Interstitial Lung Disease In Connective Tissue Diseases Research Articles

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

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

P149 Association between nailfold videocapillaroscopy findings and sKL-6 levels in patients with idiopathic inflammatory myopathies-related interstitial lung disease

Abstract Background/Aims Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired muscle diseases with distinct clinical, pathological and histological features. Interstitial lung disease (ILD) is a frequent pulmonary manifestation in IIM (IIM-ILD) and considerably influences morbidity and mortality. Krebs von den Lungen 6 (sKL-6) has been proposed as a potential biomarker reflecting the severity of ILD in connective tissue diseases. Raynaud’s phenomenon is very frequent and the presence of microvascular changes in IIM have been described however, the role of nailfold videocapillaroscopy (NVC) in diagnosis and prognosis in IIM is not clearly established. We aim to determine if there is any association between NVC findings, sKL-6 levels and pulmonary involvement in patients with inflammatory myopathies. Methods We performed a retrospective study of IIM patients followed in a reference center and compared them according to the presence of ILD. Epidemiological, clinical and immunological data, pulmonary function tests (forced vital capacity and diffusing capacity for carbon monoxide), sKL-6 levels and NVC finding were retrieved. Statistical analysis was performed by T-test and Fisher’s exact test to compare qualitative and/or quantitative variables and multiple logistic regression modelling to identify correlation between pulmonary function tests, NVC findings and sKL-6 levels. Results 95 patients were included, 47 patients (49%) with ILD. 34% were male with a median age at inclusion of 55.3±24 years. Avascular areas and capillary lossshowed a significant association with the presence of ILD (OR 2.43, 95% CI 1.3-5.7, p 0.004) and (OR 1.7, 95% CI 1.48-3.1, p 0.04). A negative correlation between capillary loss and enlarged capillaries was also found with FVC% (β=-0.46, p 0.001 and β=-0.57, p &amp;lt; 0.0001) and DLCO% (β=-0.32, p 0.04 and β=- 0.23, p 0.03), respectively. When we studied the correlation between sKL-6 levels, positive correlations with the presence of ILD (β = 0.77, p 0.0004), the presence of hemorrhages (β = 0.21, p 0.04) and avascular areas in NVC (β = 0.64, p 0.03) and negative correlations with FVC% (β=-0.47, p 0.001) and DLCO% (β=-0.59, p, 0.005) were found. Male sex, respiratory symptoms, %FVC and %DLCO, sKL-6 levels, anti-Jo1 positivity and the presence of avascular areas and enlarged capillaries in NVC were identified as IIM-ILD predictors (R2=0.974, p = 0.006). Conclusion Capillary loss and avascular areas showed a significant association with the presence of ILD, worse FVC and DLCO values and sKL-6 levels. We identified nine predictors for developing ILD in IIM. NVC assessment and sKL-6 levels can have a predictive role for studying pulmonary function and assessing the prognosis of IIM-ILD. Disclosure C. Sieiro Santos: None. J. Tandaipan: None. D. Castillo: None. L. Martínez Martínez: None. H. Codes: None. L. Sainz: None. B. Magallares: None. P. Moya: None. H. Corominas: None. E. Díez Álvarez: None. I. Castellvi: None.

The Analysis of Proteomics by Machine Learning in Separating Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Interstitial Lung Disease.

The Analysis of Proteomics by Machine Learning in Separating Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Interstitial Lung Disease.

Tropheryma whipplei infection in the lung of a patient with long COVID: a case report

BackgroundImmune dysregulation in individuals with long COVID has been detected. Differential diagnosis of diffuse infiltration on chest CT in long COVID is challenging.Case presentationA 62-year-old man presented with a 10-month history of dyspnea after COVID-19 infection. Dyspnea became worse in the one month preceding presentation. The chest CT showed multifocal, subpleural, bilateral opacities due to long-COVID, and infiltration around the bronchovascular bundle in the bilateral lower lung field. The pathology for the transbronchial cryobiopsy (TBCB) first reported chronic inflammation (mainly interstitial pneumonia). The patient had positive results on tests for the antibody, RO-52+, EJ+. The presumptive diagnosis of connective tissue disease-interstitial lung disease was made. Prednisone and cyclophosphamide were given. At follow-up one month later, the chest CT showed new diffuse ground-glass infiltration. The previous TBCB specimen was re-evaluated. Foamy macrophages were found in the alveolar air space. Periodic acid-Schiff (PAS) staining was performed. Numerous intracytoplasmic organisms were detected, with morphologic features consistent with those of Tropheryma whipplei. The patient recovered after intravenous ceftriaxone and oral trimethoprim-sulfamethoxazole. The final diagnosis was lung T. whipplei infection and long COVID-19.ConclusionThis is the first case report of Tropheryma whipplei infection in the lung of a patient with long COVID-19. T. whipplei should be considered as a potential pathogen for diffuse lung infiltration in the post-COVID-19 era.

