Effusion (Lung edema)
Another complication with lymphedema may be the build up of fluids in the cardio and or pleural cavities. There are numerous individuals on list that have experienced this complication. I had a mild one for years and suddenly this year it became extensive.
Pleural effusions appear to be more of an possibility with long term lymphedema. Conditions that would lead to it would be abdominal edema, any type of lymphatic cancer that impairs an already disfunctional lymphatic system, recurrent infections that have further damaged lymphatics, pulmonary lymphangiectasia.
If you have extensive lymphedema and experience difficulty in breathing, if your breathing is labored or you experience that "rattling" sound a simple x-ray should be sufficient to pick up and edema.
Update April 12, 2008
Since this page was first posted, our family of online support groups has grown to slightly over 4,000 members from dozens of countries throughout the world. With increasing frequency, lymphedema patients have written to me or posted comments about breathing problems, fluid on the lungs, or shortness of breath.
I have become convinced that pleural effusions (lung fluid, lung edema) associated with lymphedema is a seriously undiagnosed, under reported and significant untreated complication of this condition. It is therefore imperative that the awareness level be raised and that treating physicians and therapists become aware of the possibility that this could well effect their patient.
There are several conditions associated with lymphedema wherein pleural effusions can present.
One condition is what is generally referred to as Yellow Nail Syndrome, and this is fairly well known and documented. Another condition, much less known of, but even more serious is pulmonary lymphangiectasia. In this condition, the lymphatics of the lugns are dilated and thus become unable to transport fluid. Until very recently an infant born with this condition faced an almost certain fatal prognosis.
In my personal situation, starting in early 2005, I began to experience increasing lung fluid and serious breathing difficulty. This continued to get worse until now, I have had to have my lungs drained every month. Each time about two to two and a half quarts of fluid has been removed each time. Last Fall I had an all over lymphscintigraphy that demonstrated almost no lymphatic movement through the thoracic duct. It also became apparent that I could not continnue to go through monthly thoracocentesis to remove that fluid. In this procedure, a tube is inserted between the ribs and placed into the pleural cavity, removing the fluid. The bad thing about this procedure is you run the risk of pneumothorax (lung collapse) each time you enter the lung caivty, and I have had a number of these.
In January 2007, I underwent a pleuerodesis in the right lung. In pleurodesis, an irritant (such as Bleomycin, Tetracyclines, or talc powder) is instilled inside the space between the pleura (the two layers of tissue lining the lungs) in order to create inflammation which tacks the two pleura together. This procedure thereby obliterates the space between the pleura and prevents the reaccumulation of fluid. It is was only partially successful. While fluid accumulation in the right lung slowed, it conitnued unabated in the left lung.
This past week on April 11th, I had a Pleurx catheter system put into both lungs. Tubes were inserted into each lung cavity, running through the cavity and coming out my sides. I now will be able to drain my lungs weekly, in hopes of controlling the fluid accumulation.
I hope this revised information will be of value and help. If you have lymphedema and begin to have difficulty in breathing, it is important you let your physician know and that the proper tests be conducted to achieve an accurate diagnoses. A simply xray will pick up whether or not you have fluid. Other radiological tests can verify and evaluate the extent of the effusion.
Four Types of Pleural Space Fluid
Serous fluid (hydrothorax)
Pus (pyothorax or empyema)
Transudative pleural effusions (1)are defined as effusions that are caused bysystemic factors that alter the pleural equilibrium, or Starling forces. The components of the Starling forces–hydrostatic pressure, permeability, oncotic pressure (effective pressure due to the composition of the pleural fluid and blood)–are altered in many diseases, e.g., left ventricular failure, renal failure, hepatic failure, and cirrhosis.
Causes of transudative pleural effusions in the United States are left ventricular failure, and cirrhosis (causing hepatic hydrothorax),nephrotic syndrome leading to increased loss of albumin and resultant hypoalbuminemia and thus reducing colloid osmotic pressure is another less common cause. Pulmonary embolisms were once thought to be transudative but have been recently shown to be exudative
Exudative pleural effusions, by contrast, are caused by alterations in local factors that influence the formation and absorption of pleural fluid (e.g., bacterial pneumonia, cancer,pulmonary embolism, and viral infection)
Common causes of exudative pleural effusions are bacterial pneumonia, cancer (with lung cancer, breast cancer, and lymphoma causing approximately 75% of all malignant pleural effusions), viral infection, and pulmonary embolism. (1 ) Wikipedia
By Steven A. Sahn, MD, FCCP
chest radiograph; diagnosis; malignancy; management; pleural effusion; pneumonia
BAPE = benign asbestos pleural effusion; LDH = lactate dehydrogenase
Pleural effusions are a mirror of systemic disease. Disease affecting virtually any organ can result in a pleural effusion. Therefore, the clinician not only needs to consider chest disease as a cause of pleural effusions, but diseases of organs below the diaphragm (splenic infarction), systemic diseases (systemic lupus erythematosus), and diseases of the lymphatic system (yellow nail syndrome) need to be thought of as well, in the appropriate clinical setting.
There are a limited number of mechanisms responsible for the accumulation of pleural fluid: (1) increased hydrostatic pressure (congestive heart failure); (2) decreased oncotic pressure (hypoalbuminemia); (3) decreased pleural pressure (atelectasis); (4) increased endothelial permeability (pneumonia); (5) decreased lymphatic drainage (malignancy); (6) movement from the peritoneal space (hepatic hydrothorax); (7) thoracic duct rupture (chylothorax); and (8) iatrogenic (extravascular migration of central venous catheter).1
When pleural fluid formation exceeds efflux from the pleural space, a pleural effusion will accumulate and, when large enough (> 200 to 300 mL), can be detected on a posteroanterior chest radiograph. Smaller amounts of fluid can be detected by lateral decubitus view, ultrasonography, and CT scan.
