Scleroderma-related Interstitial Lung Disease Research Articles

Assessing disease activity in scleroderma-related interstitial lung disease: a review and practical guide to management.

Systemic sclerosis (SSc) is a heterogeneous disease with a propensity to involve multiple organ systems. There is a significant proportion of these patients with interstitial lung disease (ILD) who are at risk of mortality and morbidity. There are limited available tools to assess the severity of parenchymal lung involvement and are subject to confounding factors, including the presence of pulmonary hypertension and concomitant smoking history. The diagnostic tools include careful clinical history, examination, thoracic imaging, and pulmonary function tests. One of the limitations of assessing disease severity in SSc-ILD is the lack of standardized definitions for disease activity and serum biomarkers to predict future progression. Although there has been significant progress in managing SSc-related ILD over the last couple of decades with a few randomized double-blind clinical trials assessing the role of immunosuppression (mainly Cyclophosphamide and Mycophenolate Mofetil), the efficacy of these therapies is at best modest and is associated with significant toxicities. Furthermore, Nintedanib has shown promise in reducing forced vital capacity decline in SSc-ILD and in progressive fibrotic-ILD of a range of etiologies. Data are emerging for therapies like Rituximab and Tocilizumab, and we are likely to see further evidence of similar drugs being efficacious in this disease cohort. A relatively simplified algorithm is proposed in this review to guide clinicians dealing with ILD and SSc. It is imperative that clinicians take a multi-disciplinary approach to managing this complex disease in a changing therapeutic landscape.

Nintedanib in systemic sclerosis treatment: a case report

BackgroundNintedanib was approved for the treatment of scleroderma and scleroderma-related interstitial lung disease, as it decrease the forced expiratory volume.Case presentationA 48-year-old Asian female patient with systemic scleroderma 6 years ago developed breathlessness, nausea, heart palpation, and sudden severe occipital headache over the preceding week. She was receiving aspirin 81 mg/day and amlodipine 5 mg/day. Her diagnosis was diffuse scleroderma with pulmonary hypertension, interstitial lung involvement, and renal crisis. The modified Rodnan score was 18. We begin captopril at a dose of 12.5 mg, progressively escalating to 200 mg/day, and oral nintedanib was started at 150 mg. A total of 12 months after initiation of treatment, the patient’s kidney function was normal. The pulmonary function tests improved. The modified Rodnan score was reduced to 10. We did not encounter any side effects in our case due to nintedanib treatment.ConclusionTreatment with nintedanib is crucial for slowing lung function decline. Diarrhea was the most common adverse event. Scleroderma renal crisis occurs in 10% of patients and typically presents with an abrupt onset of hypertension and kidney failure. The optimal antihypertensive agent for scleroderma renal crisis is an ACE inhibitor. The mainstay of therapy in scleroderma renal crisis has been shown to improve or stabilize renal function in approximately 70% of patients and improve survival in nearly 80% at 1 year. Nintedanib may be effective, and fairly safe to use. Further exploration is anticipated to advance a new period of systemic sclerosis treatment.

Prevalence of the limited vs. extensive scleroderma-related interstitial lung disease at the time of diagnosis of SSc-ILD based on Goh et al. criteria. Systematic review and meta-analysis

IntroductionGoh et al. proposed in 2008 a classificatory algorithm of limited or extensive SSc-ILD. The prevalence of both at the time of diagnosis of SSc-ILD is not known with exactitude. MethodsThe review was undertaken by means of MEDLINE and SCOPUS from 2008 to 2023 and using the terms: "systemic", "scleroderma" or "interstitial lung disease" [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment for observational studies and the Jadad scale for clinical trials. The inverse variance-weighted method was performed. ResultsTwenty-seven studies were initially included in the systematic review and meta-analysis (SRMA). Of these, 17 studies had no overlapping data. They reported data from 2,149 patients, 1,369 (81.2%) were female. The mean age was 52.4 (SD 6.6) years. 45.2% of the patients had the diffuse subtype and 54.8% had the limited or sine scleroderma subtype. A total of 38.7% of the patients showed positive antitopoisomerase antibodies (ATA) and 14.2% positive anticentromere antibodies (ACA). The mean percentage of forced vital capacity (FVC) at baseline was 80.5% (SD 6.9) and of diffusing capacity of the lungs for carbon monoxide (DLco) was 59.1% (SD 9.6). Twelve studies presented SSc-ILD extension data adjusted for PFTs and were included in the meta-analysis. The 10 observational cohort studies were analyzed separately. The overall percentage of limited extension was estimated at 63.5% (95%CI 55.3–73; p < 0.001) using the random-effects model. Heterogeneity between studies (I2) was 9.8% (95%CI 0–68.2%) with the random-effects model. Extensive pulmonary involvement was estimated at 34.3% (95%CI 26–45.4; p < 0.001). Heterogeneity between studies (I2) was 0% (95%CI 0–61.6%) with the random-effects model. ConclusionThe overall percentage of limited SSc-ILD at the time of diagnosis of SSc-ILD was estimated at 63.5% and extensive at 34.3%.

Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples. Similarly, any inference on epithelial-to-mesenchymal transition occurrence driven from preclinical models should consider the limitations of cell cultures and animal models. Notwithstanding, while the occurrence or the relevance of this phenomenon in scleroderma-related interstitial lung disease have not been directly and conclusively demonstrated until now, pre-clinical and clinical evidence supports the potential role of epithelial-to-mesenchymal transition in the development and progression of lung fibrosis. Evidence consolidation on scleroderma-related interstitial lung disease epithelial-to-mesenchymal transition would pave the way for new therapeutic opportunities to prevent, slow or even reverse lung fibrosis, drawing lessons from current research lines in neoplastic epithelial-to-mesenchymal transition.

Crosstalk between the JAK2 and TGF-β1 signaling pathways in scleroderma-related interstitial lung disease targeted by baricitinib

Background and objectiveSystemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by fibrosis and vascular lesions. Interstitial lung disease is an early complication of SSc and the main cause of death from SSc. Although baricitinib shows good efficacy in a variety of connective tissue diseases, its role in systemic sclerosis-related interstitial lung disease (SSc-ILD) is unclear. The objective of our study was to explore the effect and mechanism of baricitinib in SSc-ILD.MethodsWe explored crosstalk between the JAK2 and TGF-β1 pathways. In vivo experiments, SSc-ILD mice model were constructed by subcutaneous injection of PBS or bleomycin (7.5 mg/kg) and intragastric administration of 0.5% CMC-Na or baricitinib (5 mg/kg) once every two days. We used ELISA, qRT‒PCR, western blot and immunofluorescence staining to evaluate the degree of fibrosis. In vitro experiments, we used TGF-β1 and baricitinib to stimulate human fetal lung fibroblasts (HFLs) and assessed protein expression by western blot.ResultsThe vivo experiments showed that baricitinib notably alleviated skin and lung fibrosis, decreased the concentration of pro-inflammatory factors and increased those of the anti-inflammatory factors. Baricitinib affected the expression of TGF-β1 and TβRI/II inhibitiing JAK2. In the vitro experiments, following the culture of HFLs with baricitinib or a STAT3 inhibitor for 48 h, the expression levels of TβRI/II decreased. Conversely, with successful inhibition of TGF-β receptors in HFLs, JAK2 protein expression decreased.ConclusionsBaricitinib attenuated bleomycin-induced skin and lung fibrosis in SSc-ILD mice model by targeting JAK2 and regulating of the crosstalk between the JAK2 and TGF-β1 signaling pathways.

P157 Distinct differences in complement perturbation between scleroderma-related interstitial lung disease with and without emphysema

