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COPD - Top 30 Publications

Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation.

Background Silent/asymptomatic peripheral artery disease may occur in patients with chronic obstructive pulmonary disease, but it is poorly investigated. The primary aim of this study was to evaluate in chronic obstructive pulmonary disease patients the impact of asymptomatic/silent peripheral artery disease on maximal exercise capacity; the secondary aim was to search for predictors of peripheral artery disease. Methods We prospectively enrolled chronic obstructive pulmonary disease outpatients. Data on anthropometric characteristics, lung function, cardiopulmonary exercise test and ankle-brachial index were recorded. The cut-off of ankle-brachial index used to define patients with peripheral artery disease was ≤0.90. Results We studied 47 patients and found 24 patients (51%) who showed peripheral artery disease. As compared to patients without peripheral artery disease, patients with peripheral artery disease had lower values of peak oxygen uptake, peak workload, energy expenditure (metabolic equivalents) and heart rate recovery, but showed the same degree of airflow obstruction and static and dynamic hyperinflation. In a multivariate linear regression model performed to identify variables predicting metabolic equivalents, ankle-brachial index (β 2.59; 95% confidence interval 0.51-4.67; p = 0.016) was an independent variable. In the search for predictors of peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease, whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26-0.94, p = 0.033) and inhaled corticosteroids+long-acting β2 agonists (odds ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk. Conclusions In chronic obstructive pulmonary disease outpatients, asymptomatic/silent peripheral artery disease affects the maximal exercise capacity regardless of airflow obstruction and lung hyperinflation. A delay of heart rate recovery increase the risk of peripheral artery disease, whereas high values of metabolic equivalents and the use of inhaled corticosteroids+long-acting β2 agonists reduces this risk.

Microbiome effects on immunity, health and disease in the lung.

Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), are among the leading causes of mortality and morbidity worldwide. In the past decade, the interest in the role of microbiome in maintaining lung health and in respiratory diseases has grown exponentially. The advent of sophisticated multiomics techniques has enabled the identification and characterisation of microbiota and their roles in respiratory health and disease. Furthermore, associations between the microbiome of the lung and gut, as well as the immune cells and mediators that may link these two mucosal sites, appear to be important in the pathogenesis of lung conditions. Here we review the recent evidence of the role of normal gastrointestinal and respiratory microbiome in health and how dysbiosis affects chronic pulmonary diseases. The potential implications of host and environmental factors such as age, gender, diet and use of antibiotics on the composition and overall functionality of microbiome are also discussed. We summarise how microbiota may mediate the dynamic process of immune development and/or regulation focusing on recent data from both clinical human studies and translational animal studies. This furthers the understanding of the pathogenesis of chronic pulmonary diseases and may yield novel avenues for the utilisation of microbiota as potential therapeutic interventions.

Tele-medicine in respiratory diseases.

Information and Communication Technologies applied to health care and advances in sensor and data transmission technology allowed tele-medicine based programs of care also for patients with respiratory diseases. Different sensors, transmission devices and interventions are used in tele-medicine for some indications. Patients suffering from Chronic Obstructive Pulmonary Disease, asthma, neuromuscular diseases, ventilator assisted individuals and those undergoing pulmonary rehabilitation programs may benefit from this approach. The legal problems are still unsolved. Economic advantages for health care systems, though potentially high, are still poorly investigated. Despite the hopes, we need more evidence before this modality can be considered as a real progress in the management of patients with respiratory diseases. On one hand, these technologies can improve the care of patients with difficult access to services, particularly those in rural/remote areas, on the other hand, there is the risk that they will be used only to reduce standard services in health systems of developed countries.

Clinician-Performed Bedside Ultrasound in Improving Diagnostic Accuracy in Patients Presenting to the ED with Acute Dyspnea.

Diagnosing acute dyspnea is a critical action performed by emergency physicians (EP). It has been shown that ultrasound (US) can be incorporated into the work-up of the dyspneic patient; but there is little data demonstrating its effect on decision-making. We sought to examine the impact of a bedside, clinician-performed cardiopulmonary US protocol on the clinical impression of EPs evaluating dyspneic patients, and to measure the change in physician confidence with the leading diagnosis before and after US.

Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease.

Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD) is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated.

Accelerometer- versus questionnaire-based assessment of physical activity and their changes over time in patients with COPD.