Pleural fluid formation related to disease in the lungs results from an increased interstitial-pleural pressure gradient. When fluid moves from the intravascular space into the interstitium of the lung because of increased hydrostatic pressure (as in congestive heart failure) or increased capillary permeability (pneumonia), pressure in the interstitium of the lung increases and results in a driving force towards the pleural space, which has a mean negative pressure. The interstitial fluid moves between mesothelial cell junctions into the pleural space. If fluid formation exceeds removal by the parietal pleural lymphatics, a pleural effusion will develop.2
Awareness of the symptoms and signs of specific diseases in patients who present with pleural effusions may be helpful in narrowing the differential diagnosis of the exudative effusion. For example, patients with postcardiac injury syndrome,3 lupus pleuritis,4 and malignant mesothelioma5 usually are symptomatic at presentation with a pleural effusion. In contrast, about 75% of patients with carcinomatous malignant effusions,6 50% of patients with rheumatoid pleurisy,7 and less than half of the patients with benign asbestos pleural effusion (BAPE)8 may be symptomatic at presentation.
When the only abnormality on chest radiograph is a pleural effusion, several diseases originating in the chest should be considered, such as infections (tuberculous and viral pleurisy), malignancy (cancer, non-Hodgkin's lymphoma, and leukemia), pulmonary embolism, drug-induced lung disease, BAPE, lymphatic abnormalities (chylothorax and yellow nail syndrome), uremic pleurisy, constrictive pericarditis, and hypothyroidism.9
Bilateral pleural effusions are commonly transudative due to congestive heart failure,10 nephrotic syndrome, hypoalbuminemia, peritoneal dialysis, and constrictive pericarditis.11 Patients with exudative effusions can also present with bilateral effusions, most commonly malignancy (extrapulmonic primary carcinomas, lymphoma),12 lupus pleuritis,4 and yellow nail syndrome.13
Patients with diseases of the abdomen and pelvis can present with chest radiographs that reveal only a pleural effusion while other abnormalities are not present or cannot be visualized. These include transudates such as hepatic hydrothorax,14 nephrotic syndrome,15 urinothorax,16 and peritoneal dialysis17 and exudates such as pancreatic disease,18 chylous ascites, subphrenic abscess,19 and splenic abscess or infarction.20
When pleural effusions are associated with interstitial lung disease, the differential diagnosis includes congestive heart failure, rheumatoid arthritis, asbestos-induced disease (BAPE and asbestosis),8 lymphangitic carcinomatosis, lymphangioleiomyomatosis,21 viral and mycoplasma pneumonias,22 Waldenström's macroglobulinemia, sarcoidosis,23 and Pneumocystis carinii pneumonia.24
The association of pleural effusions with pulmonary nodules most commonly occurs with metastatic carcinoma from a nonlung primary tumor. Less common causes include Wegener's granulomatosis, rheumatoid arthritis, septic emboli, sarcoidosis, and tularemia.25
Awareness of the spontaneous resolution rates of exudative pleural effusions is helpful in arriving at a presumptive cause of the pleural effusion.26 For example, in patients with pulmonary embolism without a radiographic infarction (consolidation), the effusion usually resolves completely within 7 to 10 days; when a radiographic infarction is present, resolution may require 2 to 3 weeks.27 The pleural effusion associated with acute pancreatitis will resolve as the pancreatic inflammation subsides, typically within 1 to 2 weeks.18 With continued hemodialysis, a uremic pleural effusion resolves in 4 to 6 weeks.28 Persistence of the uremic effusion suggests that either a trapped lung or fibrothorax has developed, which can be successfully treated with decortication. A tuberculous pleural effusion has a spontaneous resolution rate of 4 to 16 weeks29; corticosteroid therapy will shorten resolution time but does not appear to have an effect on pleural space sequelae.30 Rheumatoid pleural effusions have a typical resolution time of 4 to 6 months, with a range of a few weeks to 9 months.31 In patients with BAPE effusions typically resolve in 3 to 4 months, with some persisting for > 1 year and some resolving in < 1 month.32 Effusions that persist for > 1 year have a limited differential diagnosis that includes trapped lung,33 yellow nail syndrome, lymphangiectasia, Noonan's syndrome (chylothorax),34 and, rarely, rheumatoid pleurisy, BAPE, and malignancy.35
In a prospective study of 78 patients with new-onset pleural effusion, a definitive diagnosis was established by the initial pleural fluid analysis in 25% and a presumptive diagnosis in 55%, with the remaining 20% having a nondiagnostic pleural fluid analysis.36 However, in the latter group of patients, the pleural fluid analysis was helpful by excluding possible diagnoses such as infection. Thus, the initial pleural fluid analysis is either definitively or presumptively diagnostic in 80% of patients and is valuable clinically in about 90% of cases.
Diagnoses that can be definitively established by pleural fluid analysis include empyema (pus), malignancy, tuberculous pleural effusion, fungal pleural effusion, lupus pleuritis (lupus erythematosus cells), chylothorax (triglycerides > 110 mg/dL or presence of chylomicrons), hemothorax (pleural fluid/blood hematocrit > 0.5), urinothorax (pleural fluid/serum creatinine > 1.0), peritoneal dialysis (total protein < 0.5 g/dl and glucose 200 to 400 mg/dL), esophageal rupture (increased salivary amylase and pH < 7.00), rheumatoid pleurisy (pleural fluid cytology), and extravascular migration of a central venous catheter (high glucose level or pleural fluid simulating the infusate).37
Pleural fluid/serum protein ratio, pleural fluid lactate dehydrogenase (LDH) compared with the upper limits of normal of serum LDH, and pleural fluid cholesterol level can help discriminate accurately between a transudate and exudate. Helpful values include a pleural fluid/serum protein ratio of > 0.5,38-40 a pleural fluid LDH of > 0.45,38 between 0.6739 and 0.8040 of the upper limit of normal of serum LDH, and a pleural fluid cholesterol > 45 mg/dL38 or > 60 mg/dL.41 The presence of any one of the above values makes it highly likely that the effusion is exudative. When pleural fluid LDH suggests an exudate and the pleural fluid/serum protein ratio suggests a transudate, malignancy39 or an effusion secondary to Pneumocystis carinii pneumonia42 should be considered. It is important to remember that no laboratory test is 100% sensitive and specific and prethoracentesis diagnosis and clinical judgment must be used in the interpretation of pleural fluid analysis.
