Pulmonary Medicine

Bullous Lung Disease (includes HIV-related emphysema)

What every physician needs to know:

Bullous lung disease is characterized by the development of bullae within the lung parenchyma. A bulla is a permanent, air-filled space within the lung parenchyma that is at least 1 cm in size and has a thin or poorly defined wall; it is bordered only by remnants of alveolar septae and/or pleura. Bullae are to be distinguished from other air-filled spaces within the lung:

  • Blebs are air-filled collections within the layers of the visceral pleura and are <1 cm in diameter.

  • Cysts are round, well circumscribed collections that have an epithelial or fibrous lining.

  • Cavities are usually thick-walled collections formed by focal necrosis within a consolidation, mass, or nodule.

  • Pneumatoceles are temporary tents in the lung parenchyma that usually arise from blunt trauma or over-distension of the lung.

Although typically seen in the context of COPD, bullae may occasionally be noted as isolated findings within normal lung parenchyma and are not always associated with airflow obstruction.

Bullae typically grow in size over time, but both the rate and extent of growth are highly variable. If bullae grow large enough, they may limit the expansion of adjacent lung parenchyma and in severe cases may cause frank atelectasis of adjacent lung segments.

In the absence of unmanageable symptoms, bullae do not necessarily require intervention. However in patients with severe impairment despite aggressive medical therapy, surgical bullectomy may be beneficial.

Classification:

Bullous lung disease can be classified into several major categories based on the condition of the surrounding lung parenchyma:

  • Bullous emphysema refers to the formation of bullae within emphysematous lung parenchyma. In this context, multiple adjacent bullae are often created as areas of severe emphysema coalesce that is due to progressive loss of alveolar attachments. Patients generally exhibit airflow obstruction on spirometry.

  • Bullae within otherwise normal lungs are often singular and surrounded by morphologically normal lung tissue. This category is far less common than bullous emphysema. The pathogenesis is not clearly established, but it likely involves a focal anatomic defect that results in progressive air trapping. Even when symptomatic, patients with this form of disease may exhibit normal pulmonary function tests.

  • Bullae in late stage lung fibrosis, such as late stage sarcoidosis or pneumoconiosis.

  • Vanishing lung syndrome or idiopathic giant emphysematous bulla, is a rare syndrome in which bullae take up > 30% of the affected hemithorax with no identifiable underlying etiology. The upper lobes are most often involved, and the presence of subpleural bullae is a dominant feature. It tends to affect younger (4th decade) male smokers. Disease progression, like all bullous emphysema, is variable and definite treatment usually requires surgical bullectomy.

More detailed classification schemes (e.g., the Reid classification) have been proposed based on the number of bullae, their location, and the condition of surrounding lung parenchyma. These classifications are not commonly used and their clinical utility not well established.

Are you sure your patient has bullous lung disease? What should you expect to find?

Bullae cause symptoms via two distinct mechanisms:

  1. Bullae may interfere with ventilation of adjacent areas of preserved lung, preventing them from expanding fully with inspiration or, in severe cases, causing frank atelectasis.

  2. Bullae are space-occupying lesions that take up relatively large volumes of the chest cavity without contributing to functional gas exchange. Because they may enlarge with exercise as a result of air-trapping, bullae may contribute to dynamic hyperinflation, altering chest wall mechanics (e.g., diaphragm flattening and barrel chest) and increasing the work of breathing.

Although bullous lung disease is sometimes asymptomatic and found only incidentally on imaging, it commonly presents with symptoms. Typically, the symptoms are those of COPD:

  • Shortness of breath or chest tightness, particularly with exertion

  • Cough

  • Sputum production

  • Occasionally, a sense of abdominal fullness or bloating, usually associated with severe obstruction and prominent air-trapping on pulmonary function testing

  • Rarely chest pain due to air-trapping within a bulla, causing distention of visceral pleura

Symptoms are typically insidious, but sudden and severe dyspnea or chest pain in a patient with bullous lung disease should raise suspicion for pneumothorax due to a ruptured bulla or bleb. Rarely, fever and malaise +/- increased sputum production, may signal an infected bulla.

