Specific PAH Research Articles

Infrared emission of specific polycyclic aromatic hydrocarbon molecules: indene

ABSTRACT Polycyclic aromatic hydrocarbon (PAH) molecules have long been suggested to be present in the interstellar medium (ISM). Nevertheless, despite their expected ubiquity and sustained searching efforts, identifying specific interstellar PAH molecules from their infrared (IR) spectroscopy has so far been unsuccessful. However, due to its unprecedented sensitivity, the advent of the JWST may change this. Meanwhile, recent years have witnessed breakthroughs in detecting specific PAH molecules (e.g. indene, cyanoindene, and cyanonaphthalene) through their rotational lines in the radio frequencies. As JWST holds great promise for identifying specific PAH molecules in the ISM based on their vibrational spectra in the IR, in this work, we model the vibrational excitation of indene, a molecule composed of a six-membered benzene ring fused with a five-membered cyclopentene ring, and calculate its IR emission spectra for a number of representative astrophysical regions. This will facilitate JWST to search for and identify indene in space through its vibrational bands and to quantitatively determine or place an upper limit on its abundance.

The potential of polycyclic aromatic compounds as indicators for soil contamination by open-pit mining and utilization of lignite: a case study at Ptolemaida basin, Greece

AbstractThe majority of Greek lignite fields and coal-fired power plants is accumulated in the centre of Western Macedonia in the Ptolemais-Amynteo region of Northern Greece (Ptolemaida basin). The corresponding environmental impact dominantly caused by the mining process itself but also due to the burning process of lignites needs to be considered. Therefore, this study aimed at assessing the potential of PAHs to trace the environmental impact of power plant and coal mining emissions on soil pollution in the Ptolemaida basin. Noteworthy, the study area exhibits some special features (e.g. geomorphological and meteorological conditions, well-defined emission sources) that allow to prove the suitability of PAHs as indicators for specific petrogenic contaminations. The different sets of PAH emission sources followed in this study (fly ashes, lignite dust, charred woody material) reflected the pollution as derived from the coal mining activities as well as agricultural measures. Different approaches from simple (total amount) to more complex fingerprinting (ring member classification; profiles of sulphur-/nitrogen- and oxygen-containing PACs) as well as the application of established specific PAH ratios revealed no significant correlation with the detected soil contamination or rather soil PAH profiles. However, the microscopic analyses contradicted this assumption, since relevant particle concentrations were evident for fly ash as well as lignite particles. Hence, a huge superimposition by a further PAH emission source is assumed, probably the exhaust fumes of car traffic. In general, the study demonstrated that the application of PAHs as source indicators in soil systems is very complex and needs a very thorough interpretation. Hence, the need of using additionally complementary parameters for an unambiguous emission source apportionment seems obvious. Graphical abstract

HAP-TiO2 nanocomposites based electrochemical sensor for selective and simultaneous detection of para-aminohippuric acid and uric acid

Kidney diagnosis by p-aminohippuric acid (PAH) test indicates the ability of the kidney to combine benzoic acid with PAH by determination of the latter eliminated in urine or blood serum. Hippuric acid synthesis also occurs in both the liver and cortical cells of the kidney. However, the PAH test did not become popular because of the non-availability of a simple method for quick and accurate determination of the PAH at an affordable cost. Here, we report a novel electrochemical sensor based on hydroxyapatite-titanium dioxide (HAP-TiO2) nanocomposite for quantifying specific biomarkers PAH and uric acid (UA). Nanostructured HAP and TiO2 powders have been synthesized independently by microwave irradiation and hydrolysis methods respectively and the composites are prepared by mixing the appropriate amounts of HAP and TiO2 under sonication. Voltammetric studies of HAP-TiO2 modified glassy carbon electrodes exhibited improved electrocatalytic activity towards the oxidation of PAH and UA in a phosphate buffer saline (pH7.0). Under the optimized conditions, the oxidation peak currents are linearly proportional to PAH and UA concentrations over wide linear ranges of 50 nM to 5.760 mM, and the corresponding lowest detection limits are estimated to be 37 nM and 43 nM (S/N = 3). The fabricated electrode has been successfully implemented for the determination of PAH and UA in human urine samples. Performance of the device in terms of sensitivity, specificity, and linear range fulfills the requirement for screening the chosen biomarkers simultaneously making it suitable for clinical non-invasive liver and kidney diagnoses.

