Pulmonary Involvement In Systemic Sclerosis Research Articles

Systemic sclerosis associated respiratory involvement: Scopus-based analysis of articles in 2013-2022.

Systemic sclerosis (SSc), a complex autoimmune disorder, manifests as a convergence of rheumatologic, dermatologic, and pulmonary challenges. Among the severe complications contributing to morbidity and mortality are SSc Associated Interstitial Lung Disease (SSc-ILD) and pulmonary hypertension. Over the past decade, research on pulmonary involvement in SSc has intensified, leading to a heightened understanding of its pathogenesis, diagnostic methods, and therapeutic strategies. This study aims to provide a data-driven overview of the current state of systemic sclerosis research, identifying emerging trends and fostering informed decisions regarding resource allocation and research priorities. A literature search was conducted in the Scopus database, using MESH keywords such as "systemic sclerosis" AND "lungs" OR "pulmonary hypertension" OR "interstitial lung disease". After applying exclusion criteria, a thorough analysis was performed, considering factors such as document category, authorship, journal source, citation frequency, country of publication, language, and keywords. The bibliometric analysis utilized Scopus as the preferred database, leveraging its extensive coverage, user-friendly interface, and commitment to data accuracy. Visual networks were constructed using VOSviewer software to map the relationships between keywords, countries, and authors. Altmetric Attention Scores (AAS) were employed to assess the social impact of articles. The analysis revealed a total of 2538 scholarly items, with 55.7% identified as open access. The USA (n = 532), Italy (n = 458), France (n = 304), Japan (n = 271), and the UK (n = 236) emerged as primary contributors, with English being the predominant language. A notable upward tendency in annual publication and citation scores indicated sustained interest and relevance in SSc-ILD research. The top journals, including Rheumatology United Kingdom, Clinical and Experimental Rheumatology, Clinical Rheumatology, Arthritis and Rheumatology, and Journal of Rheumatology, played a pivotal role in scholarly output. Original Articles (n = 1795; 70.7%) constituted the majority of publications, followed by Reviews, Letters, Notes, and Editorials. The analysis of publication impact within different scholarly formats revealed varying citation patterns, with Original Articles and Reviews leading in influence. The identification of influential research hubs and key contributors provided insights into collaborative efforts and geographic distribution. A strong correlation (rho = 0.612, p < 0.001) was observed between the quantity of Mendeley readers and the citations received by scholarly articles. This bibliometric analysis offers a comprehensive overview of SSc-ILD research, highlighting its dynamic and interdisciplinary nature. The surge in publications, citation scores, and the identification of key contributors underscore the continued relevance and impact of this field. The nuanced relationships between social attention and scientific recognition, as revealed by Mendeley readership and AAS, contribute to a deeper understanding of the multifaceted nature of scholarly impact.

Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival: A Large Cohort Study of the German Network for Systemic Sclerosis

Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis. Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact? Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. Clinical data of 3,257 patients with a mean follow-up time of 3.45 ± 1.63 years have been included in our analysis. At baseline, ILD was present in 34.5%, whereas PH without ILD had a lower prevalence with 4.5%. At the end of follow-up, 47.6%of patients with SSc had ILD, 15.2%had ILD-PH, and 6.5%had PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), whereas PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vsILD-PH vsILD without PH were found for age at diagnosis, sex, SSc subsets, antibody status, FVC, diffusing capacity of the lung for carbon monoxide, and therapy. Overall survival at 5 years was 96.4%for patients without pulmonary involvement and differed significantly between patients with ILD without PH, PAH, and being worst in patients with ILD-PH. Female sex (hazard ratio [HR], 0.3), higher BMI (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide values (HR, 0.98) were associated with a lower mortality risk. ILD is the most prevalent pulmonary involvement in SSc, whereas the combination of ILD and PH is associated with the most detrimental survival.

Association of soluble urokinase plasminogen activator receptor levels with fibrotic and vascular manifestations in systemic sclerosis.

