scholarly journals POS0866 TWO-DIMENSIONAL HRCT-BASED RADIOMIC FEATURES IN SSC-ILD DISTINGUISH DRUG RESPONDERS FROM NON-RESPONDERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 688-689
Author(s):  
C. Meier ◽  
M. Maciukiewicz ◽  
M. Brunner ◽  
J. Schniering ◽  
H. Gabrys ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Linear Regression ◽  
Lung Disease ◽  
Treatment Response ◽  
Two Dimensional ◽  
Research Support ◽  
Pre Treatment

Background:Management of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is complicated by high inter-patient variability. To date, no validated predictors of treatment response are available for routine use. High resolution computed tomography (HRCT)-based radiomics, i.e. the high-dimensional, quantitative analysis of imaging metadata, have previously been shown to be successful in discriminating (SSc-)ILD phenotypes in preclinical and clinical studies1. Since HRCT is an integral part of the routine work-up in SSc, HRCT-based radiomic features may hold potential as non-invasive biomarkers.Objectives:To predict treatment response using two-dimensional (2D) HRCT-based radiomics in SSc-ILD patients from a prospectively followed cohort.Methods:Inclusion criteria were diagnosis of SSc-ILD in HRCT, availability of a suitable chest HRCT scan within 12 months prior to initiation of a new treatment, and availability of clinical baseline and follow-up information. Treatment response was defined as the absence of all of the following over a follow-up period of 12-24 months: relative decrease in forced vital capacity (FVC) ≥5%, increase of ILD in HRCT as assessed by a radiologist, change in treatment regimen due to insufficient response, ILD-related death or lung transplantation. Of each pre-treatment HRCT, 6 slices (15±5 mm apart, starting from the basal lung margin) were manually segmented and 1513 2D radiomic features were extracted using the in-house software Z-Rad (Python 2.7). Features were Z-score transformed and pre-filtered for inter- and intra-reader robustness (intraclass correlation coefficient >0.85) and inter-feature correlation (Spearman’s rho <0.9). A categorical linear regression model was created using 3-fold cross-validated elastic nets for feature selection. Features were then summarized and divided by their number. For generation of a score cut-off, Youden’s score was used. For two-group analyses of continuous variables, Wilcoxon’s test was performed, whereas categorical data was assessed using Fisher’s exact test.Results:A total of 64 pre-treatment HRCTs from 54 patients were analyzed. In 9 patients, >1 asynchronous treatments were assessed, while 45 patients had only 1 eligible treatment approach. The response rate within the assessed follow-up period was 45.3% (n=29). For score generation, 13 radiomic features were selected and an optimal cut-off value of -0.1589 was determined. Univariate linear regression showed significant association between our categorical radiomics-based score and treatment response (p=0.007, area under the curve = 0.65 (0.51-0.79), sensitivity=0.90, specificity=0.43), whereby a high score was predictive for treatment response.No differences between patients with high (n=46) or low (n=18) scores were detected for baseline age (mean±SD=55.5±12.0 and 55.5±13.6 years, p=0.84), duration of SSc (mean±SD=6.2±8.4 and 4.7±4.4 years, p=0.79), time since ILD diagnosis (2.7±2.9 and 2.4±3.1 years, p=0.59), FVC (77.6±20.6 and 80.1±17.9, p=0.41) or DLco (54.4±21.0 and 57.6±18.9, p=0.40). Distribution of anti-Scl-70 positivity (45.7% vs. 55.6%, p=0.58) and diffuse cutaneous disease (47.7% vs. 61.1%, p=0.41) was not significantly different between patients with high and low scores, respectively, although a trend towards higher percentages in the high score group was observed.Conclusion:Our results indicate that, following validation in external cohorts, radiomics may be a promising tool for future pre-treatment patient stratification. Moreover, our radiomics-based score seems not to be associated with commonly studied clinical predictors such as anti-Scl-70 positivity or lung function, underlining a possible additive value to ‘traditional’ clinical parameters.References:[1]Schniering, J., et al. Resolving phenotypic and prognostic differences in interstitial lung disease related to systemic sclerosis by computed tomography-based radiomics. medRxiv [Preprint] doi:10.1101/2020.06.09.20124800 (2020).Disclosure of Interests:Chantal Meier: None declared, Malgorzata Maciukiewicz: None declared, Matthias Brunner: None declared, Janine Schniering: None declared, Hubert Gabrys: None declared, Anja Kühnis: None declared, Oliver Distler Speakers bureau: Speaker fee on Scleroderma and related complications: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche. Speaker fee on rheumatology topic other than Scleroderma: MSD, iQone, Novartis, Pfizer, Roche, Consultant of: Consultancy fee for Scleroderma and its complications: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Boehringer, CSL Behring, ChemomAb, Corbus Pharmaceuticals, Horizon Pharmaceuticals, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Roivant Sciences, Sanofi, UCB. Consultancy fee for rheumatology topic other than Scleroderma: Abbvie, Amgen, Lilly, Pfizer, Grant/research support from: Research Grants to investigate the pathophysiology and potential treatment of Scleroderma and its complications: Kymera Therapeutics, Mitsubishi Tanabe, Thomas Frauenfelder: None declared, Stephanie Tanadini-Lang: None declared, Britta Maurer Speakers bureau: Speaker fees from Boehringer-Ingelheim, Grant/research support from: Grant/research support from AbbVie, Protagen, Novartis Biomedical Research, congress support from Pfizer, Roche, Actelion, mepha, and MSD

