Interleukin-17A: A Potential Therapeutic Target in Chronic Lung Diseases

2019 ◽  
Vol 19 (7) ◽  
pp. 921-928 ◽  
Author(s):  
Sadiya Bi Shaikh ◽  
Ashwini Prabhu ◽  
Yashodhar Prabhakar Bhandary
Keyword(s):  
Respiratory Diseases ◽  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Interleukin 17 ◽  
Potential Therapeutic Target ◽  
Chronic Respiratory Diseases ◽  
Chronic Lung Diseases ◽  
Interleukin 17A ◽  
Insight Into

Background: Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has gained a lot of attention because of its involvement in respiratory diseases. Interleukin-17 cytokine family includes six members, out of which, IL-17A participates towards the immune responses in allergy and inflammation. It also modulates the progression of respiratory disorders. Objective: The present review is an insight into the involvement and contributions of the proinflammatory cytokine IL-17A in chronic respiratory diseases like Idiopathic Pulmonary Fibrosis (IPF), Chronic Obstructive Pulmonary Distress (COPD), asthma, pneumonia, obliterative bronchiolitis, lung cancer and many others. Conclusion: IL-17A is a major regulator of inflammatory responses. In all the mentioned diseases, IL- 17A plays a prime role in inducing the diseases, whereas the lack of this pro-inflammatory cytokine reduces the severity of respective respiratory diseases. Thereby, this review suggests IL-17A as an instrumental target in chronic respiratory diseases.

scholarly journals The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Amy T. Hsu ◽  
Timothy A. Gottschalk ◽  
Evelyn Tsantikos ◽  
Margaret L. Hibbs
Keyword(s):  
Immune System ◽  
Respiratory Diseases ◽  
Pulmonary Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Chronic Respiratory Diseases ◽  
Chronic Lung Diseases ◽  
Pulmonary Immune System

The lung is a vital mucosal organ that is constantly exposed to the external environment, and as such, its defenses are continuously under threat. The pulmonary immune system has evolved to sense and respond to these danger signals while remaining silent to innocuous aeroantigens. The origin of the defense system is the respiratory epithelium, which responds rapidly to insults by the production of an array of mediators that initiate protection by directly killing microbes, activating tissue-resident immune cells and recruiting leukocytes from the blood. At the steady-state, the lung comprises a large collection of leukocytes, amongst which are specialized cells of lymphoid origin known as innate lymphoid cells (ILCs). ILCs are divided into three major helper-like subsets, ILC1, ILC2 and ILC3, which are considered the innate counterparts of type 1, 2 and 17 T helper cells, respectively, in addition to natural killer cells and lymphoid tissue inducer cells. Although ILCs represent a small fraction of the pulmonary immune system, they play an important role in early responses to pathogens and facilitate the acquisition of adaptive immunity. However, it is now also emerging that these cells are active participants in the development of chronic lung diseases. In this mini-review, we provide an update on our current understanding of the role of ILCs and their regulation in the lung. We summarise how these cells and their mediators initiate, sustain and potentially control pulmonary inflammation, and their contribution to the respiratory diseases chronic obstructive pulmonary disease (COPD) and asthma.

scholarly journals Cognitive Impairment in Chronic Lung Diseases

2020 ◽  
Author(s):  
Emanuela Tudorache ◽  
Monica Marc ◽  
Daniel Traila ◽  
Diana Manolescu
Keyword(s):  
Cognitive Impairment ◽  
Respiratory Diseases ◽  
Disease Incidence ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Chronic Lung Diseases ◽  
Age Related ◽  
Obstructive Sleep

The increase in life expectancy has been accompanied by an escalation of age-related disease incidence. Mild cognitive impairment (MCI) is a decline of cognitive function higher than expected for a certain age, but not severe enough to meet the criteria for dementia. Hypoxemia, smoking history, ageing and several comorbidities are risk factors for both chronic respiratory diseases and cognitive deficit. Up to 70% of patients with chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA) or idiopathic pulmonary fibrosis (IPF) have a form of cognitive impairment. Furthermore, a low neuropsychological performance is an independent predictor of disability and mortality in these populations. Efficient tools for cognitive assessment have been validated for these patients and should be used for better clinical outcomes. The physiopathological mechanisms, clinical impact and prevention strategies for cognitive dysfunction in chronic respiratory diseases will be detailed in the following chapter.