The total nucleated cell count is rarely helpful in establishing a definitive diagnosis; however, it may provide useful information. If the nucleated cell count is < 500/mL, the fluid is usually a transudate. If the nucleated cell count is > 50,000/mL, it usually represents pleural space bacterial infection (typically empyema). Nucleated cell counts between 25,000 and 50,000/mL are usually seen only with uncomplicated parapneumonic effusions, acute pancreatitis and acute pulmonary infarction.
The differential diagnosis of an exudate pleural fluid with a lymphocyte count of > 80% of the total nucleated cells includes tuberculous pleurisy, chylothorax, lymphoma, yellow nail syndrome, chronic rheumatoid pleurisy, sarcoidosis, trapped lung, and acute lung rejection.37 The differential diagnosis of pleural fluid eosinophilia (> 10% of the total nucleated cells are eosinophils) includes most commonly pneumothorax and hemothorax, as well as BAPE, pulmonary embolism with infarction, previous thoracentesis, parasitic disease (paragonimiasis), fungal disease (histoplasmosis and coccidioidomycosis), drug-induced lung disease (nitrofurantoin, dantrolene, propylthiouracil, valproic acid, isotretinoin, and bromocriptine), Hodgkin's lymphoma, and carcinoma.37 The prevalence of pleural fluid eosinophilia is similar in carcinomatous and noncarcinomatous pleural effusions.43
A pleural fluid pH < 7.30, in the setting of a normal blood pH, narrows the differential diagnosis of the exudative effusion to empyema, complicated parapneumonic effusion, chronic rheumatoid pleurisy, esophageal rupture, malignancy, tuberculous pleurisy, and lupus pleuritis.44 Finding a pleural fluid glucose < 60 mg/dL or pleural fluid/serum glucose < 0.5 provides the same differential diagnosis of the exudate as a low pleural fluid pH.45 Urinothorax, most commonly caused by obstructive uropathy, is the only cause of a low pH transudate.46 Empyema and rheumatoid pleurisy are the only effusions that can present with glucose concentrations of 0 mg/dL. A pleural fluid pH < 7.00 is usually seen only with empyema, whether it be parapneumonic or associated with esophageal rupture. Pleural fluid acidosis is due to increased acid generation by neutrophils and bacteria in empyema and an abnormal pleural membrane that inhibits glucose end products, CO2 and lactic acid, from exiting the pleural space at a normal rate. Complicated parapneumonic effusion/empyema, rheumatoid pleurisy, and pleural paragonimiasis are the only effusions with the triad of a pH < 7.30, a glucose < 60 mg/dL, and an LDH > 1,000 U/L (upper limit of normal of serum 200 IU/L).
Patients with pleural effusions from congestive heart failure will provide a history of orthopnea and paroxysmal nocturnal dyspnea typical of left ventricular failure. The usual chest radiograph will demonstrate cardiomegaly, bilateral pleural effusions (right greater than left), and evidence of pulmonary edema as demonstrated by peribronchial cuffing, interstitial or alveolar infiltrates, or Kerley-B lines. The degree of pulmonary edema correlates with the volume of pleural effusion.47 The pleural space serves as a "reservoir" for pulmonary edema fluid, which moves from the interstitium of the lung into the pleural space through mesothelial cell junctions along a pressure gradient. Pleural effusions are associated with elevated pulmonary capillary wedge pressures, typically 24 mm Hg or greater, a level that is associated with Kerley's B lines on chest radiograph.47 However, pleural effusions can occur with lower pulmonary capillary wedge pressures, particularly if the oncotic pressure is low. There is no significant relationship between right atrial pressure and the development of pleural effusions.
A diagnostic thoracentesis is indicated in suspected congestive heart failure when there is fever, pleuritic chest pain, a unilateral effusion, a left effusion greater then the right effusion, effusions of disparate size, and a PaO2 inconsistent with the clinical presentation. With the typical presentation, thoracentesis can be withheld while observing the response to treatment. If response is not appropriate, diagnostic thoracentesis should be performed. Acute diuresis can transform a transudative congestive heart failure fluid into a pseudoexudate.48
An hepatic hydrothorax results when ascitic fluid moves from the peritoneal to pleural space along a pressure gradient through congenital diaphragmatic defects that have been opened by increased peritoneal pressure. Hepatic hydrothorax occurs in approximately 5% of patients with clinical ascites but can result even in the absence of clinical ascites.14 These effusions are most commonly right-sided but may be unilateral on the left (15%) or bilateral (15%).14 A presumptive diagnosis can be established in the appropriate clinical setting by demonstrating that pleural and ascitic fluid characteristics are similar. For a definitive diagnosis, a radionuclide study should be performed. Radionuclide appearing in the chest within 1 to 2 h following injection into the ascitic fluid confirms the diagnosis.49
Management of hepatic hydrothorax includes sodium restriction, diuretic therapy and intermittent therapeutic thoracentesis. Refractory effusions can be managed with a transjugular intrahepatic portal systemic shunt50 or video-assisted thoracoscopic surgery repair of the diaphragmatic defect and pleurodesis51 in patients with a reasonable expected survival who can tolerate a surgical procedure. Chest tube drainage is contraindicated in hepatic hydrothorax, as it causes protein and lymphocyte depletion and can cause an iatrogenic empyema, precipitate renal failure, and be a source of continuous fluid leak through the thoracostomy site.52
Atelectasis causes a small transudative pleural effusion due to a decrease in pleural pressure. As the collapsed portion of the lung moves away from the chest wall, it causes a localized decrease in pleural pressure that results in an increased parietal pleural-interstitial pleural space gradient, causing increased formation of pleural fluid.1 As fluid moves into the pleural space, the pleural-interstitial pressure gradient returns to normal with pleural fluid formation equaling pleural fluid removal. Atelectatic effusions are commonly found in patients in ICUs53 but can also occur when lung cancer obstructs a mainstem or lobar bronchus, with pulmonary embolism without infarction,54 and any cause of lower chest or upper abdominal pain. Most atelectatic effusions are small in volume and resolve quickly when the atelectasis resolves.
