E. Conservative treatment

Pleural DiseasesAtul C. Mehta, MBBS, FACP, FCCPProf of Medicine, Lerner College of MedicineStaff, Respiratory InstituteCleveland Clinic, Cleveland, OHQ.1: Does this pt have a Pleural Effusion?74 y/o man, 40 PY of smoking history with 1 wk H/O dyspnea, fever &cough. You suspect pneumonia; there is a 20- 40% probability ofeffusion.What would be the most accurate physical examinationmaneuver(s) for determining if this pt has a effusion or not?A. Absence of reduced TVF makes effusion less likelyB. Increased intensity of breath sounds makes a effusionmore likelyC. Dullness to percussion makes effusion more likelyD. A or CE. None of the above, PE findings are non-specific!1

Does this pt have a Pleural Effusion?Wong C et al , JAMA 2009, 301(3): 305 Data synthesis: 310 citations 5 Prospective, N=934 8 physical maneuvers were studied: Inspection, percussion,auscultation, TVF, VR, rub, crackles Dullness: Most accurate to diagnose pleural effusion+ve LR: 8.7 (2.2-33.8,CI 95%) Absence of reduced TVF made pleural effusion less likely-ve LR: 0.21(0.12-0.37, CI 95%) CXR may not be necessaryQ.1: Does this pt have a Pleural Effusion?74 y/o man 40 PY of smoking history with 1 wk H/O dyspnea, fever &cough. You suspect pneumonia; there is a 20- 40% probability ofeffusion.What would be the most accurate physical examinationmaneuver(s) for determining if this pt has a effusion or not?A. Absence of reduced TVF makes effusion less likelyB. Increased intensity of breath sounds makes a effusionmore likelyC. Dullness to percussion makes effusion more likelyD. A or CE. None of the above, PE findings are non-specific!2

How Much Fluid (cc) is There? Blunting of CDA: AP: 250-500 Lateral: 175-200 10 mm on decubitus film: Amenable to thoracentesis CT: Pleural from parenchymal abnormalities Assess underlying lung parenchyma Ultrasound: Guides difficult thoracentesisLoculated, “dry tap”, body habitus/position Superior to CT in distinguishing fluidfrom masses or thickeningUltrasound for Pleural Effusion3

To Tap or Not to Tap? Dxtic tap should always be performed when an effusion isdetected Exceptions: < 1 cm of free fluid on a lateral decubitus X-ray Obvious cause for effusion (e.g CHF) Bleeding diathesis: INR > 2, PTT > 2 X upper limit of normalPlt: < 25,000 Local skin infection Re-expansion pulmonary edema can occur if volumes >1500are withdrawn rapidly Consider monitoring pleural pressure (keep > -20 cm H 2 O)Pleural Fluid: What is Normal? 10-20 uM width potential space between visceral & parietal pleura Volume: 0.1-0.2 mL/kg Clear liquid Low protein: 1.0-1.5 g/dL Glucose: same as serum WBC: 7.6 (active transport of HCO3 - )4

Pleural Fluid TestsAll effusions: Protein LDH pH Cell count and differential Cholesterol*On exudates: Gram stain and culture Fungal stain and culture AFB smear and culture CytologyAdditional tests: Amylase Creatinine Triglycerides-chylomicrons Hematocrit Cholesterol ANA, RF, complement Adenosine deaminase (ADA) LE cells MesothelinMechanisms Leading to Exudates and TransudatesTransudatesExudatesIncreased hydrostatic pressureCHFIncreased capillary permeabilityPneumoniaReduced osmotic pressureNephrotic syndromeDiseases of the pleural surfaceMesotheliomaIncreased negative intrapleuralpressureAcute atelectasisIncreased negative intrapleuralpressureChronic atelectasis, Trapped lungReduced lymphatic drainageMalignancy5

