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COPD - Top 30 Publications

Epithelial mesenchymal transition (EMT), a spectrum of states: role in lung development, homeostasis and disease.

Epithelial Mesenchymal Transition (EMT) plays key roles during lung development and many lung diseases such as Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. Here, integrating morphological observations with underlying molecular mechanisms, we highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. We discuss the evidence of manifestation of EMT and its potential driving role in COPD, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), and lung cancer, while noting that all cells need not display a full EMT in any of these contexts, i.e. often cells co-express epithelial and mesenchymal markers but do not fully convert to extracellular matrix-producing fibroblasts. Finally, we discuss recent therapeutic attempts to restrict EMT in chronic lung disease. This article is protected by copyright. All rights reserved.

Item usage in a multidimensional computerized adaptive test (MCAT) measuring health-related quality of life.

Examining item usage is an important step in evaluating the performance of a computerized adaptive test (CAT). We study item usage for a newly developed multidimensional CAT which draws items from three PROMIS domains, as well as a disease-specific one.

Why do physicians lack engagement with smoking cessation treatment in their COPD patients? A multinational qualitative study.

Smoking cessation is the only effective intervention to slow down the accelerated decline in lung function in smokers with chronic obstructive pulmonary disease. Nevertheless, physicians often do not routinely provide evidence-based smoking cessation treatment to their patients. To understand underlying reasons, we explored how physicians engage in smoking cessation treatment in their chronic obstructive pulmonary disease patients. In total, 21 focus group discussions were held with general practitioners and pulmonologists in seven different countries in Europe and Asia. We generated three themes, whereby some of the issues concerned smokers in general: first, 'physicians' frustration with chronic obstructive pulmonary disease patients who smoke'. These frustrations interfered with the provision of evidence-based treatment and could result in this group of patients being treated unequally. Second: 'physicians' limited knowledge of, and negative beliefs about, smoking cessation treatment'. This hindered treating smokers effectively. Third: 'healthcare organisational factors that influence the use of smoking cessation treatments'. Money and time issues, as well as the failure to regard smoking as a disease, influenced how physicians engaged in smoking cessation treatment. Our results indicate that there is a number of barriers to the provision of effective smoking cessation treatment in patients with chronic obstructive pulmonary disease and smokers in general. Introducing an informative smoking cessation programme, including communication skills and ethical issues, in the vocational and postgraduate medical training may help to address these barriers. This is important in order to increase engagement with smoking cessation treatment and to improve quality of chronic obstructive pulmonary disease care.

Association between chronic obstructive pulmonary disease and increased risk of benign prostatic hyperplasia: a retrospective nationwide cohort study.

Chronic obstructive pulmonary disease (COPD) and benign prostatic hyperplasia (BPH) are common disorders in ageing male populations. Nevertheless, the relationship between the two diseases has rarely been explored. The objective of this study was to examine whether patients with COPD are at an increased risk of BPH.

Feasibility of average volume-assured pressure support ventilation in the treatment of acute hypercapnic respiratory failure associated with chronic obstructive pulmonary disease: What are its limits?

Comparative analysis: Effectiveness of nicotine addiction treatment in people with psychiatric comorbidity.

To determine whether or not nicotine addiction treatment was less effective in psychiatric than in the healthy population.

Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).

Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.

Pulmonary (3)He Magnetic Resonance Imaging Biomarkers of Regional Airspace Enlargement in Alpha-1 Antitrypsin Deficiency.

Thoracic x-ray computed tomography (CT) and hyperpolarized (3)He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (Lm) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers.

Is There room for Theophylline in COPD?

Healthcare expenditure on Indigenous and non-Indigenous Australians at high risk of cardiovascular disease.

In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease.

Cardiorespiratory responses of air filtration: A randomized crossover intervention trial in seniors living in Beijing: Beijing Indoor Air Purifier StudY, BIAPSY.