Survival of patients with idiopathic pulmonary fibrosis and pulmonary hypertension under therapy with nintedanib or pirfenidone.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause that leads to respiratory failure and death within few years of diagnosis. Pulmonary hypertension (PH) is a common complication in IPF, where it is strongly associated with increased morbidity and mortality. Patients with IPF and PH have particularly poor prognosis, despite current best medical therapies and the anti-fibrotic therapy with pirfenidone or nintedanib. The aim of our study was to assess the clinical and prognostic impact of PH in patients affected by IPF, already treated with pirfenidone or nintedanib. Seventy-four consecutive outpatients with a diagnosis of IPF, in therapy with pirfenidone or nintedanib, were prospectively enrolled in the study. All patients underwent pulmonary and cardiology assessment by clinical exam, spirometry, DLCO test, chest CT, 6MWT and echocardiography performed by a cardiologist experienced in PH in an ambulatory setting under resting conditions. GAP index has been determinate for all patients. During follow-up, all patients were evaluated every 6months, or less if necessary. Data about mortality were then collected in a 3-year follow-up. Of the seventy-four patients enrolled, 38 were treated with pirfenidone and 36 with nintedanib. The two groups were comparable for age, gender, FVC, DLCO and PAPS. The patients were also divided in four groups, based on presence of mild/moderate/severe PH by echocardiography at baseline. Significant differences were found for DLCO and the GAP index. Severity of PH was significantly associated with a reduction of DLCO and with an increased GAP index. Survival was directly correlated with 6MWT (R = 0.48), DLCO (R = 0.29, p < 0.01), and reversely with tGAP index (- 0.31, p < 0.01 in all cases), while no significant correlation was found with PAsP. 36-month survival analysis showed an HR of 4.05 (95% CI 1.07-7.34, p = 0.02) for DLCO < 50% and of 1.56 (95% CI 1.02-2.39, p = 0.03) for GAP index. The development and progression of PH in patients affected by IPF reduce the survival and the severity of PH is associated with a reduction of DLCO value and an increase of the GAP index. Echocardiographic stratification based on PAsP values may be useful in stratifying prognosis in IPF patients and deciding specific PAH drugs.

LIF diagnostics for selective and quantitative measurement of PAHs in laminar premixed flames

Laser-induced fluorescence (LIF) technique has been widely applied in PAH measurement in sooting flames, but it is still a big challenge to quantitatively identify the specific PAH species due to the complexities of spectral characteristics and calibration method. In this study, we aimed at developing a spectral-resolved LIF analytic model that can obtain PAH mole fractions in flames. A comprehensive LIF spectrum database in the wide temperature and concentration ranges was firstly established by the LIF experiments of gas-phase PAHs in an optical cell. Then, a spectral-resolved LIF analytic model was presented based on linear superposition regulation and an optimization fitting algorithm, and the LIF spectra of PAH components can be decomposed from the LIF spectra of the flame using this model. Finally, the integral fluorescence intensities of each PAH component were calibrated to their mole fractions by the calibration factors at corresponding temperatures. In this way, we can measure the mole fractions of several PAHs. Subsequently, the presented LIF method was applied to investigate the PAH formation characteristics at different flame temperatures. The experimental results showed that the mole fractions of each PAH except naphthalene decreased around 60% to 70% when the temperature increased from 1186 K to 1483 K, while the mole fraction of naphthalene kept nearly constant. The mole fractions simulated by a chemical kinetic model well reproduce the experimental results. According to the chemical kinetic analysis, C2H2 oxidation reaction was promoted and the C2H2-addition reactions were suppressed by increasing temperatures, which suppressed the PAH formation.

