Publications

Treatment of Chronic Obstructive Pulmonary Disease

Novel mechanisms and new therapies for chronic obstructive pulmonary disease

There is a pressing requirement to develop new therapies for chronic obstructive pulmonary disease (COPD), as current therapies fail to prevent disease progression or mortality and do not deal with the underlying inflammatory process. The mainstay of current drug therapy is long-acting bronchodilators, but no treatments suppress chronic inflammation in COPD, which is corticosteroid-resistant. With better understanding of the inflammatory and destructive process in the pathophysiology of COPD, several novel therapeutic targets have been identified, leading to the development of various mediator antagonists, novel broad-spectrum anti-inflammatory treatments and drugs that may reverse the molecular mechanisms of corticosteroid resistance.

Assessment of coronary atherosclerosis by IVUS and IVUS-based imaging modalities: progression and regression studies, tissue composition and beyond

Cardiovascular disease remains the leading cause of mortality, morbidity and disability in the developed world, predominantly affecting the adult population. In the early 1990s coronary heart disease (CHD) was established as affecting one in two men and one in three women by the age of forty. Despite the dramatic progress in the field of cardiovascular medicine in terms of diagnosis and treatment of heart disease, modest improvements have only been achieved when the reduction of cardiovascular mortality and morbidity indices are assessed. To better understand coronary atherosclerosis, new imaging modalities have been introduced. These novel imaging modalities have been used in two ways: (1) for the characterization of plaque types; (2) for the assessment of the progression and regression of tissue types. These two aspects will be discussed in this review.

Randomized trials of invasive cardiovascular interventions that include a placebo control: a systematic review and meta-analysis

Aims The difference in the benefit of invasive cardiovascular interventions compared with placebo controls has not been analysed systematically. Methods and results MEDLINE and Web of Science were searched through 29 March 2020. Randomized, placebo-controlled trials of invasive cardiovascular interventions (including catheter-based interventions and pacemaker-like devices) investigating predefined primary outcomes were included. Standardized mean differences (SMD) and odds ratios were calculated for continuous and dichotomous outcomes, respectively. Meta-regression analyses were performed to assess whether estimates of treatment effects were associated with methodological characteristics of trials. Thirty trials, including 4102 patients, were analysed. The overall risk of bias was judged to be low in only 43% of the trials. Ten trials (33%) demonstrated statistically significant superiority of invasive interventions over placebo controls for the respective predefined primary outcomes. In almost half of the 16 trials investigating continuous predefined primary outcomes, the SMD between the active and placebo procedure indicated a small (n = 4) to moderate (n = 3) treatment effect of active treatment over placebo. In contrast, one trial indicated a small treatment effect in favour of the placebo procedure. In the remaining trials, there was no relevant treatment effect of active treatment over placebo. In trials with a protocol-mandated stable and symmetrical use of co-interventions, the superiority of active procedures vs. invasive placebo procedures was significantly larger as compared with trials with frequent or unbalanced changes in co-interventions (P for interaction 0.027). Conclusions The additional treatment effect of invasive cardiovascular interventions compared with placebo controls was small in most trials.

Midterm performance of a novel restorative pulmonary valved conduit: preclinical results

Aims:The Xeltis bioabsorbable pulmonary valved conduit (XPV), designed to guide functional restoration of patients' own tissue, is potentially more durable than current pulmonary bioprosthetic valves/valved conduits.The aim of this study was to assess the haemodynamic performance of the novel XPV implanted in an ovine model. Methods and results:The XPV was surgically implanted in adult sheep under general anaesthesia and cardiopulmonary bypass (XPV group, n=20).Sheep that received a Hancock bioprosthetic pulmonary valved conduit served as a control group (HPV group, n=3).Transthoracic echocardiograms from VARC-2 recommended time points at 3, 6, 9, 12, 18 and 24 months (XPV group) and at 3 and 6 months (HPV group) after the procedure were analysed in an independent core laboratory.The primary endpoint was favourable valved conduit performance, defined as peak systolic pressure gradient <40 mmHg, no severe pulmonary regurgitation (PR), and a maximum conduit patency index of -20%.In the latter, negative values denote luminal narrowing and vice versa.The valvular peak systolic pressure gradient (mmHg) was 25.6±9.7 (3 months), 19.6±7.1 (6 months), 10.0±9.2 (24 months) in the XPV group and 18.4±6.6(3 months), 17.7±4.6(6 months) in the HPV group.The patency index (%) of the conduit at the valvular level was +30.3±13.6 (6 months) and +64.1±1.4 (24 months) in the XPV group and +2.0±15.9(6 months) in the HPV group.PR was trace or mild at all visits, except in one animal with persistent moderate PR in the XPV group, up to 24 months. Conclusions:The XPV showed a favourable and durable haemodynamic performance (up to two years after implantation), without conduit narrowing/obstruction or severe regurgitation.

