Definition

Pleural disease refers to pathology of the pleural space: a space which lies between the visceral and parietal pleura on the outside of the lung parenchyma but within the thoracic cavity. Pleural disease typically comes in 2 forms: pleural effusion and pneumothorax. 

• Pleural effusion: increased volume of fluid within the pleural space either by increased production or reduced absorption of fluid.
• Pneumothorax: air in the pleural cavity.

References

• Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Pleural Effusion 

Background

Epidemiology

Pleural effusions are a common pathology seen in respiratory medicine, with approximately 200,000 new cases in the UK each year with over 50 underlying aetiologies spanning a breadth of medical specialities. Pleural effusions can largely be categorised into 2 forms: transudative and exudative. The most common underlying cause of a transudative pleural effusion is heart failure, whereas the most common cause of an exudative effusion is pneumonia. 

Pathophysiology

In normal physiological circumstances, the volume of pleural fluid is carefully governed by a balance between liquid into the pleural space (via the parietal pleura) and liquid outflow (via the parietal and visceral pleura). A small amount of fluid (estimated at 10-20mL, or 0.3mL/kg) is always present within the space to allow effective ventilation of the lungs. Several mechanisms help maintain this tightly controlled volume: Starling forces at the visceral pleura, lymphatic drainage at the parietal pleura and “electrolyte-coupled liquid absorption” via the mesothelium on both visceral and parietal pleura. 

Pleural effusions result from either increased pleural fluid production or impaired absorption via a) a change in the transpleural pressure balance and subsequently Starling’s forces, b) impairment of the lymphatic system or c) change in mesothelial permeability. 

Transudates 

Transudative pleural effusions result from increases in the systemic capillary pressure in the setting of congestive cardiac failure. This increased capillary pressure changes hydrostatic and oncotic pressures across the pleura, thus altering the normal equilibrium seen, i.e., Starling’s forces. This alteration results in pleural fluid production exceeding its absorption and resultant accumulation. As the mesothelium remains largely unaltered, protein and cell leakage into the fluid is minimal. 

Transudative pleural effusions secondary to chronic liver disease and nephrotic syndrome also result from a change in Starling’s forces at the capillary membrane, but in these cases, it is a reduction in oncotic pressure from hypoalbuminaemia. This drives the balance in favour of hydrostatic pressure, and subsequently, fluid is moved into the pleural space. 

Exudates 

Exudative pleural effusions are either a result of impaired protein and cell removal from the pleural space (via the lymphatic system) or from increased permeability of the mesothelial membrane to water and small solutes. This results in fluid accumulation that is high in cell number and protein within the pleural space.

Specifically, in parapneumonic exudative effusions (the most common form of exudative pleural effusion) it is the direct result of inflammatory-mediating cytokines and cells interacting with the mesothelial membrane, which increase its permeability to cells and protein. At times, this inflammatory-mediated damage to the mesothelium can be so significant that bacteria can enter the pleural space, resulting in the formation of an empyema (pleural infection). 

Presentation

Pleural effusion presentation can be variable due to several changeable factors (size of effusion, how quickly the effusion accumulated, its underlying cause), but the overwhelmingly common symptom is “shortness of breath.” A detailed history of the shortness of breath should be undertaken to determine character, speed of onset, duration and how limiting the symptomology is on activities of daily living. Given there is a significant range of pathologies that pleural effusions can be associated with, there is also variety in the associated symptoms. 

Important associated symptoms to consider would include presence of – 

• Constitutional symptoms (fever, night sweats, weight loss), 
• Cough and sputum production
• Recent travel history 
• Past medical history (including specifically if any current or previous cancer diagnosis), 
• Occupational history
• Smoking history. 

Signs

On clinical examination, reduced chest expansion may be noted, either unilaterally or bilaterally, dependent on the underlying effusion aetiology. The typical finding described is “stony” dull percussion over the area of the pleural effusion with associated reduced breath sounds. Bronchial breathing can also be present just superior to the uppermost point of the effusion. In massive pleural effusion tracheal deviation away from the side of effusion can also be seen. 

In addition to the effusion itself, clinical examination can give clues to the underlying aetiology: 

Clinical Sign	Possible associated aetiology
Clubbing, cachexia and tar staining	Bronchial carcinoma
Productive cough, fever	Pneumonia/ empyema
Peripheral oedema, raised JVP and displaced apex beat	Congestive cardiac failure
Multiple spider naevi (>5), palmar erythema, jaundice	Hepatic failure
AV fistula, renal transplant	Renal failure
Swan neck deformity, Boutonniere deformity	Rheumatoid arthritis

Table 1: Clinical features with their associated underlying aetiology. 

Table 1: Table adapted from – 

Bhatnagar R, Maskell N. The modern diagnosis and management of pleural effusions. BMJ. 2015;351(September).

Saguil A, Wyrick K, Hallgren J. Diagnostic approach to pleural effusion. Am Fam Physician. 2014;90(2):99–104.

Diagnosis 

A diagnosis of pleural effusion should be considered in any patient presenting to hospital with shortness of breath. The combination of history and thorough physical examination revealing findings, as detailed above, should alert the clinician to the possibility of an underlying pleural effusion. 

Chest x-ray 

Plain posteroanterior (PA) chest x-rays are the first-line imaging modality used in suspected pleural effusion and become abnormal with around 200mL of pleural fluid accumulation. The fluid results in blunting of the costophrenic angle with associated development of the meniscus. If there is air associated with the pleural effusion, called a hydropneumothorax, a straight line at the air-fluid interface will be seen, rather than a meniscus.

Image Source: Wikimedia Commons (2022). Pleural Effusion, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/Category:Pleural_effusion (Accessed on: 17 May 2022).

Image Source: Wikimedia Commons (2017). Bilateral Pleural Effusion, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/3/34/Bilateral_Pleural_Effusion.jpg (Accessed on: 17 May 2022).

Image Source: Wikimedia Commons (2017). Hydropneumothorax, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/7/7d/HydropneumoX.png (Accessed on: 17 May  2022).

Ultrasound 

Bedside pleural ultrasound can be used to identify pleural effusions and be utilised to identify a site for diagnostic aspiration of pleural fluid. It is particularly useful in the diagnosis of small pleural effusions, which may not be evident on a plain radiograph. In addition to its uses for ultrasound-guided diagnostic aspiration of pleural fluid, ultrasound can be used to determine additional characteristics of the fluid, e.g. septations, which may be suggestive of an underlying malignant or infective effusion.

Diagnostic Aspiration 

Diagnostic aspiration is the key diagnostic test in evaluating a unilateral pleural effusion. British Thoracic Guidelines (BTS) state this should be a bedside direct ultrasound-guided aspiration of fluid in the most lateral position possible to reduce associated complications. A 50mL sample of fluid is obtained and sent for: 

• Protein
• Lactate dehydrogenase 
• Gram staining
• Microbiology culture
• Cytology 
• pH (if an infected pleural effusion is suspected)

On aspiration, pleural fluid can take on many appearances. “Normal” pleural fluid is straw-coloured and inodorous. However, in the setting of pathology, many different appearances of pleural fluid can be noted, including blood-strained, frank blood, purulent (suggesting empyema), milky (suggesting chylothorax) or bile-stained.

Flowchart adapted from guidance available at – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Pleural Effusion Fluid Analysis 

The key distinction pleural fluid analysis attempts to achieve is exudative vs. transudative pleural effusions. This distinction allows a narrowing of the differential diagnosis (see below). 

