Introduction to Chronic Obstructive Lung Disease
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable group of lung diseases that make it difficult for a person to empty air out of the lungs. This difficulty in emptying air out of the lungs (airflow obstruction) can lead to breathlessness (dyspnea) and feeling tired (fatigue) because a person is working harder to breathe (1). COPD is a chronically progressive disorder that ultimately leads to disability (morbidity) and early death (mortality). Morbidity and mortality from COPD is an increasing global health problem. COPD currently ranks sixth among the causes of death globally in 1990, but is expected to be the third most common cause of death by the year 2020 (2). In addition, the health care costs and economic burden of COPD are predicted to be considerable (3).
Global Initiative for Obstructive Lung Disease (GOLD)
The term COPD is used to describe the condition of a person with chronic bronchitis, emphysema, or a combination of both (1). Two people may have COPD, but one may have more predominant symptoms of chronic bronchitis while another person may have more predominant symptoms of emphysema. Thus, COPD is a mixture of assorted, or rather a heterogeneous collection of, clinical conditions characterized by a persistent (chronic) expiratory (breathing out or exhalation) airflow limitation. The clinical features of COPD result not only from the airflow limitation but also other features, both within the lung and throughout the body.
As a result of the heterogeneous nature of COPD in the patient population, a definition for COPD has not been universally satisfying or all encompassing. Thus, the Global Initiative for Obstructive Lung Disease (GOLD) defines COPD as a disease state characterized by airflow limitation (obstruction) that is not fully reversible (4). The airflow limitation is usually progressive (increased or worsened airflow obstuction) and associated with an abnormal inflammatory response of the lung to noxious particles and gases (4). Thus, the GOLD definition refers to neither chronic bronchitis nor emphysema, but it contrasts these conditions with asthma, which by definition is associated with a reversible airflow limitation (5). The descriptions, causes, and treatment options of the chronic bronchitis and emphysema clinical syndromes will be briefly described, and a focus on surgical therapy for COPD will be presented.
COPD Clinical Syndromes
Chronic Bronchitis
Chronic bronchitis is a condition of increased swelling and mucus (phlegm or sputum) production in the breathing tubes (airways) of the lungs. Airway obstruction occurs in chronic bronchitis because the excessive swelling and extra mucus production causes the internal diameter (inside of the breathing tubes) to be smaller than normal. The diagnosis of chronic bronchitis is a clinical diagnosis based on symptoms of a cough that produces mucus or sputum on most days for 3 consecutive months for 2 or more years, in a patient whom other causes of chronic cough have been excluded (1, 5, 6). The constant swelling and excessive mucus production result in the inside of the breathing tubes (smaller airways – bronchioles and the larger airways – bronchi) being narrower, which prevents the normal amount of air from entering and exiting the lungs. The amount of airway narrowing that results in expiratory (breathing out) airflow obstruction can be measured with a breathing test called spirometry.
Emphysema
Emphysema is a condition that involves damage to the walls of the air sacs, called the alveoli, at the periphery of the lung. Normal lungs are composed of more than 300 million alveoli. The alveoli are like little individual balloons, which are normally stretchy and springy. The alveoli also function like balloons, in that it takes physical effort to blow them up; however, it takes no effort to empty the alveoli because of their spring-like elastic recoil. The elastic recoil of the alveoli allows the alveoli to return to their original size (1).
In emphysema, the walls of the alveoli have been damaged. When this happens, the alveoli lose their stretchiness and elastic recoil and trap air. Since it is difficult to push all the air out of the lungs, the lungs do not completely empty during the breathing cycle and therefore trap more air. This air trapping causes hyperinflation (overfilling) in the lungs. Constantly having extra air in the lungs combined with the extra effort required to breathe results in a person feeling short of breath. Airway obstruction and airflow limitation occur in emphysema because the alveoli that normally splint the airways open cannot do so during breathing out (exhalation). Without the supporting walls of the alveoli, the breathing tubes (smaller – bronchioles and larger – bronchi) collapse, causing obstruction to the normal outflow of air (1).
The diagnosis of emphysema is a pathologic diagnosis, and according to the American Thoracic Society (ATS), emphysema is a condition of the lungs characterized by abnormal, permanent enlargement of airspaces distal to (situated farther from) the terminal bronchiole (small airways leading to alveoli), accompanied by destruction of their walls in the absence of obvious fibrosis or scarring (7). The amount of airway narrowing that results in airflow obstruction and the amount of air trapping (hyperinflation) can be measured with multiple breathing tests called pulmonary function tests (PFTs).
Causes of COPD
COPD can be caused by many factors, although the most common is tobacco smoke. The inhalation (breathing in) of irritating tobacco smoke, toxic gases, and air pollutants can cause inflammation of the bronchial tubes. This inflammation induces the mucous glands that line the bronchial tubes to produce an abnormal amount of mucus, and causes the inflamed walls of the bronchi to thicken and swell. The increased mucus production induces coughing, frequently resulting in increased phlegm or sputum production (1). The combination of harmful effects of tobacco smoke, gaseous oxidants, chronic inflammation, and lung cell death result in lung tissue destruction (8).
Environmental and genetic factors may also contribute to cause COPD. For example, an occupational (work) exposure to certain dusts, chemicals, as well as indoor or outdoor air pollution can contribute to COPD (1). The reason why some tobacco smokers never develop COPD is not fully understood, and suggests that hereditary (genetic) factors probably play a major role in the development of COPD (1). People with an inherited (genetic) condition known as alpha-1 antitrypsin (AAT) deficiency do not have enough of the AAT protein in their blood to deactivate harmful tissue-destroying enzymes and are more prone to develop emphysema (9). Tobacco smoking is well known to accelerate the development of emphysema in a person with AAT deficiency (9).
