Pulmonary Vascular Involvement Research Articles

C17 AN UNUSUAL CASE OF RIGHT HEART FAILURE AND PULMONARY HYPERTENSION: WET BERIBERI. THE IMPORTANCE OF DIFFERENTIAL DIAGNOSIS

Abstract Introduction High–output heart failure is a rare form of heart failure. Possible causes include vitamin B1 (thiamine) deficiency. This vitamin plays an important role in the aminoacids energy metabolism and in the transmission of nerve impulses. Thiamine deficiency can affect the cardiovascular (wet beriberi), nervous, and immune systems. Case report: This case report concerns a 73–year–old man with a history of alcohol abuse affected by arterial hypertension, persistent atrial fibrillation, COPD and alcoholic liver disease. Home therapy included low–dose diuretic, mineralocorticoid antagonists, anticoagulant, hypotensive drugs and oral antidiabetic drugs. Due to the occurrence of dyspnoea and progressive swelling of the lower limbs he was hospitalized. Transthoracic echocardiogram (TTE) showed mild biventricular dilatation with normal function. The Doppler study revealed moderate–severe tricuspid regurgitation (anulus dilatation) and indirect signs of an increase in pulmonary pressures. Blood tests showed a picture of cytopenia, altered hepatic synthesis indexes and high values of natriuretic peptides. He performed invasive hemodynamic evaluation with right heart catheterization which showed mild pulmonary hypertension (mPAP 28 mmHg) with normal pulmonary vascular resistance and an increase in cardiac index (CI 4.2 L/min/m2). The cardiopulmonary testing (CPET) indicated a slight reduction in functional capacity (pVo2 77% of predicted value) and initial pulmonary vascular involvement. In the following months the patient manifested haemodynamic instability with the need for intravenous diuretic therapy. At a subsequent check–up, the dosage of thiamin was performed, which was found to be deficient, so he started supplementation. In the next period the patient reported well–being and maintained euvolemia. At a hospital re–evaluation, he performed a new TTE evaluation which showed a reduction in ventricular volumes and tricuspidal regurgitation as well as a new evaluation of invasive cardiac output which showed a reduction in right sections pressure (mPAP 22 mmHg) with normalization of the CI value (2,20 L/min/m2). CPET showed almost the same results of the previous one. Conclusion Beriberi is a possible treatable cause of high–output heart failure. Although it is a rare pathology in Western countries, it should always be suspected in some categories of patients such as alcoholics, subjects with eating disorders and those undergoing bariatric surgery.

728 GALECTINE-3 AND SST2 IN SYSTEMIC SCLEROSIS: AN EARLY DETECTION OF PULMONARY VASCULAR INVOLVEMENT IS REALLY POSSIBLE?

Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare form of pulmonary hypertension (PH) that may also be associated with connective tissue diseases (CTD). In particular, PAH may affect from 5 to 19% of patients with systemic sclerosis (SSc), leading to a significant prognostic worsening. The current challenge is an early detection of PAH in such patients, in order to provide an early referral to PH centers to supply specific therapies as soon as possible. In the latest ESC guidelines for PH, cardiopulmonary exercise testing (CPET) has been included in the diagnostic algorithm for patients with unexplained exertional dyspnoea and/or suspected PH. Patients with PAH show a typical pattern, with a low end-tidal partial pressure of carbon dioxide (PETCO2), high ventilatory equivalent for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/ HR) and low peak oxygen uptake (VO2). CPET may identify patients with SSc at low risk of PAH, to avoid unnecessary right heart catheterization (RHC). However, CPET is not available in all centers. So, we designed a preliminary study to identify new biomarkers that correlate with CPET's parameters. Material and Methods We enrolled 62 SSc patients [53 females, median age 52 years] with no other comorbidities and asymptomatic for dyspnea or other symptoms. 56% and 44% of them presented limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), respectively. For all patients we performed serum analysis for sST2, Galectine-3, pro-ANP, BNP and IL6, diagnostic imaging with echocardiography and cardiac MRI, CPET and pulmonary functionality test (PFT). Results All patients presented normal echocardiographic and RMI imaging findings. Galectin-3, sST2, pro-ANP, BNP and IL6 presented respectively the following median value: 13.45 ng/mL [11.78; 18.70], 23.25 ng/mL [13.04; 43.35], 1897 fmol/ml [1487; 2445], 12.18 pg/mL [9.34; 15.01]. Both Galectin-3 and sST2 showed a linear correlation with VE/VCO2 slope with R 0.339 (P-value 0.018) and 0.355 (P-value 0.013) respectively. After linear regression analysis, Galectin-3 and sST2 were overall statistically significant with R2 of 0.115 and 0.126, F of 5.97 and 6.62 and P-value of 0.018 and 0.013, respectively. It was found that Galectin-3 and SST2 significantly predicted VE/VCO2 slope with β = 0.364 [0,064; 0,665] for Galectin-3 and 0.137 [0,030; 0,244] for SST2. All other CPET parameters did not show correlation with the biomarkers. Conclusion Our preliminary results suggest that Galectine-3 and sST2 may be useful biomarkers for predicting increasing VE/VCO2 slope. Future analysis may confirm the role of these new biomarkers for early detection of pulmonary vascular involvement in SSc patients to allow an early referral and treatment and, conversely, to avoid unnecessary RHC.

