Diagnosis and management of pleural causes of nonexpandable lung

INTRODUCTION — Nonexpandable lung is present when the lung is unable to expand to the chest wall and achieve visceral and parietal pleural apposition [1,2]. Full expansion of the lung can be prevented by inflammatory or fibrotic processes affecting the visceral pleura or by extrapleural processes such as endobronchial obstruction, chronic lung atelectasis, or processes that will increase the elastic recoil of the lung (ie, interstitial lung disease or lymphangitic carcinomatosis) [2].

The two types of pleural disease that result in nonexpandable lung are lung entrapment and trapped lung. The diagnosis and management of these conditions will be reviewed here. The evaluation of pleural effusions, including those of undetermined etiology, the measurement of pleural pressures, and the physiology of excess pleural fluid production and accumulation are discussed separately. (See "Pleural fluid analysis in adults with a pleural effusion" and "Diagnostic evaluation of the hemodynamically stable adult with a pleural effusion" and "Ultrasound-guided thoracentesis" and "Measurement and interpretation of pleural pressure (manometry): Indications and technique" and "Mechanisms of pleural liquid accumulation in disease".)

DEFINITIONS — The two types of pleural disease that result in nonexpandable lung are lung entrapment and trapped lung. Though the pathophysiology of lung entrapment and trapped lung are different, we prefer the “umbrella term” nonexpendable lung to broadly describe this clinical group of patients. Both of these processes are associated with the presence of pleural fluid.

●Lung entrapment - In lung entrapment, the lung cannot expand fully because of an active disease, such as malignancy or infection that restricts expansion of the lung and/or visceral pleura. The pleural fluid analysis is usually consistent with an exudate.

●Trapped lung - In trapped lung, the lung cannot expand because of a remote inflammatory condition that has left behind a collagenous or fibrous peel on the visceral pleura. The pleural fluid analysis is consistent with a transudate or a protein-discordant exudate and has a mononuclear cell predominance. Most causes of trapped lung begin as a form of lung entrapment. While most cases of lung entrapment resolve with resolution of the inflammatory process, in others, the resolution is incomplete resulting in a trapped lung. Therefore, a trapped lung and lung entrapment may represent a continuum of the same disease process.

In addition to the absence of active pleural disease in patients with trapped lung, these entities can be differentiated by the particular patterns of pleural pressure or elastance (change in pleural pressure divided by the amount of pleural fluid removed) noted during thoracentesis. The key reasons to differentiate these entities are to identify active processes that require specific treatment and to avoid unnecessary pleural procedures in patients with trapped lung. The technique of measuring pleural pressure and the interpretation of the results are discussed separately. (See "Measurement and interpretation of pleural pressure (manometry): Indications and technique".)

INCIDENCE — The incidence of nonexpendable lung is poorly documented. Our experience suggests that among those undergoing thoracentesis, approximately 10 percent have nonexpandable lung, while 20 percent of those undergoing therapeutic thoracentesis and 30 percent of those undergoing therapeutic thoracentesis for malignant pleural effusion have nonexpandable lung [3].

LUNG ENTRAPMENT

Causes — Lung entrapment is most commonly caused by pleural malignancy, but can also be caused by pleural infection or inflammation (eg, rheumatoid pleuritis). Additionally, endobronchial obstruction or parenchymal processes such as pneumonia, or lung cancer can result in a pleural effusion and the lung may not expand due to the increased elastic recoil of the lung. Among malignant causes of lung entrapment, mesothelioma, primary lung cancer, and breast cancer are most common [4-6]. Lung entrapment complicates at least 30 percent of malignant pleural effusions [3].

Pathogenesis — When a malignant pleural effusion is complicated by lung entrapment, fluid formation is due to a combination of increased capillary filtration (leakiness) due to tumor involvement and decreased clearance due to infiltration of draining lymphatics on the parietal pleura. Pleural fluid accumulates until the hydrostatic and oncotic pressure gradients across the visceral and parietal pleura reach equilibrium [7] . Likewise, empyema or complicated parapneumonic effusion may be associated with lung entrapment but the mechanism of persistence of pleural fluid is often dependent on the increased elastic recoil of an atelectatic/consolidated lung and increased fluid production from the visceral pleura as opposed to reduced parietal pleura drainage. These mechanisms are described in more detail separately. (See "Mechanisms of pleural liquid accumulation in disease", section on 'Interplay of pathogenetic mechanisms in disease states'.)

