The future beyond inhalers – endobronchial intervention in COPD

Pallav L Shah

¹Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK

²Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK

³National Heart & Lung Institute, Imperial College, DoveHouse Street, London SW3 6LY, UK

Summary

Lung volume reduction surgery (LVRS) was first reported by Otto Brantigan in 1957, but was not widely adopted until Joel Cooper perfected the technique of stapled resection in the 1990s. Several bronchoscopic therapies using differing strategies for reducing hyperinflation in emphysema have been developed. The greatest experience has been with endobronchial valves which have now been in use for almost 15 years. A wealth of clinical trial data has been produced in recent years with some key randomised clinical trials.

The clinical trials with randomised endobronchial valves have demonstrated significant improvements in pulmonary function, quality of life and exercise capacity providing patients with heterogenous disease with absence of collateral ventilation are selected. ^1-4 The responder rates are improved by valve adjustment or replacement where necessary. The results for endobronchial coils have been mixed with clinically meaningful results for pulmonary function and quality of life but at one year the benefits in walk tests have been marginal.^5-6 Vapor therapy appears to promise and has the capacity for more targeted and staged therapy.^7,8

There has traditionally been a rather nihilistic attitude toward emphysema and COPD, but recent technology developments mean this approach is no longer appropriate. The safety concerns over mortality and morbidity from LVRS has driven the development of BLVR, and whilst LVRS remains a very important, evidence-based treatment, BLVR has the potential to increase the availability of treatment to those with severe emphysema. The emergence of pivotal trial and longer-term follow-up data is likely to lead to more widespread and routine use of BLVR technologies, with the range of technologies allowing a suite of interventions that can be tailored to each individual patient.  However, long-term benefit and cost-effectiveness needs to be demonstrated, and more work is needed to determine patient characteristics that best predict response to each individual technique.  Patients with severe heterogenous emphysema, evidence of hyperinflation and intact lobar fissures. Patients without collateral ventilation may be considered for endobronchial valves. Those with collateral ventilation or homogenous distribution of emphysema may be considered for endobronchial coils.

However, exciting advances have been made in interventions for non-emphysematous COPD, although technology is still at an early stage.  Targeted lung denervation (TLD) aims to disrupt the parasympathetic nerve supply to the lung, which controls the release of acetylcholine and hence smooth muscle activity, by thermal ablation of the vagus nerve complexes around the main bronchi.  Cryotherapy works by inducing cell death through repeated rapid freeze-thaw cycles with the subsequent regeneration of normal mucosa, and probe-based cryotherapy is an established bronchoscopic intervention.  There are now a number of reports of the successful use of a catheter-based liquid nitrogen cryospray in both malignant and benign airway.