scholarly journals Airway morphometry in COPD with bronchiectasis: a view on all airway generations

2019 ◽  
Vol 54 (5) ◽  
pp. 1802166 ◽  
Author(s):  
Stephanie Everaerts ◽  
John E. McDonough ◽  
Stijn E. Verleden ◽  
Iván Josipovic ◽  
Matthieu Boone ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Large Airway ◽  
Imaging Approach ◽  
Large Airways ◽  
Airway Segmentation ◽  
Airway Tree ◽  
Microct Analysis

The pathophysiological processes underlying bronchiectasis in chronic obstructive pulmonary disease (COPD) are not understood. In COPD, both small and large airways are progressively lost. It is currently not known to what extent the different airway generations of patients with COPD and bronchiectasis are involved.COPD explant lungs with bronchiectasis were compared to COPD explant lungs without bronchiectasis and unused donor lungs as controls. In order to investigate all airway generations, a multimodal imaging approach using different resolutions was conducted. Per group, five lungs were frozen (n=15) and underwent computed tomography (CT) imaging for large airway evaluation, with four tissue cores per lung imaged for measurements of the terminal bronchioles. Two additional lungs per group (n=6) were air-dried for lobar microCT images that allow airway segmentation and three-dimensional quantification of the complete airway tree.COPD lungs with bronchiectasis had significantly more airways compared to COPD lungs without bronchiectasis (p<0.001), with large airway numbers similar to control lungs. This difference was present in both upper and lower lobes. Lack of tapering was present (p=0.010) and larger diameters were demonstrated in lower lobes with bronchiectasis (p=0.010). MicroCT analysis of tissue cores showed similar reductions of tissue percentage, surface density and number of terminal bronchioles in both COPD groups compared to control lungs.Although terminal bronchioles were equally reduced in COPD lungs with and without bronchiectasis, significantly more large and small airways were found in COPD lungs with bronchiectasis.

scholarly journals Different Patterns of Lung Sirtuin Expression in Smokers With and Without Chronic Obstructive Pulmonary Disease

Medicina ◽  
2012 ◽  
Vol 48 (10) ◽  
pp. 80 ◽  
Author(s):  
Sergejs Isajevs ◽  
Gunta Strazda ◽  
Uldis Kopeika ◽  
Immanuels Taivans
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inflammatory Responses ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Nonhistone Proteins ◽  
Proinflammatory Mediators ◽  
Large Airways

Background and Objective. Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. Material and Methods. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study. Immunohistochemical and Western blot methods were used to analyze sirtuin expression in the airways. Results. The obtained results showed the nonuniform sirtuin expression throughout the bronchial tree. Smokers both with and without chronic obstructive pulmonary disease had decreased sirtuin expression in large airways. However, in small airways, sirtuin expression was decreased only in patients with chronic obstructive pulmonary disease. In addition, a correlation between airflow limitation, smoked pack-years and the number of sirtuin-positive cells in airways was found. Conclusions. Smoking is characterized by suppressed sirtuin expression in large airways, whereas chronic obstructive pulmonary disease is characterized by more severe suppression of sirtuin expression both in large and small airways.

scholarly journals Unravelling the complexity of COPD by microRNAs: it's a small world after all

2015 ◽  
Vol 46 (3) ◽  
pp. 807-818 ◽  
Author(s):  
Emmanuel T. Osei ◽  
Laura Florez-Sampedro ◽  
Wim Timens ◽  
Dirkje S. Postma ◽  
Irene H. Heijink ◽  
...  
Keyword(s):  
Lung Disease ◽  
Noncoding Rnas ◽  
Small World ◽  
Therapeutic Strategies ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Small Noncoding Rnas ◽  
Health And Disease ◽  
Therapeutic Alternatives

