scholarly journals Macrophages—the immune effector guardians of the lung: impact of corticosteroids on their functional responses

2020 ◽  
Vol 134 (13) ◽  
pp. 1631-1635
Author(s):  
Stephan F. van Eeden ◽  
Kentaro Akata
Keyword(s):  
Functional Properties ◽  
Inflammatory Responses ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Chronic Obstructive ◽  
Macrophage Phenotype ◽  
Functional Responses ◽  
Immune Effector ◽  
Effector Cells ◽  
The Impact

Abstract Lung macrophages (LMs) are key immune effector cells that protect the lung from inhaled particulate matter, noxious gases and pathogens. In Chronic Obstructive Pulmonary Disease (COPD), there is an abundance of macrophages in airspaces and lung tissues suggesting that they play an important role in the pathogenesis of the disease. Furthermore, macrophage phenotype and functional properties are altered in COPD toward a more pro-inflammatory state, characterized by reduced pathogen recognition and processing ability and dysfunctional tissue repair qualities. Inhaled corticosteroids (ICSs), used in the management of COPD, has been shown to reduce acute exacerbations of COPD but is also associated with increased occurrence of pneumonia. Corticosteroids treatment altered LM phenotypic characteristics and their functional properties, and this commentary discusses current knowledge and also the gaps in our understanding of the impact of ICS on LMs phenotype and function. A better understanding of how ICSs impact the immune-inflammatory responses in the lung, in particular ICSs’ effects on LMs, could allow more selective personalized tailoring of the use of ICSs in COPD to improve disease progression, morbidity and mortality.

scholarly journals Exacerbations of COPD

2018 ◽  
Vol 27 (147) ◽  
pp. 170103 ◽  
Author(s):  
Christian Viniol ◽  
Claus F. Vogelmeier
Keyword(s):  
Viral Infections ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Pneumococcal Vaccination ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Copd Exacerbations ◽  
Recommended Treatment ◽  
Number Of Patients ◽  
The Impact

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. While COPD is a mainly chronic disease, a substantial number of patients suffer from exacerbations. Severe exacerbations are related to a significantly worse survival outcome. This review summarises the current knowledge on the different aspects of COPD exacerbations. The impact of risk factors and triggers such as smoking, severe airflow limitation, bronchiectasis, bacterial and viral infections and comorbidities is discussed. More severe exacerbations should be treated with β-agonists and anticholinergics as well as systemic corticosteroids. Antibiotic therapy should only be given to patients with presumed bacterial infection. Noninvasive ventilation is indicated in patients with respiratory failure. Smoking cessation is key to prevent further COPD exacerbations. Other aspects include choice of pharmacotherapy, including bronchodilators, inhaled corticosteroids, phosphodiesterase-4 inhibitors, long-term antibiotics and mucolytics. Better education and self-management as well as increased physical activity are important. Influenza and pneumococcal vaccination is recommended. Treatment of hypoxaemia and hypercapnia reduce the rate of COPD exacerbations, while most interventional bronchoscopic therapies increase exacerbation risk within the first months after the procedure.

scholarly journals Targeting HIF-1 alpha transcriptional activity drives cytotoxic immune effector cells into melanoma and improves combination immunotherapy

Oncogene ◽  
2021 ◽  
Author(s):  
Audrey Lequeux ◽  
Muhammad Zaeem Noman ◽  
Malina Xiao ◽  
Kris Van Moer ◽  
Meriem Hasmim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Transcriptional Activity ◽  
Immune Cell ◽  
Tumor Resistance ◽  
Combination Strategy ◽  
Immune Effector ◽  
Effector Cells ◽  
Melanoma Patients ◽  
The Impact

AbstractHypoxia is a key factor responsible for the failure of therapeutic response in most solid tumors and promotes the acquisition of tumor resistance to various antitumor immune effectors. Reshaping the hypoxic immune suppressive tumor microenvironment to improve cancer immunotherapy is still a relevant challenge. We investigated the impact of inhibiting HIF-1α transcriptional activity on cytotoxic immune cell infiltration into B16-F10 melanoma. We showed that tumors expressing a deleted form of HIF-1α displayed increased levels of NK and CD8+ effector T cells in the tumor microenvironment, which was associated with high levels of CCL2 and CCL5 chemokines. We showed that combining acriflavine, reported as a pharmacological agent preventing HIF-1α/HIF-1β dimerization, dramatically improved the benefit of cancer immunotherapy based on TRP-2 peptide vaccination and anti-PD-1 blocking antibody. In melanoma patients, we revealed that tumors exhibiting high CCL5 are less hypoxic, and displayed high NK, CD3+, CD4+ and CD8+ T cell markers than those having low CCL5. In addition, melanoma patients with high CCL5 in their tumors survive better than those having low CCL5. This study provides the pre-clinical proof of concept for a novel triple combination strategy including blocking HIF-1α transcription activity along vaccination and PD-1 blocking immunotherapy.