Identification of Idiopathic Pulmonary Fibrosis and Prediction of Disease Severity via Machine Learning Analysis of Comprehensive Metabolic Panel and Complete Blood Count Data.

Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT. Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe. ML methodology identified IPF from CTD-ILD with AUCTEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUCTEST = 0.749, FVC moderate or mild vs severe with AUCTEST = 0.741, and FVC mild vs moderate or severe with AUCTEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils. Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.

Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT

Background Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials. Objectives To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease. Methods This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m2 body surface area. The primary end point for the study was the change in forced vital capacity at 24 weeks. Secondary end points included safety and tolerability, corticosteroid exposure, forced vital capacity change at 48 weeks and patient-reported quality of life. A cost-effectiveness analysis was undertaken to assess the impact of rituximab use in the United Kingdom National Health Service. Results One hundred and one subjects (70 females) with a mean age of 56.3 years were randomised; 51 to rituximab and 50 to cyclophosphamide. Ninety-seven were included in the modified intention-to-treat population for the primary and secondary efficacy analyses (49 in the rituximab group and 48 in the cyclophosphamide group). 38.6% had scleroderma, 44.6% idiopathic inflammatory myositis and 16.8% mixed connective tissue disease. Four subjects withdrew prior to the first dose of therapy (two in each arm). At 24 weeks, both rituximab and cyclophosphamide improved forced vital capacity from baseline [(mean ± standard deviation) 97 ± 234 and 99 ± 329 ml, respectively]. Using an adjusted mixed-effects model corrected for diagnosis and baseline forced vital capacity the difference in forced vital capacity at 24 weeks between rituximab and cyclophosphamide was −40 ml (95% CI −153 to 74 ml), p = 0.49. Other physiological and quality-of-life parameters improved in both arms following treatment but were not statistically significantly different between groups. Numerically fewer adverse events were reported by subjects receiving rituximab. Corticosteroid exposure over the 48 weeks of the trial was numerically less in the rituximab arm [13,291 (±14,657) mg of hydrocortisone equivalent per subject in the cyclophosphamide arm versus 11,469 (±10,041) mg per subject in the rituximab group; these differences did not reach statistical significance]. Limitations of the study include a disproportionate number of subjects being recruited from a single centre and insufficient subjects in each subgroup to determine whether there were treatment differences between individual connective tissue diseases. Based on the results of the trial, from a UK healthcare payer perspective, rituximab is more cost-effective than cyclophosphamide as a treatment for severe or progressive connective tissue disease-interstitial lung disease. Conclusions Rituximab improved forced vital capacity and patient-reported quality of life at 24 weeks but was not superior to cyclophosphamide. Rituximab should be considered as a therapeutic alternative to cyclophosphamide in individuals with connective tissue disease-associated interstitial lung disease requiring systemic therapy. Future work should explore the role of repeated dosing of rituximab and the use of rituximab earlier in the course of connective tissue disease-associated interstitial lung disease. Trial registration This trial is registered as ISRCTN16474148. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 11/116/03) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 4. See the NIHR Funding and Awards website for further award information.

Nailfold capillaroscopy findings of interstitial pneumonia with autoimmune features.

We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined. A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience.

Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment's efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was -0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline.

Structured report improves radiology residents' performance in reporting chest high-resolution computed tomography: a study in patients with connective tissue disease.

