What is this summary about? Inhaled corticosteroids (ICS) are a type of medication delivered via an inhaler device that are commonly used in the treatment of asthma. ICS can also be used to treat chronic obstructive pulmonary disease (COPD), a progressive respiratory condition in which the lungs become worse over time. However, unlike in asthma, ICS are only effective in a small proportion of people with COPD. ICS can cause significant side effects in people with COPD, including pneumonia. Because of this, guidelines written by COPD experts recommend that ICS should largely be prescribed to people with COPD whose symptoms flare up frequently and become difficult to manage (episodes known as exacerbations). Despite this guidance, records collected from routine clinical practice suggest that many healthcare professionals prescribe ICS to people with COPD who do not have frequent exacerbations, putting them at unnecessary risk of side effects. The over-prescription of ICS in COPD may partly be due to the recent introduction of single-inhaler combination therapies, which combine ICS with other medicines (bronchodilators). This ‘one inhaler for all’ approach is a concerning trend as it goes against global COPD treatment guidelines, which recommend ICS use in only a small proportion of people. This is a plain language summary of a review article originally published in the journal NPJ Primary Care Respiratory Medicine . In this review, we investigate the benefits and risks of ICS use in COPD. Using data from both randomized controlled trials (RCTs) and observational studies, we explain which people benefit from ICS use, and why health regulatory bodies have concluded that ICS do not help people with COPD to live longer. Lastly, we provide practical guidance for doctors and people with COPD regarding when ICS should be prescribed and when they should be withdrawn. Video abstract
The design resistance in shear of thin-walled I-sections has elicited numerous theories over the past decades. While there is a consensus on the post-buckling tension-field action that increases the ultimate resistance of thin webs in shear, the mechanism governing this tension-field action still remains debated. Presently, four constituent components for the shear resistance of I-sections are identified: (1) the resistance of the isolated web subject to a pure shear stress; (2) an increase in the web buckling stress due to flexural restraints provided by the flanges; (3) an increased web post-buckling resistance due to membrane restraint provided by the flanges; and (4) a direct contribution from the flanges to the shear resistance of the I-section. Each of these components is examined through parametric studies using finite element (FE) models analysed within Abaqus that are validated against published experimental results. A new design methodology for the resistance of I-sections in shear is presented, with closed-form expressions developed for each of the four component contributions. When compared with the current approach within EN 1993-1-5, the proposed formulae predict the shear resistance of the cross-section with greater accuracy and consistency.
Section:ChooseTop of pageAbstract <<INFLAMMATION IN COPDPROINFLAMMATORY CYTOKINEST-CELL CYTOKINESGROWTH FACTORSCHEMOKINESANTI-INFLAMMATORY CYTOKIN...THERAPEUTIC IMPLICATIONSFUTURE DIRECTIONSReferencesCITING ARTICLES
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Inflammation is known to be important for progression and disruption of atherosclerotic plaque1 as well as being a key determinant of the biological response by the arterial wall to stent placement.2 Macrophage-mediated cytokine and proteolytic activity are key drivers in both scenarios3,4 and therefore represent biologically plausible targets for therapy as well as for molecular imaging, which may significantly improve prediction of major adverse cardiovascular events arising from de novo atherosclerotic lesions or following stent placement. Furthermore, such modalities may be beneficial for the preclinical and clinical evaluation of the efficacy of local and systemic therapies aimed at reducing inflammation. Calfon Press et al. 5 have reported an interesting proof of concept study, which tests this paradigm. They aimed to evaluate whether everolimus eluting stent (EES) implantation reduced local inflammation compared with bare metal stenting in a rabbit model of atherosclerosis induced by balloon injury and cholesterol feeding. Stent placement was targeted to plaques using intra-vascular ultrasound (IVUS) guidance and paired angiographic landmarks. The investigators used in vivo through blood near infrared fluorescence (NIRF) imaging. In contrast to previous work by this group6 and others7 in which lipid-laden macrophages were imaged after administration of indocyanin green, in this study, imaging was performed after administration of the NIRF agent …
