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Find video protocols related to scientific articles indexed in Pubmed.
NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma.
Expert Opin Drug Deliv
PUBLISHED: 06-12-2014
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Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease.
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New inhaler devices - the good, the bad and the ugly.
Respiration
PUBLISHED: 05-27-2014
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Drug delivery to the lungs is an effective way of targeting inhaled therapeutic aerosols and treating obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In the past 10 years, several new drugs for the management of asthma and COPD have been marketed and more are under development. These new therapeutic respiratory drugs have been furthered by innovations in all categories of pulmonary drug delivery systems to ensure optimal aerosolisation performance, consistency in efficacy and satisfactory patient adherence. In this review, we discuss the technological advances and innovations in recent inhaler devices and the evolving roles of pressurised metered-dose inhalers, dry powder inhalers and nebulisers, as well as their impact on patient adherence to treatment.
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Small airways dysfunction in asthma: evaluation and management to improve asthma control.
Allergy Asthma Immunol Res
PUBLISHED: 02-25-2014
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The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored.
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Current evidence and future research needs for FeNO measurement in respiratory diseases.
Respir Med
PUBLISHED: 01-12-2014
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Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.
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Importin-7 mediates glucocorticoid receptor nuclear import and is impaired by oxidative stress, leading to glucocorticoid insensitivity.
FASEB J.
PUBLISHED: 08-09-2013
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Some patients with severe inflammatory disease fail to respond to glucocorticoids, and oxidative stress contributes to this insensitivity. Importin receptors are associated with nuclear translocation of the glucocorticoid receptor (GR), which is essential for glucocorticoid function. We hypothesized that importin-7 is central to GR nuclear translocation and glucocorticoid sensitivity. We investigated the effects of importin-7 siRNA on fluticasone propionate (FP)-induced GR nuclear localization and suppression of IL-1?-induced CXCL8 and the effects of hydrogen peroxide (H2O2) plus IL-1? costimulation on importin-7 expression, function, and glucocorticoid responsiveness in a human macrophagecell line (U937). H2O2 significantly reduced FP-induced GR nuclear localization (3.4±0.51- vs. 5.7±0.85-fold increase, P<0.05) and suppression of IL-1?-induced CXCL8 (62.3±2.3 vs. 85.1±7.0%, P<0.05). Knockdown of importin-7 by 38.4 ± 11.5% (compared with control siRNA) significantly reduced FP-mediated GR nuclear localization (3.5±0.5- vs. 5.7±0.85-fold increase, P<0.05) and suppression of IL-1?-induced CXCL8 expression (40.2±16.1 vs. 68.4±3.0%, P<0.05). H2O2 plus IL-1? had no direct effect on importin-7 but caused a significant loss (61.2±12.6% compared with baseline) of nuclear RanGTP, an essential cofactor for importin-7-mediated nuclear import of cargo proteins. The importin-7 complex is essential for glucocorticoid function, and the expression of its cofactor RanGTP is reduced during oxidative stress-induced glucocorticoid insensitivity.
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Inhaled long-acting ?2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD.
J. Allergy Clin. Immunol.
PUBLISHED: 03-28-2013
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Combination inhaled therapy with long-acting ?2 agonists (LABAs) and corticosteroids is beneficial in treating asthma and chronic obstructive pulmonary disease (COPD).
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Standardised exhaled breath collection for the measurement of exhaled volatile organic compounds by proton transfer reaction mass spectrometry.
BMC Pulm Med
PUBLISHED: 01-28-2013
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Exhaled breath volatile organic compound (VOC) analysis for airway disease monitoring is promising. However, contrary to nitric oxide the method for exhaled breath collection has not yet been standardized and the effects of expiratory flow and breath-hold have not been sufficiently studied. These manoeuvres may also reveal the origin of exhaled compounds.
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Assessing and treating small airways disease in asthma and chronic obstructive pulmonary disease.
Ann. Med.
PUBLISHED: 06-17-2011
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Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory disorders of the respiratory tract that are characterized by airflow limitation. They are distinct conditions with different causes, structural changes, and immunopathology. The pathophysiology in asthma and COPD involves not only the proximal large airways, but also the distal small airways, and thus the small airways are an important therapeutic target in the treatment of both diseases. The assessment of diseased distal small airways is challenging. Extensive disease can be present in the small airways with little abnormality in conventional pulmonary function tests. Recent advances in imaging technologies have led to better spatial resolution to assess small airways morphology non-invasively. New physiological tests have been developed to detect disease and response to therapy in regional airways. Improving the efficiency of existing aerosolized therapy to direct drug to the appropriate lung regions may improve clinical efficacy. Approaches to target distal lung regions include developing new drug formulations with smaller aerosol particle size or using inhaler devices that emit aerosolized drug at slow inhalation flows. Large studies are needed to determine whether better distal lung deposition leads to improvements in small airways function that are translated into clinically significant patient outcomes.
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Comparing lung regions of interest in gamma scintigraphy for assessing inhaled therapeutic aerosol deposition.