Pleural fluid protein (g/L) measurement is the key to differentiating between transudates and exudates. Pleural fluid protein >30g/L is considered exudative and protein <30g/L is considered transudative. However, the closer the level is to 30g/L, the less accurate this distinction becomes. In order to achieve a distinction between transudate and exudate in this setting we employ Light’s Criteria:

• Pleural fluid protein to serum protein ratio >0.5 
• Pleural fluid LDH to serum LDH ratio >0.6 
• Pleural LDH >0.67 x upper limit of normal for serum LDH

If any one of these criteria are met, an exudative pleural effusion diagnosis can be made. Lactate dehydrogenase is utilised in Light’s Criteria as it is a non-specific marker of inflammation – a key component of exudative pleural effusion pathology.

Microscopy, Culture and Sensitivity 

Microscopy, culture and sensitivity (M, C + S) is the gold-standard test that is sent with all diagnostic pleural aspirations as per BTS guidelines. TB cultures can be sent in addition if this is suspected in order to look for acid-fast bacilli. 

Cell differential is widely reported to be of limited diagnostic benefit as, in the majority of cases, the differential diagnosis remains wide. Pleural fluid can be predominantly lymphocytic, neutrophilic or eosinophilic. 

• Lymphocytic. Defined as >50% of pleural fluid cells being lymphocytes. In this instance differentials to consider would be tuberculosis (TB) and malignancy. If a significantly raised lymphocyte count is noted (>80%), this should prompt the clinician to think about TB, as well as rheumatological conditions: rheumatoid arthritis (RA) and sarcoidosis. 
• Neutrophilic. This is seen in acute processes and, most commonly, in parapneumonic effusions.
• Eosinophilic. Defined as >10% of pleural fluid cells, and the differential remains wide, but the most common cause is pneumothorax (air in the pleural space) or haemothorax (blood in the pleural space). Rarer conditions, such as eosinophilic granulomatosis with polyangiitis (EGPA), can cause eosinophil-predominant pleural effusions.

Specific Diagnostic Tests of Pleural Effusion 

• Amylase. A raised amylase within pleural fluid is highly sensitive for pancreatic disease, oesophageal rupture or malignancy. The presence of a raised pleural fluid amylase (defined as any pleural amylase level above the limit of normal) narrows the differential significantly to these conditions. 
• Triglycerides. High levels of pleural fluid triglyceride concentrations >110mg/dL are diagnostic of chylothorax. 
• Cholesterol. Significantly raised cholesterol (>250mg/dL) aids with diagnosis of a pseudochylothorax.
• pH. pH can be utilised in suspected non-purulent pleural infections (empyema). Normal pleural pH is around 7.60, and pleural fluid acidosis is defined as a pH <7.30 and can be seen in a range of causes: malignancy, TB and connective tissue disease. A pleural fluid pH of <7.2 though is highly suggestive of an empyema and should be treated as per pleural infection guidelines (see “Management” below). 
• Cytology. Cytological analysis can be utilised in patients with pleural effusions suspected to be secondary to malignancy and has a sensitivity of around 60%. The presence of malignant cells within a pleural fluid sample is the gold standard diagnostic test for malignant pleural effusions.

Differential Diagnosis 

The aetiology of pleural effusion is wide, with over 50 aetiologies possible spanning multiple medical specialities. A thorough clinical history, examination and diagnostic approach helps narrow the differential diagnosis. The table below is by no means exhaustive but incorporates important differentials to know for the MRCP exams.

Aetiology	Transudate or Exudate	Other pleural fluid characteristics	Clinical clues
Cardiovascular
Heart Failure	Transudate	Straw-coloured (pale yellow). Typically bilateral. Occasionally, lymphocytosis is noted on cell differential of pleural fluid.	Pulmonary or peripheral oedema Raised pro-brain natriuretic peptide (pro-BNP) level.
Gastrointestinal
Liver cirrhosis	Transudate	Straw-coloured.	Signs of chronic liver disease. Ascites. History of alcohol excess/ viral hepatitis/ non-alcoholic fatty liver disease (NAFLD).
Nephrotic syndrome	Transudate	Straw-coloured.	Generalised anasarca. Proteinuria/ haematuria.
Pancreatitis	Exudate	Pleural fluid amylase above the limit of normal reference range.	Epigastric tenderness. Raised serum amylase. History of common underlying cause of pancreatitis: gallstones/ alcohol excess.
Genitourinary
Meigs syndrome	Transudate	Straw-coloured.	History of ovarian fibroma. High serum Ca-125.
Oncology
Malignancy	Exudate* (* exception – Meigs syndrome)	Positive cytology	History of underlying malignancy (lung most common, followed by lymphoma). Weight loss. History of smoking/ tar staining/ clubbing.
Respiratory
Parapneumonic effusion	Exudate	Turbid appearance. Neutrophil-predominance. pH of fluid normal.	Associated fever/ productive cough. Consolidative changes on chest x-ray.
Tuberculosis	Exudate	Lymphocytosis. Acid-fast bacilli (but visualised in <5%). Very high protein (>50g/L) and LDH levels.	Travel history. Weight loss/ fevers/ haemoptysis. Chest x-ray or thoracic imaging suggestive of TB. Positive sputum for AAFBs.
Malignant mesothelioma	Exudate	Abnormal mesothelial cells with positive cytogenetic analysis.	Asbestos exposure previously.
Yellow nail syndrome	Exudate	Clear pleural fluid. Lymphocytosis.	Dystrophic changes to nails. Recurrent infections.
Rheumatology
Rheumatoid arthritis	Exudate	Very low pleural fluid glucose level (typically <1.6mmol/L). High cholesterol. Low pH <7.30. Milky appearance if pseudochylothorax.	Rheumatoid arthritis signs on peripheral examination: swan neck deformities, Z-thumb, for example.
SLE	Exudative	Can be unilateral or bilateral. No distinctive biochemical features noted.	Multi-system disorder with evidence of photosensitive rash/ arthropathy/ Raynaud’s, for example.
Other
Chylothorax	Exudative	Milky appearance. High triglycerides >110mg/dL. Low cholesterol. Absent cholesterol crystals.	History of preceding trauma or thoracic surgery.
Pseudochylothorax	Exudative	Milky appearance. High cholesterol and cholesterol crystals present. Normal triglycerides.	Rheumatoid arthritis. High serum cholesterol.
Haemothorax	Exudative	Frank blood appearance.	History of trauma. On anticoagulation.

Table 2: Differential diagnosis of pleural effusion with key points relating to pleural effusion and clinical presentation characteristics. 

Table adapted from – Bhatnagar R, Maskell N. The modern diagnosis and management of pleural effusions. BMJ. 2015;351(September). Saguil A, Wyrick K, Hallgren J. Diagnostic approach to pleural effusion. Am Fam Physician. 2014;90(2):99–104. UpToDate. Diagnostic evaluation of a pleural effusion in adults: Initial testing [Internet]. 2022 [cited 2022 May 17]. Available from: https://www.uptodate.com/contents/diagnostic-evaluation-of-a-pleural-effusion-in-adults-initial-testing

Empyema

An important differential diagnosis of pleural effusion is an empyema, meaning infection of the pleural fluid. The gold standard diagnostic test for empyema is the growth of an organism from the aspirated pleural fluid, but it can also be suggested by a low pleural fluid pH <7.2. Pleural infections are seen more commonly at the extremes of age: in the very young and the very old, and as such, has a high associated mortality of 20% in the UK.