scholarly journals Physiology of Midkine and Its Potential Pathophysiological Role in COVID-19

2020 ◽  
Vol 11 ◽  
Author(s):  
Giulia Sanino ◽  
Martino Bosco ◽  
Giuseppe Terrazzano
Keyword(s):  
Inflammatory Responses ◽  
Pathological Condition ◽  
Severe Pneumonia ◽  
Immune Effector ◽  
Effector Cells ◽  
Coronary Syndrome ◽  
Clinical Complications ◽  
Mediators Of Inflammation ◽  
Autoimmune Conditions ◽  
Pathogen Clearance

SARS-CoV2 infection not only causes abnormal severe pneumonia but also induces other relevant pathophysiological effects on several tissues and organs. In this regard, the clinical complications observed in COVID-19 include acute coronary syndrome, pulmonary thromboembolism, myocarditis and, in the severe cases, the occurrence of disseminated intravascular coagulation. Literature on COVID-19 highlighted the central role of the Renin Angiotensin Aldosterone System in the determinism of SARS-CoV2 cellular internalization in the target tissues. Lung degeneration and respiratory distress appear to be dependent on the perturbance of physiological mechanisms, such as the uncontrolled release of pro-inflammatory cytokines, a dysregulation of the fibrinolytic coagulative cascade and the hyperactivation of immune effector cells. In this mini review, we address the physiology of Midkine, a growth factor able to bind heparin, and its pathophysiological potential role in COVID-19 determinism. Midkine increases in many inflammatory and autoimmune conditions and correlates with several dysfunctional immune-inflammatory responses that appear to show similarities with the pathophysiological elicited by SARS-CoV2. Midkine, together with its receptor, could facilitate the virus entry, fostering its accumulation and increasing its affinity with Ace2 receptor. We also focus on Netosis, a particular mechanism of pathogen clearance exerted by neutrophils, which under certain pathological condition becomes dysfunctional and can cause tissue damage. Moreover, we highlight the mechanism of autophagy that the new coronavirus could try to escape in order to replicate itself, as well as on pulmonary fibrosis induced by hypoxia and on the release of cytokines and mediators of inflammation, correlating the interplay between Midkine and SARS-CoV2.

scholarly journals A Systematic Review of Risk Factors Associated with Near-Fatal and Fatal Asthma

2005 ◽  
Vol 12 (5) ◽  
pp. 265-270 ◽  
Author(s):  
GG Alvarez ◽  
M Schulzer ◽  
D Jung ◽  
JM FitzGerald
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Inhaled Corticosteroids ◽  
Respiratory Arrest ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Mortality And Morbidity ◽  
Factors Associated ◽  
Fatal Asthma ◽  
The Impact

BACKGROUND: Asthma mortality and morbidity continue to be a serious global problem. Systematic reviews provide an opportunity to review risk factors in detail.OBJECTIVE: To review all of the literature for risk factors associated with near-fatal asthma (NFA) and fatal asthma (FA).METHODS: A literature search from 1960 to January 2004 in MEDLINE and EMBASE was conducted. Studies were included based on the following criteria: NFA was defined as an asthma exacerbation resulting in respiratory arrest requiring mechanical ventilation or a partial pressure of CO2of at least 45 mmHg or asthma resulting in death (FA); the study reported the number of cases (NFA and/or FA) and asthmatic controls; there was explicit reporting of risk factors; cases that were adult and pediatric in nature; and all study types. Studies that included patients with chronic obstructive pulmonary disease were excluded.RESULTS: Four hundred and three articles were identified, of which 27 met the inclusion criteria. Increased use of medications such as beta-agonists via metered dose inhalers (OR=1.67, 95% CI 0.99 to 2.84, P=0.057) and nebulizers (OR=2.45, 95% CI 1.52 to 3.93, P=0.0002), oral steroids (OR=2.71, 95% CI 1.34 to 5.51, P=0.006) and oral theophylline (OR=2.02, 95% CI 1.03 to 3.98, P=0.04) and a history of hospital (OR=2.62, 95% CI 1.04 to 6.58, P=0.04) and/or intensive care unit (OR=5.14, 95% CI 1.91 to 13.86, P=0.001) admissions and mechanical ventilation (OR=6.69, 95% CI 2.80 to 15.97, P=0.0001) due to asthma were predictors of NFA and FA. Prior emergency department assessment did not confer a greater risk of NFA and FA (OR=1.13, 95% CI 0.43 to 2.92, P=0.810).The use of inhaled corticosteroids (ICS) measured in a dose-independent fashion (did the patient take ICS previously; yes or no) inferred equivocal risk of NFA and FA (OR=1.31, 95% CI 0.83 to 2.05, P=0.25). However, two studies measured the use of ICS in a dose-dependent fashion (ie, measured the number of prescriptions filled within the previous six to 12 months). Both studies showed a trend toward a protective effect against FA. One study showed that the premature cessation of ICS can hasten death.CONCLUSIONS: In the present study, risk factors of NFA and FA have been more accurately defined. Clinicians should identify patients with these characteristics to reduce their risk of NFA and FA. Further research should focus on quantifying the impact of risk factors on asthma deaths.