J Aerosol Med Pulm Drug Deliv
PUBLISHED: 03-31-2011
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Two-dimensional gamma scintigraphy is an important technique used to evaluate the lung deposition from inhaled therapeutic aerosols. Images are divided into regions of interest and deposition indices are derived to quantify aerosol distribution within the intrapulmonary airways. In this article, we compared the different approaches that have been historically used between different laboratories for geometrically defining lung regions of interest. We evaluated the effect of these different approaches on the derived indices classically used to assess inhaled aerosol deposition in the lungs. Our primary intention was to assess the ability of different regional lung templates to discriminate between central and peripheral airway deposition patterns generated by inhaling aerosols of different particle sizes.
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Inhaled corticosteroid/long-acting ??-agonist combination therapy for asthma: attitudes of specialists in Europe.
Int. Arch. Allergy Immunol.
PUBLISHED: 01-14-2011
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As new combinations of inhaled corticosteroids (ICSs) and long-acting ?(2)-agonists (LABAs) become available for the treatment of asthma, it will be important to determine criteria against which they can be evaluated. The aim of this study was to assess which attributes of combination therapy physicians consider most important.
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Clinical posters discussion: summary.
Pulm Pharmacol Ther
PUBLISHED: 08-24-2010
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At the Sixth International Cough Symposium, eleven clinical posters were presented at the podium in a formal symposium session. Here we summarize the posters and the discussions.
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Predicting the clinical effect of a short acting bronchodilator in individual patients using artificial neural networks.
Eur J Pharm Sci
PUBLISHED: 06-16-2010
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Artificial neural networks were used in this study to model the relationships between in vitro data, subject characteristics and in vivo outcomes from N=18 mild-moderate asthmatics receiving monodisperse salbutamol sulphate aerosols of 1.5, 3 and 6 ?m mass median aerodynamic diameter in a cumulative dosing schedule of 10, 20, 40 and 100 ?g. Input variables to the model were aerodynamic particle size (APS), body surface area (BSA), age, pre-treatment forced expiratory volume in one-second (FEV(1)), forced vital capacity, cumulative emitted drug dose and bronchodilator reversibility to a standard salbutamol sulphate 200 ?g dose MDI (REV(%)). These factors were used by the model to predict the bronchodilator response at 10 (T10) and 20 (T20) min after receiving each of the 4 doses for each of the 3 different particle sizes. Predictability was assessed using data from selected patients in this study, which were set aside and not used in model generation. Models reliably predicted ?FEV(1)(%) in individual subjects with non-linear determinants (R(2)) of ? 0.8. The average error between predicted and observed ?FEV(1)(%) for individual subjects was <4% across the cumulative dosing regimen. Increases in APS and drug dose gave improved ?FEV(1)(%). Models also showed trends towards improved responses in younger patients and those having greater REV(%), whilst BSA was also shown to influence clinical effect. These data show that APS can be used to discriminate predictably between aerosols giving different bronchodilator responses across a cumulative dosing schedule, whilst patient characteristics can be used to reliably estimate clinical response in individual subjects.
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Comparison of inspiratory and expiratory resistance and reactance in patients with asthma and chronic obstructive pulmonary disease.
Thorax
PUBLISHED: 03-26-2010
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The usual analysis of forced oscillometry measures respiratory resistance (Rrs) and reactance (Xrs) averaged over several tidal breaths (whole-breath analysis). Recent within-breath analyses have separated Rrs and Xrs into their mean inspiratory and mean expiratory components (inspiratory-expiratory breath analysis) but these have not been used to compare patients with asthma and those with chronic obstructive pulmonary disease (COPD). Large inspiratory-expiratory variations in Xrs at 5 Hz (DeltaX5) in an individual have been used as a surrogate marker of expiratory flow limitation.
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Suppression of GATA-3 nuclear import and phosphorylation: a novel mechanism of corticosteroid action in allergic disease.
PLoS Med.
PUBLISHED: 04-02-2009
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GATA-3 plays a critical role in regulating the expression of the cytokines interleukin (IL)-4, IL-5, and IL-13 from T helper-2 (Th2) cells and therefore is a key mediator of allergic diseases. Corticosteroids are highly effective in suppressing allergic inflammation, but their effects on GATA-3 are unknown. We investigated the effect of the corticosteroid fluticasone propionate on GATA-3 regulation in human T-lymphocytes in vitro and in vivo.
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The importance of imaging and physiology measurements in assessing the delivery of peripherally targeted aerosolized drugs.
Ther Deliv
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Considerable recent effort has been directed towards developing new aerosol formulations and delivery devices that can target drugs to the lung periphery. In order to determine the efficacy of targeted drug therapy, it is essential that the peripheral lung region be adequately assessed. Imaging of the airways structure and pathology has greatly advanced in the last decade and this rate of growth is accelerating as new technologies become available. Lung imaging continues to play an important role in the study of the peripheral airways and, when combined with state-of-the-art lung function measurements and computational modeling, can be a powerful tool for investigating the effects of inhaled medication. This article focuses on recent strategies in imaging and physiological measurements of the lungs that allow the assessment of inhaled medication delivered to the periphery and discusses how these methods may help to further optimize and refine future aerosol delivery technology.