Chest imaging reveals large, air-filled spaces within the lung parenchyma that are ≥1 cm in size with thin or poorly defined walls. Bullae are usually found within areas of emphysematous lungs, but less often, they occur in isolation with normal surrounding lung parenchyma.

Pulmonary function testing may be normal, particularly in patients whose bullae are surrounded by normal lung parenchyma. However, they usually demonstrate obstructive lung disease. Common abnormalities include airflow obstruction, hyperinflation (i.e., elevated total lung capacity), air trapping (i.e., elevated residual volume), and reduced diffusion capacity. Other signs of bullous lung disease may include hypoxemia, particularly with exertion; hypercapnea; and reduced exercise capacity.

Beware: there are other diseases that can mimic bullous lung disease:

The differential diagnosis of bullous lung disease is relatively broad since it includes any disease that can form air-filled spaces within lung parenchyma:

  • Blebs: Effectively "blisters" that occur within layers of the visceral pleura, rather than within lung parenchyma itself. They are usually < 1 cm in diameter, apical in location, and are a frequent finding in patients with spontaneous pneumothorax. Blebs may coexist with bullous lung disease.

  • Cystic lung disease: Distinguished from bullae by their round shape, well-circumscribed epithelial or fibrous lining, and their usually smaller size. Cystic lung diseases include:

    • Langerhans cell histiocytosis

    • Lymphangioleiomyomatosis

    • Tuberous sclerosis

    • Lymphocytic interstitial pneumonitis

    • Birt-Hogg-Dube syndrome

    • Pneumocystis jiroveci pneumonia (PCP)

    • Honeycomb change in idiopathic pulmonary fibrosis

  • Cystic bronchiectasis: In cystic bronchiectasis associated with cystic fibrosis, the air-filled spaces are actually dilated airways, rather than airspaces within lung parenchyma.

  • Cavitary lung disease: Cavities may occur within a consolidation, mass, or nodule; in contrast to bullae, lung cavities are often thick-walled. Examples include:

    • Lung abscess (e.g., resulting from TB or bacterial pneumonia)

    • Cavitary malignancy (e.g., non-small cell lung cancer)

    • Septic pulmonary emboli

    • Granulomatosis with polyangiitis (Wegener's granulomatosis)

    • Rheumatoid lung nodules

    • Sarcoidosis

    • Progressive massive fibrosis associated with pneumoconioses

    • Necrobiotic lung nodules associated with inflammatory bowel disease

  • Pneumatocele: Usually differentiated from a bulla by its transience and the clinical context in which it develops (blunt chest trauma or positive pressure ventilation with high plateau pressures).

  • Pneumothorax: With pneumothorax the air-filled space lies outside visceral pleura, rather than within lung parenchyma. Pneumothorax may be associated with ruptured blebs or bullae.

How and/or why did the patient develop bullous lung disease?

In bullous emphysema, bullae are created as areas of severe emphysema coalesce due to progressive loss of alveolar attachments. In contrast, bullae surrounded by normal lung likely form because of a focal anatomic defect that results in localized air trapping.

The classic teaching has been that ball-valve physiology leads to build-up of pressure within bullae, contributing to their progressive enlargement and compression of adjacent lung. However, careful studies of the anatomy and physiology of bullae demonstrate that they typically have patent connections to airways and no evidence of ball-valve physiology.

Further, the pressure within bullae is not positive but slightly negative, approximating intrapleural pressure. Therefore, the more likely mechanism for enlargement of isolated bullae is that their much higher compliance relative to surrounding lung leads to their preferential inflation during inspiration; conversely, their much lower elastic recoil leads to their impaired deflation during expiration. Thus, the more plausible explanation for development of adjacent atelectasis is that the elastic recoil of the more normal surrounding lung pulls the bulla open at the expense of its own aeration.

In general, the epidemiology of bullous lung disease closely follows that of COPD. Affected individuals tend to be older (usually > 45) and have significant exposure to tobacco smoke (usually at least 10 pack-years).

The possible exception is patients who have an isolated bulla surrounded by normal lung parenchyma. These patients may present at a younger age and may have less smoke exposure. However, there is a paucity of data to distinguish the epidemiology of isolated bullae from that of bullous emphysema.