scholarly journals Impact of pre-enrolment medication use on clinical outcomes in SUMMIT

2019 ◽  
Vol 5 (1) ◽  
pp. 00203-2018 ◽  
Author(s):  
Jørgen Vestbo ◽  
Mark Dransfield ◽  
Julie A. Anderson ◽  
Robert D. Brook ◽  
Peter M.A. Calverley ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Inhaled Corticosteroids ◽  
Controlled Trial ◽  
Prior Treatment ◽  
Study Entry ◽  
Chronic Obstructive ◽  
Severe Exacerbation ◽  
Mortality And Morbidity ◽  
Randomised Study ◽  
The Impact

The impact of prior treatment on results of clinical trials in chronic obstructive pulmonary disease (COPD) has been debated. We used data from the Study to Understand Mortality and Morbidity in COPD Trial to examine the impact of prior treatment on the effects of randomised study drugs on mortality and exacerbations.We used data on 16 417 patients with moderate COPD and heightened cardiovascular risk and information on prior medications to examine the effects of fluticasone furoate (FF), vilanterol (VI) and combined FF/VI compared to placebo on moderate and severe exacerbation as well as mortality. The study was event-driven with a median study exposure of 1.8 years. This study was registered with ClinicalTrials.gov, number NCT01313676.There were no consistent associations between treatment prior to study entry and the effects of FF, VI or FF/VI on exacerbations during the study. However, patients taking inhaled corticosteroids and one or more bronchodilators prior to study entry seemed to have a better effect of active treatments than of placebo on mortality (hazard ratio for FF/VI 0.65, 95% CI 0.48–0.89). Survival in those randomised to placebo was independent of treatment prior to study enrolment.Prior treatment appears to affect treatment effects on mortality but not exacerbations in a randomised controlled trial of patients with COPD and heightened cardiovascular risk.

scholarly journals A Regulatory Role for Interleukin 4 in Differential Inflammatory Responses in the Lung following Infection of Mice Primed with Th1- or Th2-Inducing Pertussis Vaccines

2000 ◽  
Vol 68 (3) ◽  
pp. 1383-1390 ◽  
Author(s):  
Peter McGuirk ◽  
Kingston H. G. Mills
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Th2 Cells ◽  
Infection Model ◽  
Local Production ◽  
Local Inflammatory Response ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Th1 And Th2

ABSTRACT Protection against infectious pathogens at mucosal surfaces is dependent on local antibody responses, production of inflammatory mediators, and recruitment of immune effector cells to the site of infection. Since Th1 and Th2 cells produce cytokines with pro- and anti-inflammatory activities, immunization with vaccines that induce these T-cell subtypes may regulate the subsequent inflammatory response to infection. We have demonstrated that immunization of mice with pertussis whole-cell or acellular vaccines (Pw or Pa) selectively induces Th1 and Th2 cells, respectively. In this study we have used a murine respiratory-infection model to demonstrate that priming with a Th1- or Th2-inducing pertussis vaccine can influence the local inflammatory response and immune effector cells in the lung following aerosol challenge with Bordetella pertussis. Analysis of bronchoalveolar lavage (BAL) fluid taken during the course of B. pertussis infection of naı̈ve mice or mice immunized with Pw revealed an early influx of neutrophils and local production of interleukin 1β (IL-1β) in the lungs. In contrast, neutrophil infiltration and IL-1β production were not observed following challenge of mice immunized with the Th2-inducing Pa. Conversely, during infection local production of IL-6 and IL-1ra was significantly greater in mice immunized with Pa than in those immunized with Pw. Studies of knockout mice revealed neutrophil and lymphocyte infiltration in the lungs following B. pertussis infection of IL-4-defective (IL-4−/−) mice but not in wild-type mice immunized with Pa. Furthermore, the levels of IL-1β, IL-6, and IL-1ra in Pa-immunized IL-4−/− mice were comparable to those in mice immunized with Pw. These results demonstrate distinct influences of Th1- and Th2-inducing vaccines on the protective inflammatory responses in the lungs following challenge with B. pertussis and implicate IL-4 as an important regulator of inflammatory-cell recruitment.