CRISPR/Cas9 Genome Editing Tool: A Promising Tool for Therapeutic Applications on Respiratory Diseases

2020 ◽  
Vol 20 (5) ◽  
pp. 333-346
Author(s):  
Sadiya Bi Shaikh ◽  
Yashodhar Prabhakar Bhandary
Keyword(s):  
Respiratory Diseases ◽  
Gene Editing ◽  
Epithelial Mesenchymal Transition ◽  
Respiratory Health ◽  
Chronic Obstructive ◽  
Therapeutic Tool ◽  
Obstructive Pulmonary Disease ◽  
Mesenchymal Transition ◽  
Chronic Respiratory Diseases ◽  
Promising Tool

Respiratory diseases are one of the prime topics of concern in the current era due to improper diagnostics tools. Gene-editing therapy, like Clustered regularly interspaced palindromic repeats- associated nuclease 9 (CRISPR/Cas9), is gaining popularity in pulmonary research, opening up doors to invaluable insights on underlying mechanisms. CRISPR/Cas9 can be considered as a potential gene-editing tool with a scientific community that is helping in the advancement of knowledge in respiratory health and therapy. As an appealing therapeutic tool, we hereby explore the advanced research on the application of CRISPR/Cas9 tools in chronic respiratory diseases such as lung cancer, Acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF). We also address the urgent need to establish this gene-editing tool in various other lung diseases such as asthma, Chronic obstructive pulmonary disease (COPD) and Idiopathic pulmonary fibrosis (IPF). The present review introduces CRISPR/Cas9 as a worthy application in targeting epithelial-mesenchymal transition and fibrinolytic system via editing specific genes. Thereby, based on the efficiency of CRISPR/Cas9, it can be considered as a promising therapeutic tool in respiratory health research.

scholarly journals Hospitalisation for COPD in Puglia: the role of hospital discharge database to estimate prevalence and incidence

2016 ◽  
Vol 70 (3) ◽  
Author(s):  
P. Trerotoli ◽  
N. Bartolomeo ◽  
A.M. Moretti
Keyword(s):  
Disease Management ◽  
Hospital Discharge ◽  
Respiratory Diseases ◽  
Hospital Admissions ◽  
Diagnostic Procedures ◽  
Chronic Respiratory Disease ◽  
Chronic Obstructive ◽  
Chronic Respiratory Diseases ◽  
Hospital Discharge Database ◽  
Discharge Database

Background and aim. Chronic Obstructive Pulmonary Disease (COPD), although largely preventable, is a great health burden in all the countries worldwide. Statistics of morbidity and mortality of COPD show the need for correct management of the disease. Chronic Obstructive Respiratory Diseases (DRG 88) are in 9th place for discharge in in-patient hospital admission. It is necessary to establish specific indicators which are efficacious and relevant for the patient, the doctor and the health manager. This study will analyse the information in respect of hospital admissions (Hospital discharge database) in Puglia for the period 2000-2005. Methods. The analysis was carried out utilising the Puglia Region hospital patient discharge database, selecting those patients with admission for chronic respiratory disease as principal or secondary diagnosis. Results. Chronic respiratory diseases are more frequent in males and in people over 45 years old with frequency increasing with age. Geographical distribution shows that there are greater rates of hospitalisation in big cities and in the neighbourhood of industrial areas. Although the trend over time is slight. A higher percentage of re-admission has been found for patients with COPD, and the interval between the two admissions occurs within one or two months; the diagnosis at the second admission is the same as for the first. 10.6% of discharge forms report one diagnosis, especially in patients older than 65 years of age. Little could be said about diagnostic procedures because these are not reported on the discharge form. Conclusion. Hospitalisation data confirms expectations regarding age and sex of patients. The high hospitalisation rates indicate that in-patients care still remains the only viable treatment for COPD and other chronic respiratory diseases. The high number of exacerbations reflect the absence of out-patients service or community care, and the same diagnosis in more than one episode shows the lack of efficiency of health services and disease management. This data is necessary to understand disease distribution and the modification of disease management in order to reduce health care costs, to increase efficacy in disease control and to limit repeated exacerbation and so to obtain the maximum benefit for the patients.

scholarly journals Chronic respiratory diseases at primary health care level in Georgia: the results of the pilot study

