Pathophysiology

Emphysema is a pulmonary disease that is one of the conditions that are together characterized as chronic obstructive pulmonary disease (COPD). The other diseases that are also constituents of the diagnosis of COPD are chronic bronchitis, formally defined as the presence of a productive cough for any three months of any two consecutive years, and hyperreactive airway conditions, particularly asthma. Any of these three disease processes can exist independently, but some overlap and coexistence is common. Figure 7-1 displays and discusses the interrelationships between these subsets of COPD which typically coexist.¹ “Asthma” in the figure should be understood as representing all hyperreactive airway conditions. The important understanding is that pure emphysema is uncommon.

Emphysema literally means to inflate. As illustrated in Fig. 7-2, emphysema is defined as enlargement of the airways distal to the terminal bronchiole in association with destruction of the normal architecture.² This is a result of a permanent and irreversible loss of alveolar septi as well as loss of the elastic tissues. This tissue loss is not recoverable and distinguishes emphysema from compensatory air space distention that, for example, is frequently seen in the remaining lung following pneumonectomy. Nearly all emphysema is secondary to the injury caused by cigarette smoke although there is a rare hereditary abnormality that is associated with α₁-protease inhibitor deficiency.

After the cigarette smoke has damaged the airways and parenchyma causing loss of tissue and destruction of anatomic integrity, the natural tendency is for continued enlargement of the air spaces distal to the terminal bronchial. Although this disease progression is caused by multiple factors, the predominant factor is now thought to be continued traction on the damaged and weakened areas by the unopposed traction by the elastic tissue of the surrounding and less-damaged lung. These air spaces enlarge and eventually coalesce and are defined as bullae when their diameter is 2 cm or more. The expression “bullous” does not identify any particular size and the actual size may be as small as 2 cm or considerably larger, constituting the so-called giant bullae. All emphysema is bullous but the sizes of the bullae vary considerably. In most patients, the disease and the bullae are diffuse throughout the lung, although upper-lobe disease is more common than the lower-lobe disease. As the disease progresses and the bullae distend further, the actual lung size as well as total and residual lung volumes increase. Ultimately, the increase in lung volume and size causes an anatomic change in the chest with an increase in chest size including the anteroposterior dimensions of the rib cage with downward flattening of the diaphragm.

The most important physiologic alteration with diffuse emphysema is an increased tendency to premature collapse of smaller airways during expiration. The primary factor for this is the loss of normal elastic tissue with the recoil properties that hold the bronchioles open, although there is some compression of functional tissue by the bullae or air spaces. As pleural pressure increases during expiration, the relatively unsupported airways close, trapping air that is measured as residual volume.

Large or so-called giant bullae are relatively uncommon. They are usually multiple and nearly always associated with true, diffuse emphysema in the rest of the lung. The pathophysiology of these giant bullae is a variation on the previously described theme of diffuse, bullous emphysema. Once an area of parenchymal weakness is of sufficient size, it continues to fill with air preferentially. The force of elastic recoil in the better lung then retracts away from the bulla. The surrounding lung is not, as previously thought, compressed by high pressure within the bulla. Rather, the relatively more normal lung retracts away from the bulla and the lack of elastic recoil in adjoining airways leads to occlusion and atelectasis.

Clinical Features

Although many patients with emphysema will also have bronchitis and/or hyperreactive airways, the following symptoms are typical. Dyspnea or difficulty breathing is the most frequently encountered symptom and generally present in all patients. Depending on the severity of the disease, this may occur at rest, even requiring oxygen supplementation, or may be more subtle and manifested by a decrease in exercise tolerance. Many patients also have a cough that may or may not be productive of sputum. Wheezing is another very common symptom as well as excess mucous production. Some patients may exhibit cyanosis. In all circumstances, emphysema results in a diminished ability to deliver oxygen to the tissues. For example, if the brain is not receiving enough oxygen, the patient may demonstrate irritability, confusion, and/or mental instability.

Diagnosis

The hallmark of emphysema is air-flow obstruction during expiration caused by the collapse of small airways that have lost the usual surrounding elastic tissue which promotes airway expansion. Pulmonary function testing (PFT) is essential to establish the diagnosis. Spirometry indicates expiratory air-flow obstruction with a reduction in the forced expiratory volume in 1 s (FEV₁) as well as a reduction in the ratio FEV₁/FVC (forced expiratory capacity). With worsening severity of the disease, lung volumes increase which leads to increases in total lung capacity, functional residual capacity, and residual volume. Further, eventually the diffusing capacity to carbon monoxide (DLCO) diminishes, which is a result and a measure of the severity of the parenchymal destruction and tissue loss characteristic of emphysema.