Physical Symptoms of COPD
COPD can cause an increased shortness of breath (dyspnea) due to the obstruction in the bronchial tubes, which makes it difficult to inhale and completely exhale. This increased work of breathing can lead to fatigue. COPD can cause increased sputum production that induces coughing that does not go away. Airway narrowing and airflow obstruction in COPD may produce an expiratory wheeze during a forced exhalation, and this wheezing may be increased during a COPD exacerbation precipitated by a bacterial or viral respiratory tract infection. These physical signs and symptoms, in addition to a history of tobacco smoking or significant exposure to air pollutants will usually suggest a diagnosis of COPD. Further testing, such as pulmonary function tests (PFTs) and chest imaging, can help determine if a patient has COPD.
Lung Function Tests and Chest Image Evaluation for COPD
Several lung physiology tests and lung imaging methods can be performed to determine if a person has COPD. Each test serves a different purpose: to measure how much air you move in and out of your lungs, how successful your lungs are at transferring oxygen into your bloodstream, and if there are any radiographic structural changes in your lungs consistent with a diagnosis of COPD. Each test will be discussed briefly, but for further information the reader is referred to the American Thoracic Society Patient Education Series (10) and web site links at the end of this Knol.
Pulmonary Functions Tests
Pulmonary function tests (PFTs) are breathing tests to determine how well you move air in and out of your lungs, how much air is in your lungs, and how well oxygen enters your body. The most common PFTs are spirometry, body plethysmography, and diffusion studies.
Spirometry is the most commonly ordered test to determine if a patient has COPD. The test is performed by having a patient breathe into a tube connected to a machine, which measures the amount of air moved in and out of the lungs (airflow). Lung spirometry, measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the ratio of FEV1/FVC, will determine if a patient has any airflow limitation or obstruction.
Body plethysmography is a test to measure not only the amount of air a patient breathes in and out of their lungs, but also the amount of air that is remaining in the lungs after a complete exhalation. This is provides a measure of air trapping and hyperinflation. With COPD, the amount of air remaining (air trapping) in patients’ lungs will be larger than normal and will provide the healthcare provider information about the severity of COPD.
Diffusion tests determine how well your lungs take in air and exchange the oxygen in the air into the bloodstream. Therefore, this test measures how well gases in the air enter the lungs, move into the alveoli and then into the bloodstream surrounding the alveoli. This lung function of diffusion is commonly referred to as gas exchange. Diffusion and gas exchange measure the oxygen and carbon dioxide exchange at the alveolar-capillary membrane bed (called DLCO), which is destroyed in COPD. This information also will provide the healthcare provider information about the severity of COPD.
Pulse Oximetry and Arterial Blood Gases
Pulse oximetry testing is a non-invasive way of indirectly measuring blood oxygen levels, and is performed by placing a probe on your skin (finger or ear). An oximeter test is performed to determine the oxygen saturation, called SpO2, in your body and red blood cells. Unfortunately, pulse oximetry machines can be unreliable and inaccurate due to skin or nail color, low red blood cell count (anemia), or poor circulation. Therefore, when a healthcare provider needs a more accurate determination about how much oxygen is in your blood, an arterial blood gas (ABG) is the preferred test. Arterial blood gas (ABG) is the most precise and direct way to determine how well your lungs are transporting oxygen to the bloodstream and transferring carbon dioxide from the body. However, an ABG is an invasive test that requires arterial blood to be obtained from an artery, and involves a needle stick usually in the radial artery of the wrist (11).
Chest Radiographs and Chest Computed Tomography Scans
Chest x-rays (CXRs) are a standard test for evaluating COPD. A CXR allows the healthcare provider the ability to evaluate not only the lung fields, but also the heart and major blood vessels in the chest (11). CXRs are also useful to evaluate for other conditions, such as pneumonia, pleural effusions, lung nodules, or masses. CXRs are a good initial screening tool; however, they may also appear normal in patients with milder forms of lung disease and are thus not very sensitive (capable of determining the diagnosis) (11). Chest computed tomography (CT) scans are a specialized radiographic procedure that takes multiple pictures, or slices, of the chest with or without intravenous contrast to highlight the blood vessels (11). These slices, obtained at 1 – 10 mm/slice, allow the healthcare provider and radiologist the ability to evaluate for lung tissue damage or structural changes as a result of COPD. These imaging methods are important in evaluating a patient for the pattern of COPD and a patient’s potential for surgical candidacy.
Ventilation/Perfusion Lung Scan (V/Q scan)
A pulmonary ventilation/perfusion scan (V/Q scan) is a pair of nuclear scan tests that use inhaled and injected radioactive material (radioisotopes) to measure breathing (ventilation) and circulation (perfusion), respectively, in all areas of the lungs. The ventilation scan is used to see how well air reaches all areas of the lungs. The perfusion scan measures the blood supply through the lungs. A V/Q scan is most often performed to detect a blood clot in the lungs (pulmonary embolus), but for patients with COPD who are being considered for surgery, a V/Q scan is used to evaluate regional lung function (12). By analyzing the V/Q scan, areas of matched decreased ventilation and perfusion (emphysema) can be identified (target areas) and will tell the healthcare provider about the severity of COPD. These target areas of non-function emphysematous lung contribute to dead-space ventilation due to the loss of the pulmonary-alveolar capillary bed, and may be amenable to surgical resection (removal).
Present State of Treatment for COPD
The goals of therapy in COPD are to halt the progressive decline in lung function, prevent and shorten exacerbations of the disease, improve exercise capacity, quality of life, and prolong survival. Unfortunately, the only treatment known to alter the rate of progression of COPD is smoking cessation (13). Whereas, long-term in-home oxygen therapy in hypoxemic patients is the only treatment for COPD known to decrease mortality rates (14, 15).
