Pleural fluid analysis is used to help diagnose the cause of accumulation of fluid in the chest cavity (pleural effusion). There are two main reasons for fluid accumulation and an initial set of tests, including fluid protein, albumin, or LD level, cell count, and appearance, is used to differentiate between the two types of fluid that may be produced, transudate or exudate.

• Transudate: an imbalance between the pressure within blood vessels (which drives fluid out of the blood vessel) and the amount of protein in blood (which keeps fluid in the blood vessel) can result in accumulation of fluid. Transudates are most frequently caused by congestive heart failure or cirrhosis. If the fluid is determined to be a transudate, then usually no more tests on the fluid are necessary.
• Exudate: injury or inflammation of the pleurae may cause abnormal collection of fluid. If the fluid is an exudate, then additional testing is often ordered. Exudates are associated with a variety of conditions and diseases, including:
  • Infectious diseases – caused by viruses, bacteria, or fungi. Infections may originate in the pleurae or spread there from other places in the body. For example, pleuritis and pleural effusion may occur along with or following pneumonia.
  • Bleeding – bleeding disorders, pulmonary embolism, or trauma can lead to blood in the pleural fluid.
  • Inflammatory conditions – such as lung diseases, chronic lung inflammation for example due to prolonged exposure to large amounts of asbestos (asbestosis), sarcoidosis, or autoimmune disorders such as rheumatoid arthritis and lupus
  • Malignancies – such as lymphoma, leukemias, lung cancer, metastatic cancers
  • Other conditions – idiopathic, cardiac bypass surgery, heart or lung transplantation, pancreatitis, or intra-abdominal abscesses

Additional testing on exudate fluid may include:

• Pleural fluid glucose, lactate, amylase, triglyceride, and/or tumor markers
• Microscopic examination – a laboratory professional may place a sample of the fluid on a slide and examine it under a microscope. Normal pleural fluid has small numbers of white blood cells (WBCs) but no red blood cells (RBCs) or microorganisms.
• Cytology – a laboratory professional may use a special centrifuge (cytocentrifuge) to concentrate the fluid's cells on a slide. The slide is treated with a special stain and evaluated for abnormal cells, such as malignant cells (cancer cells).
• Gram stain – for direct observation of bacteria or fungi under a microscope. There should be no organisms present in pleural fluid.
• Bacterial culture and susceptibility testing – ordered to detect any bacteria that may be present in the pleural fluid and to guide antimicrobial therapy.
• Fungal tests – may include fungal culture and susceptibility testing
• Adenosine deaminase – may help detect tuberculosis (TB)
• Less commonly, tests for infectious diseases, such as tests for viruses, mycobacteria (AFB testing), and parasites.

Pleural fluid analysis may be ordered when a healthcare practitioner suspects that a person has a condition or disease that is causing pleuritis and/or pleural effusion. It may be ordered when someone has some combination of the following signs and symptoms:

• Chest pain that worsens with deep breathing
• Coughing
• Difficulty breathing, shortness of breath
• Fever, chills
• Fatigue

Test results can help distinguish between types of pleural fluid and help diagnose the cause of fluid accumulation. The initial set of tests performed on a sample of pleural fluid helps determine whether the fluid is a transudate or exudate:

Transudate

Transudates are most often caused by either congestive heart failure or cirrhosis. Typical fluid analysis results include:

• Physical characteristics—fluid appears clear
• Protein, albumin, or LDH level—low
• Cell count—few cells are present

Exudate

Exudates can be caused by a variety of conditions and diseases. Initial test results may include:

• Physical characteristics—fluid may appear cloudy
• Protein, albumin, or LD level—high
• Cell count—increased

Additional test results and their associated causes may include:

Physical characteristics – the normal appearance of a sample of pleural fluid is usually light yellow and clear. Abnormal results may give clues to the conditions or diseases present and may include:

• Reddish pleural fluid may indicate the presence of blood.
• Cloudy, thick pleural fluid may indicate an infection and/or the presence of white blood cells. It may also indicate leakage of fluid from the lymphatic system (lymph). Lymph drains from the lymphatic system into the venous system in the chest and either trauma or lymphoma can cause lymph to be present in pleural fluid.

Chemical tests – tests that may be performed in addition to protein or albumin may include:

• Glucose—typically about the same as blood glucose levels; may be lower with infection and rheumatoid arthritis.
• Lactate levels can increase with infections.
• Amylase levels may increase with pancreatitis, esophageal rupture, or malignancy.
• Triglyceride levels may be increased when there is leakage from the lymphatic system.
• Tumor markers, such as CEA, may be increased with some cancers.

Microscopic examination – Normal pleural fluid has small numbers of white blood cells (WBCs) but no red blood cells (RBCs) or microorganisms. Results of an evaluation of the different kinds of cells present may include:

• Total cell counts—the WBCs and RBCs in the sample are counted. Increased WBCs may be seen with infections and other causes of pleuritis. Increased RBCs may suggest trauma, malignancy, or pulmonary infarction.
• WBC differential—determination of percentages of different types of WBCs. An increased number of neutrophils may be seen with bacterial infections. An increased number of lymphocytes may be seen with cancers and tuberculosis.
• Cytology—a cytocentrifuged sample is treated with a special stain and examined under a microscope for abnormal cells. This is often done when a mesothelioma or metastatic cancer is suspected. The presence of certain abnormal cells, such as tumor cells or immature blood cells, can indicate what type of cancer is involved.

Infectious disease tests – these tests may be performed to look for microorganisms if infection is suspected:

• Gram stain—for direct observation of bacteria or fungi under a microscope. There should be no organisms present in pleural fluid.
• Bacterial culture and susceptibility testing—If bacteria are present, susceptibility testing can be performed to guide antimicrobial therapy. If there are no bacteria present, it does not rule out an infection; they may be present in small numbers or their growth may be inhibited because of prior antibiotic therapy.
• Fungal tests—if a culture is positive, the fungus or fungi causing the infection will be identified in the report and susceptibility testing may be done to guide therapy.
• Adenosine deaminase—a markedly elevated level in pleural fluid in a person with symptoms that suggest tuberculosis means it is likely that the person tested has a Mycobacterium tuberculosis infection in their pleurae. This is especially true when there is a high prevalence of tuberculosis in the geographic region where a person lives. (For more details, see the test article on Adenosine Deaminase.)

Other less common tests for infectious diseases may be performed and may identify a virus, mycobacteria (such as the mycobacterium that causes tuberculosis), or a parasite as the cause of an infection and fluid accumulation.

A blood glucose, protein, albumin, or LD may be ordered to compare concentrations with those in the pleural fluid.