C4 Drugs for the treatment of airway disease

Both asthma and chronic obstructive pulmonary disease (COPD) are characterized by airflow obstruction and chronic inflammation of the airways, but there are important differences in inflammatory mechanisms and response to therapy between these diseases [1, 2]. This chapter discusses the pharmacology of the drugs used in the treatment of obstructive airways diseases. These drugs include bronchodilators, which act mainly by reversing airway smooth muscle contraction and anti-inflammatory drugs, which in asthma suppress the inflammatory response in the airways. The most effective anti-inflammatory treatment for asthma is corticosteroids, which are covered in chapter C13. In COPD, no effective anti-inflammatory drugs are available, but several new classes of drug are now in development.

A randomized comparison of the magnetic navigation system versus conventional percutaneous coronary intervention

Objective : A randomized comparison of the magnetic navigation system (MNS) to conventional guidewire techniques in percutaneous coronary interventions. Background : The MNS precisely directs a magnetized guidewire in vivo through two permanent external magnets. Methods : A total of 111 consecutive patients were enrolled. Crossing success, crossing‐/fluoroscopy times, and contrast usage were directly compared. Lesions were classified according to the AHA/ACC criteria. Three tertiles of vessel/lesion complexity [low (&lt;5), medium (6–10) and high (&gt;10)] were defined using 3D reconstructions and angiographic information. Results : The crossing success for magnetic and the conventional wires were 93.3and 95.6%, respectively. Crossing and fluoroscopy times were longer with the magnetic wires (72.9 ± 50.3 sec vs. 58.1 ± 47.2 sec, P &lt; 0.001 and 66.2 ± 44.1 sec vs. 55.2 ± 44.4 sec, P = 0.03, respectively). In vessels with low and medium complexity the magnetic wires had significantly longer times ( P &lt; 0.001) but for those with high scores (&gt;10) a trend towards shorter times was observed. The MNS resulted in a small but significant reduction in contrast usage (2.3 ± 3.5 ml vs. 4.5 ± 4.4 ml, P &lt; 0.001). Moreover by superimposing a virtual roadmap of the vessel on the live fluoroscopy image 48% of the lesions were crossed without requiring contrast agents with the MNS. Conclusion : The MNS has comparable crossing success to conventional PCI. It is relatively slower but there is a trend to support a potential advantage in more complex vessels. By simultaneously employing a virtual roadmap there is a small but significant reduction in contrast usage. © 2008 Wiley‐Liss, Inc.

Single vessel dilatation in patients with unstable angina and multivessel disease

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary

Section:ChooseTop of pageAbstract <<IntroductionDefinition and Factors Th...Diagnosis and Initial Ass...Prevention and Maintenanc...Rehabilitation, Education...Supportive, Palliative, E...Other TreatmentsInterventional TherapyManagement of Stable COPDTreatment of Stable COPDMonitoring and Follow-upTreatment OptionsCOPD and ComorbiditiesReferencesCITING ARTICLES

Early invasive strategy should be performed within 72 hours in high-risk patients with non-ST-elevation myocardial infarction

Commentary on : Jobs A, Mehta SR, Montalescot G, et al . Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials. Lancet 2017;390:737–46. The mainstay of treatment for patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) is medical therapy, early coronary angiography and revascularisation. A routine invasive strategy has been shown to reduce all-cause death and myocardial infarction  compared with a conservative approach at 5 years.1 Therefore, an early invasive strategy with intent to perform revascularisation is advocated in the 2014 American and European guidelines with a class I recommendation.2 3 While immediate angiography is recommended for extremely high-risk patients (eg, haemodynamic or electrical instability, persistent angina, heart failure or worsening mitral regurgitation), the optimal timing for an invasive approach in patients …

Revisiting late loss and neointimal volumetric measurements in a drug‐eluting stent trial: Analysis from the SPIRIT FIRST trial

