Advantages of pulsed electric field ablation for COPD: Excellent killing effect on goblet cells.

Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.

Challenges in clinical practice, biological mechanism and prospects of physical ablation therapy for COPD.

Chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death globally by 2030. Despite the limited treatment options available for advanced COPD, which are mostly restricted to costly lung transplants, physical ablation therapy offers promising alternatives. This technique focuses on ablating lesioned airway epithelium, reducing secretions and obstructions, and promoting normal epithelial regeneration, demonstrating significant therapeutic potential. Physical ablation therapy primarily involves thermal steam ablation, cryoablation, targeted lung denervation, and high-voltage pulsed electric field ablation. These methods help transform the hypersecretory phenotype, alleviate airway inflammation, and decrease the volume of emphysematous lung segments by targeting goblet cells and damaged lung areas. Compared to traditional treatments, endoscopic physical ablation offers fewer injuries, quicker recovery, and enhanced safety. However, its application in COPD remains limited due to inconsistent clinical outcomes, a lack of well-understood mechanisms, and the absence of standardized guidelines. This review begins by exploring the development of these ablation techniques and their current clinical uses in COPD treatment. It then delves into the therapeutic effects reported in recent clinical studies and discusses the underlying mechanisms. Finally, the review assesses the future prospects and challenges of employing ablation technology in COPD clinical practice, aiming to provide a practical reference and a theoretical basis for its use and inspire further research.