scholarly journals Physiologic and histopathologic effects of targeted lung denervation in an animal model

2019 ◽  
Vol 126 (1) ◽  
pp. 67-76 ◽  
Author(s):  
James P. Hummel ◽  
Martin L. Mayse ◽  
Steve Dimmer ◽  
Philip J. Johnson

Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures. NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects.

2021 ◽  
pp. 26-31
Author(s):  
I. V. Demko ◽  
M. G. Mamaeva ◽  
E. A. Sobko ◽  
A. Yu. Kraposhina ◽  
N. V. Gordeeva

Chronic obstructive pulmonary disease (COPD) today remains one of the most important problems of modern medicine. The social significance of this disease is determined by the annual health care costs for treating patients with exacerbated COPD, as well as the still high mortality and disability rates worldwide. The main goals of COPD treatment are to slow the rate of disease progression, control the symptoms, reduce the frequency of exacerbations and hospitalizations, and reduce the risk of future exacerbations. Currently, the main groups of drugs for basic therapy of COPD are inhaled prolonged bronchodilators from the groups of β2-adrenergic agonists and M-anticholinergics, as well as their combinations. Patients with COPD and bronchial asthma, as well as patients with COPD with elevated levels of eosinophils and frequent exacerbations, inhaled glucocorticosteroids (ICS) are used. It has been proven that the addition of corticosteroids to LABA in patients with moderate to severe COPD and frequent exacerbations has a more effective influence on pulmonary function and the number of exacerbations. Clinical studies have shown the relationship between the level of blood eosinophilia and the clinical effects of preventing future exacerbations when using iCS in combination with LABA. In our clinical observation, in patient with moderate COPD and blood eosinophilia > 300 cells/μL, when prescribing monotherapy with long-acting agonists, frequent exacerbations of the disease were noted. The addition of corticosteroids to monotherapy with a long-acting agonist made it possible to influence the frequency of exacerbations and reduce the level of eosinophils in the blood.


2019 ◽  
Vol 91 (3) ◽  
pp. 76-85
Author(s):  
S N Avdeev ◽  
N V Trushenko

Currently, combinations of long-acting beta2-agonists and long-acting anticholinergics are considered as the basic therapy for majority of patients with chronic obstructive pulmonary disease (COPD). These combinations have different pharmacological characteristics and delivery devices that provides different clinical effects and new opportunities for personalized treatment of COPD. Aclidinium/formoterol fixed combination differs from other dual bronchodilators by twice-daily dosing regimen, good safety profile and a specific delivery system. Recent information on clinical efficacy and safety of aclidinium/formoterol combination in COPD patients is given in this article.


2021 ◽  
Vol 31 (1) ◽  
pp. 75-87
Author(s):  
I. V. Leshchenko ◽  
A. S. Meshcheryakova

Chronic obstructive pulmonary disease (COPD) is the leading cause of death in the structure of respiratory diseases. The problem of rational pharmacotherapy of COPD have attracted attention of the medical scientific society for many years. The understanding of the pathogenesis of the disease has deepened and approaches to the therapy have changed. Some COPD patients need regular fixed-combination therapy: long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS) in order to prevent exacerbations and reduce the severity of symptoms of the disease. Blood eosinophils count is one of criteria for choosing regular therapy. The appearance of fixed triple combinations of ICS/LABD increased the effectiveness of COPD therapy, and a new delivery device for fixed combination of budesonide/formoterol makes it possible to use ICS successfully in the most severe patients.


MedAlliance ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 32-39

Chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (TB) are a common pathology among respiratory diseases. Both conditions may have common risk factors, aggravating each other, accom-panied by the development of bronchial obstructive syndrome, requiring mandatory medical correction to increase the effectiveness of therapy for both the main and concomitant pathologies. The aim of the study was to study the effectiveness of treatment of TB in patients with COPD first diagnosed with tuberculosis, including those associated with HIV when prescribing long-acting β2-agonists. Materials and methods. A simple com-parative study included 60 patients of a TB dispensary aged 30–65 years. Patients were divided into 2 groups of 30 people (TB+COPD and TB+COPD+HIV), each of whom for 2 months received a long-acting β-agonist (indacaterol) as an accompanying therapy for the cor-rection of bronchial obstructive syndrome (BOS), with subsequent assessment of the effectiveness of therapy. Results. Subjectively, patients of both groups noted the rapid development of positive dynamics (short-ness of breath decreased from 1–3 days of taking the drug, coughing — within a week, tolerance to physical exertion improved), which was confirmed by indica-tors of the function of external respiration (FEV1). The state of the cardiovascular system was assessed by the results of daily monitoring of blood pressure (BPM). In the COPD+TB group, there is a certain average daily systolic blood pressure (SBP) with a tendency to nor-malize indicators, which is possibly associated with a decrease in the severity of hypoxia during bronchodi-lator therapy. In the COPD+TB+HIV group, the average daily level of SBP increased by 1 mm Hg, but given the very low starting rates, the increase in blood pressure had a positive effect on the patients' condition. The average heart rate (HR) during bronchodilator thera-py did not tend to increase. The best TB treatment re-sults were obtained in the TB+COPD group. In terms of the closure rate of TB+COPD decay cavities — 26.6%, TB+COPD+HIV — 20.0%), the TB+COPD+HIV group had longer periods of abacillation and closure of decay cav-ities, which is associa ted with the severity of the under-lying and associated diseases. The drug was well toler-ated in both groups. Conclusion. The use of 300 mcg long-acting β-adrenomimetics in the complex therapy of β2-adrenergic agonists for patients with TB+COPD and TB+ COPD+HIV can reduce the severity of bronchial obstruction syndrome, improve quality of life, increase adherence to TB treatment, thereby shortening hospi-talization and reduce the likelihood of disability of pa-tients, without the development of side effects from other organs and systems.


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