Evaluation and medical management of giant bullae

INTRODUCTION — A bulla is defined as an air space in the lung measuring more than one centimeter in diameter in the distended state. The term giant bulla is used for bullae that occupy at least 30 percent of a hemithorax [1-4]. A single giant bulla may be present, or a giant bulla may be accompanied by a number of smaller adjacent bullae.

The evaluation and management of giant bullae in patients with emphysema will be reviewed here. The general management of chronic obstructive pulmonary disease and the roles of bullectomy, lung volume reduction surgery, and lung transplantation in the management of advanced emphysema are discussed separately. (See "Stable COPD: Initial pharmacologic management" and "Bullectomy for giant bullae" and "Lung volume reduction surgery in COPD" and "Lung transplantation: General guidelines for recipient selection".)

ETIOLOGY — Giant bullae typically develop as a consequence of cigarette smoking, although some are idiopathic and others have less common associations. Marijuana smoking has been associated with giant bullae in a few patients, although this observation may be confounded by concomitant cigarette smoke exposure [5].

Bullous lung disease has also been described in association with HIV infection [6-8] and in intravenous drug users, particularly following injection of methadone, methylphenidate, cocaine [9], or talc-containing drugs, although these relationships are not clearly established. In methylphenidate injectors, the pattern of emphysema is basilar, similar to that seen in patients with alpha-1 antitrypsin deficiency. (See "Overview of pulmonary disease in people who inject drugs", section on 'Bullous lung disease and emphysema'.)

Patients with Marfan syndrome or Loeys-Dietz syndrome occasionally develop apical bullae, but these rarely meet criteria for giant bullae [10,11]. Similarly, bullae have been described in Ehlers-Danlos type IV, polyangiitis with granulomatosis, Sjögren's disease, and sarcoidosis, but usually not giant bullae [10,12-16]. Bullae, including giant bullae, have been reported with COVID-19 infection [17,18]. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders".)

CLINICAL MANIFESTATIONS — Patients with giant bullae may be asymptomatic, dyspneic on exertion, or dyspneic with rest and exertion [19]. Other manifestations of chronic obstructive pulmonary disease (COPD), such as cough and sputum production, may or may not be present.(See "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Symptoms and pattern of onset'.)

Some have characterized a "shrinking lung syndrome" to represent giant bullous disease [8,20-22]. (See "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Shrinking lung syndrome'.)

Patients with an infected bulla typically have symptoms and signs of systemic infection, as described below. Rarely, patients have acute hemorrhage into the bulla with hemoptysis [23,24]. (See 'Fluid-containing bullae' below.)

Physical examination may be normal or may reveal tachypnea, a barrel-shaped chest, hyperresonance on chest percussion, and decreased breath sounds. Findings may be unilateral or bilateral.

EVALUATION — Giant bullae are often detected when a chest radiograph is performed to evaluate dyspnea or symptoms of a respiratory infection; chest computed tomography (CT) is usually needed to exclude a pneumothorax and confirm the presence of a giant bulla. Further evaluation generally includes alpha-1 antitrypsin serum levels, pulmonary function tests, gas exchange assessment, and computed tomography.

Laboratory testing — Routine laboratory testing in the evaluation of giant bullae typically includes the measurement of hemoglobin and hematocrit, an alpha-1 antitrypsin level, and sometimes a room air arterial blood gas.

●The hemoglobin concentration is assessed to exclude anemia as a contributor to dyspnea and to evaluate for secondary polycythemia due to chronic hypoxemia. Polycythemia is suggested by hemoglobin concentrations greater than 16.5 or 18.5 g/dL in females or males, respectively. (See "Diagnostic approach to the patient with erythrocytosis/polycythemia", section on 'Secondary polycythemia'.)

●The diagnosis of severe AAT deficiency is made by demonstrating a serum level of alpha-1 antitrypsin below 11 micromol/L (corresponding to 80 mg/dL in some assays and 50 mg/dL by nephelometry) in combination with confirmation of a severely deficient genotype, generally determined by isoelectric focusing or genotyping. (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency".)

