Future treatment for asthma

Charriot, Jeremy; Vachier, Isabelle; Halimi, Laurence; Gamez, Anne‐Sophie; Boissin, Clément; Salama, Marine; Cucu-Jarjour, Alina; Ahmed, Engi; Bourdin, Arnaud

doi:10.1183/16000617.0069-2015

Cited by 19 publications

(10 citation statements)

References 148 publications

(140 reference statements)

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“…Combination therapy with inhaled corticosteroids (ICS) and long-acting β agonists (LABAs) remains the mainstay pharmacotherapeutic approach in asthma management (Ye et al, 2017). ICS are effective in suppressing inflammation while LABAs act as bronchodilators (Charriot et al, 2016). Airway remodeling is thought to be a secondary event in asthma following persistent airway inflammation.…”

Section: Effects Of Current Asthma Medicinesmentioning

confidence: 99%

Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia

et al. 2019

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Increased ASM mass, primarily due to ASM hyperplasia, has been recognized as a hallmark of airway remodeling in asthma. Increased ASM mass is the major contributor to the airway narrowing, thus worsening the bronchoconstriction in response to stimuli. Inflammatory mediators and growth factors released during inflammation induce increased ASM mass surrounding airway wall via increased ASM proliferation, diminished ASM apoptosis and increased ASM migration. Several major pathways, such as MAPKs, PI3K/AKT, JAK2/STAT3 and Rho kinase, have been reported to regulate these cellular activities in ASM and were reported to be interrelated at certain points. This article aims to provide an overview of the signaling pathways/molecules involved in ASM hyperplasia as well as the mapping of the interplay/crosstalk between these major pathways in mediating ASM hyperplasia. A more comprehensive understanding of the complexity of cellular signaling in ASM cells will enable more specific and safer drug development in the control of asthma.

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Section: Effects Of Current Asthma Medicinesmentioning

confidence: 99%

Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia

et al. 2019

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“…On the other hand, attenuation of locally produced cytokines is currently a focus of research on targeted therapies [52, 53] and can be a new approach in personalized medicine. Therefore, inhibitors directed against IL-13 or IL-4Rα have been developed as new asthma therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Human lung tissue provides highly relevant data about efficacy of new anti-asthmatic drugs

et al. 2018

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Subgroups of patients with severe asthma are insensitive to inhaled corticosteroids and require novel therapies on top of standard medical care. IL-13 is considered one of the key cytokines in the asthma pathogenesis, however, the effect of IL-13 was mostly studied in rodents. This study aimed to assess IL-13 effect in human lung tissue for the development of targeted therapy approaches such as inhibition of soluble IL-13 or its receptor IL-4Rα subunit. Precision-cut lung slices (PCLS) were prepared from lungs of rodents, non-human primates (NHP) and humans. Direct effect of IL-13 on human lung tissue was observed on inflammation, induction of mucin5AC, and airway constriction induced by methacholine and visualized by videomicroscopy. Anti-inflammatory treatment was evaluated by co-incubation of IL-13 with increasing concentrations of IL-13/IL-13 receptor inhibitors. IL-13 induced a two-fold increase in mucin5AC secretion in human bronchial tissue. Additionally, IL-13 induced release of proinflammatory cytokines eotaxin-3 and TARC in human PCLS. Anti-inflammatory treatment with four different inhibitors acting either on the IL-13 ligand itself (anti-IL-13 antibody, similar to Lebrikizumab) or the IL-4Rα chain of the IL-13/IL-4 receptor complex (anti-IL-4Rα #1, similar to AMG 317, and #2, similar to REGN668) and #3 PRS-060 (a novel anticalin directed against this receptor) could significantly attenuate IL-13 induced inflammation. Contrary to this, IL-13 did not induce airway hyperresponsiveness (AHR) in human and NHP PCLS, although it was effective in rodent PCLS. Overall, this study demonstrates that IL-13 stimulation induces production of mucus and biomarkers of allergic inflammation in human lung tissue ex-vivo but no airway hyperresponsiveness. The results of this study show a more distinct efficacy than known from animals models and a clear discrepancy in AHR induction. Moreover, it allows a translational approach in inhibitor profiling in human lung tissue.

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“…Continuing to keep abreast of the evolving clinical evidence, new devices and treatment combinations, and support strategies for the care of patients with asthma is also important. It is becoming clear that asthma is a highly heterogeneous disease, and that ascertaining asthma phenotype may also guide therapeutic decisions in suboptimally controlled asthma 20. However, there are very few clinical trials apart from those of targeted monoclonal therapies that examine treatment response in relation to phenotype.…”

Section: Practical Considerations For the Management Of Patients Withmentioning

confidence: 99%

<p>Barriers to achieving asthma control in adults: evidence for the role of tiotropium in current management strategies</p>

Jenkins

2019

TCRM

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Despite the availability of a range of treatment options and management guidelines, a high proportion of adults with asthma remain uncontrolled. The challenge of managing uncontrolled asthma includes providing efficacious treatment while limiting side effects, recognizing situations when a change in asthma therapy is required, and considering patient preferences and satisfaction. In line with the Global Initiative for Asthma report, asthma management is based on a backbone of inhaled corticosteroid (ICS) therapy and use of add-on therapies to achieve disease control. This review considers whether add-on options could be better utilized in clinical practice. A number of long-acting muscarinic antagonists are in development, but tiotropium is the most widely studied for use in asthma. Evidence demonstrating the efficacy of tiotropium as an add-on therapy to at least ICS in adults with symptomatic mild, moderate, and severe asthma is presented from randomized controlled trials and real-world evidence. In addition, the benefit of tiotropium therapy in a wide range of patient phenotypes and disease severities without the need for biomarker assessment is discussed. Additional strategies that complement this approach, such as recognizing and overcoming barriers to adherence, ensuring optimal device use, and education and support to enhance patient–physician communication, are discussed. Physician education can also help raise awareness that additional management options are available for patients with moderate-to-severe asthma who remain uncontrolled on ICS/long-acting β2-agonist treatment.

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Future treatment for asthma

Cited by 19 publications

References 148 publications

Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia

Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia

Human lung tissue provides highly relevant data about efficacy of new anti-asthmatic drugs

<p>Barriers to achieving asthma control in adults: evidence for the role of tiotropium in current management strategies</p>

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