Clinical and laboratory features — Patients with a pleural effusion due to lung entrapment may be asymptomatic though they typically have shortness of breath, decreased exercise tolerance, or chest discomfort. Patients with pleural infection often have fever and may have cough or sputum production. Lung entrapment due to rheumatoid pleuritis may be associated with other clinical manifestations of rheumatoid arthritis, although pleural disease can be the presenting manifestation. (See "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis" and "Clinical manifestations of rheumatoid arthritis".)

A key feature of lung entrapment is that although dyspnea typically improves with thoracentesis, the underlying lung does not fully expand radiographically after draining the pleural fluid. It is important to understand that if patients experience an improvement in dyspnea, even if the lung does not re-expand, they can achieve significant pleural palliation by placement of indwelling pleural catheters (IPCs).

Some patients may develop chest discomfort during therapeutic thoracentesis despite having a considerable amount of residual pleural fluid [8]. It is thought that the chest discomfort is related to the negative pleural pressure created in the pleural space when the lung does not re-expand to fill the space created by fluid removal. (See "Imaging of pleural effusions in adults", section on 'Conventional radiography'.)

The pleural fluid is typically exudative [9]. When lung entrapment is caused by pleural malignancy, malignant cells may be present on cytology.

Imaging — Lung entrapment may be identified during imaging studies after pleural drainage. On computed tomography or ultrasound, the visceral pleural surface may appear nodular, thickened, or hyperechoic and the pleural fluid is often hyperechoic and/or loculated [10]. (See "Imaging of pleural effusions in adults", section on 'Malignant pleural effusion'.)

Diagnosis — The presence of lung entrapment is not always obvious but sometimes can be suspected during the initial evaluation of a pleural effusion. In the presence of a large effusion, contralateral shift of the mediastinum is expected. If the mediastinum is not shifted, or is shifted ipsilaterally, lung entrapment should be suspected. The diagnosis should also be suspected when a patient with known rheumatoid arthritis, empyema, or malignancy presents with a pleural effusion. Identification of lung entrapment in a patient with a malignant pleural effusion is important, because if the lung cannot re-expand, pleurodesis will likely not be successful. In this case, IPCs are an option for management of dyspnea in these patients [11].

Lung entrapment may also be suspected if there is a lack of lung re-expansion with thoracentesis. Computed tomography of the chest can help exclude extrapleural causes of nonexpandable lung (image 1).

When lung entrapment is suspected, support for the diagnosis is provided by compatible elastance findings (ie, a decrease in pleural pressure of -20 cm H₂O or lower per liter of fluid removed) and an increased pleural elastance measured at the end of thoracentesis when minimal pleural fluid remains (ie, the terminal elastance) (figure 1 and figure 2) [8,9,11]. The technique of measuring pleural pressure and the interpretation of the results are discussed separately. (See "Measurement and interpretation of pleural pressure (manometry): Indications and technique".)

After a thoracentesis, nonexpandable lung should be suspected if a post-thoracentesis radiograph shows air in the pleural space, especially when it appears at the base of the lung. The presence of air may not indicate pneumothorax due to a puncture of the visceral pleura but may point to the entry of air alongside the pleural drainage catheter, or from small visceral pleural defects that are created by local deformation forces in response to the negative pleural pressure generated when the lung cannot re-expand to fill the hemithorax [12]. Post-drainage imaging may also reveal visceral pleural thickening.