Pleuropulmonary involvement in patients with collagen vascular diseases

Background Collagen vascular diseases are a diverse set of autoimmune disorders that can affect any part of the pulmonary system. Purpose This study aimed to identify the frequency, severity, pattern, and outcome of pleuropulmonary involvement in collagen vascular diseases among a cohort of Egyptian population. Patients and methods This cross-sectional study was carried out on 50 cases, who were diagnosed as collagen vascular disease (fulfilling the published classification criteria for each disease) and developed respiratory symptoms. The included cases were subjected to detailed history, clinical examination, and investigations included mainly chest imaging (high-resolution computed tomography for all cases, chest ultrasound, and computed tomography pulmonary angiography when needed), pulmonary functions tests, and echo. Follow-up of patients was done at the end of hospital stay and at 1 month after discharge. Results The mean age of the studied population was 44.34 ± 14.22 years with female predominance representing 74% of cases. The most common diagnosed collagen vascular disease was rheumatoid arthritis in 42% of cases, followed by systemic lupus in 38% of the cases. Dyspnea was the most common presenting symptom among the studied patients in 70% of cases. Parenchymal involvement was the most common involvement among 86% of the cases followed by pulmonary vascular involvement in 62% of the cases. The outcome among the included patients was improvement in 54% of cases, partial improvement in 20% of cases, stationary in 20% of cases, and 6% of included cases died at the end of hospital stay. Conclusion Parenchymal involvement and pulmonary hypertension were, respectively, the most pleuropulmonary involvement in collagen vascular diseases among a cohort of Egyptian population. Mortality rate was higher among systemic lupus patients in activity with other parenchymal involvement group and interstitial lung disease.

Sleep-related breathing disorders in idiopathic pulmonary fibrosis are frequent and may be associated with pulmonary vascular involvement.

Sleep-related breathing disorders (SRBD) may be associated with a worse prognosis in idiopathic pulmonary fibrosis (IPF). However, the prevalence of sleep disorders in IPF and the pathophysiological link between SRBD and IPF is unclear. In this prospective trial, consecutive patients with stable IPF underwent polysomnography and cardiopulmonary exercise testing. Epworth sleepiness scale, Regensburg insomnia scale, and Pittsburgh sleep quality index were evaluated. Exclusion criteria were oxygen supplementation therapy, lung emphysema, and heart failure. For pairwise comparison of categorical data, the two-proportion z-test was applied. Correlation between continuous variables was assessed via the Pearson correlation coefficient. Patients without and with SRBD were compared. To find predictors for SRBD in IPF, multivariable logistic regression was applied. A total of 74 IPF patients were evaluated and 45 patients (11 female, median age 74years, forced vital capacity 71.3%, DLCO 53.9%) were analyzed. Any kind of sleep disorder was found in 89% of patients. SRBD was present in 49% (81% obstructive sleep apnea, 19% central sleep apnea), insomnia in 40%, and periodic leg movements in 47% of subjects. The SRBD subgroup presented with a significantly lower performance (workload(peak)%pred 86.5 vs. 101.0 (p = 0.036); V'O2(AT) 618.5ml/min vs. 774.0ml/min (p = 0.043)) and exhibited a significantly higher V'E/V'CO2(peak) of 43.0l/l vs. 38.5l/l (p = 0.037). In search of predictors for SRBD by logistic regression, workload(peak)%pred was identified as a significant variable (p = 0.033). SRBD is frequent in IPF. Pulmonary vascular limitations may represent the pathophysiological link between IPF and SRBD. Workload(peak)%pred may be an independent risk factor for the occurrence of SRBD.