●Arterial blood gases are usually only necessary in patients with severe respiratory impairment and those who are being considered for bullectomy. The arterial partial pressure of oxygen (PaO₂) is usually reduced and the arterial partial pressure of carbon dioxide (PaCO₂) is normal or mildly increased [25,26]. A PaCO₂ greater than 45 mmHg is considered a relative contraindication for bullectomy (table 1) [27,28]. (See "Bullectomy for giant bullae", section on 'Contraindications'.)

Pulmonary function tests — Pulmonary function tests (PFTs) are indicated in all patients with a giant bulla to assess airflow limitation and air trapping. This information is used to guide medical therapy for chronic obstructive pulmonary disease (COPD) and recommendations regarding possible bullectomy (table 1). (See "Stable COPD: Initial pharmacologic management".)

The typical PFT values for patients who undergo bullectomy cover a broad range. In case series of patients who underwent bullectomy, moderate to severe airflow limitation and air trapping were reported [2,3,29,30]. The mean forced expiratory volume in one second (FEV₁) ranged from 32 to 64 percent predicted, FEV₁/forced vital capacity (FVC) ratio 37 to 53 percent, total lung capacity (TLC) 110 to 131 percent of predicted, and residual volume (RV) 226 to 268 percent predicted. (See "Bullectomy for giant bullae", section on 'Indications'.)

The difference in lung volume measurements obtained by the body plethysmography and helium dilution techniques can be compared to estimate the volume of nonventilated lung. A larger nonventilated volume suggests that the patient is likely to derive a greater benefit from bullectomy. Chest computed tomography (CT) scanning provides a direct visual assessment of the extent to which normal lung is compressed by bullae and complements the physiologic measures by indicating the integrity of the remaining unaffected lung. (See "Overview of pulmonary function testing in adults", section on 'Lung volumes'.)

Gas transfer is assessed with a diffusing capacity for carbon monoxide (DLCO) and pulse oximetry. In case series of patients who underwent bullectomy, the baseline DLCO ranged from 57 to 70 percent predicted [2,3,29]. In general, the lower the DLCO, the greater the likelihood that the patient has diffuse underlying emphysema, which increases the risk of bullectomy [28]. Emphysematous changes in the lung surrounding the giant bulla make the lung more fragile and increase the likelihood of air leaks and diffuse emphysema increases general perioperative risks. Thus, a DLCO less than 40 percent predicted is considered a contraindication to bullectomy [28]. (See "Diffusing capacity for carbon monoxide" and "Bullectomy for giant bullae", section on 'Contraindications'.)

Oxygenation is usually assessed by pulse oximetry at rest and during a six-minute walk to quantify the gas exchange abnormality and guide oxygen supplementation. Parameters of oxygenation and exercise tolerance to guide management decisions regarding bullectomy are lacking. In an observational series of patients who underwent bullectomy, the six-minute walk distance was 311 m at baseline, 375 m after pulmonary rehabilitation, and 424 m six months after bullectomy [29]. (See "Lung volume reduction surgery in COPD", section on 'Indications'.)

A cardiopulmonary exercise test may be useful, especially as part of longitudinal assessments for progression, to indicate the degree of impairment capacity, as well as unmask unrecognized cardiac abnormalities. (See "Cardiopulmonary exercise testing in cardiovascular disease".)

Imaging — Giant bullae are typically visible on a plain chest radiograph (image 1), although they may be mistaken for a pneumothorax and the extent of underlying emphysema may not be apparent [31]. Thus, chest CT is typically obtained to confirm the presence of giant bullae, examine the adjacent lung tissue, and rule out a pneumothorax (image 2) [32].

On plain chest radiographs, the characteristics of the pleural line help to differentiate a giant, thin-walled bulla from a pneumothorax. In general, the pleural line associated with a large bulla is usually concave (open angle) relative to the lateral chest wall, whereas the pleural line associated with a pneumothorax is convex (narrow angle) relative to the lateral chest wall (image 1 and image 3). Sometimes a chest radiograph obtained weeks or months in the past will demonstrate the same finding making it less likely that it is a pneumothorax. Lung ultrasonography has also been used to separate the entities [33]. However, the two conditions are more easily differentiated by CT of the chest [34,35]. (See "Treatment of secondary spontaneous pneumothorax in adults" and "Clinical presentation and diagnosis of pneumothorax", section on 'Diagnostic imaging'.)