PURPOSE To evaluate the performance of radiology residents (RRs) when using a dedicated structured report (SR) template for chest HRCT in patients with suspected connective tissue disease-interstitial lung disease (CTD-ILD), compared to the traditional narrative report (NR). METHODS We retrospectively evaluated 50 HRCT exams in patients with suspected CTD-ILD. A chest-devoted radiologist reported all the HRCT exams as the reference standard, pointing out pulmonary fibrosis findings (i.e., honeycombing, traction bronchiectasis, reticulation, and volume loss), presence and pattern of ILD, and possible other diagnoses. We divided four RRs into two groups according to their expertise level. In each group, RRs reported all HRCT examinations alternatively with NR or SR, noting each report's reporting time. The Cohen's Kappa, Wilcoxon, and McNemar tests were used for statistical analysis. RESULTS Regarding the pulmonary fibrosis findings, we found higher agreement between RRs and the reference standard reader when using SR than NR, regardless of their expertise level, except for volume loss.RRs' accuracy for "other diagnosis" was higher when using SR than NR, moving from 0.48 to 0.66 in the novel group (p = 0.035) and from 0.44 to 0.80 in the expertise group (p < 0.001). No differences in accuracy were found between ILD presence and ILD pattern. The reporting time was significantly lower (p = 0.001) when using SR than NR. CONCLUSION SR is of value in increasing the reporting of critical chest HRCT findings in the complex CTD-ILD scenario and should be used early and systematically during the residency.

Radioresistant cells in STING gain-of-function mice initiate lymphocyte dependent lung inflammation and IFNγ dependent mortality

Abstract Pediatric patients with gain-of-function (GOF) mutations in the cytosolic dsDNA sensing adaptor STING develop an autoinflammatory syndrome known as STING Associated Vasculopathy with onset in Infancy (SAVI). SAVI patients show elevated interferon signature genes and suffer from interstitial lung disease (ILD) with lymphocyte predominate bronchus associated lymphoid tissue (BALT). We genetically engineered SAVI mice (STING V154M or VM) that recapitulates human disease, including lymphocyte rich ILD, and found by genetic ablation that lymphocytes are required for lung pathology. However, while ablation of either T or B lymphocytes prolongs survival, lung immune aggregates persist, indicating either can independently be recruited as BALT. Using radiation chimeras, we found that hematopoietic stem cell (HSC) derived STING GOF was neither sufficient nor required for VM lung disease, suggesting a role for lung radioresistant parenchymal and stromal cell STING GOF in SAVI. We identified lung endothelia as putative radioresistant cells which express STING and confirmed expression by IF microscopy and FACS. FACS analysis also revealed SAVI lung endothelia upregulate MHCII, but only when sufficient for IFNgR. VM T cells produce IFNg, and IFNgR deficiency was sufficient to prevent endothelial MHCII upregulation and attenuate mortality. However, HSC STING GOF was not required for endothelial MHCII upregulation, suggesting stromal intrinsic STING GOF initiates this outcome. These findings suggest that activation of STING in stromal and parenchymal cells play a key role the initiation of lung inflammation in patients with connective tissue disease ILD. Supported by: T32 GM107000 (MSTP); T32 AI132152 (KMG); F30 HL154674 (KMG); AI128358 (AMR/KAF); Lupus Research Alliance

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.

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;

[Treatment of lung fibrosis in systemic rheumatic diseases (new treatment)].

Eine interstitielle Lungenerkrankung stellt eine relevante Organmanifestation bei vielen rheumatischen Systemerkrankungen dar (CTD-ILD [„connective tissue disease-interstitial lung disease“]). In 10 % der Fälle geht eine Lungenfibrose einer zugrunde liegenden Systemerkrankung sogar voraus. Häufig sind CTD-ILDs mit einer schlechten Prognose assoziiert. Daher ist es wichtig, Patienten mit rheumatischen Systemerkrankungen früh und regelmäßig auf das Vorliegen einer ILD („interstitial lung disease“) hin zu untersuchen. Therapieentscheidungen, besonders bezogen auf die Einleitung einer spezifischen Therapie, sollten gemeinsam von Pneumologe und Rheumatologe getroffen werden. Die Therapien beruhen nur in wenigen Fällen auf randomisierten Studien, meist gehen diese auf Fallkontrollstudien zurück. Bei systemischer Sklerose-assoziierter ILD (SSc-ILD) ist neben einer immunsuppressiven Therapie nun auch eine antifibrotische Therapie mit Nintedanib zugelassen. Bei anderen CTD-ILDs ist eine antifibrotische Therapie je nach Grunderkrankung entsprechend einer progredient fibrosierenden ILD interdisziplinär zu diskutieren.