Common in ClinicalPracticeTransudative Pleural EffusionCommon in theBoard Exam CHF Peritoneal dialysis Myxoedema Nephrotic Syndrome SVC Syndrome Meig’s Syndrome Cirrhosis Fontan’s procedure Sarcoidosis Hypoproteinemia Urinothorax Pleural Amyloid Atelectesis Myxoedema PEExudate vs. TransudateLight’s Criteria (Chest,1972; 77: 507)Pl/S Protein Ratio Pl/S LDH Ratio LDH IU/L*Transudate 200* 2/3 of ULN serum values Sensitivity: 98% Specificity: 82%6

Exudate vs. Transudate:Newer CriteriaLDH %(Serum ULN)Cholesterol(mg/dl)Protein(g/dl)Transudate 45 >2.9 Lower threshold for LDH No need for phlebotomy No diagnostic improvement over Light’s Criteria Cholesterol may be helpful in diuretic treated CHF (Pro 3-4 g/dl)Hefner et al , CHEST 1997; 111:970 (Meta-analysis)Pleural effusion in CHF: Pt on diuretics! Light’s criteria erroneously identify ~ 25% of transudates asexudates in pts with CHF Rxed with diuretics andRBC >10 000/mm Albumin gradient: (SA-PA): > 1.2 g/dl Total protein gradient: Pleural NT-proBNP: : Pleuarl BNP: Cholesterol Criteria:> 3.1 g/dL> 1300 pg/ml> 115pg/ml< 45 mg/dlRespirology 2011; 16: 44–52Chest 2009; 136: 671–7.7

Q. 2: 30 y/o AAM from Miami, Fl, with acuteexcruciating Rt. flank pain, N/V: PH: Single episode of hematuria1 y ago FH: Twin sister with Sarcoid OE: In distress with pain, Rt flank tenderness & UQguarding, Rt dullness and reduced TVF CXR: Moderate Rt effusion KUB film couldn’t be doneQ. 2: 30 y/o AAM from Miami, Fl with acuteexcruciating Rt. flank pain, N/V:Pleural Fluid: Appearance: Amber pH: 6.9 LDH: 40 IU/Dl Protein: 0.5 g/dl Cholesterol:0 mg/dl Hb: +18

Q. 2: 30 y/o AAM from Miami, with acuteexcruciating Rt. flank pain, N/V:Following administration of adequate analgesia, most appropriateaction would be:A. US of gallbladder and pancreasB. CTPEC. PleuroscopyD. Urology consultE. EGDQ. 2: 30 y/o AAM from Miami, with acuteexcruciating Rt. flank pain, N/V:Following administration of adequate analgesia, most appropriateaction would be:A. US of gallbladder and pancreasB. CTPEC. PleuroscopyD. Urology consultE. EGD9

Urinothorax Urinary obstruction Retroperitoneal leakage Effusion Trauma Calculi Ca Renal Bx Failed nephrostomy Rare (more in the board exam) Diagnosis: Appearance Odor Transudate Low pH Pl/S Creatinine: >1The Journal of Urology 1986, 135: 805Definitive Diagnoses Based on Pleural Fluid AnalysisDiagnosisCriteriaUrinothorax pH < 7, transudate, Pl/S Creat. >1.0EmpyemaMalignancyPus, Positive Gram stain or culturePositive cytologyChylothoraxTriglycerides >110 mg/dL, ChylomicronsTB, FungalPositive stains, culturesHemothoraxHct. > 50% of bloodPeritoneal dialysisProt. < 1g/dL, Gluc. 300-400 mg/dLEsophageal rupture pH < 7, high amylase (salivary)Lupus pleuritis LE cells, Pl/s ANA >1.010

Rule of ThumbIndications For Chest Tube Drainage Frank pus Positive pleural fluid gram stain Positive pleural fluid culture Pleural fluid pH < 7.0Rheumatoid Pleural Effusion Incidence 3% Male > Female (4-15 x) Above age 35 Pleuritic pain: 20-30% Rheumatoid nodule: 80% Precedes arthritis: 10% Bilateral: 25% High RA serum titers Exudate Low glucose:

Lupus Effusion Common: 75% pts Small-moderate Pleuritic pain common Precedes sytemic disease: 6% ANA titer: 1:160 Pl/s ANA titers >1 Low complements LE cell (Spec > Sen)Drug Induced LupusDrugs: Procainamide, Hydralazine, Dilantin, INHPleural and lung involvement is commonCNS and renal involvement is rareANA +ve, Anti-DNA –veHydralazine: Effusion 25-30%Procainamide: Effusion 33%, Lung infiltrates: 30%13

TB PleurisySecondaryPrimaryLymphocytes: >50%Mesothelial cells : 200 pg/ml*Closed pleural Bx: 60+% yieldInfrequentHypersensitivity reactionPolymorphonuclear LeukocytosisExudateResolves spontaneously-ve PPD doesn’t R/O TBQ.3: 30 y/o female with slowly progressing SOB of6 months PH: Pneumo-once on either side 4 wks apart;1 yr ago OE: Increased dullness, reduced TVF at Ltbase, Rt basilar crackles, small ascites CXR: Hyperinflation, vague interstitialchanges, Lt effusion Pleural fluid: Milky white fluid, Triglycerides 200mg/dl14

Q.3: Most likely diagnosis is?A. LymphomaB. Catamenial PneumothoraxC. Gorham’s SyndromeD. LymphangioleiomyomatosisE. Histiocytosis-XQ.3: Most likely diagnosis is?A. LymphomaB. Catamenial PneumothoraxC. Gorham’s SyndromeD. LymphangioleiomyomatosisE. Histiocytosis-X15

ChylothoraxTriglyceride Level (mg/dl)Interpretation> 110 Chylothorax50-110 Borderline*

ChylothoraxQ.4: 63 y/m with RA… 63 y/o male with crippling RA, in wheel chair x 2 yrsAnnual CXR revealed mod bil effusions; No CP, cough or SOB Old CXR: Bil subpulmonic effusion x 5 years PPD –ve Pleural Fluid: Milky-white, Shiny WBC 2000/cc, L: 90% Glucose 16 mg/dl LDH 1200 IU/dl Triglycerides 30mg/ml Cholesterol 150 mg/dl Large amount of cholesterol crystals17

Q.4: 63 y/o male with RA….Most appropriate treatment would be:A. Start MCT dietB. LymphangiogramC. Serology for W. Bancrofti infestationD. Bil pleuroperitoneal pumpE. Conservative treatmentQ.4: 63 y/o male with RA….Most appropriate treatment would be:A. Start MCT dietB. LymphangiogramC. Serology for W. Bancrofti infestationD. Bil pleuroperitoneal pumpE. Conservative treatment(“Enemy of good is perfection”)18

Chyliform Effusion (Pseudochylothorax) Milky, high lipid content fluid w/o thoracic duct involvement Rare With long standing TB, RA, Trapped lung Cholesterol: >200 mg/dl W or W/O cholesterol crystals LPEP: No chylomicrones May have high triglyceridesChylous vs. Chyliform EffusionsChylousChyliformAppearance: Milky MilkyTriglycerides: >110 mg/dL < 50 mg/dLCholesterol: < 200 mg/dL (50-200) >200 mg/dL (200-4500)Chylomicrons: Present AbsentCholesterol crystals: Absent Present19

Bilious Effusion Looks like bile P/S Bili ratio >1 BT pleural fistula in allcases Trauma, PCLB, T tubes,stents, parasitesQ. 5: Dyspnea following thoracentesis 70 y/o male with H/O CHF, onoptimal Rx underwentthoracentesis in ER for a large Rteffusion using a 16g spinalneedle. 3.5 lt of serosanguinousfluid was removed uneventfully.Minutes following the procedurethe pt developed progressiveSOB and required 100% FiO2 OE: Tachypnea, BP: 100/70,P:100/min;Rt lung wheeze and basilar rales20