The causative organisms vary depending on whether the pleural infection was community-acquired or hospital-acquired in origin. In the community, gram-positive aerobic organisms such as Streptococcus and Staphylococci are the most commonly seen organisms, but the incidence of gram-negative isolates from these patients is increasing. In the hospital setting, the most common organism seen is Staphylococcal aureus (S aureus), with a high proportion of patients growing methicillin-resistant staphylococcal aureus (MRSA). Gram-negative organisms such as E coli, Enterobacter and Pseudomonas species are seen in higher proportion in hospital-acquired cases when compared to the community.

Setting	Common Organisms
Community-acquired	Streptococcus spp. (52%) Streptococcus pneumonia Streptococcus milleri Staphylococcus aureus Gram negative aerobes e.g. Escherichia coli Anaerobes
Hospital-acquired	Staphylococci spp Staphylococcus aureus Methicillin-resistant staphylococcus aureus (MRSA) – 25% Gram negative anaerobes e.g. Escherichia coli, Pseudomonas aeruginosa.

Table 3: Common causative organisms of empyema. 

Table adapted from – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9.  

Strange C. Management and prognosis of parapneumonic pleural effusion and empyema in adults [Internet]. UpToDate. 2021 [cited 2022 May 30]. Available from: https://www.uptodate.com/contents/management-and-prognosis-of-parapneumonic-pleural-effusion-and-empyema-in-adults

Empyema, or pleural infection, should be suspected in any patient who has remained persistently unwell with high inflammatory markers and temperatures despite appropriate antimicrobial treatment. Signs and symptoms consistent with sepsis can develop if a pleural infection remains untreated. The gold standard diagnostic test for pleural infection is pleural fluid culture, and would be the main way to differentiate from the other causes of pleural effusion detailed above, alongside a pleural pH level. 

Haemothorax 

Haemothorax refers to the presence of frank blood in the pleural space most commonly secondary to thoracic trauma. Its appearance on a plain chest x-ray is identical to a standard pleural effusion, but clinical history, pleural ultrasound features and diagnostic aspiration can help differentiate it. 

Haemothorax tends to develop in the context of polytrauma, both in the young and old, and these patients may have evidence of haemodynamic instability from bleeding: hypotension or tachycardia. In addition to radiological features, a haemothorax may be suggested by a significant serum haemoglobin drop. Radiologically, it appears identical to all other causes of pleural effusion on chest x-ray, but on pleural ultrasound, it is a cause of a loculated pleural effusion (other causes being malignancy and pleural infection). The key to diagnosis, though, is on diagnostic aspiration with identification of pleural fluid: blood haematocrit ratio >50%. 

If identified, haemothorax should be managed urgently (see management below).

Management 

Given there is a wide range of aetiologies resulting in the formation of a pleural effusion, there are also a variety of management options available to treat them. The mainstay of treatment is related to treating the underlying condition once identified, with or without drainage of the effusion. For example, pleural effusions secondary to cardiac failure should initially be treated with optimising treatment for the underlying cardiac disease. There are 3 specialised circumstances where management is altered: pleural infection, haemothorax and malignant pleural effusions. 

The majority of bilateral pleural effusions can be treated by managing the underlying condition: optimising medical management of cardiac failure, consideration of transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis or consideration of haemofiltration in renal failure. 

Management of Unilateral Pleural Effusion 

Unilateral effusions, once a cause has been identified, can be managed conservatively in the majority of cases as long as they remain uncomplicated (absence of organisation and septation features on pleural ultrasound) and asymptomatic. Following a diagnostic aspiration, in this setting of the asymptomatic patient with pleural effusion, a repeat chest x-ray can be requested to follow up in 6 weeks’ time to assess for resolution. However, if a patient is symptomatic, there is a general consensus that drainage should be carried out under ultrasound guidance. The only exceptions relate to asymptomatic pleural infections or haemothoraces, which should be drained regardless. 

Drainage of a pleural effusion can happen in one of two ways:

• Therapeutic thoracentesis (also referred to as therapeutic aspiration). This procedure, performed under ultrasound guidance, simultaneously allows samples for diagnostic purposes as well as removal of a larger volume of pleural fluid to provide symptomatic benefit. This procedure leaves some residual pleural fluid, which can be utilised if the original samples are non-diagnostic in more invasive procedures.
• Intercostal drain insertion. Ultrasound (US) guided drain insertion allows complete drainage of pleural fluid as well as diagnostic sampling. The advantage of complete drainage means attempts at pleurodesis can be made, e.g. talc pleurodesis to prevent reaccumulating fluid. This can be utilised in patients who already have a known cause for their pleural effusion or in patients who would be unsuitable for further invasive investigation of the underlying cause (poor performance status, non-ambulatory).

When pleural fluid is drained, BTS recommends no more than 1.5L of fluid removal at once due to the risk of re-expansion pulmonary oedema. The development of this condition can be suggested by the development of a cough and chest pain, followed by significant respiratory deterioration, instability and potentially collapse. 

Flowchart adapted from guidance available at –  Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Li D, Ajmal S, Tufail M, Panchal RK. Modern-day management of a unilateral pleural effusion. Clin Med J R Coll Physicians London. 2021;21(6):E561–6.

Refractory Non-Malignant Pleural Effusions 

Non-malignant pleural effusions that are refractory to management of the underlying cause should be considered for intercostal drainage to reduce symptomatic burden on these patients. Patients should receive optimal medical management of the underlying medical problem, ideally for 72 hours before proceeding to invasive procedures.

Management of Malignant Pleural Effusion 

The presence of malignant cells in pleural fluid is diagnostic of metastatic cancer, most commonly secondary to an underlying bronchial malignancy. Management options of malignancy-associated pleural effusions are largely determined by the patient’s performance status, as per the WHO performance status categories, alongside the primary tumour, symptomatology and the predicted degree of lung re-expansion following removal of pleural fluid. 

• Performance status 0. Able to carry out all normal activities without restriction. 
• Performance status 1. Restricted in strenuous activity but ambulatory and able to carry out light work. 
• Performance status 2. Ambulatory and capable of all self-care, but unable to carry out any work activities; up and about >50% of waking hours. 
• Performance status 3. Symptomatic and chair/bed-bound>50% of the day. 
• Performance status 4. Cannot carry out any self-care; confined to bed/chair. 

Patients who are asymptomatic of their malignant pleural effusion should not undergo drainage routinely and should be observed in the outpatient setting. Drainage of asymptomatic pleural effusions does not prevent re-accumulation and progression of the effusion; hence, the observation method is recommended in these patients. 

Patients who are symptomatic at presentation with a known malignant pleural effusion can undergo one of several options: therapeutic pleural aspiration, intercostal drainage without pleurodesis or intercostal drainage with pleurodesis. Therapeutic aspiration is not recommended for routine use in known malignant pleural effusions due to the high rate of re-accumulation but can be utilised in patients with very poor prognosis (<1 month). As such, those patients whose prognosis is >1 month should undergo intercostal drainage with the aim of pleurodesis once all pleural fluid has been removed. A chest x-ray should be completed prior to talc pleurodesis to confirm full reinflation of the lung and absence of pleural fluid.

