scholarly journals Pharmacological Rationale for Targeting IL-17 in Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Experimental Models ◽  
Airflow Limitation ◽  
Interleukin 17 ◽  
Asthma Phenotype ◽  
T Helper 2 ◽  
Bronchial Biopsies

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

scholarly journals Mast cells are associated with exacerbations and eosinophilia in children with severe asthma

2016 ◽  
Vol 48 (5) ◽  
pp. 1320-1328 ◽  
Author(s):  
Guillaume Lezmi ◽  
Louise Galmiche-Rolland ◽  
Sabine Rioux ◽  
Francis Jaubert ◽  
Isabelle Tillie-Leblond ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Eosinophilic Inflammation ◽  
Symptomatic Group ◽  
Mucosal Mast Cells ◽  
Bronchial Biopsies ◽  
Positive Correlations

The role of mast cells in the pathogenesis of childhood asthma is poorly understood. We aimed to estimate the implication of airway mucosal mast cells in severe asthma and their relationship with clinical, functional, inflammatory and remodelling parameters.Bronchial biopsies were performed in 36 children (5–18 years) with severe asthma: 24 had frequent severe exacerbations and/or daily symptoms in the previous year (symptomatic group), and 12 had few symptoms and a persistent obstructive pattern (paucisymptomatic group). Nine children without asthma were included as control subjects. We assessed mast cells in the submucosa and airway smooth muscle using c-kit antibodies and in the entire biopsy area using Giemsa.The number of submucosal mast cells was higher in the symptomatic group than in the paucisymptomatic group (p=0.02). The number of submucosal mast cells correlated with the number of severe exacerbations (p=0.02, r=0.37). There were positive correlations between the number of submucosal mast cells (p<0.01, r=0.44), airway smooth muscle mast cells (p=0.02, r= 0.40), mast cells stained by Giemsa (p<0.01, r=0.44) and submucosal eosinophils.Mast cells are associated with severe exacerbations and submucosal eosinophilic inflammation in children with severe asthma.

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 Interleukin-17 cytokine signalling in patients with asthma

2014 ◽  
Vol 44 (5) ◽  
pp. 1319-1331 ◽  
Author(s):  
Anders Lindén ◽  
Barbro Dahlén
Keyword(s):  
Smooth Muscle ◽  
Severe Asthma ◽  
Interleukin 17 ◽  
Causative Role ◽  
Neutrophil Accumulation ◽  
T Helper 17 ◽  
Clinical Investigations ◽  
T Helper 17 Cell ◽  
Global Health Problem

Asthma remains a global health problem and, therefore, more effective pharmacotherapy is needed. This is particularly true for chronic and severe asthma. In these clinical phenotypes, chronic inflammation involving neutrophils is likely to play a pathogenic role, making it interesting to target cytokine signalling involved in the accumulation of neutrophils. Therefore, it is of interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A, perhaps also IL-17F, controls neutrophil accumulation, mucus secretion, macrophage mobilisation and smooth muscle reactivity in various experimental airway models. However, much less is known about the involvement of signalling via IL-17 cytokines in humans with asthma. Existing evidence suggests that these cytokines are released from several types of immune cells in asthma and, for IL-17A, there is a local increase associated with disease severity, with the mobilisation of neutrophils and smooth muscle cells locally in the airways. Even though the causative role of IL-17 cytokines remains unclear, there is potential for clinical utility in targeting IL-17A specifically in patients with moderate-to-severe asthma and high reversibility. There is a need for new and well-powered clinical investigations of signalling via IL-17 cytokines in this clinical phenotype.

scholarly journals The Potential Role of Interleukin-17 in Severe Asthma

2011 ◽  
Vol 11 (5) ◽  
pp. 388-394 ◽  
Author(s):  
Yui-Hsi Wang ◽  
Marsha Wills-Karp
Keyword(s):  
Severe Asthma ◽  
Potential Role ◽  
Interleukin 17

scholarly journals Role of interleukin-23/interleukin-17 axis in T-cell-mediated actions in hypertension

