Targeted lung denervation for moderate to severe COPD: a pilot study
Dirk-Jan Slebos, Karin Klooster, Coenraad F N Koegelenberg, Johan Theron, Dorothy Styen, Arschang Valipour, Martin Mayse, Chris T Bolliger, Dirk-Jan Slebos, Karin Klooster, Coenraad F N Koegelenberg, Johan Theron, Dorothy Styen, Arschang Valipour, Martin Mayse, Chris T Bolliger
Abstract
Background: Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms.
Aims: To evaluate 'targeted lung denervation' (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD.
Methods: This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted). Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators. Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD. The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year. Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life.
Results: Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W). The procedures were technically feasible 93% of the time. Primary safety endpoint was achieved in 95%. Asymptomatic bronchial wall effects were observed in 3 patients at 20 W. The clinical safety profiles were similar between the two energy doses. At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (-11.1 points ±9.1 vs -0.9 points ±8.6, p=0.044).
Conclusions: Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated. Further investigation of this novel therapy is warranted.
Trial registration number: NCT01483534.
Keywords: Bronchoscopy; COPD ÀÜ Mechanisms.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Figures
References
- Canning B. Reflex regulation of airway smooth muscle tone. J Appl Physiol 2006;101:971–85. 10.1152/japplphysiol.00313.2006
- Belmonte K. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. Proc Am Thor Soc 2005;2:297–305. 10.1513/pats.200504-043SR
- Pera T, Zuidhof A, Valadas J, et al. . Tiotropium inhibits pulmonary inflammation and remodeling in a guinea pig model of COPD. Eur Respir J 2011;38:789–96. 10.1183/09031936.00146610
- Klassen KD, Morton DR. The effect of vagus section on the cough reflex, bronchial caliber, and clearance of bronchial secretions. Surgery 1951;29:483–90.
- Jammes Y, Mei N. Assessment of the pulmonary origin of bronchoconstrictor vagal tone. J Physiol 1979;291:305–16. 10.1113/jphysiol.1979.sp012814
- Abbott OA, Hopkins WA, Van Fleit WE, et al. . A new approach to pulmonary emphysema. Thorax 1953;8:116–31. 10.1136/thx.8.2.116
- Dimitrov-Szokodi D, Husveti A, Balogh G. Lung Denervation in the Therapy of Intractable Bronchial Asthma. J Thoracic Surg 1957;33:166–84.
- Gosens R, Zaagsma J, Meurs H, et al. . Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res 2006;7:73 10.1186/1465-9921-7-73
- Vincken W, van Noord JA, Greefhorst APM. Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Eur Respir J 2002;19:209–16. 10.1183/09031936.02.00238702
- Tashkin DP, Celli B, Decramer M, et al. . Bronchodilator responsiveness in patients with COPD. Eur Respir J 2008;31:742–50. 10.1183/09031936.00129607
- Tashkin DP, Celli B, Senn S, et al. . A 4-year trial of tiotropium in chonic obstructive pulmonary disease. NEJM 2008;359:1543–54. 10.1056/NEJMoa0805800
- Maltais F, Hamilton A, Marciniuk D, et al. . Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD. Chest 2005;128;1168–78. 10.1378/chest.128.3.1168
- Global Strategy for the Diagnosis, Management and Prevention of COPD. 2014. []
- Qaseem A, Wilt T, Weinberger S, et al. . Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice Guideline update from the ACP, ACCP, ATS and ERS. Ann intern Med 2011;155:179–91. 10.7326/0003-4819-155-3-201108020-00008
- Meguro M, Barley E, Spencer S, et al. . Development and Validation of an Improved, COPD-Specific Version of the St. George Respiratory Questionnaire. CHEST 2007;132:456–63.
- Van der Molen T, Willemse B, Schokker S, et al. . Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes 2003;1:13 10.1186/1477-7525-1-13
- Bestall JC, Paul EA, Garrod R, et al. . Usefulness of the Medical Research Council (MRC) dyspnea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581–6. 10.1136/thx.54.7.581
- Maltais F, Hamilton A, Marciniuk D, et al. . Improvement in Symptom-Limited Exercise Performance over 8 h With Once-Daily Tiotropium in Patients with COPD. Chest 2005;128:1168–78. 10.1378/chest.128.3.1168
- Miller M, Hankinson J, Brusasco V, et al. . Series “ATS/ERS Task Force: Standardization of Lung Function Testing”. Eur Respir J 2005;26:319–38. 10.1183/09031936.05.00034805
- Wagner J, Clausen J, Coates A, et al. . Series “ATS/ERS Task Force: Standardization of Lung Function Testing”. Eur Respir J 2005;26:511–22. 10.1183/09031936.05.00035005
- Weisman IM, Beck KC, Casaburi R, et al. . ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211–77. 10.1164/ajrccm.167.10.952
- ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111–7. 10.1164/ajrccm.166.1.at1102
- Breekveldt-Postma NS, Koerselmana J, Erkensa JA, et al. . Enhanced persistence with tiotropium compared with other respiratory drugs in COPD. Respir Med 2007;101:1398–405. 10.1016/j.rmed.2007.01.025
- Maesen FPV, Smeets JJ, Sledsens TJH, et al. . Iprotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD). Eur Respir J 1995;8:1506–13.
- Anderson P. Use of Respimat Soft Mist Inhaler in COPD patients. Int J Chron Obstruct Pulmon Dis 2006;1:251–9. 10.2147/copd.2006.1.3.251
- Profita M, Albano GD, Riccobono L, et al. . Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients. Immunobiology 2014;219:392–401. 10.1016/j.imbio.2014.01.004
Source: PubMed