Chest CT Findings in Hospitalized Patients with SARS-CoV-2: Delta versus Omicron Variants.

BackgroundCT manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may differ among variants.PurposeTo compare the chest CT findings of SARS-CoV-2 between the Delta and Omicron variants.Materials and MethodsThis retrospective study collected consecutive baseline chest CT images of hospitalized patients with SARS-CoV-2 from a secondary referral hospital when the Delta and Omicron variants predominated. Two radiologists categorized CT images based on the Radiological Society of North America classification system for coronavirus disease 2019 (COVID-19) and visually graded pneumonia extent. Pneumonia, pleural effusion, and intrapulmonary vessels were segmented and quantified on CT images using a priori developed neural networks, followed by reader confirmation. Multivariable logistic and linear regression analyses were performed to examine the associations between the variants and CT category, distribution, severity, and peripheral vascularity.ResultsIn total, 88 patients with the Delta (mean age, 67 years±15; 46 men) and 88 patients with the Omicron (mean age, 62 years±19; 51 men) variants were included. Omicron was associated with a less frequent typical peripheral, bilateral ground-glass opacity (32% [28/88] versus 57% [50/88]; P=.001), more frequent peri-bronchovascular predilection (38% [25/66] versus 7% [5/71]; P<.001), lower visual pneumonia extent (5.4±6.0 versus 7.7±6.6; P=.02), similar pneumonia volume (5%±10 versus 7%±11; P=.14), and a higher proportion of vessels with a cross-sectional area smaller than 5 mm2 relative to the total pulmonary blood volume (BV5%; 48%±11 versus 44%±8; P=.004). In adjusted analyses, Omicron was associated with a non-typical appearance (odds ratio, 0.34; P=.006), peri-bronchovascular predilection (odds ratio, 9.2; P<.001), and higher BV5% (β value, 3.8; P=.01) but similar visual pneumonia extent (P=.17) and pneumonia volume (P=.67) relative to Delta variant.ConclusionsOn chest CT, the Omicron SARS-COV-2 variant showed nontypical, peri-bronchovascular pneumonia and less pulmonary vascular involvement than the Delta variant in hospitalized patients with comparable CT disease severity.

Evaluation of pulmonary arterial stiffness and comparison with right ventricular functions in patients with cirrhosis preparing for liver transplantation.

