Which of the following conditions is most closely associated with exudative pleural effusion

Background

A pleural effusion is collection of fluid abnormally present in the pleural space, usually resulting from excess fluid production and/or decreased lymphatic absorption. [1] It is the most common manifestation of pleural disease, and its etiologies range in spectrum from cardiopulmonary disorders and/or systemic inflammatory conditions to malignancy. Approximately 1.5 million pleural effusions are diagnosed in the United States each year (see images below).

Anatomy

The pleural space (cavity) in a healthy patient is a potential space sandwiched between the parietal and visceral pleurae. The parietal pleura completely lines the inner chest wall surface of the thoracic cavity, inclusive of the bilateral medial mediastinum, the subcostal left and right diaphragmatic leaflets, and the innermost muscle surface of the ribs and associated musculature. The visceral pleura tightly envelopes both lungs completely, folding into the interlobar fissures, meeting the parietal pleura at the hilar root of the lungs. The right and left pleural cavities are separated in healthy people by the anterior and posterior mediastinum.

Playing a vital role in respiration, the potential space of the pleural cavity in healthy patients conjoins the natural outward movement of the chest wall to that of the natural inward movement of the lungs via two mechanisms. First, the potential space's relative vacuum sustains the visceral and parietal pleurae's extreme adherence and is uninterrupted and not disrupted. Second, a diminutive volume of pleural fluid (calculated at 0.13 mL/kg of body weight under normal situations) serves as the lubricant to facilitate the normal physiologic sliding motion of both pleural surfaces against each other during inspiration and expiration. [2] This small volume of lubricating fluid is maintained via a delicate balance of hydrostatic and oncotic pressure and peripheral sulcal lymphatic drainage; disturbances in any of these mechanisms may lead to pathology and, possibly, manifest as a pleural effusion. [3]

Etiology

The normal pleural space contains approximately 10 mL of fluid, representing the balance between (1) hydrostatic and oncotic forces in the visceral and parietal pleural capillaries and (2) persistent sulcal lymphatic drainage. Pleural effusions may result from disruption of this natural balance.

Presence of a pleural effusion heralds an underlying disease process that may be pulmonary or nonpulmonary in origin and, furthermore, that may be acute or chronic. [4, 5] Although the etiologic spectrum of pleural effusion can be extensive, most pleural effusions are caused by congestive heart failure, pneumonia, malignancy, or pulmonary embolism.

The following mechanisms may play a role in the formation of pleural effusion:

• Altered permeability of the pleural membranes (eg, inflammation, malignancy, pulmonary embolism)

• Reduction in intravascular oncotic pressure (eg, hypoalbuminemia due to nephrotic syndrome or cirrhosis)

• Increased capillary permeability or vascular disruption (eg, trauma, malignancy, inflammation, infection, pulmonary infarction, drug hypersensitivity, uremia, pancreatitis)

• Reduction of pressure in the pleural space (ie, due to an inability of the lung to fully expand during inspiration); this is known as "trapped lung" (eg, extensive atelectasis due to an obstructed bronchus or contraction from fibrosis leading to restrictive pulmonary physiology)

• Decreased lymphatic drainage or complete lymphatic vessel blockage, including thoracic duct obstruction or rupture (eg, malignancy, trauma)

• Increased peritoneal fluid with microperforated extravasation across the diaphragm via lymphatics or microstructural diaphragmatic defects (eg, hepatic hydrothorax, cirrhosis, peritoneal dialysis)

• Movement of fluid from pulmonary edema across the visceral pleura

• Persistent increase in pleural fluid oncotic pressure from an existing pleural effusion, causing further fluid accumulation

The net result of effusion formation is a flattening or inversion of the diaphragm, a mechanical dissociation of the visceral and parietal pleura, and an eventual restrictive ventilatory defect as measured by pulmonary function testing. [6]

Pleural effusions are generally classified as transudates or exudates, based on the mechanism of fluid formation and pleural fluid chemistry. Transudates result from an imbalance of oncotic and hydrostatic pressures, whereas exudates are the result of inflammatory processes of the pleura and/or decreased lymphatic drainage. In some cases, it is not rare for pleural fluid to exhibit mixed characteristics of transudate and exudate.

Transudates

Transudates result from an imbalance in oncotic and hydrostatic pressures. Transudative effusions are usually ultrafiltrates of plasma squeezed out of the pleura as a result of an imbalance in hydrostatic and oncotic forces in the chest. However, other mechanisms of injury may include upward movement of fluid from the peritoneal cavity or, in iatrogenic cases, direct infusion into the pleural space from misplaced (or even migrated) central venous catheters or nasogastric feeding tubes.

Transudates are caused by a small, defined group of etiologies, including the following:

• Congestive heart failure

• Cirrhosis (hepatic hydrothorax)

• Atelectasis (may be due to occult malignancy or pulmonary embolism)

• Hypoalbuminemia

• Nephrotic syndrome

• Peritoneal dialysis

• Myxedema

• Constrictive pericarditis

• Urinothorax (usually due to obstructive uropathy)

• Cerebrospinal fluid (CSF) leaks to the pleura (in the setting of ventriculopleural shunting or of trauma/surgery to the thoracic spine)

• Duropleural fistula (rare, but may be a complication of spinal cord surgery)

• Extravascular migration of central venous catheter [7]

• Glycinothorax (rare complication of bladder irrigation with 1.5% glycine solution following urologic surgery)

Exudates

Produced by a variety of inflammatory conditions (and often requiring a more extensive evaluation and treatment strategy than transudates), exudative effusions develop from inflammation of the pleura or from decreased lymphatic drainage at pleural edges. 