Medications commonly prescribed for COPD are directed at widening the airways (bronchodilators), reducing airway swelling and inflammation (steroids), and treating infection (antibiotics). Bronchodilators improve lung function, exercise capacity, and quality of life in patients with COPD but are of limited benefit to patients without reversible airway disease, such as asthma (16). Oral corticosteroids can decrease the airway swelling and inflammation, and some patients may benefit from inhaled corticosteroids (ICS). However, steroid therapy does not alter the natural history of COPD, nor does it preserve lung function; chronic steroid therapy can have major health side effects. Prophylactic (preventive) influenza and pneumonia vaccination are recommended to prevent potential life-threatening infections. Pulmonary rehabilitation, including aerobic exercise conditioning, education, and psychosocial support, improves exercise capacity in patients with COPD and may reduce the rate of hospitalization (17). Adjunctive forms of therapy, such as mucolytics to control respiratory secretions or anti-anxiety medications or narcotics to relieve dyspnea, have been used in some COPD patients.
Although these interventions are believed to shorten the duration of individual episodes and to minimize symptoms, there is little evidence that they alter the course of the disease or reduce mortality. In patients with far advanced COPD, single or double lung transplantation has been used as a last resort. However, the small number of donor organs available for transplantation limits the option of lung transplantation.
Surgical Therapy for COPD
Despite pharmacotherapy, pulmonary rehabilitation, and supplemental oxygen, patients with advanced COPD typically remain very dyspneic (short of breath) and disabled (18). These relentless symptoms have fueled many surgical attempts to treat the disease (18). A variety of operative techniques aimed at correcting the underlying pathophysiology and/or alleviating symptoms of dyspnea in patients with COPD have been reported and reviewed throughout the surgical literature (19, 20, 21).
Initially, operations were designed to correct the anatomical deficiencies that were presumed to be the cause of the COPD. A variety of procedures were based on the contemporaneous beliefs, but often misunderstanding of the physiology of COPD (18). These operations were quickly abandoned, as it was recognized that these early procedures did not prove effective or withstand the test of time. A New England Journal of Medicine article in 1972 (22), commented on these early procedures, writing “The alleged benefits of those maneuvers were frequently lost on patients whose worsening dyspnea left them little energy with which to debate their surgeons.”
Further advances in surgical technique and the realization of the critical importance of patient selection have resulted in a renewed enthusiasm for surgical treatment for COPD. However, only three surgical therapies have stood the test of time: giant bullectomy, lung volume reduction surgery (LVRS), and lung transplantation. Only a small number of people with COPD, predominantly the emphysema type and not chronic bronchitis, will benefit from two types of non-lung transplant surgery. The two major types of non-transplant surgery for COPD are giant bullectomy and lung volume reduction surgery (LVRS).
Surgical therapy for emphysema is usually an elective procedure, and as such, all efforts should be taken to instruct the patient in the risks of these procedures (23). Smoking cessation is an absolute in the selection of appropriate candidates for these procedures. Medical therapy should be optimized to reverse airway obstruction, bronchospasm, and intercurrent pulmonary infections prior to surgery. A reduction or cessation of oral corticosteroid therapy should be achieved, as these medications may be associated with poor tissue healing (23). In addition, preoperatively a patient must be instructed in the techniques of coughing, deep breathing, and chest physiotherapy. Intensive pulmonary rehabilitation prior to the planned procedure is critical to successful outcomes following bullectomy or LVRS. Several pulmonary function tests, cardiopulmonary exercise tests, and additional imaging techniques are required to determine a patient’s candidacy for these surgical procedures.
Pathophysiology of Emphysema to be Corrected by Surgery
Pathophysiology
Emphysema is characterized by air-space destruction and loss of the pulmonary capillary bed, which is needed for gas exchange (Oxygen [O2] exchanged for waste Carbon Dioxide [CO2]). Physiologically, these changes result in the loss of elastic recoil, leading to airflow limitation and hyperinflation. These, in turn, lead to increased work of breathing, respiratory-muscle fatigue, and the sensation of dyspnea. Loss of the pulmonary capillaries leads to ventilation-perfusion mismatching and increases in pulmonary vascular resistance (pulmonary vascular pressure). In chronic severe disease, dyspnea and exercise intolerance become very disabling for patients with emphysema. Significant mortality occurs in patients once the forced expiratory volume in 1 second (FEV1) falls to less than 30% of predicted values (23).
Proposed Mechanisms of Improvement
The improvements in pulmonary function reported after giant bullectomy and/or LVRS have been attributed to increased elastic recoil, correction of ventilation-perfusion mismatching, improved respiratory muscle efficiency, and improved right ventricular performance (24). These mechanisms are not mutually exclusive, and it is likely that one or more are operative to varying degrees in individual patients. Patients with compressed normal lung would be expected to have increased elastic recoil and perfusion after surgery. Those with predominantly emphysematous lung may see little improvement in these measures but may have improved respiratory muscle function and cardiac performance due to the decrease in lung hyperinflation. If areas of abnormal ventilation and perfusion are removed with more areas of normal ventilation-perfusion matching remaining, dead-space ventilation will be decreased, and arterial oxygenation (PaO2) at rest and during exercise will improve (23).
Reduction Pneumoplasty for Giant Bullous Emphysema
Emphysema causes alveoli air-space destruction and loss of the pulmonary capillary bed and results in the alveoli becoming over-inflated (hyperinflated). When the hyperinflated air sacs become extremely large, they are called bullae. Bullae are formed from hundreds of destroyed alveoli. A bullectomy is the surgical removal of these extra-large areas of emphysematous lung that are pressing on collapsed healthy lung, preventing those alveoli from functioning normally (23). Very few individuals have these extra-large bullae that would be amenable to surgical resection and removal, which would allow the compressed non-emphysematous adjacent lung to function normally.
Rationale and Indications for Surgery
Bullectomy is performed to (1) relieve compressive changes in the normal lung adjacent to a giant bulla, (2) increase compliance and airway diameter in the remaining lung, (3) improve ventilation-perfusion matching in the nonbullous lung, (4) decrease dead-space ventilation, (5) decrease elevated intrathoracic pressure generated by the bulla, and (6) treat complications related to the bulla (25).
