COPD is associated with chronic inflammation affecting predominantly lung parenchyma and peripheral airways, which results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increasing numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly Tc1, Th1, and Th17 cells), and innate lymphoid cells (ILC) that are recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines chemokines, growth factors, and lipid mediators. Although most COPD patients have a predominantly neutrophilic inflammation, some have an increase in eosinophils, which may be orchestrated by Th2 and ILC2 cells through the release of IL-33 from epithelial cells. These patients may be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD inflammation, even in ex-smokers, and may result in activation of the proinflammatory transcription factor NF-κB, impaired antiprotease defenses, DNA damage, cellular senescence, generation of autoantibodies, and corticosteroid resistance through inactivation of histone deacetylase-2. Systemic inflammation is also found in COPD patients and may worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in COPD lungs may also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients that show optimal responses to more specific therapies and the development of biomarkers that identify the therapeutic phenotypes will be important.
Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer amongst smokers. Cigarette smoke induces the release of many inflammatory mediators and growth factors including TGF-β, EGFR, IL-1, IL-8 and G-CSF through oxidative stress pathways and this inflammation may persist for decades after smoking cessation. Mucus production is also increased by these inflammatory mediators, further linking airway inflammation to an important mechanism of lung cancer. A greater understanding of the molecular and cellular pathobiology that distinguishes smokers with lung cancer from smokers with and without COPD is needed to unravel the complex molecular interactions between COPD and lung cancer. By understanding the common signalling pathways involved in COPD and lung cancer the hope is that treatments will be developed that not only treat the underlying disease process in COPD, but also reduce the currently high risk of developing lung cancer in these patients.
Intracoronary papaverine is used as a means to induce a strong and short‐lasting hyperemia in several recently developed methods to measure coronary flow reserve. Changes in stenosis geometry from papaverine would influence the measured coronary flow reserve. Therefore, we investigated the influence of intracoronary papaverine on stenosis geometry with quantitative analysis of the coronary angiogram and assessed the influence of papaverine on pressure‐flow characteristics of the stenosis and coronary flow reserve. The cross‐sectional areas (mean ± SD) of the stenosis increased 18% ± 7% after papaverine. The normal proximal and distal parts of the coronary artery dilated 5% ± 2% after papaverine. This results in a decrease of the calculated pressure drop over the stenosis varying from 20% to 30%. Coronary flow reserve of a flowlimiting epicardial stenosis is overestimated by 16% when papaverine is used to induce hyperemia. These papaverine‐induced changes can nevertheless be circumvented by maximal vasodilation of the major epicardial coronary artery with 3 mg intracoronary isosorbidedinitrate prior to the investigation of the coronary flow reserve with papaverine.
Both high-strength steel and high-strength concrete are gaining increasing use in the construction industry. At the same time, the benefits of composite construction are also being increasingly recognized and exploited. In the present study, high-strength steel and high-strength concrete are considered in combination in high-strength concrete-filled high-strength steel tubular (HSCFST) members, with a focus on their behaviour under transverse impact loading, resistance to which is important for resilient infrastructure. Tests on thirteen HSCFST specimens and six reference CFST specimens under drop weight impact loading are presented. Hot-finished high-strength S890 steel sections were employed for the outer tubes of the HSCFST specimens, while hot-finished S355 steel tubes were used for the reference CFST specimens. Two core concrete strengths of approximately 60 MPa and 100 MPa were considered. The instantaneous impact force and deformation histories of the specimens were recorded at high frequencies throughout the impact process. A single-degree-of-freedom (SDOF) model was developed and used to facilitate the analysis of the experimental results. The dynamic moment capacities of the test specimens were obtained using the developed SDOF model and a dynamic increase factor (Rd) was introduced to quantify the enhancement in moment capacity relative to the static values. The influence of the test parameters on the dynamic increase factors was then analysed. The test results indicated that Rd is positively correlated with the impact velocity and negatively correlated with the steel grade, steel ratio and specimen length, while being insensitive to the concrete strength.
Introduction: It is well recognized that a lesion that does not cause a hemodynamically significant stenosis can trigger a sudden cardiac event through plaque rupture. As a diagnostic tool, intravascular imaging was developed to circumvent limitations of coronary angiography; however, none of the intravascular imaging devices are individually able to provide complete assessment of the plaque morphology, geometry, physiology and biology. Therefore, over the past few years an effort was made to develop hybrid intravascular imaging catheters to provide more complete evaluation of coronary plaque pathobiology.Areas covered: This paper aims to give an overview of the recent developments on 1) single-modality intravascular imaging devices; 2) hybrid intravascular imaging devices and 3) the hemodynamic analysis in models reconstructed from the fusion of intravascular imaging and angiographic data.Expert commentary: Within five years, most of the hybrid imaging techniques which are now in pre-clinical phase will be utilized in the clinical arena, as NIRS-IVUS. Software for online blood simulation is likely to be developed that will enable ESS calculation while the patient is in the catheterization laboratory.