2020 ◽  
Author(s):  
Akinori Higaki ◽  
Ahmad U M Mahmoud ◽  
Pierre Paradis ◽  
Ernesto L Schiffrin
Keyword(s):  
Observational Studies ◽  
Current Knowledge ◽  
Interleukin 17 ◽  
Preclinical Studies ◽  
Rodent Models ◽  
Blood Pressure Elevation ◽  
Immune Mechanisms ◽  
Treatment Of Hypertension ◽  
Interleukin 23

Abstract Current knowledge suggests that hypertension is in part mediated by immune mechanisms. Both interleukin (IL)-23 and IL-17 are up-regulated in several experimental hypertensive rodent models, as well as in hypertensive humans in observational studies. Recent preclinical studies have shown that either IL-23 or IL-17A treatment induce blood pressure elevation. However, the IL-23/IL-17 axis has not been a major therapeutic target in hypertension, unlike in other autoimmune diseases. In this review, we summarize current knowledge on the role of these cytokines in immune mechanisms contributing to hypertension, and discuss the potential of IL-23/IL-17-targeted therapy for treatment of hypertension.

scholarly journals Problematic, severe asthma in children: a new concept and how to manage it

2010 ◽  
Vol 17 (1-2) ◽  
pp. 51-64
Author(s):  
Andrew BUSH
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Treatment Plan ◽  
Airflow Limitation ◽  
Steroid Resistance ◽  
Single Intramuscular Injection ◽  
Children With Asthma ◽  
Oral Corticosteroids ◽  
The Stability ◽  
Future Work

Most children with asthma respond to low doses of inhaled corticosteroids, but a few remain symptomatic despite being prescribed the routine usual asthma medications. The first steps are to ensure that the diagnosis is correct and that the inhaled medications are being given regularly with an appropriately used device. If the children continue to be symptomatic, with any or all of chronic symptoms, acute exacerbations, the need for regular oral corticosteroids, or persistent airflow limitation, then they are considered to have problematic, severe asthma. The next step is to perform a detailed evaluation, including a nurse-lead home visit, to determine whether the child has difficult to treat asthma which improves if the basics are got right, or severe, therapy-resistant asthma; the latter group would be candidates for cytokine-specific therapies. If severe, therapy-resistant asthma is the likely issue, then a detailed invasive investigation is performed, including bronchoscopy, bronchoalveolar lavage and endobronchial biopsy, and trial of adherence with a single intramuscular injection of depot triamcinolone. After detailed phenotyping, an individualised treatment plan is determined. Future work will determine the roles of proximal and distal inflammation, as well as the relative importance of intramural (mucosal) and intraluminal infection. The stability of paediatric asthma phenotypes over time is more variable than those of adults, and the implications of a change of phenotype are yet to be determined. Keywords: steroid resistance, allergen exposure, passive smoking, omalizumab, prednisolone, steroid-sparing agent, phenotype, nitric oxide, induced sputum, endobronchial biopsy

scholarly journals Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation

2008 ◽  
Vol 104 (2) ◽  
pp. 394-403 ◽  
Author(s):  
Ronald L. Sorkness ◽  
Eugene R. Bleecker ◽  
William W. Busse ◽  
William J. Calhoun ◽  
Mario Castro ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Pathological Process ◽  
Airflow Limitation ◽  
Care Utilization ◽  
Air Trapping ◽  
Asthma Phenotype ◽  
Blood Institute ◽  
National Heart Lung

Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV1)/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV1/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV1/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV1 reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV1 after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV1 when baseline FEV1 was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.

scholarly journals Herbal Medicines for the Treatment of Nonalcoholic Steatohepatitis: Current Scenario and Future Prospects

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Ravirajsinh Jadeja ◽  
Ranjitsinh V. Devkar ◽  
Srinivas Nammi
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Metabolic Disorders ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Herbal Medicines ◽  
Experimental Models ◽  
Treatment Schedule ◽  
Herbal Extracts ◽  
Current Scenario

