scholarly journals Airway inflammation in severe asthmatics with acid gastro-oesophageal reflux

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216304
Author(s):  
Nicole Tanner ◽  
Sejal Saglani ◽  
Albert M Li ◽  
Andrew Bush ◽  
Louise Fleming
Keyword(s):  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Systemic Inflammation ◽  
Childhood Asthma ◽  
Host Defence ◽  
Oesophageal Reflux ◽  
Epithelial Integrity ◽  
The Relationship

The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma.

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.

Childhood asthma: Exhaled markers of airway inflammation, asthma control score, and lung function tests

2004 ◽  
Vol 38 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Philippe P.R. Rosias ◽  
Edward Dompeling ◽  
Mieke A. Dentener ◽  
Herman J. Pennings ◽  
Han J.E. Hendriks ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Asthma Control ◽  
Childhood Asthma ◽  
Lung Function Tests ◽  
Control Score ◽  
Function Tests

Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children

Allergy ◽  
2009 ◽  
Vol 64 (12) ◽  
pp. 1753-1757 ◽  
Author(s):  
G. L. Piacentini ◽  
D. G. Peroni ◽  
A. Bodini ◽  
E. Bonafiglia ◽  
E. Rigotti ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Asthma Control ◽  
Childhood Asthma ◽  
Control Test ◽  
Asthma Control Test ◽  
Asthmatic Children

Sex differences in the relationship of sleep-disordered breathing and asthma control among children with severe asthma

2021 ◽  
pp. 1-14
Author(s):  
Sigfus Gunnlaugsson ◽  
Kimberly F. Greco ◽  
Carter R. Petty ◽  
Gabriella C. Sierra ◽  
Natalie P. Stamatiadis ◽  
...  
Keyword(s):  
Sex Differences ◽  
Asthma Control ◽  
Severe Asthma ◽  
Sleep Disordered Breathing ◽  
Relationship Of ◽  
The Relationship ◽  
Disordered Breathing

Biologic Therapy and Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 100-114 ◽  
Author(s):  
Ravi Viswanathan ◽  
William Busse
Keyword(s):  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Clinical Characteristics ◽  
Biologic Therapy ◽  
Severe Disease ◽  
Asthma Patient ◽  
Clinical Heterogeneity ◽  
Patient Responsiveness

AbstractAlthough airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest.

scholarly journals The relationship of morphometric changes of the brain with IL-6 levels, systemic inflammation and immune disturbances in the patients with schizophrenia

2021 ◽  
Vol 190 ◽  
pp. 553-559
Author(s):  
Irina K. Malashenkova ◽  
Vadim L. Ushakov ◽  
Sergey A. Krynskiy ◽  
Daniil P. Ogurtsov ◽  
Nikita A. Khailov ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

scholarly journals Effects of Obesity on Airway and Systemic Inflammation in Asthmatic Children

2021 ◽  
pp. 1-11
Author(s):  
Emine Vezir ◽  
Ersoy Civelek ◽  
Emine Dibek Misirlioglu ◽  
Muge Toyran ◽  
Murat Capanoglu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Systemic Inflammation ◽  
Adiponectin Level ◽  
Inflammatory Cells ◽  
Prick Test ◽  
Asthmatic Children ◽  
Asthmatic Patients ◽  
Reactive Protein ◽  
Type 2 Cytokines ◽  
Asthma In Children

Background: Obese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. Objectives: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. Methods: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. Results: A total of 153 participants aged 6–18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). Conclusion: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.

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