scholarly journals Reversal of emphysema by restoration of pulmonary endothelial cells

2021 ◽  
Vol 218 (8) ◽  
Author(s):  
Shu Hisata ◽  
Alexandra C. Racanelli ◽  
Pouneh Kermani ◽  
Ryan Schreiner ◽  
Sean Houghton ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Biology ◽  
Therapeutic Potential ◽  
Transcriptional Profiling ◽  
Airflow Obstruction ◽  
Cell Loss ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Lung Endothelial Cells

Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema. Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state. This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells. Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression. Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema.

scholarly journals COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

2018 ◽  
Vol 8 (1) ◽  
pp. 204589401875852 ◽  
Author(s):  
Francesca Polverino ◽  
Bartolome R. Celli ◽  
Caroline A. Owen
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cigarette Smoke ◽  
Angiotensin Receptor Blockers ◽  
Airflow Obstruction ◽  
Endothelial Injury ◽  
Chronic Obstructive ◽  
Converting Enzyme Inhibitors ◽  
Pulmonary Lesions ◽  
Copd Patients

Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients.

scholarly journals Implementation of a Targeted Screening Program to Detect Airflow Obstruction Suggestive of Chronic Obstructive Pulmonary Disease within a Presurgical Screening Clinic

2015 ◽  
Vol 22 (4) ◽  
pp. 209-214 ◽  
Author(s):  
Chantal Robitaille ◽  
Esther Dajczman ◽  
Andrew M Hirsch ◽  
David Small ◽  
Pierre Ernst ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Screening Program ◽  
Tertiary Care ◽  
Airflow Obstruction ◽  
University Hospital ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Targeted Screening ◽  
History Of

BACKGROUND: Targeted spirometry screening for chronic obstructive pulmonary disease (COPD) has been studied in primary care and community settings. Limitations regarding availability and quality of testing remain. A targeted spirometry screening program was implemented within a presurgical screening (PSS) clinic to detect undiagnosed airways disease and identify patients with COPD/asthma in need of treatment optimization.OBJECTIVE: The present quality assurance study evaluated airflow obstruction detection rates and examined characteristics of patients identified through the targeted screening program.METHODS: The targeted spirometry screening program was implemented within the PSS clinic of a tertiary care university hospital. Current or ex-smokers with respiratory symptoms and patients with a history of COPD or asthma underwent prebronchodilator spirometry. History of airways disease and smoking status were obtained during the PSS assessment and confirmed through chart reviews.RESULTS: After exclusions, the study sample included 449 current or ex-smokers. Abnormal spirometry results were found in 184 (41%) patients: 73 (16%) had mild, 93 (21%) had moderate and 18 (4%) had severe or very severe airflow obstruction. One hundred eighteen (26%) new cases of airflow obstruction suggestive of COPD were detected. One-half of these new cases had moderate or severe airflow obstruction. Only 34% of patients with abnormal spirometry results had reported a previous diagnosis of COPD. More than one-half of patients with abnormal spirometry results were current smokers.CONCLUSIONS: Undiagnosed airflow obstruction was detected in a significant number of smokers and ex-smokers through a targeted screening program within a PSS clinic. These patients can be referred for early intervention and secondary preventive strategies.

scholarly journals Household Food Insecurity, Lung Function, and COPD in US Adults

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2098
Author(s):  
Francisca de Castro Mendes ◽  
Kirstie Ducharme-Smith ◽  
Gustavo Mora-Garcia ◽  
Saleh A. Alqahtani ◽  
Maria Stephany Ruiz-Diaz ◽  
...  
Keyword(s):  
Lung Function ◽  
Food Insecurity ◽  
Representative Sample ◽  
Airflow Obstruction ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Us ◽  
Nationally Representative ◽  
Lung Health

Increasing epidemiological evidence suggests that optimal diet quality helps to improve preservation of lung function and to reduce chronic obstructive pulmonary disease (COPD) risk, but no study has investigated the association of food insecurity (FI) and lung health in the general population. Using data from a representative sample of US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles, we investigated the association between FI with lung function and spirometrically defined COPD in 12,469 individuals aged ≥ 18 years of age. FI (high vs. low) was defined using the US Department of Agriculture’s Food Security Scale). Population-weighted adjusted regression models were used to investigate associations between FI, and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio, and spirometrically defined restriction (FVC below the lower limit of normal) and airflow obstruction (COPD). The prevalence of household FI was 13.2%. High household FI was associated with lower FVC (adjusted β-coefficient −70.9 mL, 95% CI −116.6, −25.3), and with higher odds (OR) of spirometric restriction (1.02, 95% CI 1.00, 1.03). Stratified analyses showed similar effect sizes within specific ethnic groups. High FI was associated with worse lung health in a nationally representative sample of adults in the US.

scholarly journals Chronic obstructive pulmonary disease Assessment Test na avaliação de pacientes com doença pulmonar obstrutiva crônica em reabilitação pulmonar: há relação com nível de dispneia nas atividades de vida diária e com índice preditor de mortalidade? Estudo transversal

2013 ◽  
Vol 20 (4) ◽  
pp. 379-386
Author(s):  
Júlia Gianjoppe-Santos ◽  
Samantha Maria Nyssen ◽  
Bruna Varanda Pessoa ◽  
Renata Pedrolongo Basso-Vanelli ◽  
Mauricio Jamami ◽  
...  
Keyword(s):  
Daily Living ◽  
Research Council ◽  
Medical Research Council ◽  
Airflow Obstruction ◽  
Disease Assessment ◽  
Chronic Obstructive ◽  
Activity Of Daily Living ◽  
Obstructive Pulmonary Disease ◽  
Copd Assessment Test ◽  
Indice Bode