Aspirin and P2Y12 Inhibitors in platelet-mediated activation of neutrophils and monocytes

2015 ◽  
Vol 114 (09) ◽  
pp. 478-789 ◽  
Author(s):  
Waltraud Schrottmaier ◽  
Julia Kral ◽  
Sigrun Badrnya ◽  
Alice Assinger
Keyword(s):  
Immune Responses ◽  
Antiplatelet Therapy ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cardiovascular Complications ◽  
P2y12 Inhibitors ◽  
Beneficial Effects ◽  
Cox Inhibitor ◽  
The Impact

SummaryPlatelets are key players in haemostasis and represent a pivotal link between inflammation, immunity and atherogenesis. Depending on the (patho)physiological environment platelets modulate various leukocyte functions via release of inflammatory mediators and direct cell-cell interactions. Elevated levels of circulating platelet-leukocyte aggregates are found in patients suffering from several thrombotic or inflammatory conditions. Platelet-monocyte and platelet-neutrophil interaction can trigger pro- and anti-inflammatory responses and modulate effector functions of all leukocyte subpopulations. These platelet-mediated immune responses have implications for the progression of cardiovascular diseases and also play a crucial role during infections, cancer, transplantations and other inflammatory diseases of several organs. Antiplatelet therapy including the COX inhibitor aspirin and/or ADP receptor P2Y12 inhibitors such as clopidogrel, prasugrel and ticagrelor are the therapy of choice for various cardiovascular complications. Both aspirin and P2Y12 inhibitors attenuate platelet-leukocyte interactions, thereby also modulating immune responses. This may have beneficial effects in some pathological conditions, while it might be detrimental in others. This review aims to summarise the current knowledge on platelet-leukocyte interactions and the impact of aspirin and P2Y12 inhibition on platelet-mediated immune responses and to give an overview on the effects of antiplatelet therapy on platelet-leukocyte interplay in various diseases.

scholarly journals Informal caregivers of patients with COPD: Home Sweet Home?

2015 ◽  
Vol 24 (137) ◽  
pp. 498-504 ◽  
Author(s):  
Nienke Nakken ◽  
Daisy J.A. Janssen ◽  
Esther H.A. van den Bogaart ◽  
Emiel F.M. Wouters ◽  
Frits M.E. Franssen ◽  
...  
Keyword(s):  
Emotional Support ◽  
Current Knowledge ◽  
Informal Caregivers ◽  
Chronic Obstructive ◽  
Subjective Burden ◽  
Obstructive Pulmonary Disease ◽  
Anxiety Depression ◽  
The Impact ◽  
Optimal Quality

The burden of chronic obstructive pulmonary disease (COPD) on society is increasing. Healthcare systems should support patients with COPD in achieving an optimal quality of life, while limiting the costs of care. As a consequence, a shift from hospital care to home care seems inevitable. Therefore, patients will have to rely to a greater extent on informal caregivers. Patients with COPD as well as their informal caregivers are confronted with multiple limitations in activities of daily living. The presence of an informal caregiver is important to provide practical help and emotional support. However, caregivers can be overprotective, which can make patients more dependent. Informal caregiving may lead to symptoms of anxiety, depression, social isolation and a changed relationship with the patient. The caregivers' subjective burden is a major determinant of the impact of caregiving. Therefore, the caregiver's perception of the patient's health is an important factor. This article reviews the current knowledge about these informal caregivers of patients with COPD, the impact of COPD on their lives and their perception of the patient's health status.

scholarly journals Particulate matter and the airway epithelium: the special case of the underground?

2019 ◽  
Vol 28 (153) ◽  
pp. 190066 ◽  
Author(s):  
Dawn M. Cooper ◽  
Matthew Loxham
Keyword(s):  
Particulate Matter ◽  
Epithelial Cells ◽  
Airway Epithelium ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Airborne Particulate Matter ◽  
Initial Response ◽  
Mitigation Strategies ◽  
Chronic Obstructive ◽  
Potential Health

Airborne particulate matter (PM) is a leading driver of premature mortality and cardiopulmonary morbidity, associated with exacerbations of asthma and chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung cancer. The airway epithelium, as the principal site of PM deposition, is critical to the effects of, and initial response to, PM. A key mechanism by which PM exerts its effects is the generation of reactive oxygen species (ROS), inducing antioxidant and inflammatory responses in exposed epithelial cells. However, much of what is known about the effects of PM is based on research using particulates from urban air. PM from underground railways is compositionally highly distinct from urban PM, being rich in metals associated with wheel, rail and brake wear and electrical arcing and component wear, which endows underground PM with potent ROS-generating capacity. In addition, underground PM appears to be more inflammogenic than urban PM in epithelial cells, but there is a lack of research into effects on exposed individuals, especially those with underlying health conditions. This review summarises current knowledge about the effects of PM on the airway epithelium, how the effects of underground PM may be different to urban PM and the potential health consequences and mitigation strategies for commuters and workers in underground railways.

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