Which individuals are at greatest risk of developing bullous lung disease?

Exposures and environmental factors:

In most cases, bullous lung disease is caused by prolonged exposure to smoke from combustion of tobacco or other biomass fuels used for heating or cooking, such as wood, coal, peat, and kerosene. Cigarette smoke accounts for the vast majority of disease, but smoke from burning of biomass fuels in poorly ventilated stoves or open fires used for cooking and heating is an important secondary cause worldwide.

Although exposure to organic or inorganic dusts, industrial chemicals, and outdoor air pollution have all been postulated to play a role, the evidence linking these exposures to bullous lung disease is not nearly as strong as that for cigarette and biomass fuel smoke.

IV injection of heroin or crushed oral tablets (e.g., methylphenidate) has been associated with basilar-predominant bullous lung disease. The pathophysiology of this condition is not clearly established and is confounded by a high prevalence of concomitant cigarette smoking among IV drug users. The mechanism is thought to involve destruction of lung parenchyma associated with foreign body granulomatosis. Talc, cellulose, or corn starch, all used as cutting agents for heroin or as inert fillers for oral tablets, are injected into bloodstream and preferentially distributed to the lung bases because of their relatively higher blood flow compared with the apices. In chronic users, inflammation and fibrosis in response to accumulating insoluble particles may progress to parenchymal destruction and formation of bullae.

Genetic factors:

May also contribute to development of bullous lung disease:

  • Alpha-1 antitrypsin deficiency increases susceptibility to smoke-induced bullous emphysema and, much less commonly, may cause significant emphysema in the absence of smoking. Alpha-1 antitrypsin deficiency classically causes basilar predominant emphysema with a relatively young age of onset (often younger than 40-45), but it can also cause apical-predominant or homogeneous emphysema in older individuals. Hence the absence of basilar predominance or young age should not preclude its consideration.

  • Heritability studies of COPD suggest that there are likely other genetic risk factors, and a number of genetic epidemiology studies suggest new potential candidates.

  • Inherited connective tissue disorders, such as Marfans and Ehlers-Danlos syndrome, have been linked to increased risk of bullous lung disease and pneumothorax. However, these disorders more commonly cause small apical blebs, rather than large intraparenchymal bullae.

  • Other genetic diseases, such as Neurofibromatosis 1 and Birt-Hogg-Dube, have been associated with giant bullae in case reports. These diseases typically cause cystic lung disease, and as such CT chest shows giant bullae along with numerous smaller cysts.

Human immunodeficiency virus (HIV):

HIV-positive smokers have an increased tendency towards development of emphysema. Multiple observational studies have shown that even after adjustment for other risk factors, these patients develop COPD at a slightly younger age and with slightly lower levels of tobacco exposure compared to HIV-negative controls. One retrospective study showed that, despite similar smoking histories, HIV-positive subjects have higher rates of radiographic emphysema (15%) compared to HIV-negative subjects (2%).

The pathogenesis of emphysema occurring in HIV is not clearly understood. HIV-positive smokers with emphysema have increased concentrations of inflammatory cytokines in the lung microenvironment and upregulated expression of matrix metalloproteinases, proteolytic enzymes involved in development of emphysema. HIV infection leads to induction of both native and innate responses, and evidence indicates possible increased activity of both Th-1 and Th-17 cellular immune responses. Oxidative stress, induction of microvascular endothelial cell apoptosis, malnutrition, and lung damage due to opportunistic infections, particularly PCP may play additional roles in the early development of emphysema in these patients.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

Bullous lung disease is typically diagnosed by chest imaging. Although there are no specific laboratory tests useful in its diagnosis, laboratory testing may be of some use in exploring etiology and assessing the risk of operative intervention. The laboratory workup of a patient with bullous emphysema is not standardized, but it may include the following considerations:

  • Particularly in those with disease onset at a young age (<45), a strong family history of emphysema, or emphysema out of proportion to tobacco exposure, alpha-1 antitrypsin level and phenotype may be considered in basilar-predominant bullous disease.

  • HIV testing is indicated in patients with potential risk factors, particularly in those at a comparatively young age or with emphysema out of proportion to tobacco exposure.