In this Beijing Indoor Air Purifier StudY (BIAPSY), we conducted a randomized crossover intervention trial in a panel of 35 non-smoking senior participants with free-living, with and without chronic obstructive pulmonary disease (COPD). Portable air filtration units were randomly allocated to active-(filter in) for 2weeks and sham-mode (filter out) for 2weeks in the households. We examined the differences in indoor air pollutant concentrations in 20 study homes and a suite of cardio-respiratory biomarker levels in study participants between filtration modes, with and without adjustment for potential confounders. Following active filtration, we observed significant reductions from 60±45 to 24±15μg/m(3) in ten-day averages of indoor PM2.5 and reductions from 3.87±1.65 to 1.81±1.19m(-1).10(-5) in ten-day averages of indoor BC, compared to sham-mode filtration. The major components of indoor PM2.5, including water soluble organics, NO3(-), SO4(2-), Zn(2+), Pb(2+) and K(+), were also reduced significantly by 42% to 63%. However, following active filtration, we only observed significant reductions on systemic inflammation measured as of IL-8 at 58.59% (95% CI: -76.31, -27.64) in the total group of participants and 70.04% (95% CI: -83.05, -47.05) in the subset of COPD patients, with adjustments. We were not able to detect improvements on lung function, blood pressure, and heart rate variability, following short-term intervention of two-week active air filtration. In conclusion, our results showed that indoor air filtration produced clear improvement on indoor air quality, but no demonstrable changes in the cardio-respiratory outcomes of study interest observed in the seniors living with real-world air pollution exposures.

Context Relevant Prediction Model for COPD Domain Using Bayesian Belief Network.

In the last three decades, researchers have examined extensively how context-aware systems can assist people, specifically those suffering from incurable diseases, to help them cope with their medical illness. Over the years, a huge number of studies on Chronic Obstructive Pulmonary Disease (COPD) have been published. However, how to derive relevant attributes and early detection of COPD exacerbations remains a challenge. In this research work, we will use an efficient algorithm to select relevant attributes where there is no proper approach in this domain. Such algorithm predicts exacerbations with high accuracy by adding discretization process, and organizes the pertinent attributes in priority order based on their impact to facilitate the emergency medical treatment. In this paper, we propose an extension of our existing Helper Context-Aware Engine System (HCES) for COPD. This project uses Bayesian network algorithm to depict the dependency between the COPD symptoms (attributes) in order to overcome the insufficiency and the independency hypothesis of naïve Bayesian. In addition, the dependency in Bayesian network is realized using TAN algorithm rather than consulting pneumologists. All these combined algorithms (discretization, selection, dependency, and the ordering of the relevant attributes) constitute an effective prediction model, comparing to effective ones. Moreover, an investigation and comparison of different scenarios of these algorithms are also done to verify which sequence of steps of prediction model gives more accurate results. Finally, we designed and validated a computer-aided support application to integrate different steps of this model. The findings of our system HCES has shown promising results using Area Under Receiver Operating Characteristic (AUC = 81.5%).

Chronic Respiratory Infection in Patients with Chronic Obstructive Pulmonary Disease: What Is the Role of Antibiotics?

Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD). The major objective of the management of these patients is the prevention and effective treatment of exacerbations. Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy. It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens. In some patients, systemic corticosteroids are also indicated to improve symptoms. In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence. It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy. Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition. Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations. Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations. There is a need to design long-term studies to evaluate these interventions in the natural history of the disease. The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions.

Palliative oxygen for chronic breathlessness: what new evidence?

Supplemental oxygen improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia, but the effect of oxygen therapy in mild or moderate hypoxaemia to reduce symptomatic chronic breathlessness remains unclear. This review provides an overview of recent evidence about the role of oxygen therapy for the relief of chronic breathlessness in advanced illness.

Role of Breathing Conditions During Exercise Testing on Training Prescription in Chronic Obstructive Pulmonary Disease.

This study investigated whether different breathing conditions during exercise testing will influence measures of exercise capacity commonly used for training prescription in chronic obstructive pulmonary disease. Twenty-seven patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 sec = 45.6 [9.4]%) performed three maximal exercise tests within 8 days, but at least 48 hrs apart. Subjects were thereby breathing either room air through a tightly fitting face mask like during any cardiopulmonary exercise test (MASK), room air without mask (No-MASK), or 10 l/min of oxygen via nasal cannula (No-MASK + O2). Cycling protocols were identical for all tests (start = 20 watts, increment = 10 males/5 females watts/min). Maximal work rate (90.4 [33.8], 100.3 [34.8], 107.4 [35.9] watts, P < 0.001) and blood lactate at exhaustion (4.3 [1.5], 5.2 [1.6], 5.0 [1.4] mmol/l, P < 0.001) were lowest for MASK when compared with No-MASK and No-MASK + O2, respectively, whereas maximal heart rate did not differ significantly. Submaximal exertion (Borg rating of perceived exertion = 12-14) was perceived at lower intensity (P = 0.008), but higher heart rate (P = 0.005) when MASK was compared with No-MASK and No-MASK + O2. Different breathing conditions during exercise testing resulted in an 18.8% difference in maximal work rate, likely causing underdosing or overdosing of exercise in chronic obstructive pulmonary disease. Face masks reduced whereas supplemental oxygen increased patients' exercise capacity. For accurate prescription of exercise in chronic obstructive pulmonary disease, breathing conditions during testing should closely match training conditions.