Mycophenolate in scleroderma-associated interstitial lung disease: Real-world data from rheumatology and pulmonology clinics in South Asia

2021 ◽  
pp. 239719832110244
Author(s):  
Ramya Janardana ◽  
Aparna Irodi ◽  
Pramod P Chebbi ◽  
Ruchika Goel ◽  
Leena R Vimala ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Mycophenolate Mofetil ◽  
Systemic Sclerosis ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
High Resolution Computed Tomography

Introduction: There is a paucity of real-world data on mycophenolate mofetil/mycophenolate sodium in systemic sclerosis-related interstitial lung disease. Aim: To study the efficacy of mycophenolate mofetil/ mycophenolate sodium in systemic sclerosis-related interstitial lung disease. Methods: In this single-centre study, clinical, laboratory and imaging details of consecutive patients with systemic sclerosis-related interstitial lung disease receiving mycophenolate mofetil/mycophenolate sodium from rheumatology and pulmonology clinics between January 2008 and March 2017 were retrospectively retrieved. The change in percentage of predicted normal forced vital capacity at last follow-up visit as compared with baseline was studied. In addition, high-resolution computed tomography scans at baseline and 2-year follow-up visit were scored as either stable/improved or worsened by experienced thoracic radiologists blinded to the clinical details of patients. Results: Altogether, 88 patients (85.2% females) with mean age (SD) of 33.8 years (± 11.3) and median (interquartile range) duration of disease since non-Raynaud’s symptoms of 36 months (13.5–60) were studied. Diffuse systemic sclerosis comprised 85.2% of them. The mean baseline forced vital capacity was 61.2 ± 17.9% and median scores for ground glass opacities and fibrosis in high-resolution computed tomography were 0.5 (0–1.3) and 1 (0–1.3), respectively. At a median follow-up duration of 30 months (interquartile range = 16.5–49), the percentage of forced vital capacity improved by 1.8% (–3.82 to 9.07) as compared with baseline visit ( p = 0.02). In the 2-year follow-up, the ground glass opacity and fibrosis scores in high-resolution computed tomography improved in 17.3% and 7.7% of patients and stabilized in 63.5% and 78.8% patients, respectively. Conclusion: Mycophenolate mofetil/mycophenolate sodium was efficacious in improving /stabilizing forced vital capacity irrespective of the baseline high-resolution computed tomography lung scores in our patients with systemic sclerosis-related interstitial lung disease during the ⩾ 2-year follow-up period.

scholarly journals OP0267 SHORT-TERM CHANGES IN THE RADIOGRAPHIC EXTENT OF INTERSTITIAL LUNG DISEASE PREDICT LONG-TERM MORTALITY IN SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 162.2-163
Author(s):  
E. Volkmann ◽  
D. Tashkin ◽  
M. Roth ◽  
J. Goldin ◽  
G. Kim
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cox Proportional Hazards ◽  
Research Support ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival

Background:The forced vital capacity (FVC) is often used as the primary endpoint in treatment trials for systemic sclerosis-interstitial lung disease (SSc-ILD), and while trends in FVC have been found to predict mortality in SSc-ILD,1,2 FVC measurements are also influenced by extra-pulmonary factors, such as cutaneous sclerosis, myopathy, and patient/technician effort. Change in the quantitative extent of ILD (QILD) on HRCT is an emerging endpoint in clinical trials; however, no studies have evaluated whether changes in radiographic extent ILD predict mortality in SSc-ILD.Objectives:To evaluate the relationship between changes QILD in the whole lung (WL) and long-term survival in patients who participated in the Scleroderma Lung Study (SLS) I3 and II.4Methods:SLS I randomized 158 SSc-ILD patients to 12 months of cyclophosphamide (CYC) vs. placebo. SLS II randomized 142 SSc-ILD patients to 12 months of CYC, followed by 12 months of placebo vs. 24 months of mycophenolate (MMF). QILD-WL scores were calculated at baseline and 12 months (SLS I) and 24 months (SLS II). Participants were followed for up to 12 (SLS I) and 8 years (SLS II). Using landmark survival analysis, Kaplan Meier curves were generated to compare survival between participants who had worse QILD-WL scores (≥2% increase) and those who had stable/improved QILD-WL scores (<2% increase). Cox proportional hazards models were created to determine whether the change in QILD-WL scores predicted survival after controlling other variables found to affect survival in these cohorts.Results:Among all the SLS I and II participants, 82 and 90 had follow up HRCT scans, respectively, and were included in these analyses. SLS I participants with an increase in QILD-WL scores of ≥2% at 12 months had significantly worse long-term survival (P= 0.01; Figure). Similarly, SLS II participants with an increase in QILD-WL scores of ≥2% at 24 months had significantly worse long-term survival (P= 0.019; Figure). After adjusting for baseline FVC, age, and modified Rodnan skin score (mRSS), an increase in QILD-WL scores of ≥2% remained associated with worse long-term survival in SLS I (trend: P=0.089) and SLS II (P=0.014).Conclusion:Progression of the radiographic extent of ILD of ≥2% was associated with worse long-term survival in two independent SSc cohorts with extensive long-term follow up. The findings provide compelling evidence that short-term changes in the radiographic extent of ILD may serve as a surrogate endpoint for mortality in patients with SSc.References:[1]Goh NS, et al. Arthritis Rheum 2017.[2]Volkmann ER, et al. Ann Rheum Dis 2019.[3]Tashkin DP, et al. NEJM 2006.[4]Tashkin DP, et al. Lancet Resp Med 2016.Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Forbius, Corbus, Donald Tashkin: None declared, Michael Roth Grant/research support from: Genentech/Roche, Jonathan Goldin: None declared, Grace Kim: None declared

Thoracic lymphadenopathy as possible predictor of the onset of interstitial lung disease in systemic sclerosis patients without lung involvement at baseline visit: A retrospective analysis

2020 ◽  
Vol 5 (3) ◽  
pp. 210-218
Author(s):  
Cinzia Rotondo ◽  
Livio Urso ◽  
Emanuela Praino ◽  
Fabio Cacciapaglia ◽  
Addolorata Corrado ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Confidence Interval ◽  
Lung Disease ◽  
Disease Onset ◽  
High Resolution Computed Tomography ◽  
Anticentromere Antibodies

