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chronic obstructive pulmonary disease - Top 30 Publications

Early discharge hospital at home.

Early discharge hospital at home is a service that provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital inpatient care. This is an update of a Cochrane review.

Genetic and epigenetic alterations in normal and sensitive COPD-diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM2.5.

Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface. Thereafter, they were repeatedly exposed to air pollution-derived PM2.5 to study the occurrence of some relevant genetic and/or epigenetic endpoints. Concentration-, exposure- and season-dependent increases of OH-B[a]P metabolites in NHBE, and to a lesser extent, COPD-DHBE cells were reported; however, there were more tetra-OH-B[a]P and 8-OHdG DNA adducts in COPD-DHBE cells. No increase in primary DNA strand break nor chromosomal aberration was observed in repeatedly exposed cells. Telomere length and telomerase activity were modified in a concentration- and exposure-dependent manner in NHBE and particularly COPD-DHBE cells. There were a global DNA hypomethylation, a P16 gene promoter hypermethylation, and a decreasing DNA methyltransferase activity in NHBE and notably COPD-DHBE cells repeatedly exposed. Changes in site-specific methylation, acetylation, and phosphorylation of histone H3 (i.e., H3K4me3, H3K9ac, H3K27ac, and H3S10ph) and related enzyme activities occurred in a concentration- and exposure-dependent manner in all the repeatedly exposed cells. Collectively, these results highlighted the key role played by genetic and even epigenetic events in NHBE and particularly sensitive COPD-DHBE cells repeatedly exposed to air pollution-derived PM2.5 and their different responsiveness. While these specific epigenetic changes have been already described in COPD and even lung cancer phenotypes, our findings supported that, together with genetic events, these epigenetic events could dramatically contribute to the shift from healthy to diseased phenotypes following repeated exposure to relatively low doses of air pollution-derived PM2.5.

Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice.

Sepsis is a life-threatening syndrome accompanied by an overwhelming inflammatory response and organ dysfunction. Selective targeting of phosphodiesterase 4 (PDE4) is currently being investigated as an effective therapeutic approach for inflammation-associated diseases. Roflumilast is a selective PDE4 inhibitor, used for the treatment of severe chronic obstructive pulmonary disease in clinic. However, its role in the treatment of sepsis-induced liver damage remains unclear. In the present study, we evaluated the effects of roflumilast in mice with cecal ligation and puncture-induced sepsis, and investigated the underlying mechanism. We found that roflumilast treatment improved survival in septic mice by reducing bacterial load locally and systemically, inhibiting the expression of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor alpha, and alleviating liver injury. These effects were associated with the inhibition of nuclear translocation of nuclear factor-kappa B (NF-κB), as well as degradation of NF-κB inhibitory protein alpha. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also markedly inhibited by roflumilast. Moreover, roflumilast significantly suppressed the activation of signal transducer and activator of transcription 3 (STAT3) and its upstream Janus kinase 1 and Janus kinase 2. Taken together, these results indicate that roflumilast prevents polymicrobial sepsis likely by suppressing NF-κB, p38 MAPK, and STAT3 pathways.Laboratory Investigation advance online publication, 26 June 2017; doi:10.1038/labinvest.2017.59.

Screening tools for evaluation of depression in Chronic Obstructive Pulmonary Disease (COPD). A systematic review.

Background: Anxiety and depression are common comorbid disorders in patients with chronic obstructive pulmonary disease (COPD), though estimates of their prevalence vary considerably. Depressive symptoms/depression are important comorbidities in COPD and an increasing interest is shown to these disorders. Depression may lead to reduced quality of life and increased morbidity and mortality. These statements underline the importance of implementing the use of screening instruments for depressive symptoms in a clinical setting. This systematic review evaluates four commonly used screening tools for depression in COPD. Furthermore we assess the prevalence of depression in COPD in the evaluated studies. Design: A literature search identified studies dealing with screening for depression in patients with COPD. We focused on the instruments: Beck Depression Inventory, Geriatric depression scale, Centre for Epidemiological Studies scale on Depression and Hospital and Anxiety Depression Scale. Results: Overall prevalence of depression was 30%. Demographic variations and severity of COPD influenced prevalence. The inter-prevalence of the four screening tools was consistent. We found a low variation between studies using the same tool. Few studies used control groups or compared the screening tool to a psychiatrist evaluation. Conclusions: This article calls for further investigation of the association between COPD and depressive symptoms. The subject is highly relevant for everyday life of patients with COPD and attention needs to be drawn to this issue in both an out- and in-patients.