Abstract Background/Aims Aberrant complement activation is associated with autoimmune diseases including systemic sclerosis (SSc). As a leading cause of death in SSc, interstitial lung disease (ILD) can coexist with emphysema in non-smoking patients, worsening prognosis. It has been suggested that the airway destruction observed in SSc patients may be an exaggerated inflammatory response related to increased complement activation. Methods We analysed 10 complement proteins in plasma samples of 16 non-smoking SSc patients with emphysema (SSc-Emp), 8 SSc no-ILD, 8 SSc-ILD patients and 8 healthy controls (HC) (Table.1) selected from 1800 SSc patients under active follow up at our centre. The extent and distribution of emphysema was evaluated on high resolution computed tomography (HRCT) and enzyme-linked immunosorbent assays (ELISA) were performed for C1q, MASP-2, Factor B, Factor Bb, Factor H, C3, C3a, C4, C5, C5a and TCC (terminal complement complex). One-way ANOVA and post-hoc Tukey test were used for analysis. Results HRCT confirmed that amongst the emphysema cohort, there was a spectrum of mild to severe destruction including both paraseptal and centrilobular emphysema. All 16 SSc-Emp patients had ILD and 9 of the 16 patients demonstrated perivascular emphysema not previously described in SSc. The SSc-ILD group was characterised by extensive lung fibrosis on CT, mean FVC 71% predicted. Across the four groups, C1q was significantly reduced in the SSc-ILD cohort (SSc-Emp 950±404µg/mL, SSc-ILD 355±116µg/mL, SSc-no ILD 1087±206µg/mL, HC 858±210µg/mL, p= 0.0002). In contrast, the ratio of C3a/C3 was significantly increased in the SSc-ILD group compared with the SSc-Emp group (SSc-ILD 0.12±0.07 vs SSc-Emp 0.06±0.03, p= 0.0283). The ratio of Bb/B was significantly increased in the SSc no-ILD group compared with all other groups (SSc-Emp 1.57±0.80µg/mL, SSc-ILD 1.27±0.56µg/mL, SSc-no ILD 3.86±1.12µg/mL, HC 1.89±0.75µg/mL, p&amp;lt; 0.0001). There was a trend towards an increased ratio of C5a/C5 in SSc-ILD and SSc-Emp compared with HC and reduced MASP2 in the SSc groups compared with HC. Conclusion This data demonstrates dysregulated complement levels in three SSc subgroups. Notably, the perturbed C1q and C3a:C3 pathways in SSc-ILD are reversed in SSc-emphysema, supporting complement activation as part of the divergent tissue remodelling responses in these distinct SSc lung phenotypes. Disclosure C. Beesley: Grants/research support; Versus Arthritis [grant number 558800]. A. Cole: None. N. Goldman: None. J. Barnett: None. D. Abraham: None. C. Denton: None. R. Mageed: None. V. Ong: None.

Minimal Clinically Important Differences (MCID) for the Functional Assessment of Chronic Illness Therapy Fatigue Scale in Patients with Systemic Sclerosis.

(1) Background: Systemic sclerosis (SSc) is characterized by significant fatigue, causing diminished quality of life (QoL). The aim of this study was to examine fatigue levels and their associations with clinical factors and determine the minimal clinically important difference (MCID) value for the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS). (2) Methods: A total of 160 SSc patients and 62 individuals without SSc were followed-up over a 12-month period by measuring the FACIT-FS and the Visual Analogue Scale and the Short Form 36 Vitality Score analyzing changes in exhaustion. (3) Results: Fatigue was strongly correlated with HRQoL, level of pain, emotional disorders, physical capability and functionality. The MCID values for FACIT-FS were calculated as -3 for deterioration and +4 for improvement after a 12-month follow-up. The predictors of improvement of fatigue from baseline parameters were the significant disease activity, the patients' poorer functionality and the short disease duration. Patients with scleroderma-related interstitial lung disease at baseline had approximately tripled risks for worsening fatigue. The independent influential factors regarding the changing of FACIT-FS were improving or worsening in the same direction in reference to physical condition, gastrointestinal and emotional factors. (4) Conclusions: Fatigue is a multi-dimensional symptom, which is strongly correlated to HRQoL. MCID values of FACIT-FS can be useful tools in monitoring the changes of HRQoL in clinical trials and in daily practice among patients with SSc.

Fever of Unknown Origin Secondary to Pulmonary Histoplasmosis in Scleroderma-Related Interstitial Lung Disease

Permission was obtained by the patient to include his health information for the purposes of this case report.

Analyzing recurrent and nonrecurrent terminal events data in discrete time.

