Articles
Endobronchial coils for the treatment of severe emphysema with hyperinflation (RESET): a randomised controlled trial

https://doi.org/10.1016/S2213-2600(13)70047-XGet rights and content

Summary

Background

Few treatment options exist for patients with severe emphysema. We assessed the clinical benefits and safety of lung volume reduction coils (LVRCs) for the treatment of patients with severe emphysema with hyperinflation.

Methods

In a randomised study, we recruited patients with severe emphysema (aged ≥35 years) from three centres in the UK. Using a computer-generated randomisation sequence, we randomly allocated patients in a one-to-one ratio (block sizes of four and stratified by centre) to either LVRC treatment (treatment group) or best medical care (usual care group). The primary endpoint was the difference in response in the St George's Respiratory Questionnaire (SGRQ) between treatment and usual care groups at 90 days after final treatment (by intention-to-treat analysis). The trial is registered with ClinicalTrials.gov, number NCT01334307.

Findings

Between Jan 27, 2010, to Oct 25, 2011, we recruited and randomly allocated 47 patients: 23 to treatment and 24 to usual care (23 patients in each group were included in the intention-to-treat analysis). SGRQ response at 90 days after final treatment was greater in the treatment group than it was in the usual care group (between-group difference in change from baseline −8·36 points [95% CI −16·24 to −0·47]; p=0·04). We detected no between-group difference in serious adverse events.

Interpretation

Our findings suggest that treatment with endobronchial coils can improve quality of life for patients with severe emphysema and hyperinflation.

Funding

PneumRx.

Introduction

Severe emphysema is a challenging respiratory disease with few treatment options. In 2010, 4·3 million adults in the USA were diagnosed with emphysema.1 Corresponding statistics for Europe are difficult to estimate because patients are often classified as having chronic obstructive pulmonary disease (COPD). However, the prevalence of emphysema is about 3·2% with an overall pooled prevalence for COPD of 7·6%.2 Globally, COPD is the third most common cause of death.3

Emphysema is one of the key pathological features of COPD. It is characterised by alveolar destruction, which, combined with a loss of surrounding connective tissue, reduces the degree of tethering of small airways and the elastic recoil of the lung. The resultant expiratory airway collapse leads to gas trapping and increased lung volumes which increases the effort needed to breathe, causing breathlessness. Physical exertion exacerbates the problem because increased respiratory rate further diminishes expiratory time, leading to dynamic hyperinflation. Because of the restricted success of pharmacological treatment in these patients and the early morbidity and mortality associated with lung volume reduction surgery,4 alternative bronchoscopic techniques for volume reduction have been developed.5, 6, 7

Endobronchial valve placement has shown benefit, especially in upper lobe-predominant emphysema,6, 8, 9 but it is only effective in the absence of collateral ventilation, which restricts its application for a broader population of patients with emphysema. Few treatment options exist for homogeneous or lower lobe-predominant distribution of emphysema. Airway bypass has been shown to release trapped gas and improve lung function, but the beneficial effects are short-lived.7 Endobronchial lung volume reduction coils (LVRC; PneumRx Inc, Mountain View, CA, USA), which, when deployed, re-tension lung tissue and reduce dynamic airway collapse, have shown evidence of efficacy and a good safety profile in two small cohorts of patients with emphysema.10, 11 The objective of this randomised, prospective, multicentre study was to assess the clinical benefits and safety of LVRCs for the treatment of severe emphysema with hyperinflation.

Section snippets

Study design and participants

This study was a prospective, randomised, multicentre trial. Patients with severe emphysema (FEV1 <45% predicted) who were on optimum medical treatment were eligible for inclusion (panel 1). Eligible patients were screened and recruited at three sites in the UK from Jan 27, 2010, to Oct 25, 2011.

The final protocol was approved by the National and Local Ethical Committees. However, due to an administrative error the trial was not registered until after enrolment of 20 patients and before any

Results

We randomly allocated 47 patients to either treatment (23 patients) or usual care (24 patients (figure 1); 23 patients in each group were included in the intention-to-treat analysis. Baseline characteristics were much the same between the two groups, apart from SGRQ total score and mMRC dyspnoea scale, which were both higher in the treatment group, with all participants having severe airflow obstruction and substantial hyperinflation (table 1). The imbalance in SGRQ and total score mMRC

Discussion

In this study, LVRC placement improved quality of life, exercise capacity, and pulmonary function in patients with severe emphysema who were already on best possible medical treatment. The primary efficacy endpoint, SGRQ, improved by more than the 4-point reduction considered to be clinically meaningful,14 and also exceeded the 8-point response defined as clinically significant in the NETT trial (panel 2).4

However, these results should be interpreted with caution because this was not a blinded

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