Anti-inflammatory effects of targeted lung denervation in patients with COPD

Kistemaker, Loes; Slebos, Dirk‐Jan; Kerstjens, Huib A. M.; Gosens, Reinoud

doi:10.1183/13993003.00413-2015

Cited by 35 publications

(21 citation statements)

References 10 publications

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“…This is supported by more recent clinical data of long‐acting anticholinergics as effective bronchodilators in asthma 6,7 . ACh can contribute to AHR not only via ASM contraction, but also by inducing airway inflammation and structural remodeling via the muscarinic M3 receptor 8‐11 . While the downstream effects of enhanced neuronal activity on airway structure/function have been explored, the upstream mechanisms by which neuronal plasticity occurs are less known 12 …”

Section: Introductionmentioning

confidence: 91%

Cholinergic neuroplasticity in asthma driven by TrkB signaling

et al. 2020

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Parasympathetic neurons in the airways control bronchomotor tone. Increased activity of cholinergic neurons are mediators of airway hyperresponsiveness (AHR) in asthma, however, mechanisms are not elucidated. We describe remodeling of the cholinergic neuronal network in asthmatic airways driven by brain‐derived neurotrophic factor (BDNF) and Tropomyosin receptor kinase B (TrkB). Human bronchial biopsies were stained for cholinergic marker vesicular acetylcholine transporter (VAChT). Human lung gene expression and single nucleotide polymorphisms (SNP) in neuroplasticity‐related genes were compared between asthma and healthy patients. Wild‐type (WT) and mutated TrkB knock‐in mice (Ntrk2tm1Ddg/J) with impaired BDNF signaling were chronically exposed to ovalbumin (OVA). Neuronal VAChT staining and airway narrowing in response to electrical field stimulation in precision cut lung slices (PCLS) were assessed. Increased cholinergic fibers in asthmatic airway biopsies was found, paralleled by increased TrkB gene expression in human lung tissue, and SNPs in the NTRK2 [TrkB] and BDNF genes linked to asthma. Chronic allergen exposure in mice resulted in increased density of cholinergic nerves, which was prevented by inhibiting TrkB. Increased nerve density resulted in AHR in vivo and in increased nerve‐dependent airway reactivity in lung slices mediated via TrkB. These findings show cholinergic neuroplasticity in asthma driven by TrkB signaling and suggest that the BDNF‐TrkB pathway may be a potential target.

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Section: Introductionmentioning

confidence: 91%

Cholinergic neuroplasticity in asthma driven by TrkB signaling

et al. 2020

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“…We provided the first evidence that acetylcholine might act as a pro-inflammatory mediator in patients with COPD, because airway inflammation is attenuated after TLD [62]. From different trials, including the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial, it is known that tiotropium reduces the number of exacerbations [1].…”

Section: Clinical Implications: Copdmentioning

confidence: 98%

Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling

Kistemaker

Gosens

2015

Trends in Pharmacological Sciences

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“…Airway smooth muscle is neither hypertrophic or hyperplastic in COPD, unlike in asthma. Interestingly, taking the lead from severe asthma, a modified form of bronchial thermoplasty called “targeted lung denervation” (TLD), which uses a water-cooled probe tip to ablate nerve fibers rather than smooth muscle, has proven effective in several small and uncontrolled trials but it is not known whether this approach truly reduces cholinergic drive or interrupts afferent sensory fibers that contribute to the sensation of dyspnea 8 .…”

Section: New Bronchodilatorsmentioning

confidence: 99%

Advances in understanding COPD

Anderson

2016

F1000Res

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In recent years, thousands of publications on chronic obstructive pulmonary disease (COPD) and its related biology have entered the world literature, reflecting the increasing scientific and medical interest in this devastating condition. This article is a selective review of several important emerging themes that offer the hope of creating new classes of COPD medicines. Whereas basic science is parsing molecular pathways in COPD, its comorbidities, and asthma COPD overlap syndrome (ACOS) with unprecedented sophistication, clinical translation is disappointingly slow. The article therefore also considers solutions to current difficulties that are impeding progress in translating insights from basic science into clinically useful treatments.

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Anti-inflammatory effects of targeted lung denervation in patients with COPD

Cited by 35 publications

References 10 publications

Cholinergic neuroplasticity in asthma driven by TrkB signaling

Cholinergic neuroplasticity in asthma driven by TrkB signaling

Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling

Advances in understanding COPD

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