Direct visualization via thoracoscopy may confirm the diagnosis, but is usually only necessary when the cause of nonexpandable lung is unclear or the patient has refractory symptoms. Ideally, this would be performed under general anesthesia with positive pressure ventilation so that the anesthesiologist could inflate the lung under direct vision. Occasionally, the diagnosis of nonexpendable lung only becomes apparent at the time of a thoracoscopy performed to evaluate a persistent undiagnosed effusion. That being said, it can be difficult to predict nonexpandable lung at the time of medical thoracoscopy, which is commonly performed during spontaneous (ie, negative inspiratory pressure) breathing [13]. (See "Medical thoracoscopy (pleuroscopy): Equipment, procedure, and complications" and "Medical thoracoscopy (pleuroscopy): Diagnostic and therapeutic applications".)

Treatment — In general, the treatment of lung entrapment is focused on treating the underlying disease process (eg, infection, inflammation, malignancy). For patients with a treatable underlying condition such as infection or inflammation, lung entrapment often resolves with treatment of the underlying process (eg, antibiotics, anti-inflammatory drugs). (See "Overview of pleuropulmonary diseases associated with rheumatoid arthritis", section on 'Treatment of rheumatoid pleural effusion' and "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults".)

Lung entrapment due to pleural malignancy rarely responds to chemotherapy [1]. Since the dyspnea of pleural effusions is not related to lung collapse, low oxygen levels or loss of FEV₁, but is more likely a chest wall phenomenon due to flattening and inefficiency of the length-tension relationship of the diaphragm, patients with lung entrapment can achieve significant improvements in dyspnea after pleural fluid drainage despite lack of lung expansion [14]. Options for managing lung entrapment in this setting include placement of an indwelling tunneled pleural catheter, occasionally placement of a pleuroperitoneal shunt, and rarely pleurectomy/decortication which is associated with a high morbidity and mortality. It should be noted that approximately 50 percent of patients who have cancer-related nonexpandable lung treated with IPCs achieve lung re-expansion after six months [15].

Recurrent symptoms after relief of dyspnea with thoracentesis — Symptomatic improvement with thoracentesis suggests efforts to reduce pleural fluid accumulation will provide continued symptomatic relief. Because patients with malignancy may have many causes of dyspnea (ie, pulmonary emboli, deconditioning, airway obstruction), if patients do not feel better after thoracentesis, causes other than the effusion should be investigated.

●Pleurodesis ─ Pleurodesis is commonly used to treat recurrent and persistent malignant pleural effusions without lung entrapment. However, it is unlikely to be successful in patients with entrapped lung, because the lung is unable to expand adequately to achieve apposition between the parietal and visceral pleura. One study found that pleurodesis failed in all 19 patients with pleural malignancy and lung entrapment demonstrated by a drop in pleural pressure greater than 19 cm H₂O after removal of 500 mL of pleural fluid (38 cm H₂O/L) [11]. (See "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)'.)

●Indwelling pleural catheter ─ For patients who have symptomatic improvement with removal of pleural fluid, the recommended treatment is implantation of an indwelling pleural catheter for intermittent drainage at home [16-20]. IPCs are less invasive than placement of pleuroperitoneal shunt and avoid frequent visits for therapeutic thoracentesis. Indwelling pleural catheters are also used for patients with malignant pleural effusions without lung entrapment [21]. (See "Management of malignant pleural effusions", section on 'Indwelling pleural catheter (IPC)'.)

Placement of indwelling pleural catheters is performed under moderate sedation with local anesthesia or local anesthesia alone. In a series of 250 patients with lung entrapment due to pleural malignancy, placement of an indwelling pleural catheter resulted in partial or complete symptomatic improvement in the majority. The risk of infection with IPCs, even in patients receiving chemotherapy, is quite low (approximately 5 percent) [22].

●Pleuroperitoneal shunt ─ Insertion of a pleuroperitoneal shunt is a rarely used option for patients with lung entrapment who do not want a chronic transcutaneous device with the accompanying need for special cleaning and drainage [4,16,23,24]. These shunts are placed via thoracoscopic guidance under general anesthesia. In the hands of experienced operators, placement of a pleuroperitoneal shunt is reasonably safe, although shunt-related complications (eg, infection, occlusion) occur in approximately 15 percent. Because pressure is generally higher in the peritoneal than in the pleural space, the patient must compress the pump chamber multiple times a day to move fluid "uphill." (See "Management of malignant pleural effusions", section on 'Shunt'.)

