Patients with previously untreated pulmonary arterial hypertension who were randomly assigned to combination therapy with ambrisentan and tadalafil had a significantly lower risk of a composite ...clinical failure outcome at 20 months than did the pooled monotherapy group.
Regardless of the initiating trigger, pulmonary arterial hypertension results in the altered synthesis of a variety of vasoactive substances derived from the endothelium.
1
Current therapies for pulmonary arterial hypertension
2
target abnormalities in one of three intracellular pathways with signaling dysfunction: the prostacyclin, nitric oxide, or endothelin pathway.
1
However, no single class of drug is consistently effective in treating all patients, which suggests that no single pathway plays a dominant pathogenic role.
3
,
4
Combination therapy with agents that target several different pathways may potentially increase the overall therapeutic effect on the mechanisms of this disease
5
and provide additional clinical benefits.
6
– . . .
Few data are available in regards to the prevalence of pulmonary hypertension (PH) in the broad spectrum of COPD. This study was aimed at assessing the prevalence of PH in a cohort of COPD patients ...across the severity of airflow limitation, and reporting the hemodynamic characteristics at rest and during exercise.
We performed a retrospective analysis on COPD patients who underwent right-heart catheterization in our center with measurements obtained at rest (n=139) and during exercise (n=85). PH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg and pulmonary capillary wedge pressure <15 mmHg. Exercise-induced PH (EIPH) was defined by a ratio of ΔmPAP/Δcardiac output >3.
PH was present in 25 patients (18%). According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, PH prevalence in GOLD 2 was 7% (3 patients); 25% (14 patients) in GOLD 3; and 22% (8 patients) in GOLD 4. Severe PH (mPAP ≥35 mmHg) was identified in four patients (2.8%). Arterial partial oxygen pressure was the outcome most strongly associated with PH (r=-0.29, P<0.001). EIPH was observed in 60 patients (71%) and had a similar prevalence in both GOLD 2 and 3, and was present in all GOLD 4 patients. Patients with PH had lower cardiac index during exercise than patients without PH (5.0±1.2 versus 6.7±1.4 L/min/m(2), respectively; P=0.001).
PH has a similar prevalence in COPD patients with severe and very-severe airflow limitation, being associated with the presence of arterial hypoxemia. In contrast, EIPH is highly prevalent, even in moderate COPD, and might contribute to limiting exercise tolerance.
BackgroundRecent progress in pulmonary arterial hypertension (PAH) research has made possible the expansion of treatment options improving the prognosis of patients. Due to multimorbidity and ...increasing age, patients are much more likely to be exposed to polypharmacy. As a result, there is an increased risk of drug–drug interactions affecting efficacy as well as the toxicity of the treatment. In 2012, the pulmonary hypertension unit of our hospital was designated as a reference unit by regional health authorities.PurposeTo identify potential drug–drug interactions (PDDIs) between oral drugs (OD) for PAH and medications used to treat concomitant illnesses.Material and methodsA cross sectional study was conducted in April 2016 in a tertiary hospital. All outpatients on OD for PAH with their chronic medication recorded in the regional electronic database were included. We collected demographic data, concomitant pharmacotherapy and PAH treatment. PDDIs were identified using the local Guide of Interactions in Pulmonary Hypertension.Results174 patients (224 OD) were included: 63.8% women, mean age 59 years (range 18–91). Most of the OD prescribed were bosentan and sildenafil (both 29%) followed by tadalafil (15.2%), ambrisentan (13.8%), riociguat (8.5%) and macitentan (4.5%). Approximately 30% of the patients received combined oral therapy. Median number of drugs per patient was 9 (range 2–19) and 83.9% were polymedicated (≥ 5 drugs). We identified a total of 237 PDDIs (67% of patients had at least one and over 30% more than two): 83% were moderate and 16% contraindicated according to their possible clinical relevance; 62% were pharmacokinetic and 38% pharmacodynamic; 70% affected the co-medication, 27% the OD and 3% both; 68% resulted in an increase in toxicity, 29% in decreased of efficacy and 3% both. The main contraindicated PDDIs were: beta-blockers with bosentan (n=10) and sildenafil (n=8), and bosentan with immunosuppressants (n=7). Polymedicated patients were more likely to have PDDIs (p<0.05).ConclusionPDDIs represent a significant issue among patients with PAH. Evaluation of these PDDIs could result in the establishment of a better treatment plan for these patients. However, more prospective studies are required to investigate the clinical relevance of PDDIs and their influence on therapeutic outcomes.References and/or acknowledgementsCiraci R, et al. Pulm Pharmacol Ther2014;28:1–8.No conflict of interest
Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of ...PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pulmonary vascular abnormalities are a characteristic feature of chronic obstructive pulmonary disease (COPD). Cigarette smoking is the most important risk factor for COPD. It is believed that its ...constant exposure triggers endothelial cell damage and vascular remodelling. Under pathological conditions, progenitor cells (PCs) are mobilized from the bone marrow and recruited to sites of vascular injury. The aim of the study was to investigate whether in COPD the number of circulating PCs is related to the presence of bone marrow-derived cells in pulmonary arteries and the association of these phenomena to both systemic and pulmonary endothelial dysfunction.