The decision to operate on symptomatic patients with giant bullae and otherwise normal lung function is not difficult. More problematic is the decision to operate on patients who are asymptomatic or on dyspneic patients with generalized emphysema. In asymptomatic patients, surgery is indicated primarily for complications related to the bulla (26). Bullae predispose patients to spontaneous pneumothorax (collapsed lung due to air leaks), which may be difficult to manage due to further physiologic impairment of already limited patients, difficulty diagnosing the pneumothorax in the presence of diffuse bullous disease, prolonged air leaks, and a high rate of recurrence. Infection of the bullae is uncommon and typically responds to conservative therapy, although medical therapy may be unsuccessful due to poor communication between the bronchial tree and the bulla. Indications for surgery are hemoptysis (coughing up blood), infected fluid in the bulla rupture into the pleural space (chest cavity), or failure to respond to 4 to 6 weeks of antibiotic therapy. On rare occasions, surgery may be recommended to an asymptomatic patient with a giant bulla seen by chest radiography. Given that the natural history of untreated asymptomatic bullae is unpredictable and poorly documented (27,28), it is generally agreed that surgery is indicated only if the bulla occupies more than half of the hemithorax (one half of the chest cavity). In certain patients, surgery may be indicated to reduce the risk of spontaneous pneumothorax.
In emphysema patients, it is critical to estimate the potential improvement in the function of the nonbullous lung, as well as the effects of the bulla on the lung. Since the rationale for surgery is the restoration of elastic recoil and the reduction of airway and pulmonary vascular resistance, re-expansion of previously compressed lung may increase airflow (vital capacity and FEV1). Pulmonary vascular resistance may decrease, and a decrease in the total lung volume may restore the normal curvature of the diaphragm, resulting in improved length-tension relationships and improved function. However, if the patient’s symptoms are due primarily to emphysema, it is unlikely that surgery will be beneficial.
Selection for Surgery
Clinical, Physiologic, and Radiographic Evaluation
No single preoperative variable is an absolute predictor of outcome, but several variables (as determined by clinical, physiologic, and radiographic means) have been postulated to predict a favorable outcome (Table I) (Adapted from 23). Therefore, patients should undergo a thorough evaluation of their overall physical conditioning, pulmonary function and reserve, and cardiac status. This preoperative evaluation is designed to determine a patient’s overall medical condition and his or her ability to withstand the risks of thoracotomy (open chest surgery). Age, medical and surgical history (particularly of thoracic trauma or surgery), comorbid diseases, chronic bronchitis, cardiac status, smoking history, and unexplained weight loss are all important predictors of outcome. Once a patient has been selected for surgery, optimization of medical therapy (including aggressive rehabilitation, physical therapy, and smoking cessation) may reduce postoperative risk and improve pulmonary function.
TABLE I. Selection Criteria for Bullectomy: Predictors of Outcomes
Clinical Parameter Good Outcome Poor Outcome
Age < 50 yr > 50 yrWeight Loss < 10% > 10%
Dyspnea Rapidly progressive Slowly progressive
Spirometry Normal - Mild Decrease Markedly Decreased
Diffusion Normal Decreased
Arterial Oxygen (PaO2) Normal Hypoxemia
Arterial CO2 (PaCO2) Normal Increased
Lung Imaging
CXR Bulla > 1/3 hemithorax Diffuse multiple small bullae
Vascular crowding “Vanishing lung” syndrome
CT Large localized bullae Multiple bilateral bullae
Vascular crowding Adjacent Lung Emphysema
Normal Adjacent Lung
V/Q scan Matched defect Diffuse defects
Normal V/Q adjacent lung Poor V/Q adjacent lung
Bullectomy Surgical Techniques
In general, the bullectomy procedure aims to relieve compression while preserving all vascularized and potentially functioning lung tissue. This is best accomplished by limited resections such as local excision, plication (folding out) of the bulla, or both (29). A variety of approaches have been described, including unilateral thoracotomy or video-assisted thoracoscopic surgery (VATS). For patients with bilateral disease, exposure is gained via bilateral posterolateral thoracotomy or bilateral anterolateral thoracotomy (with or without transverse sternotomy) or through a median sternotomy. All have been advocated, and each has its own advantages and disadvantages (23). Other surgeons prefer a two-stage bilateral procedure, which allows functional assessment of the first procedure before proceeding with the contralateral procedure (23). In general, bilateral procedures should be limited to patients without severe emphysema, with the bullectomy done first on the lesser-functioning lung as determined by preoperative physiologic and imaging studies (23). The final operative results may be adversely affected by persistent postoperative air spaces and prolonged air leaks. These may be limited by the use of pleural tents or buttressed staple lines with bovine pericardium (27, 30).
Bullectomy Outcomes
Although successfully performed for more than four decades, bullectomy remains an option for a limited number of patients who have this form of emphysema. Operative mortality appears to be approximately 0% to 8% (23). Morbidity due to prolonged air leaks can be significant, ranging from 5% to 20%. Subjective and objective results have been excellent in carefully selected patients, and symptoms improve within a few months postoperatively. Improvement in FEV1 ranges from 10% to 500%. For the majority of patients, FEV1 improves by 10% to 30% (23). Increases in partial pressure of arterial oxygen (PaO2) and forced vital capacity and decreases in partial pressure of arterial carbon dioxide (PaCO2) and symptom scores have also been reported. Although long-term follow-up is not described in most reports, approximately 30% to 50% of patients maintained the improvement in FEV1 for 5 or more years (23). These series were retrospective in nature and did not contain control groups. Nonetheless, surgical experience with these patients suggests that acceptable candidates have bullae that occupy more than one-third of the hemithorax, computed tomographic (CT) evidence of compressed lung tissue, and an FEV1 of less than 50% of the predicted value. Other predictors of physiologic improvement include a large volume of trapped gas, preservation of the diffusing capacity, and a near-normal PaCO2.