Flowchart adapted from guidance available at – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Heffner JE. Management of malignant pleural effusions [Internet]. UpToDate. 2022 [cited 2022 May 30]. Available from: https://www.uptodate.com/contents/management-of-malignant-pleural-effusions

Pleurodesis 

Pleurodesis refers to a procedure that sticks the pleura to the chest wall, with the aim of preventing re-accumulation of pleural fluid. In the case of malignant pleural effusions, BTS recommends sterile talc pleurodesis once drainage and re-expansion of the lung has been confirmed. Sterile talc pleurodesis is quoted as being between “81% and 100% effective”.

Trapped Lung 

Trapped lung, otherwise known as nonexpendable lung, is seen more commonly in patients with malignant pleural effusions. It refers to the inability of the lung to fully re-expand, and radiologically, the previous fluid is replaced with air in the pleural space on a chest x-ray. It can be suggested clinically by failure to improve symptomatology despite satisfactory drainage of the pleural effusion. In this situation, pleurodesis is of no benefit as visceral and parietal pleura do not come back together. In addition, recurrent thoracentesis does not improve the “trapped lung”, so repeated thoracentesis is not recommended. In patients who are significantly symptomatic with this condition, an indwelling pleural catheter (IPC) can be placed to assist with control of symptoms. 

Recurrent symptomatic malignant pleural effusions 

In patients who have recurrent symptomatic pleural effusions that reaccumulate despite attempts at pleurodesis, then a tunnelled pleural catheter can be considered to help alleviate symptoms associated with pleural fluid accumulation. It is particularly important for those patients with “trapped lung,” as above, but can also be utilised in patients without this phenomenon. 

Management of Pleural Infection/ Empyema

Pleural infections are an ever-increasing complication of pleural fluid accumulation, particularly seen in the very young and very old populations or in those considered to be immunosuppressed. Management of pleural infections focuses on removing the source alongside intravenous antibiotics, guided by the causative agent and its sensitivities. 

Pleural infections can be identified in a number of ways, and the way they are identified or suspected are important for their management strategy. The key to diagnosis is the diagnostic pleural aspiration once a pleural effusion has been identified: 

• Frankly purulent pleural fluid on aspiration. Any fluid during a diagnostic aspiration which appears to be frank pus or is significantly turbid/cloudy should be considered to be a pleural infection, and immediate intercostal drainage should be completed. 

• Low pH pleural fluid <7.2. In those patients who have features suggestive of possible pleural infection (high inflammatory markers, vulnerable population demographic, recurrent fevers despite antibiotics) but not a frankly purulent aspiration, pleural pH should be completed. A pH <7.2 is highly suggestive of pleural infection, and proceeding to intercostal drainage is recommended. 

• Gram stain or culture-positive pleural fluid. The presence of organisms identified within pleural fluid should prompt discussion with respiratory physicians regarding the need for drainage. In some situations, these can be managed by antibiotics alone, but this is assessed on a case-by-case basis. 
• Loculated pleural effusions identified on pleural USS. Locules on pleural ultrasound are suggestive of organisation of the pleural fluid and are commonly seen in pleural infection but also in haemothorax and malignant pleural effusions. It is this appearance on ultrasound that allows clinicians to refer to it as a “complicated” pleural effusion. Drainage of loculated pleural effusion is recommended due to the potential for individual locules to become infected in isolation.

Flowchart adapted from guidance available at – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Strange C. Management and prognosis of parapneumonic pleural effusion and empyema in adults [Internet]. UpToDate. 2021 [cited 2022 May 30]. Available from: https://www.uptodate.com/contents/management-and-prognosis-of-parapneumonic-pleural-effusion-and-empyema-in-adults

In addition to drainage of the pleural infection, all patients should receive antibiotics. The antibiotics each patient gets will be dependent on several factors: the organisms identified on gram staining/ culture, the sensitivity profile of these organisms, whether the pleural infection was community or hospital-acquired and local resistance patterns. 

Pleural infections have the potential to be caused by aerobic and anaerobic organisms, gram-positive and gram-negative organisms, meaning broad-spectrum cover may be needed in those patients who do not grow a specific organism from pleural sampling. Penicillin-based regimes remain the preferred choice due to both the good penetration into the pleural space and the broad-spectrum of cover they provide. Aminoglycosides, e.g. gentamicin, should be avoided due to their poor penetration into the pleural space. All antimicrobial therapy for pleural infection should be discussed with local microbiology teams to allow local resistance patterns to be accounted for. Initially, intravenous antibiotics are recommended, but these can be stepped down to the oral route once biochemical and clinical improvement is noted. Duration of treatment will be guided by local microbiology input, but it is recommended they are continued for at least 3 weeks. 

Type of Pleural Infective	Recommended First-Line Antibiotics	Penicillin-allergy
S. pneumoniae infection S. milleria infection	Penicillin-based therapy, e.g. amoxicillin. Or third-generation cephalosporin + metronidazole.	Carbapenem-based monotherapy, e.g. meropenem.
Unknown organism. Community-acquired pleural infection	Penicillin + beta-lactamase inhibitor e.g. co-amoxiclav or amoxicillin + metronidazole combination. Or third-generation cephalosporin + metronidazole.	Clindamycin Or, Clindamycin + ciprofloxacin/ cephalosporin.
Unknown organism. Hospital-acquired pleural infection.	Penicillin + beta-lactamase inhibitor with good anaerobic cover and anti-pseudomonal cover e.g. piperacillin-tazobactam. MRSA cover, e.g. vancomycin or teicoplanin, until results available.	Clindamycin + ciprofloxacin/ cephalosporin. Or antipseudomonal carbapenem e.g. meropenem. MRSA cover, e.g. vancomycin or teicoplanin, until results available.

Table 4: Common causative organisms of empyema. 

Table adapted from – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Strange C. Management and prognosis of parapneumonic pleural effusion and empyema in adults [Internet]. UpToDate. 2021 [cited 2022 May 30]. Available from: https://www.uptodate.com/contents/management-and-prognosis-of-parapneumonic-pleural-effusion-and-empyema-in-adults

In patients who do not respond to drainage and antibiotic therapy after a 5-7-day treatment period, a CT thorax and referral to cardiothoracic surgeons for consideration of surgical management of pleural infection should be completed. A CT thorax allows further evaluation of pathology and planning of subsequent surgical procedures. The type of surgical procedure selected will be dependent on many factors, guided by the expertise of cardiothoracic colleagues. 

Management of Haemothorax

The essential management of haemothorax is intercostal drainage, alongside appropriate resuscitation such as intravenous fluid and red blood cell replacement as required. In the case of haemothorax, large-bore chest drains should be used in order to allow the passage of clots. If there is persistent bleeding or haemodynamic stability, an urgent referral to cardiothoracic surgery for consideration of urgent thoracotomy should be completed. 

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Pneumothorax 

Background

Pneumothorax refers to air within the pleural cavity. There are several definitions to be aware of when considering pneumothorax: 

• Primary spontaneous pneumothorax. Refers to the development of a pneumothorax in the absence of an external event without the presence of underlying lung disease. 
• Secondary spontaneous pneumothorax. Refers to the development of a pneumothorax in the absence of an external event, with the presence of underlying lung disease, e.g. asthma or chronic obstructive pulmonary disease (COPD). 
• Traumatic pneumothorax. Refers to the development of a pneumothorax following an external event. This can further be subdivided into iatrogenic (secondary to a medical procedure) and non-iatrogenic (secondary to blunt or penetrating chest injury). 