On chest CT scanning, giant bullae are predominantly located in the upper lobes and are generally subpleural [32,36]. However, in patients with alpha-1 antitrypsin deficiency, the bullae are most commonly located at the lung bases (image 4). (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency".)

About half of the patients have bilateral bullae and half will have predominantly unilateral disease. In the area of lung adjacent to the giant bulla, bronchovascular markings are usually compressed [32]. Occasionally, deviation of the mediastinal structures to the contralateral side may be noted (image 2) [37].

The wall thickness of giant bullae is approximately 1 mm. When the wall is thicker, other possibilities should be considered, such as cavitary mycobacterial or fungal infection, cavitating granulomas, and bronchogenic carcinoma. Bronchogenic carcinoma can arise in the wall of the bulla, causing focal thickening or nodularity, or can present as a cavitating mass with central necrosis.

Bronchoscopy — In general, flexible fiberoptic bronchoscopy is not useful in the routine evaluation of giant bullae unless an associated nodule or mass is noted on CT. In a study that assessed the role of bronchoscopy in 52 patients with fluid-filled bullae, bronchoscopy was performed in two-thirds and was noncontributory in all cases [38].

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS — The diagnosis of a giant bulla is based on imaging studies (chest radiograph or computed tomography [CT]) showing a bulla that occupies at least 30 percent of a hemithorax. Sometimes it is difficult to differentiate a giant bulla from a pneumothorax on the chest radiograph, and a CT scan is needed. (See 'Imaging' above.)

The differential diagnosis of large lung air cysts includes idiopathic giant bullae, COPD, alpha-1 antitrypsin deficiency, Birt-Hogg-Dubé syndrome, and malignancy in the airway causing distal air trapping (eg, adenocarcinoma, sarcomas, pleuropulmonary blastoma) [39]. Diffuse cystic lung diseases (eg, lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis) are usually associated with smaller air cysts and have a perceptible wall, whereas the airspaces in emphysema are not actually cysts and the "walls" are inapparent. The causes of cystic lung disease are discussed separately [40,41]. (See "High resolution computed tomography of the lungs", section on 'Cystic lung disease' and "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency" and "Hereditary kidney cancer syndromes", section on 'Birt-Hogg-Dubé syndrome' and "Sporadic lymphangioleiomyomatosis: Epidemiology and pathogenesis" and "Pulmonary Langerhans cell histiocytosis".)

MANAGEMENT — The management of giant bullae depends on the degree of symptoms and development of complications.

Asymptomatic patients — For patients with asymptomatic giant bullae, the key intervention is smoking cessation to prevent further progression of COPD [42]. Additional medical and surgical therapy is usually deferred pending development of symptoms or other complications. Periodic reassessment of symptoms, pulmonary function tests, exercise tests, and chest radiograph is appropriate, as the natural history of giant bullae is characterized by progressive enlargement and increasing dyspnea [36].

Dyspneic patients — For patients who have symptomatic obstructive airways disease after smoking cessation, the next step is optimization of medical therapy and supportive care (eg, bronchodilators, inhaled glucocorticoids, vaccinations, supplemental oxygen, pulmonary rehabilitation) for COPD. The management of COPD is discussed separately. (See "Stable COPD: Overview of management" and "Stable COPD: Initial pharmacologic management".)

Refractory dyspnea due to giant bulla — For patients whose dyspnea and exercise intolerance persist despite optimization of medical therapy and pulmonary rehabilitation, bullectomy may be beneficial [2,3,29,42-47]. Bullectomy involves the surgical removal of one or more giant bullae by thoracotomy or video-assisted thoracoscopic surgery. (See "Bullectomy for giant bullae", section on 'Potential benefits'.)

The indications, contraindications, technique, and outcomes of bullectomy are discussed separately. (See "Bullectomy for giant bullae".)

For those patients who are incapacitated by dyspnea, but are not candidates for surgical bullectomy, experimental bronchoscopic approaches have been described [48-52]. (See "Bullectomy for giant bullae", section on 'Use of bronchoscopic techniques' and "Bronchoscopic treatment of emphysema".)

COMPLICATIONS — The clinical course of giant bullae may be complicated by pneumothorax, bronchogenic carcinoma, or fluid accumulation within the bulla. The exact incidence of these complications is not known.

