Martin Mayse

Targeted lung denervation for moderate to severe COPD: a pilot study

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 Georges 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.

Self-stenting with a crack pipe: The ultimate in 'managed care'

Accessible online at: www.karger.com/res Fig. 1. Posterior-anterior chest radiograph showing a cylindrical object in the left mainstem bronchus. Fig. 2. Computerized tomography of the chest showing a radioopaque hollow object in the left mainstem bronchus. Fig. 3. ‘Crack pipe’ fragments after removal. A 30-year-old man presented to the emergency department with hemoptysis. He was a habitual ‘crack-cocaine’ user and had last smoked 1 week prior. He had no other complaints. He was treated with oral antibiotics for presumed bronchitis and discharged home. Two weeks later he again presented with hemoptysis. Chest radiography and computed tomography (fig. 1, 2) at that time revealed a cylindrical density in the lumen of the left mainstem bronchus resembling a stent. The patient had no recall of stenting. Bronchoscopy revealed a 1-cm diameter glass tube with jagged edges facing proximally that was removed from the left mainstem bronchus by rigid bronchoscopy (fig. 3). Following a 10-day course of oral steroids and antibiotics, repeat bronchoscopy revealed a normal left mainstem bronchus. Interestingly, the patient had no recollection of aspiration and denied having broken his crack pipe. ‘Crack-cocaine’ is the free-base of cocaine hydrochloride formed by boiling a mixture of cocaine, baking soda and water. ‘Crack-cocaine’ is heat stable allowing it to be smoked, often through a glass pipe. Smoking is desirable to the user because it provides an onset of action that is quicker than either nasal inhalation or intravenous injection. It is estimated that 6% of habitual ‘crack-cocaine’ smokers report at least occasional hemoptysis following use [1]. Hemoptysis associated with ‘crack-cocaine’ use may be the result of diffuse alveolar hemorrhage induced by vasoconstriction or direct toxicity of cocaine, cocaine induced rhabdomyolysis, pulmonary infarction, cocaine-induced thrombocytopenia [2], or foreign body as in this case. The syndrome of crack lung may include pulmonary hemorrhage in combination with chest pain, pulmonary edema, and an interstitial lung process.

Long-term safety of bilateral targeted lung denervation in patients with COPD

Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation. The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure. Patients and methods This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%–60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators. The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year. Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life. Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up. Results A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min. Primary safety end point of freedom from worsening of COPD was 100%. There were no procedural complications reported. Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD. Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy. Conclusion TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years.

Antimuscarinic Bronchodilator Response Retained after Bronchoscopic Vagal Denervation in Chronic Obstructive Pulmonary Disease Patients

Emphysema is a very common cause of morbidity and mortality in South Africa (SA). Therapeutic options in severe emphysema are limited. Endoscopic lung volume reduction (ELVR) is increasingly being used internationally for the treatment of advanced emphysema in a subset of patients with advanced disease, aiming to obtain the same functional advantages as surgical lung volume reduction while reducing risks and costs. In addition to endobronchial valves, ELVR using endobronchial coils is now available in SA. The high cost of these interventions underscores the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The Assembly on Interventional Pulmonology of the South African Thoracic Society appointed a committee comprising both local and international experts to extensively review all relevant evidence and provide advice on the use of ELVR in SA based on published evidence, expert opinion and local access to the various devices.