Publications

Background The highest burden of chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries. Low-cost oral medications, if effective, could enable affordable, accessible COPD treatment. Methods In this randomised, three-arm, double-blind, double-dummy, placebo-controlled study conducted in 37 centres in China, symptomatic patients with moderate to very severe COPD were randomised 1:1:1 to placebo twice daily plus placebo once daily, low-dose theophylline 100 mg twice daily plus placebo once daily or low-dose theophylline 100 mg twice daily plus low-dose oral prednisone 5 mg once daily for 48 weeks. The primary end-point was annualised exacerbation rate. Results 1670 subjects were randomised and 1242 completed the study (1142 with acceptable data at week 48). Subjects (75.7% male) had a mean age of 64.4 years, with mean± sd baseline post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) 1.1±0.4 L (42.2% predicted) and St George's Respiratory Questionnaire (SGRQ) score 45.8±20.1. There were negligible differences between annualised exacerbation rates across the three treatments: 0.89 (95% CI 0.78–1.02) on theophylline plus prednisone, 0.86 (95% CI 0.75–0.99) on theophylline plus placebo and 1.00 (95% CI 0.87–1.14) on placebo. The rate ratio for theophylline plus prednisone versus pooled theophylline plus placebo and placebo was 0.96 (95% CI 0.83–1.12), for theophylline plus placebo versus placebo was 0.87 (95% CI 0.73–1.03; p=0.101) and for theophylline plus prednisone versus placebo was 0.90 (95% CI 0.76–1.06; p=0.201). Secondary outcomes of hospitalisations, FEV 1 , SGRQ and COPD Assessment Test score showed no statistically significant difference between treatment arms. Serious adverse events other than exacerbations were <2% and did not differ between treatment arms. Conclusions Low-dose theophylline alone or in combination with prednisone did not reduce exacerbation rates or clinically important secondary end-points compared with placebo.

Abstract Background Statins are lipid-lowering agents that also exhibit pleiotropic effects in decreasing oxidative stress and inflammation. There have been several published studies reporting the use of statins in the treatment of asthma patients, but their results are not consistent. The aim of this study is to determine whether statins are beneficial for asthma administration, and explore the potential covariables that may affect their clinical effectiveness. Methods A systematic literature search was performed in PubMed, Embase and Cochrane Center Register of Controlled Trials from inception to September 2012. Randomized controlled trials (RCT), retrospective studies and controlled clinical trials which reported the use of statins in the treatment of asthma patients were eligible. Quality evaluation was conducted for RCT using Jadad criteria. Results A total of 18 articles were included. In our study, we found no conclusive evidence to demonstrate that statins could enhance the lung function in asthmatics, although, they may reduce airway inflammation. Additionally, the results were not consistent across studies with respect to symptoms, quality of life, maintenance medication, asthma hospitalization/emergency department (ED) visits. Conclusions Statins may reduce airway inflammation in asthmatics, without having a significant effect on lung function. Further large sample and multicenter clinical trials are needed to confirm this and to see if there are more responsive phenotypes of asthma.

The availability of some supplementary cementitious materials, especially fly ash, is of imminent concern in Europe due to the projected closure of several coal-fired power generation plants. Pure kaolinitic clays, which arguably have the potential to replace fly ash, are also scarce and expensive due to their use in other industrial applications. This paper examines the potential utilisation of low-grade kaolinitic clays for construction purposes. The clay sample was heat-treated at a temperature of 800 °C and evenly blended with Portland cement in substitutions of 10–30% by weight. The physical, chemical, mineralogical and mechanical characteristics of the blended calcined clay cement were determined. The Frattini test proved the pozzolanic potential of the calcined impure clay, as a plot of its CaO and OH− was found below the lime solubility curve. The 28 days compressive strengths trailed the reference cement by 5.1%, 12.3% and 21.7%, respectively, at all replacement levels. The optimum replacement level between the three blends was found to be 20 wt.%.

Objectives The aim of this study was to evaluate the progression of atherosclerotic coronary plaques at bifurcations, using combined intravascular ultrasound–virtual histology (IVUS-VH) and optical coherence tomography (OCT). Background Pathological findings reveal that atherosclerotic plaques characterized by the presence of large necrotic cores (NCs) with fibrous cap thicknesses < 65 μm are more prone to rupture. Accuracy in the detection of high-risk plaques could be improved by the combined use of IVUS-VH and OCT. Methods IVUS-VH and OCT are 2 imaging modalities with different lateral resolutions and different depths of penetration. To provide a precise matching of the images, bifurcations were used as landmarks. IVUS-VH and OCT were performed in 56 bifurcations from 24 patients at baseline and at 6-month follow-up. All patients were treated with standard medical therapy. Bifurcations were studied at the proximal, in-bifurcation, and distal regions. Plaques were classified according to their composition as assessed by IVUS-VH and fibrous cap thickness as quantified by OCT. Results At baseline, 27 NC-rich plaques were found. At 6-month follow-up, 22 (81%) did not show any significant change. Four new NC-rich lesions developed. At both time points, percent NC was higher and the fibrous cap was thinner at the proximal bifurcation rim compared with the distal. There were no significant changes in percent NC and fibrous cap thickness in the 3 bifurcation regions between baseline and follow-up examinations. No major cardiovascular events due to bifurcation lesion progression were observed. Conclusions The combined use of IVUS-VH and OCT is a reliable tool to serially assess plaque progression and regression, and in the present study it was demonstrated to be safe and feasible. At 6-month follow-up, in this post–percutaneous coronary intervention patient population, most high-risk plaques remained unchanged, retaining their imaging classifications, nevertheless appearing to have remained clinically silent.

Coronary artery stenting is currently the most frequently performed percutaneous coronary intervention for the treatment of coronary artery disease. The endothelium is a single layer of endothelial cells lining the vascular wall and plays an integral part in maintaining vascular homeostasis. Stenting however causes significant injury to the vascular wall and endothelium, resulting in inflammation, repair and the development of neointimal hyperplasia. The ability of the endothelium to repair itself depends on both the migration of surrounding mature endothelial cells, and the attraction and adhesion of circulating endothelial progenitor cells (EPCs) to the injured region, which then differentiate into endothelial-like cells. Current therapies with drug-eluting stents interrupt the natural response to damage. Accelerating the reendothelialization of the damaged arterial segment following stent implantation is an attractive form of therapy as it is seen as hastening the natural process of repair. It potentially has the benefit of reducing the amount of neointimal hyperplasia and stent thrombosis. Studies have been performed to identify agents that augment the mobilisation and recruitment of EPCs to the injured area (statins, exercise, estrogen and cytokines). Other studies have looked at seeding stents with endothelial cells or EPCs. The most current approach is to coat anti-CD34 antibodies on a stent surface to attract circulating EPCs to the stent which then differentiate into endothelial-like cells. This approach is currently being tested in safety and feasibility clinical studies.

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No abstract is provided for this article.