Summary
In appropriately selected patients, bullectomy is associated with modest increases in pulmonary function and significant improvement in dyspnea. In general, the size of the bulla with evidence of lung compression is predictive of successful outcome postoperatively. Bullae must occupy more than 30% to 50% of the hemithorax and must show definite compression of adjacent lung. Furthermore, there should be no evidence of “vanishing lungs” syndrome or chronic bronchitis. Regardless of the technique and approach, as much normal lung as possible should be preserved to facilitate re-expansion, limit air leaks, and optimize postoperative function. More experience with video-assisted thoracoscopy (VATS) may establish it as the procedure of choice, rather than open thoracotomy.
Lung Volume Reduction Surgery
History and Background
In the 1957, Brantigan and Mueller (31) proposed the technique of multiple wedge resections for patients with nonbullous emphysema. They theorized that decreasing the volume of the lung could increase traction on the distal airways, enlarging them and improving airflow. Since hyperinflation of the lung forces the diaphragm down in the thorax, changing its length-tension relationships, Brantigan and Mueller further speculated that decreasing the lung volume would restore the shape of the dome of the diaphragm and restore the diaphragm’s efficiency as the respiratory pump. They emphasized that the operation was “directed at the restoration of a physiologic principle, not the removal of pathologic tissue,” since the entire lung is involved with emphysema to varying degrees. Despite improved clinical pulmonary symptoms in 75% of patients, the procedure was soon abandoned because there was no objective measurement of improved pulmonary function and because the procedure was associated with significant morbidity and a mortality of 18%.
The re-introduction of multiple wedge resections for emphysema occurred in 1995, when Cooper and colleagues (32), using a modification of Brantigan’s technique, reported their results in 20 patients undergoing the procedure. The operation was performed via a median sternotomy (middle of the chest approach) with a linear stapler and bovine pericardium to minimize air leaks along the staple lines. They reported no operative or late mortality, a mean improvement in FEV1 airflow of 82%, increased PaO2 (arterial oxygenation), and an increase in 6-minute walk distance, along with improved dyspnea and quality of life scores. Following this report, many centers started performing LVRS in an uncontrolled fashion, making it difficult to assess entry criteria and outcomes.
A number of centers have reported their outcomes following bilateral LVRS (33). From these combined experiences, 738 patients reported a mean improvement of 61% in FEV1 airflow and a mean improvement of 45.7% in 6-minute walk distance; 62% of the oxygen-dependent patients became oxygen independent. Operative mortality ranged from 2.5% to 10%, and the mean hospital length of stay was 10.9 to 17 days (33). However, these favorable results of these previously published series contrast with data collected from Medicare claims by using the LVRS billing code between October 1995 and January 1996 (34). In this group of 722 patients, mortality rates at 3 and 12 months postsurgery were 14.4% and 23%, respectively. For these patients, acute care hospitalization, the use of long-term care and rehabilitation services, and the average number of days in hospital, for the surgical group as a whole, were also greater postsurgery (34). These conflicting results and its high potential costs led Medicare to refuse payment for the LVRS procedure in December 1995. This led to the collaboration of the Health Care Financing Administration (HCFA); the National Heart, Lung and Blood Institute (NHLBI); and the Agency for Healthcare Research and Quality in organizing a national registry and funding a controlled clinical trial, the National Emphysema Treatment Trial (NETT) (33).
National Emphysema Treatment Trial
The National Emphysema Treatment Trial (NETT) is a 5-year multicenter trial that intends to enroll 2,500 patients with severe emphysema to compare bilateral LVRS via median sternotomy or VATS to each other and to maximal medical therapy that includes intensive pulmonary rehabilitation and education. The trial is meant to (1) provide information on the role of LVRS in the management of emphysema, (2) define patient selection criteria and identify a subset of patients (if any) likely to benefit from LVRS, and (3) provide a basis upon which HCFA can determine reimbursement for LVRS (33). The trial was conducted at 18 academic medical centers in the United States. Following enrollment and completion of pulmonary rehabilitation, patients have been randomized to continued medical therapy or to LVRS and medical therapy. At centers performing LVRS by both VATS and median sternotomy, patients randomized to surgery are being randomized between the two approaches.
NETT Preoperative Evaluation
The preoperative evaluation of the potential LVRS candidate should include pulmonary-function tests, with assessment of lung volume and diffusion capacity, inspiratory and expiratory chest radiography, CT scan of the chest, assessment by arterial blood gases, a 6-minute walk test, quantitative ventilation-perfusion (V/Q) lung scanning, cardiac, and psychosocial evaluations (23, 33).
Pulmonary-function testing should be the initial screening test for evaluating candidates for LVRS. Spirometry determines the degree of airflow limitation and whether there is a significant reversible component consistent with reactive airways disease. Lung volumes should be measured by body plethysmography, to accurately assess the volume of trapped gas and the residual lung volumes. Diffusion capacity evaluates the severity of the destruction of the alveolar capillary bed. Arterial blood gases are indicative of the level of pulmonary reserve, with either severe hypoxemia (low O2) or hypercapnia (high CO2) representing severe lung tissue destruction. The 6-minute walk test provides insight into the level of a patient’s functional reserve (23, 33).
Inspiratory and expiratory chest radiography provides useful information about the degree of hyperinflation, the position of the diaphragm, and the presence of chest wall abnormalities. Computed tomography (CT) scans provide information on the degree of heterogeneity, the location of so-called target areas, and the severity of lung tissue destruction. Quantitative ventilation-perfusion (V/Q) lung scans also provide information on heterogeneity and the function of the remaining lung tissue (23).
Cardiac evaluation typically consists of a history, physical examination, electrocardiography, and echocardiography to assess left and right ventricular function and to estimate pulmonary artery pressures. Right heart catheterization is performed in patients with evidence of pulmonary hypertension on echocardiography. In patients with multiple coronary risk factors or a prior history of coronary artery disease, a nuclear stress test, or left heart catheterization is indicated (23, 33).
