Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States.^1–3 Emphysema is one component of COPD, and it is estimated that 3.1 million adults in the United States are currently diagnosed with emphysema. Emphysema is associated with permanent enlargement and destruction of the lung alveoli. The destruction of the alveolar walls of the distal terminal bronchioles results in loss of gas exchange surface area, air-trapping, and hyperinflation of the alveoli.⁴ Emphysema often manifests with large air-containing bullae that do not contribute to gas exchange. These bullae are overventilated and underperfused, creating ventilation-perfusion (V/Q) mismatch from increased dead-space ventilation. They can physically compress neighboring normal tissue, thus worsening gas exchange. The progression of the disease ultimately results in compromised lung mechanics, hyperinflation, hypercapnia, dyspnea through airflow limitation, and hypoxia that often require oxygen therapy.

Emphysema

Emphysema changes are widespread in the general population and in the smoking population in particular. In smokers, there appears to be an augmented response to tobacco byproducts resulting in an excessively inflammatory destructive cycle. It is a progressive, debilitating disease, which in its final stages, greatly impacts the patient’s quality of life (QOL), his/her family, as well as the cost of medical care.

Other components of COPD, such as chronic bronchitis and bronchospasm usually coexist with emphysema and contribute to obstructive dysfunction and expiratory airflow obstruction.

The hyperinflation leads to flattening of the diaphragm and widening of the chest cavity and intercostals spaces, putting the mechanics of these respiratory muscles at a tension-length disadvantage. Smoking-related emphysema most commonly manifests heterogeneously distributed throughout the lung, which predominantly affects the upper lobes of the lung. Destruction of lung tissue may lead to increased compliance of the remaining lung, with change in compliance directly related to the amount and severity of emphysema present.⁵ In normal lungs, the diameter of airways during exhalation progressively decreases in conjunction with the decrease in lung volume. This leads to progressively decreasing flow rates throughout expiration, as exemplified by the characteristic downward slope of the expiratory limb of the flow-volume loop measured by spirometry. The airways are tethered open during exhalation by the integrity of the lung parenchyma. The degree to which the diameter of the airways decreases during exhalation is directly related to this tethering effect, measured as the elastic recoil of the lung. The obstruction to expiratory airflow may become severe enough to prevent complete exhalation of inspired air. Progressive “air trapping” may eventually lead to chronic hyperinflation of the lungs and increased total lung capacity (TLC). Hyperinflation in turn disrupts the mechanical advantage in the ventilatory design of the thorax, pushing the diaphragm downward toward the abdomen and pushing the ribcage outward. Hyperinflation is a significant contributor to dyspnea and decreased exercise tolerance in such patients, with a commensurate negative impact on QOL.

The increase in TLC in a patient with COPD is mostly caused by an increase in residual volume (RV) in patients with very severe emphysema and hyperinflation; the RV may be as high as 150% to 200% of its predicted value.

Thus patients with emphysema have been categorized as “pink puffers”: cachectic with increased anterior-­posterior (AP) dimensions of the chest and demonstrable increased work of breathing. They do not generally exhibit the ­abundant sputum production of chronic bronchitis or the periodic exacerbations of asthma.⁶

As depicted in Fig. 29.1 several attempts were made in the past to treat emphysema. Some of them were directed in an effort to reduce the size of the hyperinflated chest cavity to improve the lung mechanics. These techniques were not clinically effective.

There is no cure for the reduction of the gas exchange surface in emphysema, and the treatment only focuses on attempting to slow the progression of the disease by offering symptomatic therapy. These may includes steroids, bronchodilators, expectorant nebulizers, treatment of infection, and oxygen therapy or ventilatory support at the end-stage phase. When advanced, emphysema causes severe dyspnea that markedly diminishes QOL. Despite medical therapy, the course of advanced disease is slowly and relentlessly progressive. Lung transplantation is the only definitive treatment, but this has its own associated morbidity and mortality. However, donor availability and patient suitability do not make this an option for many patients with emphysema. Surgical techniques, such as lung volume reduction surgery (LVRS) and newer endoscopic lung reduction surgery (see Chapter 32), are the only effective procedures that have been developed to alleviate the dyspnea and can temporarily improve the patient QOL.

As mentioned earlier, no procedure can cure the disease except bilateral lung transplant, an option available to extremely select few patients because of assorted available organs. It became clear that these sick, debilitated patients would need innovative, alternative, nonsurgical procedures to potentially alleviate their symptoms. In recent years, a variety of noninvasive endoscopic lung volume reduction procedures were developed with the hope of improving the respiratory status of these patients. The common principle behind bronchoscopic lung volume reduction (BLVR) is the goal of reducing the extent of the hyperinflation because of emphysema via a flexible bronchoscope, which would result in a similar beneficial effect to surgical resection.^7–9

Lung Volume Reduction Surgery

LVRS was initially introduced in 1957 by Otto C. Brantigan who published a series of 16 patients who underwent surgical treatment for nonbullous emphysema.¹⁰ The procedure attempted to reduce overall lung volume as a means to restoring the outward traction on the smaller airways, thereby reducing airway resistance and air trapping. The Brantigan procedure, consisting of multiple wedge excisions, would restore the elastic “pull” on the small airways and thereby improve pulmonary mechanics. Because surgical staplers were not yet introduced, surgery was performed with a hand-sutured line of resection. Surgery resulted in a high incidence of persistent air leaks and asignificant mortality rate of 16%. Because no surgeon would associate with such a high mortality, the procedure did not gain wide acceptance.