In general, we prefer using an indwelling pleural catheter rather than a pleuroperitoneal shunt due to the fewer problems and less invasive process for placement of indwelling pleural catheters.

Inadequate improvement with pleural fluid removal — Patients with lung entrapment due to malignancy and inadequate or no improvement with pleural fluid removal generally do not require pleural palliation. Other causes of dyspnea, such as pulmonary embolism, however, need to be investigated.

TRAPPED LUNG — Trapped lung develops when the visceral pleura becomes encased with a fibrous peel or rind, but the inflammation that led to development of the rind has resolved. The incidence of trapped lung is unknown but is probably much higher than is generally recognized.

Causes — The event producing the initial pleural inflammation is usually pneumonia or a hemothorax, but other causes include spontaneous pneumothorax, thoracic operations including coronary artery bypass surgery, uremia, and rheumatoid pleuritis [25-27]. Trapped lung can also be a late consequence of nonmalignant lung entrapment, if the underlying inflammatory condition is successfully treated but the restricting fibrinous peel becomes organized into a fibrous peel with wide separation of the visceral and parietal pleurae. Rarely, patients with heart failure develop a trapped lung and a pleural effusion if they have a pleural effusion for many months [28].

Pathogenesis — In trapped lung, the fibrotic process affecting the visceral pleura prevents the lung from expanding to fill the thoracic cavity when pleural fluid is removed. In this situation, the negative pleural pressure increases the entry of liquid into the space and reduces the exit of pleural fluid by pleural lymphatics and, thereby, leads to the formation of the effusion. Consequently, a steady state of fluid formation and removal is established, leading to persistence of a negative pressure pleural effusion of constant volume. The sole mechanism for the persistence of the pleural effusion is mechanical and can be considered a "pleural effusion ex-vacuo," that is, it is the negative pleural pressure that causes the pleural effusion [28,29]. (See "Mechanisms of pleural liquid accumulation in disease", section on 'Extrinsic factors'.)

Clinical and laboratory features — The majority of patients with trapped lung do not have symptoms referable to the pleural effusion. These patients typically present for a routine examination, are found to have findings consistent with an effusion (decreased breath sounds, dullness to percussion, and decreased fremitus) and are referred for a thoracentesis. These patients will typically have discomfort throughout the thoracentesis due to further reductions in intrathoracic pressure. Some patients, however, complain of shortness of breath due to a restrictive ventilatory defect. Symptoms of acute pleural inflammation such as pleuritic chest pain or fever are rarely present, but a careful history will often elicit these symptoms in the remote past.

Over time, the size of an effusion due to trapped lung remains remarkably constant [30]. If thoracentesis is performed, the effusion recurs rapidly. The pleural fluid lactic dehydrogenase (LDH) is usually in the transudative or borderline exudative range, while pleural fluid protein may be either in the transudative or exudative range. Typically, the pleural fluid white blood cell count is relatively low and primarily consists of mononuclear cells. (See "Pleural fluid analysis in adults with a pleural effusion".)

Imaging — Imaging studies such as upright and decubitus radiographs, chest computed tomography (CT), and ultrasound of trapped lung often show visceral pleural thickening and loculation; the fluid may shift somewhat with changes in position but will not be free flowing. The paradoxical finding that the hemithorax with the effusion is reduced in size compared to the contralateral side suggests that pleural pressure on the affected side is more negative than on the opposite side, providing further evidence for the diagnosis of trapped lung. (See "Imaging of pleural effusions in adults", section on 'Loculated pleural effusions'.)

As mentioned for entrapped lung, a post-thoracentesis radiograph can show air in the pleural space (see 'Lung entrapment' above). In the situation of trapped lung, the air can appear with the same size and shape as the prior effusion; in this setting, the air does not represent a complication of thoracentesis, but replacement of the fluid by air which has entered due to the low pressure, probably along the catheter tract or due to a minor break in technique [12].