Pulmonary complications are common in patients with liver cirrhosis. Devolopment of pulmonary hypertension (PH) is associated with a poor prognosis in these patients. Pulmonary arterial stiffness (PAS) is considered an early sign of pulmonary vascular remodeling. The aim of this study is to investigate PAS and compare it with right ventricular (RV) functions in patients with cirrhosis who are scheduled for liver transplantation. The study included 52 cirrhosis patients (mean age 51.01 ± 12.18 years, male gender 76.9%) who were prepared for liver transplantation and 59 age and sex matched (mean age 51.28 ± 13.63 years, male gender 62.7%) healthy individuals. Patients with left ventricular ejection fraction (LVEF) less than 55%, ischemic heart disease, more than mild valvular heart disease, chronic pulmonary disease, congenital heart disease, rheumatic disease, moderate to high echocardiographic PH probability, rhythm or conduction disorders on electrocardiography were excluded from the study. In addition to conventional echocardiographic parameters, PAS value, pulmonary vascular resistance (PVR) and RV ejection efficiency was calculated by the related formulas with transthoracic echocardiography (TTE). Demographic characteristics and cardiovascular risk factors of the groups were similar. PAS, PVR, and sPAP values were found to be significantly higher in the patient group (20.52 ± 6.52 and 13.73 ± 2.05; 1.43 ± 0.15 and 1.27 ± 0.14; 27.69 ± 3.91 and 23.37 ± 3.81 p < 0.001, respectively). RV FAC and RV Ee were significantly lower and RV MPI was significantly higher in the patient group (45.31 ± 3.85 and 49.66 ± 3.62, p < 0.001; 1.69 ± 0.35 and 1.85 ± 0.23, p=0.005; 0.39 ± 0.07 and 0.33 ± 0.09, p=0.001, respectively). PAS was significantly correlated with RV FAC and MPI (r=-0.423, p < 0.001; r=0.301, p=0.001, respectively). Increased PAS in cirrhosis patients may be associated with early pulmonary vascular involvement. Evaluation of RV functions is important to determine the prognosis in these patients. FAC, MPI, and RV Ee measurements instead of TAPSE or RV S' may be more useful in demonstrating subclinical dysfunction. The correlation of PAS with RV FAC and MPI may indicate that RV subclinical dysfunction is associated with early pulmonary vascular remodeling in patients with liver cirrhosis.

Endothelial Dysfunction through Oxidatively Generated Epigenetic Mark in Respiratory Viral Infections.

The bronchial vascular endothelial network plays important roles in pulmonary pathology during respiratory viral infections, including respiratory syncytial virus (RSV), influenza A(H1N1) and importantly SARS-Cov-2. All of these infections can be severe and even lethal in patients with underlying risk factors.A major obstacle in disease prevention is the lack of appropriate efficacious vaccine(s) due to continuous changes in the encoding capacity of the viral genome, exuberant responsiveness of the host immune system and lack of effective antiviral drugs. Current management of these severe respiratory viral infections is limited to supportive clinical care. The primary cause of morbidity and mortality is respiratory failure, partially due to endothelial pulmonary complications, including edema. The latter is induced by the loss of alveolar epithelium integrity and by pathological changes in the endothelial vascular network that regulates blood flow, blood fluidity, exchange of fluids, electrolytes, various macromolecules and responses to signals triggered by oxygenation, and controls trafficking of leukocyte immune cells. This overview outlines the latest understanding of the implications of pulmonary vascular endothelium involvement in respiratory distress syndrome secondary to viral infections. In addition, the roles of infection-induced cytokines, growth factors, and epigenetic reprogramming in endothelial permeability, as well as emerging treatment options to decrease disease burden, are discussed.

Pulmonary vascular involvement in COVID‐19 pneumonitis: Is this the first and final insult?

See related article

Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion.

Three to four months after hospitalisation for COVID-19 pneumonia, the most frequently described alteration in respiratory function tests (RFTs) is decreased carbon monoxide transfer capacity (DLCO). Methods: This is a prospective cohort study that included patients hospitalised because of SARS-CoV-2 pneumonia, three months after their discharge. A clinical evaluation, analytical parameters, chest X-ray, six-minute walk test, spirometry and DLCO–DLNO analysis were performed. Demographic variables, comorbidities, and variables related to the severity of the admission were recorded. Results: Two hundred patients completed the study; 59.5% men, age 62 years, 15.5% admitted to the intensive care unit. The most frequent functional alteration, in 27% of patients, was in the DLCO–DLNO combination. This alteration was associated with age, male sex, degree of dyspnoea, poorer perception of health, and limited ability for physical effort. These patients also presented higher levels of D-Dimer and more residual radiological alterations. In 42% of the patients with diffusion alterations, only reduced DLNO was presented, along with lower D-Dimer levels and less capillary volume involvement. The severity of the process was associated with the reduction in DLCO–DLNO. Conclusions: The most sensitive RFT for the detection of the sequelae of COVID-19 pneumonia was the combined measurement of DLCO–DLNO and this factor was related to patient health status and their capacity for physical exertion. In 40% of these cases, there was only a reduction in DLNO, a finding that may indicate less pulmonary vascular involvement.

