Airway Mucosal Remodeling: Mechanism of Action and Preclinical Data of Pulsed Electric Fields for Chronic Bronchitis and Mucus Hypersecretion

Abstract

Patients living with chronic bronchitis (CB) suffer from physical limitations and poor quality of life. In general, treatment options that directly address the mucus hypersecretion component of CB are quite limited. Chronic airway inflammation and the associated hypersecretion and cough that are pathognomonic for CB generally result from long-term exposure to airway irritants such as tobacco use and other environmental insults. This, in turn, results in an increase in the quantity and change in composition of the airway mucosa as a consequence of altered goblet cells, club cells, and submucosal glands. Pulsed electric fields (PEFs) provide a method for eradicating the cellular constituents of tissue with limited impact on the stromal proteins. Preclinical evidence in porcine airways demonstrated that particular PEF waveforms allowed for salutary remodeling of the epithelial and submucosal airway tissue layers and appeared to foster rapid regeneration and recovery of the tissue. Therefore, a therapeutic opportunity might exist whereby the application of a specific form of PEF may result in a reduction of the cellular secretory constituents of the airway while also reducing airway mucosal inflammation. This review discusses the use of such PEF to address the underlying disease processes in CB including challenges around device design, dosing, and appropriate delivery methods. Further, we outline considerations for the transition to human airways along with a brief examination of the initial work treating CB patients, suggesting that the therapy is well tolerated with limited adverse events.