Patients with nephrotic syndrome have an estimated 20% prevalence of small bilateral pleural effusions, which have a tendency to be subpulmonic in location.55 Thrombotic complications including deep venous thrombosis, renal vein thrombosis, arterial thrombosis, and pulmonary embolism are a common occurrence in this hypercoagulable state.56,57 The hypercoagulable state is due, in part, to loss of clotting inhibitors (protein S, protein C, and antithrombin III) in the urine, volume depletion, and platelet abnormalities.57 The presence of a large volume of pleural fluid, a unilateral effusion, effusions of disparate size, pleuritic chest pain or acute dyspnea, or an exudate, hemorrhage, or neutrophil predominance on pleural fluid analysis should prompt an immediate evaluation for pulmonary thromboembolic disease.
Approximately a million patients per year in the United States present with parapneumonic effusions. Parapneumonic effusions can be uncomplicated (small, free-flowing effusion with pleural fluid pH > 7.30, resolves with antibiotics alone) or complicated (large, loculated effusion with pleural fluid pH < 7.30, requires pleural space drainage for resolution of pleural sepsis).58 The end stage of a complicated parapneumonic effusion is an empyema. Empyema is defined as pus in a body cavity and, therefore, empyema thoracis is pus in the pleural space. Pus assumes its character because it is composed of coagulable pleural fluid, cellular debris, fibrin, and collagen. Pus appears as a thick, yellow-white, opaque fluid.
The three stages of a parapneumonic effusion are the exudative (capillary leak) stage, the fibrinopurulent (transitional) stage, and the organizational (empyema) stage. The exudative stage covers the approximate time period from the beginning of pleural fluid collection and the next 5 to 10 days. When neutrophils migrate to the lung to control pneumonitis, they adhere to the capillary endothelium and release oxygen radicals and proteases that result in capillary leak. With its high protein concentration, this extravascular fluid moves along a pressure gradient from the interstitium of the lung to the pleural space. If formation exceeds removal, a pleural effusion will develop. This effusion is usually small to moderate in volume and exudative, with a neutrophil predominance, a pH > 7.30, a glucose > 60 mg/dL, and an LDH < 700 IU/L.58 Almost all patients treated with appropriate antibiotics for pneumonia in this stage will have complete resolution of the pleural effusion over 1 to 2 weeks without clinically significant pleural space sequelae.58
If the infection remains untreated or inappropriately treated, the effusion evolves into the fibrinopurulent stage, which is characterized by increasing pleural fluid volume, continued fever, and pleural fluid that contains a large number of neutrophils and possibly organisms identified by Gram's stain or culture. Later in this stage, which covers a period of approximately 7 to 14 days following initial fluid formation, loculation ensues and pleural fluid pH falls to < 7.30, the glucose decreases to < 60 mg/dL, and the LDH rises to > 1,000 IU/L. However, the fluid may not be purulent. Without treatment or inadequate therapy over the next 2 to 3 weeks, an empyema will develop. The empyema may reside in a single loculus or in multiple loculi, and aspiration of the pleural fluid demonstrates pus that will usually culture an organism, if the patient has not been on prior antimicrobial therapy and the fluid is placed immediately in transport media.58 The most common organisms responsible for empyema are anaerobes, Staphylococcus aureus, Streptococcus pneumoniae, and Gram-negative aerobes, with the responsible organism(s) dependent upon the patient's underlying risk factors for pneumonia.59-62 Once a patient enters the late fibrinopurulent stage or empyema stage, a contrast chest CT scan should be obtained to better delineate pleural space anatomy and to evaluate the underlying lung parenchyma.63 Depending on the pleural space pathologic findings, these patients require treatment with either surgery (video-assisted thoracoscopic surgery64 or thoracotomy65) or image-guided chest tubes and fibrinolytic therapy.66 There is a high failure rate if patients in the late fibrinopurulent or empyema stage are treated with antibiotics alone, therapeutic thoracentesis, or chest tube drainage without imaging; and a second procedure is usually necessary to resolve pleural sepsis.63 Furthermore, mortality is highest in patients with complicated parapneumonic effusions and empyemas treated with medical therapy alone, therapeutic thoracentesis, or chest tube drainage.
Clinical features that increase the likelihood that a parapneumonic effusion will require drainage include prolonged symptoms, anaerobic infection, failure to respond to antibiotic therapy, and virulence of the bacterial pathogen.58,67 Chest radiograph and CT findings that increase the likelihood that a parapneumonic effusion requires drainage includes an effusion > 40% of the hemithorax, an air/fluid level, loculation, multiple loculations, large loculations, and pleural enhancement or thickening on CT scan.58,67 Pleural fluid characteristics that increase the likelihood that a parapneumonic effusion requires drainage include empyema, positive Gram's stain or culture, low pleural fluid pH (< 7.30), low pleural fluid glucose, and high pleural fluid LDH.58,67,68
The options for pleural space drainage of a complicated parapneumonic effusion and empyema include chest tube drainage with or without fibrinolytic therapy, image-guided catheter drainage with or without fibrinolytic therapy, thoracoscopy with decortication, standard thoracotomy with decortication, and open drainage. The clinical decision concerning drainage is relatively straightforward for the patients in the exudative stage or those with empyema; the former need antibiotics alone without drainage, while the latter always require pleural space drainage. Patients in the fibrinopurulent stage must be evaluated thoughtfully to estimate the probability of needed drainage. Factors such as the volume of pleural fluid, pleural fluid analysis, presence or absence of loculation, duration of the pneumonia, comorbid disease, immune status, and presence or absence of positive pleural fluid bacteriology, and the organism involved must be considered in the clinical decision.
