scholarly journals The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6351
Author(s):  
Gillian A. Kelly-Robinson ◽  
James A. Reihill ◽  
Fionnuala T. Lundy ◽  
Lorcan P. McGarvey ◽  
John C. Lockhart ◽  
...  
Keyword(s):  
Serine Protease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Stable Form ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Mechanism Of Inhibition ◽  
Serine Protease Activity ◽  
Alpha 1 Antitrypsin ◽  
The Relationship

Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. In COPD, the relationship between the neutrophil serine protease, neutrophil elastase, and its endogenous inhibitor, alpha-1-antitrypsin (AAT) is the best characterised. AAT belongs to a superfamily of serine protease inhibitors known as serpins. Advances in screening technologies have, however, resulted in many members of the serpin superfamily being identified as having differential expression across a multitude of chronic lung diseases compared to healthy individuals. Serpins exhibit a unique suicide-substrate mechanism of inhibition during which they undergo a dramatic conformational change to a more stable form. A limitation is that this also renders them susceptible to disease-causing mutations. Identification of the extent of their physiological/pathological role in the airways would allow further expansion of knowledge regarding the complexity of protease regulation in the lung and may provide wider opportunity for their use as therapeutics to aid the management of COPD and other chronic airways diseases.

scholarly journals Venous Thromboembolic Disease in Chronic Inflammatory Lung Diseases: Knowns and Unknowns

2021 ◽  
Vol 10 (10) ◽  
pp. 2061
Author(s):  
George Keramidas ◽  
Konstantinos I. Gourgoulianis ◽  
Ourania S. Kotsiou
Keyword(s):  
Lung Diseases ◽  
Thrombotic Event ◽  
Interstitial Lung Diseases ◽  
Chronic Obstructive ◽  
Predisposing Factor ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Increased Risk ◽  
Chronic Pulmonary Diseases ◽  
The Relationship

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases. There is evidence supporting that chronic lung diseases are associated with a higher risk of venous thromboembolism (VTE). However, the relationship between lung diseases and/or lung function with VTE is unclear. Understanding the role of chronic lung inflammation as a predisposing factor for VTE may help determine the optimal management and aid in the development of future preventative strategies. We aimed to provide an overview of the relationship between the most common chronic inflammatory lung diseases and VTE. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, or tuberculosis increase the VTE risk, especially pulmonary embolism (PE), compared to the general population. However, high suspicion is needed to diagnose a thrombotic event early as the clinical presentation inevitably overlaps with respiratory disorders. PE risk increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. Conversely, all VTE patients should be asked for lung comorbidities before determining anticoagulant therapy duration, as those patients are at increased risk of recurrent PE episodes rather than DVT. Further research is needed to understand the underlying pathophysiology of in-situ thrombosis in those patients.

scholarly journals Chronic Obstructive Pulmonary Disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

2014 ◽  
Vol 11 (Supplement 3) ◽  
pp. S154-S160 ◽  
Author(s):  
M. Bradley Drummond ◽  
A. Sonia Buist ◽  
James D. Crapo ◽  
Robert A. Wise ◽  
Stephen I. Rennard
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Primary Prevention ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases

scholarly journals Does cystic fibrosis constitute an advantage in COVID-19 infection?

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Valentino Bezzerri ◽  
Francesca Lucca ◽  
Sonia Volpi ◽  
Marco Cipolli
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Diseases ◽  
Respiratory Viruses ◽  
Chronic Obstructive ◽  
Veneto Region ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Italian Regions ◽  
Pulmonary Impairment

Abstract The Veneto region is one of the most affected Italian regions by COVID-19. Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), may constitute a risk factor in COVID-19. Moreover, respiratory viruses were generally associated with severe pulmonary impairment in cystic fibrosis (CF). We would have therefore expected numerous cases of severe COVID-19 among the CF population. Surprisingly, we found that CF patients were significantly protected against infection by SARS-CoV-2. We discussed this aspect formulating some reasonable theories.

scholarly journals Hallmarks of the ageing lung

2015 ◽  
Vol 45 (3) ◽  
pp. 807-827 ◽  
Author(s):  
Silke Meiners ◽  
Oliver Eickelberg ◽  
Melanie Königshoff
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Specific Effects ◽  
Chronic Lung Diseases

Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, “dysregulation of the extracellular matrix”, which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases.

scholarly journals Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series)