Joint analysis of recurrent and nonrecurrent terminal events has attracted substantial attention in literature. However, there lacks formal methodology for such analysis when the event time data are on discrete scales, even though some modeling and inference strategies have been developed for discrete-time survival analysis. We propose a discrete-time joint modeling approach for the analysis of recurrent and terminal events where the two types of events may be correlated with each other. The proposed joint modeling assumes a shared frailty to account for the dependence among recurrent events and between the recurrent and the terminal terminal events. Also, the joint modeling allows for time-dependent covariates and rich families of transformation models for the recurrent and terminal events. A major advantage of our approach is that it does not assume a distribution for the frailty, nor does it assume a Poisson process for the analysis of the recurrent event. The utility of the proposed analysis is illustrated by simulation studies and two real applications, where the application to the biochemists' rank promotion data jointly analyzes the biochemists' citation numbers and times to rank promotion, and the application to the scleroderma lung study data jointly analyzes the adverse events and off-drug time among patients with the symptomatic scleroderma-related interstitial lungdisease.

CLASSIC PRESENTATION OF SCLERODERMA-RELATED INTERSTITIAL LUNG DISEASE IN A YOUNG FEMALE

CLASSIC PRESENTATION OF SCLERODERMA-RELATED INTERSTITIAL LUNG DISEASE IN A YOUNG FEMALE

Targeted nanotherapy with everolimus reduces inflammation and fibrosis in scleroderma-related interstitial lung disease developed by PSGL-1 deficient mice.

Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy therapeutic approaches to ILD treatment is an urgent need. The interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin initiates leukocyte extravasation and deletion of the corresponding gene (Selplg) induces a SSc-like syndrome with high incidence of ILD in aged mice. Aged PSGL-1 KO (Selplg-/- ) mice were used to assess the therapeutic effects of nanotherapy with everolimus, included in liposomes decorated with high MW hyaluronic acid (LipHA+Ev) and administered intratracheally to specifically target CD44-expressing lung cells. PSGL-1 KO mice had increased numbers of CD45+ and CD45- cells, including alveolar and interstitial macrophages, eosinophils, granulocytes and NK cells, and myofibroblasts in bronchoalveolar lavage (BAL). CD45+ and CD45- cells expressing pro-inflammatory and pro-fibrotic cytokines were also increased. Lungs from PSGL-1 KO mice showed increased immune cell infiltration and apoptosis and exacerbated interstitial and peribronchial fibrosis. Targeted nanotherapy with LipHA+Ev decreased the myofibroblasts in BAL, cells producing proinflammatory and profibrotic cytokines, and the degree of lung inflammation at histology. LipHA+Ev treatment also decreased the severity of peribronchial and interstitial lung fibrosis, from moderate to mild levels. In PSGL-1 KO mice, targeted nanotherapy with LipHA+Ev was an effective treatment for SSc-ILD, reducing the number of inflammatory and fibrotic cells in BAL and reducing inflammation and fibrosis in lungs.

Mycotic Aortic Pseudoaneurysm Following ECMO Cannulation

<h3>Introduction</h3> Mycotic aortic pseudoaneurysms (MAP) are a rare but often fatal complication of thoracic surgery. Recently, our institution has transitioned to performing all lung transplants on venous-arterial extracorporeal membrane oxygenation (VA-ECMO) support when possible. Reinforcement of aortic cannulation sites with pledgeted sutures is often necessary to control bleeding; however, pledgets could also represent an iatrogenic risk for infection. Here we present a fatal case of MAP at the cannulation site in a lung transplant recipient (LTR). <h3>Case Report</h3> We present a 56-year-old female who underwent bilateral lung transplant for scleroderma-related interstitial lung disease. Two months following transplant, she was admitted with methicillin-resistant staphylococcus aureus bacteremia. Initial echocardiogram was inconclusive for endocarditis and thus she was treated with IV vancomycin for six weeks with clinical improvement. Unfortunately, two months later she presented with recurrent bacteremia. Initial imaging revealed evidence of ascending MAP formation, confirmed by positron emission tomography (Figure 1). She underwent surgical repair with identification of a palpable MAP and pathology consistent with acute and organizing inflammation with microabscess formation. Despite aggressive medical and surgical management, our patient suffered a catastrophic embolic stroke. <h3>Summary</h3> While performing lung transplant on ECMO support has many potential benefits, it is not without risk. Closure of ECMO cannulation sites with pledgets in immunosuppressed patients may lead to the development of an infected MAP and can have devastating consequences. To our knowledge this is the first case of an infected MAP at pledget site in a LTR.