Distribution of Polycyclic Aromatic Hydrocarbons in Water and Sediments in the Euphrates River, Iraq

The monitoring of lotic ecosystems is important for environmental health after war crisis. This study aimed to detect the fate of the sixteen polycyclic aromatic hydrocarbon compounds (PAHs) as priority pollutants in the water and sediment of Al-Hussainya River in Karbala Province. The results indicated that the concentrations in water samples ranged from 0.24–58.72 ηg.L-1 for each of the benzo(a) pyrene and benzo(g, h, i)perylene. The concentrations in sediment samples have been observed to be in a range of 0.36–119.06 μg.g-1 for naphthalene and benzo(g,h,i)perylene. Benzo(g,h,i)perylene recorded the highest concentrations in each of water and sediment samples as compared with the other compounds. The ratios of the specific PAH compounds were calculated to evaluate the possible sources of PAH contamination. These ratios reflected pyrogenic and petrogenic origins in both water and sediments.

P2267CTEPH patients long term follow-up: results from a single center

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a thrombotic pulmonary disease associated with pulmonary vasculopathy. Pulmonary endarterectomy (opus, PEA) is the first treatment choice in CTEPH, and specific PAH medication when there is a contraindication for surgery or residual pulmonary arterial hypertension (rPAH) occurs. In the presence of PAH balloon pulmonary angioplasty (BPA) might be also recommended if available. Objective We investigated the long term outcome of our CTEPH patients. Methods CTEPH from our institution retrospectively analyzed (data between 2003 and 2018). Baseline, treatment and outcome data were documented. We compared the outcome, together with mortality in those with and without surgery (PEA vs. non PEA group). NYHA class, 6 minutes walking distance (6MWD) and NT-proBNP were also reported during follow-up. Results Of 29 CTEPH patients (mean age was 62±19 years, 52% male) 16 (55%) were accepted for PEA, and further 12 of them had a long term follow-up post surgery (n=3 periop exit, n=1 waiting for surgery). Half of the PEA patients were cured (n=6) and the other half (n=6) required specific PAH treatment (n=1, in combination with BPA) for rPAH. All patients from the non-PEA group (n=13) were started on specific PAH treatment (n=1 in combination with BPA). Patients with or without PEA did not differ hemodynamically. At the late follow-up there was a significant improvement in PEA group for NYHA class and NT-proBNP (p&lt;0,001, and p=0,046), and in non PEA group for NYHA class and the 6MWD (p=0,012, and 0,006). We found significant difference in mortality at 1,3,5 year (Kaplan-Meier survival analysis) follow-up, for PEA group 100%-100%-100% and non PEA group 100%-85%-78% (p=0,013), respectively. Conclusions 55% of CTEPH patients were suitable for PEA, and those who survived the surgery 50% were cured. Non PEA patients improved functionally on the long term, but had worse survival.

PRS20 CRITICAL MODEL OF THE INDIVIDUAL AND GLOBAL COST OF THE MEDICAL TREATMENT OF THE PULMONARY ARTERIAL HYPERTENSION IN COLOMBIA

