The hope is that completion of the surgical fissure will increase the number of patients who can benefit from endobronchial LVR therapy and give this group of COPD patients an effective adjunct to medical treatment, which for them is not was previously not an option.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) or emphysema affects one in 20 Australians over the age of 45 years. It is the fifth leading cause of death, with more than 7,000 people died from the disease in 2018 in Australia. COPD disproportionately affects people from lower socioeconomic 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, i.e. the alveoli. It is accompanied by destruction of the alveolar walls and leads to the trapping of gases, an alteration in the flow of expiratory air and a reduction in 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 hospitalization and prolonged periods of disability. Re, up to one in three Australians living with severe emphysema report some level of disability due to the disease. Additionally, those affected are four times more likely than those without emphysema to experience very high levels of psychological distress, with shortness of breath or fear of shortness of breath, often 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-drug interventions include pulmonary rehabilitation and, in advanced stages of the disease, supplemental oxygen.
However, despite maximum medical care, many patients still experience debilitating symptoms and an impaired quality of life. This led to the search for other treatment options. Enter the lung volume reduction (LVR).
Lung volume reduction
The underlying pathophysiology of COPD/emphysema of a hyperinflated lung in an ineffectively enlarged chest cavity led to the idea of LVR surgery (LVRS) which was first offered in the 1950s. The idea was that by removing the inefficient and hyperinflated bubbles from the lung, the remaining lung parenchyma would be better able to function in gas exchange. Although perioperative techniques improved over the following decades, these patients are very fragile and therefore not good surgical candidates, and the results of surgery were varied at best.
This prompted the US National Institutes of Health (NIH) to carry out a randomized clinical trial with more than 1200 patients. The results defined the subpopulations of patients with emphysema who might benefit from intervention, as well as those for whom the risks were significantly higher.
This evidence of the physiological benefit of lung volume reduction paved the way 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 some emphysema patients.
Endobronchial valves
These one-way valves are placed in the segmental bronchi of patients with emphysema via a bronchoscope, thereby avoiding the need for open surgery. The procedure usually takes less than an hour. Air is exhaled from the diseased and overinflated lung segment, but cannot return, resulting 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 effectiveness of endobronchial valves, and were used to define the subset of patients who benefit most. Additionally, the valves can be removed, making the reversible treatment in case of complications or lack of benefit.
Endobronchial valve therapy 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 much of the emphysema population, connections between different areas of the lung mean that even if an incoming airway is obstructed, 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 issue and thus extend the benefits of endoscopic LVR, St Vincent’s Hospital in Melbourne embarked on the COVE study.
The COVE study
The idea is relatively simple. If the endobronchial valves cannot collapse the lung due to collateral ventilation through incomplete fissures, surgical repair of the fissures, followed by valve insertion, should remedy the situation. The study was presented as a phase 1 clinical trial to assess the safety of the procedure.
Patients who would otherwise be candidates for endoscopic therapy of LVR, but who are excluded due to collateral ventilation, are recruited into the study. They will be brought in for surgery and the fissures surgically completed in a minimally invasive surgical approach (video-assisted thoracic surgery). They will then be monitored for complications and brought back for endobronchial valve placement a month later.
A valid question about the study is: why not just perform surgical LVR at first setting rather than just complete the fissure?
- A disadvantage of surgical LVR is that it is irreversible, so once the lung parenchyma has been resected there is no turning back.
- There are morbidity associated with long hospital stays, which often result from prolonged air leaks after LVR surgery. This results from the resection of diseased bullous lung tissue. The assumption with the completion of the crack is that the tissue at the crack is less diseased and the incidence of prolonged air leaks should be much less.
- The indications for surgical LVR are more limited than those for endoscopic LVR. Surgical therapy works best if there is heterogeneous disease with upper lobe predominance on CT scan (CT) imaging. This limit does not affect endobronchial valvesthat work in the lower lobes, as well as with more homogeneous emphysema.
- Prior completion of the fissure does not preclude subsequent lung volume reduction surgery. In fact, if an excellent symptomatic outcome is obtained by endoscopic LVR and then later fails due to a device problem, the patient is confirmed as a good candidate for the more permanent surgical LVR.
Therefore, more patients should be able to be offered the therapy.
Study inclusion criteria
Patients 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], 100%) and gas entrapment (residual volume, > 150%). They will have limited exercise tolerance (6 minutes walk between 150 and 450 meters) and should have ruled out underlying heart disease by normal dobutamine stress echocardiography. They will also have incomplete cracks 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 the completion of the surgical fissure will greatly increase the number of patients who can benefit from endobronchial treatment of LVR and give this group of COPD patients an effective adjunct to medical treatment, which for them, was previously not an option. .
If you have patients age 40 or older who have been diagnosed with severe or very severe emphysema, refer them to the COVE Study today.
To learn more about the COVE study, visit www.covestudy.com.au
Dr Naveed Alam is Principal Investigator of the COVE Study and Consultant Thoracic Surgeon at St Vincent’s Hospital, East Melbourne Heart and Lung, and Epworth HealthCare, Melbourne. He is also 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 conducts training for students, registrars and qualified surgeons locally, nationally and internationally.
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