ObjectiveWe assessed the association of suPAR (soluble urokinase plasminogen activator receptor) plasma levels with fibrotic and vascular manifestations in patients with systemic sclerosis (SSc).MethodssuPAR plasma levels were measured in 121 consecutive patients with SSc and correlated to pulmonary and vascular features of SSc, including interstitial lung disease as characterized by percentage of predicted CO diffusing capacity (DLco) and forced vital capacity (FVC), pulmonary fibrosis by computed tomography, and pulmonary arterial hypertension, telangiectasias, and digital ulcers.ResultsOverall, 121 SSc patients (84% females; mean age, 57 ± 12 [range: 22–79] years) were enrolled; 35% had diffuse cutaneous SSc. suPAR plasma levels ranged from 1.3–10.2 [median: 2.9 (p25–p75: 2.3–3.9)] ng/mL. Log(suPAR) levels correlated with DLco (r = -0.41, p <0.0001) and FVC (r = -0.26, p = 0.004), also when adjusted for age, sex, and pulmonary hypertension. A suPAR cut-off level of >2.5 ng/mL showed a sensitivity of 91% for identifying patients with either DLco <50% or FVC < 60% of the predicted values. Similarly, 19 (90%) had a suPAR >2.5 ng/mL among those diagnosed with pulmonary fibrosis vs. 59 (60%) among those who did not (p = 0.008). suPAR values were not associated with vascular manifestations.ConclusionsuPAR levels strongly correlated with pulmonary involvement in SSc. Future studies should test if suPAR estimation can be used for surveillance of severe pulmonary involvement in SSc.

Demographic characteristics and clinical manifestations of interstitial lung disease with systemic sclerosis in eastern part of Libya

Abstract Introduction: Pulmonary involvement, such as Interstitial Lung Disease (ILD) and Pulmonary Hypertension (PH ), accounts for significant morbidity and is the leading cause of Systemic sclerosis (SSc)-related morbidity and mortality. The aim of the current study was to study the frequency of occurrence of ILD in SSc and to describe the clinical and radiological picture of pulmonary involvement in SSc. Patients and Methods: Forty patients attending different rheumatology clinics in eastern part of Libya between January 2018 and September 2020 were included. Basic details including age, gender, disease duration, detailed history, and clinical examination were noted. Autoimmune profiling included rheumatoid factor, antinuclear antibodies, and anti-Scl-70 antibodies. Pulmonary function test, chest X-ray (CXR), and high-resolution computed tomography of the chest (HRCT) in all patients were recorded. Data presented either as frequencies and percentages or as means ± standard deviation. Results: The male: female ratio was 1:9 with a mean age of 37.5 ± 9.6 years and duration of illness 6 ± 4 years. diffuse cutaneous SSc was seen in 62.5% of the patients. 77.5% of the participants had bilateral crepitation and 57.5% had loud P2. Presenting complaints included gastrointestinal reflux in 72.5%, digitalis ulcerations in 40%, and synovitis/arthritis of all patients. Other comorbidities included congestive heart failure in 12.5%, PH in 15%, and renal impairments in 7.5% of all patients. Anti-Scl-70 antibody was the most common in all patients (45%), followed by anti-centromere Ab (25%), anti-U3 RNP (10%), and anti-U1 RNP (5%). 72.5% of the participants had reticulonodular shadows on CXR. HRCT showed honeycombing as the predominant finding (37.5%). Echocardiograms showed that 15% of all patients have signs of PH. Duration of disease, dyspnea, cough, bilateral crepitations, and CXR were found to be significantly associated with extensive ILD (P &lt; 0.05). Conclusion: ILD is a serious complication of SSc, it is more common among patients with dcSSc. Chest HRCT is very sensitive to detect ILD. A significant association was found in Libyan patients between the severity of ILD and the duration of disease, dyspnea, cough, bilateral crepts, and CXR.

Bronchoalveolar Lavage in Systemic Sclerosis Patients: A Systematic Review.

We performed a systematic review of the literature to determine the value of bronchoalveolar lavage (BAL) in evaluating the pulmonary involvement of systemic sclerosis (SSc). Articles published between 1980 and 2019 were retrieved from the databases: PubMed and Scielo. The search was restricted to clinical trials published in English, utilizing the keywords "scleroderma, systemic sclerosis, interstitial lung disease, and bronchoalveolar lavage". Twenty-two papers were analyzed. A positive correlation was observed between increased BAL cellularity (alveolitis) and worsening clinical symptoms, pulmonary function, and radiological pattern in 2, 11, and 15 studies, respectively. The majority of BAL studies that evaluated interleukin levels, including TNF-α, IL-6, IL-7, and IL-8, observed higher levels in patients with impaired pulmonary function and increased lung involvement. Alveolitis and the increase of some cytokines/chemokines in BAL were related to more severe pulmonary disease in SSc in the majority of the studies and seemed to be markers of worse prognosis, but it is unknown whether BAL adds clinical value to the use of the other non-invasive diagnostic procedures.