To estimate the costs of specific PAH treatment in Colombia in terms of monotherapy and / or its various combinations (Niza 2018). Costing of the estimated treatment was carried out assuming an indicator patient (adult, 60 kg) with diagnosis of PAH and candidate for pharmacological treatments available in Colombia, according to clinical practice guidelines. Frequency of use and unit costs of pharmacological treatment (official price source, SISMED) were estimated as the minimum, average and maximum price in 2018. We assume the assumption of a 100% adherence for all the analyzed technologies. The data was analyzed. The cost is presented in both COP (USD, €) and normalizing all of the current legal minimum wage (SMLV) in Colombia. The annual treatment with specific drugs for PAH has a wide range of cost (USD 200-243,000, equivalent to 2-16 SMLV) in Colombia. The combination of two drugs (USD 4600-283000; 18-1076 SMLV) and three of them (USD 5200-287000; 20-1092 SMLV) imposes a much higher direct cost to the health system. There was no data on adherence, delay in dispensing or overall percentage of patients under treatment. As in other countries, the cost of pharmacological treatment of PAH in Colombia is high. This impact on costs at the national level will increase significantly due to the improvements that are being made in detection, treatment, adherence and survival in patients with PAH, as it will increase the number of patients and duration of said specific treatments. This forecast makes the indication, prescription and dispensation of these drugs a priority for improvement through integrated actions of HAPREDCO with the Colombian health management system.

Urinary biomarkers of polycyclic aromatic hydrocarbons in pre- and peri-pubertal girls in Northern California: Predictors of exposure and temporal variability

BackgroundPolycyclic aromatic hydrocarbons (PAHs), a class of chemicals produced as combustion by-products, have been associated with endocrine disruption. To understand exposure in children, who have been less studied than adults, we examined PAH metabolite concentrations by demographic characteristics, potential sources of exposure, and variability over time, in a cohort study of pre- and peri-pubertal girls in Northern California. MethodsUrinary concentrations of ten PAH metabolites and cotinine were quantified in 431 girls age 6–8 years at baseline. Characteristics obtained from parental interview, physical exam, and linked traffic data were examined as predictors of PAH metabolite concentrations using multivariable linear regression. A subset of girls (n = 100) had repeat measures of PAH metabolites in the second and fourth years of the study. We calculated the intraclass correlation coefficient (ICC), Spearman correlation coefficients, and how well the quartile ranking by a single measurement represented the four-year average PAH biomarker concentration. ResultsEight PAH metabolites were detected in ≥ 95% of the girls. The most consistent predictors of PAH biomarker concentrations were cotinine concentration, grilled food consumption, and region of residence, with some variation by demographics and season. After adjustment, select PAH metabolite concentrations were higher for Hispanic and Asian girls, and lower among black girls; 2-naphthol concentrations were higher in girls from lower income households. Other than 1-naphthol, there was modest reproducibility over time (ICCs between 0.18 and 0.49) and the concentration from a single spot sample was able to reliably rank exposure into quartiles consistent with the multi-year average. ConclusionsThese results confirm diet and environmental tobacco smoke exposure as the main sources of PAHs. Controlling for these sources, differences in concentrations still existed by race for specific PAH metabolites and by income for 2-naphthol. The modest temporal variability implies adequate exposure assignment using concentrations from a single sample to define a multi-year exposure timeframe for epidemiologic exposure-response studies.

Pulmonary Hypertension Complicating Fibrosing Mediastinitis.

Fibrosing mediastinitis is caused by a proliferation of fibrous tissue in the mediastinum with encasement of mediastinal viscera and compression of mediastinal bronchovascular structures. Pulmonary hypertension (PH) is a severe complication of fibrosing mediastinitis caused by extrinsic compression of the pulmonary arteries and/or veins.We have conducted a retrospective observational study reviewing clinical, functional, hemodynamic, radiological characteristics, and outcome of 27 consecutive cases of PH associated with fibrosing mediastinitis diagnosed between 2003 and 2014 at the French Referral Centre for PH.Fourteen men and 13 women with a median age of 60 years (range 18–84) had PH confirmed on right heart catheterization. The causes of fibrosing mediastinitis were sarcoidosis (n = 13), tuberculosis-infection confirmed or suspected (n = 9), mediastinal irradiation (n = 2), and idiopathic (n = 3). Sixteen patients (59%) were in NYHA functional class III and IV. Right heart catheterization confirmed moderate to severe PH with a median mean pulmonary artery pressure of 42 mm Hg (range 27–90) and a median cardiac index of 2.8 L/min/m2 (range 1.6–4.3). Precapillary PH was found in 22 patients, postcapillary PH in 2, and combined postcapillary and precapillary PH in 3. Severe extrinsic compression of pulmonary arteries (>60% reduction in diameter) was evidenced in 2, 8, and 12 patients at the main, lobar, or segmental levels, respectively. Fourteen patients had at least one severe pulmonary venous compression with associated pleural effusion in 6 of them. PAH therapy was initiated in 7 patients and corticosteroid therapy (0.5–1 mg/kg/day) was initiated in 3 patients with sarcoidosis, with 9 other being already on low-dose corticosteroids. At 1-year follow-up, 3 patients had died and among the 21 patients evaluated, 3 deteriorated, 14 were stable, and only 4 patients with sarcoidosis improved (4 receiving corticosteroids and 1 receiving corticosteroids and PAH therapy). Survival was 88%, 73%, and 56% at 1, 3, and 5 years, respectively.We found no clear clinical improvement with the use of specific PAH therapy. Corticosteroid therapy may be associated with clinical improvement, in some patients with fibrosing mediastinitis due to sarcoidosis. Although never performed for this indication, lung transplantation may be proposed in eligible patients with severe PH and fibrosing mediastinitis.