Interest in the Brantigan proposal was renewed by Cooper et al., following their experience with lung transplantation.¹¹ Initially, concern was that the smaller donor lung would not fit inside the overexpanded thorax, which will result in continuous air leak; instead they noticed that the lung recipient’s distended chest reconfigured to the smaller volume of the donor lung. The idea behind LVRS is that by reducing the large RV, the diaphragm will reverse its flattened shape to resume its normally curved shape configuration. This will reduce the mismatching between the hyperinflated lungs and the chest cavity and improve the lung function, thereby restoring the outward circumferential pull and improving expiratory airflow. The first report by Dr. Cooper’s group was of 20 patients who underwent this revived “pneumectomy” procedure.¹² As described in this landmark report: “We undertook surgical bilateral lung volume reduction in 20 patients with severe COPD to relieve thoracic distention and improve respiratory ­mechanics. The operation, done through median sternotomy, involves excision of 20% to 30% of the volume of each lung. The most affected portions are excised with the use of a linear stapling device fitted with strips of bovine pericardium attached to both the anvil and the cartridge to buttress the staple lines and eliminate air leakage through the staple holes (see Fig. 29.2 A and B). Preoperative and postoperative assessment of results has included grading of dyspnea and QOL, exercise performance, and objective measurements of lung function by spirometry and plethysmography. There has been no early or late mortality and no requirement for immediate postoperative ventilatory assistance. Follow-up ranges from 1 to 15 months (mean 6.4 months). The mean forced expiratory volume in 1 second (FEV₁) has improved by 82% and the reduction in TLC, RV, and trapped gas has been highly significant. These changes have been associated with marked relief of dyspnea and improvement in exercise tolerance and QOL. Although the follow-up period is short, these preliminary results suggest that bilateral surgical volume reduction may be of significant value for selected patients with severe COPD.”

LVRS gained in popularity despite evidence of limited short-term beneficial effects.^13–15 These favorable results and a patient population eager to improve their QOL, led to a dramatic increase in the number of centers offering LVRS for COPD patients via thoracoscopic LVRS and laser pneumoplasty.¹⁶

In a subsequent prospective cohort study of 200 stringently selected patients undergoing LVRS from 1993 to 1998, at Washington University in St Louis, there were substantial beneficial effects far more beneficial than those achieved with optimized medical therapy. They enrolled 200 patients who underwent LVRS with a follow-up of 6 months, 3 years, and 5 years after surgery; dyspnea scores were improved in 81%, 52%, and 40% of patients, respectively. Good-to-excellent satisfaction with the outcomes was reported by 96% (6 months), 89% (3 years), and 77% (5 years) of patients. The FEV₁ was improved in 92% (6 months), 72% (3 years), and 58% (5 years) of patients. During follow-up, 15 of these patients underwent subsequent lung transplantation.¹⁷

In a later study from the same group, LVRS produced significant functional improvement for selected patients with emphysema, and the benefits appeared to last at least 5 years. The authors enrolled a total of 250 consecutive patients who underwent bilateral LVRS through median sternotomy. All patients had end-stage COPD with disabling dyspnea, thoracic hyperinflation, and a heterogeneous pattern of emphysema that is a suitable target area for resection. Preoperative pulmonary rehabilitation was required and postrehabilitation data were used as the baseline for data analysis. Follow-up ranged from 1.8 to 9.1 years (Figs. 29.3–29.5). The authors reported that prolonged air leaks of at least 7 days were the most common complication (45.2%). Reexploration rates for air leak and bleeding were 3.2% and 1.2%, respectively. Eighteen patients (7.2%) required reintubation and support by mechanical ventilation. The in-hospital mortality in this series was 4.8%. Survivals after LVRS were 93.6%, 84.4%, and 67.7% at 1, 3, and 5 years, respectively. Spirometry values, lung volumes, and gas exchange parameters improved after surgery. The FEV₁ and the RV and health-related QOL showed significant improvements between preoperative values and each time.¹⁸

It must be emphasized that LVRS is a palliative procedure. It does not remove the pathology, or restore the destructed alveoli. It is however allowing for some restoration in the elastic recoil so that smaller airways have a reduced tendency to prematurely collapse and therefore have a lower resistance to airflow to the intact alveoli and improve the gas exchange.