Abstract No. 598 Clinical manifestations of patients with novel mutations associated with hereditary hemorrhagic telangiectasia and related vascular anomalies

In this series, 4 patients with HHT were identified with novel GDF2 mutations. They were compared to an individual with capillary malformation-arteriovenous malformation syndrome (CM-AVM) secondary to a RASA1 mutation to highlight the clinical similarity between the two diseases. With IRB exemption, the electronic medical record was searched with the search term HHT, genetic mutation, pulmonary arteriovenous malformation. The eligibility criteria included only those patients with a novel mutation in the GDF2 and RASA1 locus. The initial search resulted in 776 total patients with a suspected diagnosis of HHT. 162 patients had genetic testing done. We derived 5 patients with HHT-like clinical presentations found to have a novel (GDF2, n = 4) or related (RASA1, n = 1) mutation. 5 patients were included with a mean age of 17 years (range, < 1–37) with 60% female. 4 patients had a mutation or deletion in the GDF2 gene, and 1 patient had a RASA1 mutation and was diagnosed with CM-AVM. See Table. All GDF2 patients reported childhood nosebleeds, but only 1/ 4 patients continue to experience epistaxis by adulthood. 2/4 patients reported self-limited nosebleeds that resolved by adulthood. Mucocutaneous telangiectasia was observed only in 1/4 patients and in an atypical location. Unlike classic HHT, AVM and telangiectasia were not observed in the pulmonary or the hepatic vasculatures of GDF2 patients. 1 patient with a missense GDF2 mutation was found to have a hepatic focal nodular hyperplasia. The patient with CM-AVM also did not exhibit pulmonary or hepatic vascular involvement. GDF2 mutations predominately affected the cerebrovasculature. 2/4 GDF2 mutated patients suffered from brain vascular malformation. A third patient presented for evaluation after her daughter was diagnosed with a brain AVM. A frontal AVM and macrocephaly were diagnosed in the CM-AVM patient.3 patients with GDF2 mutations and one with RASA1 mutation were found to have some form of cardiac abnormalities. Clinical manifestations of HHT secondary to GDF2 mutations presented differently and exhibit overlapping features as CM-AVM due to RASA1 mutation.Tabled 1SexAge (years)DiagnosisGeneNucleotide ChangeProtein ChangeMutation TypeSignificanceF3CM-AVMRASA1c.2131C >Tp.Arg711TerNonsensePathogenicF37HHTGDF2c.1063G >Cp.Glu355GlnMissenseUnknownM32HHTGDF2c.1207G >Ap.Val403IleMissenseUnknownF13HHTGDF25.10-Mb deletion of 10q11.22 to 10q11.2336 genes deletedDeletionLikely pathogenicM0HHTGDF25.5-Mb deletion of 10q11.22 to 10q11.23UndeterminedDeletionLikely pathogenic Open table in a new tab

Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C-C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. We conducted cross-sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9years. Serum CCL20 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed with the Mann-Whitney U test, the Kruskal-Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient. SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti-mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.

Rheumatoid arthritis: Extra-articular manifestations and comorbidities.

Although synovitis is the pathological hallmark of rheumatoid arthritis (RA), many extra-articular manifestations (EMs) and comorbidities likely occur due to the complex, chronic, inflammatory, and autoimmune features of RA. Cardiovascular (CV) disease is the most common cause of death in patients with RA. Compared to the general population, patients with RA have twice the risk of myocardial infarction and up to 50% increased CV mortality risk. Severe and prolonged disease activity, genetics, and inflammation (e.g. CRP, ACPA, cytokines, matrix-degrading enzymes) play important roles in CV disease and atheroscleroticdamage. The second major cause of death in patients with RA is respiratory disease, which occurs in 30-40% of patients. RA may affect the lung interstitium, airways, and pleurae, while pulmonary vascular involvement is less frequent. Central and peripheral nervous system involvement is usually due to small vessel vasculitis, joint damage, or drug toxicity. There is also evidence that microvascular cerebral damage caused by systemic inflammation is associated with the development of Alzheimer's disease and vascular dementia. Some observational studies have hinted how Disease Modified Anti-Rheumatic Drugs and biologics could reduce the incidence of dementia. Primary gastrointestinal and renal involvements are rare and often relate to drug therapy. To minimize morbidity and mortality, physicians must manage RA disease activity (treat-to-target) and monitor risk factors and concomitant conditions (e.g. smoking cessation; weight regulation; monitoring blood pressure, lipids, thyroid hormone, folic acid and homocysteine; screening for depression, anxiety, atlantoaxial instability, and atherosclerosis). This article aims to provide an overview of the most prevalent and important EMs and comorbidities associated with RA.