More than expectorant: new scientific data on ambroxol in the context of the treatment of bronchopulmonary diseases.

Ambroxol has been established for decades in the treatment of acute and chronic respiratory diseases. In 2015, the European Medicines Agency reassessed the clinical benefit-risk ratio of the drug.

Repair of Thoracoabdominal Aortic Aneurysm with Thrombosed Infrarenal Component: A Modified Hybrid Technique without Aortic Cross Clamping.

The authors report the successful repair of a Crawford type III thoracoabdominal aortic aneurysm (TAAA) with a thrombosed infrarenal component using a modified hybrid technique without aortic clamping in a high-risk patient. A 64-year-old male with a history of hypertension, diabetes, and severe chronic obstructive pulmonary disease presented with acute on chronic backache and bilateral short distance claudication. A computerized tomography scan demonstrated a large, nonleaking Crawford type III TAAA with thrombosed infrarenal component of the aneurysm. In addition, both common iliac arteries were occluded with the chronic thrombus. A single-stage, modified hybrid procedure involving an aortobifemoral bypass without aortic clamping, debranching of right renal, superior mesenteric, and celiac arteries as well as an endovascular repair of the thoracic aneurysm was performed. Unfortunately, despite a technically sound repair, the patient died postoperatively from a massive pulmonary embolism. TAAA with a thrombosed infrarenal aorta and bilateral common iliac arteries can be repaired using a single-stage modified hybrid procedure without aortic clamping in high-risk patients who cannot tolerate thoracotomy and aortic cross clamping.

Prescription opioid use in advanced COPD: benefits, perils and controversies.

Predictors of long-term smoking cessation in patients with COPD: results from a randomised controlled trial.

Aclidinium bromide improves symptoms and sleep quality in COPD: a pilot study.

Prescription opioid use in advanced COPD: benefits, perils and controversies.

Run-in bias in randomised trials: the case of COPD medications.

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10(-7)). Sex stratification indicated that the separation was driven by females (p=2.4×10(-7)) relative to males (p=4.0×10(-4)). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10(-3)) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin-lysoPA axis, are associated with disease mechanisms and/or prevalence.

Long-term volume-targeted pressure-controlled ventilation: sense or nonsense?

The technology underlying the development of novel ventilatory modes for long-term noninvasive ventilation of patients with chronic hypercapnia is continuously evolving. Volume-targeted pressure-controlled ventilation is a hybrid ventilation mode designed to combine the advantages of conventional ventilation modes, while avoiding their drawbacks. However, manufacturers have created different names and have patented algorithms and set-up variables, which can result in confusion for physicians and respiratory therapists. In addition, clear evidence for the superiority of this novel mode has not yet been established. These factors have most likely hindered more widespread use of this mode in clinical practice. The current review presents the rationale, working principles, characteristics and set-up recommendations associated with volume-targeted modes. In addition, it summarises the clinical and laboratory studies that have challenged this mode.

Predicting risk of undiagnosed COPD: development and validation of the TargetCOPD score.