NETT Inclusion and Exclusion Criteria
The inclusion criteria were developed to enroll patients with emphysema with diverse patterns of distribution, to determine whether anatomic emphysema distribution affects the response to therapy. Mandatory inclusion criteria include radiographic evidence of emphysema, evidence of severe airflow obstruction and hyperinflation on pulmonary-function tests, and the ability to participate in and achieve preset goals of pulmonary rehabilitation. The exclusion criteria were designed to exclude patients at risk for perioperative morbidity and mortality, patients with obstructive disease not suitable for LVRS, and patients with comorbid conditions that would prevent those patients from completing the trial. For a complete list of inclusion and exclusion criteria, the reader is referred to the National Emphysema Treatment Trial Research Group’s statement on the rationale and development of NETT (33, 35), these criteria are briefly summarized in Table II.
Table II. National Emphysema Treatment Trial Criteria
Inclusion Criteria
History and Physical Examination consistent with Emphysema
Disabling Dyspnea
CT scan evidence of bilateral emphysema
Spirometry Airflow Limitation (FEV1 < 45% Predicted Value)
Lung Volume Hyperinflation by PFT
Pre-rehabilitation Room Air Resting PaO2 > 45 mm Hg and PaCO2 < 60 mm Hg
Nonsmoker for 4 months
Adherence to Medical Therapy
Non-Obese – Body Mass Index < 30
Approval for Surgery by Cardiologist if evaluation suggestive of cardiac disease
Completion of all pre-rehabilitation assessments
Completion of NETT rehabilitation program
Ongoing disabling symptoms following completion of pulmonary rehabilitation
Approval for LVRS by Pulmonary Physician and Thoracic Surgeon
Consent for LVRS
Exclusion Criteria
Severe Emphysema, FEV1 < 20% predicted value and/or Diffusion (DLCO) < 20%
Non-heterogeneous Emphysema by CT scan
Severe hypoxia (Room Air PaO2 < 45mm Hg) or hypercarbia (PaCO2 > 60mm Hg)
Inability to provide diffusion (DLCO) measurement
Six-minute walk distance < 140 meters post-rehabilitation
CT scan of diffuse emphysema unsuitable for LVRS
Prior thoracic surgery that would interfere with lung resection
Pleural or Interstitial Lung Disease (ILD)
Giant bullae (> 1/3 Volume of the Lung)
Mucous hyperexcretion or Significant Bronchiectasis
Myocardial Infarction or Congestive Heart Failure within 6 months
Uncontrolled Systemic Hypertension
Pulmonary Hypertension
Severe Obesity or Malnutrition
Prednisone usage > 20 mg/day
Poor functional capacity due to non-pulmonary disease
Systemic diseases which limits survival (e.g. cancer)
LVRS Operative Techniques
Several review groups compared unilateral stapled resection to bilateral procedures (23). In general, bilateral LVRS produced better physiologic results than unilateral procedures. Operative mortalities with the two procedures were similar, but there have been contradictory reports in the published literature. Long-term survival has been reported to be greater with bilateral procedures (23). This prompted the NETT centers to use bilateral LVRS as the procedure of choice and to reserve the unilateral procedure for patients who are not candidates for bilateral procedures because of prior thoracic surgery or trauma, tumor location, or unilateral disease as seen by screening radiography.
The overall goal of LVRS resection is to decrease the volume of both lungs by 20% to 35%. The use of bovine pericardial strips to buttress the staple lines decreases the incidence, duration, and severity of air leaks (30). Most authorities now consider the stapled procedure, with or without buttressing, to be the technique of choice for LVRS. A number of approaches for stapled resections have been advocated, including median sternotomy, thoracotomy, clamshell incision, and VATS, but the choice of one procedure over another has generally been a matter of personal preference of the surgeon.
Intraoperative and Postoperative Management
Intraoperatively, care must be taken to avoid overdistension of the lungs due to positive pressure ventilation. This may result in impaired venous return, decreased cardiac output, and cause hypotension. Excessive hyperinflation may also result in tension pneumothorax (collapsed lung pressing on the heart and great vessels) due to rupture of a bleb, bulla, or emphysematous tissue. Despite the presence of hypercarbia and hypoxemia, permissive hypercapnic ventilation is allowed and, if necessary, the patient is removed from the ventilator circuit to allow adequate exhalation and decompression. Peak airway pressure should be limited to less than 30 mm Hg, and the inspiratory/expiratory ratio should be as great as possible. Patients are intubated (breathing tube inserted and patient placed on a ventilator) with double-lumen endotracheal tubes (breathing tubes). The use of long-acting narcotics or anesthetics is avoided to facilitate early extubation (removal of breathing tube) at the end of the procedure. Prior to extubation, patients undergo fiberoptic bronchoscopy to remove blood and secretions and to obtain material for cultures. Almost all patients are extubated at the end of the procedure or shortly thereafter, thus limiting the exposure to positive pressure and decreasing the severity of any air leaks from the staple lines. Routine chest tube suction is not employed except in the case of large pneumothoraces or persistent large air leaks (23).
Adequate pain control is initially achieved by the use of a thoracic (chest) epidural catheter. Later, the patients receive patient-controlled analgesia with narcotics. This approach may decrease gastrointestinal complications and allows for aggressive respiratory therapy, chest physiotherapy, and physical therapy. Respiratory care includes breathing exercises, inhaled bronchodilators, and early mobilization. Instruction in these techniques is given preoperatively to all patients. Routine monitoring of oxygen saturation, blood pressure, heart rate, temperature, and urine output is performed for the first few postoperative days. A stress dose of corticosteroids is given to those patients who were steroid dependent preoperatively. Antibiotic prophylaxis directed against respiratory tract organisms common to COPD patients (pending bronchoscopic cultures), gastric ulcer prophylaxis, and subcutaneous heparin or pneumatic stockings for deep venous thrombosis prophylaxis are used in all patients (23).
Postoperative mortality has been reported to be from 5% to 10% and to be primarily due to acute respiratory failure, pneumonia, or cardiac events. Typical complications include prolonged air leaks (in 10% to 50% of cases), pneumonia, respiratory insufficiency requiring invasive or noninvasive ventilation, colonic perforation or overdistension, and panic attacks. Careful attention to preoperative selection criteria, perioperative respiratory therapy, the use of epidural catheters for pain control, and care in an active center that performs LVRS and/or lung transplantation regularly most likely will limit the incidence and severity of these complications (23).
