Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial

Abstract

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV₁, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

Keywords: lung diseases; bronchial diseases; chronic obstructive pulmonary disease; obstructive; pulsed electric field; respiratory tract diseases.

Figure 1.

Disposition of study patients (CONSORT [Consolidated Standards of Reporting Trials] diagram). *The original version of the protocol required an FEV₁/FVC ratio < 0.70. This requirement was removed in a later protocol amendment.

Figure 2.

Pre- and post-treatment bronchoscopic images from a study patient. Note the thick mucus before treatment, with resolution after treatment. The images show the endoscopic view of the left upper lobe carina with both upper and lower lobe airways visible.

Figure 3.

Histological findings from the right bronchus intermedius of a study patient. The goblet cells, with magenta-colored cytoplasmic mucin highlighted by periodic acid–Schiff staining, are seen in the superficial bronchial epithelium. (A) On Day 0 immediately before therapy, significant goblet cell hyperplasia can be seen (score of 2). (B) Right bronchus intermedius 120 days after the initial treatment, demonstrating complete regeneration of the pseudostratified columnar epithelium with a reduction of goblet cell numbers (semiquantitative assessment score of 1).

Figure 4.

Quality-of-life outcomes. The 3-, 6-, and 12-month time points are in relation to the second treatment procedure. Box plots indicate minimum, first-quartile, median (solid horizontal line), third-quartile, and maximum values. Diamonds indicate mean values. (A) Total CAT score. (B) Total SGRQ score. CAT = Chronic Obstructive Pulmonary Disease Assessment Test; SGRQ = St. George’s Respiratory Questionnaire.