Physical activity (PA) is an important outcome parameter in patients with COPD regarding hospitalizations and mortality. Both objective assessment by accelerometers and self-evaluation by questionnaires were used in studies investigating PA in COPD. Whether self-reported questionnaires can adequately reflect PA and its changes over time compared to objective assessments has not been thoroughly investigated in COPD. In this COPD cohort study, we evaluated whether PA measured by accelerometer and its annual changes can also be assessed by self-reported questionnaires.

Peripheral leukocyte microRNAs as novel biomarkers for COPD.

COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors. The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue. Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found. For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls. Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction. Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients. For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated. Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D. Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups. In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD. The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment.

Burden of asthma, dyspnea, and chronic cough in South Asia.

Asthma, dyspnea, and chronic cough are well-established risk factors of COPD and often associated with exacerbation of the disease, which is a leading cause of morbidity and mortality in South Asian countries.

Magnitude of exercise capacity and quality of life improvement following repeat pulmonary rehabilitation in patients with COPD.

Maintenance and repeated pulmonary rehabilitation programs (PRPs) for patients with COPD have attempted to prolong PRP benefits beyond 12-24 months. However, there is limited evidence as to the magnitude of benefit or the ideal interval between repeating the program under "real-world" conditions in which patients are referred based on clinical necessity. Therefore, we reviewed the effects of repeating PRP in a physician-referred cohort of patients with COPD.

Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies.

Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.

Pulmonary rehabilitation for COPD improves exercise time rather than exercise tolerance: effects and mechanisms.

COPD patients undergoing pulmonary rehabilitation (PR) show various responses. The purpose of this study was to investigate the possible mechanisms and predictors of the response to PR in COPD patients.

Automated versus manual oxygen titration in COPD exacerbation: machine or hands, this is the question.

Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study.

The study investigated the effects of exercise on epigenetic signals and systemic cytokine levels in chronic obstructive pulmonary disease (COPD) individuals. Ten participants of a pulmonary rehabilitation program were submitted to 24 sessions of a supervisioned exercise protocol thrice-weekly (90min/session). Blood samples were collected at baseline, after the 1st session, before and after the 24th session. A DNA hypomethylation status was observed after the 1st session when compared at baseline, while global histone H4 acetylation status was unaltered in any time-points evaluated. No significant changes were observed on cytokine levels after the 1st session. A significant enhancement on interleukin 6 (IL-6) and a decrease on transforming growth factor-beta (TGF-β) levels were found after the 24th session when compared to the pre 24th session. Moreover, 23 sessions of exercise were able to diminish significantly the basal levels of IL-6 and interleukin 8 (IL-8). These data suggest a potential role of epigenetic machinery in mediating the anti-inflammatory effects of exercise in COPD patients.

Activation of the Serotonin Pathway is Associated with Poor Outcome in COPD Exacerbation: Results of a Long-Term Cohort Study.

Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation.

Antibiotic Decision in Severe Chronic Obstructive Pulmonary Disease Exacerbations.

Pulmonary rehabilitation referral and participation are commonly influenced by environment, knowledge, and beliefs about consequences: a systematic review using the Theoretical Domains Framework.

What are the barriers and enablers of referral, uptake, attendance and completion of pulmonary rehabilitation for people with chronic obstructive pulmonary disease (COPD)?

Psiguajadials A-K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava.

Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A-K (1-11), along with 17 known ones (12-28). Their structures and absolute configurations were elucidated by spectroscopic methods and comparison of experimental and calculated ECD. Compounds 1 and 2 represent two unprecedented skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3 is the first example of Psidium meroterpenoids coupling via an oxepane ring. Putative biosynthetic pathways towards 1 and 2 are proposed. Compounds 1-13 and 16-26 exhibited moderate inhibitory activities against phosphodiesterase-4 (PDE4), a drug target for asthma and chronic obstructive pulmonary disease, with IC50 values in the range of 1.34-7.26 μM.

A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD.

The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.

Effect of 4(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoylbenzoic acid (Am80) on alveolar regeneration in adiponectin deficient-mice showing a chronic obstructive pulmonary disease like pathophysiology.

Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease that causes widespread and irreversible alveolar collapse. Although COPD occurs worldwide, only symptomatic therapy is currently available. The objective of the present study was the development of therapeutic agents to eradicate COPD. Therefore, we focused on 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid (Am80), which is a derivative of all-trans retinoic acid. We evaluated the effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient mice. This mouse model has more symptoms similar to human COPD than the classic elastase-induced emphysema mouse model. Lung volume, CT values, low attenuation area (LAA) ratios, and bone and fat mass were measured by computed tomography. However, the administration of Am80 did not affect these results. To examine the degree of destruction in the alveoli, the mean linear intercept of the alveolar walls was calculated, and assessment of this value confirmed that there was a significant difference between the control (46.3 ± 2.3 μm) and 0.5 mg/kg Am80-treated group (34.4 ± 1.7 µm). All mice survived because of treatment that lasted for more than 6 months, and we did not observe any abnormalities in autopsies performed at 80 weeks of age. These results suggested that Am80 was effective as a novel therapeutic compound for the treatment of COPD.