Outcome measurement instrument selection for lung physiology in systemic sclerosis associated interstitial lung disease: A systematic review using the OMERACT filter 2.1 process

ObjectiveThe Outcome Measures in Rheumatology (OMERACT) is a research organization focused on improving health care outcomes for patients with autoimmune and musculoskeletal diseases. The Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Working Group on Lung Physiology is a group within OMERACT charged with identifying outcome measures that should be implemented in studies of patients with CTD-ILD. The OMERACT Filter 2.1 is an evidence-based algorithm used to identify outcome measures that are truthful, feasible, and able to discriminate between groups of interest. Our objective was to summate evidence (published literature, key opinion leader input, patient perspectives) that would influence the CTD-ILD Working Group's vote to accept or reject the use of two measures of lung physiology, the forced vital capacity (FVC) and the diffusion capacity of carbon monoxide (DLco) for use in randomized controlled trials (RTCs) and longitudinal observational studies (LOSs) involving patients with systemic sclerosis associated ILD (SSc-ILD). MethodsPatient Research Partners (those afflicted with SSc-ILD) and the CTD-ILD Working Group on Lung Physiology were polled to assess their opinion on the FVC and DLco in terms of feasibility; the CTD-ILD Working Group was also queried on these instruments’ face and content validity. We then conducted a systematic literature review to identify articles in the SSc-ILD population that assessed the following measurement properties of FVC and DLco: (1) construct validity, (2) test-retest reliability, (3) longitudinal construct validity, (4) clinical trial discrimination/sensitivity to detect change in clinical trials, and (5) thresholds of meaning. Results were summarized in a Summary of Measurement Properties (SOMP) table for each instrument. OMERACT CTD-ILD Working Group members discussed and voted on the strength of evidence supporting these two instruments and voted to endorse, provisionally endorse, or not endorse either instrument. ResultsForty Patient Research Partners reported these two measures are feasible (are not an unnecessary burden or represent an infeasible longitudinal assessment of their disease). A majority of the 18 CTD-ILD Working Group members voted that both the FVC and DLco are feasible and have face and content validity. The systematic literature review returned 1,447 non-duplicated articles, of which 177 met eligibility for full text review. Forty-eight studies (13 RCTs, 35 LOSs) were included in the qualitative analysis. The FVC SOMP table revealed high quality, consistent data with evidence of good performance for all five measurement properties, suggesting requisite published evidence to proceed with endorsement. The DLco SOMP table showed a lack of data to support test-retest reliability and inadequate evidence to support clinical trial discrimination. There was unanimous agreement (15 [100%]) among voting CTD-ILD Working Group members to endorse the FVC as an instrument for lung physiology in RCTs and LOSs in SSc-ILD. Based on currently available evidence, DLco did not meet the OMERACT criteria and is not recommended for use in RCTs to represent lung physiology of SSc-ILD. The OMERACT Technical Advisory Group agreed with these decisions. ConclusionThe OMERACT Filter 2.1 was successfully applied to the domain of lung physiology in patients with SSc-ILD. The FVC was endorsed for use in RCTs and LOSs based on the Working Group's vote; DLco was not endorsed.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS W. Joseph McCuneW. Joseph McCuneDr W. Joseph McCune MD is Michael and Marcia Klein Professor of Rheumatic Diseases and Director of the Lupus Program at the University of Michigan. Following an Internal Medicine residency at the University of Michigan and a fellowship in Immunology and Rheumatology at Harvard Medical School and the Brigham and Woman's Hospital, Dr McCune has been a member of the faculty at the University of Michigan where he specializes in the epidemiology, diagnosis, and treatment of lupus and systemic vasculitis. Bryant R. EnglandBryant R. EnglandDr Bryant R. England is a clinician-investigator at the University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System. He focuses on improving long-term outcomes in patients with rheumatoid arthritis (RA), and conducts clinical and epidemiologic research in RA-associated lung disease, cardiovascular disease, cancer, and multimorbidity using several large observational datasets. He also leads prospective studies in RA-associated lung disease and connective tissue disease-interstitial lung disease. Clinically, Dr England is a rheumatologist focused on the care of patients with inflammatory arthritis and incorporates the use of musculoskeletal ultrasound into the diagnosis and management of rheumatic diseases. He also directs the UNMC Autoimmune Lung Disease Clinic, a multi-specialty clinic that specializes in treating autoimmune lung diseases (e.g. RA-interstitial lung disease and other connective tissue disease-interstitial lung disease). Dr England is actively involved in the American College of Rheumatology and teaches medical students, residents, and fellows in the areas of rheumatology, musculoskeletal ultrasound, and clinical research as well as serving as a research mentor to students, residents, and fellows.

