scholarly journals “Targeted Therapy in Eosinophilic Chronic Obstructive Pulmonary Disease”

2021 ◽  
pp. 00437-2020
Author(s):  
Mathieu Fieldes ◽  
Chloé Bourguignon ◽  
Said Assou ◽  
Amel Nasri ◽  
Aurélie Fort ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Airway Inflammation ◽  
Pulmonary Disease ◽  
Public Health Problem ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Eosinophilic Asthma ◽  
Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a common and preventable airway disease causing significant worldwide mortality and morbidity. Lifetime exposure to tobacco smoking and environmental particles are the two major risk factors. Over the last decades, COPD has become a growing public health problem with an increase in incidence. COPD is defined by airflow limitation due to airway inflammation and small airway remodelling coupled to parenchymal lung destruction. Most patients exhibit neutrophil-predominant airway inflammation combined with an increase in macrophages and CD8+ T-cells. Asthma is a heterogeneous chronic inflammatory airway disease. The most studied subtypes is T2 high eosinophilic asthma, for which there are an increasing number of biologic agents developed. However, both asthma and COPD are complex and share common pathophysiologic mechanisms. They are known as overlapping syndromes as approximately 40% of patients with COPD present an eosinophilic airway inflammation. Several studies suggest a putative role of eosinophilia in lung function decline and COPD exacerbation. Recently, pharmacological agents targeting eosinophilic traits in uncontrolled eosinophilic asthma, especially monoclonal antibodies directed against interleukins (IL5, IL4, IL13) or their receptors, have shown promising results. This review examines data on the rationale for such biological agents and assesses efficacy in T2-endotype COPD patients.

scholarly journals Emerging Therapeutic Options for the Management of COPD

2013 ◽  
Vol 7 ◽  
pp. CCRPM.S8140 ◽  
Author(s):  
Debra J. Reid ◽  
Nga T. Pham
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Airway Inflammation ◽  
Pulmonary Disease ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Current Management ◽  
Efficacy Data ◽  
Obstructive Pulmonary Disease ◽  
Safety And Efficacy ◽  
The Third

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is projected to be the third by 2020. COPD is characterized by chronic airflow limitation caused by airway inflammation and parenchymal destruction that is usually progressive. Inhaled bronchodilators continue to be the mainstay of the current management of COPD. Safety and efficacy data of the recently approved medications including aclidinium, glycopyrronium, roflumilast, and indacaterol are reviewed here.

scholarly journals Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
◽  
Ying-Huang Tsai ◽  
Chin-Chou Wang ◽  
Shih-Feng Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Dna Methylations

AbstractWe hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

scholarly journals Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 161
Author(s):  
Lucas A. Gillenwater ◽  
Katerina J. Kechris ◽  
Katherine A. Pratte ◽  
Nichole Reisdorph ◽  
Irina Petrache ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Sex Differences ◽  
Pulmonary Disease ◽  
Specific Effect ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Female Specific

Susceptibility and progression of lung disease, as well as response to treatment, often differ by sex, yet the metabolic mechanisms driving these sex-specific differences are still poorly understood. Women with chronic obstructive pulmonary disease (COPD) have less emphysema and more small airway disease on average than men, though these differences become less pronounced with more severe airflow limitation. While small studies of targeted metabolites have identified compounds differing by sex and COPD status, the sex-specific effect of COPD on systemic metabolism has yet to be interrogated. Significant sex differences were observed in 9 of the 11 modules identified in COPDGene. Sex-specific associations by COPD status and emphysema were observed in 3 modules for each phenotype. Sex stratified individual metabolite associations with COPD demonstrated male-specific associations in sphingomyelins and female-specific associations in acyl carnitines and phosphatidylethanolamines. There was high preservation of module assignments in SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) and similar female-specific shift in acyl carnitines. Several COPD associated metabolites differed by sex. Acyl carnitines and sphingomyelins demonstrate sex-specific abundances and may represent important metabolic signatures of sex differences in COPD. Accurately characterizing the sex-specific molecular differences in COPD is vital for personalized diagnostics and therapeutics.

Chronic obstructive pulmonary disease

2010 ◽  
pp. 3311-3344 ◽  
Author(s):  
William MacNee
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Case History ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Small Airway Disease ◽  
Variable Extent ◽  
Considerable Morbidity

Case History—A 37 yr old woman with slowly progressive breathlessness. Case History—A 45 yr old man with increasing symptoms from his known COPD. Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition that produces considerable morbidity and mortality. It is characterized by airflow limitation that is not fully reversible and is associated with an enhanced inflammatory response in the airways and the lungs to noxious particles or gases. COPD is a group of lung conditions—chronic bronchitis (a chronic productive cough on most days for 3 months, in each of two consecutive years), small-airway disease (obstructive bronchiolitis), and emphysema (abnormal, permanent enlargement of the air spaces, distal to the terminal bronchioles, accompanied by destruction of their walls) that are present to a variable extent in different individuals resulting in heterogeneous presentations of the condition. Exacerbations and comorbidities contribute to the overall severity of the condition in individual patients....