Pneumothorax — Secondary spontaneous pneumothorax (SSP) is a well-described complication of giant bullae. The typical presentation is a sudden onset or worsening of dyspnea with or without pleuritic chest pain. When a pneumothorax is suspected, chest computed tomography (CT) scan is key to differentiating a giant bulla from a pneumothorax. (See 'Imaging' above.)

A few case reports have described a pneumothorax occurring when a bronchogenic carcinoma eroded through the wall of a bulla [53]. (See 'Bronchogenic carcinoma' below.)

Patients with a SSP should be hospitalized because the diminished pulmonary reserve due to underlying lung disease increases the risk of an adverse outcome (eg, persistent air leak, hypoxemia, respiratory failure). Tube thoracostomy drainage of pleural air is often needed, depending on the size of the pneumothorax and the degree of respiratory impairment.

Subsequent management is directed at preventing recurrence. For patients with a giant bulla and a SSP, we recommend pleurodesis using mechanical abrasion of the pleura via video-assisted thoracoscopic surgery (VATS). For patients with minimal surrounding diffuse emphysema, a bullectomy is typically performed at the time of pleurodesis. However, for patients with diffuse bullous emphysema, pleurodesis is often performed without bullectomy. Data supporting these choices are lacking. The management of SSP is discussed in more detail separately. (See "Treatment of secondary spontaneous pneumothorax in adults".)

Some clinicians advise bullectomy when a bulla is larger than 50 percent of the hemithorax even when symptoms are minimal, because of the risk of spontaneous pneumothorax. However, prospective data to support this practice are lacking.

Bronchogenic carcinoma — A number of case reports and case series have described bronchogenic carcinoma arising within or adjacent to giant bullae [54-59]. Presenting manifestations include pneumothorax and hemoptysis. However, the carcinoma is sometimes identified incidentally at the time of surgery for resection of a giant bulla or during evaluation of a persistent air-fluid level in the bulla [56].

Several different CT features have been reported for bronchogenic carcinoma associated with giant bullae, including a nodule or mass extruding from the wall of the bulla, a nodule or mass confined within the lumen, a soft-tissue density thickening the wall of the bulla, a pneumothorax, an air-fluid level, and hemorrhage [54,57-60]. A classification system has been suggested, including a nodule abutting a cyst wall, a nodule arising from the cyst wall and protruding into the cyst lumen, a soft tissue density extending or thickening the cyst wall, and a multicystic aspect [61]. Lung cancer detection errors have been associated with overlooking wall thickening of bullae [62].

For patients with these CT findings, tissue examination is generally required for diagnosis. However, studies such as positron emission tomography (PET), alone or integrated with CT, are usually performed to assess the likelihood that a nodule is malignant and the radiographic extent of disease. Flexible bronchoscopy is typically performed preoperatively or intraoperatively to stage the airway. Brushings, washings, and endobronchial biopsy obtained during preoperative bronchoscopy have a low yield when bronchogenic carcinoma is the cause of a small peripheral or intrabulla nodule. Patients with severe dyspnea due to the bulla and underlying COPD will need an assessment of whether bullectomy/lobectomy will improve their respiratory function adequately for them to tolerate resectional surgery. (See "Overview of the initial treatment and prognosis of lung cancer" and "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Bronchoscopic techniques' and "Bullectomy for giant bullae".)

Fluid-containing bullae — The etiology of fluid accumulating in a bulla includes an inflammatory, sterile reaction to an adjacent pneumonia, infection within the bulla, hemorrhage, malignancy, and unknown benign causes [38,57,58,63-65]. In a case series of 52 patients with fluid containing emphysematous bullae, a third of the patients were asymptomatic, 32 percent were febrile, 42 percent had purulent sputum, 43 percent had an adjoining lung opacity, and 10 percent had a severe lung infection [38]. None of the patients in this series had malignancy.

Imaging characteristics — Usually, an air-fluid level is initially noted on a chest radiograph, but ascertainment of the exact location and identity of the structure containing the air-fluid level generally requires a CT scan. The determination that the air-fluid level is in a bulla and not in a newly formed cyst or cavity is based on the new appearance of fluid in a previously identified bulla or the presence of other bullae in a patient with known COPD [38]. CT imaging is also used to identify any surrounding pneumonitis, adjacent pulmonary nodule, or increase in bulla wall thickness or nodularity.