Multidisciplinary team obviates biopsy in most patients with diffuse parenchymal lung diseases—A retrospective study from India

The inflammation and fibrosis in diffuse parenchymal lung diseases (DPLDs) in varied proportions give rise to different patterns in radiology and histopathology. The radiological pattern on CT of the thorax most often allows us to make a diagnosis with varying levels of confidence, to optimize management. With a multidisciplinary team bringing the strengths of their individual domains of knowledge, clinical, radiological, histopathological, and in many cases rheumatological, the level of confidence in making this diagnosis increases, often to the stage where the diagnosis is most often right, is concordant with the diagnosis achieved at histopathology and therefore obviates the need for lung biopsy which carries its own costs and risks of complications. Our study emphasizes the role of the multidisciplinary team (MDT) in the management of DPLDs at a tertiary care referral center. Every case of DPLD presenting to our pulmonology department was discussed in an MDT meeting before subjecting them to any diagnostic intervention or therapy. A clinico-radiological diagnosis was made according to the 2002 ATS/ERS guidelines initially. Later an official ATS/ERS/JRS/ALAT statement on idiopathic pulmonary fibrosis and a 2013 ATS/ERS consensus for the classification and diagnosis of idiopathic interstitial pneumonia was used. The concordance in our study was defined as the percentage of histopathological diagnoses that were identical to the clinico-radiological MDT diagnosis prior to the biopsy. A total of 434 patients with DPLDs were evaluated. The MDT suggested biopsy for only 38.7% (168/434) patients since the pattern was very clear in 266 (61.3%) cases. As not all patients consented to undergo the biopsy procedure when recommended, histopathology was obtained in 102 patients. The histological diagnosis was concordant with the initial MDT diagnosis in 80.3% (82/102) of samples. On an individual basis, connective tissue disease-interstitial lung disease and sarcoidosis showed the best concordance (87%). In idiopathic non-specific interstitial pneumonitis (NSIP) cases, the histopathological diagnosis concurred in only 53.3% (8/15), out of which 8 were NSIP, 4 were usual interstitial pneumonia, and 3 were reported as inadequate sampling on histopathology. The MDT plays a crucial role in the diagnosis of DPLDs. Not every pattern requires biopsy confirmation. However, an idiopathic non-specific interstitial pneumonitis diagnosis by the MDT should probably be better confirmed by biopsy.

Multi-disciplinary team approach in the management of connective tissue disease-interstitial lung disease: The way forward

Multi-disciplinary team approach in the management of connective tissue disease-interstitial lung disease: The way forward

COMPARISON OF PRE- VS POST-LUNG TRANSPLANT CAUSE OF INTERSTITIAL LUNG DISEASE

SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The aim of this study is to compare the clinical diagnosis of interstitial lung disease to that determined on post-explant evaluation. METHODS: Retrospective study conducted through chart review of 50 consecutive lung transplants performed in patients with interstitial lung disease (ILD) at The University of Health Sciences Center at San Antonio. All charts of patients over 18 years of age who underwent lung transplantation with the diagnosis of ILD were carefully reviewed to determine the clinical pre-transplant diagnosis. Studies included high-resolution computed tomography (HRCT), serologic evaluation of connective tissue disease in all patients. Data from transbronchial biopsy or open lung biopsy were reviewed in determining the pre-transplant diagnosis. We compared the pre-lung transplant diagnosis to the post-transplant, pathologic diagnosis determined from the explanted lungs. RESULTS: A total of 50 patients with ILD who had either single or bilateral lung transplant were analyzed. Thirty-three patients (66%) had pre-transplant (pre-tx) diagnosis of usual interstitial pneumonia (UIP), eight patients (16%) had pre-tx diagnosis of nonspecific interstitial pneumonia (NSIP), six patients (12%) had a pre-tx diagnosis of connective tissue disease – ILD (CTD-ILD), one patient (2%) with pre-tx diagnosis of hypersensitivity pneumonitis (HSP) while four patients (8%) had other diagnoses, including indeterminate end stage lung disease (ESLD), type I congenital cystic adenomatoid malformation (CCAM) and constrictive bronchiolitis with fibrosis. After lung explant biopsies were reviewed, seventeen (34%) cases were reclassified compared to the pre-tx diagnoses. However, out of these seventeen cases, only six cases (12%) were clinically significant. Out of the six clinically significant misdiagnoses, three had a final diagnosis of HSP and three had a final diagnosis of NSIP. The remaining discrepancies in diagnosis were disorders t hat are known to progress to UIP. CONCLUSIONS: Almost two-thirds (66%) of all cases had consistent pre-transplant diagnoses when compared to post- transplant diagnoses. Most of the remaining cases (22%) had disorders known to progress to UIP. However, in 12% of cases, the diagnosis changed from a disorder with a progressive course to one that carries a different prognosis and might have responded to alternative therapies (NSIP and HSP). CLINICAL IMPLICATIONS: Definitive diagnosis in patients with ILD is both difficult and challenging. However, it is imperative to be cautious and observant when searching for disorders that are more responsive to environmental changes or responsive to immunotherapy. Early diagnosis of accurate ILD along with the use of multi-disciplinary discussion (MDD) can improve appropriate therapy in patients with ILD. DISCLOSURES: No relevant relationships by Sarah Hackman, source=Web Response No relevant relationships by Tasnim Islam, source=Web Response No relevant relationships by Jay Peters, source=Web Response