There are approximately 300,000 cases of malignant pleural effusions diagnosed in the United States annually. Dyspnea is the most common presenting symptom, followed by cough.6 Of patients presenting with a massive pleural effusion, approximately two thirds will have malignancy.69 When there is contralateral mediastinal shift with a large or massive effusion, the effusion is usually caused by a carcinoma that is not a lung primary. When there is a large or complete opacification of the hemithorax without contralateral shift or ipsilateral shift, lung cancer is the most likely cause, usually squamous cell carcinoma involving the mainstem bronchus; other diagnoses to consider with this radiographic finding include a fixed mediastinum from malignant lymph nodes, malignant mesothelioma, and parenchymal tumor invasion. Bilateral effusions with a normal heart size should also suggest malignancy as the underlying cause; malignancy was the cause in 50% of 78 patients who presented with these radiographic findings.12 The other 50% of the patients had transudative effusions from hepatic hydrothorax, nephrotic syndrome, severe hypoalbuminemia, and constrictive pericarditis, and exudates from lupus pleuritis, esophageal rupture, and tuberculous pleurisy (rare except in HIV-positive patients).
Lung and breast cancer are the most common causes of a malignant pleural effusion, accounting for about 65% of cases; ovarian and gastric cancer are the two next most common carcinomas to metastasize to the pleura and represent 6 to 10% of cases. Lymphoma represents about 10% of cases in series of malignant pleural effusions. Less than 10% of malignant effusions have an unknown primary tumor at the time of diagnosis.70
Virtually all cancers have been found to metastasize to the pleura. Paramalignant effusions are effusions associated with a known malignancy but malignant cells cannot be demonstrated in pleural fluid or pleural tissue.71 Lymphatic obstruction and increased capillary permeability caused by cytokines are important mechanisms causing pleural fluid formation. Endobronchial obstruction resulting in pneumonia and a parapneumonic effusion and atelectasis with a transudative effusion also are causes of a paramalignant effusion. Pulmonary embolism, superior vena cava syndrome, chylothorax, radiation therapy, drug reactions, and severe hypoalbuminemia also can cause paramalignant effusions.
Malignant pleural effusions are typically exudative but on rare occasion can be transudative.6,72 Transudative malignant effusions are most commonly caused by concomitant disease, particularly congestive heart failure, but also may be due to early lymphatic obstruction and endobronchial obstruction producing an atelectatic effusion. The pleural fluid glucose and the pH are low in about 30% of patients who present with malignant effusions.35 The low glucose is generally in the range of 30 to 50 mg/dL and the pH in the range of 7.05 to 7.29. Between 10 and 14% of patients with malignant pleural effusions are amylase-rich73,74; isoenzyme analysis shows that the amylase is primarily of salivary origin. The pleural fluid–to-serum ratio of amylase in malignancy is in the range of 5:1, much lower than in pancreatic disease.74
Finding a low pleural fluid pH (< 7.30) in malignant pleural effusions is associated with a poorer prognosis, a higher positive yield for malignant cells on cytology and pleural biopsy, and less success with chemical pleurodesis than when the pH is > 7.30.35 However, a meta-analysis of more than 400 patients with malignant effusions demonstrated that, even when the pH was in the range of 6.70 to 7.26, 46% of the patients were still alive at 3 months from the time of initial pleural fluid analysis.75 Furthermore, 65% of patients in the lowest quartile of pH (6.70 to 7.26) had successful pleurodesis, compared with 88% of patients who had a pH of > 7.27.76 Although pH directly correlates with survival and less successful pleurodesis, the relationships are not strong, and therefore pH should not be used as the sole criterion for whether or not to recommend pleurodesis; other factors, such as performance status77 and primary tumor,75 also need to be considered. Patients should be evaluated on a case-by-case basis when deciding whether or not to recommend pleurodesis.
A low pH and low glucose level occur in far advanced malignant involvement of the pleural space when significant tumor burden and tumor-induced fibrosis35,78 involve the pleural surface. The tumor burden and fibrosis inhibit, but not completely, glucose transfer from blood to pleural fluid. The glucose that does move into pleural fluid is utilized at a rate similar to other noninfected pleural fluids, to its end products CO2 and lactic acid. Because these end products are not removed from the pleural space at a normal rate, they accumulate and result in a lower pH.78
The yield of cytologic examination and pleural biopsy is high in malignant effusions with a pH of < 7.30 because of the larger tumor burden on the pleural surfaces.35 Pleurodesis tends to be unsuccessful when the pH is low because the lung may be trapped by tumor or fibrosis or because the tumor burden prevents the chemical agent from initiating mesothelial cell injury that initiates the inflammatory cascade that leads to fibrosis.79 Furthermore, tumor and fibrosis on the pleural surface may block submesothelial fibroblast migration into the coagulable pleural fluid, preventing collagen deposition.
Adenocarcinoma of the lung is the most common malignancy causing an amylase-rich pleural effusion, followed by adenocarcinoma of the ovary.73 These tumors produce an ectopic salivary-like isoamylase. A salivary-rich amylase effusion occurring in the absence of esophageal perforation has a high likelihood of being malignant.
