Osteopontin Expression in Small Airway Epithelium in Copd is Dependent on Differentiation and Confined to Subsets of Cells

Abstract Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small airways and in scattered cells within the epithelial cell layer. Staining revealed higher OPN concentrations in tissue showing moderate to severe COPD compared to that in controls. In addition, OPN expression was confined to goblet and club cells, and was absent from ciliated and basal cells as detected via immunohistochemistry. However, OPN expression was up-regulated in submerged basal cells cultures exposed to cigarette smoke (CS) extract. Cell fractioning of air-liquid interface cultures revealed increased OPN production from basal compartment cells compared to that in luminal fraction cells. Furthermore, both constitutive and CS-induced expression of OPN decreased during differentiation. In contrast, cultures stimulated with interleukin (IL)-13 to promote goblet cell hyperplasia showed increased OPN production in response to CS exposure. These results indicate that the cellular composition of the airway epithelium plays an important role in OPN expression and that these levels may reflect disease endotypes in COPD.

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Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in COPD

10.1101/2020.11.11.379099 ◽

2020 ◽

Author(s):

Jaspreet K. Osan ◽

Sattya N. Talukdar ◽

Friederike Feldmann ◽

Beth Ann DeMontigny ◽

Kailey Jerome ◽

...

Keyword(s):

Goblet Cell ◽

Airway Epithelium ◽

Critical Role ◽

Syncytium Formation ◽

Goblet Cells ◽

Severe Illness ◽

Chronic Obstructive ◽

Cell Hyperplasia ◽

Obstructive Pulmonary Disease ◽

Goblet Cell Hyperplasia

SummarySARS-CoV-2 has become a major problem across the globe, with approximately 50 million cases and more than 1 million deaths and currently no approved treatment or vaccine. Chronic obstructive pulmonary disease (COPD) is one of the underlying conditions in adults of any age that place them at risk for developing severe illness associated with COVID-19. We established an airway epithelium model to study SARS-CoV-2 infection in healthy and COPD lung cells. We found that both the entry receptor ACE2 and the co-factor transmembrane protease TMPRSS2 are expressed at higher levels on nonciliated goblet cell, a novel target for SARS-CoV-2 infection. We observed that SARS-CoV-2 infected goblet cells and induced syncytium formation and cell sloughing. We also found that SARS-CoV-2 replication was increased in the COPD airway epithelium likely due to COPD associated goblet cell hyperplasia. Our results reveal goblet cells play a critical role in SARS-CoV-2 infection in the lung.

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Correlation between Level of Autophagy and Amount of CD8+T Cells in Chronic Obstructive Pulmonary Disease

10.21203/rs.3.rs-36595/v1 ◽

2020 ◽

Author(s):

Songming Zhuo ◽

Hong Zhuang ◽

Na Li ◽

Sida Chen ◽

Wugen Zhan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lung Function ◽

Normal Lung ◽

Stable Phase ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Normal Lung Function ◽

Healthy Control ◽

Function Group

Abstract Background: This study aimed to shed light on the correlation between the amounts of CD8+ T cells and autophagy level in COPD. Results: The objects (n = 90) were divided into three groups: COPD group (patients in the stable phase; n = 30), SN group (healthy control of smoking with normal lung function group; n = 30), and NSN groups (healthy control of non-smoking with normal lung function group; n = 30). The amounts of CD8+ (32.33 ± 4.23%), CD8+ effector (25.63 ± 8.57%) and CD8+memory (11.94 ± 5.77%) T cell in the COPD group were significantly higher those in the other two groups, while the apoptotic rate was lower in the COPD group (P < 0.05). Significant linear correlations were found of P62/GAPDH (‰) with CD8+, CD8+effector, and CD8+ memory- T cell amounts (P<0.001). Conclusions: Autophagy level is positively and linearly associated with the amounts of CD8+ T cells, suggesting that cell autophagy might be involved in COPD pathogenesis.

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Asthma‐chronic obstructive pulmonary disease overlap: A clinical entity?

Journal of Precision Respiratory Medicine ◽

10.2500/jprm.2020.3.200003 ◽

2020 ◽

Vol 3 (1) ◽

pp. 2-8

Author(s):

Robert A. Wise

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Middle Age ◽

Clinical Manifestations ◽

Normal Lung ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Neutrophilic Inflammation ◽

Normal Lung Function

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.

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

European Respiratory Journal ◽

10.1183/13993003.02139-2014 ◽

2015 ◽

Vol 46 (3) ◽

pp. 807-818 ◽

Cited By ~ 38

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.

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Cigarette smoke affects dendritic cell maturation in the small airways of patients with chronic obstructive pulmonary disease

Molecular Medicine Reports ◽

10.3892/mmr.2014.2759 ◽

2014 ◽

Vol 11 (1) ◽

pp. 219-225 ◽

Cited By ~ 18

Author(s):

SHI-XIA LIAO ◽

TING DING ◽

XI-MIN RAO ◽

DE-SHENG SUN ◽

PENG-PENG SUN ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Dendritic Cell ◽

Pulmonary Disease ◽

Cigarette Smoke ◽

Dendritic Cell Maturation ◽

Cell Maturation ◽

Chronic Obstructive ◽

Small Airways ◽

Obstructive Pulmonary Disease

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Emphysema

Chest Imaging ◽

10.1093/med/9780199858064.003.0056 ◽

2019 ◽

pp. 325-329

Author(s):

Travis S. Henry ◽

Brent P. Little

Keyword(s):

Lung Disease ◽

Pulmonary Function Tests ◽

Disease Process ◽

Normal Lung ◽

Chronic Obstructive ◽

Common Disease ◽

Obstructive Pulmonary Disease ◽

Cystic Lung ◽

Emphysematous Lung ◽

Different Parts

Emphysema is the abnormal, permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by destruction of alveolar walls, but without obvious fibrosis. Chronic obstructive pulmonary disease (COPD) is a spectrum of obstructive lung diseases that includes emphysema and chronic bronchitis – diseases that frequently coexist, especially in smokers. Emphysema is an extremely common disease and in most cases the diagnosis is established with clinical data including pulmonary function tests (PFTs). CT may be helpful for clarifying the diagnosis in mild cases or if another disease process (such as interstitial lung disease) is suspected. The three different types of emphysema (centrilobular, paraseptal, and panlobular) affect different parts of the secondary pulmonary lobule and are easily distinguished on CT. Emphysema distorts the normal lung anatomy and can cause superimposed processes (e.g. pneumonia or pulmonary edema) to look atypical on chest radiography and CT. Similarly, lung cancer may have an unusual morphology when it arises within emphysematous lung. Cystic lung disease and honeycombing in pulmonary fibrosis should not be confused with emphysema. Cysts and honeycombing have defined walls on CT, whereas centrilobular emphysema manifests as areas of low attenuation without perceptible walls.

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Regenerative pharmacology for COPD: breathing new life into old lungs

Thorax ◽

10.1136/thoraxjnl-2018-212630 ◽

2019 ◽

Vol 74 (9) ◽

pp. 890-897 ◽

Cited By ~ 8

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.

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

BioMed Research International ◽

10.1155/2016/2891810 ◽

2016 ◽

Vol 2016 ◽

pp. 1-17 ◽

Cited By ~ 2

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.

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