Pulmonary involvement in systemic sclerosis: exploring cellular, genetic and epigenetic mechanisms.

Systemic sclerosis (SSc) is a chronic progressive autoimmune disease characterized by immune inflammation, vasculopathy, and fibrosis. There are still numerous uncertainties in the understanding of disease initiation and progression. Pulmonary involvement in SSc, and particularly pulmonary fibrosis, is critical for all organ systems affections in this disease. This review is aimed to describe and analyze new findings in the pathophysiology of SSc-associated pulmonary involvement and to explore perspective diagnostic and therapeutic strategies. A myriad of cellular interactions is explored in the dynamics of progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in SSc. The role of exosomes, microvesicles, and apoptotic bodies is examined and the impact of micro and long non-coding RNAs, DNA methylation, and histone modification in SSc is discussed.

MPA AUC Monitoring in Patients Receiving MMF for Diffuse Cutaneous or Pulmonary Involvement in Systemic Sclerosis

MPA AUC Monitoring in Patients Receiving MMF for Diffuse Cutaneous or Pulmonary Involvement in Systemic Sclerosis

Effect of season on clinical outcomes of Thai systemic sclerosis: Analysis of the Thai national healthcare database

Objectives: We aimed to determine rate of admission, mortality rate, and causes of death in systemic sclerosis (SSc) patients after stratifying by season.Method: A cross-sectional analysis was performed of patients over 15 in the national database with a primary diagnosis of SSc (ICD-10:M34) covered by the National Health Security Office hospitalized between 2014 and 2018. The seasons were stratified into hot, rainy, and Cool dry seasons.Results: Included were 2480 SSc patients with 3684 admissions: most (64.3%) were female. The respective mean age and median length of stay was 56.9 ± 12.3 years and 3 days (IQR 2–6). The admission rate was highest during the rainy season (1574 visits, 42.7%), followed by the cool dry season (1183 visits, 32.1%) then the hot season (927 visits, 25.2%). During the 13,180 person-days, 1660 SSc patients died resulting in a mortality rate of 12.1 per 100 person-days. The proportion of SSc patients who died in the Cool dry season was significantly higher than in the hot or rainy season (p = .04). Pulmonary involvement in SSc was the most common cause of death in the hot season, which is greater than in the other seasons (p = .004). By comparison, death due to cardiac involvement in SSc was common during the rainy season and cool dry seasons (p = .04).Conclusion: The admission rate among Thai SSc patients was greatest during the rainy season, while mortality was highest during the cool dry season. The most common causes of death were SSc-related irrespective of season, particularly cardiopulmonary involvement.

Kidney transplantation in patients with systemic sclerosis: a nationwide multicentre study.

Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period. Initial kidney disease was scleroderma renal crisis in 76.4%. Extrarenal involvement of SS was generally stable, except cardiac and gastrointestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases, respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3 and 5years post-transplant, respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3years, and 92.8% after 5years. Recurrence of scleroderma renal crisis was diagnosed in three cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extrarenal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation.

Effectiveness of Thoracic Ultrasonography in the Evaluation of the Severity of Pulmonary Involvement in Patients With Systemic Sclerosis.

This study aims to investigate the effectiveness of thoracic ultrasonography (USG) in a single session in the evaluation of the severity of pulmonary involvement in systemic sclerosis. A total of 48 consecutive systemic sclerosis patients (2 males, 46 females; mean age 50.8±11.9 years; range 21 to 76 years) followed-up in our center were included. A thoracic USG using a linear probe was performed for each patient to evaluate the parenchymal involvement by two pulmonary disease specialists. The number of B-lines (B-lines described USG sign of interstitial lung fibrosis) was recorded. Systolic pulmonary artery pressure was measured by means of using a phase probe to evaluate pulmonary hypertension in the same sequence. The same day, pulmonary function tests were conducted. Warrick score was calculated according high resolution computed tomography (HRCT) images which were evaluated independently from each other by a radiologist and a pulmonary disease specialist. Medsger severity scale was calculated for each patient according to the results of HRCT findings, pulmonary function test, and systolic pulmonary artery pressure. The number of B-lines detected on thoracic USG was correlated with the Warrick score (r=0.89; p=0.0001) and Medsger disease scale (r=0.55; p=0.0001) and negatively correlated with diffusing capacity of carbon monoxide (r= -0.56; p=0.0001) and forced vital capacity (r= -0.46; p=0.001). When HRCT was accepted as the gold standard; the sensitivity, specificity, positive predicted value, and negative predicted value for thoracic USG were 100%, 84.2%, 90.6%, and 100%, respectively. If thoracic USG was used instead of HRCT for the evaluation of Medsger scale, the results changed in only one of the 48 patients. Thoracic USG showed good correlation with HRCT findings for the evaluation of pulmonary parenchymal involvement in systemic sclerosis. Therefore, USG might be a noninvasive and useful tool for the long-term follow-up of systemic sclerosis patients after initial examination with USG and HRCT.