Pleural effusions are found in approximately 40% of patients with a pulmonary embolism.27 These effusions are virtually always less than a third of a hemithorax, present on the initial chest radiograph, and unilateral.27 Approximately 50% of patients have evidence of consolidation (pulmonary infarction) on chest radiograph at presentation.27 In a small series of 26 patients, 27% had transudates.54 Presumably, the exudative effusions are due to pulmonary ischemia/infarction; and the transudates are caused by atelectasis secondary to chest pain. Features that suggest that a pulmonary embolism is an unlikely cause for a pleural effusion include a large or massive effusion, bilateral effusions, effusions delayed in onset > 24 h from time of presentation, increase in the size of the effusion after 72 h, and effusions unaccompanied by ipsilateral chest pain.27 Pleural effusions that increase after 3 days with a documented pulmonary embolism suggest the following diagnoses: recurrent embolization, an infected pulmonary infarction, another diagnosis such as pneumonia, or spontaneous hemothorax with heparin therapy.
In summary, pleural effusions due to pulmonary embolism are small and unilateral and their onset occurs soon after the initial symptoms. These effusions tend to reach their maximum size within a few days. Pulmonary infarctions are associated with larger hemorrhagic pleural effusions that resolve more slowly than effusions without infarction, which are smaller and serous. Ipsilateral chest pain occurs in virtually all patients with pleural effusions from pulmonary embolism. Effusions that are delayed in onset or increase in size later in the course tend to be associated with recurrent embolism, secondary infection or another diagnosis.
Tuberculous pleural effusion presents a spectrum from an acute illness simulating pneumonia to indolent disease. The most common symptoms are fever (86%), cough (80%), and chest pain (75%). Tuberculous pleural effusions are small to moderate in size, and a parenchymal infiltrate is seen in < 50% of patients on a standard chest radiograph.80 Approximately 80% of patients will have a subpleural infiltrate identified on CT.81 A purified protein derivative (PPD) skin test can be negative on presentation in up to 30% of patients81,82 and is probably best explained by mononuclear suppressor cells in the peripheral circulation that are not found in the pleural space.83 Over time, the PPD will become positive.
The classic pleural fluid analysis in tuberculous pleurisy shows 90 to 95% lymphocytes37; however, in acute tuberculous pleurisy84 and tuberculous empyema,85 neutrophils predominate. The effusion is serous with a protein in the range of 4 to 5 g/dL.39 The pH is virtually always < 7.40 and is < 7.30 in approximately 20% of cases.44 Pleural fluid glucose is similar to serum glucose in most cases and is < 60 mg/dL in 20%.45 The finding of > 10% mesothelial cells86 and pleural fluid eosinophilia87 make the diagnosis unlikely. The nucleated cell count is generally < 5,000/mL.
The diagnostic test with the greatest sensitivity is percutaneous pleural biopsy.88 The sensitivity of pleural tissue culture ranges from 55 to 85%, and pleural tissue histology from 50 to 85%. The average sensitivity of pleural fluid culture is 30% with the pleural fluid acid-fast bacilli smear being positive in < 10% of patients. When pleural fluid and pleural tissue culture and histology are combined with sputum analysis, a diagnosis should be established in 80 to 90% of patients.
Tuberculous pleural effusion can be treated with a 6-month regimen of isoniazid and rifampin with pyrazinamide for the first 2 months,89 or with 6 months of isoniazid and rifampin alone in areas with a low percentage of isoniazid resistance.90 Patients with HIV infection may require longer treatment. Untreated patients with tuberculous pleurisy have a 65% chance of developing pulmonary or extrapulmonary tuberculosis in the ensuing 5 years.29 The administration of corticosteroids can result in more rapid lysis of fever and resolution of the effusion; however, it probably does not affect pleural fibrosis.30
Rheumatoid pleural effusions occur most commonly in male patients with active articular disease and rheumatoid nodules.7,31,91 The most common time of onset is within the first 5 years following diagnosis. However, rheumatoid effusions can appear 3 years before or > 20 years after diagnosis is established.92 A rheumatoid pleural effusion may be turbid, have a yellow-green tint,93 or appear to contain debris. Nucleated cell counts vary from 100 cells/mL in chronic effusions to 15,000/mL in acute rheumatoid pleurisy. Neutrophils predominate in the acute disease and lymphocytes in the chronic form. The pleural fluid total protein can be as high as 7 g/dL. Chronic rheumatoid pleurisy has the classic triad of a glucose level of < 30 mg/dL, an LDH of > 1,000 IU/L, and a pH of 7.0094; acute effusions usually will not have the triad. Pleural fluid complement levels are low and pleural fluid rheumatoid factor tends to be > 1:320, but this is a nonspecific finding.95,96 Definitive diagnosis of rheumatoid pleurisy can be made by cytologic examination. The pattern of round or oval giant multinucleated cells, large elongated "tadpole"- or "comet"-shaped cells, and a background of granular necrotic material is considered specific for rheumatoid pleurisy.97 This cytologic picture represents exfoliation of pleural inflammatory cells or necrobiotic nodules into the pleural space, predominantly from the visceral pleura. Corticosteroids may be effective in symptom resolution in acute disease but do not appear to alter the course of pleural fibrosis.
Trapped lung occurs when a fibrous membrane covers the visceral pleura, preventing lung expansion.33,98-100 Causes of trapped lung include empyema, rheumatoid pleurisy, malignancy, uremic pleuritis, BAPE, hemothorax, coronary artery bypass graft, and pneumothorax therapy for tuberculosis. Patients with trapped lung can be dyspneic if the area of lung trapped is large or asymptomatic with a small trapped lung. The effusion recurs rapidly following thoracentesis to the pre-thoracentesis volume. Pleural fluid forms with trapped lung because failure of lung expansion creates a space en vacuo, and this negative pressure space fills with fluid.1 The unilateral pleural effusion can vary from small to large, depending upon the extent of trapped lung.