The focus of this is going to be on primary and secondary spontaneous pneumothorax. 

Epidemiology

Primary and secondary spontaneous pneumothoraces are common pathologies that emergency physicians, respiratory physicians and intensive care physicians encounter. Combined hospital admission rates are quoted at 16.7/100,000 for men and 5.8/100,000 for women. Both primary and secondary pneumothoraces are seen at a higher incidence in the male population, with risk factors such as being tall, with low BMI, and cigarette smoking identified. 

Primary spontaneous pneumothoraces are seen in a younger population demographic (typically 20-30 years old), whereas secondary spontaneous pneumothoraces are seen in an older population (typically 60-65 years old), reflecting the development of underlying lung disease. 

Pathophysiology

In normal breathing, air does not enter the pleural cavity at any point. Therefore, The presence of air signifies the development of pathology from communication between the alveolar spaces and pleura, from communication between the outside atmosphere and the pleural space, or from the presence of gas-producing organisms within the pleural space. 

Primary Spontaneous Pneumothorax (PSP) 

The mechanism which results in a primary spontaneous pneumothorax is not currently fully understood; however, it has been identified that the majority of patients who present with PSP do have an underlying anatomical abnormality, even in the absence of known lung disease. These “anatomical abnormalities” are typically described as subpleural blebs and bullae, more commonly found at the lung apex. Risk factors for the development of these anatomical abnormalities include cigarette smoke, poor nutritional status with low BMI, connective tissue disease (including Marfan’s syndrome) and hereditary predisposition. It is thought that these subtle anatomical differences, when combined with the appropriate precipitating factor, result in the development of the primary spontaneous pneumothorax. Lung inflammation and oxidative stress are also likely to play an important role in the development of PSP.

Smoking is one of the biggest implicating factors for spontaneous pneumothorax (with BTS quoting a healthy smoking male having a 12% lifetime risk of pneumothorax development, whereas the same demographic non-smoking male is just 0.1%). 

Secondary Spontaneous Pneumothorax (SSP) 

Secondary spontaneous pneumothorax (SSP) is pneumothorax associated with underlying lung disease, and many underlying chronic lung diseases have been recognised to increase the risk of pneumothorax development. The most common association is with airways disease: chronic obstructive pulmonary disease (COPD), severe asthma and cystic fibrosis. Infections such as pneumocystis carinii can also increase the risk of SSP development. 

Tension Pneumothorax 

A tension pneumothorax is a potentially life-threatening medical emergency that occurs as a result of the development of a one-way valve system in the pleural space. This one-way system allows air in during inspiration but fails to let air out in expiration, causing progressively larger volumes of air within the pleural space. This raises intrapleural pressures, impairing venous return to the heart, which eventually results in hypotension, tachycardia and, ultimately, cardiovascular collapse. 

Presentation

The classical presentation of a spontaneous pneumothorax is sudden-onset ipsilateral pleuritic chest pain, associated shortness of breath and hypoxia. However, these symptoms in PSP can be relatively minor, so patients may not present at the exact time of onset. Patients who have underlying lung disease are typically more symptomatic, with dyspnoea the most commonly reported symptom due to the already damaged underlying lung parenchyma. This can result in patients with SSP reporting symptoms out of proportion to the size of pneumothorax identified on diagnostic imaging (see diagnosis). 

An important clinical distinction to make is between the ‘simple’ spontaneous pneumothorax and the tension pneumothorax. Tension pneumothoraces are medical emergencies that are more commonly seen among the most unwell patients: in major trauma, in the critical care environment, but they can also be seen in the medical on-call take environment. The typical symptoms of simple pneumothorax are present (dyspnoea, chest pain), but these are more frequently accompanied by respiratory distress, with or without cardiovascular collapse. Tension pneumothorax is also an important reversible cause of respiratory and cardiac arrest with prompt treatment (see management). 

Signs 

Simple spontaneous pneumothorax (primary or secondary) 

In the very small pneumothorax, there may be little to no clinical findings to appreciate on examination. When a larger pneumothorax has developed, clinical findings that can be elicited include: 

• Asymmetrical chest expansion. Due to air building up within the pleural space, the lung itself becomes gradually more compressed. This results in reduced lung expansion on inspiration on the affected side. 
• Hyper-resonant percussion.
• Diminished breath sounds. 
• Central trachea. 
• Evidence of respiratory distress. This includes high respiratory rate, use of accessory muscles of respiration and hypoxia. Patients who have secondary spontaneous pneumothoraces are more likely to present in this way. 

Tension pneumothorax 

A tension pneumothorax is an uncommon clinical condition but should ideally undergo diagnosis based on clinical history and examination. Prompt recognition and treatment of the below features can result in rapid resolution of respiratory distress and dramatic clinical improvement for patients. 

• Asymmetrical chest expansion. 
• Hyper-resonant percussion.
• Diminished breath sounds. 
• Tracheal deviation away from the side of the above clinical findings. 
• Hypotension and tachycardia – suggestive of impending cardiovascular collapse. 
• Respiratory distress.

Diagnosis 

A diagnosis of a pneumothorax can be made clinically with the identification of appropriate clinical signs; however, these signs are not always present. In any patient presenting with sudden onset dyspnoea and pleuritic chest pain pneumothorax should remain as part of the differential diagnosis. The mainstay of confirming a pneumothorax diagnosis comes from imaging. 

A subset of patients with large pneumothoraces or tension pneumothoraces are haemodynamically unstable, and quick diagnosis is required. In this setting, if available, bedside ultrasound can be utilised to confirm the diagnosis with subsequent rapid initiation of management (see management section). However, the majority of patients who present are haemodynamically stable, and it is these patients who can undergo less urgent, non-bedside imaging. 

PA Chest X-ray

Image Source: Wikimedia Commons (2017). Spontaneous pneumothorax, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/b/b1/Spontanpneumothorax.jpg (Accessed on: 21 June 2022).

The posterior-anterior (PA) erect chest x-ray is the mainstay of diagnostic imaging in stable patients (and can also be utilised in unstable patients at the bedside if ultrasound is not available). It allows identification of the pathology and size of the pneumothorax, which is important in considering subsequent management strategies. 

Features that can be seen on a PA erect chest x-ray are: 

• Visible lung edge
• Lung markings absent beyond visible lung edge (and the absence of lung markings to the chest wall should prompt the clinician to look for pneumothorax evidence) 
• Radiolucent space beyond visible lung edge, i.e. darker, from increased air without lung parenchyma. 
• Increased distance between rib spaces on affected hemithorax. 
• Mediastinal shift and tracheal shift away in cases of tension pneumothorax. 
• Subcutaneous emphysema. 

A “simple” pneumothorax on PA chest x-ray is the presence of pneumothorax without mediastinal shift. A tension pneumothorax is diagnosed when mediastinal shift is identified either clinically or on diagnostic imaging. 

In order to measure the size of pneumothorax present, 2 methods can be used: the American method and the British method. In the American method, it is the distance between the apex and top of the lung (cupola). The British method, and the method utilised in BTS guidelines, is the measurement of the interpleural distance at the level of hilum between the visible collapsed lung edge and chest wall. A “small” pneumothorax is typically referred to as a pneumothorax that is <2cm in size and a large pneumothorax one that is >2cm in size. However, it is important to clinically assess and correlate patients (especially those with secondary spontaneous pneumothoraces) as size of pneumothorax does not always correlate with clinical symptomatology and distress. 