TREM2-ligand interactions in health and disease.

The protein Triggering receptor expressed on myeloid cells-2 (TREM2) is an immunomodulatory receptor with a central role in myeloid cell activation and survival. In recent years, the importance of TREM2 has been highlighted by the identification of coding variants that increase risk for Alzheimer's disease and other neurodegenerative diseases. Animal studies have further shown the importance of TREM2 in neurodegenerative and other inflammatory disease models including chronic obstructive pulmonary disease, multiple sclerosis, and stroke. A mechanistic understanding of TREM2 function remains elusive, however, due in part to the absence of conclusive information regarding the identity of endogenous TREM2 ligands. While many TREM2 ligands have been proposed, their physiological role and mechanism of engagement remain to be determined. In this review, we highlight the suggested roles of TREM2 in these diseases, recent advances in our understanding of TREM2, and discuss putative TREM2-ligand interactions and their potential roles in signaling during health and disease. We develop a model based on the TREM2 structure to explain how different TREM2 ligands might interact with the receptor and how disease-risk variants may alter ligand interactions. Finally, we propose future experimental directions to establish the role and importance of these different interactions on TREM2 function.

Etiological analysis and epidemiological comparison among adult CAP and NHCAP patients in Okinawa, Japan.

Etiological epidemiology and diagnosis are important issues for CAP and NHCAP. Despite the availability of effective therapies, significant morbidity and mortality ensues.

Statin use and other factors associated with mortality after major lower extremity amputation.

Above-knee amputations (AKAs) and below-knee amputations (BKAs) are associated with high postoperative mortality rates. In this study, we examined factors associated with 30-day, 90-day, and 1-year mortality in patients who underwent a major lower extremity amputation.

Barriers to referral to pulmonary rehabilitation in COPD patients from the perspective of general practitioners.

In spite of recommendations of the highest level of proof (rank A), the respiratory rehabilitation remains very widely sub-prescribed by general practitioners, who are nevertheless in the front line in the care and the follow-up of the patients affected by BPCO.

Clenbuterol Hydrochloride.

Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including spectrophotometric, electrochemical, chromatographic, immunochemical methods, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior, and the pharmacology of the drug are also provided.

Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung.

Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined.

Understanding the impact of symptoms on the burden of COPD.

Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities. We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis. In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered. The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden.

Outcomes after early and delayed rehabilitation for exacerbation of chronic obstructive pulmonary disease: a nationwide retrospective cohort study in Japan.

The effectiveness of early pulmonary rehabilitation (PR) for exacerbation of chronic obstructive pulmonary disease (COPD) remains controversial. The present study aimed to compare the outcomes between early and delayed PR for exacerbation of COPD, using a national inpatient database.

Asthma-COPD overlap syndrome (ACOS) in primary care of four Latin America countries: the PUMA study.

Asthma-COPD overlap syndrome (ACOS) prevalence varies depending on the studied population and definition criteria. The prevalence and clinical characteristics of ACOS in an at-risk COPD primary care population from Latin America was assessed.

Asthma-COPD overlap syndrome and precision medicine.

Ambient PM2.5 exposure and premature mortality burden in the holy city Varanasi, India.

More than 3 million population residing in the holy city Varanasi and sub-urban areas is exposed to very high level of fine particulate matter (PM2.5) from various sources. Continuous monitoring by Central Pollution Control Board started only in 2015; therefore what was the pollution level in the past and how it has changed over the years are not known. We use MODIS aerosol products to infer PM2.5 and examine 15-year climatology. Data shows a rapid (1.5-3% per year) increase in PM2.5 in the last 15 years and high (87% days in a year) persistence of PM2.5 above the national air quality standard. It translates to a burden of 5700 (2800-7500) annual premature deaths (0.16% of the population), of which 29%, 18%, 33%, 19% and remaining 1% are attributed to ischemic heart disease, stroke, chronic obstructive pulmonary disease, acute lower respiratory infection and lung cancer respectively. If the region achieves the Indian (WHO) air quality standard, 1900 (3800) premature deaths can be avoided every year.