  • A CBC may exclude anemia as a contributor to dyspnea, and in severely affected patients, may occasionally reveal polycythemia associated with hypoxemia.

  • Pulse oximetry with exercise will reveal which patients require supplemental oxygen.

  • ABG can evaluate for hypercapnia in those with severe respiratory impairment; hypercapnia increases risks of operative intervention and may alter medical management.

  • In rare cases, genetic testing may be considered in patients with disease onset at a young age and who have characteristic physical features of inherited connective tissue diseases, such as Marfans or Ehlers-Danlos syndrome.

What imaging studies will be helpful in making or excluding the diagnosis of bullous lung disease?

Chest imaging is the basis for diagnosing bullous lung disease. Although CXRs may reveal focal areas of radiolucency surrounded by thin curvilinear density, suggesting the presence of bullae, this test is not very sensitive for bullous lung disease. Cross-sectional imaging using CT allows more detailed characterization of the number, size, and location of bullae, as well as the condition of the surrounding lung parenchyma. Characteristic findings of the chest CT include:

  • Air-filled spaces >1 cm in diameter within lung parenchyma with poorly defined or very thin-walled borders (<1 mm).

  • Apical-predominant bullae, which are most commonly associated with emphysema in the surrounding lung parenchyma. Basilar-predominant disease may be associated with alpha-1 antitrypsin deficiency or IV drug use.

  • Bilateral bullae, though asymmetric disease or even unilateral disease is not uncommon.

  • Thin, irregular, linear stranding within the bulla that represent residual strands of alveolar septae or blood vessels.

  • Presence of atelectasis adjacent to a giant bulla (defined as bullae occupying >30% of affected hemithorax); this suggests a favorable prognosis with surgical intervention.

A number of radiographic features should prompt consideration of an alternate diagnosis:

  • Multiple, small, round, clearly demarcated airspaces in the lung parenchyma, particularly in the absence of surrounding emphysema, should raise suspicion for cystic lung disease (e.g., Langerhans cell histiocytosis, lymphangioleiomyomatosis). The clinical context and other imaging findings may help to narrow the differential. For example, multiple cysts in otherwise normal lungs of a young woman with a renal angiomyolipoma are highly suggestive of lymphangioleiomyomatosis. Langerhans cell histiocytosis, which may cause multiple, irregular, air-filled spaces in the upper lung zones of an older smoker, is often mistaken for the far more common bullous emphysema. The presence of multiple nodules or significant fibrosis between air-filled spaces may help distinguish Langerhans cell histiocytosis from bullous emphysema.

  • Thick-walled airspaces within the lung parenchyma or the presence of an air-fluid level within the cavity should prompt consideration of cavitating infection or malignancy with central necrosis. Although bullae may rarely become secondarily infected, infected bullae are far less common than lung abscesses.

  • Focal thickening in one wall of a bulla raises possibility of lung cancer arising in adjacent lung tissue.

  • Significant hilar or mediastinal lymphadenopathy is not seen in uncomplicated bullous lung disease, so its presence may raise suspicion for cavitating infection, malignancy, or possibly fibrocavitary sarcoidosis.

  • On CXR, cystic bronchiectasis associated with cystic fibrosis may be mistaken for bullae, but CT scans clearly demonstrate that the air-filled spaces are dilated airways rather than holes in the parenchyma itself.

  • A CXR in which an acute angle is observed where the edge of the air-filled space meets the chest wall may signal a pneumothorax rather than a bulla. Typically, a bulla meets the chest wall at an obtuse angle.

In severely symptomatic patients, certain imaging features may suggest a favorable outcome from surgical intervention. Features that suggest possible benefit from bullectomy (resection of one or more giant bullae) are a single bulla occupying >30% of hemithorax (>50% is even more favorable), atelectasis adjacent to bulla and absence of significant emphysema in the surrounding lung. Patients that could benefit from lung volume reduction surgery are those with severe apical-predominant emphysema (even without a dominant bulla) and relative preservation of parenchyma in the mid and lower lung zones.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of bullous lung disease?