IPAF should receive early treatment for sharing similar clinical characteristics as CTD-ILD: a report from 273 Chinese patients.

The clinical characteristics of interstitial pneumonia with autoimmune features (IPAF) and connective tissue disease interstitial lung disease (CTD-ILD) have not been adequately compared. We compared the clinical characteristics of these two conditions and analyzed the changes in lung function before and after treatment of IPAF. A total of 412 patients were enrolled in the study, and their clinical characteristics were assessed. The treatment-related changes in 12 cases of IPAF were analyzed. Complete clinical data were available for 126 patients with CTD-ILD and 147 with IPAF. All IPAF patients showed autoantibody positivity. The proportion of patients showing extrapulmonary symptoms in the CTD-ILD group was higher than that in the IPAF group (P < 0.05). Patients with IPAF demonstrated lower P(A-a)O2 and higher PaO2 and PaCO2 than those with CTD-ILD (P < 0.05 for all comparisons). Forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) in IPAF patients were higher than those in CTD-ILD patients (P = 0.023 for FVC; P = 0.011 for DLCO). Among patients with IPAF, only the proportions of honeycombing and nodules were lower than those in CTD-ILD patients (P < 0.05). Both FVC and DLCO values increased after treatment in patients with IPAF (P < 0.05). IPAF showed autoantibody positivity and similar computed tomography (CT) findings as CTD-ILD, and lung function in patients with IPAF improved after immunosuppressive treatment, indicating that IPAF should receive attention and early immunosuppressive treatment like CTD-ILD, even though IPAF exhibits no extrapulmonary symptoms. Key Points • Clinical characteristics of IPAF.

Current and EmergingDrug Therapies for Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD).

Interstitial lung disease (ILD) can be associated with all connective tissue diseases and is an important cause of morbidity and mortality. The management of connective tissue disease-interstitial lung disease (CTD-ILD) is challenging due substantial heterogeneity in disease behaviour and paucity of controlled clinical trials to guide treating clinicians. Not all patients require treatment, and the decision to treat needs to be individualised based on a patient's observed disease behaviour, baseline and longitudinal lung function measurements, extent of lung involvement on radiology and patient factors including age, co-morbidities and personal preference. If indicated, treatment of the CTD-ILD is largely with immunomodulation, with the aim to prevent progression of the ILD before further irreversible lung injury and disability occurs. Corticosteroids, cyclophosphamide, mycophenolate mofetil and azathioprine are the most common immunosuppressive agents currently used to treat CTD-ILD, demonstrating stability of lung function in case series and a small number of randomised controlled trials in ILDassociated with systemic sclerosis. Biological and non-biological disease-modifying anti-rheumatic drugs, and the anti-fibrotics nintedanib and pirfenidone, have revolutionised the treatment of connective tissue diseases and idiopathic ILD, respectively. Furthermore, anti-fibrotics have recently demonstrated safety and efficacy in ILD associated with systemic sclerosis. There remains a critical unmet need to clarify when and in whom to initiate treatment, and which agent(s) to utilise to achieve optimal outcomes for CTD-ILD patients whilst minimising harms through prospective multicentre trials. This review highlights the challenges faced when treating patients with CTD-ILD and summarises available evidence for current, emerging and novel therapies.