Quantification of pulmonary perfusion in idiopathic pulmonary fibrosis with first pass dynamic contrast-enhanced perfusion MRI

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fatal disease of lung scarring. Many patients later develop raised pulmonary vascular pressures, sometimes disproportionate to the interstitial disease. Previous therapeutic approaches that have...

Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Guideline-Driven Care Should Be Our Natural Reflex.

Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Guideline-Driven Care Should Be Our Natural Reflex.

Complete occlusion of right pulmonary artery in Behçet disease.

Key messageWhen a patient with Behçet disease presents with haemoptysis, pulmonary vascular involvement should be considered.

Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis.

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.

The role of pulmonary arterial hypertension-targeted therapy in systemic sclerosis.

Pulmonary arterial hypertension, categorized as group 1 pulmonary hypertension by the World Health Organization classification system, represents a major complication of systemic sclerosis resulting from pulmonary vascular involvement of the disease. The high mortality seen in systemic sclerosis-associated pulmonary arterial hypertension is likely due to the impairment of right ventricular systolic function and the coexistence of other non-group-1 pulmonary hypertension phenotypes that may negatively impact clinical response to pulmonary arterial hypertension-targeted therapy. This review highlights two areas of recent advances regarding the management of systemic sclerosis patients with pulmonary hypertension: the tolerability of pulmonary arterial hypertension-targeted therapy in the presence of mild to moderate interstitial lung disease and the potential clinical significance of the antifibrotic effect of soluble guanylate cyclase stimulators demonstrated in preclinical studies.

Fli1 deficiency induces endothelial adipsin expression, contributing to the onset of pulmonary arterial hypertension in systemic sclerosis.

Adipsin, or complement factor D, is a serine proteinase catalysing complement factor C3 breakdown, leading to the production of opsonin (C3b), membrane attack complex (C5b-C9) and anaphylatoxins (C3a and C5a). Since adipsin is potentially associated with pulmonary arterial hypertension in SSc, we investigated adipsin expression in dermal small vessels of SSc-involved skin, the mechanism regulating adipsin expression in endothelial cells, and the correlation of serum adipsin levels with SSc clinical symptoms. Adipsin expression was assessed by immunohistochemistry with skin sections of SSc and healthy subjects. mRNA levels of target genes and transcription factor binding to the ADIPSIN promoter were evaluated by quantitative reverse transcription PCR and chromatin immunoprecipitation, respectively. Serum adipsin levels were determined by enzyme-linked immunosorbent assay. Adipsin expression was remarkably increased in dermal small vessels of SSc-involved skin as compared with those of healthy control skin. Consistent with the notion that Fli1 deficiency induces SSc-like phenotypes in various types of cells, FLI1 siRNA enhanced adipsin expression at protein and mRNA levels and Fli1 bound to the ADIPSIN promoter in human dermal microvascular endothelial cells. Serum adipsin levels were significantly lower in diffuse cutaneous SSc patients than in limited cutaneous SSc patients and healthy controls, and were associated positively with elevated right ventricular systolic pressure and inversely with interstitial lung disease by multivariate regression analysis. Adipsin is up-regulated at least partially by Fli1 deficiency in endothelial cells, potentially contributing to the development of pulmonary vascular involvement in SSc.

Computer tomography features of pulmonary vascular involvement in Behçet's disease

Computer tomography features of pulmonary vascular involvement in Behçet's disease

An insider view on the World Symposium on Pulmonary Hypertension

An insider view on the World Symposium on Pulmonary Hypertension