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321773980 ◽  
Author(s):  
Jonathan A. Kropski ◽  
Bradley W. Richmond ◽  
Christa F. Gaskill ◽  
Robert F. Foronjy ◽  
Susan M. Majka
Keyword(s):  
Progenitor Cells ◽  
Lung Diseases ◽  
Normal Function ◽  
Interstitial Lung Diseases ◽  
Chronic Obstructive ◽  
Mesenchymal Progenitor Cells ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Co Morbidity ◽  
Progression Of Disease

Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD), is the fourth leading cause of mortality worldwide. Both are debilitating pathologies that impede overall tissue function. A common co-morbidity in CLD is vasculopathy, characterized by deregulated angiogenesis, remodeling, and loss of microvessels. This substantially worsens prognosis and limits survival, with most current therapeutic strategies being largely palliative. The relevance of angiogenesis, both capillary and lymph, to the pathophysiology of CLD has not been resolved as conflicting evidence depicts angiogenesis as both reparative or pathologic. Therefore, we must begin to understand and model the underlying pathobiology of pulmonary vascular deregulation, alone and in response to injury induced disease, to define cell interactions necessary to maintain normal function and promote repair. Capillary and lymphangiogenesis are deregulated in both PF and COPD, although the mechanisms by which they co-regulate and underlie early pathogenesis of disease are unknown. The cell-specific mechanisms that regulate lung vascular homeostasis, repair, and remodeling represent a significant gap in knowledge, which presents an opportunity to develop targeted therapies. We have shown that that ABCG2pos multipotent adult mesenchymal stem or progenitor cells (MPC) influence the function of the capillary microvasculature as well as lymphangiogenesis. A balance of both is required for normal tissue homeostasis and repair. Our current models suggest that when lymph and capillary angiogenesis are out of balance, the non-equivalence appears to support the progression of disease and tissue remodeling. The angiogenic regulatory mechanisms underlying CLD likely impact other interstitial lung diseases, tuberous sclerosis, and lymphangioleiomyomatosis.

scholarly journals Correlation between bronchopulmonary diseases and vitamin D level

2020 ◽  
Vol 98 (11) ◽  
pp. 57-64
Author(s):  
O. V. Velikaya ◽  
L. V. Vasilieva ◽  
S. А. Nedomolkina ◽  
S. V. Nedomolkin
Keyword(s):  
Vitamin D ◽  
Lung Diseases ◽  
Serum Vitamin ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Impaired Lung Function ◽  
Bronchopulmonary Diseases ◽  
The Relationship

The review presents data from 56 publications about functions of vitamin D in the human body, the mechanisms of its action and the relationship between lung diseases and the level of vitamin D in the blood. Low serum vitamin D levels are associated with impaired lung function and an increase in inflammatory, infectious, or neoplastic diseases. The results of numerous studies allow considering vitamin D not only a marker of different courses of bronchopulmonary diseases but also as a therapeutic target in the treatment of patients with chronic obstructive pulmonary disease while maintaining the immune system and anti-infectious protection.

scholarly journals COVID-19 and restrictive lung disease: A deadly combo to trip off the fine balance

2020 ◽  
Vol 90 (2) ◽  
Author(s):  
Kamal Kant Sahu ◽  
Ajay Kumar Mishra ◽  
Kevin Martin ◽  
Iryna Chastain
Keyword(s):  
Risk Factors ◽  
Chronic Obstructive Pulmonary Disease ◽  
Risk Factor ◽  
Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Immunocompromised Patients ◽  
Obstructive Pulmonary Disease ◽  
Restrictive Lung Disease ◽  
Chronic Lung Diseases

Coronavirus Disease (COVID-19) pandemic has so far led to innumerable deaths worldwide. The risk factors so far that have been most studied as poor prognostic factors are old age, individuals with multiple comorbidities and immunocompromised patients. Amongst the chronic lung diseases, most patients with COVID-19 reported so far had asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease. Herein, we discuss the significance of restrictive lung disease during the COVID-19 pandemic as a potential risk factor via an example of a patient with kyphoscoliosis who succumbed to death due to COVID-19 pneumonia.

scholarly journals Potential Association Between Changes in Microbiota Level and Lung Diseases: A Meta-Analysis

2022 ◽  
Vol 8 ◽  
Author(s):  
Lan Chai ◽  
Qi Wang ◽  
Caijuan Si ◽  
Wenyan Gao ◽  
Lun Zhang
Keyword(s):  
Subgroup Analysis ◽  
Lung Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Meta Analysis ◽  
Mean Deviation ◽  
Chronic Obstructive ◽  
Healthy Individuals ◽  
Obstructive Pulmonary Disease ◽  
Potential Association ◽  
The Relationship