Flowchart adapted from guidance available at – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Gary Lee Y. Clinical presentation and diagnosis of pneumothorax [Internet]. UpToDate. 2021 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-pneumothorax?search=pneumothorax &source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H3647761918

CT Thorax 

CT Thorax can be utilised when there is diagnostic uncertainty following a PA chest x-ray or in the diagnosis of a small pneumothorax, where it should be considered the “gold standard” for evaluation of size and the underlying anatomy. CT Thorax can not only easily identify a pneumothorax, but it can also alert the clinician to any underlying changes, e.g. emphysematous lung disease or bullae, which may be related to the aetiology of the pneumothorax. 

CT remains superior to chest x-ray and ultrasound in terms of accurately identifying a pneumothorax; however, it is not as readily available and exposes patients to a significant dose of radiation.

Ultrasound 

Bedside pleural ultrasound can provide rapid diagnosis of pneumothorax in the unstable patient, but it is also highly sensitive for identification of small pneumothoraces. 

In the normal lung utilising the straight linear array high-frequency probe, pleural ultrasound shows the lung ‘sliding’ as the patient respires. Alongside the sliding pleural ‘Z lines’ can be seen, which are vertical comet tails (artefacts) running down from the pleura.  By switching the probe into M-mode in the normal lung, the “seashore” sign can be visualised, which represents the sliding pleura moving on a motionless chest wall. Several signs on ultrasound can suggest the presence of a pneumothorax: 

• Absence of lung sliding. 
  • On M mode – this can be referred to as the “barcode” sign. 
• Absence of comet tail artefacts. These artefacts are lost due to the build-up of air within the pleural space. 
• Lung point sign. This nearly 100% specific sign for pneumothorax refers to identifying the junction between sliding lung and non-sliding lung. This is useful in small pneumothoraces as in larger-sized pneumothoraces, entire lung collapse can occur, and therefore, global absence of lung sliding is noted. 
  • This sign can also be helpful in estimating size of the pneumothorax if present. 
• Absence of lung pulse. 

Differential Diagnosis 

The differential diagnosis of pneumothorax is wide and relates to any condition that can present with acute-onset chest pain and dyspnoea. Clinical history and examination findings are key to establishing the underlying diagnosis, as many cardiac and respiratory conditions can present similarly. The table below summaries some common differential diagnoses of this presentation to be aware of. 

Diagnosis	Clinical History Points	Clinical Examination Findings
Respiratory
Pulmonary Embolism	VTE risk factor identified: active malignancy, combined oral contraceptive pill, recent travel >4 hours or surgery. Pleuritic chest pain. Haemoptysis associated.	Clinical examination in PE is typically normal in uncomplicated PE. In large PE – signs of right heart failure may be present: peripheral oedema, raised JVP, pulsatile hepatomegaly. Chest x-ray: normal.
Acute asthma exacerbation	Acute shortness of breath + wheeze. Increased use of PRN salbutamol inhaler. Cough +- sputum production +- fever. Trigger prior to onset.	Bilateral wheeze. Often young patient demographic. Chest x-ray: normal, or consolidation if infective exacerbation.
Acute COPD exacerbation	Acute shortness of breath. Wheeze +- cough +- sputum production history. Not associated with chest pain typically.	Bilateral wheeze. Prolonged expiratory phase +- tar staining. Type 2 respiratory failure in some cases. Chest x-ray: hyper-inflated lung fields, flattened hemidiaphragms.
Cardiac
Acute myocardial infarction	Crushing, central chest pain. Sweating, nausea/ vomiting and dizziness associated. Other cardiac risk factors: type 2 diabetes, smoking, alcohol, increased BMI.	In acute myocardial infarction – grey, sweaty appearance. Respiratory examination normal. Raised BMI, tar staining may be noted. Chest x-ray: normal or acute pulmonary oedema.
Aortic dissection	‘Tearing’ central chest pain through to the back. Pre-syncopal/ syncopal episode.	Difference in blood pressure between 2 arms. Radial-radial delay. Acute aortic regurgitation (early diastolic murmur) Chest x-ray: mediastinal widening.
Acute pulmonary oedema	Cough with pink frothy sputum Progressive dyspnoea followed by sudden onset nature. Orthopnoea and paroxysmal nocturnal dyspnoea.	Respiratory distress Bilateral crackles throughout both lung fields. +- signs of right heart failure. Chest x-ray: bilateral pleural effusions, pulmonary congestion.

Table 5: Differential diagnosis of pneumothorax with key history and clinical examination characteristics. 

Table adapted from – 

Gary Lee Y. Clinical presentation and diagnosis of pneumothorax [Internet]. UpToDate. 2021 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-pneumothorax?search=pneumothorax &source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H3647761918

UpToDate. Evaluation of the adult with chest pain in the emergency department [Internet]. 2022 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/evaluation-of-the-adult-with-chest-pain-in-the-emergency-department?search=chest pain&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H18

UpToDate. Evaluation of the adult with dyspnea in the emergency department [Internet]. [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/evaluation-of-the-adult-with-dyspnea-in-the-emergency-department?search=shortness of breath&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H4

Management 

Several pieces of information are key to the management of a spontaneous pneumothorax. The first is the question of haemodynamic stability. If haemodynamic instability is noted, urgent management is required (see Management: Tension Pneumothorax). If the patient, like in the majority of cases, is haemodynamically stable, then an important distinction between primary and secondary pneumothorax needs to be made. These distinctions are important as secondary pneumothoraces are often tolerated much less well and, therefore, may require more significant management, e.g. intercostal drainage. The third question to ask is how symptomatic is that patient’s pneumothorax? Patients who are significantly dyspnoeic are likely to need more active intervention than those who are asymptomatic. The fourth and final question to consider is the size of the pneumothorax, which can be assessed on the PA chest x-ray or CT Thorax. 

What defines a secondary pneumothorax? ‘Secondary’ simply means there is either a known history of underlying lung disease or there is evidence to suggest this: 

• Age >50 with significant smoking history. 
• Clinical examination consistent with evidence of chronic lung disease. 
• Radiological evidence of chronic lung disease. 

Tension Pneumothorax 

Tension pneumothorax is a life-threatening medical emergency that requires prompt treatment to avoid cardiovascular collapse. If identified either clinically or radiologically, it should be treated with high-flow oxygen and urgent needle decompression with a large-bore needle into the 2nd intercostal space, midclavicular line. This initial life-saving treatment releases some air to decrease risk of progress to cardiovascular collapse but is not definitive management in itself and should be followed by prompt insertion of an intercostal drain for drainage of the pneumothorax. The needle decompression should remain in place until the full procedure for intercostal drain insertion is completed. 

Primary Spontaneous Pneumothorax 

In small (<2cm) primary spontaneous pneumothoraces which are asymptomatic, a conservative approach to management can be utilised, providing the patient is able to seek medical attention again should they become more unwell at home. Lifestyle advice on smoking cessation should be provided to reduce the risk of recurrence with early review in clinic to ensure resolution of the pneumothorax. 

In PSP that is symptomatic with dyspnoea or considered large (>2cm using British measurements), an initial trial of needle aspiration should be utilised alongside high-flow oxygen. Needle aspiration, in the context of PSP, has been shown to have equal success in management of the pneumothorax as insertion of chest drain. It involves the use of a needle and 50mL syringe to drain up to 2.5L of air from the chest. If this fails to improve the patient symptomatically or radiologically (considered to be pneumothorax <2cm), then proceeding to chest drain is the recommendation.

