scholarly journals The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease

2017 ◽  
Vol 97 (2) ◽  
pp. 529-552 ◽  
Author(s):  
James C. Hogg ◽  
Peter D. Paré ◽  
Tillie-Louise Hackett
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Molecular Mechanisms ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Major Site ◽  
Obstructive Pulmonary Disease ◽  
Airways Resistance ◽  
Conducting Airways ◽  
Normal Lungs

The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways <2 mm in diameter. Shortly thereafter, Hogg, Macklem, and Thurlbeck used this technique to show that small airways become the major site of obstruction in lungs affected by emphysema. These and other observations led Mead to write a seminal editorial in 1970 that postulated the small airways are a silent zone within normal lungs where disease can accumulate over many years without being noticed. This review provides a progress report since the 1970s on methods for detecting chronic obstructive pulmonary disease, the structural nature of small airways' disease, and the cellular and molecular mechanisms that are thought to underlie its pathogenesis.

scholarly journals Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study

2018 ◽  
Vol 6 (8) ◽  
pp. 591-602 ◽  
Author(s):  
Hyun-Kyoung Koo ◽  
Dragoş M Vasilescu ◽  
Steven Booth ◽  
Aileen Hsieh ◽  
Orestis L Katsamenis ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cross Sectional Study ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Sectional Study ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease

scholarly journals THE ROLE OF INTERLEUKIN-6 SIGNALING IN DEVELOPMENT OF SYSTEMIC INFLAMMATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

2018 ◽  
Vol 1 (69) ◽  
pp. 97-106 ◽  
Author(s):  
Татьяна Виткина ◽  
Tatyana Vitkina ◽  
К Сидлецкая ◽  
K Sidleckaya
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Systemic Inflammation ◽  
Interleukin 6 ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Damage Initiation

The review focuses on the role of interleukin-6 (IL-6) signaling in the development of a systemic inflammatory process in chronic obstructive pulmonary disease (COPD). In most researches the attention is paid to local inflammation in COPD. However, it is known that the pathology is characterized by a systemic inflammatory process, which is manifested in the increased levels of proinflammatory mediators in blood flow, and the study of the molecular mechanisms of its development is very important for the therapy of the disease. One of the key mediators of systemic inflammation is cytokine IL-6 which has pro- and antiinflammatory properties. Its effect on the cells is determined by the type of signaling. Nowadays three types of IL-6 signaling are identified: transsignaling, classical and cluster signaling. The review presents the known pathophysiological mechanisms of the development of systemic inflammation in COPD involving IL-6. As a proinflammatory cytokine, IL-6 performs the following functions: transmission of a signal on lung tissue damage, initiation of leukocyte migration into the inflammation site, inhibition of T-cell apoptosis into the inflammation site, influence on T helper differentiation, participation in pathophysiological reactions of development of emphysema and fibrosis. The significance of IL-6 transsignaling for the development of inflammation in COPD has been confirmed by many studies, while there are practically no works devoted to the study of classical IL-6 signaling in COPD. The data presented in the review indicate the need for further study of the role of different types of IL-6 signaling, especially classical signaling, in the regulation of systemic inflammation in COPD.

scholarly journals The role of airway remodeling in the pathogenesis and treatment of chronic obstructive pulmonary disease

2021 ◽  
Vol 8 (3) ◽  
pp. 96-102
Author(s):  
Nightingale Syabbalo
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Epithelial Cells ◽  
Pulmonary Disease ◽  
Airway Remodeling ◽  
Inflammatory Cells ◽  
Lymphoid Cells ◽  
Standards Of Care ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is currently considered the third leading cause of death in the world. COPD represents an important public health challenge and a socio-economical problem that is preventable and treatable. The main cause of COPD is chronic inhalation of cigarette smoke, and other harmful constituents of air pollution, which cause epithelial injury, chronic inflammation and airway remodeling. Airway remodeling is most prominent in small airways. It is due to infiltration of the airways by inflammatory cells, such as neutrophils, eosinophils, macrophages, and immune cells, including CD8+ T-cells, Th1, Th17 lymphocytes, and innate lymphoid cells group 3. Fibroblasts, myofibroblasts, and airway smooth muscle (ASM) cells also contribute to airway remodeling by depositing extracellular matrix (ECM) proteins, which increase the thickness of the airway wall. Activated inflammatory cells, and structural cells secrete cytokines, chemokines, growth factors, and enzymes which propagate airway remodeling. Airway remodeling is an active process which leads to thickness of the reticular basement membrane, subepithelial fibrosis, peribronchiolar fibrosis, and ASM cells hyperplasia and hypertrophy. It is also accompanied by submucosal glands and goblet cells hypertrophy and mucus hypersecretion, and angiogenesis. Epithelial mesenchymal transmission (EMT) plays a key role in airway remodeling. In patients with COPD and smokers, cellular reprograming in epithelial cells leads to EMT, whereby epithelial cells assume a mesencymal phenotype. Additionally, COPD is associated with increased parasympathetic cholinergic activity, which leads to ASM cells hypercontractility, increased mucus secretion, and vasodilatation. Treatment of COPD is intricate because of the heterogeneous nature of the disease, which requires specific treatment of the pathophysiological pathways, such as airway inflammation, ASM cell hypercontractility, and parasympathetic cholinergic hyperreactivity. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 strategy report recommends personalized approach for the treatment of COPD. However, some patients with COPD are unresponsive to the standards of care. They may require a triple combination of LABA/LAMA/ICS. Single-inhaler triple therapy (SITT), such as fluticasone fuorate/vilanterol/umeclidinium has been shown to significantly improve symptoms and asthma control, reduce moderate and severe exacerbations, and to improve lung function.

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