for biopsy when the clinical-radiological diagnosis is uncertain.

14. A severe case of connective tissue disease related interstitial lung disease in a young woman

14. A severe case of connective tissue disease related interstitial lung disease in a young woman

Clinical characteristics of connective tissue disease-related interstitial lung disease: an analysis of 186 cases

Objective To analyze the clinical characteristics of connective tissue disease related interstitial lung disease (CTD-ILD). Methods The demographic data, clinical manifestations, blood gas analysis, lung function, chest high resolution CT (HRCT), histopathology of 186 patients with CTD-ILD admitted in Jinhua Central Hospital from January 2013 to December 2017 were retrospectively analyzed. Results In 186 patients with CTD-ILD,70 were males and 116 were females, with a mean age of 56.22±12.27. Among them, 61 cases were polymyositis/dermatomyositis (DM/PM)-ILD, 44 cases were rheumatoid arthritis (RA)-ILD, 26 cases were interstitial pneumonia with autoimmune features (IPAF), 16 cases were systemic sclerosis (SSc)-ILD, 14 cases were Sjogren syndrome (SS)-ILD, 11 cases were overlap syndrome (OS)-ILD, 7 cases were systemic lupus erythematosus (SLE)-ILD, 5 cases were undifferentiated connective tissue disease (UCTD)-ILD, and 2 cases were mixed connective tissue disease (MCTD)-ILD. The incidence of respiratory symptoms was higher than that of systemic symptoms, and the incidence of systemic symptoms was higher than that of skin symptoms. Cough was the most common symptom of respiratory system, and arthralgia was the most common symptom of systemic symptoms, accounting for 54.9% (101/186) and 48.9% (91/186) respectively. Blood gas analysis showed that hypoxemia accounted for 56.5% (83/147) and type Ⅰ respiratory failure accounted for 26.5% (39/147) . The proportion of restrictive ventilation dysfunction in pulmonary function tests was 70.9% (105/148) and the diffuse dysfunction was 81.1% (120/148) . The manifestations on HRCT were reticular linear shadow (44.1%), ground-glass opacity (54.3%), consolidation (23.1%), nodules shadow (20.9%) and cystic low density shadow (9.1%) . The histopathological diagnosis mainly was non-specific interstitial pneumonia (NSIP, 43.0%) and usual interstitial pneumonia (UIP,40.0%). Conclusion The arterial blood gas analysis, lung function and chest HRCT screening, and lung histopathological examination are important for early identification and diagnosis of CTD-ILD. Key words: Connective tissue diseases; Lung diseases, interstitial; Blood gas analysis

Patient Perspectives in OMERACT Provide an Anchor for Future Metric Development and Improved Approaches to Healthcare Delivery in Connective Tissue Disease Related Interstitial Lung Disease (CTD-ILD).

The impact and natural history of connective tissue disease related interstitial lung disease (CTD-ILD) are poorly understood; and have not been previously described from the patient's perspective. This investigation sought insight into CTD-ILD from the patients' perspective to add to our knowledge of CTD-ILD, identify disease-specific areas of unmet need and gather potentially meaningful information towards development of disease-specific patient-reported outcome measures (PROMs). A mixed methods design incorporating patient focus groups (FGs) querying disease progression and life impact followed by questionnaires with items of importance generated by >250 ILD specialists were implemented among CTD-ILD patients with rheumatoid arthritis, idiopathic inflammatory myopathies, systemic sclerosis, and other CTD subtypes. FG data were analyzed through inductive analysis with five independent analysts, including a patient research partner. Questionnaires were analyzed through Fisher's Exact tests and hierarchal cluster analysis. Six multicenter FGs included 45 patients. Biophysiologic themes were cough and dyspnea, both pervasively impacting health related quality of life (HRQoL). Language indicating dyspnea was unexpected, unique and contextual. Psycho-social themes were Living with Uncertainty, Struggle over Self-Identity, and Self-Efficacy - with education and clinician communication strongly emphasised. All questionnaire items were rated 'moderately' to 'extremely' important with 10 items of highest importance identified by cluster analysis. Patients with CTD-ILD informed our understanding of symptoms and impact on HRQoL. Cough and dyspnea are central to the CTD-ILD experience. Initial FGs have provided disease-specific content, context and language essential for reliable PROM development with questionnaires adding value in recognition of patients' concerns.

Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.MethodsThe mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.ResultsThe mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.ConclusionsThe mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

RationaleClinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue...

AB0815 Living with connective tissue disease related interstitial lung disease: Patient experiences of the disease over time

BackgroundVery limited information is available about the patient experience of connective tissue disease-related interstitial lung disease (CTD-ILD), in terms of global effects on functioning in various psychological and social spheres...

THU0486 Peroxisome Proliferator Activated Receptorγ Anti-Fibrosis Mechanism in Connective Tissue Disease Related Interstitial Lung Disease

BackgroundConnective tissue disease (CTD) is a disease with a high incidence and a poor therapeutic effect. In recent years, in vitro and in vivo experimental studies have confirmed that the...

P9 Mycophenolate mofetil in connective tissue disease related interstitial lung disease—experience from a teaching tertiary care centre from South India

P9 Mycophenolate mofetil in connective tissue disease related interstitial lung disease—experience from a teaching tertiary care centre from South India