Combating cigarette smoking-induced COPD through Dual Bronchodilators

Chitra Roy, University of Calcutta

Cigarette smoking is one of the major risk factors and causes of chronic obstructive pulmonary disease (COPD). Cigarette smoking accounts for almost 90% of COPD risk. Smoking can destroy the lung parenchyma and also contribute to the development of emphysema in which the walls of the air sacs(alveoli) in the lungs gets damaged leading to significant changes in the airway dynamics in bronchial tubes with impaired gas exchange and progressive air trapping, all of which is a characteristic of COPD. Cigarette smoking also induces the macrophages the release various neutrophil chemotactic factors and elastases which ultimately damages the tissues. Moreover, secondhand smoke or environmental tobacco smoke also increases the risks of respiratory infections which can lead to a measurable reduction in pulmonary function. 

COPD severity is found to be correlated with the extent of cigarette smoking. In smokers, it induces cell death in structural lung cells which is responsible for emphysema and COPD development. The epithelial cells of the alveoli function as a protective barrier in preserving the pulmonary function. These epithelial cells are vulnerable to insults from cigarette smoke (CS)/cigarette smoke extract (CSE) exposure which induces apoptosis (programmed cell death) and autophagy (self-eating/self-degradation). Therefore, protecting these epithelial cells from CS-induced alterations can show positive impacts. 

Tiotropium and olodaterol are bronchodilators which can regulate various components like M3R and β2AR that are involved in the cell death mechanism and can lead to the contraction and relaxation of airway smooth muscles, respectively. Tiotropium comes as an inhalation spray for long-term COPD treatment to reduce disease flare-ups. Olodaterol is a bronchodilator belonging to the class of drugs known as long-acting beta-agonists (LABA). Like most of the beta-agonists, olodaterol mimics the role of epinephrine at β2 receptors in the lung, which upon activation causes smooth muscles of the lungs to relax and the air spaces to open up and dilate hence improving patient’s respiratory performance.

 It was recently reported that tiotropium and olodaterol, as a dual bronchodilator had a better performance in reducing ROS-reactive oxygen species generation which can induce cell death. However, its mechanism is unclear. So, a team of researchers hypothesized that dual bronchodilators might impart some protective function to the epithelial cells upon exposure to CSE-mediated cell death. They used BEAS-2B (human bronchial epithelial cell line), and exposed these cells to various doses of CSE and performed cell viability assay-MTT assay and observed a reduction in cell viability indicating significant cell injury. To determine the effect of dual bronchodilators on CSE exposed cells, they pretreated the cell for 4hours with dual bronchodilators and then measured cell viability and observed it to increase. This indicated a protective role of using the combined bronchodilators. They also observed reduced mitochondrial dysfunction and increased autophagy activation. Using dual bronchodilators significantly reduced autophagy event. Their results indicated that tiotropium/olodaterol protects the bronchial epithelial cells from deleterious effects of CSE exposure which is related to autophagy regulation. This research successfully provides future insights to improve treatment plans for combating cigarette smoke-induced COPD by targeting autophagy mechanisms.

Also read: Does microbe in the gut protect against hazardous exposure ?

Reference: https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-020-00451-0

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