Mechanisms of exudative formation include pleural or parenchymal inflammation, impaired lymphatic drainage of the pleural space, transdiaphragmatic cephalad movement of inflammatory fluid from the peritoneal space, altered permeability of pleural membranes, and/or increased capillary wall permeability or vascular disruption. Pleural membranes are involved in the pathogenesis of the fluid formation. Of note, the permeability of pleural capillaries to proteins is increased in disease states with elevated protein content.

The more common causes of exudates include the following:

• Parapneumonic causes [8]

• Malignancy (most commonly lung or breast cancer, lymphoma, and leukemia; less commonly ovarian carcinoma, stomach cancer, sarcomas, melanoma) [9]

• Pulmonary embolism

• Collagen-vascular conditions (rheumatoid arthritis, systemic lupus erythematosus [10, 11] )

• Tuberculosis (TB)

• Pancreatitis

• Trauma

• Postcardiac injury syndrome

• Esophageal perforation

• Radiation pleuritis

• Sarcoidosis [12]

• Fungal infection

• Pancreatic pseudocyst

• Intra-abdominal abscess

• Status post coronary artery bypass graft (CABG) surgery

• Pericardial disease

• Meigs syndrome (benign pelvic neoplasm with associated ascites and pleural effusion) [13]

• Ovarian hyperstimulation syndrome [14]

• Drug-induced pleural disease (see Pneumotox.com for an extensive and searchable list of drugs that may cause pleural effusion)

• Asbestos-related pleural disease

• Yellow nail syndrome (yellow nails, lymphedema, pleural effusions)

• Uremia

• Trapped lung (localized pleural scarring with the formation of a fibrin peel prevents incomplete lung expansion, at times leading to pleural effusion)

• Chylothorax (acute illness with elevated triglycerides in pleural fluid)

• Pseudochylothorax (chronic condition with elevated cholesterol in pleural fluid)

• Fistula (ventriculopleural, biliopleural, gastropleural)

Epidemiology

Occurrence in the United States

Since pleural effusion is usually the manifestation of an underlying disease process, its precise incidence is difficult to determine. Nevertheless, the incidence in the United States is estimated to be at least 1.5 million cases annually. [15]  Most of these cases are caused by congestive heart failure, bacterial pneumonia, malignancy, and pulmonary embolism.

International occurrence

The estimated prevalence of pleural effusion is 320 cases per 100,000 people in industrialized countries, with a distribution of etiologies related to the prevalence of underlying diseases. [4]

Sex-related demographics

Although certain etiologies have a sex predilection, the general understanding is that the incidence of pleural effusion is equal between the sexes. Nearly two thirds of malignant pleural effusions occur in women, in whom they are associated with breast and gynecologic malignancies.

Pleural effusion associated with systemic lupus erythematosus is specifically more common in women than in men. In the United States, the incidence of pleural effusion in the setting of malignant mesothelioma is higher in men, probably because of their higher occupational exposure to asbestos.

Pleural effusions associated with chronic pancreatitis are more common in men, with the majority of male cases having alcohol abuse as the impetus. Rheumatoid effusions also occur more commonly in males than in females.

Race- and age-related demographics

Since pleural effusion is usually the manifestation of an underlying disease process, racial differences most likely reflect racial variation in incidence of the causative disorder.

Pleural effusions usually occur in adults. However, they appear to be increasing in children, often in the setting of underlying pneumonia. [16] Fetal pleural effusions have also been reported and under certain circumstances may be treated prior to delivery. [17]

Prognosis

The prognosis in pleural effusion varies in accordance with the condition’s underlying etiology. However, patients who seek medical care earlier in the course of their disease and those who obtain prompt diagnosis and treatment have a substantially lower rate of complications than do patients who do not.

Morbidity and mortality

Morbidity and mortality of pleural effusions are directly related to cause (and if applicable, staging) of the underlying disease at the time of presentation, as well as biochemical findings in the pleural fluid.

Morbidity and mortality rates in patients with pneumonia and pleural effusions are higher than those in patients with pneumonia alone. Parapneumonic effusions, when recognized and treated promptly, typically resolve without significant sequelae. However, untreated or inappropriately treated parapneumonic effusions may lead to empyema, constrictive fibrosis, and sepsis.

Development of a malignant pleural effusion is associated with a very poor prognosis, with median survival of 4 months and mean survival of less than 1 year. [18, 19] The most common associated malignancy in men is lung cancer. The most common associated malignancy in women is breast cancer. Median survival ranges from 3-12 months, depending on the malignancy. Effusions from cancers that are more responsive to chemotherapy, such as lymphoma or breast cancer, are more likely to be associated with prolonged survival, compared with those from lung cancer or mesothelioma. [20, 21]

Cellular and biochemical findings in the fluid may also be indicators of prognosis. For example, a lower pleural fluid pH is often associated with a higher tumor burden and a worse prognosis. [22]

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Author

Chief Editor

Guy W Soo Hoo, MD, MPH Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Medical Intensive Care Unit, Chief, Pulmonary, Critical Care and Sleep Section, West Los Angeles VA Healthcare Center, Veteran Affairs Greater Los Angeles Healthcare System

Guy W Soo Hoo, MD, MPH is a member of the following medical societies: American Association for Respiratory Care, American College of Chest Physicians, American College of Physicians, American Thoracic Society, California Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Acknowledgements

Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi

Disclosure: See below for list of all activities None None

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

What is exudative pleural effusion?

What is the most common cause of pleural effusion?

Which of the following is characteristic of an exudate effusion?

Which of the following are associated with a transudative pleural effusion?