Chronic obstructive pulmonary disease (COPD) is greatly underdiagnosed worldwide and more efficient methods of case-finding are required. We developed and externally validated a risk score to identify undiagnosed COPD using primary care records.We conducted a retrospective cohort analysis of a pragmatic cluster randomised controlled case-finding trial in the West Midlands, UK. Participants aged 40-79 years with no prior diagnosis of COPD received a postal or opportunistic screening questionnaire. Those reporting chronic respiratory symptoms were assessed with spirometry. COPD was defined as presence of relevant symptoms with a post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. A risk score was developed using logistic regression with variables available from electronic health records for 2398 participants who returned a postal questionnaire. This was externally validated among 1097 participants who returned an opportunistic questionnaire to derive the c-statistic, and the sensitivity and specificity of cut-points.A risk score containing age, smoking status, dyspnoea, prescriptions of salbutamol and prescriptions of antibiotics discriminated between patients with and without undiagnosed COPD (c-statistic 0.74, 95% CI 0.68-0.80). A cut-point of ≥7.5% predicted risk had a sensitivity of 68.8% (95% CI 57.3-78.9%) and a specificity of 68.8% (95% CI 65.8.1-71.6%).A novel risk score using routine data from primary care electronic health records can identify patients at high risk for undiagnosed symptomatic COPD. This score could be integrated with clinical information systems to help primary care clinicians target patients for case-finding.

Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability. However, the molecular changes that cause this barrier disruption and the interaction between adhesion proteins and the cytoskeleton are not well defined. We hypothesized that CS alters monolayer integrity by increasing cell contractility and decreasing cell adhesion in epithelia.

Anti-TNFα Therapy in Inflammatory Lung Diseases bn.

Increased levels of tumor necrosis factor (TNF) α have been linked to a number of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sarcoidosis, and interstitial pulmonary fibrosis (IPF). TNFα plays multiple roles in disease pathology by inducing an accumulation of inflammatory cells, stimulating the generation of inflammatory mediators, and causing oxidative and nitrosative stress, airway hyperresponsiveness and tissue remodeling. TNF-targeting biologics, therefore, present a potentially highly efficacious treatment option. This review summarizes current knowledge on the role of TNFα in pulmonary disease pathologies, with a focus on the therapeutic potential of TNFα-targeting agents in treating inflammatory lung diseases.

Changes in biophysical membrane properties induced by the Budesonide/Hydroxy-β-cyclodextrin complex.

Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a biocompatible cyclodextrin known to interact with cholesterol, is used as a drug-solubilizing agent in pharmaceutical formulations. Budesonide administered as an inclusion complex within HPβCD (BUD:HPβCD) required a quarter of the nominal dose of the suspension formulation and significantly reduced neutrophil induced inflammation in a COPD mouse model exceeding the effect of each molecule administered individually. This suggests the role of lipid domains enriched in cholesterol for inflammatory signaling activation. In this context, we investigated the effect of BUD:HPβCD on the biophysical properties of membrane lipids. On cellular models (A549, lung epithelial cells), BUD:HPβCD extracted cholesterol similarly to HPβCD. On large unilamellar vesicles (LUVs), by using the fluorescent probes diphenylhexatriene (DPH) and calcein, we demonstrated an increase in membrane fluidity and permeability induced by BUD:HPβCD in vesicles containing cholesterol. On giant unilamellar vesicles (GUVs) and lipid monolayers, BUD:HPβCD induced the disruption of cholesterol-enriched raft-like liquid ordered domains as well as changes in lipid packing and lipid desorption from the cholesterol monolayers, respectively. Except for membrane fluidity, all these effects were enhanced when HPβCD was complexed with budesonide as compared with HPβCD. Since cholesterol-enriched domains have been linked to membrane signaling including pathways involved in inflammation processes, we hypothesized the effects of BUD:HPβCD could be partly mediated by changes in the biophysical properties of cholesterol-enriched domains.

Two components of the new ESPEN diagnostic criteria for malnutrition are independent predictors of lung function in hospitalized patients with chronic obstructive pulmonary disease (COPD).

Low fat free mass index (FFMI) is a component of the ESPEN diagnosis criteria of malnutrition, that only when accompanied with weight loss is considered to be a determinant of malnutrition. Our aims were to assess the prevalence of malnutrition in patients with chronic obstructive pulmonary disease (COPD) applying the ESPEN criteria, and to examine the ability of different components of the criteria to predict COPD severity, length of stay (LOS), hospital readmissions within 30 days and mortality.

Health Effects of Airline Cabin Environments in Simulated 8-Hour Flights.

Commercial air travel is usually without health incidents. However, there is a view that cabin environments may be detrimental to health, especially flights of 8 h or more. Concerns have been raised about deep vein thrombosis, upper respiratory tract infections, altitude sickness, and toxins from the engines.