The fluid is serous and is typically borderline between a transudate and exudate. If the inflammation is remote, the effusion is usually transudative; if there is active or recent inflammation, it is usually exudative. In chronic trapped lung, the nucleated cell count is generally < 1,000 and predominantly mononuclear; pH and glucose are normal. Closer to the time of acute inflammation, the cell count and percentage of neutrophils will be higher.
The diagnosis of trapped lung should be considered when an effusion has been present for several months or longer. The diagnosis is presumptive when there is failure of lung expansion on a chest radiograph immediately following thoracentesis (in the absence of endobronchial obstruction) and can be confirmed by finding an initial negative pleural liquid pressure (< –4 to –7 cm H2O).98,99 A pleural space elastance > 19 cm H2O also correlates strongly with trapped lung.100 Pleural space elastance is determined by measuring the change in pleural pressure following removal of a volume of pleural fluid. Others have found that the pleural elastance curve is not linear with higher values in the early and late phases of thoracentesis.98
Decortication is effective if the underlying lung is relatively normal, and can be performed years after the diagnosis is established. Only patients with large trapped-lung effusions who are symptomatic should be considered for decortication.
The majority of pleural effusions will resolve with effective treatment of the underlying disease, such as congestive heart failure and lupus pleuritis. Chest tube drainage is used for complicated parapneumonic effusions, chylothoraces, and large hemothoraces. Chest tubes are also placed for symptomatic malignant effusions in preparation for chemical pleurodesis. Decortication is commonly used in the management of empyema and should be considered in patients with trapped lung or fibrothorax from any cause. If patients with trapped lung or fibrothorax have significant pulmonary impairment (FVC or total lung capacity < 40% predicted) and are good surgical candidates with relatively normal underlying lung parenchyma, decortication should be performed. Patients with lupus pleuritis, postcardiac injury syndrome, sarcoid pleurisy, and drug-induced pleural disease generally respond to corticosteroid therapy with rapid resolution of symptoms and effusion.
Alternative NamesFluid in the chest; Pleural fluid
A pleural effusion is an accumulation of fluid between the layers of the membrane that lines the lungs and chest cavity.Causes
Your body produces pleural fluid in small amounts to lubricate the surfaces of the pleura, the thin membrane that lines the chest cavity and surrounds the lungs. A pleural effusion is an abnormal collection of this fluid.
Two different types of effusions can develop:
There may be no symptoms.Exams and Tests
During a physical examination, the doctor will listen to the sound of your breathing with a stethoscope and may tap on your chest to listen for dullness.
The following tests may help to confirm a diagnosis:
The cause and type of pleural effusion is usually determined by thoracentesis (a sample of fluid is removed with a needle inserted between the ribs).Treatment
Treatment may be directed at removing the fluid, preventing its re-accumulation, or addressing the underlying cause of the fluid buildup.
Therapeutic thoracentesis may be done if the fluid collection is large and causing pressure, shortness of breath, or other breathing problems, such as low oxygen levels. Treatment of the underlying cause of the effusion then becomes the goal.
For example, pleural effusions caused by congestive heart failure are treated with diuretics and other medications that treat heart failure. Pleural effusions caused by infection are treated with antibiotics specific to the causative organism. In patients with cancer or infections, the effusion is often treated by using a chest tube to drain the fluid. Chemotherapy, radiation therapy, or instilling medication within the chest that prevents re-accumulation of fluid after drainage may be used in some cases.Outlook (Prognosis)
The expected outcome depends upon the underlying disease.Possible Complications
Call your health care provider if symptoms suggestive of pleural effusion develop.
Call your provider or go to the emergency room if shortness of breath or difficulty breathing occurs immediately after thoracentesis.Update Date: 8/7/2006
Updated by: David A. Kaufman, M.D., Assistant Professor, Division of Pulmonary, Critical Care & Sleep Medicine, Mount Sinai School of Medicine, New York, NY. Review provided by VeriMed Healthcare Network.http://www.nlm.nih.gov/medlineplus/ency/article/000086.htm
Abstracts and Clinical Articles
Predictors of talc pleurodesis outcome in patients with malignant pleural effusions.
Lung Cancer. 2008 Apr 8
Osmangazi University, Medical Faculty, Department of Chest Disease, 26480 Meselik, Eskisehir, Turkey.
Keywords: Malignant pleural effusions; Talc; Pleurodesis; pH; ADA
OBJECTIVE: Chemical pleurodesis is an accepted palliative therapy for patients with recurrent, symptomatic, malignant pleural effusions (MPE). The purpose of the study was to determine the factors that have an effect on successful pleurodesis for MPE.
PATIENTS AND INTERVENTIONS: Eighty-four consecutive patients with biopsy-proven malignant pleural disease and recurrent, symptomatic MPE were eligible to participate in this study. Five grams of talc mixed in 150ml of normal saline were administered via tube thoracostomy or small-bore catheters after complete drainage of the pleural effusion.
RESULTS: Seven patients did not return for their 30-day follow-up visit and were excluded from further analysis. Successful pleurodesis was achieved in 63 of 77 eligible patients (81.8%) with MPE. In the univariate analysis, female gender, Karnofsky performance status, pleural fluid pH, cholesterol, and adenosine deaminase level showed a significant association with the probability of success. Multivariate logistic regression analysis showed that pleural fluid pH and ADA levels were independent predictors of talc pleurodesis outcome.
CONCLUSION: Our results show that pleurodesis using talc as the sclerosing agent is a simple and acceptable procedure with high efficacy for controlling MPE, especially when used in appropriate patients.
Pleural fluid viscosity may help identifying malignant pleural effusions.
Respirology. 2008 May
Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Keelung, Taiwan.