This study was conducted to reevaluate the significance of angiographic late loss and to assess the agreement between new proposed neointimal volumetric measurements derived from quantitative coronary angiography (QCA) and standard intravascular ultrasound (IVUS)-based parameters. Neointimal volumetric measurements may better estimate the magnitude of neointimal growth after stenting than late loss. In 56 in-stent segments (27, everolimus; 29, bare metal) in the SPIRIT FIRST study, we compared QCA measures with the corresponding IVUS parameters. Two IVUS-late loss models were derived from minimal luminal diameter (MLD) using either a circular model or a so-called projected MLD. QCA-neointimal volume was calculated as follows: stent volume (mean area of the stented segment x stent length) at post procedure - lumen volume (mean area of the stented segment x stent length) at follow-up (the stent length either from nominal stent length or the length measured by QCA). Videodensitometric neointimal volume was also evaluated. Each of the three neointimal volume and percentage volume obstruction by QCA showed significant correlation with the corresponding IVUS parameters (r = 0.557-0.594, P < 0.0001), albeit with a broad range of limits of agreement. Late loss and volumetric measurements by QCA had a broader range of standard deviation than those by IVUS. QCA-volumetric measurements successfully confirmed the efficacy of everolimus-eluting stents over bare metal stents (P < 0.05). Our proposed QCA volumetric measurements may be a practical surrogate for IVUS measurements and a discriminant methodological approach for assessment of treatment effects of drug-eluting stents.

A role for M2 and M3 muscarinic receptors in the contraction of rat and human small airways

TCT-33 Mortality After Repeat Revascularization Following PCI or CABG for Left Main Coronary Artery Disease: The EXCEL Trial

No abstract is provided for this article.

Expression and Release of Interleukin-8 by Human Airway Smooth Muscle Cells: Inhibition by Th-2 Cytokines and Corticosteroids

Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES

Heme Oxygenase 1 Determines Atherosclerotic Lesion Progression Into a Vulnerable Plaque

The molecular regulation for the transition from stable to vulnerable plaque remains to be elucidated. Heme oxygenase 1 (HO-1) and its metabolites have been implicated in the cytoprotective defense against oxidative injury in atherogenesis. In this study, we sought to assess the role of HO-1 in the progression toward plaque instability in carotid artery disease in patients and in a murine model of vulnerable plaque development.Atherectomy biopsy from 112 patients with clinical carotid artery disease was collected and stratified according to characteristics of plaque vulnerability. HO-1 expression correlated closely with features of vulnerable human atheromatous plaque (P<0.005), including macrophage and lipid accumulation, and was inversely correlated with intraplaque vascular smooth muscle cells and collagen deposition. HO-1 expression levels correlated with the plaque destabilizing factors matrix metalloproteinase-9, interleukin-8, and interleukin-6. Likewise, in a vulnerable plaque model using apolipoprotein E(-/-) mice, HO-1 expression was upregulated in vulnerable versus stable lesions. HO-1 induction by cobalt protoporphyrin impeded lesion progression into vulnerable plaques, indicated by a reduction in necrotic core size and intraplaque lipid accumulation, whereas cap thickness and vascular smooth muscle cells were increased. In contrast, inhibition of HO-1 by zinc protoporphyrin augmented plaque vulnerability. Plaque stabilizing was prominent after adenoviral transduction of HO-1 compared with sham virus-treated animals, providing proof that the observed effects on plaque vulnerability were HO-1 specific.Here we demonstrate in a well-defined patient group and a murine vulnerable plaque model that HO-1 induction reverses plaque progression from a vulnerable plaque to a more stable phenotype as part of a compensatory atheroprotective response.

VizieR Online Data Catalog: First results from Mopra HCO + maps (Barnes+)

Differential expression of IL‐10 receptor by epithelial cells and alveolar macrophages

Background: Interleukin (IL)‐10 is a pleiotropic cytokine with a broad spectrum of immunosuppressive and anti‐inflammatory effects. IL‐10 secretion from alveolar macrophages is defective in patients with asthma and lower concentrations of IL‐10 are found in bronchoalveolar lavage (BAL) from asthmatic patients than in normal control subjects. Reduced IL‐10 may result in exaggerated and more prolonged inflammatory responses in asthmatic airways. IL‐10 acting through the IL‐10 receptor (IL‐10R) stimulates the transcription factors STAT1 and STAT3. Methods: We investigated IL‐10 and IL‐10R expression in normal and asthmatic bronchial epithelium and BAL macrophages using reverse transcription‐polymerase chain reaction, immunohistochemistry and Western blotting. The functional effect of IL‐10 was examined using granulocyte–macrophage‐colony stimulating factor, enzyme‐linked immunosorbent assay and Western blotting for phosphorylated STAT1 and STAT3. Results: IL‐10 was not expressed in epithelial cells; furthermore these cells did not express the IL‐10R and had no functional response to exogenous IL‐10. Bronchial epithelial cells expressed variable levels of phosphorylated STAT1 and STAT3 with no change in expression between normal subjects and asthmatics. IL‐10 protein and IL‐10R expression was detected in alveolar macrophages from all subjects. Conclusion: Our study suggests that the bronchial epithelium is not a source of IL‐10 and cannot respond to exogenous IL‐10 because of a lack of IL‐10R expression.

TCT-752 Transcatheter Aortic Valve Replacement in Europe: The 2013 Update

No abstract is provided for this article.