Flowchart adapted from guidance available at – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Secondary Spontaneous Pneumothorax 

Patients with secondary spontaneous pneumothorax (SSP) tolerate pneumothoraces less well due to their underlying chronic lung disease, which significantly alters the management strategy for this set of patients. In addition to increased symptomatology, SSPs are less likely to spontaneously resolve, meaning active management with insertion of intercostal drainage is more frequently needed. 

Given the above, in any SSP that is symptomatic of their pneumothorax, you should proceed immediately to intercostal drainage with a small-bore intercostal drain (8-14Fr), with admission and early input from the respiratory specialist team. In the setting where the patient is asymptomatic, the size of the pneumothorax determines the ongoing management. Pneumothoraces 1-2cm can undergo a trial of needle aspiration up to 2.5L of air with response assessed afterwards. If the pneumothorax is subsequently <1cm, then no further intervention is required other than high-flow oxygen (with caution in those with known hypercapnic respiratory failure) and admission to hospital for at least a 24-hour monitoring period. If needle aspiration fails to create a pneumothorax <1cm in size, then proceeding to drainage is the most appropriate next step. 

Flowchart adapted from guidance available at – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 

Persistent Air Leak Management in Primary and Secondary Spontaneous Pneumothorax 

In some cases, pneumothoraces fail to resolve despite initial management as guided by the algorithms above. This is seen more frequently in secondary spontaneous pneumothorax than primary but is possible in both subtypes. A persistent air leak is usually defined as a failure for the pneumothorax to fully resolve despite 24-48 hours of appropriate management. There are some management options available: 

• Suction. Low-grade suction can be considered in patients with a persistent leak at 24-48 hours to help with re-expansion of the lung. The recommendation is to start with low rates of suction, approximately -10cm H20, which can be increased to -20cmH20 dependent on resolution and how well the patient tolerates the added pressure. 
• Referral to cardiothoracic surgeons for consideration of surgical management. Consideration of early referral to cardiothoracic surgeons (with persistent air leak at 3-5 days) for surgical management is important in patients fit for surgical procedure and can provide patients with definitive management. This is especially important in patients with SSP.
• Chest drainage with ambulatory drainage device. In selected patients with persistent air leak, a chest drain can remain in situ with a drainage device attached. This drainage device can allow ongoing drainage of air in the community. Decisions to utilise this lie with specialised respiratory colleagues. 
• Pleurodesis. 

Preventing Recurrence 

Patients who present with their first episode of PSP do not typically require definitive treatment, e.g. surgical management unless they have a persistent air leak at the initial presentation or they have a repeat episode. 

On the other hand, patients who present with SSP are at high risk of recurrence. As such, in SSP, consideration of definitive management during their initial admission should be completed. In patients considered fit for surgery, surgical methods for definitive management are the preferred option. In those where surgery is not an option or not the patient’s preferred course of action, then chemical pleurodesis with sterile talc pleurodesis or tetracycline pleurodesis can be used (BTS recommends tetracycline pleurodesis over talc if available). Talc or tetracycline pleurodesis results in pleural inflammation and formation of adhesions to cause pleural effusion and prevention of further episodes of pneumothorax. 

Management of Recurrent Pneumothorax Episodes 

Recurrent pneumothoraces are a common clinical event with an estimated recurrence rate of around 30% in PSP and 50% in SSP, although data on this varies. In PSP, recurrence is thought to be related to some risk factors: being tall, low BMI, smoking and anatomical changes identified on CT (small blebs or bullae). The key risk factor for a further pneumothorax, though, is having had one previously. 

In the initial setting, recurrent pneumothoraces should be managed with insertion of an intercostal drain. Recurrent pneumothoraces should prompt the clinician to consider early discussion with cardiothoracic surgical colleagues for definitive management. The agreed criteria for referral, as per BTS guidelines, are the following: 

• Second ipsilateral pneumothorax. 
• First contralateral pneumothorax. 
• Synchronous bilateral spontaneous pneumothorax. 
• Persistent air leak at 5-7 days despite intervention, or failure of lung re-expansion. 
• Spontaneous haemothorax. 
• At risk Profession, e.g. pilots, divers
• Pregnancy. 

In patients not suitable for surgery, chemical pleurodesis can be completed (see Management: Preventing Recurrence). 

Special Circumstances 

Air Travel following Pneumothorax 

The British Thoracic Society provided guidance on air travel and history of pneumothorax in 2022. It recommends that any patient with a current, unresolved pneumothorax should not travel by air. In those who have a resolved pneumothorax, they should wait for 7 days after full resolution is confirmed on a chest x-ray before travelling. 

Diving following Pneumothorax 

The British Thoracic Society published specific recommendations for diving and respiratory disease in 2003. It recommends that anyone with evidence of bullae on CT imaging should not dive due to the increased risk of barotrauma during the activity. In addition, any previous spontaneous pneumothorax is a contraindication to diving (unless specifically treated with bilateral pleurectomy and subsequent normal lung function and imaging following the procedure). 

If a patient has had a previous traumatic pneumothorax, this is not a contraindication to diving, providing they have been left with normal lung function and imaging. 

References 

• BMJ Best Practice. Pneumothorax [Internet]. 2022 [cited 2022 Jun 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/3000083
• Bobbio A, Dechartres A, Bouam S, Damotte D, Rabbat A, Régnard JF, et al. Epidemiology of spontaneous pneumothorax: Gender-related differences. Thorax. 2015;70(7):653–8. 
• British Thorax Society Fitness to Dive Group. British Thoracic Society guidelines on respiratory aspects of fitness for diving. Thorax. 2003;58:3–13.
• Carroll D. Pneumothorax (Ultrasound) [Internet]. Radiopedia. 2021 [cited 2022 Jun 1]. Available from: https://radiopaedia.org/articles/pneumothorax-ultrasound-1?lang=gb
• Coker RK, Armstrong A, Church AC, Holmes S, Naylor J, Pike K, et al. BTS Clinical Statement on air travel for passengers with respiratory disease. Thorax. 2022;77(4):329–50.
• Gary Lee Y. Clinical presentation and diagnosis of pneumothorax [Internet]. UpToDate. 2021 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-pneumothorax?search=pneumothorax &source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H3647761918
• Gary Lee Y. Pneumothorax in adults: Epidemiology and etiology [Internet]. UpToDate. 2022 [cited 2022 May 31]. Available from: https://www.uptodate.com/contents/pneumothorax-in-adults-epidemiology-and-etiology?search=pneumothorax&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H23
• Gary Lee Y. Pneumothorax: Definitive management and prevention of recurrence [Internet]. UpToDate. 2021 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/pneumothorax-definitive-management-and-prevention-of-recurrence?search=pneumothorax&source=search_result&selectedTitle=6~150&usage_type=default&display_rank=6#H2851443018
• Gary Lee Y. Treatment of primary spontaneous pneumothorax in adults [Internet]. UpToDate. 2020 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/treatment-of-primary-spontaneous-pneumothorax-in-adults?search=pneumothorax&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#H1914656627
• Gary Lee Y. Treatment of secondary spontaneous pneumothorax in adults [Internet]. UpToDate. 2021 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/treatment-of-secondary-spontaneous-pneumothorax-in-adults?search=pneumothorax&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H1
• Husain, Lubna F et al. “Sonographic diagnosis of pneumothorax.” Journal of emergencies, trauma, and shock vol. 5,1 (2012): 76-81. doi:10.4103/0974-2700.93116
• Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9. 
• McKnight CL, Burns B. Pneumothorax. [Updated 2022 May 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441885/
• Niknejad M. Pneumothorax [Internet]. Radiopedia. 2022 [cited 2022 Jun 1]. Available from: https://radiopaedia.org/articles/pneumothorax?lang=gb#nav_radiographic-features
• Noppen M. Spontaneous pneumothorax: Epidemiology, pathophysiology and cause. Eur Respir Rev. 2010;19(117):217–9. 
• Roberts DJ, Leigh-Smith S, Faris PD, Blackmore C, Ball CG, Robertson HL, et al. Clinical presentation of patients with tension pneumothorax: A systematic review. Ann Surg. 2015;261(6):1068–78. 
• UpToDate. Evaluation of the adult with chest pain in the emergency department [Internet]. 2022 [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/evaluation-of-the-adult-with-chest-pain-in-the-emergency-department?search=chest pain&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H18
• UpToDate. Evaluation of the adult with dyspnea in the emergency department [Internet]. [cited 2022 Jun 1]. Available from: https://www.uptodate.com/contents/evaluation-of-the-adult-with-dyspnea-in-the-emergency-department?search=shortness of breath&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H4