2016 ◽  
Vol 71 (4) ◽  
Author(s):  
I. Chkhaidze ◽  
T. Maglakelidze ◽  
N. Khaltaev
Keyword(s):  
Allergic Rhinitis ◽  
Respiratory Diseases ◽  
Chronic Obstructive ◽  
Official Statistics ◽  
Global Alliance ◽  
Care Level ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Chronic Morbidity ◽  
Official Data

Background and aim. Millions of people suffer from chronic respiratory diseases (CRD). To address this serious global health problem WHO formed the Global Alliance against Chronic Respiratory Diseases (GARD). Chronic obstructive pulmonary disease (COPD) is a major priority of GARD due to high chronic morbidity and mortality; however, there is still little prevalence data available. The prevalence of COPD in Georgia, as well as other CRD, is suspected to be high. Methods. GARD Pilot Survey (GAPS) in Georgia had been carried out by the Georgian Respiratory Association. The survey was conducted in the Sagarejo and Mtskheta districts with total population of about 70.000. All subjects provided information on asthma, bronchitis, respiratory symptoms, smoking, allergic conditions, CRD comorbidity and lifestyle via an interviewer-administered questionnaire. A total of 3,646 questionnaires were analysed. Results. It was discovered that official data concerning allergic rhinitis, TB and asthma are almost equal, but readings in relation to CRD are about five times lower according to official data of the Ministry of Health of Georgia. The data results: for allergic rhinitis - 218 in GAPS vs. 177 in the official statistics (for 100.000 population); for TB -105 in GAPS vs. 147 in the official statistics; for asthma -250 in GAPS vs. 374 in the official statistics; the data about CRD according to our survey is almost five times higher - 365 in GAPS vs. 84 in the official statistics (for 100.000 population). Conclusions. It is necessary to expand the survey to the entire country population. Country results are likely to be useful and interesting for local doctors and managers, as well as for officials.

scholarly journals cAMP metabolism controls caspase-11 inflammasome activation and pyroptosis in sepsis

2019 ◽  
Vol 5 (5) ◽  
pp. eaav5562 ◽  
Author(s):  
Ruochan Chen ◽  
Ling Zeng ◽  
Shan Zhu ◽  
Jiao Liu ◽  
Herbert J. Zeh ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Poly I:C ◽  
Inflammasome Activation ◽  
Proof Of Concept ◽  
Potential Therapeutic Target ◽  
Camp Metabolism ◽  
Camp Hydrolysis ◽  
Insight Into

The ability of cytosolic lipopolysaccharide (LPS) to activate caspase-11–dependent nonclassical inflammasome is intricately controlled to avoid excessive inflammatory responses. However, very little is known about the regulatory role of various metabolic pathways in the control of caspase-11 activation. Here, we demonstrate that l-adrenaline can act on receptor ADRA2B to inhibit the activation of the caspase-11 inflammasome by cytosolic LPS or Escherichia coli infection in macrophages. l-adrenaline–induced cAMP production via the enzyme ADCY4 promotes protein kinase A (PKA) activation, which then blocks the caspase-11–mediated proteolytic maturation of interleukin-1β, gasdermin D (GSDMD) cleavage, and consequent DAMP release. Inhibition of PDE8A-mediated cAMP hydrolysis limits caspase-11 inflammasome activation and pyroptosis in macrophages. Consequently, pharmacological modulation of the ADRA2B-ADCY4-PDE8A-PKA axis, knockout of caspase-11 (Casp11−/−), or Gsdmd inactivation (GsdmdI105N/I105N) similarly protects against LPS-induced lethality in poly(I:C)-primed mice. Our results provide previously unidentified mechanistic insight into immune regulation by cAMP and represent a proof of concept that immunometabolism constitutes a potential therapeutic target in sepsis.

scholarly journals The ABCs of Rhinoviruses, Wheezing, and Asthma

2010 ◽  
Vol 84 (15) ◽  
pp. 7418-7426 ◽  
Author(s):  
James E. Gern
Keyword(s):  
Respiratory Diseases ◽  
Chronic Obstructive Lung Disease ◽  
Allergic Diseases ◽  
Chronic Respiratory Disease ◽  
Chronic Obstructive ◽  
Respiratory Illnesses ◽  
Chronic Respiratory Diseases ◽  
Acute Exacerbations ◽  
Close Relationship ◽  
Viral Diagnostics

