Statistics from Altmetric.com
Lung volume reduction can give substantial benefit to selected patients with emphysema. However, the high morbidity associated with surgery has fuelled the development of bronchoscopic lung volume reduction. Investment in research has primarily focused on the development of endobronchial valves. Three large randomised controlled trials with endobronchial valves have only shown marginal clinical benefit overall, although some patients had significant improvement in pulmonary function.1–3 Cohort studies have also demonstrated a survival benefit in patients who developed lobar atelectasis.4 5 Collateral ventilation appears to be the key factor that limits the effectiveness of endobronchial valves.6 Support for this theory has been enhanced by subgroup analysis of the Endobronchial Valve for Emphysema Palliation Trial (VENT) study, which has shown the greatest improvements in lung function (17.9% improvement in forced expiratory volume in 1 s [FEV1] at 12 months) in patients who had evidence of an intact fissure on the treatment side providing the endobronchial valves were correctly positioned.1 The absence of any clinical benefit in patients treated with incomplete bilateral lobar occlusion further supports the theory that complete isolation of the lobe is required for blocking devices to be effective.3
Spiracles or transthoracic passages were described by the late Peter Macklem as a method for reducing trapped gas in lungs when there is a high degree of collateral ventilation.7 This can be achieved in patients with emphysema by creating an artificial passage between the chest wall and emphysematous lungs with a valve that directs the flow of air out of the lung.8 However, this approach is not well tolerated by patients. An alternative strategy is to create artificial air passages within the lung and bronchial segments that allow trapped gas to escape. This technique (airway bypass) has the greatest benefit in patients with a high degree of collateral ventilation, but benefits reported so far have been only transient.9
The development of bronchoscopic treatments that are independent of collateral ventilation is essential and Ingenito et al first described the use of a fibrin glue in a sheep model of emphysema to induce lung volume reduction.10 This strategy has evolved for human use and Magnussen et al report on the use of a polymeric foam sealant in advanced emphysema.11 A polymeric solution (4.5 ml of 2% aminated polyvinylalcohol in phosphate buffer) is mixed with a cross linker (0.5 ml of buffered pentane 1–5 dial). The mixture is then mixed with 15 ml of air to create a foam and the solution is then instilled into the target bronchial segment during flexible bronchoscopy via catheter. The air within the foam is gradually resorbed and the adherent pulmonary tissue in the treatment area also shrinks with the foam. The authors have amalgamated the data from three separate but similar clinical trial protocols and subsequently assessed treatment response according to fissure integrity based on the CT scans. The results for this study are impressive, with improvements in FEV1 of 19%, exercise capacity by 30 m and quality of life (St George's Respiratory Questionnaire, SGRQ) by about 11 points. Furthermore, the proportion of patients who had a clinically significant improvement was 64% for FEV1 (12% improvement in FEV1), 31% for exercise capacity (6 min walk test of more than 54 m) and 71% for SGRQ (reduction by four points). However, the degree of improvement needs to be interpreted with caution as small open-label cohort studies tend to consistently demonstrate a greater degree of benefits than are ultimately observed in large-scale randomised trials. This effect may be exaggerated as the authors have only looked at a subgroup (28 patients who had derivable information on fissure status on CT scans) rather than the whole cohort of 54 patients treated.
This study has not reported on the safety aspects but a previous study of 25 patients suggests an early transient systemic inflammatory response with fevers, flu-like symptoms and chest discomfort.12 There were exacerbations of chronic obstructive pulmonary disease (COPD) in eight patients requiring hospitalisation and one needed treatment in an intensive care unit. The event rate may seem high but should be considered in the context of this population of patients who have severe disease, frequent exacerbations and limited treatment options. However, treatment with the polymeric foam sealant is irreversible. It remains in situ in the lung and induces permanent sclerosis. Longer-term effects remain unclear and it should be used with caution in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III disease.
Bronchoscopic lung volume reduction should be considered in patients with severe emphysema with evidence of hyperinflation (residual volume >180% predicted) who are symptomatic despite maximal medical therapy. Endobronchial valves which are easily removed should be considered initially in patients who have an intact fissure on CT scans or evidence of low collateral ventilation. Patients who have significant collateral ventilation may need to be considered for alternative treatments such as the polymeric foam sealant.
Competing interests PS has been involved in a number of clinical trials on bronchoscopic lung volume reduction and the host centres (Royal Brompton Hospital and the Chelsea & Westminster Hospital) have been reimbursed for clinical trial expenses. There are no competing interests with respect to the emphysematous lung sealant (AeriSeal®). DM has no competing interests.
Provenance and peer review Not commissioned; internally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.