Patients with severe chronic obstructive pulmonary disease who fail maximal medical therapy and bronchoscopic interventions have surgical options to improve lung function, quality of life, and exercise performance. Carefully selected patients with upper lobe predominant emphysema can consider lung volume reduction surgery. Patients with upper lobe-predominant emphysema and low exercise performance have a survival advantage. Patients with large bulla compressing adjacent lung tissue occupying more than one-third of the lung benefit from bullectomy. Patients with advanced chronic obstructive pulmonary disease ineligible for or failing other surgical or bronchoscopic interventions can consider lung transplantation if free from major comorbidities.
Key points
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Lung volume reduction surgery improves lung function and quality of life in patients with severe hyperinflation and upper lobe predominant emphysema.
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Bullectomy should be considered when the bulla occupies at least one-third of the hemithorax, compresses adjacent lung tissue, and a forced expiratory volume in 1 second of 50% predicted or less.
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Lung transplantation is reserved for patients with severe chronic obstructive pulmonary disease.
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Criteria include a BODE Score of greater than 7, forced expiratory volume in 1 second and/or carbon monoxide diffusing capacity of 20% predicted or less, Pa co 2 greater than 50 mm Hg, or presence of cor pulmonale.
Introduction
Medical therapy for chronic obstructive pulmonary disease (COPD) has improved with many options now available that improve dyspnea, reduce exacerbations, improve exercise performance, and enhance quality of life. Despite these therapeutic interventions, COPD remains a leading cause of death in the world and even with maximal medical therapy patients often have disabling dyspnea and a poor quality of life. For those having disabling symptoms despite maximal medical therapy, surgical options are available to help alleviate those symptoms. Because of the morbidity associated with these procedures, careful patient selection is essential to increase the likelihood of a successful outcome. This review focuses on surgical interventions (lung volume reduction surgery [LVRS], bullectomy, and lung transplantation) available to patients with advanced COPD refractory to maximal medical therapy.
Rationale for lung volume reduction
Lung hyperinflation has been recognized as a major contributor to poor respiratory function and has been associated with increased mortality as well. , In addition to poor respiratory function, hyperinflation increases the sensation of dyspnea and causes a reduction in exercise capacity owing to distortions of the chest wall and pulmonary muscle mechanics. Furthermore, hyperinflation is associated with decreased cardiac function. Thus, hyperinflation has been an ever important target of therapy in patients with COPD.
History of lung volume reduction surgery
LVRS was initially described in the 1950s. He described the surgery as “an operation directed at restoration of a physiologic principle … not concerned with the removal of pathologic tissue.” Despite sound physiology and some promising outcomes, the surgery was never widely used or studied until the 1990s. A case series of 20 patients with severe emphysema and hyperinflation was published showing that surgical resection of 20% to 30% of each lung resulted in improvements in lung volume, spirometry, walk distance, and quality-of-life measures. A case series of 150 patients followed, showing similar results with a 90-day surgical mortality of only 4%. These studies preceded the first randomized controlled trials in LVRS, which were published in 1999 and 2000. These trials confirmed that LVRS succeeded at improving lung function, walk distance, and quality of life in select patients, but were underpowered to show a difference in mortality. ,
The National Emphysema Treatment Trial
The earlier studies, while confirming the potential benefits of LVRS left questions regarding patient selection and mortality, paving the way for The National Emphysema Treatment Trial (NETT). , The NETT was a randomized trial that enrolled more than 1200 subjects from 17 centers into 2 groups; maximal medical therapy versus LVRS plus maximal medical therapy. Patients in both arms were medically optimized and participated in a pulmonary rehabilitation program before baseline testing and randomization. , The patient population was meticulously characterized with lung function testing, cardiopulmonary exercise testing and lung perfusion chest imaging. Computed tomography scans were reviewed and classified by distribution of emphysema as upper lobe predominant emphysema or non-upper lobe predominant emphysema. The primary outcomes included maximal exercise capacity and mortality. Secondary outcomes included quality of life measures, 6-minute walk distance, and lung function parameters. ,
The study population consisted of subjects with severe COPD (mean forced expiratory volume in 1 second [FEV 1 ] of 27% predicted) with gas trapping (mean residual volume of >220% predicted) and hyperinflation (mean total lung capacity of >125% predicted). Nearly two-thirds of patients were classified as having predominantly upper lobe emphysema. Key exclusion criteria included an FEV 1 of greater than 45% predicted, total lung capacity of less than 100% predicted, residual volume of less than 150% predicted, lung nodule requiring follow-up, previous sternotomy, or large lung bulla. The results of NETT proved the importance of comprehensive patient characterization and proper patient selection, because the different subgroups had vastly different outcomes. Patients with upper lobe predominant emphysema and low exercise capacity, defined as less than 40 W in men and less than 25 W in women, had improved exercise capacity and a significant mortality benefit with surgical intervention. Patients with upper lobe emphysema but high exercise capacity had an improvement only in their exercise capacity and symptom score, but no mortality benefit. A long-term analysis with a median follow-up of 4.3 years confirmed the mortality benefit in the upper lobe emphysema and low exercise tolerance group ( Fig. 1 ) along with long-term improvements in exercise capacity and health-related quality of life in the group with upper lobe emphysema and high exercise capacity. Conversely, patients with both an FEV 1 and carbon monoxide diffusing capacity of less than 20% predicted or FEV 1 and homogeneous emphysema had increased mortality (16% vs 0%) when compared with medical management. , Patients with homogeneous or non-upper lobe predominant emphysema achieved no durable benefit with LVRS ( Table 1 ). Based on the mortality benefit in NETT, patients with upper lobe emphysema and low exercise capacity should be considered for LVRS. Additionally, patients with upper lobe emphysema with high exercise tolerance can be considered for LVRS based on improved symptoms and exercise capacity. Follow-up studies have also shown that a subset of these patients with low perfusion to the upper lobe have a mortality benefit with LVRS. Another benefit of LVRS is a decrease in rate of acute exacerbation of COPD. An analysis of the NETT data showed a 30% decrease in the exacerbation rate for LVRS patients when compared with the control arm. The improvement in the exacerbation rate was most pronounced in patients with at least a 200 mL improvement in FEV 1 at 6 months after surgery. A follow-up analysis confirmed that LVRS significantly improves exercise capacity and health-related quality of life up to 3 and 5 years out from surgery, respectively.