Objective: To evaluate clinical, laboratory, or radiographic predictors of the onset of interstitial lung disease in systemic sclerosis. Methods: Sixty-five out of 220 systemic sclerosis outpatients, without interstitial lung disease at baseline and with ⩾3 chest high resolution computed tomography scans during follow-up were recruited. Thoracic lymphadenopathy and interstitial lung disease were assessed by chest high resolution computed tomography. Hazard ratio (95% confidence interval) of interstitial lung disease occurrence was assessed by Cox regression models, adjusting patient’s demographics and disease characteristics. Sensitivity, specificity, and accuracy of the interstitial lung disease predictors were evaluated by receiver operating characteristic analysis. Results: The development of interstitial lung disease was observed in 44/65 (68%) patients. Thoracic lymphadenopathies was detected in 40/65 (61%) patients, of whom 36 (82%) developed interstitial lung disease, but only four patients with thoracic lymphadenopathies did not develop ILD at last visit of follow-up (19%) (p = 0.0001). Adjusted hazard ratio of systemic sclerosis-interstitial lung disease onset was 5.8 (95% confidence interval, 2.0–16.5) for thoracic lymphadenopathy, which preceded by 108 ± 98 weeks the systemic sclerosis-interstitial lung disease detection. Thoracic lymphadenopathy had 84% specificity, 81% sensitivity, and 0.82 accuracy to predict interstitial lung disease. In particular, anticentromere antibodies or limited cutaneous subset of systemic sclerosis patients with thoracic lymphadenopathy showed earlier interstitial lung disease onset than those without lymphadenopathy. In addition, patients who developed interstitial lung disease had higher frequency of anti-Scl-70 (57% vs 19%; p = 0.009) and diffuse cutaneous subset (29% vs 3%; p = 0.02) than those who did not. Conclusions: Thoracic lymphadenopathy was the strongest independent predictor of systemic sclerosis-interstitial lung disease, mostly in anticentromere antibodies and limited cutaneous subset of systemic sclerosis patients. Further prospective studies are needed to confirm our preliminary data and to understand whether thoracic lymphadenopathies may have a pathogenetic role in interstitial lung disease development.

scholarly journals AB0605 CLINICAL PROFILE AND CHEST HIGH-RESOLUTION COMPUTED TOMOGRAPHY (HRCT) FINDINGS IN PATIENTS WITH CONNECTIVE TISSUE DISEASES AND INTERSTITIAL LUNG DISEASE: EXPERIENCE OF A SINGLE REFERENCE RHEUMATOLOGY CENTER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1598.2-1599
Author(s):  
I. Rusu ◽  
L. Muntean ◽  
M. M. Tamas ◽  
I. Felea ◽  
L. Damian ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Connective Tissue Diseases ◽  
High Resolution Computed Tomography ◽  
Hrct Patterns

Background:Interstitial lung disease (ILD) is a common manifestation of connective tissue diseases (CTDs), and is associated with significant morbidity and mortality. Chest high-resolution computed tomography (HRCT) play an important role in the diagnosis of ILD and may provide prognostic information.Objectives:We aimed to characterize the clinical profile and chest HRCT abnormalities and patterns of patients diagnosed with CTDs and ILD.Methods:In this retrospective, observational study we included 80 consecutive patients with CTDs and ILD referred to a tertiary rheumatology center between 2015 and 2019. From hospital charts we collected clinical data, immunologic profile, chest HRCT findings. HRCT patterns were defined according to new international recommendations.Results:Out of 80 patients, 64 (80%) were women, with a mean age of 55 years old. The most common CTD associated with ILD was systemic sclerosis (38.8%), followed by polymyositis (22.5%) and rheumatoid arthritis (18.8%). The majority of patients had dyspnea on exertion (71.3%), bibasilar inspiratory crackles were present in 56.3% patients and 10% had clubbing fingers. Antinuclear antibodies (ANA) were present in 78.8% patients, and the most frequently detected autoantibodies against extractable nuclear antigen were anti-Scl 70 (28.8%), followed by anti-SSA (anti-Ro, 17.5%), anti-Ro52 (11.3%) and anti-Jo (7.5%). Intravenous cyclophosphamide therapy for 6-12 months was used in 35% of patients, while 5% of patients were treated with mycophenolate mofetil.The most frequent HRCT abnormalities were reticular abnormalities and ground glass opacity. Non-specific interstitial pneumonia (NSIP) was identified in 46.3% CTDs patients. A pattern suggestive of usual interstitial pneumonia (UIP) was present in 32.5% patients, mainly in patients with systemic sclerosis. In 21.3% patients the HRCT showed reticulo-nodular pattern, micronodules and other abnormalities, not diagnostic for UIP or NSIP pattern.Conclusion:Nonspecific interstitial pneumonia (NSIP) is the most common HRCT pattern associated with CTDs. Further prospective longitudinal studies are needed in order to determine the clinical and prognostic significance of various HRCT patterns encountered in CTD-associated ILD and for better patient management.References:[1]Ohno Y, Koyama H, Yoshikaua T, Seki S. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD). Curr Rheumatol Rep. 2015;17(12):69.[2]Walsh SLF, Devaraj A, Enghelmeyer JI, Kishi K, Silva RS, Patel N, et al. Role of imaging in progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150)Disclosure of Interests:None declared

