Cellular and molecular mechanisms of asthma and COPD

2017 ◽  
Vol 131 (13) ◽  
pp. 1541-1558 ◽  
Author(s):  
Peter J. Barnes
Keyword(s):  
Molecular Mechanisms ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
Inflammatory Cells ◽  
Response To Therapy ◽  
Chronic Obstructive ◽  
Cellular Mechanisms ◽  
Obstructive Pulmonary Disease ◽  
Curative Therapy ◽  
New Treatments

Asthma and chronic obstructive pulmonary disease (COPD) both cause airway obstruction and are associated with chronic inflammation of the airways. However, the nature and sites of the inflammation differ between these diseases, resulting in different pathology, clinical manifestations and response to therapy. In this review, the inflammatory and cellular mechanisms of asthma and COPD are compared and the differences in inflammatory cells and profile of inflammatory mediators are highlighted. These differences account for the differences in clinical manifestations of asthma and COPD and their response to therapy. Although asthma and COPD are usually distinct, there are some patients who show an overlap of features, which may be explained by the coincidence of two common diseases or distinct phenotypes of each disease. It is important to better understand the underlying cellular and molecular mechanisms of asthma and COPD in order to develop new treatments in areas of unmet need, such as severe asthma, curative therapy for asthma and effective anti-inflammatory treatments for COPD.

scholarly journals Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daisuke Morichika ◽  
Akihiko Taniguchi ◽  
Naohiro Oda ◽  
Utako Fujii ◽  
Satoru Senoo ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Cigarette Smoke Extract ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Porcine Pancreas ◽  
Obstructive Pulmonary Disease ◽  
Quantitative Morphometry ◽  
Cytokines And Chemokines

Abstract Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33−/− mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33−/− mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33−/− and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33−/− mice than WT mice. IL-33−/− mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

scholarly journals Chronic Obstructive Lung Disease in young: Alpha 1 anti trypsin deficiency

2015 ◽  
Vol 3 (2) ◽  
pp. 65-67
Author(s):  
S.S. Dhakal ◽  
K.K. Agrawaal ◽  
N.K. Bhatta
Keyword(s):  
Bronchial Asthma ◽  
Clinical Manifestations ◽  
Lower Lobe ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Severe Deficiency ◽  
History Of ◽  
Pulmonary Arterial ◽  
Alpha 1 Antitrypsin

Alpha-1 antitrypsin (AAT) deficiency is a clinically under recognized inherited disorder. The main clinical manifestations relate to three separate organs: the lung, the liver, and the skin. In the lung, severe deficiency of AAT predisposes to chronic obstructive pulmonary disease. We present a case of 34 years male with a history of recurrent chest infections in past and treated in the line of bronchial asthma but not relieved. He was admitted on 22nd May 2011 at BPKIHS. He presented with type 2 respiratory failure and had features of severe pulmonary arterial hypertension and left lower lobe pneumonia. The patient got improved with the treatment and is doing well on follow up. The diagnosis should be strongly suspected in patients with history suggestive of bronchial asthma and with obstructive features.Journal of Advances in Internal Medicine 2014;3(2):65-67

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

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

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.

scholarly journals Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema

2020 ◽  
Vol 11 ◽  
Author(s):  
Lokesh P. Tripathi ◽  
Mari N. Itoh ◽  
Yoshito Takeda ◽  
Kazuyuki Tsujino ◽  
Yasushi Kondo ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Integrative Approach ◽  
Chronic Obstructive ◽  
Lung Pathology ◽  
Obstructive Pulmonary Disease

While both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are multifactorial disorders characterized by distinct clinical and pathological features, their commonalities and differences have not been fully elucidated. We sought to investigate the preventive roles of tetraspanins Cd151 and Cd9 -that are involved in diverse cellular processes in lung pathophysiology- in pulmonary fibrosis and emphysema, respectively, and to obtain a deeper understanding of their underlying molecular mechanisms toward facilitating improved therapeutic outcomes. Using an integrative approach, we examined the transcriptomic changes in the lungs of Cd151- and Cd9-deficient mice using functional-enrichment-analysis, pathway-perturbation-analysis and protein-protein-interaction (PPI) network analysis. Circadian-rhythm, extracellular-matrix (ECM), cell-adhesion and inflammatory responses and associated factors were prominently influenced by Cd151-deletion. Conversely, cellular-junctions, focal-adhesion, vascular-remodeling, and TNF-signaling were deeply impacted by Cd9-deletion. We also highlighted a “common core” of factors and signaling cascades that underlie the functions of both Cd151 and Cd9 in lung pathology. Circadian dysregulation following Cd151-deletion seemingly facilitated progressive fibrotic lung phenotype. Conversely, TGF-β signaling attenuation and TNF-signaling activation emerged as potentially novel functionaries of Cd9-deletion-induced emphysema. Our findings offer promising avenues for developing novel therapeutic treatments for pulmonary fibrosis and emphysema.

scholarly journals Multi-omic molecular profiling of lung cancer in COPD

2018 ◽  
Vol 52 (1) ◽  
pp. 1702665 ◽  
Author(s):  
Brian J. Sandri ◽  
Adam Kaplan ◽  
Shane W. Hodgson ◽  
Mark Peterson ◽  
Svetlana Avdulov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Chronic Obstructive ◽  
Tissue Samples ◽  
Obstructive Pulmonary Disease ◽  
Predictive Variables ◽  
Variation Explained ◽  
Underlying Mechanisms ◽  
And Control

Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis.We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets.JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase–protein kinase B signalling pathways as important signals in the tumour adjacent stroma.The multi-omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer.

scholarly journals Coinfection and delayed diagnosis of visceral leishmaniasis: Died predecessors factors

2019 ◽  
Vol 6 (1) ◽  
pp. 19
Author(s):  
Jaciel de Oliveira Clementino ◽  
Daniel Gallina Martins Abrahão ◽  
Manoel Sebastião Da Costa Lima Junior ◽  
Herintha Coeto Neitzke Abreu
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Septic Shock ◽  
Human Immunodeficiency Virus ◽  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Immunodeficiency Virus

Visceral leishmaniasis (VL) is an anthropozoonosis caused by Leishmania infantum in most Brazilian states and is known for its significant lethality resulting from improper diagnosis and treatment. VL is difficult to diagnose because its clinical manifestations and laboratory abnormalities are analogous to several other pathologies. We report a case of a 54-year-old man, negative for Human Immunodeficiency Virus (HIV), with VL who was initially diagnosed with anemia, consumptive syndrome, pneumonia, chronic obstructive pulmonary disease, and septic shock and died due to a delayed diagnosis of VL. 

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