Miscellaneous Pleural Disease

Background

In addition to the common forms of pleural disease discussed above, there are some less common forms of pleural disease to consider: pleural plaques and mesothelioma (cancer of the mesothelial cells within the pleura). Both conditions typically occur following exposure to asbestos, a naturally occurring fibre composed of hydrated magnesium silicates. Asbestos exposure also has the ability to cause interstitial lung changes, termed asbestosis.

Asbestos was a fibre used commonly in many industries up until around the 1970s. It was subsequently banned in the UK in 1999. It was mainly used in construction and insulation, and patients who have worked within the following vocations may be at risk of previous asbestos exposure: 

• Plumbers
• Electricians 
• Boilermakers 
• Welders
• Insulation workers 

The development of pleural changes is a hallmark of asbestos exposure. 

Pleural Plaques

Pleural plaques refer to the benign development of clearly defined areas of pleural thickening following previous exposure to asbestos. The mean time to onset following exposure is quoted at 20-30 years and preferentially involves the parietal pleura in the majority of cases. 

When visualised directly pleural plaques appear as grey-white thickened regions of pleura with a “holly-leaf appearance.” They are composed of collagen deposits thought to arrive at the pleural space via the lymphatic system. Subsequent inflammation of the pleura is then thought to create the characteristic pleural plaque seen. Patients may well be asymptomatic of these and only have them picked up on chest radiograph for another reason. On a chest x-ray, plaques that have become calcified are the easiest to see. They are typically found in the lower zones bilaterally with an associated “incomplete border sign.”

Image Source: Wikimedia Commons (2017). Pleurosis calcarea wohl nach, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/1/13/Pleurosis_calcarea_wohl_nach_Tbc_93W_-_CR_pa_-_001.jpg?20201125151008  (Accessed on: 21 June 2022).

Importantly, pleural plaques are benign entities, and no further follow-up is required. However, as they are a marker of asbestos exposure, if a patient develops any sign which may be suggestive of an underlying cancer (see below), urgent imaging under the 2-week-wait pathway should be arranged.

Malignant Mesothelioma 

Malignant mesothelioma (MM) is a rare cancer of the pleura arising from mesothelial cells within the pleural cavity. It is highly associated with asbestos exposure, typically developing 30-40 years after exposure to the fibre, and unfortunately carries a poor prognosis. The median survival following diagnosis is quoted at 9.5 months by the British Thoracic Society. 

Clinical Features and Diagnosis 

MM can present insidiously with non-specific symptoms such as chest pain, prolonged cough, shortness of breath and weight loss with a significant male-predominance of disease. Clinical signs may be limited unless pleural effusion (see Pleural Effusion Clinical Features) or lymphadenopathy are present.

In NICE’s guideline NG12: Suspected cancer: recognition and referral, an urgent chest x-ray under the 2-week-wait pathway would be the first-line investigation to assess for MM. Their criteria recommend that in those aged over 40 with previous asbestos exposure, 1 of the following symptoms would trigger this referral: 

• Cough 
• Fatigue 
• Shortness of breath 
• Chest pain 
• Weight loss 
• Appetite loss 

A chest x-ray in MM may show evidence of pleural effusion, unilateral focal pleural thickening, a pleural mass or pleural plaques. If suspicion is high, then proceeding to a CT Thorax with contrast can allow further evaluation of this pathology. Changes can be identified on CT imaging, but to establish a definitive diagnosis of MM, a tissue diagnosis is required. This can be achieved either via pleural biopsy with confirmation histologically or via the presence of abnormal mesothelial cells obtained from pleural fluid sampling (either via diagnostic aspiration or via medical thoracoscopy). 

Once a tissue sample is obtained, immunohistochemistry can be utilised to differentiate MM from other forms of bronchial carcinoma. At least two positive mesothelial markers need to be present to make a diagnosis of MM: calretinin, cytokeratin 5/6, Wilms tumour 1, D-240. In addition to the positive markers, markers for lung adenocarcinoma should also be negative.

Management 

As highlighted above, the prognosis of MM, once diagnosed, is poor. In those patients with a good performance status (WHO performance status 0-1), combination chemotherapy can be utilised as a first-line management option with cisplatin-based chemotherapy. In those with a lower performance status (WHO performance status >2), palliative management of symptoms should be considered first-line.

Management of pleural effusions in MM can be completed in the same way as all other malignant pleural effusions (see Pleural Effusion Management section for further details). 

References 

• British Thoracic Society. BTS Guideline for the investigation and management of malignant pleural mesothelioma Appendix 2: Evidence tables. Thorax. 2018;73(March). 
• King T. Asbestos-related pleuropulmonary disease [Internet]. UpToDate. 2021 [cited 2022 Jun 21]. Available from: https://www.uptodate.com/contents/asbestos-related-pleuropulmonary-disease
• NICE. Suspected Cancer: Recognition and Referral – PubMed – NCBI. NICE Guidel [Internet]. 2015;(July 2017):1–378. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26180880%5Cnhttps://www.nice.org.uk/guidance/ng12/evidence/full-guidance-74333341
• Radiopedia. Pleural plaque [Internet]. 2021 [cited 2022 Jun 21]. Available from: https://radiopaedia.org/articles/pleural-plaque?lang=gb
• Sternam, D; Litzky, Leslie; Kaiser L. Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma [Internet]. UpToDate. 2020 [cited 2022 Jun 21]. Available from: https://www.uptodate.com/contents/presentation-initial-evaluation-and-prognosis-of-malignant-pleural-mesothelioma?search=malignant pleural mesothelioma&source=search_result&selectedTitle=1~23&usage_type=default&display_rank=1
• Sternam, D; Litzky, Leslie; Kaiser L. Epidemiology of malignant pleural mesothelioma [Internet]. UpToDate. 2022 [cited 2022 Jun 21]. Available from: https://www.uptodate.com/contents/epidemiology-of-malignant-pleural-mesothelioma?search=epidemiology of malignant pleural&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1