Thirty-nine subjects, 25 with COPD, undergoing pulmonary resection because of a localized carcinoma, were included. The number of circulating PCs was assessed by flow cytometry using a triple combination of antibodies against CD45, CD133 and CD34. Infiltrating CD45
cells were identified by immunohistochemistry in pulmonary arteries. Endothelial function in systemic and pulmonary arteries was measured by flow-mediated dilation and adenosine diphosphate-induced vasodilation, respectively.
COPD patients had reduced numbers of circulating PCs (p < 0.05) and increased numbers of CD45
cells (< 0.05) in the pulmonary arterial wall than non-COPD subjects, being both findings inversely correlated (r = - 0.35, p < 0.05). In pulmonary arteries, the number of CD45
cells correlated with the severity of vascular remodelling (r = 0.4, p = 0.01) and the endothelium-dependent vasodilation (r = - 0.3, p = 0.05). Systemic endothelial function was unrelated to the number of circulating PCs and changes in pulmonary vessels.
In COPD, the decrease of circulating PCs is associated with their recruitment in pulmonary arteries, which in turn is associated with endothelial dysfunction and vessel remodelling, suggesting a mechanistic link between these phenomena. Our findings are consistent with the notion of an imbalance between endothelial damage and repair capacity in the pathogenesis of pulmonary vascular abnormalities in COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Global Influenza Hospital Surveillance Network (GIHSN) aims to determine the burden of severe influenza disease and Influenza Vaccine Effectiveness (IVE). This is a prospective, active ...surveillance and hospital-based epidemiological study to collect epidemiological data in the GIHSN. In the 2016-2017 influenza season, 15 sites in 14 countries participated in the GIHSN, although the analyses could not be performed in 2 sites. A common core protocol was used in order to make results comparable. Here we present the results of the GIHSN 2016-2017 influenza season.
A RT-PCR test was performed to all patients that accomplished the requirements detailed on a common core protocol. Patients admitted were included in the study after signing the informed consent, if they were residents, not institutionalised, not discharged in the previous 30 days from other hospitalisation with symptoms onset within the 7 days prior to admission. Patients 5 years old or more must also complied the Influenza-Like Illness definition. A test negative-design was implemented to perform IVE analysis. IVE was estimated using a logistic regression model, with the formula IVE = (1-aOR) × 100, where aOR is the adjusted Odds Ratio comparing cases and controls.
Among 21,967 screened patients, 10,140 (46.16%) were included, as they accomplished the inclusion criteria, and tested, and therefore 11,827 (53.84%) patients were excluded. Around 60% of all patients included with laboratory results were recruited at 3 sites. The predominant strain was A(H3N2), detected in 63.6% of the cases (1840 patients), followed by B/Victoria, in 21.3% of the cases (618 patients). There were 2895 influenza positive patients (28.6% of the included patients). A(H1N1)pdm09 strain was mainly found in Mexico. IVE could only be performed in 6 sites separately. Overall IVE was 27.24 (95% CI 15.62-37.27. Vaccination seemed to confer better protection against influenza B and in people 2-4 years, or 85 years old or older. The aOR for hospitalized and testing positive for influenza was 3.02 (95% CI 1.59-5.76) comparing pregnant with non-pregnant women.
Vaccination prevented around 1 in 4 hospitalisations with influenza. Sparse numbers didn't allow estimating IVE in all sites separately. Pregnancy was found a risk factor for influenza, having 3 times more risk of being admitted with influenza for pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal ...homocysteine levels to cortical degeneration in PD remains elusive.
To characterize the cortical structural correlates of homocysteine levels in PD.
From the COPPADIS cohort, we identified a subset of PD patients and healthy controls (HC) with available homocysteine and imaging data. Surface-based vertex-wise multiple regression analyses were performed to investigate the cortical macrostructural (cortical thinning) and microstructural (increased intracortical diffusivity) correlates of homocysteine levels in this sample.
A total of 137 PD patients and 43 HC were included. Homocysteine levels were increased in the PD group (t = −2.2, p = 0.03), correlating in turn with cognitive performance (r = −0.2, p = 0.03). Homocysteine in PD was also associated with frontal cortical thinning and, in a subset of patients with available DTI data, with microstructural damage in frontal and posterior-cortical regions (p < 0.05 Monte-Carlo corrected).
Homocysteine in PD appears to be associated with cognitive performance and structural damage in the cerebral cortex. These findings not only reinforce the presence and importance of cortical degeneration in PD, but also suggest that homocysteine plays a role among the multiple pathological processes thought to be involved in its development.
•Parkinson's disease (PD) patients appear to show increased homocysteine levels.•Homocysteine correlated in turn with cognitive performance in our PD sample.•Homocysteine was also associated with cortical macro- and microstructural alterations.•This metabolic marker may play a role in cortical degeneration in the PD population.
Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not ...improved as much as the increase in hemoglobin concentration (Hb) would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to Hb. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO (Hb = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in Hb, peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in Hb produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of Hb, O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.
PDF