Integrative characterization of chronic cigarette smoke-induced cardiopulmonary comorbidities in a mouse model.

Cigarette smoke-triggered inflammatory cascades and consequent tissue damage are the main causes of chronic obstructive pulmonary disease (COPD). There is no effective therapy and the key mediators of COPD are not identified due to the lack of translational animal models with complex characterization. This integrative chronic study investigated cardiopulmonary pathophysiological alterations and mechanisms with functional, morphological and biochemical techniques in a 6-month-long cigarette smoke exposure mouse model. Some respiratory alterations characteristic of emphysema (decreased airway resistance: Rl; end-expiratory work and pause: EEW, EEP; expiration time: Te; increased tidal mid-expiratory flow: EF50) were detected in anaesthetized C57BL/6 mice, unrestrained plethysmography did not show changes. Typical histopathological signs were peribronchial/perivascular (PB/PV) edema at month 1, neutrophil/macrophage infiltration at month 2, interstitial leukocyte accumulation at months 3-4, and emphysema/atelectasis at months 5-6 quantified by mean linear intercept measurement. Emphysema was proven by micro-CT quantification. Leukocyte number in the bronchoalveolar lavage at month 2 and lung matrix metalloproteinases-2 and 9 (MMP-2/MMP-9) activities in months 5-6 significantly increased. Smoking triggered complex cytokine profile change in the lung with one characteristic inflammatory peak of C5a, interleukin-1α and its receptor antagonist (IL-1α, IL-1ra), monokine induced by gamma interferon (MIG), macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) at months 2-3, and another peak of interferon-γ (IFN-γ), IL-4, 7, 13, 17, 27 related to tissue destruction. Transient systolic and diastolic ventricular dysfunction developed after 1-2 months shown by significantly decreased ejection fraction (EF%) and deceleration time, respectively. These parameters together with the tricuspid annular plane systolic excursion (TAPSE) decreased again after 5-6 months. Soluble intercellular adhesion molecule-1 (sICAM-1) significantly increased in the heart homogenates at month 6, while other inflammatory cytokines were undetectable. This is the first study demonstrating smoking duration-dependent, complex cardiopulmonary alterations characteristic to COPD, in which inflammatory cytokine cascades and MMP-2/9 might be responsible for pulmonary destruction and sICAM-1 for heart dysfunction.

A 10-year institutional experience with open branched graft reconstruction of aortic aneurysms in connective tissue disorders versus degenerative disease.

Aortic reconstruction for complex thoracoabdominal aortic aneurysms (TAAAs) can be challenging, especially in patients with connective tissue disorders (CTDs) in whom tissue fragility is a major concern. Branched graft reconstruction is a more complex operation compared with inclusion patch repair of the aorta but is frequently necessary in patients with CTDs or other pathologies because of anatomic reasons. We describe our institutional experience with open branched graft reconstruction of aortic aneurysms and compare outcomes for patients with CTDs vs degenerative pathologies.

Minimal Clinically Important Differences (MCIDs) of the Thai Version of the Leicester Cough Questionnaire for Subacute and Chronic Cough.

To investigate the minimal clinically important differences (MCIDs) of the Thai version of the Leicester Cough Questionnaire (LCQ-T) in patients with subacute and chronic cough.

Mechanisms of cytoskeleton and PI3Kδ-RhoA in fine particulate matter deteriorating phagocytosis defect of alveolar macrophage in mice with chronic obstructive pulmonary disease.

