Effect of Nebulized Hypertonic Saline, Menthol, and Capsaicin on the Distal Airway Transport Properties
Date
2025-02-18
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ORCID
Type
Thesis
Degree Level
Masters
Abstract
Cystic fibrosis (CF) is a rare genetic disease characterized by a loss of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, in which most of the mortality arises from lung disease. Loss of the CFTR channel in the lungs results in dehydration of the airway surface liquid (ASL) and a viscous mucin layer, hindering mucociliary clearance (MCC). Bacteria that enter the airways will become trapped, resulting in a cycle of infection and inflammation, and eventually respiratory failure. This phenomenon accounts for 80-95% of deaths in people with CF (pwCF). Nebulized hypertonic saline (HTS) is a treatment protocol being used for this issue. Nebulized HTS was believed to increase hydration by producing an osmotic gradient. However, our laboratory discovered that the osmotic effect of HTS only accounts for approximately 50% of HTS-triggered ASL rehydration. The other 50% of the HTS effect is due to activation of A delta and C fibers in the trachea. Furthermore, the contribution of HTS and the nervous system to airway hydration in the distal airways is unclear. The aim of this research project is to evaluate the distal airway epithelium fluid transport properties after treatment with nebulized HTS, with and without the addition of menthol or capsaicin. The hypothesis is that neural agonists will stimulate to increase ion transport in the distal airway epithelia of wild type pig lungs. We conducted ex vivo experiments on samples of distal airways from male and female swine. Distal airway sections were short-circuited in Ussing chambers, and the resulting short-circuit current, resistance and voltage was measured after stimulation with forskolin and isobutylmethylxanthine (IBMX), with or without neural agonists. The results indicated that direct application of capsaicin and menthol stimulated epithelial ion transport. However, it did not increase the response to the cyclic adenosine monophosphate (cAMP) elevating agents, forskolin and IBMX. Nebulization with HTS, menthol, or capsaicin was not sufficient to stimulate the distal airways, suggesting that the nebulized particles may not reach the distal airways. This research contributes to the development of more effective novel HTS-nebulized treatments to improve airway rehydration methods of the distal airways.
Description
Keywords
Nebulized Hypertonic Saline, Menthol, Capsaicin, Distal Airways, Ussing Chamber, Short Circuit Current
Citation
Degree
Master of Science (M.Sc.)
Department
Anatomy, Physiology, and Pharmacology
Program
Anatomy, Physiology, and Pharmacology