NETT Outcome Measures
The primary outcome measures are survival and maximal exercise capacity. A number of secondary measures will be used to assess outcomes. Quality of life and related disease-specific quality of life will be assessed using questionnaires, which were developed and validated for use in COPD patients. Cost-efficacy will be determined by dividing the incremental costs by the incremental quality-adjusted life-years. Pulmonary function and gas exchange measures will include spirometry, lung volume assessment by plethysmography, diffusing capacity, arterial blood gases at rest, and maximal inspiratory and expiratory mouth occlusion pressures. Selected centers are performing complete pulmonary mechanics and arterial blood gas analysis with maximal exercise. To determine whether the pattern or severity of emphysema influences outcome, patients are studied with chest radiography, CT, and ventilation-perfusion scanning. Oxygen requirements and 6-minute walk distance are being assessed in all patients, and psychomotor testing is being done as well. Cardiac evaluation includes echocardiography at baseline and at least once postoperatively. Patients with evidence of pulmonary hypertension undergo right heart catheterization. Selected centers are performing right heart catheterization at rest and with exercise, at baseline and postoperatively.
NETT Results
Between January 1998 and July 2002, 3777 patients were evaluated, and 1218 patients underwent randomization – 608 to bilateral LVRS and 610 to medical therapy. All patients received optimal medical therapy and underwent pulmonary rehabilitation before randomization. The NETT results were published in 2003 (35) after a median follow-up time of 2.4 years and again in 2006 (36) after a median follow-up time of 4.3 years. The 90-day mortality rate was six-fold higher in the LVRS population, which was not unexpected when comparing a surgical therapy with medical therapy. Although overall mortality did not differ between the treatment groups initially, patients randomized to LVRS had a 6.6% lower absolute mortality rate during the extended follow-up period compared with those in the medical treatment arm. Improvements in exercise capacity and health-related quality of life were more frequent in the LVRS group. In addition, the LVRS patients were also more likely to have improvements in FEV1 airflow, 6-minute walk distance, and dyspnea.
One of the goals of the NETT was to identify subgroups of emphysema patients who derived the greater benefit or harm from LVRS (33). In post hoc analysis, the NETT investigators found that outcomes varied by emphysema upper lobe predominance and maximal exercise capacity. The findings of each subgroup are described.
Emphysema patients who should not undergo LVRS:
Patients with an FEV1 of 20% predicted or less, who also had a DLCO (diffusion) of 20% predicted or less, a homogeneous pattern of emphysema on Chest CT scan had a four-fold increased risk of death at 1 year. Similar outcomes were reported after extended follow-up of these patients. In addition, patients who have non-upper lobe emphysema and a high exercise capacity do not appear to benefit from LVRS. Also, there was no improvement in exercise capacity in this subgroup (non-upper lobe emphysema and high exercise capacity). Thus, these patients should not be considered for LVRS (35, 36).
Emphysema patients who should be considered for LVRS:
Patients who have a low exercise capacity and upper lobe emphysema on Chest CT scan should be considered for LVRS. Those patients in the LVRS group had an improvement in survival (12% verses 24%) and were more likely to have improvements in exercise capacity and quality of life at 2 years as compared to those in the medical treatment group (35, 36).
Emphysema patients who have questionable benefit from LVRS:
LVRS did not provide a survival benefit to those with high exercise capacity and upper lobe-predominant emphysema, but was associated with an increased likelihood of improvement in exercise capacity and quality of life at 2 years post-LVRS when compared with medical therapy alone. Patients with non-upper lobe emphysema and low exercise capacity in the LVRS arm did not have a survival or exercise capacity benefit, but did have an improved quality of life at 2 years postoperatively (35, 36).
LVRS Summary
Lung volume reduction surgery has recently enjoyed a resurgence as a potential treatment of emphysema. The greatest functional improvement appears to occur in patients with marked hyperinflation, airflow obstruction secondary to the loss of elastic recoil, and heterogeneous disease as determined by chest radiography, CT, or ventilation-perfusion scanning. The goal of the operation is to reduce the volume of the lung by resecting areas of severe lung tissue destruction while leaving adjacent lung with preserved function intact. The importance of careful patient selection and several preoperative variables, such as clinical, physiologic, and radiographic evaluations can safely predict a favorable outcome in a limited number of appropriate patients. In some centers and in appropriate patients, LVRS can be used as an alternative or bridge to lung transplantation. This approach can prolong a patient’s survival and reduce risks of prolonged immunosuppression.
More Information
Web Resources
COPD
American Thoracic Society: Patient Information Series:
COPD
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/copd.html
Alpha-1 Antitrypsin Deficiency
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/alpha1.html
COPD Signs and Symptoms
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/signs-and-symptoms-of-copd.html
Pulmonary Function Tests
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/pulmonary-function-tests-in-copd.html
Medicine Used to Treat COPD
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/medicines-used-to-treat-copd.html
Surgery for COPD
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/surgery-copd.html
COPD Guidelines: For Patients and Their Families
http://www.thoracic.org/sections/copd/for-patients/index.html
American College of Chest Physicians: Patient Education Guides
http://chestnet.org/patients/guides/
American Lung Association: http://www.lungusa.org/
National Heart Lung & Blood Institute: http://www.nhlbi.nih.gov/index.htm
Books about COPD
Chronic Obstructive Lung Diseases. N.F. Voelkel and W. MacNee eds. B.C. Decker. Edition 1, 2001 London, UK. ISBN: 1550091336.
Clinical Management of Chronic Obstructive Lung Disease. S.I. Rennard, R. Rodriguez-Roisin, G. Huchon eds. Informa Healthcare. Edition 2, 2008 London, UK. ISBN: 0849375878.