scholarly journals SAT0286 BIOLOGICAL CORRELATES OF RADIOGRAPHIC FEATURES OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS: AN IN DEPTH ANALYSIS OF BRONCHOALVEOLAR PROTEINS OF SCLERODERMA LUNG STUDY I PARTICIPANTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1087.1-1088
Author(s):  
E. Volkmann ◽  
D. Tashkin ◽  
N. Li ◽  
G. Kim ◽  
J. Goldin ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Research Support ◽  
Radiographic Features ◽  
Depth Analysis ◽  
Specific Proteins ◽  
Clinical Measures ◽  
The Relationship

Background:Systemic sclerosis-related interstitial lung disease (SSc-ILD) involves a combination of inflammation, fibrosis and vascular pathology that is typically assessed on CT imaging as a mixture of ground-glass opacification (GGO) and fibrotic changes. We hypothesized that proteins recovered from bronchoalveolar lavage (BAL) could be used to probe the underlying pathobiology associated with GGO and fibrotic changes.Objectives:(1) To assess the relationship between 68 unique BAL proteins measured in participants of Scleroderma Lung Study (SLS) I1and radiographic and physiologic measures of ILD; (2) To identify inter-correlations among specific proteins to enlighten our understanding of how specific biological pathways contribute to SSc-ILD.Methods:Bronchoscopy was performed on 144 of the 158 participants in SLS I with 103 BAL samples available for analysis. BAL was lyophilized, concentrated 10X and used in a multiplex protein analysis for 68 different cytokines, chemokines and other factors. Kendall tau correlations were performed to assess the relationship between individual proteins and baseline measures of pulmonary function and quantitative CT scores for fibrosis, GGO and total ILD. Those proteins found to correlate significantly with at least 2 clinical measures of ILD were entered into a cluster analysis with inter-correlations expressed as a heatmap.Results:Significant correlations were observed between fibrosis scores and several biologic pathways including pro-fibrotic factors (transforming growth factor beta [TGF-β], platelet-derived growth factor [PDGF]), proteins involved in tissue remodeling (Matrix metallopeptidase [MMP]-1,7,8,9; Hepatocyte growth factor [HGF]), and those involved in monocyte/macrophage migration and activation (Monocyte chemoattractant protein [MCP]-1,3; macrophage colony-stimulating factor [MCSF]). These same pathways correlated with the diffusing capacity for carbon monoxide (DLCO). In contrast, GGO scores correlated primarily with immune and inflammatory mediators (interleukin [IL]-5,8,13,15, IL-1 receptor antagonist and interferon gamma) with only limited overlap to proteins that related to fibrosis. Vascular endothelial growth factor (VEGF) levels were lower in patients with more extensive GGO, fibrosis and diffusion impairment, suggesting that vascular changes are a central feature of SSc-ILD. Specific proteins were highly correlated with one another in a pattern suggesting biologically-related networks (Figure) that might provide additional insight regarding disease pathogenesis.Conclusion:Combining a diverse analysis of BAL proteins with the rich dataset available from SSc-ILD patients participating in SLS I, the study findings suggest the involvement of distinct biologic pathways, inter-related networks, and specific biologic signatures associated with unique radiographic features of ILD. The relationship of these factors to other SSc disease features, patient outcomes and as predictors of treatment responses will be studied in future analyses.References:[1]Tashkin DP, et al. NEJM 2006.Figure.Correlation heatmap of BAL proteins associated with at least 2 clinical measures of ILD in SSc patients. Absolute correlations are depicted, and darker colors signify stronger correlations.Disclosure of Interests:Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Donald Tashkin: None declared, Ning Li: None declared, Grace Kim: None declared, Jonathan Goldin: None declared, Airi Harui: None declared, Michael Roth Grant/research support from: Genentech/Roche