scholarly journals The Heterogeneity of Inflammatory Response and Emphysema in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xia Xu ◽  
Ke Huang ◽  
Fen Dong ◽  
Shiwei Qumu ◽  
Qichao Zhao ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Inflammatory Response ◽  
Airway Inflammation ◽  
Pulmonary Disease ◽  
Airway Remodeling ◽  
Neutrophil Infiltration ◽  
Airway Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Alveolar Septa

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic inflammation, emphysema, airway remodeling, and altered lung function. Despite the canonical classification of COPD as a neutrophilic disease, blood and airway eosinophilia are found in COPD patients. Identifying the tools to assess eosinophilic airway inflammation in COPD models during stable disease and exacerbations will enable the development of novel anti-eosinophilic treatments. We developed different animal models to mimic the pathological features of COPD. Our results show that eosinophils accumulated in the lungs of pancreatic porcine elastase-treated mice, with emphysema arising from the alveolar septa. A lipopolysaccharide challenge significantly increased IL-17 levels and induced a swift change from a type-2 response to an IL-17-driven inflammatory response. However, lipopolysaccharides can exacerbate cigarette smoking-induced airway inflammation dominated by neutrophil infiltration and airway remodeling in COPD models. Our results suggest that eosinophils may be associated with emphysema arising from the alveolar septa, which may be different from the small airway disease-associated emphysema that is dominated by neutrophilic inflammation in cigarette smoke-induced models. The characterization of heterogeneity seen in the COPD-associated inflammatory signature could pave the way for personalized medicine to identify new and effective therapeutic approaches for COPD.

scholarly journals COPD Guidelines in the Asia-Pacific Regions: Similarities and Differences

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1153
Author(s):  
Shih-Lung Cheng ◽  
Ching-Hsiung Lin
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Global Strategy ◽  
Airflow Limitation ◽  
Asia Pacific ◽  
Pharmacologic Therapy ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Country Level ◽  
Similarities And Differences

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that is associated with significant morbidity and mortality, giving rise to an enormous social and economic burden. The Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) report is one of the most frequently used documents for managing COPD patients worldwide. A survey was conducted across country-level members of Asia-Pacific Society of Respiratory (APSR) for collecting an updated version of local COPD guidelines, which were implemented in each country. This is the first report to summarize the similarities and differences among the COPD guidelines across the Asia-Pacific region. The degree of airflow limitation, assessment of COPD severity, management, and pharmacologic therapy of stable COPD will be reviewed in this report.

scholarly journals Alternative methods for assessing bronchodilator reversibility in chronic obstructive pulmonary disease

Thorax ◽  
2001 ◽  
Vol 56 (9) ◽  
pp. 713-720
Author(s):  
J Hadcroft ◽  
P M A Calverley
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Lung Volume ◽  
Tidal Flow ◽  
Airflow Limitation ◽  
Alternative Methods ◽  
Chronic Obstructive ◽  
Flow Limitation ◽  
Inspiratory Capacity ◽  
Obstructive Pulmonary Disease

BACKGROUNDBronchodilator reversibility testing is recommended in all patients with chronic obstructive pulmonary disease (COPD) but does not predict improvements in breathlessness or exercise performance. Two alternative ways of assessing lung mechanics—measurement of end expiratory lung volume (EELV) using the inspiratory capacity manoeuvre and application of negative expiratory pressure (NEP) during tidal breathing to detect tidal airflow limitation—do relate to the degree of breathlessness in COPD. Their usefulness as end points in bronchodilator reversibility testing has not been examined.METHODSWe studied 20 patients with clinically stable COPD (mean age 69.9 (1.5) years, 15 men, forced expiratory volume in one second (FEV1) 29.5 (1.6)% predicted) with tidal flow limitation as assessed by their maximum flow-volume loop. Spirometric parameters, slow vital capacity (SVC), inspiratory capacity (IC), and NEP were measured seated, before and after nebulised saline, and at intervals after 5 mg nebulised salbutamol and 500 μg nebulised ipratropium bromide. The patients attended twice and the treatment order was randomised.RESULTSMean FEV1, FVC, SVC, and IC were unchanged after saline but the degree of tidal flow limitation varied. FEV1 improved significantly after salbutamol and ipratropium (0.11 (0.02) l and 0.09 (0.02) l, respectively) as did the other lung volumes with further significant increases after the combination. Tidal volume and mean expiratory flow increased significantly after all bronchodilators but breathlessness fell significantly only after the combination treatment. The initial NEP score was unrelated to subsequent changes in lung volume.CONCLUSIONSNEP is not an appropriate measurement of acute bronchodilator responsiveness. Changes in IC were significantly larger than those in FEV1and may be more easily detected. However, our data showed no evidence for separation of “reversible” and “irreversible” groups whatever outcome measure was adopted.

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