New bronchoscopic treatment modalities for patients with chronic bronchitis

Abstract

Chronic bronchitis is a chronic, progressive disease that is difficult to treat. Despite much effort, patients remain highly symptomatic. Currently, a number of innovative bronchoscopic treatments for this disease are under investigation. Liquid nitrogen metered cryospray, bronchial rheoplasty and balloon desobstruction all aim to destroy the hyperplastic goblet cells and excess submucous glands using different strategies. These therapies are in an early phase of clinical research and larger randomised controlled trials are needed to confirm the pilot data available and to evaluate the treatment durability. The fourth technique, targeted lung denervation (TLD), aims to decrease the release of acetylcholine, which regulates smooth muscle tone and mucus production by ablating the parasympathetic nerves running alongside the main bronchi. Evaluation of this treatment is at a more advanced stage and promising effects on exacerbation frequency have been shown. However, confirmation of the benefit in improvement in chronic bronchitis symptoms is still needed.

FIGURE 1

Bronchoscopic images of treatment catheters. a) RejuvenAir System delivering metered cryospray; b) RheOx bronchial rheoplasty, reproduced with permission from Gala Therapeutics (San Carlos, CA, USA); c) Karakoca balloon desobstruction, reproduced from [31] with permission; d) targeted lung denervation.

FIGURE 2

Schematic overview of mechanisms of action of bronchoscopic interventions for chronic bronchitis. a) Chronic bronchitis airway epithelium with an increased number of hyperplasic goblet cells causing increased mucus secretion. b) The Karakoca resector balloon consists of a latex balloon with a mesh structure of polyurethane/lycra fibres. Inside the airway the balloon is repeatedly inflated and deflated resulting in a force applied to the bronchial mucosa, which mechanically disrupts the hyperplasic goblet cells. c) The RheOx bronchial rheoplasty catheter delivers short bursts of high-frequency electrical energy to the airway epithelium and submucosal tissue layers targeting the goblet cells and glands, aiming to replace the destroyed cells with healthier tissue. d) The RejuvenAir System Metered Cryospray catheter delivers liquid nitrogen at −196°C to the airways, aiming to destroy the goblet cells and inducing a nonscarring healing response with healthier tissue regeneration as a result. e) The Nuvaira dual-cooled balloon catheter uses radiofrequency to disrupt the local vagal nerve branches and therefore the parasympathetic nerve transmission, aimed to decrease acetylcholine levels, resulting in a decreased airway smooth muscle contraction and mucus production.