A New Era in the Treatment of Scleroderma-associated Interstitial Lung Disease?

Pulmonary involvement in systemic sclerosis or scleroderma (SSc) is mainly represented by SSc-associated interstitial lung disease (SSc-ILD) and pulmonary hypertension1,2. SSc-ILD is a major challenge: It is both a very frequent and a very severe complication of SSc. According to the literature, SSc-ILD is or will be present in around one-half of patients with diffuse SSc, and one-third of patients with limited cutaneous SSc3. SSc-ILD is now one of the leading causes of death in SSc4. This explains why much effort has been expended to understand and better know the characteristics of patients with SSc-ILD as well as to manage them properly. However, despite decades of observational studies and a few randomized ones, the optimal management of patients with SSc-ILD is still a matter of debate. From an historic point of view, the cornerstone of SSc-ILD treatment has mainly been immunosuppressants. This can be explained by the fact that SSc is a connective tissue disease in which inflammation and immune abnormalities play a central role5. The immune system, especially in regards to B and T lymphocytes, is fully involved in fibroblast activation and fibrogenesis by secreting proinflammatory and profibrotic cytokines and growth factors6. The most common immunosuppressant, cyclophosphamide (CYC), has been tested in many open-label studies and a few randomized control trials (RCT), as well as being recommended in the European League Against Rheumatism Scleroderma Trials and Research group guidelines7. However, the results of those RCT are still dividing the medical community. In the FAST study, there was no significant … Address correspondence to Prof. D. Launay, Service de Medecine Interne, Hopital Claude-Huriez, CHRU Lille, rue Michel Polonovski, F-59037 LILLE Cedex, France. E-mail: david.launay{at}univ-lille2.fr

Pulmonary involvement in systemic sclerosis.

Systemic sclerosis (SSc) is a multi-systemic autoimmune disease that mainly affects the skin, lungs, gastrointestinal tract, heart and kidneys. Pulmonary disease in patients with SSc is strongly associated with mortality. The mechanisms involved into its pathophysiology include the activation of autoimmune cells and hyperplasia of fibroblasts with an increased capacity to produce collagen and diminished collagen breakdown. Although pulmonary biopsy is the gold standard for the diagnosis of interstitial lung disease in SSc, the most commonly used method is high-resolution computed tomography due to its high sensitivity and specificity. Herein, a comprehensive review on the pulmonary involvement in SSc is presented highlighting the radiologic-pathologic correlations.

Pulmonary involvement in systemic sclerosis: A clinical profile.

Background:Systemic sclerosis is a generalized disorder of connective tissue affecting skin and internal organs. Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients.Objectives:This study intends to study the frequency of occurrence of pulmonary involvement in progressive systemic sclerosis (PSS) and to describe the clinical and radiological picture of pulmonary involvement in PSS.Materials and Methods:This was a descriptive cross-sectional study. A detailed history, modified Rodnan score, clinical examination, routine investigation, antinuclear antibody, immuno biot, chest X-ray (CXR), pulmonary function test (PFT), and 6 min walk test (6MWT) were performed on all patients. High resolution computed tomography was done on those who consented.Results:Hundred subjects with PSS were included in the study; 90 were females and 10 were males. Common presenting complaints were skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in 92%. Chest wall thickening was seen in 40 subjects (40%). 90 (90%) of the studied subjects had pulmonary involvement, longer duration of disease was significantly associated with pulmonary involvement (P < 0.05). Dyspnea, cough, bilateral crepitations, CXR, Borg score, and Rodnan score was found to be significantly associated with severe pulmonary involvement (P < 0.05).Conclusion:The prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3rd of patients, that is 29 (29%) were detected to have pulmonary involvement despite being asymptomatic for respiratory complaints, hence early screening and evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and easily available screening tests which can be used in resource-limited settings.

Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis.

Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

Pulmonary involvement in systemic sclerosis: an imaging study from kashmir.

Background:Systemic sclerosis (SS) is a chronic, multisystem collagen vascular disorder of undefined etiology, whose prognosis and overall survival is determined by visceral especially the lung involvement.Aim:To evaluate the pulmonary involvement in SS by imaging methods.Materials and Methods:Clinical examination, pulmonary function tests, chest X-ray and high resolution computed tomography (HRCT) scans were carried out in a series of 25 patients prospectively over a period of 3 years (2009-2011AD).Results:Of the total 25 patients of the study, the group with abnormal HRCT chest (n = 20), 16 had clinical symptoms of respiratory involvement, only 7 had an abnormal chest X-ray and 15 had abnormal forced expiratory volume/forced vital capacity (FEV1/FVC) spirometric parameter. While the group with normal HRCT chest (n = 5), 1 had clinical symptoms of respiratory involvement and 4 had abnormal FEV1/FVC spirometric parameter. The differences in these parameters between the two groups were statistically significant, while the differences for mean skin tethering index, mean disease duration and female/male sex ratio were statistically meaningless. Most common HRCT finding observed in the study was ground glass opacities (GGO) (9/20). Only 4 of total 9 patients who had only GGO in HRCT were symptomatic for respiratory involvement as compared to 100% (11/11) in the group who had HRCT findings other than or in addition to GGO.Conclusion:The HRCT outscores Chest X-ray in detecting early lung involvement in SS patients more so early in the course of the disease thereby underscoring its importance in identifying SS patients who will be potential candidates for early institution of therapy that might reverse/limit pulmonary involvement by the disease.

FRI0497 Lung Ultrasound for Evaluation of Pulmofibrosis in Systemic Sclerosis

BackgroundPulmofibrosis and in general pulmonary involvement is very common feature in patients with systemic sclerosis (SSc). It is detectable in more than 80% of SSc population and is one of...

Clinical and autoantibody profile in systemic sclerosis: baseline characteristics from a West Malaysian cohort

To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort. Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay. The association between clinical features and autoantibody profile was evaluated. There were 31, predominantly Chinese (45.2%), subjects. Limited cutaneous disease was the most common subtype (71%). Raynaud's phenomenon was the most commonly observed feature (83.9%). Nine (29%) had esophageal dysmotility symptoms and 23 (74.2%), including all patients with diffuse SSc, had symptoms of gastro-esophageal reflux disease (GERD). Restrictive pattern on pulmonary function test and evidence of lung fibrosis were seen in more than 70% of patients. Echocardiographic evidence of pulmonary arterial hypertension was seen in 58.1%. Telangiectasia, calcinosis, digital ulcers, digital pulp loss or pitting were seen more commonly in the diffuse subtype. The two most prevalent autoantibodies were anti-Scl-70 and anti-Ro-52. The presence of anti-Scl-70 was significantly associated with restrictive lung disease (P = 0.05). Anti-Ro-52 was associated with control subjects with other autoimmune diseases (P = 0.043). The presence of anti-PM-Scl-75 was associated with overlap syndrome (P = 0.032). Patients with anticentromere antibodies were more likely to have vasculitic rash (P = 0.012). In Malaysia, SSc most commonly affects the Chinese. Limited cutaneous is more common than diffuse subtype. Features of CREST (calcinosis, Reynaud disease, esophageal dysmotility, sclerodactyly, telangiectasia) are more commonly observed in the diffuse cutaneous subgroup. Anti-Scl-70 and anti-Ro-52 antibodies are promising biomarkers for pulmonary involvement in SSc.

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH). sCD90 serum concentrations were assessed in 76 patients with SSc and related to clinical data, lung function, 6-minute walk distance, echocardiography, bronchoalveolar lavage fluid, and laboratory parameters. Thirty-one healthy volunteers and 29 patients with idiopathic retroperitoneal fibrosis (IRF) served as controls. sCD90 serum concentrations were elevated in patients with SSc compared to healthy volunteers (P = 0.001) and patients with IRF (P = 0.01). SSc patients with pulmonary fibrosis (P = 0.006) and patients with PAH (P < 0.001) had increased sCD90 serum concentrations compared to patients without the respective pulmonary manifestation of SSc. sCD90 levels correlated with diffusing capacity for carbon monoxide (n = 65; r = -0.348, P = 0.005) and systolic pulmonary artery pressure (n = 53; r = 0.469, P < 0.001). Receiver operating characteristic curve testing determined an optimal cutoff value of ≥626 ng/ml with a sensitivity of 68% and a specificity of 83% for PAH (area under the curve 0.773, 95% confidence interval 0.648-0.898; P < 0.001). sCD90 concentrations were increased in the sera of SSc patients, particularly in patients with vascular involvement of the lungs. These data suggest that sCD90 should be further evaluated as a marker for diagnosis of PAH in SSc.