Nonalcoholic steatohepatitis (NASH) is a multifactorial disease and has close correlations with other metabolic disorders. This makes its treatment difficult using a single pharmacological drug. Use of plant extract/decoction or polyherbal formulation to treat various liver diseases is very well mentioned in various traditional systems of medicine (Ayurveda, Japanese or traditional Chinese Medicine, and Kampo medicine). Medicinal herbs are known for their multifaceted implications and thus can form an effective treatment schedule against NASH. Till date, several plant extracts, polyherbal formulations, and phytochemicals have been evaluated for their possible therapeutic potential in preventing onset and progression of NASH in experimental models, but clinical studies using the same are sparse. Herbal extracts with antioxidants, antidiabetic, and antihyperlipidemic properties have been shown to ameliorate symptoms of NASH. This review article is a meticulous compilation of our current knowledge on the role of natural products in alleviating NASH and possible lacunae in research that needs to be addressed.

scholarly journals Translating Recent Microbiome Insights in Otitis Media into Probiotic Strategies

2019 ◽  
Vol 32 (4) ◽  
Author(s):  
Marianne F. L. van den Broek ◽  
Ilke De Boeck ◽  
Filip Kiekens ◽  
An Boudewyns ◽  
Olivier M. Vanderveken ◽  
...  
Keyword(s):  
Otitis Media ◽  
Pathogenic Bacteria ◽  
Current Knowledge ◽  
Experimental Models ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Beneficial Action ◽  
Next Generation Sequencing Ngs ◽  
Clinical Potential

SUMMARYThe microbiota of the upper respiratory tract (URT) protects the host from bacterial pathogenic colonization by competing for adherence to epithelial cells and by immune response regulation that includes the activation of antimicrobial and (anti-)inflammatory components. However, environmental or host factors can modify the microbiota to an unstable community that predisposes the host to infection or inflammation. One of the URT diseases most often encountered in children is otitis media (OM). The role of pathogenic bacteria likeStreptococcus pneumoniae,Haemophilus influenzae, andMoraxella catarrhalisin the pathogenesis of OM is well documented. Results from next-generation-sequencing (NGS) studies reveal other bacterial taxa involved in OM, such asTuricellaandAlloiococcus. Such studies can also identify bacterial taxa that are potentially protective against URT infections, whose beneficial action needs to be substantiated in relevant experimental models and clinical trials. Of note, lactic acid bacteria (LAB) are members of the URT microbiota and associated with a URT ecosystem that is deemed healthy, based on NGS and some experimental and clinical studies. These observations have formed the basis of this review, in which we describe the current knowledge of the molecular and clinical potential of LAB in the URT, which is currently underexplored in microbiome and probiotic research.

scholarly journals Bronchial Thermoplasty in the Treatment of Severe Asthma

2020 ◽  
pp. 1-9
Author(s):  
Nightingale Syabbalo ◽  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
High Dose ◽  
Eosinophilic Asthma ◽  
Bronchial Thermoplasty ◽  
Long Acting ◽  
Refractory Asthma

Asthma is a chronic inflammatory airway disease with several distinct phenotypes, characterized by different immunopathological pathways, clinical presentation, severity of the disease, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma. Approximately 3.6-10% of patients with asthma have severe refractory disease, which is unresponsive to high dose inhaled corticosteroids (ICS), and long-acting β2-agonists (LABA). Most patients with eosinophilic asthma are responsive to corticosteroids, and interleukintargeted biologics, whereas, patients from other phenotypes, such as neutrophillic and paucigranullocytic asthma are resistant to treatment with ICS and biotherapeutics. The hallmark of severe refractory asthma is airway hyperresponsiveness, and remodeling. Histopathologically, patients with severe asthma have airway smooth muscle (ASM) hyperplasia and hypertrophy; subepithelial basement membrane thickening and fibrosis; all which contribute to fixed airflow limitation. Severe refractory asthma is very difficult to treat pharmacologically. It requires innovative therapies, such as bronchial thermoplasty which reduces the hypertrophied ASM mass and relieves the AHR, and broncoconstriction. Bronchial thermoplasty has been shown to improve asthma control, reduce severe exacerbations, hospitalizations, emergency room visits, and improve the quality of life, which persist up to 5 years following the procedure

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