The thickness of the bulla wall on chest CT also helps to differentiate an air-fluid level within a bulla from cavitary diseases such as tuberculosis, fungal disease, lung abscess, or bronchogenic lung cancer. The latter processes typically have substantially thicker cavity walls, than the <1 mm thickness typical of bullae. However, a narrower wall thickness does not entirely exclude the possibility of carcinoma, as bronchogenic carcinoma can rarely arise in the wall of a giant bulla [56,57]. The various manifestations of bronchogenic carcinoma associated with bullae are described above. (See 'Bronchogenic carcinoma' above.)

Benign, sterile bullous fluid — Benign, noninfectious fluid accumulations are thought to result in bleeding or poorly functioning bronchial communications with inadequate drainage of normally accumulating fluid.

●No adjacent pneumonitis or nodule – For patients who are asymptomatic and have a thin-walled bulla without chest CT evidence of an adjacent pneumonitis or nodule, continued observation without specific therapy is usually indicated [38,63]. Repeat evaluation and chest CT scan are typically performed at six to twelve week intervals to ensure that an infection or bronchogenic carcinoma is not being overlooked [57]. Resolution of benign, sterile accumulations may take 10 to 270 days [57,63]. (See 'Bronchogenic carcinoma' above.)

●Adjacent pneumonia — Fluid can develop in a bulla due to inflammation from pneumonia in the adjacent lung parenchyma (analogous to a parapneumonic pleural effusion). For patients with clinical and radiographic evidence of adjacent pneumonia (eg, fever, purulent sputum, leukocytosis, radiographic opacity), antibiotic therapy is indicated, following guidelines for community-acquired pneumonia in a patient with COPD. The air-fluid level may persist for weeks to months after resolution of other clinical evidence of active infection [38]. If the patient has responded clinically to treatment, persistence of fluid in the bulla is not an indication for prolonged antibiotic therapy, but should be followed at intervals until resolution. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Comorbidities, age 65 years or older, or recent antibiotic use'.)

Infected bullae — Patients with giant bullae occasionally develop superimposed infection within one or more bullae without evidence of an adjacent pneumonitis on imaging [38,66,67]. Clinical manifestations may include fever, cough, purulent sputum production, dyspnea, and pleuritic chest pain. Laboratory findings may include leukocytosis and positive sputum cultures. The diagnosis of an infected bulla is based on the clinical evidence of respiratory infection, absence of other source, and presence of new air-fluid level in a bulla. As noted above, bronchoscopy does not appear to be helpful in the evaluation of infected bullae. (See 'Bronchoscopy' above.)

●Initial therapy – When clinical and radiographic findings suggest that a bulla is infected, empiric antibiotics are initiated. The initial choice of antibiotics follows that for community-acquired pneumonia in a patient with COPD. Bacterial species that have been identified from aspiration and culture of bullous fluid include methicillin-resistant Staphylococci (MRSA), Bacteroides, and Pseudomonas aeruginosa [38,64]. The reported range of infecting organisms provides support for direct culture of bullous fluid, when clinically feasible [38,68]. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Comorbidities, age 65 years or older, or recent antibiotic use'.)

The optimal duration of antimicrobial therapy has not been established, but six weeks or longer may be needed. Close clinical and radiographic re-evaluation over the first four to six weeks is generally recommended. If the fluid persists after clinical resolution of infection, malignancy should be excluded. (See 'Malignancy' below.)

●Failure to respond to antibiotics – If a patient fails to improve with empiric antibiotics, percutaneous aspiration of bullous fluid can be performed under CT or fluoroscopic guidance to confirm the presence of infection and to identify the antibiotic sensitivities of the infecting organism [38]. Drainage of infected bullae with a small catheter (eg, 6 to 11.5 Fr catheter) that is left in the bulla for hours to days has been associated with clinical improvement in case reports [66,69-71]. The fluid was manually aspirated or attached to a drainage system (eg, 10 cm negative pressure under water seal) for approximately 24 to 48 hours, although longer durations have been reported [66,71]. As an alternative, the catheter can be placed under thoracoscopic guidance [66]. Catheter drainage of infected bullae carries an increased risk of pneumothorax and empyema if infected bullous fluid spills into the pleural space. However, this risk is lower when the bulla abuts the chest wall. (See "Overview of minimally invasive thoracic surgery".)

