scholarly journals Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease

2015 ◽  
Vol 79 (5) ◽  
pp. 767-776 ◽  
Author(s):  
Vandana Gupta ◽  
Antonia Banyard ◽  
Aoibheann Mullan ◽  
Srividya Sriskantharajah ◽  
Thomas Southworth ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Inflammatory Response ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

Biologia ◽  
2008 ◽  
Vol 63 (1) ◽  
Author(s):  
Eva Slabá ◽  
Pavol Joppa ◽  
Ján Šalagovič ◽  
Ružena Tkáčová
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Inflammatory Response ◽  
Candidate Genes ◽  
Pulmonary Disease ◽  
Gene Polymorphisms ◽  
Association Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Positional Candidate ◽  
Linkage Analyses

AbstractChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20–30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.

scholarly journals Pneumonic versus Nonpneumonic Exacerbations of Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 41 (06) ◽  
pp. 817-829
Author(s):  
Ernesto Crisafulli ◽  
Alessandra Manco ◽  
Miquel Ferrer ◽  
Arturo Huerta ◽  
Claudio Micheletto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Inflammatory Response ◽  
Pulmonary Disease ◽  
Defense Mechanisms ◽  
Community Acquired Pneumonia ◽  
Systemic Inflammatory Response ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Reactive Protein ◽  
The Impact

AbstractPatients with chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations (AECOPD) and community-acquired pneumonia (CAP), named nonpneumonic and pneumonic exacerbations of COPD, respectively. Abnormal host defense mechanisms may play a role in the specificity of the systemic inflammatory response. Given the association of this aspect to some biomarkers at admission (e.g., C-reactive protein), it can be used to help to discriminate AECOPD and CAP, especially in cases with doubtful infiltrates and advanced lung impairment. Fever, sputum purulence, chills, and pleuritic pain are typical clinical features of CAP in a patient with COPD, whereas isolated dyspnea at admission has been reported to predict AECOPD. Although CAP may have a worse outcome in terms of mortality (in hospital and short term), length of hospitalization, and early readmission rates, this has only been confirmed in a few prospective studies. There is a lack of methodologically sound research confirming the impact of severe AECOPD and COPD + CAP. Here, we review studies reporting head-to-head comparisons between AECOPD and CAP + COPD in hospitalized patients. We focus on the epidemiology, risk factors, systemic inflammatory response, clinical and microbiological characteristics, outcomes, and treatment approaches. Finally, we briefly discuss some proposals on how we should orient research in the future.

scholarly journals Evolutionary and Prognostic Particularities in Patients with COPD, Chronic Cor Pulmonale and COVID-19

2021 ◽  
Vol 26 (3) ◽  
pp. 34-36
Author(s):  
Nicoleta-Alina Popa ◽  
Adina-Marieta Sipos ◽  
Mircea Ioachim Popescu
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Chronic Disease ◽  
Inflammatory Response ◽  
Pulmonary Disease ◽  
Cor Pulmonale ◽  
Chronic Obstructive ◽  
Toxic Substances ◽  
Obstructive Pulmonary Disease ◽  
Chronic Cor Pulmonale ◽  
A Current

Abstract Chronic obstructive pulmonary disease (COPD) is a chronic disease of the respiratory airways due to the partially reversible obstruction of the airflow caused by an abnormal inflammatory response to toxic substances, most often to cigarette smoke.(1) COVID-19 is a mild to severe respiratory disease caused by a coronavirus from the genus Betacoronavirus.(2) Patients with COPD have a major risk of COVID-19 infection. Treating patients with COPD, chronic cor pulmonale and COVID-19 is a current challenge.

scholarly journals Molecular mechanisms of phenotypic heterogeneity of chronic obstructive pulmonary disease: the role of JAK / STAT-, NFKB1-signaling pathway and inflammatory response molecules

