Assessment of airway inflammation and remodeling in children with severe asthma: The next challenge

2018 ◽  
Vol 53 (9) ◽  
pp. 1171-1173 ◽  
Author(s):  
Guillaume Lezmi ◽  
Jacques de Blic
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma

scholarly journals Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Emma J. Raftis ◽  
Margaret I. Delday ◽  
Philip Cowie ◽  
Seánín M. McCluskey ◽  
Mark D. Singh ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Bifidobacterium Breve ◽  
Asthma Model

scholarly journals Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Michael E. Wechsler ◽  
Chris E. Brightling
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Human Monoclonal Antibody ◽  
Unmet Need ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
Asthma Exacerbations

Abstract Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.

Exercise training and airway inflammation in severe-asthma: results from a feasibility study

2018 ◽  
Author(s):  
Sally Majd ◽  
Sally Singh ◽  
Peter Bradding ◽  
Stacey Hewitt ◽  
Lindsay Apps ◽  
...  
Keyword(s):  
Exercise Training ◽  
Airway Inflammation ◽  
Severe Asthma ◽  
Feasibility Study

scholarly journals S133 Eosinophilic airway inflammation is associated with FEV1 decline in severe asthma

Thorax ◽  
2010 ◽  
Vol 65 (Suppl 4) ◽  
pp. A61-A61
Author(s):  
J. Agbetile ◽  
D. Desai ◽  
B. Hargadon ◽  
P. Bradding ◽  
A. J. Wardlaw ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Fev1 Decline

scholarly journals Budesonide/formoterol Turbuhaler® as needed in mild asthma: results of SYGMA-1 and SYGMA-2 trials (SYmbicort® Given as needed in Mild Asthma)

2019 ◽  
Vol 29 (4) ◽  
pp. 419-427
Author(s):  
S. N. Avdeev ◽  
Z. R. Aisanov ◽  
A. S. Belevskiy ◽  
A. V. Emelyanov ◽  
N. P. Knyazheskaya ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Asthma Exacerbation ◽  
Chronic Inflammatory Disease ◽  
Mild Asthma ◽  
Exacerbation Rate ◽  
Regular Treatment ◽  
High Dependency ◽  
Anti Inflammatory ◽  
Chronic Airway

According to the modern concepts, asthma is a heterogeneous disease characterized by chronic airway inflammation and respiratory symptoms, which vary in time and intensity and manifest together with variable obstruction of the airways. Asthma is responsible for the deterioration of health status and quality of life in approximately 339 million of adult patients and children worldwide. Despite the fact that asthma is a chronic inflammatory disease, patients with asthma generally inadequately receive anti-inflammatory therapy in real clinical practice and rely on short-acting beta2-agonists (SABA) too much; this can “mimic” worsening of asthma symptoms. SABA monotherapy “on demand” does not affect chronic airway inflammation, underlying asthma occurrence and progression. As a result, such patients still have the risk of asthma exacerbation and disease progression. Therefore, the need of a new therapeutic strategy for patients with milder asthma (steps 1 and 2), which would provide anti-inflammatory treatment considering the low adherence to the regular maintenance therapy and high dependency on SABA, is obvious. Such approach has become available after the SYGMA (SYmbicort® Given as needed in Mild Asthma) trial was completed. According to the results of this trial, budesonide/formoterol 160/4.5 µg/dose as needed was superior to as needed SABA in better asthma control and decrease in severe asthma exacerbation rate by 64% (p < 0.001). Results of SYGMA 1 and 2 trials also demonstrated that budesonide/formoterol 160/4.5 µg/dose as needed was noninferior compared to regular treatment with budesonide in preventing severe asthma exacerbations while the cumulative dose of budesonide was reduced by ≥75%. 

scholarly journals Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma

2019 ◽  
Vol 316 (5) ◽  
pp. L843-L868 ◽  
Author(s):  
Jon M. Evasovic ◽  
Cherie A. Singer
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
High Dose ◽  
Persistent Symptoms ◽  
Immune Factors ◽  
Tgf Β1

Severe asthma develops as a result of heightened, persistent symptoms that generally coincide with pronounced neutrophilic airway inflammation. In individuals with severe asthma, symptoms are poorly controlled by high-dose inhaled glucocorticoids and often lead to elevated morbidity and mortality rates that underscore the necessity for novel drug target identification that overcomes limitations in disease management. Many incidences of severe asthma are mechanistically associated with T helper 17 (TH17) cell-derived cytokines and immune factors that mediate neutrophilic influx to the airways. TH17-secreted interleukin-17A (IL-17A) is an independent risk factor for severe asthma that impacts airway smooth muscle (ASM) remodeling. TH17-derived cytokines and diverse immune mediators further interact with structural cells of the airway to induce pathophysiological processes that impact ASM functionality. Transforming growth factor-β1 (TGF-β1) is a pivotal mediator involved in airway remodeling that correlates with enhanced TH17 activity in individuals with severe asthma and is essential to TH17 differentiation and IL-17A production. IL-17A can also reciprocally enhance activation of TGF-β1 signaling pathways, whereas combined TH1/TH17 or TH2/TH17 immune responses may additively impact asthma severity. This review seeks to provide a comprehensive summary of cytokine-driven T cell fate determination and TH17-mediated airway inflammation. It will further review the evidence demonstrating the extent to which IL-17A interacts with various immune factors, specifically TGF-β1, to contribute to ASM remodeling and altered function in TH17-driven endotypes of severe asthma.

Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma

2022 ◽  
Vol 14 (627) ◽  
Author(s):  
Sarah E. Headland ◽  
Hart S. Dengler ◽  
Daqi Xu ◽  
Grace Teng ◽  
Christine Everett ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Oncostatin M ◽  
Mucus Secretion ◽  
Mucus Hypersecretion

Bacterial-associated LPS drives oncostatin M–dependent airway inflammation and mucus hypersecretion in severe asthma.

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