Objective:Lung microbiota is increasingly implicated in multiple types of respiratory diseases. However, no study has drawn a consistent conclusion regarding the relationship between changes in the microbial community and lung diseases. This study verifies the association between microbiota level and lung diseases by performing a meta-analysis.Methods:Literature databases, including PubMed, ISI Web of Science, Embase, Google Scholar, PMC, and CNKI, were used to collect related articles published before March 20, 2021. The standard mean deviation (SMD) and related 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were also conducted.Results:Six studies, comprising 695 patients with lung diseases and 176 healthy individuals, were included in this meta-analysis. The results indicated that the microbiota level was higher in patients with lung diseases than in healthy individuals (SMD = 0.39, 95% CI = 0.22–0.55, I2 = 91.5%, P < 0.01). Subgroup analysis based on country demonstrated that the microbiota level was significantly higher in Chinese (SMD = 1.90, 95% CI = 0.87–2.93, I2 = 62.3%, P < 0.01) and Korean (SMD = 0.24, 95% CI = 0.13–0.35, I2 = 78.7%, P < 0.01) patients with lung diseases. The microbiota level of patients with idiopathic pulmonary fibrosis (IPF) (SMD = 1.40, 95% CI = 0.42–2.38, I2 = 97.3%, P = 0.005), chronic obstructive pulmonary disease (COPD) (SMD = 0.30, 95% CI = 0.09–0.50, I2 = 83.9%, P = 0.004), and asthma (SMD = 0.19, 95% CI = 0.06–0.32, I2 = 69.4%, P = 0.004) were significantly higher than those of the healthy group, whereas a lower microbiota level was found in patients with chronic hypersensitivity pneumonitis (CHP). The microbiota level significantly increased when the disease sample size was >50. Subgroup analysis based on different microbiota genera, indicated that Acinetobacter baumannii and Pseudomonas aeruginosa were significantly increased in COPD and asthma diseases.Conclusion:We observed that patients with IPF, COPD, and asthma had a higher microbiota level, whereas patients with CHP had a lower microbiota level compared to the healthy individuals. The level of A. baumannii and P. aeruginosa were significantly higher in patients with COPD and asthma, and thus represented as potential microbiota markers in the diagnosis and treatment of lung diseases.

scholarly journals Metabolic reprogramming in the pathogenesis of chronic lung diseases, including BPD, COPD, and pulmonary fibrosis

2018 ◽  
Vol 314 (4) ◽  
pp. L544-L554 ◽  
Author(s):  
Haifeng Zhao ◽  
Phyllis A. Dennery ◽  
Hongwei Yao
Keyword(s):  
Fatty Acids ◽  
Pulmonary Fibrosis ◽  
Lung Diseases ◽  
Cellular Proliferation ◽  
Inflammatory Responses ◽  
Tricarboxylic Acid Cycle ◽  
Metabolic Reprogramming ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases

The metabolism of nutrient substrates, including glucose, glutamine, and fatty acids, provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, as well as metabolites for the biosynthesis of biomolecules, including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All of these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. Recent studies demonstrate that metabolic reprogramming occurs in patients with and animal models of chronic lung diseases, suggesting that metabolic dysregulation may participate in the pathogenesis and progression of these diseases. In this review, we briefly discuss the catabolic pathways for glucose, glutamine, and fatty acids, and focus on how metabolic reprogramming of these pathways impacts cellular functions and leads to the development of these chronic lung diseases. We also highlight how targeting metabolic pathways can be utilized in the prevention and treatment of these diseases.

SLPI and trappin-2 as therapeutic agents to target airway serine proteases in inflammatory lung diseases: current and future directions

2011 ◽  
Vol 39 (5) ◽  
pp. 1441-1446 ◽  
Author(s):  
Marie-Louise Zani ◽  
Annabelle Tanga ◽  
Ahlame Saidi ◽  
Hélène Serrano ◽  
Sandrine Dallet-Choisy ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Lung Diseases ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
Cathepsin G ◽  
Chronic Obstructive ◽  
Inhaled Drugs ◽  
Future Directions ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases

It is now clear that NSPs (neutrophil serine proteases), including elastase, Pr3 (proteinase 3) and CatG (cathepsin G) are major pathogenic determinants in chronic inflammatory disorders of the lungs. Two unglycosylated natural protease inhibitors, SLPI (secretory leucocyte protease inhibitor) and elafin, and its precursor trappin-2 that are found in the lungs, have therapeutic potential for reducing the protease-induced inflammatory response. This review examines the multifaceted roles of SLPI and elafin/trappin-2 in the context of their possible use as inhaled drugs for treating chronic lung diseases such as CF (cystic fibrosis) and COPD (chronic obstructive pulmonary disease).

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