PP.32.25

Objective: Pulmonary hypertension (PH) is a group of chronic progressive diseases that have different etiology, but similar clinical presentation. Two conservative ways of treatment are available for such patients: calcium-channel blockers and specific PAH therapy. To define the right strategy right heart catheterization with acute vasodilator test (AVT) is performed. The aim of our study was to analyze the group of «true» responders, non-responders and patients in the «grey zone». Design and method: We analyzed 164 patients with verified diagnosis of PH who underwent right heart catheterization with AVT. Responders met the traditional criteria: reduction at 10 mm Hg. or more in mean pulmonary artery pressure with the aim of 40 mm Hg. and less with no evidence reduction in cardiac output. Non-responders did nit meet any of these criteria, while patients who are neither non-responders nor responders were defined as a “grey zone”. Results: All patients finally were divided into three groups: 34 responders, 28 non-responders and the largest group of 101 patients in a “grey zone”. Among the last group there was a big amount of patients with high reduction in pulmonary vascular resistance (PVR) (24,7 patients with reduction in PVR more than 300 dyn*sec/m2/cm5 with maximum of 1384 dyn*sec/m2/cm5), though they did not meet the criteria of cardiac output or/and mean pulmonary artery pressure. Among these 101 patients there were 26 with chronic thromboembolic pulmonary hypertension, 7 with PH associated with cardiac shunts, 12 with systemic connective tissue diseases and up to 48 of patients with Idiopathic pulmonary hypertension. The amount of patients with a high reduction in PVR (more than 300 dyn*sec/m2/cm5) is 26 with more than a half of patients with idiopathic pulmonary hypertension. Conclusions: In our national register we observed a huge amount of patients, who may present a great reduction in PVR in response to AVT - so called «grey zone». We need more research to specify the strategy for these patients.

Syndrome des antisynthétases compliqué d’une hypertension pulmonaire : 4 observations originales

IntroductionPulmonary hypertension (PH) may occur in patients with antisynthetase syndrome (ASS) but this association is poorly studied. In this article, we report 4 new cases of PH associated with ASS, and we discuss PH mechanisms in this specific disease. CasesFour patients (3 females, 1 male) with confirmed ASS associated with anti-Jo1 (n=3), anti-PL7 (n=1), and anti-Ro52 (n=3) antibodies were analyzed. They presented with subacute dyspnea in average ten years after they were first diagnosed as ASS. Diagnosis of pre-capillary PH was made (mean of mPAP: 34mmHg): PAH (n=1), group 3 PH (n=2) and PH associated to hyperthyroidism (n=1). Among three patients who received specific PAH therapy, two had significant improvement in both clinical and hemodynamic parameters. ConclusionDuring ASS, PH may occur in 5 to 10 % of cases, caused by various mechanisms. Unexplained dyspnea may be due to PH among ASS patients.