O objetivo do estudo foi investigar se há relação entre o impacto da Doença Pulmonar Obstrutiva Crônica (DPOC) no estado de saúde com o nível de dispneia nas atividades de vida diária (AVD) e o índice preditor de mortalidade em pacientes em reabilitação pulmonar (RP). Trata-se de um estudo transversal, em que foram avaliados 32 pacientes com DPOC moderada a muito grave (23 homens; 66,6±12,0 anos; VEF1: 40,6±15,6% previsto) por meio do COPD Assessment Test (CAT), Índice de Massa Corpórea (IMC), Teste de Caminhada de Seis Minutos (TC6), London Chest Activity of Daily Living Scale (LCADL), modified Medical Research Council (mMRC) e Índice BODE (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity). Observaram-se correlações positivas moderadas do CAT com o questionário mMRC (r=0,35; p=0,048), a pontuação total da LCADL (r=0,60; p<0,001) e com a porcentagem da pontuação total da LCADL (r=0,57; p=0,001). Apenas a pontuação total da LCADL é capaz de predizer independentemente a pontuação do questionário CAT (p<0,05; r²=0,61). Não foram constatadas correlações significativas entre o CAT e o Índice BODE, IMC, TC6 e VEF1. Dessa forma, quanto maior o nível de dispneia nas AVD, maior o impacto da DPOC no estado de saúde do paciente, entretanto, o mesmo não ocorre em relação ao prognóstico de mortalidade nos pacientes com DPOC em RP.

Identification of endothelial cell genes by combined database mining and microarray analysis

2003 ◽  
Vol 13 (3) ◽  
pp. 249-262 ◽  
Author(s):  
Michael Ho ◽  
Eugene Yang ◽  
George Matcuk ◽  
David Deng ◽  
Nick Sampas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Biology ◽  
Soft Tissues ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Primary Data ◽  
Database Mining ◽  
Novel Genes

Vascular endothelial cells maintain the interface between the systemic circulation and soft tissues and mediate critical processes such as inflammation in a vascular bed-selective fashion. To expand our understanding of the genetic pathways that underlie these specific functions, we have focused on the identification of novel genes that are differentially expressed in all endothelial cells, as well as restricted groups of this cell type. Virtual subtraction was conducted employing gene expression data deposited in public databases and 384 genes identified.11 The microarray data derived through these experiments have been deposited in the GEO expression database at the NCBI and has been given the accession number GPL217 , with others pending. Primary data and supplementary material associated with this manuscript are being deposited at the following website: http://quertermous.stanford.edu . These genes were spotted on custom microarrays, along with 288 genes identified through subtraction cloning from TGF-β-stimulated endothelial cells. Arrays were evaluated with RNA samples representing endothelial cells cultured from four vascular sources and five non-endothelial cell types. These studies identified 64 pan-endothelial markers that were differentially expressed with at least a threefold difference (range 3- to 55-fold). In addition, differences in gene expression profiles among endothelial cells from different vascular beds were identified. Validation of these findings was performed by RNA blot expression studies, and a number of the novel genes were shown to be expressed under angiogenic conditions in the developing mouse embryo. The combined tools of database mining and transcriptional profiling thus provide expanded knowledge of endothelial cell gene expression and endothelial cell biology.

scholarly journals Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease

2010 ◽  
Vol 5 ◽  
Author(s):  
Deniz Inal-Ince ◽  
Sema Savci ◽  
Melda Saglam ◽  
Ebru Calik ◽  
Hulya Arikan ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Disease Severity ◽  
Airflow Obstruction ◽  
Muscle Endurance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Bode Index ◽  
Peripheral Muscle ◽  
St George's Respiratory Questionnaire

Background and aims: Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD). Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Materials and methods: Twenty-two patients with COPD (aged 52-74 years) took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Results: Thirteen patients (59%) had severe fatigue, and their St George’s Respiratory Questionnaire scores were significantly higher (p < 0.05). The SAFE index score was significantly correlated with the number of sit-ups, number of squats, FSS score and FIS score (p < 0.05). The BODE index was signif- icantly associated with the numbers of sit-ups, squats and modified push-ups, and with the FSS and FIS scores (p < 0.05). Conclusions: Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.

scholarly journals A literature review on depression and its risk factors among people suffering from chronic obstructive pulmonary disease in Asian sub-continent

2020 ◽  
Vol 7 (11) ◽  
pp. 4653
Author(s):  
Amrit Sharma
Keyword(s):  
Risk Factors ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Low Income ◽  
Airflow Obstruction ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Inflammatory Response ◽  
Basic Activity

Chronic obstructive pulmonary disease (COPD) is defined as persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. It has been suggested that emotional disturbances such as depression and anxiety are common among patients with COPD. This review aims to highlight the presence of depression and associated risk factors among patients suffering from COPD in Asia. Fifty-eight observational studies were retrieved through data sources like PubMed, Medical subject heading (MeSH) search and Google scholar. After thorough screening total thirteen studies were identified and included in this review. Based on the results of these studies, the south and west Asian countries had higher proportion of depression. However, risk factor results were mixed which includes severity of obstruction/global initiative for obstructive lung disease (GOLD) criteria, Stage 2 COPD, teetotallers, smoking, alcohol consumption, body mass index, airflow obstruction, dyspnoea, and exercise (BODE) index, urban residence, female gender, education level, dyspnoea, low income, poor Quality of life (QOL) scores, age, poor self-reported health, basic activity of daily living (BADL) disability. Further superior research studies with larger sample size are required on Asian population. All in all, it is recommended that early diagnosis and treatment of depression should be included as a part of management in COPD as it can help to minimize the risk of morbidity and mortality in the patients.

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