Another positive consequence of LVRS as depicted in the dynamic magnetic resonance imaging (Figs. 29.6–29.8) is the reduction of the hyperinflation and air which restores the diaphragm to a more curved position and the chest wall to a less expanded diameter, thereby improving the tension-length relationship and the respiratory mechanical advantage. The comparison between preoperative and ­postoperative is illustrated. In the preoperative images, the diaphragm is flat from hyperinflation, the AP diameter is large, and the patient sits using his accessory muscles to help in inspiration. In the postoperative images, the size of the chest decreased, the diaphragm has assumed its dome-shape, and shoulders of the patient are more relaxed because the accessory muscles are not engaged to help with inspiration.

Facing a nationwide increase in LVRS, the enthusiasm was tempered by the purported lack of convincing evidence of this new surgical intervention’s safety, efficacy, and appropriate patient selection. The large number of potential procedures, specifically targeting the older population, could increase cost in the Medicare patient population. In the absence of sufficient evidence of beneficial outcome, the National Institutes of Health and the Health Care Financing Administration concluded in 1995 that “although initial results were promising, LVRS was often being performed with sufficient evaluation and a randomized study should be undertaken to evaluate the procedure critically.” In an attempt to determine the potential beneficial outcome of the procedure, a nationwide “National Emphysema Treatment Trial” (NETT) was proposed.¹⁹ This was a randomized multicenter prospective clinical trial of medical versus surgical treatments of patients with severe bilateral emphysema. Initially, the NETT would enroll 4700 patients with the primary outcomes of survival and maximum exercise capacity. Secondary outcomes studied would include QOL, cost effectiveness, oxygen requirements, cardiovascular measures, and surgical approach (thoracoscopy versus median sternotomy).

In 2001 the NETT Research Group published a preliminary report (n = 1033 patients) entitled “Patients at High Risk of Death After Lung Volume–Reduction Surgery.” This report recommended not performing surgery on the highest-risk patients with emphysema. These high-risk patients were defined as having an FEV₁ under 20% predicted and either homogeneous distribution of emphysema on computed tomography (CT) scan or a carbon monoxide diffusing capacity (DLCO) under 20% predicted. When compared with the medically treated group, the surgical patients had a higher 30-day mortality rate after surgery (16% vs. 0%; 95% confidence interval [CI], 8.2–26.7%, P < .001) and overall mortality rate was higher in surgical patients than medical patients (0.43 deaths per person-year vs. 0.11 deaths per person-year; relative risk, 3.9; 95% CI, 1.9–9.0). The investigators concluded that the operation harmed some patients and did not benefit those who survived.²⁰ In an accompanying editorial, Dr. Jeffrey Drazen, the Editor-in-Chief of the New England Journal of Medicine, agreed: “At this time, it does not make sense to use lung-volume–reduction surgery in patients whose emphysema is so severe that they meet these exclusion criteria.”²¹ These preliminary results decreased dramatically the number of LVRS performed nationwide because of the lack of beneficial evidence for the procedure.

The final NETT study results were reported in 2003 and were somewhat disappointing. There were 1228, randomized patients were divided into four subgroups, depending on the extent of the emphysema and their exercise capacity²²

• • Patients with upper lobe predominant emphysema and a low exercise capacity. Surgery was significantly more likely to lead to short-term and long-term improvement of exercise capacity and health-related QOL (Fig. 29.9).
  
• • Patients with upper lobe predominant emphysema and high exercise capacity. Surgery did not impact the 90-day, short-term, or long-term mortality of this group (Fig. 29.10).
  
• • Patients with diffuse emphysema and low exercise capacity. LVRS slightly increased 90-day mortality, but did not affect mortality at 24 months (Fig. 29.11).
  
• • Patients with diffuse emphysema and high exercise capacity. LVRS increased 90-day mortality (Fig. 29.12).

Because of that initial impression that the mortality risk was higher with surgery, LVRS was met with significant skepticism by the pulmonary community. Concerns were raised relating to safety, patient selection, effectiveness, choice of surgical technique, and cost. The concern was based on the risk of performing a major thoracic surgery on patients with very poor lung function, which inherently imparts significant risk to individual patients while providing benefit to only a limited subgroup of patients with emphysema. The cost-effectiveness ratio in this subgroup was $98,000 per quality-adjusted life-year gained at 3 years and $21,000 at 10 years. The authors concluded that LVRS is costly relative to medical therapy, but that it may be cost effective if benefits can be maintained over time.^23,24 Because of these concerns, general acceptance by the medical community rapidly declined, from the peak of 1990s when more than 4000 LVRS were done annually in the United States.²⁵ Several other studies reported the potential benefit of LVRS,^26–28 including some that compared medical therapy with surgical therapy.^29–31 Rather than acceptance of LVRS by the medical community, effort was focused on improving the less invasive endoscopic techniques, broadly described as BLVR (as described in Chapter 32).