Pulmonary function testing is not diagnostic of bullous lung disease, but it is critical in evaluating its functional significance, guiding medical therapy, and evaluating the likelihood of benefit from surgical intervention:

  • Spirometry establishes the presence or absence of airflow obstruction and reflects its severity. The forced expiratory volume in 1 second (FEV1) is used to grade severity, as well as selects appropriate candidates for surgical bullectomy (see below).

  • Measurement of lung volumes, specifically total lung capacity (TLC) and residual volume (RV), is used to evaluate for hyperinflation and air-trapping respectively. Because of the frequency of severe air trapping in patients with bullous lung disease, gas dilution methods may underestimate true lung volumes. Consequently, plethysmography when it is available is the preferred method for lung volume measurement.

  • A decreased diffusing capacity for carbon monoxide (DLCO) can support the diagnosis of emphysema or bullous disease, but is nonspecific. The DLCO is also used to select candidates for surgical treatment (see below).

What diagnostic procedures will be helpful in making or excluding the diagnosis of bullous lung disease?

Diagnostic procedures like bronchoscopy and lung biopsies have essentially no role in the evaluation of bullous lung disease.

In patients with severe respiratory impairment and those being considered for bullectomy or lung volume reduction surgery, cardiac testing like echocardiography, stress testing, and cardiac catheterization may be considered as appropriate, in evaluating for pulmonary arterial hypertension. In addition, testing for coexistent ischemic heart disease may be warranted. These conditions may be contraindications for bullectomy and lung volume reduction surgery.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of bullous lung disease?

Testing for alpha-1 antitrypsin deficiency is often performed in patients with bullous lung disease but is not necessary in every case. Clinical context should help guide the decision to test individual patients.

In patients presenting with a strong family history of emphysema (especially early-onset disease), bullous lung disease out of proportion to tobacco history, age at onset < 45, or basilar-predominant bullous disease, an alpha-1 antitrypsin level and phenotype can be considered.

If you decide the patient has bullous lung disease, how should the patient be managed?

The patient with bullous disease should be educated about significance and possible complications related to the presence of bullae. Possibility of spontaneous or traumatic pneumothorax needs to be discussed with the patient and the patient needs to be aware of the severity of this complication and risks of not reacting promptly with a visit to medical care.

When airflow obstruction is present, management of bullous lung disease is the same as COPD:

  • Smoking cessation treatment and lifestyle modifications

  • Pulmonary function testing to assess severity of airflow obstruction and air-trapping

  • Pharmacologic therapy using short- and long-acting bronchodilators, inhaled corticosteroids, or anti-inflammatory agents as appropriate

  • Supplemental oxygen for those with hypoxia on room air

  • Vaccination to reduce complications of infection

  • Pulmonary rehabilitation for symptomatic patients with exercise limitations.

HIV-associated emphysema is treated in the same way as emphysema in non-HIV patients, and the control of HIV infection is likely to reduce otherwise accelerated progression of emphysema. One important exception is that HIV patients taking ritonavir as part of their antiretroviral regimen should use fluticasone with great caution. Ritonavir, a potent inhibitor of cytochrome P450 enzymes in the liver, interferes with the metabolism of fluticasone, causing a marked increase in systemic fluticasone exposure from inhaled or intranasal delivery. As such, co-administration of ritonavir with either inhaled or intranasal fluticasone has been associated with reports of Cushing's syndrome and adrenal suppression. Other inhaled or intranasal steroids appear to be safe in patients who are taking ritonavir.

In addition to standard COPD therapies, patients with bullous lung disease due to alpha-1 antirypsin deficiency may benefit from alpha-1 antitrypsin replacement. Exactly which patients are most likely to benefit and the magnitude of the benefit remain controversial.

Patients with bullous lung disease of any etiology who are of appropriate age (<65) with very severe airflow obstruction (FEV1 ≤25% predicted), poor quality of life despite therapy, and absence of severe comorbid disease may be candidates for lung transplantation.

Selected patients with severe impairment characterized by significant apical-predominant emphysema and severe obstruction with prominent air trapping and dynamic hyperinflation may benefit from lung volume reduction surgery.