BACKGROUND: Regular inhaled beta 2 agonist therapy is associated with loss of bronchoprotection to indirect bronchial provocation challenges such as allergen or adenosine monophosphate (AMP), while directly acting challenge is less affected, implying preferential mast cell tolerance. Glucocorticosteroids may reverse such beta 2 adrenoreceptor tolerance and upregulate mast cell beta 2 adrenoceptor function. METHODS: The effect of single high dose glucocorticosteroids on terbutaline induced loss of bronchoprotection was studied in a placebo controlled, double blind, cross-over study. Fifteen asthmatic subjects who were not taking inhaled glucocorticosteroids underwent two 10-day treatment periods with terbutaline (500 micrograms four times daily via Turbohaler), each followed by a single dose of inhaled budesonide (800 micrograms via Turbohaler) or identical placebo. RESULTS: Regular treatment with terbutaline resulted in significant loss of bronchoprotection to AMP (mean difference (95% CI) -1.7 (-3.0 to 0.4) doubling dilutions) but not to methacholine (mean difference -0.1 (-1.0 to 0.8) doubling dilutions). Single high dose budesonide increased the protective effect of terbutaline more to AMP than to methacholine challenge (+0.76 (0.3) doubling dilutions compared with +0.13 (0.4) doubling dilutions, respectively). The mean (SE) difference between budesonide and placebo for methacholine challenge was 0.08 (0.14) whereas that for AMP was 0.075 (0.15); p = NS. The difference in PC20 was not statistically significant when compared with placebo for either challenge agent. CONCLUSIONS: Inhaled glucocorticosteroids in a single dose had no significant effect in restoring terbutaline induced loss of bronchoprotection, implying that mast cell beta 2 adrenoceptor sensitivity is not restored by a single dose of an inhaled glucocorticosteroid in asthma.
Advanced age plays an important role in the pathogenesis of atherosclerosis.Therefore, older individuals with coronary artery disease tend to have more complex lesions (e.g.left main coronary artery disease or multivessel disease) than younger individuals.However, many randomised trials have excluded elderly patients based on their age or associated comorbidities, making it unclear what the optimal treatment strategy is for elderly patients with complex coronary artery disease.A higher prevalence of concomitant diseases and increased frailty may make clinicians hesitate to opt for a high-risk invasive strategy, such as cardiac surgery, and instead select a less invasive treatment, because of the potentially higher risk of periprocedural complications.In this issue of the Netherlands Heart Journal, Gimbel et al. report that in their retrospective cohort of patients aged ≥75 years with multivessel disease or left main coronary artery disease, coronary artery bypass grafting (CABG) was associated with significantly lower risks of mortality, acute coronary syndrome, repeat revascularisation and recurrent angina than percutaneous coronary intervention (PCI) [1].In this trial, the completeness of revascularisation was not independently associated with the outcomes.However, the complete revascularisation rate was rel-
The mechanism of bradykinin-induced bronchoconstriction was studied in anesthetized guinea pigs after both i.v. administration and direct airway instillation. We monitored airway opening pressure as an index of airway caliber, and the provocative dose of bradykinin required to produce 100% increase in airway opening pressure (PD100) was determined. Animals were pretreated with propranolol (1 mg/kg i.v.) to inhibit adrenergic bronchodilatation. After i.v. administration, the bronchoconstrictor dose-response curve to bradykinin (PD100 = 0.93 nmol/kg) was shifted significantly to the right by atropine (PD100 = 2.34 nmol/kg, P less than .05) and indomethacin (PD100 = 61.7 nmol/kg, P less than .05). Depletion of tachykinins by capsaicin pretreatment had no significant effect on the response to i.v. bradykinin. After tracheal instillation, the bronchoconstrictor dose-response curve to bradykinin (PD100 = 24.5 nmol) was shifted to the right by atropine (PD100 greater than 150 nmol, P less than .05) and capsaicin pretreatment (PD100 greater than 150 nmol, P less than .05). After atropine the response to instilled bradykinin was almost abolished in capsaicin-pretreated animals. Indomethacin had no effect on the bronchoconstrictor response to instilled bradykinin. We conclude that i.v. bradykinin causes bronchoconstriction predominantly by the release of cyclooxygenase products but that a cholinergic reflex is also involved, whereas sensory neuropeptides are not important. By contrast the bronchoconstrictor response to instilled bradykinin is mediated by neural mechanisms involving both cholinergic nerves and sensory neuropeptides but not by cyclooxygenase products.