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Standardization of techniques for using planar (2D) imaging for aerosol deposition assessment of orally inhaled products.
J Aerosol Med Pulm Drug Deliv
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Two-dimensional (2D or planar) imaging with (99m)Tc radiolabels enables quantification of whole-lung and regional lung depositions for orally inhaled drug products. This article recommends standardized methodology for 2D imaging studies. Simultaneous anterior and posterior imaging with a dual-headed gamma camera is preferred, but imaging with a single-headed gamma camera is also acceptable. Correction of raw data for the effects of gamma ray attenuation is considered essential for accurate quantification, for instance, using transmission scanning with a flood-field source of (99m)Tc or (57)Co. Evidence should be provided of the accuracy of the quantification method, for instance, by determining "mass balance." Lung deposition may be expressed as a percentage of ex-valve or ex-device dose, but should also be given as mass of drug when possible. Assessment of regional lung deposition requires delineation of the lung borders, using X-ray computed tomography, radioactive gas scans ((133)Xe or (81m)Kr), or transmission scans. When quantifying regional lung deposition, the lung should be divided into outer (O) and inner (I) zones. A penetration index should be calculated, as the O/I ratio for aerosol, normalized to that for a radioactive gas or transmission scan. A variety of methods can be used to assess lung deposition and distribution. Methodology and results should be documented in detail, so that data from different centers may be compared. The use of appropriate methodology will provide greater confidence in the results of 2D imaging studies, and should allay concerns that such studies are qualitative or semiquantitative in nature.
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Treating the small airways.
Respiration
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The final article in this series evaluates the approaches undertaken to treating the small-airway region of the lungs and the clinical implications of inhaled therapy targeting the periphery in patients with asthma and chronic obstructive pulmonary disease.
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Small airways, big challenge: measuring the unseen?
Nat. Med.
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An imaging technique adapted to differentiate between chronic obstructive pulmonary disease phenotypes can identify small-airway pathophysiology, locate the disease and potentially track disease progression. This approach may be used as a biomarker to identify the small-airway lesion in chronic obstructive pulmonary disease, at an individual level in the clinic (pages 1711-1715).
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Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma.
PLoS ONE
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Severe asthma accounts for a small number of asthmatics but represents a disproportionate cost to health care systems. The underlying mechanism in severe asthma remains unknown but several mechanisms are likely to be involved because of a very heterogeneous profile. We investigated the effects of a p38MAPK inhibitor in corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from severe asthmatics and the profile of its responders.
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Corticosteroid resistance and novel anti-inflammatory therapies in chronic obstructive pulmonary disease: current evidence and future direction.
Drugs
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Corticosteroids are widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, in contrast to their use in mild-to-moderate asthma, they are much less effective in enhancing lung function and have little or no effect on controlling the underlying chronic inflammation. In most clinical trials in COPD patients, corticosteroids have shown little benefit as monotherapy, but have shown a greater clinical effect in combination with long-acting bronchodilators. Several mechanisms of corticosteroid resistance have been postulated, including a reduction in histone deacetylase (HDAC)-2 activity and expression, impaired corticosteroid activation of the glucocorticoid receptor (GR) and increased pro-inflammatory signalling pathways. Reversal of corticosteroid resistance in COPD patients by restoring HDAC2 levels has proved effective in a small study, and long-term studies are needed to determine whether novel HDAC2 activators or theophylline improve disease progression, exacerbations or mortality. Advances in the understanding of the cellular and molecular mechanisms of corticosteroid resistance in COPD pathophysiology have supported the development of new emerging classes of anti-inflammatory drugs in COPD treatment. These include treatments such as inhibitors of phosphoinositide-3-kinase-delta (PI3K?), phosphodiesterase-4 (PDE4), p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-?B), and therapeutic agents such as chemokine receptor antagonists. Of these, PI3K?, PDE4, p38 MAPK inhibitors and chemokine receptor antagonists are in clinical patient trials. Of importance, patient adverse effects associated with oral administration of these novel agents needs to be addressed in order to optimize therapy and patient compliance. Combinations of these drugs with corticosteroids may have additional benefits.
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Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung.
Thorax
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Small airways function studies in lung disease have used three promising multiple breath washout (MBW) derived indices: indices of ventilation heterogeneity in the acinar (S(acin)) and conductive (S(cond)) lung zones, and the lung clearance index (LCI). Since peripheral lung structure is known to change with age, ventilation heterogeneity is expected to be affected too. However, the age dependence of the MBW indices of ventilation heterogeneity in the normal lung is unknown.
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A novel approach to partition central and peripheral airway nitric oxide.
Chest
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Determining the site of airways inflammation may lead to the targeting of therapy. Nitric oxide (NO) is a biomarker of airway inflammation and can be measured at multiple exhalation flows to allow partitioning into bronchial (JawNO) and peripheral airway contributions (CANO) using a linear regression. This requires a minimum of three exhalations. We developed a simple and practical method to partition NO.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.