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LVRS works, but can we make it safer?
There are now five controlled trials showing that lung reduction for emphysema can alter lung function, increase walking distance, and improve quality of life.1–5 There are problems with each study in terms of design, duration, and small sample size but, taken together, they give a strong message that lung volume reduction surgery (LVRS) has a role in the management of chronic obstructive pulmonary disease (COPD). However, we need much more evidence before we can define exactly what this role is and when to recommend surgery. In particular, we need better ways of predicting benefit and risk. We also need to understand how LVRS works in order to develop better and safer ways of doing it. The large National Emphysema Treatment Trial (NETT) study6 which began 2 years ago and is expected to take 4 years to complete will provide some of the answers, and early results are helping to define a high risk group. In an unusual move the New England Journal of Medicine allowed the president of the American Thoracic Society to e-mail all members warning them in advance of the publication of a report from NETT. Patients in the trial who had a low forced expiratory volume in 1 second (<20% predicted) and either homogenous emphysema or a very low transfer factor (<20% predicted) were at high risk of death and were unlikely to benefit from surgery.7 Based on these results, patients with severe emphysema will no longer be randomised to LVRS.
This means that the most needy group of patients can no longer hope to gain from this operation. Furthermore, emphysema is more often diffuse and homogeneous than limited and patchy, so only a minority are suitable for the operation. What, then, are the prospects for the large number with severe diffuse disease? Fortunately, at the same time as discouraging news came from the NETT trial, early evidence of success using a bronchoscopic approach was published.8 Ingenito et al developed a sheep model of emphysema by exposing them to inhaled papain and then compared surgical volume reduction with a bronchoscopic technique in which a fibrin based glue was used to collapse, seal, and scar target regions of abnormal lung. The residual volume and total lung capacity were increased by the papain induced emphysema and then reduced towards baseline by both volume reduction techniques. This volume reduction was sustained at 2–3 months and the magnitude of the changes was similar for both the surgical and the bronchoscopic techniques. The bronchoscopic approach produced fewer complications overall than surgery, although some target zones developed sterile abscesses distal to the glue.
“Vast sums of money are being spent on developing new drug treatments for COPD . . . only a fraction may do more good just by altering lung mechanics”
Several methods have been proposed to induce bronchial obstruction and distal collapse as a means of achieving volume reduction in emphysema, and two worldwide patents (WO01/02042 and WO01/13839) were published in January this year. These proposed techniques include obstructed stents, biopolymers, and tissue glue, all of which might be inserted at fibreoptic or combined fibreoptic and rigid bronchoscopy. Joel Cooper, who pioneered volume reduction surgery9 and remains a leader in the field, has suggested an alternative approach. This takes forward an older idea of bypassing the flow limiting segment of the emphysematous airway by making holes to connect the peripheral lung units to the major cartilaginous airways. These “spiracles” could allow deflation of emphysematous lung units and so achieve volume reduction. All these methods seek to exploit the pathophysiology of emphysema and its correction by volume reduction. Naturally, better understanding of the mechanisms of benefit following LVRS would inform these ideas.
No trials of bronchoscopic volume reduction have yet been done in humans and many questions remain. In particular, it is not known whether, in the context of advanced human emphysema, lobar or segmental occlusion would result in partial lung collapse and what would be its time course. It is possible that collateral air drift would keep the emphysematous lung aerated. Similarly, there are theoretical risks of infection, sterile necrosis, air leaks, and distortion of other lung units or vessels. Conversely, there may be major benefits of this approach to add to the likely improvement in safety. For example, it might be possible to assess the effects of temporary occlusion of the bronchus in patients with diffuse disease to determine who will get a worthwhile clinical benefit from volume reduction before doing a definitive procedure. Also, it may be possible to design techniques of bronchial occlusion that would allow the infusion of drugs distally to encourage scarring or to treat any infection.
This is an exciting area of research with real prospects of early benefit for the large number of patients whose lives are restricted by breathlessness. Vast sums of money are being spent on developing new drug treatments for COPD, a condition in which most patients present for medical treatment when the lung is largely destroyed. Only a fraction of these funds may do more good just by altering lung mechanics.
LVRS works, but can we make it safer?
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