Hypertension pulmonaire et maladies hépatiques

Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH.

Primary porcine proximal tubular cells as an alternative to human primary renal cells in vitro: an initial characterization

BackgroundA good in vitro model should approximate an in vivo-like behavior as closely as possible in order to reflect most likely the in vivo situation. Regarding renal physiology of different species, humans are more closely related to pigs than to rodents, therefore primary porcine kidney cells (PKC) and their subsequent cell strain could be a valid alternative to primary human cells for renal in vitro toxicology. For this PKC must display inherent characteristics (e.g. structural organization) and functions (e.g. transepithelial transport) as observed under in vivo conditions within the respective part of the kidney.ResultsWe carried out a comprehensive characterization of PKC and their subsequent cell strain, including morphology and growth as well as transporter expression and functionality. The data presented here demonstrate that PKC express various transporters including pMrp1 (abcc1), pMrp2 (abcc2), pOat1 (slc22a6) and pOat3 (slc22a8), whereas pMdr1 (abcb1) and pOatp1a2 (slco1a2) mRNA could not be detected in either the PKCs or in the porcine cortical tissue. Functionality of the transporters was demonstrated by determining the specific PAH transport kinetics.ConclusionsOn the basis of the presented results it can be concluded that PKC and to some extent their subsequent cell strain represent a valuable model for in vitro toxicology, which might be used as an alternative to human primary cells.

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

Pulmonary Hypertension Associated to Sarcoidosis: Data from the Swiss PH Registry

Purpose Although rare and heterogeneous, pulmonary hypertension is a well-recognized complication of sarcoidosis. The aim of this study was to investigate the epidemiology and the clinical course of pulmonary hypertension associated to sarcoidosis (PHAS) in Switzerland. Methods and Materials The Swiss Registry of Pulmonary Hypertension was retrospectively analysed to identify PHAS cases from 2000-2011. Clinical parameters at baseline included gender, age, NYHA functional class, exercise capacity (6MWD) and mean pulmonary arterial pressure (mPAP). Survival curve according to Kaplan Meier, number of pulmonary transplants and the introduced treatment for pulmonary hypertension were recorded during the follow-up. Results Among 999 registered patients, 22 met the inclusion criteria for PHAS. The predominant sex was female (13) and the mean age was 55 ± 12 years. At diagnosis half of the patients were at NHYA class III and 5 patients in class IV. The 6MWD was 369 ± 124 meters and the mPAP was 44 ± 13 mmHg. The median follow-up was 14 months. The 1 and 3-year survival was 77 % and 56 %, respectively. During the follow-up period 5 patients underwent lung transplantation, with 2 post-operative deaths. The most frequently prescribed treatment at baseline was endothelin receptor antagonists (7) as well as at the end of follow-up (10). At this point, 5/18 patients were on combined therapy. Conclusions PHAS is a rare condition with a poor prognosis despite the off-label use of specific PAH therapy. As for PAH, the diagnosis is often made at an advanced stage. The mPAP is already highly elevated and the exercise limitation moderate to severe. Therefore a low threshold for echocardiographic screening should be proposed for patients with sarcoidosis.

Influence of Age on Outcome in Treatment of Pulmonary Arterial Hypertension

Background: The advent of specific oral therapies for pulmonary arterial hypertension has allowed for meaningful improvement in the outcome of this condition. There is limited long term follow up data with regard to the influence of age on outcome. Aims: We sought to review the long term outcome of treatment with specific PAH therapies (endothelin receptor antagonists and phosphodiesterase inhibitors) in a cohort of patients followed at a tertiary centre with particular focus on the influence of age on long term clinical outcome. Methods: We reviewed the clinical outcome data in a cohort of patients treated with PAH specific therapies at the John Hunter Hospital since 2004. We evaluated the influence of age on outcome in terms of serial change in 6min walk test distance (6MWT) and the need for hospitalisation, death and transplantation. Results: A total of 119 patients (88% female; mean age 65± 12 years) with a baseline 6min walk test distance of 304m have been treated since 2004 with 52% having PAH complicating connective tissue disease. Age was independently associated with a greater risk of need for hospitalisation, transplant or death. Furthermore, agewas associated with a greater rate of decline in 6MWT over time. Conclusions: In a large cohort of patients treated with PAH specific therapies, age independently predicted a greater rate of deterioration in 6MWT distance and a greater need for hospitalisation and transplantation as well as an increased risk of death. This likely reflects concomitant co-morbidity limiting response to treatment.

