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

Arschang Valipour, Sebastian Fernandez-Bussy, Alvin J Ing, Daniel P Steinfort, Gregory I Snell, Jonathan P Williamson, Tajalli Saghaie, Louis B Irving, Eli J Dabscheck, William S Krimsky, Jonathan Waldstreicher, Arschang Valipour, Sebastian Fernandez-Bussy, Alvin J Ing, Daniel P Steinfort, Gregory I Snell, Jonathan P Williamson, Tajalli Saghaie, Louis B Irving, Eli J Dabscheck, William S Krimsky, Jonathan Waldstreicher

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.

Figures

Figure 1.
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.
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.
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.
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.

References

    1. Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Eur Respir J. 2017;49:1700214.
    1. Verra F, Escudier E, Lebargy F, Bernaudin JF, De Crémoux H, Bignon J. Ciliary abnormalities in bronchial epithelium of smokers, ex-smokers, and nonsmokers. Am J Respir Crit Care Med. 1995;151:630–634.
    1. Saetta M, Turato G, Baraldo S, Zanin A, Braccioni F, Mapp CE, et al. Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med. 2000;161:1016–1021.
    1. Innes AL, Woodruff PG, Ferrando RE, Donnelly S, Dolganov GM, Lazarus SC, et al. Epithelial mucin stores are increased in the large airways of smokers with airflow obstruction. Chest. 2006;130:1102–1108.
    1. Vestbo J, Prescott E, Lange P Copenhagen City Heart Study Group. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Am J Respir Crit Care Med. 1996;153:1530–1535.
    1. Pelkonen M, Notkola IL, Nissinen A, Tukiainen H, Koskela H. Thirty-year cumulative incidence of chronic bronchitis and COPD in relation to 30-year pulmonary function and 40-year mortality: a follow-up in middle-aged rural men. Chest. 2006;130:1129–1137.
    1. Guerra S, Sherrill DL, Venker C, Ceccato CM, Halonen M, Martinez FD. Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk. Thorax. 2009;64:894–900.
    1. Burgel PR. Chronic cough and sputum production: a clinical COPD phenotype? Eur Respir J. 2012;40:4–6.
    1. Kim V, Davey A, Comellas AP, Han MK, Washko G, Martinez CH, et al. COPDGene Investigators. Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study. Respir Res. 2014;15:52.
    1. Kim V, Zhao H, Boriek AM, Anzueto A, Soler X, Bhatt SP, et al. COPDGene Investigators. Persistent and newly developed chronic bronchitis are associated with worse outcomes in chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016;13:1016–1025.
    1. Lahousse L, Seys LJM, Joos GF, Franco OH, Stricker BH, Brusselle GG. Epidemiology and impact of chronic bronchitis in chronic obstructive pulmonary disease. Eur Respir J. 2017;50:1602470.
    1. Kim V, Criner GJ. Chronic bronchitis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187:228–237.
    1. Çolak Y, Nordestgaard BG, Vestbo J, Lange P, Afzal S. Prognostic significance of chronic respiratory symptoms in individuals with normal spirometry. Eur Respir J. 2019;54:1900734.
    1. Lindberg A, Eriksson B, Larsson LG, Rönmark E, Sandström T, Lundbäck B. Seven-year cumulative incidence of COPD in an age-stratified general population sample. Chest. 2006;129:879–885.
    1. de Marco R, Accordini S, Cerveri I, Corsico A, Antó JM, Künzli N, et al. Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm. Am J Respir Crit Care Med. 2007;175:32–39.
    1. Kohansal R, Martinez-Camblor P, Agustí A, Buist AS, Mannino DM, Soriano JB. The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort. Am J Respir Crit Care Med. 2009;180:3–10.
    1. Baye J. Roflumilast (daliresp): a novel phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. P&T. 2012;37:149–161.
    1. Martinez FJ, Rabe KF, Sethi S, Pizzichini E, McIvor A, Anzueto A, et al. Effect of roflumilast and inhaled corticosteroid/long-acting β2-agonist on chronic obstructive pulmonary disease exacerbations (RE(2)SPOND): a randomized clinical trial. Am J Respir Crit Care Med. 2016;194:559–567.
    1. Valipour A, Ing A, Williamson J, Saghaie T, Steinfort D, Irving L, et al. Late breaking abstract - first-in-human results of bronchial rheoplasty: an endobronchial treatment for chronic bronchitis (CB) [abstract] Eur Respir J. 2018;52:OA2162.