In some patients, the visceral pleural rind associated with trapped lung is difficult to visualize on routine CT. To improve visualization of the pleural rind, an air contrast CT can be performed by injecting 200 to 400 mL of air at the termination of a therapeutic thoracentesis and obtaining a chest CT [27,30]. The air in the pleural space allows a clear demarcation on CT images of the thickness of the visceral pleura, and will also allow for an increase in the negative pleural pressure, alleviating the patient's discomfort. In a case series, air contrast CT allowed visualization of visceral pleural rinds that were less than 3 mm, which is thicker than the minimally visible normal pleura but difficult to visualize in the absence of air contrast [27]. After injection of air into the pleural space, travel and scuba diving must be avoided until the air is mostly absorbed, although this maneuver is controversial.

Diagnosis — The diagnosis of trapped lung should be suspected in any patient with a stable chronic pleural effusion, particularly if there is a history of pneumonia, pneumothorax, thoracic surgery, or hemothorax. If there is a suspicion of trapped lung, assessment of intrapleural pressure during thoracentesis can determine whether features of trapped lung are present [8,30,31]. In patients with trapped lung, the initial pleural pressure is usually slightly negative, and the pressure decreases quickly as pleural fluid is withdrawn [1]. These patients typically have pain/discomfort throughout the procedure. The pleural space elastance (change in pleural pressure divided by the amount of pleural fluid removed) exceeds 14.5 cm H₂O/L in the presence of trapped lung [27] (figure 1). (See "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Technique' and "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Interpretation of pleural pressures'.)

The diagnosis of trapped lung based on pleural pressures can be complicated in patients with more than one cause of pleural effusion. As an example, a patient may have heart failure with hydrostatic accumulation of pleural fluid in addition to trapped lung. In this situation, the initial pleural elastance is normal, correlating with partial lung re-expansion when fluid due to the hydrostatic component is removed, but the terminal elastance is abnormally high correlating with the presence of nonexpandable lung [1,27]. (See "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Pleural elastance' and "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Interpretation of pleural pressures'.)

The presence of characteristic pleural pressure changes is strongly suggestive of trapped lung and may be sufficient diagnostically in patients with minimal or absent symptoms. However, confirmation that visceral pleural thickening (a pleural rind) is present requires direct visualization via video-assisted thoracoscopy or air contrast CT. (See 'Imaging' above.)

Management of trapped lung — The management of a pleural effusion caused by trapped lung largely depends on the patient's symptoms. As the majority of patients are asymptomatic, no further therapy is indicated, because performing further pleural drainage procedures will just lead to fluid reaccumulation [30]. Rarely, a patient's quality of life is limited by shortness of breath because the constricting fibrous rind involves a large portion of the lung causing a restrictive ventilator defect. For these patients, decortication of the visceral pleura (removal of fibrous pleural rind) may allow re-expansion of the trapped lung and resolution of the dyspnea [1,32].

The evidence in favor of decortication comes from case reports, small case series, and clinical experience [1,26,27]. In a series of patients with trapped lung following coronary artery bypass grafting, three of the four patients who underwent decortication had successful lung re-expansion [26].

Prior to decortication, other potential causes of dyspnea should be excluded by noninvasive testing (see "Approach to the patient with dyspnea"). As an example, a patient with rheumatoid pleuritis may have underlying interstitial lung disease (ILD) that may contribute to their dyspnea. In that case, high resolution computed tomography (HRCT) of the chest can be used to assess for ILD in the underlying lung parenchyma. Finally, candidates for decortication need to be acceptable surgical candidates who understand the risks associated with general anesthesia and thoracotomy or thoracoscopy.

SUMMARY AND RECOMMENDATIONS

●Lung entrapment

•Lung entrapment refers to visceral pleural restriction caused by an active process (malignancy, infection or inflammation). (See 'Definitions' above.)

•The diagnosis of lung entrapment is suspected when a patient with known rheumatoid arthritis, empyema, or malignancy presents with a pleural effusion and the lung does not fully re-expand with pleural fluid drainage. (See 'Clinical and laboratory features' above.)

•In patients with lung entrapment, direct measurement of pleural pressure at the time of thoracentesis reveals a gradual decrease in pressure as fluid is withdrawn, culminating in a steep decrease in pressure when minimal fluid remains in the pleural space. (See 'Diagnosis' above and "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Interpretation of pleural pressures'.)