Inhibition of Apoptosis Signal-regulating Kinase 1 (ASK1) Attenuates Uremic Toxins’ Detrimental Effects on Cardiac and Renal Cells: Therapeutic Potential of ASK1 Inhibitors in Cardiorenal Syndrome

Background: The advent of specific oral therapies for pulmonary arterial hypertension has allowed for meaningful improvement in the outcome of this condition. There is limited long term follow up data with regard to the influence of age on outcome. Aims: We sought to review the long term outcome of treatment with specific PAH therapies (endothelin receptor antagonists and phosphodiesterase inhibitors) in a cohort of patients followed at a tertiary centre with particular focus on the influence of age on long term clinical outcome. Methods: We reviewed the clinical outcome data in a cohort of patients treated with PAH specific therapies at the John Hunter Hospital since 2004. We evaluated the influence of age on outcome in terms of serial change in 6min walk test distance (6MWT) and the need for hospitalisation, death and transplantation. Results: A total of 119 patients (88% female; mean age 65± 12 years) with a baseline 6min walk test distance of 304m have been treated since 2004 with 52% having PAH complicating connective tissue disease. Age was independently associated with a greater risk of need for hospitalisation, transplant or death. Furthermore, agewas associated with a greater rate of decline in 6MWT over time. Conclusions: In a large cohort of patients treated with PAH specific therapies, age independently predicted a greater rate of deterioration in 6MWT distance and a greater need for hospitalisation and transplantation as well as an increased risk of death. This likely reflects concomitant co-morbidity limiting response to treatment.

Determination of polycyclic aromatic hydrocarbons in urban street dust: Implications for human health

The determination of sixteen polycyclic aromatic hydrocarbons in urban street dust has been done. Samples were collected from 12 sampling locations in a city centre location (Newcastle upon Tyne, north east England) and extracted using in situ pressurised fluid extraction followed by gas chromatography mass spectrometry. From the results it was possible to identify three groups, with respect to PAH concentration, with PAH contents ranging between 0.6–2.3 mg kg −1, 15.6–22.5 mg kg −1 and 36.1–46.0 mg kg −1. The total PAH content of samples from these sampling sites has been compared to 22 urban locations around the world; comparable levels were found in these samples compared to the other cities around the world. The potential source of PAHs has been investigated by investigating the proportion of pyrogenic and petrogenic material in urban street dust using specific individual PAH ratios. The results indicate that the PAH content of urban street dust from the chosen sites are more likely to be due to pyrogenic sources i.e. vehicle exhaust emissions. The particle size fractions (<63 μm; 63–125 μm; 125–250 μm; 250–500 μm; 500–1000 μm; and 1000–2000 μm) of individual PAHs in three selected sampling sites was investigated. In two of the selected sites the PAH content was independent of particle size whereas in sampling site 10 elevated PAH levels are noted in the <63 μm size fraction. Sampling site 10 is located at the junction of three road tributaries which are used as major access points to the east of the city centre. Finally, the potential health risk for unintentional consumption of PAHs was assessed in terms of a mean daily intake (based on an ingestion rate of 100 mg d −1). It was found that all 4–6 membered ring PAHs had concentrations in excess of the mean daily intake thereby reflecting a potential health risk, particularly in the smallest size particle fractions.

Not too old to be closed….

Not too old to be closed….