ABSTRACT Human rhinoviruses (HRVs) were discovered as common cold pathogens over 50 years ago. Recent advances in molecular viral diagnostics have led to an appreciation of their role in more-significant respiratory illnesses, including bronchiolitis in infancy, childhood pneumonia, and acute exacerbations of chronic respiratory diseases such as asthma, chronic obstructive lung disease, and cystic fibrosis. Until a few years ago, only two groups of HRVs (A and B) had been recognized. However, full and partial sequencing of HRVs led to the discovery of a third species of HRV (HRV-C) that has distinct structural and biologic features. Risk factors and pathogenic mechanisms for more-severe HRV infections are being defined, and yet fundamental questions persist about mechanisms relating this common pathogen to allergic diseases and asthma. The close relationship between HRV infections and asthma suggests that antiviral treatments could have a major impact on the morbidity associated with this chronic respiratory disease.

scholarly journals Evidence for pulmonary rehabilitation in chronic respiratory diseases in sub-Saharan Africa: a systematic review

2020 ◽  
Vol 24 (10) ◽  
pp. 991-999
Author(s):  
F. M. Bickton ◽  
C. Fombe ◽  
E. Chisati ◽  
J. Rylance
Keyword(s):  
Pulmonary Rehabilitation ◽  
Respiratory Diseases ◽  
Sub Saharan Africa ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Exercise Regimen ◽  
Home Based ◽  
Sub Saharan ◽  
Randomised Controlled

BACKGROUND: Pulmonary rehabilitation (PR) is a highly effective non-pharmacological treatment for patients with chronic respiratory diseases.OBJECTIVE: To synthesise the evidence for PR practice and efficacy in sub-Saharan Africa.METHODS: We searched in PubMed and Scopus for relevant studies and scanned reference lists of relevant studies from these databases for additional studies. Articles meeting the inclusion criteria were included. Pre-determined data were extracted independently by two reviewers. A narrative synthesis approach was used in the interpretation of findings.RESULTS: Six studies were included, totalling 275 participants. Indications for PR were chronic obstructive pulmonary disease, asthma, pulmonary tuberculosis and post-tuberculosis lung disease. Programmes ran for 6–12 weeks, universally incorporated exercise, and variously used home-based and hospital-based delivery models. All were interventional studies, of which two were randomised controlled trials, and primarily reported pulmonary function and exercise tolerance endpoints. Evidence for individualising the exercise regimen was available in three studies.CONCLUSIONS: There is limited evidence on PR design and efficacy in sub-Saharan Africa, but available data support its use in a variety of chronic respiratory conditions. Future studies should report core outcome sets and their individualised exercise and education regimens.

scholarly journals The microbiome in respiratory medicine: current challenges and future perspectives

2017 ◽  
Vol 49 (4) ◽  
pp. 1602086 ◽  
Author(s):  
Rosa Faner ◽  
Oriol Sibila ◽  
Alvar Agustí ◽  
Eric Bernasconi ◽  
James D. Chalmers ◽  
...  
Keyword(s):  
Respiratory Diseases ◽  
Future Research ◽  
Chronic Obstructive ◽  
Gene Expressions ◽  
Obstructive Pulmonary Disease ◽  
Bacterial Gene ◽  
Chronic Respiratory Diseases ◽  
Culture Techniques ◽  
Negative Results ◽  
Cultivable Bacteria

The healthy lung has previously been considered to be a sterile organ because standard microbiological culture techniques consistently yield negative results. However, culture-independent techniques report that large numbers of microorganisms coexist in the lung. There are many unknown aspects in the field, but available reports show that the lower respiratory tract microbiota: 1) is similar in healthy subjects to the oropharyngeal microbiota and dominated by members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows changes in smokers and well-defined differences in chronic respiratory diseases, although the temporal and spatial kinetics of these changes are only partially known; and 3) shows relatively abundant non-cultivable bacteria in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and bronchiectasis, with specific patterns for each disease. In all of these diseases, a loss of diversity, paralleled by an over-representation of Proteobacteria (dysbiosis), has been related to disease severity and exacerbations. However, it is unknown whether dysbiosis is a cause or a consequence of the damage to bronchoalveolar surfaces.Finally, little is known about bacterial functionality and the interactions between viruses, fungi and bacteria. It is expected that future research in bacterial gene expressions, metagenomics longitudinal analysis and host–microbiome animal models will help to move towards targeted microbiome interventions in respiratory diseases.

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