Endobronchial valves (EBV) can be used for bronchoscopic lung volume reduction, a method extensively studied over recent years for select patient populations. EBV has been used to treat symptomatic giant bullae with reasonable success in a number of case reports and series. Large trials investigating the use of EBV for treatment of apical-predominant emphysema, such as the VENT study, excluded patients with large bullae. The small number of cases using EBV for treatment of large bullae shows post-procedure increase in FEV1, reduction in TLC, and improvement in symptoms lasting 3-4 years after placement. Furthermore these cases often include patients with FEV1 <40%, a population typically excluded from bullectomy. EBV may be a promising treatment option for patients who are not surgical candidates, particularly those with FEV1 <40%, but additional studies are warranted.

Bullectomy is a classic surgical method for an isolated bulla. It involves surgical resection or ablation of one or more bullae. In carefully selected patients, bullectomy may improve lung function, symptom control, and exercise tolerance.

Bullectomy may help ventilation by allowing more preserved lung to reexpand and reduce atelectasis, help lung mechanics by reducing air-trapping, dynamic hyperinflation, and help chest wall mechanics by reducing diaphragm flattening, barrel chest and work of breathing. As the remaining lung stretches to fill the space previously occupied by the bulla, elastic recoil is increased, helping to pull open small airways and improve expiratory airflow. In this sense, bullectomy is functionally similar to lung volume reduction surgery. However, bullectomy and lung volume reduction surgery are distinct surgical procedures with different indications.

Bullectomy should be considered in patients with severe dyspnea associated with a giant bulla (defined as a bulla occupying >30% of affected hemithorax) and who have had an inadequate response to aggressive medical therapy. Occasionally, bullectomy is performed in patients who present with spontaneous secondary pneumothorax in order to decrease the risk of recurrence.

Several clinical features may impact the likelihood of benefit from bullectomy:

  • Bulla size: Bullectomy may be considered for any patient with a bulla that occupies >30% of affected hemithorax, but case series suggest that bullae that occupy >50% of affected hemithorax may be even more likely to benefit.

  • Condition of adjacent lung parenchyma: Patients with relative preservation of lung parenchyma adjacent to bulla are more likely to benefit from bullectomy than are those with surrounding emphysema.

  • Signs of collapsed adjacent lung: Findings of atelectasis or vascular crowding are associated with a favorable outcome.

  • Moderate to severe obstruction: In published series, most patients who underwent bullectomy had an FEV1 40-80% predicted. In some series, an FEV1 <40% predicted appears to predict lower likelihood of benefit from bullectomy; however, other series report successful outcomes in groups with FEV1 of 32-34% predicted. The available data do not support any absolute contraindications to bullectomy based on FEV1.

  • Air-trapping: Most who undergo bullectomy have a TLC >100% predicted and a RV ≥ 150% predicted (often >200%). Published data do not support any specific cutoffs for these measures in predicting benefit from bullectomy. However, based on the proposed mechanisms, greater degrees of air-trapping likely predict greater benefit.

  • Relatively preserved diffusing capacity: Because diffusion inversely correlates with the degree of emphysema in the surrounding lung, severe diffusion impairment is thought to predict worse outcomes. Some studies have suggested that a DLCO <40% predicted should be a contraindication to bullectomy, but the data supporting this cutoff are limited.

Referring physician should be aware of contraindications to bullecotmy:

  • Excess operative risk: As with any thoracic surgery, advanced age and severe comorbid disease increase risks of surgery and may tip risk-benefit ratio against surgery.

  • Ongoing smoking: Most programs require that potential candidates demonstrate sustained smoking cessation (e.g., four months) prior to consideration of bullectomy.

  • Multiple small or poorly defined bullae: The finding of "vanishing lung" from severe emphysema without a clear, predominant giant bulla, should preclude consideration for bullectomy. In some of these cases, lung volume reduction surgery may still be an option.

  • Severe diffusion impairment: Although supportive data are scarce, DLCO <40% predicted has been suggested as a contraindication to bullectomy.

  • Hypercapnia: A PaCO2 >45 mmHg is often considered a contraindication to bullectomy.

  • Pulmonary hypertension: Pulmonary artery systolic pressure >45 mmHg, especially when associated with right ventricular dysfunction, increases the risk of thoracic surgery.

