The hope is that surgical fissure completion will expand the number of patients that will be able to benefit from endobronchial LVR therapy, and give this group of patients with COPD an effective adjunct to medical therapy, which, for them, was previously not an option.

CHRONIC obstructive pulmonary disease (COPD) or emphysema affects one in 20 Australians above the age of 45 years. It is the fifth leading cause of death, with more than 7000 people dying from the disease in 2018 in Australia. COPD disproportionately affects those in lower socio-economic strata, and places a heavy burden on our health care system.

The term “emphysema” is often used interchangeably with COPD. Emphysema is defined as an abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, that is, the alveoli. It is accompanied by destruction of the alveolar walls, and leads to gas trapping, impaired expiratory airflow, and reduced gas exchange.

Patients typically experience emphysema as progressive shortness of breath, which eventually compromises their activities of daily living, and is accompanied by exacerbations that often result in hospitalisation and prolonged periods of disability. Concerningly, up to one in three Australians living with severe emphysema report some level of disability due to the disease. Moreover, those affected are four times more likely than those without emphysema to experience very high levels of psychological distress, with breathlessness, or the fear of breathlessness, commonly causing anxiety and depression.

Current treatment guidelines are aimed at symptom management and prevention of exacerbations, and include medical therapies such as bronchodilators, inhaled steroids, and antibiotics. Non-medicinal interventions include pulmonary rehabilitation, and in later stages of the disease, supplementary oxygen.

However, despite maximal medical management, many patients still experience debilitating symptoms and impaired quality of life. This led to the search for other treatment options. Enter lung volume reduction (LVR).

Lung volume reduction

The underlying pathophysiology in COPD/emphysema of a hyperinflated lung in an inefficiently expanded chest cavity led to the idea of LVR surgery (LVRS) that was first proposed in the 1950s. The idea was that by removing the ineffective and hyperinflated bullae of the lung, the remaining lung parenchyma would be better able to function in gas exchange. While perioperative techniques improved over the subsequent decades, these patients are very frail, and hence do not make for good surgical candidates, and the results from surgery were varied at best.

This prompted the American National Institutes of Health (NIH) to perform a randomised clinical trial with over 1200 patients. The results defined the subpopulations of emphysema patients that could benefit from intervention, as well as those for whom the risks were substantially higher.

This evidence for the physiological benefit of lung volume reduction set the scene for the innovation of minimally invasive lung volume reduction methods, first and foremost, the advent of endobronchial valves. These valves were first used in the early 2000s and have now become an important tool in the management of selected patients with emphysema.

Endobronchial valves

These one-way valves are placed in the segmental bronchi of patients with emphysema via a bronchoscope, thereby obviating the need for open surgery. The procedure usually takes less than an hour. Air is exhaled from the diseased, overinflated lung segment, but cannot return, which results in collapse or atelectasis of the targeted area of the lung (usually a lobe). This in turn, allows the remaining lung to function more efficiently in gas exchange. Numerous studies have established the safety and efficacy of endobronchial valves, and have served to define the subset of patients who benefit the most. Furthermore, the valves can be removed, rendering the treatment reversible in the event of complications or lack of benefit.

Endobronchial valve treatment is now included in COPD treatment guidelines, including the widely used Global Initiative for Chronic Lung Disease (GOLD Evidence A), and the Australian and New Zealand clinical practice guidelines (COPD-X).

However, endoscopic LVR cannot help everyone.

In a large proportion of the emphysema population, connections between the various areas of the lung mean that even if an incoming airway is occluded, the target area does not collapse due to collateral ventilation through incomplete fissures that separate the lobes. A recent study found that incomplete fissures occurred in more than half of patients who would otherwise be candidates for endoscopic LVR.

To address this problem, and thereby expand the benefits of endoscopic LVR, St Vincent’s Hospital Melbourne has embarked on the COVE Study.

The COVE Study

The idea is relatively straightforward. If endobronchial valves cannot collapse the lung due to collateral ventilation across incomplete fissures, then surgical completion of the fissures, followed by valve insertion, should remedy the situation. The study has been set out as a phase 1 clinical trial to assess the safety of the procedure.

Patients who would otherwise be candidates for endoscopic LVR therapy, but are ruled out due to collateral ventilation, are being recruited in the study. They will be brought to surgery and the fissures completed surgically in a minimally invasive surgical approach (video-assisted thoracic surgery). They will then be monitored for complications and brought back for placement of endobronchial valves a month later.

A valid question about the study is: why not just perform surgical LVR at the first setting rather than simple fissure completion?

  1. One disadvantage of surgical LVR is that it is irreversible, hence once the lung parenchyma has been resected, there is no turning back.
  2. There is morbidity associated with long hospitalisations, which often result from prolonged air leaks after surgical LVR. This results from resecting diseased, bullous lung tissue. The hypothesis with fissure completion is that the tissue at the fissure is less diseased, and the incidence of prolonged air leaks should be much less.
  3. Indications for surgical LVR are narrower than for endoscopic LVR. Surgical therapy works best if there is heterogenous disease with upper lobe predominance on computed tomography (CT) imaging. This limitation does not affect endobronchial valves, which work in lower lobes, as well as with more homogenously distributed emphysema.
  4. Previous fissure completion does not preclude later lung volume reduction surgery. In fact, if an excellent symptomatic result is achieved by endoscopic LVR, then later fails due to a device problem, the patient is confirmed as a good candidate for the more permanent surgical LVR.

Hence more patients should be able to be offered the therapy.

Study inclusion criteria

The patients who are included in the study will have been diagnosed with severe emphysema as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (forced expiratory volume in one second [FEV1], < 50%) with hyperinflation (total lung capacity, > 100%) and gas trapping (residual volume, > 150%). They will have limited exercise tolerance (6-minute walk between 150 and 450 metres) and must have ruled out underlying cardiac disease by a normal dobutamine stress echocardiogram. They will also have incomplete fissures measured by software on CT scans.

The pilot study will include 20 patients, and the objectives, in addition to safety, will be to assess improvements in pulmonary function tests, dyspnoea, exercise tolerance, and quality of life at 6 months.

The hope is that surgical fissure completion will greatly expand the number of patients that will be able to benefit from endobronchial LVR therapy, and give this group of patients with COPD an effective adjunct to medical therapy, which, for them, was previously not an option.

If you have patients aged 40 years or over, who have been diagnosed with severe, or very severe emphysema, refer them to the COVE Study today.

To learn more about the COVE Study, head to

Dr Naveed Alam is the COVE Study Lead Investigator and a Consultant Thoracic Surgeon at St Vincent’s Hospital, East Melbourne Heart and Lung, and Epworth HealthCare, Melbourne. He also serves as a Senior Lecturer at the University of Melbourne. Dr Alam’s research and clinical interests include minimally invasive thoracic surgery, airway surgery and thoracic oncology. Dr Alam regularly organises training for students, registrars and qualified surgeons locally, nationally and internationally. 



The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.

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2 thoughts on “Patients with COPD wanted for trial

  1. Anonymous says:

    I am interested in the trial

  2. muz says:

    every life is important
    everyone has the right to get treated for preventable diseases

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