•Compatible pleural pressure findings are strongly supportive of the diagnosis of lung entrapment. Direct visualization by thoracoscopy to confirm the diagnosis is performed when the cause of lung entrapment is unclear or the patient has refractory symptoms. (See "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Interpretation of pleural pressures' and 'Diagnosis' above.)

•In general, the treatment of lung entrapment is focused on treating the underlying disease process (eg, infection, inflammation, malignancy). (See 'Treatment' above.)

•For patients with dyspnea due to a malignant pleural effusion with lung entrapment and a pleural elastance greater than 38 cm H₂O/L (after the first 500 mL of fluid removed), pleurodesis is unlikely to be successful. For such patients who obtain at least partial relief of symptoms after thoracentesis, we recommend implantation of an indwelling pleural catheter for intermittent drainage at home, rather than placement of a pleuroperitoneal shunt or decortication (Grade 1B). Placement of an indwelling catheter is preferred because IPC placement is less invasive and has fewer complications. (See 'Recurrent symptoms after relief of dyspnea with thoracentesis' above.)

•A very few carefully selected patients with lung entrapment due to malignancy who have improvement in dyspnea after pleural fluid removal, are good surgical candidates. These patients have a slowly progressive malignancy with a long expected survival. In such patients, we suggest consideration of decortication (removal of pleural rind) with pleurectomy (resection of visceral and parietal pleura) (Grade 2C). (See 'Inadequate improvement with pleural fluid removal' above.)

●Trapped lung

•Trapped lung results when the visceral pleura becomes encased with a fibrotic rind that prevents re-expansion of the lung. (See 'Definitions' above.)

•Causes of pleural inflammation that eventually lead to trapped lung include pneumonia with parapneumonic effusion (bacterial and mycobacterial), hemothorax, spontaneous pneumothorax, thoracic operations including coronary artery bypass surgery, uremia, and rheumatoid pleuritis, however, active pleural inflammation is generally not present. (See 'Causes' above.)

•Many patients with trapped lung do not have symptoms referable to the pleural effusion, although some patients complain of shortness of breath due to a restrictive ventilatory defect. Symptoms of acute pleural inflammation such as pleuritic chest pain or fever are generally absent. (See 'Clinical and laboratory features' above.)

•On chest radiography of trapped lung, the hemithorax with the effusion is reduced in size, indicating that the pleural pressure on the side with the effusion is more negative than that on the contralateral side. Computed tomography (CT) often reveals loculation and pleural thickening, although sometimes pleural thickening is only apparent on an air contrast CT. (See 'Imaging' above.)

•In patients with trapped lung, direct measurement of pleural pressure at the time of thoracentesis usually reveals a negative initial pressure. With fluid removal, a rapid decrease in pleural pressure occurs, correlating with a pleural elastance (change in pleural pressure divided by the amount of pleural fluid has been removed) greater than 14.5 cm H₂O/L (often greater than 25 cm H₂O/L). (See 'Diagnosis' above and "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Interpretation of pleural pressures'.)

•The presence of characteristic pleural pressure changes is strongly suggestive of trapped lung and may be sufficient diagnostically in patients with minimal or absent symptoms. However, confirmation that visceral pleural thickening (a pleural rind) is present requires air contrast CT or direct visualization via video-assisted thoracoscopy. (See 'Diagnosis' above and "Measurement and interpretation of pleural pressure (manometry): Indications and technique", section on 'Interpretation of pleural pressures'.)

•For patients who have asymptomatic trapped lung, pleural drainage procedures are NOT indicated, because the pleural fluid will reaccumulate due to the negative pleural pressure. (See 'Management of trapped lung' above.)

•For patients without malignant pleural effusion who are surgical candidates and have disabling shortness of breath due to trapped lung, we recommend decortication of the pleural rind on the visceral pleura (Grade 1B). (See 'Management of trapped lung' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Peter Doelken, MD, FCCP, who contributed to an earlier version of this topic review.

The UpToDate editorial staff also acknowledges Richard W Light, MD, now deceased, who contributed to an earlier version of this topic review.