Regarding the bullectomy itself, it has been performed successfully using several surgical approaches. In a patient who requires bilateral intervention, median sternotomy is often used to allow access to both lungs via one incision. For those who require only unilateral intervention, both open thoracotomy and video-assisted thoracoscopic surgery have been used. No compelling data supports one approach over another, so the choice is based on individual patient factors.

What is the prognosis for patients managed in the recommended ways?

Untreated, the natural history of bullous lung disease is generally one of gradual increase in the size and extent of bullae, as well as gradual progression of dyspnea and airflow obstruction.

However, both the rate and extent of progression over time are highly variable and depend on many factors. Smoking cessation is the most important intervention to slow the progression of bullous lung disease. Rarely, if a bulla becomes infected, it may shrink or even disappear, probably because of cicatricle contraction associated with the inflammatory response.

Symptomatic patients often experience clinically significant improvements in symptom control and exercise tolerance from usual COPD treatment such as bronchodilators, inhaled corticosteroids, and oxygen as needed, and pulmonary rehabilitation.

With smoking cessation and medical therapy, many patients with bullous lung disease experience stabilization of lung function. However, even patients who are aggressively treated may occasionally experience progressive dyspnea, airflow obstruction, exercise limitation, and poor quality of life. In these patients, procedural therapies are often considered.

Patients with bullous lung disease are at increased risk for developing spontaneous secondary pneumothorax because of rupture of blebs or bullae. This risk may be increased further by air travel, but adequate data to quantify this increase in risk are not available.

No controlled clinical trials of bullectomy have been conducted, but published case series suggest that, in carefully selected patients, bullectomy improves symptoms, pulmonary function, and exercise capacity--at least in the short-term in the majority of cases. Emphysema in the lung surrounding the bulla appears to increase the risks of bullectomy and decrease the likelihood of sustained benefit relative to bullae surrounded by relatively normal lung.

However even those with bullous emphysema appear to derive benefit from bullectomy:

  • Dyspnea: Both subjective and objective assessments of dyspnea improve in the vast majority of subjects though the symptomatic response in patients with surrounding emphysema is variable.

  • Spirometry: Published series report improvements in FEV1 of 20-84% over baseline, corresponding to absolute increases of 350-945 mL. Improvements in FVC are less consistently reported.

  • Lung volumes: Changes in residual volume have not been reported in all series, but in two recent series, residual volumes dropped from an average of 226% and 262% predicted at baseline to 87% and 154% predicted, respectively, corresponding to absolute decreases of 1.5-3 liters.

  • Oxygen: Improvements in oxygenation have not been consistently reported, but in two recent series, PaO2 improved by ~10 mmHg on average; one series reported a decrease in the percentage of subjects requiring continuous supplemental oxygen from 42% to 9%.

  • Exercise capacity: Recent series have noted significant improvements in exercise tolerance as measured by six-minute walk distance and cardiopulmonary exercise testing.

Case series following patients for 3-5 years after bullectomy consistently demonstrate that improvements in dyspnea, lung function, and exercise capacity wane over time. However, even after 5 years, these parameters typically remain at least marginally better than baseline values. Subjects with emphysema surrounding their bullae decline faster than do those with relative preservation of the surrounding lung.

Bullectomy does carry risks of complications. Reported operative mortality has ranged between 0-7%; the higher estimate includes all deaths within one year following bullectomy. Causes of death generally reflect those seen commonly in severe COPD, including pneumonia, acute-on-chronic respiratory failure, pulmonary embolism, and myocardial infarction. Patients with diffuse emphysema surrounding their bullae appear to have a higher mortality rate than those with normal surrounding lung.

Prolonged air leak (>7 days) requiring chest tube drainage is by far the most common complication in the immediate post-op period, affecting approximately half of patients. Emphysema in the lung surrounding the bulla appears to increase the risk of prolonged air leak. In a recently reported series of 43 patients, other frequently encountered complications included atrial fibrillation (11.6%), a requirement for post-operative mechanical ventilation (9.3%), massive subcutaneous emphysema (7%), hemothorax (7%), and pneumonia (4.7%).

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