BACKGROUND AND OBJECTIVE: Cancer cells are larger in size and more rigid than blood cells. As the size and rigidity of cells contribute to blood viscosity, an association may exist between high pleural fluid viscosity and cancer cells in pleural effusions. The aim of this study was to determine the correlation between pleural fluid viscosity and cell constituents or laboratory data in pleural diseases with different aetiologies.
METHODS: Fluid viscosities were determined in pleural effusions obtained via thoracocentesis. Pleural fluid viscosities were correlated with the laboratory data and with the percentages of different cellular constituents as assessed by cytological examination.
RESULTS: Pleural fluid viscosity was highest in malignant pleural effusions with positive results on cytological examination, and was correlated with the percentages of tumour cells (Spearman's rho = 0.24, P = 0.037) and mitotic figures (rho = 0.23, P = 0.041) in the exudates. Multivariate logistic regression analysis showed that pleural fluid viscosity was a significant determinant of positive results on cytological examination (odds ratio (OR) 6.26, 95% confidence interval (CI) 1.32-29.8), as were the levels of protein (OR 1.48, 95% CI 1.01-2.16) and LDH (OR 1.001, 95% CI 1-1.002).
CONCLUSION: High pleural fluid viscosity may suggest a potential diagnosis of malignant pleural effusion.
Zoledronic Acid is Effective Against Experimental Malignant Pleural Effusion
Am J Respir Crit Care Med. 2008 Apr 3
Department of Critical Care and Pulmonary Services, Applied Biomedical Research and Training Center "Marianthi Simou" and "George P. Livanos" Laboratory, General Hospital "Evangelismos", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
* To whom correspondence should be addressed. E-mail: email@example.com .
Key words: pleural disease, monocyte chemoattractant protein, vascular endothelial growth factor, angiogenesis, aminobiphosphonate
RATIONALE: Aminobiphosphonates, such as zoledronic acid (ZA), exert potent indirect anti-tumor effects and are currently tested against human solid tumors. The anti-tumor actions of aminobiphosphonates, including angiostasis, are relevant to the pathogenesis of malignant pleural effusion (MPE), but no study has addressed the efficacy of these compounds against malignant pleural disease.
OBJECTIVES: Here we hypothesized that treatment of immunocompetent mice with ZA would halt tumor progression in a mouse model of adenocarcinoma-induced MPE.
METHODS: To induce MPE in mice, Lewis lung carcinoma (LLC) cells were delivered directly into the pleural space. Subsequently, animals were treated with ZA in both a prevention and a regression protocol.
MEASUREMENTS AND MAIN RESULTS: ZA treatment resulted in significant reductions in pleural fluid accumulation and tumor dissemination, while it significantly prolonged survival. These effects of ZA were linked to enhanced apoptosis of pleural tumor cells, decreased formation of new vessels in pleural tumors, and reduced pleural vascular permeability. In addition, ZA was able to inhibit the recruitment of mononuclear cells to pleural tumors, with concomitant reductions in matrix metalloproteinase (MMP)-9 release into the pleural space. Finally, ZA limited the expression of proinflammatory and angiogenic mediators, as well as the activity of small GTP-proteins Ras and RhoA, in tumor cells in vivo and in vitro.
CONCLUSIONS: ZA is effective against experimental MPE, suggesting that this intervention should be considered for testing in clinical trials.
Pleural effusion associated with primary
lymphedema: a perspective on the yellow nail syndrome.
Beer DJ, Pereira W Jr, Snider GL.
A 28-year-old woman with bilateral pleural effusions and generalized, primary lymphedema beginning with facial erysipelas at 6 years of age is presented. The pleural effusions were exudates with 250 cells per mm3, 92 per cent of which were lymphocytes. Lymphatic stasis was demonstrated by persistence of the blue dye in the dorsa of her feet 3 months after a lymphangiogram of both lower extremities, pelvis, and abdomen. Her nails were not remarkable. Our patient represents the twentieth recorded case of pleural effusion in association with primary lymphedema. Women have been afflicted more than twice as often as men, and the age of onset has varied from birth to the eighth decade. Yellow dystrophic nails may precede or follow lymphedema or the pleural effusion and have occurred in only 11 of the 20 patients.
PMID: 629489 [PubMed - indexed for MEDLINE]
--------------------------------------------------Bilateral pleural effusions associated with generalized primary lymphoedema and erysipelas. A case report and the probable pathogenesis.
Hereditary late-onset lymphedema with
pleural effusion and laryngeal edema.
Herbert FA, Bowen PA.
We examined two middle-aged male cousins with unexplained edema of postpubertal onset involving the upper and lower limbs, face, and larynx and, in one of them, a persistent pleural effusion. Scintilymphangiography detected an apparent paucity or absence of lymph nodes in the axillae and above the inguinal ligaments, indicating a defect in the lymphatic systems. Laryngeal edema, confirmed endoscopically, produced changes in one of them in the flow volume loop characteristic of a variable extrathoracic obstruction. A family study showed autosomal dominant transmission of the disorder. The nosology of late-onset lymphedema is briefly discussed, with particular reference to the so-called yellow nail syndrome.
PMID: 6679236 [PubMed - indexed for MEDLINE]
Yellow nails, lymphedema
and pleural effusion. Treatment of chronic pleural
effusion with pleuroperitoneal shunting
JD Brofman, JB Hall, W Scott and AG Little
Department of Medicine, University of Chicago Medical Center.
Hereditary late-onset lymphedema with pleural effusion and laryngeal edema
F. A. Herbert and P. A. Bowen - Archives of Internal Medicine
Pleurx - Pleural Catheter
Chronic indwelling pleural catheter for malignant pleural effusion in 25 patients
Identification of clinical factors predicting Pleurx catheter removal in patients treated for malignant pleural effusion.
Emergent Management of Pleural Effusion
ICD-10 and ICD-9 Diagnostic Codes and Resources
ICD-10: J90 - Pleural effusion, not elsewhere classified
Pleurisy with effusion
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