Medical Therapy

Smoking cessation is essential and by far the most important therapeutic maneuver available to treat patients. Although not curative, middle-aged smokers who stop smoking experience a significant improvement in the rate of decline in pulmonary function and return to the annual changes seen in nonsmokers. To achieve this benefit, all possible aid to achieve this goal should be provided to these patients, including the use of pharmacologic agents and nicotine-replacement therapy.

Bronchodilator agents (both oral and inhalers) can also provide symptomatic benefit in patients with COPD and, in particular, those with emphysema. The inhaled route is preferable as side effects are less common with this route compared with parenterally delivered medications. β-Agonist drugs, such as albuterol, which are also bronchodilators, provide symptomatic benefit. Side effects including tremor and tachycardia are associated with these agonists.

The use of glucocorticoids is mildly controversial. Although inhaled glucocorticoids can reduce the frequency of disease exacerbations, their use has been associated with increased rates of oral pharyngeal candidiasis and bone density loss. In general, the chronic use of oral glucocorticoids is not recommended because of what is considered to be an unfavorable risk-to-benefit ratio.

Surgical Therapy

Indications

The history of surgery for emphysema is a fascinating one.^2,3 On the basis of flawed but well-intentioned logic, the early 20^th century first saw interest in surgical enlargement of the chest cavity and therefore presumably lung capacity by operations such as transverse sternotomy with costocondrectomy. Initially employed in horses, this operation failed to improve pulmonary function. Subsequently, on the basis of the observation that the chest and lungs in emphysema patients were abnormally large, operations to reduce chest capacity became attractive. Accordingly, procedures such as reduction thoracoplasty and even phrenic nerve interruption to elevate the diaphragm were performed. Again, benefits did not result from these approaches.

Surgical efforts culminated in the 1950s and 1960s with a series of reports from Brantigan.^4–6 His prescient insight into the pathophysiology of emphysema led him to conclude that removal or exclusion of volume occupying, peripheral, and bullous regions of the lung would improve pulmonary function by restoring the chest wall to a more effective configuration. He also reasoned that, with resection of the diseased lung, the more normal remaining lung would be expanded by its preserved elastic recoil properties. Applying his theories to patients, the operations he performed were successful in improving pulmonary function in operative survivors, but the operations were associated with unacceptably high perioperative mortality rates and ultimately failed, in part because patients continued to smoke postoperatively. Consequently, this approach to emphysema patients was abandoned.

Brantigan’s ideas and concepts were resuscitated in the 1990s. The first report by Wakabayashi and colleagues used a video-assisted thoracic surgical (VATS) approach and laser contraction/consolidation of the peripherally diseased areas.⁷ Ultimately, this approach was shown to be less effective than operative resection of the more diseased areas when this concept was reintroduced by Cooper and his associates in 1994.⁸

The current operative procedure is termed lung volume reduction surgery (LVRS). Due to controversies and uncertainties surrounding patient selection for LVRS and, to a lesser extent, operative technique (i.e., sternotomy or VATS), a multi-institutional prospective, randomized investigation, identified as the National Emphysema Treatment Trial (NETT), was conducted. The impact of multiple clinical and laboratory variables on perioperative and long-term outcomes was assessed as LVRS was compared with “maximal” medical management in a prospective and randomized fashion. Tables 7-1 and 7-2 provide a detailed summary of the NETT conclusions regarding the indications and appropriate patient selection for LVRS.^9,10 In general, patients who benefit the most from LVRS are those with a low exercise capacity and upper-lobe predominant, heterogeneously distributed emphysema. Figure 7-3 is an illustrative chest CT scan. The upper lobes display severe emphysematous change, whereas the lower lobes are much less diseased. Appropriate candidates experience dyspnea that restricts their activities related to daily living and diminishes their quality of life. These characteristics must be present despite the patient’s compliance with an appropriate medical regimen, including smoking cessation. On the other hand, the patient must have sufficiently diminished pulmonary function to require intervention but enough reserve to both tolerate the operation and possess the capacity for improvement. Appropriate LVRS candidates can, in part, be identified as having an FEV₁ greater than 20 percent of predicted but less than 45 percent. Tables 7-1 and 7-2 provide additional criteria used to identify appropriate and reasonable candidates for LVRS.