Objective: To explore the mechanism of cytoskeleton and PI3Kδ-RhoA in fine particulate matter deteriorating phagocytosis defect of alveolar macrophage (AM) in chronic obstructive pulmonary disease (COPD) mice. Methods: Forty mice were randomly divided into four groups: health control group, COPD group, health PM2.5 group, COPD PM2.5 group and with ten in each group. A mouse model of COPD was established by cigarette smoke exposure, and health PM2.5 group and COPD PM2.5 group mice were given PM2.5 (588 μg/m(3)) aerosol inhalation for 90 days. AM were isolated from lung tissue by discontinuous density gradient centrifugation. Mean fluorescence intensity (MFI) and the percent of alveolar macrophage engulfing flurescein isothiocyanate-labeled Escherichia coli (FITC-E.coli) AM (AM%) were detected by flow cytometry. The mRNA and protein expression were measured by real time polymerase chain reaction (RT-PCR) and Western blot. The activity of RhoA was measured by GTPase linked immunosorbent assay (G-LISA) Kit. Cytoskeleton was observed by laser scanning confocal microscopy. Results: The MFI and the AM% in COPD group [4 512±517, (32.19±4.57)%] and health PM2.5 group [7 631±585, (50.78±4.58)%] were significantly lower than those in health control group [9 857±1 042, (68.53±2.88)%], while those in COPD PM2.5 group [3 121±393, (21.90±2.58)%] were lower than those in COPD group (all P<0.01). The mRNA and protein of PI3Kδ in COPD group (3.41±0.54, 0.84±0.08)and health PM2.5 group (1.52±0.35, 0.71±0.11) were higher than those in health control group (1.00±0.00, 0.57±0.07) (all P<0.05), and in COPD PM2.5 group (5.53±0.42, 1.17±0.25), the above parameters were remarkably increased as compared to those in COPD group (all P<0.01). The mRNA, protein and activity of RhoA in COPD group (0.70±0.07, 0.41±0.10, 0.70±0.06) and health PM2.5 group (0.84±0.06, 0.46±0.11, 0.87±0.07) were lower than those in health control group (1.00±0.00, 0.56±0.09, 1.19±0.09) (all P<0.05), and above parameters of COPD PM2.5 group (0.42±0.05, 0.31±0.06, 0.44±0.04) were significantly lower than COPD group (all P<0.01). Cytoskeleton of AM: long and dense filopodia and membrane fold could been seen clearly around the AM of health control group; in COPD group and health PM2.5 group, short and sparse filopodia and slightly deformed AM can been seen. Filopodia remarkably decreased and rigid cells with impaired capacity of engulfing FITC-E.coli can be generally observed in COPD PM2.5 group. Negative correlations were existed between PI3Kδ mRNA, protein and RhoA mRNA, protein, activity in all groups (all P<0.01). Negative correlations were existed between PI3Kδ mRNA, protein and MFI, and positive correlations were existed between RhoA mRNA, protein, activity and MFI in all groups (all P<0.05). Conclusion: Fine particulate matter (PM2.5) can deteriorate the phagocytosis of AM from COPD mice through over activating PI3Kδ and inhibiting the activity of RhoA then causing cytoskeleton abnormal rearrangement.

Importance of GOLD Guidelines for Chronic Obstructive Pulmonary Disease.

In December 2011, a major revision of GOLD 2011 guidelines was published based on the evidence-based medicine. The goal of GOLD 2011 is to determine the severity of the disease, its impact on the patient's health, and the risk of future events; all of which eventually guide therapy. A combined COPD assessment according to GOLD 2011 considers the patient's level of symptoms, spirometry abnormalities, risk of exacerbation, and the presence of comorbidities. GOLD 2011 stratifies patients into four basic groups labeled A, B, C, and D. The aim of the present study was to assess the importance of updated GOLD guidelines for the diagnosis, treatment, and prevention of COPD. We found that the multicomponent 2011 guidelines offer a significant advantage over the previous mono-component COPD assessment according to GOLD 2006 in terms of disease control and therapy management, with patients enjoying better spirometry values and a higher arterial oxygen content considered the primary outcomes of interest.

Biochemical parameters as monitoring markers of the inflammatory reaction by patients with chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is an airway inflammatory disease caused by inhalation of toxic particles, mainly cigarette smoking, and now is accepted as a disease associated with systemic characteristics.

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.

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.

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.

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.

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.

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.