Books about Surgery for COPD
Lung Volume Reduction Surgery for Emphysema. H.E. Fessler, J.J. Reilly, D.J. Sugarbaker eds. Informa Healthcare Edition 1, 2003. London, UK. ISBN: 0824708970.
Sabiston & Spencer Surgery of the Chest. F. Selike, S. Swanson, P.J. del Nido eds. W.B. Saunders Co. Edition 7, 2005. ISBN: 0721600921.
References
1. American Thoracic Society. Patient Information Series. Chronic Obstructive Pulmonary Disease (COPD). Am J Respir Crit Care Med (2005) 171: P3-4.
2. Murray, C.J. and Lopez, A.D. Alternative projections of mortality and disability by cause 1990-2020: Global burden of disease study. Lancet (1997) 349: 1498-1504.
3. Sullivan, S.D., Ramsey, S.D., and Lee, T.A. The economic burden of COPD. Chest (2000) 117: 5S-9S.
4. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med (2001) 163: 1256-1276.
5. American Throacic Society: Chronic bronchitis, asthma and pulmonary emphysema: A statement by the committe on diagnostic standards for nontuberculous respiratory diseases. Am Rev Respir Dis (1962) 85: 762-768.
6. Ciba Foundation Guest Synposium: Terminology, definitions and classifications of chronic pulmonary emphysema and related conditions. Thorax (1959) 14: 286-299.
7. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med (1995) 152: S77-S121.
8. Taraseviciene-Stewart, L. and Voelkel, N.F. Molecular pathogenesis of emphysema. J Clin Invest (2008) 118: 394-402.
9. American Thoracic Society. Patient Information Series. What is Alpha-1 Antitrypsin Deficiency ? Am J Respir Crit Care Med (2006) 173: P5-6.
10. American Thoracic Society. Patient Information Series. Pulmonary Function Tests in COPD. Am J Respir Crit Care Med (2005) 172: P5-6.
11. http://www.thoracic.org/sections/copd/for-patients/index.html
12. http://www.nlm.nih.gov/medlineplus/ency/article/003828.htm
13. Ries, A.L. Rehabilitation in chronic obstructive pulmonary disease and other respiratory disorders. In Fishman AP, ed. Pulmonary Diseases and Disorders, 3rd ed. New York, NY: McGraw-Hill, 1997; 709-719.
14. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trail. Ann Intern Med (1980) 93: 391-398.
15. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet (1981) 1: 681-686.
16. Jones, P.W., Bosh, T.K. Quality of life in COPD patients treated with salmeterol. Am J Respir Crit Care Med (1997) 155: 1283-1289.
17. American College of Chest Physicians and teh American Association of Cardiovascular and Pulmonary Rehabilitation Pulmonary Rehabilitation Guidelines Panel. Pulmonary rehabilitation: joint ACCP/AACVPR evidence based guidelines. Chest (1997) 112: 1363-1396.
18. Brown, C.D. and Fessler, H.E. Clinical Reveiw. Lung Volume Reduction Surgery. COPD (2005) 3: 363-375.
19. Knudson RJ, Gaensler EA. Surgery for emphysema. Ann Thorac Surg (1965) 1: 332–362.
20. Deslauriers J. A perspective on the role of surgery in chronic obstructive lung disease. Chest Surg Clin N Am (1995) 5(4): 575–602.
21. Cooper JD. The history of surgical procedures for emphysema. Ann Thorac Surg (1997) 63: 312–319.
22. Laforet EG. Surgical management of chronic obstructive lung disease. N Engl J Med (1972) 287: 175–178.
23. Zamora, M.R. Surgical Therapy for Chronic Obstructive Lung Disease. (2002) In Chronic Obstructive Lung Diseases. N.F. Voelkel and W. MacNee eds. B.C. Decker. London, UK.
24. Fein AM. Lung volume reduction surgery: answering the crucial questions. Chest (1998) 113: 277S–282S.
25. Mehran RJ, Deslauriers J. Indications for surgery and patient work-up for bullectomy. In: Surgery for Emphysema. pg 717–34. Chest Surg Clin N Am, Vol. 5: 4,1995.
26. Gaensler, E.A., Cugell, D.W., Knudson, R.J., et al. Surgical management of emphysema. Clin Chest Med (1983) 4: 443-463.
27. Boushy, S.F., Billig, D.M., Lohen, R. Changes in pulmonary function after bullectomy. Am J Med (1969) 47: 916–923.
28. Spear, H.G., Daughty, D.C., Chesney, J.G., et al. The surgical management of large pulmonary blebs and bullae. Am Rev Respir Dis (1961) 84: 186.
29. Deslauriers J, Leblanc P, McClish A. Bullous and bleb diseases in the lung. In: Shields TW, editor. General Thoracic Surgery. 3rd ed. Philadelphia: Lea and Febiger; 1989.
30. Cooper JD. Technique to reduce air leaks after resection of emphysematous lung. Ann Thorac Surg (1994) 57: 1038.
31. Brantigan O.C., Mueller E. Surgical treatment of emphysema. Am Surg (1957) 23:789–804.
32. Cooper J.D., Trulock, E.P., Triantafillou, A.N., et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg (1995) 109: 106–119.
33. National Emphysema Treatment Trial Research Group. Rationale and design of lung volume reduction surgery: a prospective randomized trial of lung volume reduction surgery. Chest (1999) 116: 1750–1761.
34. Health Care Financing Administration (US). Report to Congress: lung volume reduction surgery and Medicare coverage policy; implication of recently published evidence. Washington (DC): Department of Health and Human Services, 1998.
35. Fishman, A., Martinez, F., Naunheim, K. et. al. A randomized trial comparing lung voulme reduction surgery with medical therapy for severe emphysema. N Engl J Med (2003) 348: 2059-2073.
36. Naunheim, K.S., Wood, D.E., Mohsenifar, Z., et. al. Long-term follow-up of patients receiving lung volume reduction surgery verses medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group. Ann Thorac Surg (2006) 82: 431-443.
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