2020 ◽  
pp. 100-104
Author(s):  
Г.Ф. Корытина ◽  
Ю.Г. Азнабаева ◽  
М.Ю. Темнов ◽  
Ш.Р. Зулькарнеев ◽  
Л.З. Ахмадишина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Obstructive Pulmonary Disease ◽  
Inflammatory Response ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Peripheral Blood ◽  
Phenotypic Heterogeneity ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Хроническая обструктивная болезнь легких (ХОБЛ) - это многофакторное хроническое воспалительное заболевание респираторной системы. Одной из причин трудностей в идентификации маркеров ХОБЛ является фенотипическая гетерогенность. Цель - идентификация новых молекулярных маркеров патогенетических изменений, связанных с фенотипической гетерогеностью ХОБЛ на основе анализа профиля экспрессии генов вовлеченных в развитие иммунного ответа в мононуклеарных клетках периферической крови и анализа ассоциации полиморфных вариантов новых кандидатных генов с развитием ХОБЛ. Проведен сравнительный анализ профиля экспрессии панели 84 генов, кодирующих цитокины, хемокины в PBMC пациентов с различными фенотипами ХОБЛ: с частыми обострениями N=10 и редкими обострениями N=10 и контрольной группе N=10. Для анализа ассоциации использовали образцы ДНК больных ХОБЛ (N=601) и контроля (N=617), методом ПЦР в реальном времени проведен анализ 56 полиморфных локусов генов JAK/STAT-, NFKB1-сигнального путей, кодирующих белки, вовлеченные в реализацию реакций иммунного ответа и воспаления. Выявлены значимые изменения профиля экспрессии ряда генов в группе больных ХОБЛ с частыми обострениями. Впервые получены данные по вкладу полиморфных локусов генов JAK1, JAK3, STAT3, ICAM1, PECAM1, SAA1, NFKB1, IL17A, CCR2, CCR6, CCL8, CRP, CX3CL1, CXCR2, CXCR1, TNFRSF1A, IL20, IL19, в развитие данного заболевания. Выявлены специфические генетические маркеры развития фенотипа с частыми обострениями: CXCR2, TNFRSF1B, CCR6, TNF, IL1B, IL10, JAK3, PECAM1. Установлена ассоциация полиморфных вариантов генов TNFRSF1B, TNFRSF1A, CCL23, CXCR2, JAK1, NFKB1, PECAM1, ICAM1, STAT1, LTA, CD14, CXCL12, CCL20, ADIPOR1 и CX3CR1 с показателями функции внешнего дыхания. Определена взаимосвязь аллельных вариантов генов: IL17A, JAK1, JAK3, NFKB1, CCL5, CCL11, CCL17, CXCL8, TNFRSF1A, CX3CL1, CCL8, CCR6, CXCR2, IL19, IL20 с индексом курения. Chronic obstructive pulmonary disease (COPD) is a multifactorial heterogeneous chronic inflammatory disease of the respiratory system predominantly affecting the lower respiratory pathways and the lung parenchyma. One of the reason for difficulties in identifying of COPD markers is phenotypic heterogeneity. The goal of the study is the identification of new molecular markers of pathogenetic changes associated with phenotypic heterogeneity of COPD based on the analysis of the expression profile of genes involved in the development of the immune response in peripheral blood mononuclear cells and analysis of the association of polymorphic variants of new candidate genes with COPD. Methods: to identify differential gene expression in COPD we performed expression profiling of 84 cytokines and chemokines genes in peripheral blood samples from COPD (N=10 with frequent exacerbation phenotype, N=10 rare exacerbation phenotype) and N=10 smoking controls. RNA was isolated from PBMCs, and gene expression was assessed using RT2 Profiler PCR Arrays «Human Cytokines & Chemokines PCR Array»» (Qiagen, Valencia, CA, USA). 56 SNPs of JAK / STAT-, NFKB1-signaling pathway and inflammatory response molecules genes were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case-control study (601 COPD patients and 617 controls). Results. Significant changes were revealed in the expression profile of several genes in “frequent exacerbator» COPD phenotype. The results indicate a down-regulation of inflammatory molecules in “frequent exacerbator» COPD phenotype. For the first time, we indicated the contribution of JAK1, JAK3, STAT3, ICAM1, PECAM1, SAA1, NFKB1, IL17A, CCR2, CCR6, CCL8, CRP, CX3CL1, CXCR2, CXCR1, TNFRSF1A, IL20, IL19 genes polymorphisms to COPD. Specific genetic markers of “frequent exacerbator” COPD phenotype have been identified, which are modifiers of COPD progression, including polymorphic loci of the CXCR2, TNFRSF1B, CCR6, TNF, IL1B, IL10, JAK3, PECAM1 genes. A significant genotype-dependent variation of lung function parameters was observed for CXCR2, JAK1, NFKB1, PECAM1, ICAM1, STAT1, LTA, CD14, CXCL12, CCL20, ADIPOR1 and CX3CR1 genes. The relationship of IL17A, JAK1, JAK3, NFKB1, CCL5, CCL11, CCL17, CXCL8, TNFRSF1A, CX3CL1, CCL8, CCR6, CXCR2, IL19, IL20 genes with smoking pack-years was found.

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