Abstract 17047: Nintedanib And Cardiomyopathy: A Vascular Failure?

Description of the Case: Patient 1 is a 61-year-old woman with a history of rheumatoid arthritis-related interstitial lung disease (ILD). Six months after initiation of nintedanib, she was diagnosed with new-onset heart failure. Cardiac magnetic resonance imaging (CMR) was consistent with nonischemic cardiomyopathy (NICM) with ejection fraction (EF) of 15-25%. EKG showed new bifascicular block (right bundle branch block and left anterior fascicular block). Nintedanib was discontinued, and four months later, echocardiogram showed recovered EF (50-54%). EKG abnormalities resolved with biventricular pacing. Patient 2 is a 57-year-old-man with a history of scleroderma-related ILD and stable diastolic heart failure (EF = 55-60%). Six months after initiation of nintedanib, he was admitted for heart failure exacerbation. CMR showed NICM with EF = 35%, and EKG showed prolonged QRS (130 ms). Given the rapid progression of cardiomyopathy, nintedanib was discontinued. Discussion: We report two patients with underlying connective tissue disease who developed significant nonischemic cardiomyopathy in temporal association with initiation of nintedanib. Nintedanib is a tyrosine kinase inhibitor, antagonizing three angiogenic signaling pathways mediated by vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet derived growth factor receptor (PDGFR). The nintedanib-treated cohorts of the TOMORROW and INPULSIS trials for idiopathic pulmonary fibrosis showed a high incidence of myocardial infarction (MI). With the recent SCENSIS trial, nintedanib was approved in 2019 for ILD associated with systemic sclerosis. There are likely multifactorial effects of this triple angiokinase inhibitor, seeing that it inhibits multiple growth factors essential for vascular homeostasis, the balance between mesenchymal and endothelial cell fates. Thus, there may be multiple pathways for cardiomyopathy due to “vascular failure,” including MI and importantly, cardiac fibrosis. Based on our observations, we urge other clinicians to report their experience with nintedanib use in patients with underlying connective tissue disease and to carefully monitor these patients for adverse cardiovascular effects.

The disconnect between visual assessment of air trapping and lung physiology for assessment of small airway disease in scleroderma-related interstitial lung disease: An observation from the Scleroderma Lung Study II Cohort.

To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

Diagnóstico y manejo de la enfermedad pulmonar intersticial de la esclerosis sistémica en condiciones sanitarias desafiantes

A 51-year-old woman presented with swelling in both hands and a 3-months history of triphasic Raynaud phenomenon. She denied cough and dyspnea. The physical examination was notable for swollen hands, facial telangiectasia and salt and pepper lesions. She had no skin fibrosis. The determination of antinuclear antibodies and antitopoisomerase were positive. A spirometry demonstrated a forced vital capacity of 86% of the predicted. High resolution chest computed tomography revealed bilateral, basal and subpleural ground glass opacities. These findings were consistent with the diagnosis of Scleroderma-Related Interstitial Lung Disease. Moreover, due to the absence of skin fibrosis, a diagnosis of systemic sclerosis sine scleroderma was made. Infusions of endovenous cyclophosphamide were indicated at 4-week intervals, followed by oral azathioprine. This case showed that using PFT as the single screening method for SSc-ILD may cause clinicians to miss a significant number of patients and that the absence of pulmonary symptoms does not exclude lung disease in patients with normal FVC.

Determining progression of scleroderma-related interstitial lung disease.

Interstitial lung disease occurs in the majority of patients with systemic sclerosis. Although interstitial lung disease is the number one cause of death in systemic sclerosis, interstitial lung disease progression rates vary considerably among patients with systemic sclerosis. Some patients with systemic sclerosis-associated interstitial lung disease have sub-clinical disease and may not derive benefit from immunosuppression, while others have a more aggressive interstitial lung disease phenotype. Reliable predictors of interstitial lung disease progression are lacking. The present review describes our current approach to monitoring systemic sclerosis-associated interstitial lung disease progression in clinical practice. To illustrate the marked heterogeneity that exists in interstitial lung disease progression rates in systemic sclerosis, this review presents the individual disease course of five unique patients with systemic sclerosis-associated interstitial lung disease who participated in the Scleroderma Lung Study II. These cases illustrate that treatment response rates vary in systemic sclerosis-associated interstitial lung disease and more research is needed to determine how to predict treatment response in systemic sclerosis-associated interstitial lung disease and to develop personalized treatment approaches for patients with this devastating disease.