    1. Valipour A, Ing A, Williamson JP, Saghaie T, Irving L, Steinfort D, et al. First-in-human results of bronchial rheoplasty: an endobronchial treatment for chronic bronchitis (CB) [abstract] Am J Respir Crit Care Med. 2019;199:A7037.
    1. Valipour A, Ing A, Williamson J, Saghaie T, Steinfort D, Irving L, et al. Late breaking abstract - bronchial rheoplasty for treatment of chronic bronchitis: 6 month results from a prospective multi-center study [abstract] Eur Respir J. 2019;54:RCT448.
    1. Kon SS, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, et al. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med. 2014;2:195–203.
    1. Jones PW. St. George’s respiratory questionnaire: MCID. COPD. 2005;2:75–79.
    1. Hollander M, Wolfe DA. Nonparametric statistical methods. 2nd ed. New York: John Wiley & Sons; 1999.
    1. Burgel PR, Nesme-Meyer P, Chanez P, Caillaud D, Carré P, Perez T, et al. Initiatives Bronchopneumopathie Chronique Obstructive (BPCO) Scientific Committee. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest. 2009;135:975–982.
    1. Wells JM, Arenberg DA, Barjaktarevic I, Bhatt SP, Bowler RP, Christenson SA, et al. Safety and tolerability of comprehensive research bronchoscopy in chronic obstructive pulmonary disease: results from the SPIROMICS bronchoscopy substudy. Ann Am Thorac Soc. 2019;16:439–446.
    1. Kim V, Oros M, Durra H, Kelsen S, Aksoy M, Cornwell WD, et al. Chronic bronchitis and current smoking are associated with more goblet cells in moderate to severe COPD and smokers without airflow obstruction. PLoS One. 2015;10:e0116108.
    1. Jones PW. Health status and the spiral of decline. COPD. 2009;6:59–63.
    1. Coxson HO, Leipsic J, Parraga G, Sin DD. Using pulmonary imaging to move chronic obstructive pulmonary disease beyond FEV1. Am J Respir Crit Care Med. 2014;190:135–144.
    1. Jetmalani K, Thamrin C, Farah CS, Bertolin A, Chapman DG, Berend N, et al. Peripheral airway dysfunction and relationship with symptoms in smokers with preserved spirometry. Respirology. 2018;23:512–518.
    1. D’Anci KE, Lynch MP, Leas BF, Apter AJ, Bryant-Stephens T, Kaczmarek JL, et al. ECRI Institute. Effectiveness and safety of bronchial thermoplasty in management of asthma. Rockville, MD: Agency for Healthcare Research and Quality; 2017. AHRQ Publication No. 18-EHC003-EF.
    1. Slebos DJ, Breen D, Coad J, Klooster K, Hartman J, Browning R, et al. Safety and histological effect of liquid nitrogen metered spray cryotherapy in the lung. Am J Respir Crit Care Med. 2017;196:1351–1352.
    1. Lim JU, Lee JH, Kim TH, Lee JS, Lee SD, Oh YM, et al. Alternative definitions of chronic bronchitis and their correlation with CT parameters. Int J Chron Obstruct Pulmon Dis. 2018;13:1893–1899.
    1. Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, et al. SPIROMICS Research Group. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med. 2016;374:1811–1821.
    1. Celli BR, Decramer M, Wedzicha JA, Wilson KC, Agustí A, Criner GJ, et al. ATS/ERS Task Force for COPD Research. An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur Respir J. 2015;45:879–905.
    1. Slebos DJ, Shah PL, Herth FJF, Pison C, Schumann C, Hübner RH, et al. AIRFLOW-2 Study Group. Safety and adverse events after targeted lung denervation for symptomatic moderate to severe chronic obstructive pulmonary disease (AIRFLOW): a multicenter randomized controlled clinical trial. Am J Respir Crit Care Med. 2019;200:1477–1486.
    1. Davey C, Zoumot Z, Jordan S, McNulty WH, Carr DH, Hind MD, et al. Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial. Lancet. 2015;386:1066–1073.
    1. Shah PL, Slebos DJ, Cardoso PF, Cetti E, Voelker K, Levine B, et al. EASE trial study group. Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial. Lancet. 2011;378:997–1005.
    1. Gordon IO, Husain AN, Charbeneau J, Krishnan JA, Hogarth DK. Endobronchial biopsy: a guide for asthma therapy selection in the era of bronchial thermoplasty. J Asthma. 2013;50:634–641.
    1. Mullen JB, Wright JL, Wiggs BR, Pare PD, Hogg JC. Reassessment of inflammation of airways in chronic bronchitis. Br Med J (Clin Res Ed) 1985;291:1235–1239.
    1. Nagai A, West WW, Thurlbeck WM. The National Institutes of Health Intermittent Positive-Pressure Breathing trial: pathology studies. II. Correlation between morphologic findings, clinical findings, and evidence of expiratory air-flow obstruction. Am Rev Respir Dis. 1985;132:946–953.

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