Occasionally, after resolution of infection, a giant bulla will collapse on itself and the patient's respiratory function will improve such that spirometry and exercise tolerance are better than prior to the infection [65].

Malignancy — Occasionally, a malignancy is the cause of fluid within a bulla. The fluid may result from tumor debris or local bleeding. More than half of the reported cases of bleeding within a bulla have been associated with a concomitant malignancy [58]. As noted above, clues to the presence of malignancy include persistence of the fluid, a nodule or mass extruding from the wall of the bulla, a nodule or mass within the lumen, or thickening or nodularity of the wall. (See 'Bronchogenic carcinoma' above.)

SUMMARY AND RECOMMENDATIONS

●Definition – A bulla is defined as an air space in the lung measuring more than one centimeter in diameter in the distended state; the term giant bulla is used for bullae that occupy at least 30 percent of a hemithorax. A single giant bulla may be present, or a giant bulla may be accompanied by a number of smaller adjacent bullae. (See 'Introduction' above.)

●Etiology – Giant bullae most commonly develop as a consequence of cigarette smoking, but may be idiopathic or due to other processes such as alpha-1 antitrypsin deficiency, injection drug use, or COVID-19 infection. (See 'Etiology' above.)

●Clinical presentation and evaluation – Giant bullae are often detected when a chest radiograph is performed to evaluate dyspnea or symptoms of a respiratory infection. Further evaluation generally includes assessment of alpha-1 antitrypsin serum levels, pulmonary function tests, gas exchange, and computed tomography. (See 'Evaluation' above.)

●Management – Asymptomatic giant bullae do not require specific therapy, other than smoking cessation. For patients with giant bullae who have symptomatic obstructive airways disease despite smoking cessation, the first step is optimization of medical and supportive therapy for chronic obstructive pulmonary disease (COPD). (See 'Management' above and "Stable COPD: Overview of management".)

●Bullectomy – For patients with inadequate relief of dyspnea with medical therapy and pulmonary rehabilitation for COPD, resection of a giant bulla (also known as bullectomy) may provide a symptomatic and functional improvement. Surgical aspects of bullectomy are discussed separately. (See 'Refractory dyspnea due to giant bulla' above and "Bullectomy for giant bullae".)

●Pneumothorax – Secondary spontaneous pneumothorax is a well-described complication of giant bullae and requires initial hospitalization. Chest computed tomography (CT) scan is key to differentiating a giant bulla from a pneumothorax and clarifying the anatomy. Tube thoracostomy drainage of pleural air is often needed, depending on the size of the pneumothorax and the degree of respiratory impairment. Subsequent management is directed at preventing recurrence. (See 'Pneumothorax' above.)

●Pleurodesis – For most patients with a giant bulla and a secondary spontaneous pneumothorax, we recommend video-assisted thoracoscopic surgery (VATS) with pleurodesis, due to the high risk of recurrence (Grade 1B). For patients with minimal surrounding diffuse emphysema, a bullectomy is typically performed at the time of pleurodesis. However, for patients with diffuse bullous emphysema, pleurodesis may be performed without bullectomy. (See 'Pneumothorax' above and "Treatment of secondary spontaneous pneumothorax in adults".)

●Bronchogenic carcinoma – Bronchogenic carcinoma is another potential complication of giant bullae. The high resolution computed tomography (HRCT) appearance of bronchogenic carcinoma complicating the course of a giant bulla includes a nodule or mass extruding into the lung parenchyma from the wall of the bulla, a nodule or mass confined within the lumen, a soft-tissue density thickening the wall of the bulla, and an air-fluid level. (See 'Bronchogenic carcinoma' above.)

●Air-fluid level – Occasionally, an air-fluid level develops within a giant bulla due to an inflammatory, sterile reaction to an adjacent pneumonia, an infection within the bulla, a malignancy, or an unknown benign process. (See 'Fluid-containing bullae' above.)

●Infected bulla – Initial antibiotic treatment of pneumonia adjacent to a bulla or infection within a bulla follows guidelines for community-acquired pneumonia in a patient with COPD. Rare patients with infection within a bulla require CT guided aspiration to obtain specific culture and sensitivity information. (See 'Infected bullae' above and "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Comorbidities, age 65 years or older, or recent antibiotic use'.)