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the fourth leading cause of death worldwide. Chronic inflammation and repair processes in the small airways are characteristic of COPD. Despite extensive efforts from researchers and industry, there is still no cure for COPD, hence an urgent need for new therapeutic alternatives. MicroRNAs are such an option; they are small noncoding RNAs involved in gene regulation. Their importance has been shown with respect to maintaining the balance between health and disease. Although previous reviews have discussed the expression of microRNAs related to lung disease, a detailed discussion regarding the function of differential miRNA expression in the pathogenesis of COPD is lacking.In this review we link the expression of microRNAs to different features of COPD and explain their importance in the pathogenesis of this disease. We further discuss their potential to contribute to the development of future therapeutic strategies.

scholarly journals Regenerative pharmacology for COPD: breathing new life into old lungs

Thorax ◽  
2019 ◽  
Vol 74 (9) ◽  
pp. 890-897 ◽  
Author(s):  
John-Poul Ng-Blichfeldt ◽  
Reinoud Gosens ◽  
Charlotte Dean ◽  
Mark Griffiths ◽  
Matthew Hind
Keyword(s):  
Large Scale ◽  
Biologically Active ◽  
Health Concern ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Molecular Control ◽  
Mild Disease ◽  
Peripheral Airway ◽  
Alveolar Tissue

Chronic obstructive pulmonary disease (COPD) is a major global health concern with few effective treatments. Widespread destruction of alveolar tissue contributes to impaired gas exchange in severe COPD, and recent radiological evidence suggests that destruction of small airways is a major contributor to increased peripheral airway resistance in disease. This important finding might in part explain the failure of conventional anti-inflammatory treatments to restore lung function even in patients with mild disease. There is a clear need for alternative pharmacological strategies for patients with COPD/emphysema. Proposed regenerative strategies such as cell therapy and tissue engineering are hampered by poor availability of exogenous stem cells, discouraging trial results, and risks and cost associated with surgery. An alternative therapeutic approach is augmentation of lung regeneration and/or repair by biologically active factors, which have potential to be employed on a large scale. In favour of this strategy, the healthy adult lung is known to possess a remarkable endogenous regenerative capacity. Numerous preclinical studies have shown induction of regeneration in animal models of COPD/emphysema. Here, we argue that given the widespread and irreversible nature of COPD, serious consideration of regenerative pharmacology is necessary. However, for this approach to be feasible, a better understanding of the cell-specific molecular control of regeneration, the regenerative potential of the human lung and regenerative competencies of patients with COPD are required.

scholarly journals The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Xianyan Liu ◽  
Binwei Hao ◽  
Ailing Ma ◽  
Jinxi He ◽  
Xiaoming Liu ◽  
...  
Keyword(s):  
Disease Severity ◽  
Transforming Growth Factor ◽  
Smooth Muscles ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Small Airway ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Functions ◽  
Copd Patients

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factorβ(TGF-β) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-β, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM markerα-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-βin the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-βsignaling in the pathogenesis of COPD, which warrants further investigation.

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

Image Based Simulation of Pulmonary Airflow Using Multi-Level Voxel Modeling

2007 ◽  
Author(s):  
Yohsuke Imai ◽  
Takahito Miki ◽  
Masanori Nakamura ◽  
Takuji Ishikawa ◽  
Shigeo Wada ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Airflow Obstruction ◽  
Three Dimensional ◽  
Patient Specific ◽  
Chronic Obstructive ◽  
Local Domain ◽  
Local Flow ◽  
Obstructive Pulmonary Disease ◽  
Multi Level ◽  
Cfd Method

Chronic Obstructive Pulmonary Disease (COPD) refers to a group of diseases that are characterized by airflow obstruction. Currently, COPD is the fourth leading cause of death worldwide, but fluid dynamics in airways of COPD patients has not been well understood. Multi-slice Computer Tomography (CT) images provide three-dimensional realistic geometry of patient airways. Computational Fluid Dynamics (CFD) analysis using the patient-specific geometry will greatly help the understanding of the mechanism of COPD. However, few studies have performed such a patient-specific pulmonary airflow simulation. Our aim is to develop a patient-specific CFD method applicable to multi-scale airways, involving trachea, bronchi, bronchioles, and alveoli. We propose a CFD method using multi-level voxel modeling of airway geometry, in which voxel size in a local domain is adaptively refined or coarsened to the local flow scale.

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