| Mortality | Exercise Capacity | Symptoms | |
|---|---|---|---|
| Upper lobe predominant emphysema, low exercise | Improved | Improved | Improved |
| Upper lobe predominant emphysema, high exercise | No change | Improved | Improved |
| Non-upper lobe predominant emphysema, low exercise | No change | No change | No change |
| Non-upper lobe predominant emphysema, high exercise | Worsened | No change | No change |
Further analysis showed that LVRS improved cardiovascular function and pulmonary mechanics. Jörgensen and colleagues evaluated left ventricular filling pressures and hemodynamics using a pulmonary artery catheter and echocardiography to show that patients undergoing LVRS for relief of hyperinflation had significant improvements in end-diastolic filling, left ventricular function, and cardiac index. Lammi and colleagues showed that noninvasive surrogates for stroke volume such as pulse pressure and O 2 pulse were increased at 6 months postoperatively in patients who had undergone LVRS. LVRS also improves respiratory muscle function and dynamic hyperinflation. Before NETT, 1 study showed an improvement in end-expiratory lung volume during exercise in patients who had undergone LVRS at least 3 months prior. Criner and colleagues found that LVRS resulted in deeper, slower breathing with decreased dead space and improved ventilation during exercise. A further analysis of the NETT population shows that patients who have undergone LVRS use less supplemental oxygen. Resting Pa o 2 was found to be significantly higher in the LVRS cohort 2 years after surgery when compared with medical management alone.
Lung volume reduction surgery: current state
Despite clear benefits in carefully selected patients, LVRS has not been used as a mainstay of therapy in the population with emphysema. In fact, LVRS was only performed about 3300 times in the United States from 2000 to 2010 with numbers decreasing in the latter part of the decade. Although still relatively few, in 2013 numbers had increased with 605 surgeries performed, nearly doubling the total from 2007. The relatively low number of lung volume reduction surgeries is certainly due in part to the emergence of less invasive and bronchoscopic techniques of achieving lung volume reduction, along with the perceived risk of perioperative morbidity and mortality. There has also been concern that LVRS may preclude patients from undergoing lung transplantation. An analysis of patients undergoing lung transplantation after LVRS showed no significant difference in 5-year mortality as compared with patients who did not have prior LVRS. There was potential for increased postoperative bleeding and renal injury. Prior LVRS must be taken into consideration preoperatively, but it should not be a contraindication to lung transplantation. With the caveat that LVRS has proven more costly than medical management and should only be performed in experienced centers, the GOLD guidelines maintain that LVRS is a potential option for patients with upper lobe emphysema and low exercise tolerance.
Bullectomy
A bulla is defined as an airspace in the lung with a diameter of greater than 1 cm. Most bullae are clinically insignificant and not amenable to surgery. A giant bulla is an air space in the lung that occupies about 30% or more of the hemithorax. Giant bullae are rare and typically associated with cigarette smoking. Additionally, marijuana smoking, intravenous drug use, and human immunodeficiency virus infection have all been linked to the development of giant bullae.
The clinical effect of bullous lung disease can vary widely. Some patients have relatively normal lung function and mild dyspnea, whereas others are severely limited in their daily life. The clinical effect largely depends on the degree of hyperinflation and the extent of compression of normal lung tissue adjacent to the bulla. Surgical resection is reserved for those patients with considerable impairment and the best chance of improved lung function postoperatively. The majority of published outcomes data comes from case series. Snider published a review of 22 articles ranging from 1950 to 1996 analyzing more than 450 bullectomy cases performed mainly for persistent dyspnea. The review found that bullectomy was most successful in patients with an FEV 1 of less than 50% predicted, compressed adjacent lung tissue, and bullae covering more than one-third of the hemithorax. These criteria have since become the foundation for patient selection in bullectomy cases. Fig. 2 is a chest radiograph and computed tomography scan of a patient meeting these criteria preoperatively and postoperatively.