Lung transplantation in scleroderma: recent advances and lessons.

The purpose of this review is to highlight recent data regarding feasibility and outcomes following lung transplantation for patients with systemic sclerosis related pulmonary disease as well as to emphasize areas of uncertainly in need of further study. We include a description of our centre's approach to lung transplant evaluation and posttransplant management in this complex patient population. Historical data have demonstrated that patients with scleroderma have an increased risk of complications following lung transplantation owing to the multisystem nature of disease, particularly concurrent gastrointestinal, cardiac and renal involvement. Emerging data support the safety of lung transplant in appropriately selected patients with scleroderma-related interstitial lung disease and pulmonary arterial hypertension. Accumulating evidence validates that a diagnosis of scleroderma is not a priori a contraindication to lung transplant. In the carefully selected patient, both short-term and long-term outcomes following lung transplantation are comparable to counterparts with fibrotic lung disease or pulmonary arterial hypertension. However, further prospective study to detail how these patients should be evaluated and managed posttransplant is definitely needed. Cardiac disease is an emerging cause of morbidity and mortality in the scleroderma population and deserves particular attention during the pre and posttransplant period.

Longitudinal Changes in Quantitative Interstitial Lung Disease on Computed Tomography after Immunosuppression in the Scleroderma Lung Study II.

The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously. The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval. Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe). At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, -4.00 to -1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (-2.66%) and mycophenolate (-2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = -0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = -0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = -0.26). Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.

PULMONARY FUNCTION TEST PARAMETERS IN DIFFUSE AND LIMITED SCLERODERMA

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Scleroderma is characterized by varying degrees of organ fibrosis and obliterative vasculopathy. Lung involvement is the leading cause of morbidity in Scleroderma. The spectrum of Pulmonary Function Test (PFT) abnormalities in Scleroderma has been reported to be variable, with a recent study revealing that PFTs have a low sensitivity in detecting Scleroderma-related interstitial lung disease, with false negative cases more common in diffuse Scleroderma. The objectives of this study are to determine the spectrum of PFT abnormalities in Scleroderma and to compare PFTs in limited and diffuse Scleroderma. METHODS: We reviewed the records of 174 Scleroderma patients followed at the rheumatology clinic in our institution. Patient demographics and PFT parameters [FEV1, FVC, FEV1/FVC, TLC and DLCO percent predicted (%)] were noted in patients with limited (Scl-Ltd) and diffuse (Scl-Diffuse) disease. Obstruction was defined as FEV1/FVC < 70%; restriction as TLC < 80% and impaired diffusion as DLCO < 80%. Severity of restriction was defined per ATS criteria. PFT parameters in the two groups were compared by Student’s t-test. p < 0.05 was deemed statistically significant. RESULTS: Mean age: 65 +/- 12.2 years; 91% were females; 76.4% had Scl-Ltd. Mean FEV1 was: 92 +/- 22%; mean FVC: 88.5 +/- 21.3%; mean TLC: 91.5 +/- 18%; mean DLCO:70.5 +/- 23%. Twenty-eight % patients had normal PFTs; 12 % had obstruction, 32% had restriction and 28% patients had isolated reduction in DLCO. Thirty-five % patients with Scl-Ltd and 24.4% patients with Scl-Diffuse had a normal DLCO. In patients with restriction, 40% had mild, 51% moderate and 9% had severe restriction. PFT abnormalities were seen in 37.6% Scl-Ltd, and 56% Scl-Diffuse. PFT parameters in the 2 groups are shown below. PFT parameters in 2 groups (Table) CONCLUSIONS: Majority of Scleroderma-patients have abnormal PFTs. Restriction and impairment in diffusion were the most common abnormalities. Over 1/3rd patients with limited disease had PFT abnormalities. CLINICAL IMPLICATIONS: Whether restriction defined by TLC corelates with fibrosis on imaging need to be studied. DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Carol Halasan, source=Web Response No relevant relationships by Sophie Korzan, source=Web Response