scholarly journals OP0268 TREATMENT STATUS AFFECTS HOW PULMONARY BIOMARKERS PREDICT PROGRESSION OF SYSTEMIC SCLEROSIS-RELATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 163.1-163
Author(s):  
E. Volkmann ◽  
D. Tashkin ◽  
M. Leng ◽  
N. LI ◽  
G. Kim ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Transforming Growth Factor ◽  
Selection Process ◽  
Linear Regression Models ◽  
Research Support ◽  
Gm Csf ◽  
Treatment Status

Background:The course of interstitial lung disease (ILD) varies considerably in patients with systemic sclerosis (SSc), and no biomarkers have been found to consistently predict ILD progression in this population. Treatment may affect how a candidate biomarker correlates with improvement/worsening of SSc-ILD. We hypothesized that specific proteins recovered from bronchoalveolar lavage (BAL) would differentially predict progression of SSc-ILD based on whether a patient was receiving ILD therapy.Objectives:(1) To assess the relationship between 68 unique BAL proteins measured in participants of Scleroderma Lung Study (SLS) I1 and changes in radiographic extent of SSc-ILD; (2) To determine if treatment affects whether a specific protein predicts improvement or worsening of SSc-ILD.Methods:Bronchoscopy was performed on 144 of the 158 participants in SLS I (Cyclophosphamide [CYC] vs. placebo) with 103 BAL samples available for analysis. BAL was lyophilized, concentrated 10X and used in a multiplex protein analysis of 68 distinct cytokines, chemokines and growth factors. Quantitative imaging analysis (QIA) was used to calculate the extent of radiographic fibrosis (QLF) in the whole lung using HRCT of the chest at baseline and 12 months. Multivariable linear regression models were created to determine the key BAL proteins associated with change in QLF scores using a backward selection process adjusting for treatment arm and ILD severity. The bootstrap procedure was employed for internal validation.Results:A number of BAL proteins were significantly associated with change in QLF scores at 12 months; however, the directionality of these associations was often based on the presence/absence of treatment. For example, increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, monocyte chemoattractant protein (MCP)-3, chemokine ligand (CCL)-5, transforming growth factor (TGF)-β, hepatocyte growth factor (HGF), stem cell factor (SCF), IL-4, TGF-α, were associated with worse QLF scores in patients who received placebo; whereas, increased levels of these same proteins were associated with improved QLF scores in patients who received CYC (Figure). Increased levels of Fractalkine were associated with worse in QLF scores, and increased levels of IL-7 were associated with improved QLF scores, regardless of treatment arm. In the multivariable model adjusting for treatment arm and baseline severity of ILD, IL-1, MCP-3, surfactant protein C, IL-7, and CCL-5 were independently associated with change in QLF scores.Figure 1.Example of a specific BAL protein (GM-CSF) that predicts worse QLF scores in patients receiving placebo (Group B, Red dotted line) and improved QLF scores in patients receiving CYC (Group A, Blue solid line). Shaded areas represent 95% confidence intervals.Conclusion:Proteins that mediate both inflammation and fibrosis differentially affected progression of SSc-ILD based on treatment status. Higher levels of certain proteins predicted worsening of ILD in patients receiving placebo, but improvement in patients receiving CYC. Measuring these proteins could help to identify patients who: (1) are at risk for ILD progression, and (2) may preferentially benefit from treatment with immunosuppression.References:[1]Tashkin DP, et al. NEJM 2006.Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Donald Tashkin: None declared, Mei Leng: None declared, Ning Li: None declared, Grace Kim: None declared, Jonathan Goldin: None declared, Airi Harui: None declared, Michael Roth Grant/research support from: Genentech/Roche

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