Pulmonary blood volume indexed to lung volume is reduced in newly diagnosed systemic sclerosis compared to normals--a prospective clinical cardiovascular magnetic resonance study addressing pulmonary vascular changes.

BackgroundPulmonary involvement, manifested as pulmonary arterial hypertension or pulmonary fibrosis, is the most common cause of death in systemic sclerosis (SSc). We aimed to explore the feasibility of detecting early pulmonary involvement in SSc using recently developed non-invasive quantitative measures of pulmonary physiology using cardiovascular magnetic resonance (CMR).MethodsTwenty-seven SSc patients (9 men, 57 ± 13 years) and 10 healthy controls (3 men, 54 ± 9 years) underwent CMR to determine the pulmonary blood volume (PBV) and the PBV variation (PBVV) throughout the cardiac cycle. Patients underwent Doppler echocardiography, high-resolution computed tomography (HRCT), and pulmonary function testing by spirometry. Comparisons were performed using the unpaired t-test and linear regression analysis was performed with Pearson’s correlation coefficient (r).ResultsCompared to healthy controls, the PBV indexed to lung volume (PBVI) was lower in patients (16 ± 4 vs 20 ± 5%, p < 0.05). There was no difference in PBV (466 ± 87 vs 471 ± 122 mL, p = 0.91) or PBVV/stroke volume (45 ± 10 vs 40 ± 6%, p = 0.09). There were no significant correlations between PBVI and pulmonary artery pressure estimated by Doppler (p = 0.08) the lung’s diffusion capacity for carbon monoxide (DLCO) (p = 0.09), vital capacity (p = 0.45), or pulmonary fibrosis by HRCT (p = 0.74).ConclusionsThis study is the first to measure the PBV in humans using CMR. Compared to healthy controls, newly diagnosed SSc patients have a reduced amount of blood in the pulmonary vasculature (PBVI) but unchanged pulmonary vascular distensibility (PBVV/stroke volume). PBVI is unrelated to DLCO, pulmonary artery pressure, vital capacity, and the presence of pulmonary fibrosis. PBVI may be a novel parameter reflecting vascular lung involvement in early-stage SSc, and these findings may be consistent with pathophysiological changes of the pulmonary vasculature.

Systematic review: the relationship between interstitial lung diseases and gastro‐oesophageal reflux disease

BACKGROUND A potential relationship has been suggested between gastro-oesophageal reflux disease (GERD) and interstitial lung diseases (ILDs). AIM To evaluate whether there is a causal relationship between GERD and different ILDs. METHODS We conducted a systematic search of literature published between 1980 and 2010. After a review by two independent authors, each study was assigned an evidence-based rating according to a standard scoring system. RESULTS We identified 319 publications and 22 of them met the entry criteria. Of those, the relationship between GERD and idiopathic pulmonary fibrosis (IPF) was investigated in 14 articles, pulmonary involvement in systemic sclerosis (SSc) in six articles and pulmonary involvement in mixed connective tissue disease (MCTD) in two articles. We found the prevalence of GERD and/or oesophageal dysmotility to be higher in patients with different types of ILD as compared with those without ILD [Evidence B]. Among patients with IPF, 67-76% demonstrated abnormal oesophageal acid exposure off PPI treatment. No relationship was demonstrated between severity of GERD and severity of IPF [Evidence B]. Data are scant on outcomes of antireflux treatment in patients with IPF. There is a correlation between the severity of ILD and the degree of oesophageal motor impairment in patients with SSc and MCTD [Evidence B]. CONCLUSIONS Based on the currently available data, a causal relationship between GERD and idiopathic pulmonary fibrosis cannot be established. There is scant evidence about antireflux therapy in idiopathic pulmonary fibrosis patients. There may be an association between lung and oesophageal involvement in systemic sclerosis and mixed connective tissue disease, but a causal relationship cannot be established.