Q. 5: Dyspnea following thoracentesisThe most appropriate statement regarding the eventwould be:A. Place a large bore chest tube for tension pneumoB. Transfuse 2 U of pack cells for a hemothoraxC. Inj Lasix 60 mg IVD. Intrapleural pressure measurement could haveavoided the eventE. Check troponin levelsQ. 5: Dyspnea following thoracentesisThe most appropriate statement regarding the eventwould be:A. Place a large bore chest tube for tension pneumoB. Transfuse 2 U of pack cells for a hemothoraxC. Inj Lasix 60 mg IVD. Intrapleural pressure measurement could haveavoided the eventE. Check troponin levels21

Q. 6: Relief of dyspneaWhat is the most important mechanism for the relief ofdyspnea following thoracentesis?A. Increase PaO2B. Placebo effectC. Reduced intrathoracic volumeD. Improved FEV1 and FVCE. Increased lung complianceQ. 6: Relief of dyspneaWhat is the most important mechanism for the relief ofdyspnea following thoracentesis?A. Increase PaO2B. Placebo effectC. Reduced intrathoracic volumeD. Improved FEV1 and FVCE. Increased lung compliance22

Finally 15-20% of pleural effusions will defy a definitive dx: obscureetiology even after several thoracenteses (and closed pleuralbiopsies). Pleuroscopy is indicatedBoard Review CourseNumber 1 RuleAttend the course to attain medical excellence and notjust to pass the exam.23

Board Review CourseRule number 2Don’t fail the exam!Good Luck24

Q: Match Highlighted Effusion with the AppropriatePtProtein(g/dl)LDH(IU/L)pHGlucose(mg/dl)Cholesterolmg/dl)Triglyceride(mg/dl)1 3.3 1000 7.8 30 200 302 3.6 300 6.5 60 200 103 3.2 200 7.3 93 150 3354 3.3 100 7.4 88 30 305 3.6 700 7.2 25 400 406 4.1 1100 7.0 50 180 15A. 70 y/o M with an indwelling Foley catheter and & grade feverB. 55 y/o Fexperiencing chest pain & fever after an EGDC. 33 y/o F with lymphomaD. 67 y/o M with CAD 3 d after hospitalization for CHFE. 40 y/o alcoholic male with pneumonia & persistent high fever despiteI.V. antibiotics.Q: Match Highlighted Effusion with the AppropriatePtProtein(g/dl)LDH(IU/L)pHGlucose(mg/dl)Cholesterolmg/dl)Triglyceride(mg/dl)1 3.3 1000 7.8 30 200 302 3.6 300 6.5 60 200 103 3.2 200 7.3 93 150 3354 3.3 100 7.4 88 30 305 3.6 700 7.2 25 400 406 4.1 1100 7.0 50 180 15A. 70 y/o M with an indwelling Foley catheter and & grade feverB. 55 y/o F experiencing chest pain & fever after an EGDC. 33 y/o F with lymphomaD. 67 y/o M with CAD 3 d after hospitalization for CHFE. 40 y/o alcoholic male with pneumonia & persistent high fever despiteI.V. antibiotics.25

Q: Match highlighted effusion with appropriate Rx strategy ina pt with PneumoniaGlucose (mg/dl) pH LDH U/L Gram Stain Culture1 70 7.3 250 N N2 55 7.15 1000 N N3 35 6.9 1000 N N4 30 7.0 1000 Positive Pending5 30 7.0 1000 N PositiveA. Simple parapneumonic effusion, Rx with appropriate antibioticsB. Borderline parapneumonic effusion, needs serial thoracentesis plus antibioticsC. Complicated parapneumonic effusion, needs tube thoracostomy plus antibioticsD. Empyema, needs tube thoracostomy plus antibioticsQ: Match highlighted effusion with appropriate Rx strategy ina pt with PneumoniaGlucose (mg/dl) pH LDH U/L Gram Stain Culture1 70 7.3 250 N N2 55 7.15 1000 N N3 35 6.9 1000 N N4 30 7.0 1000 Positive Pending5 30 7.0 1000 N PositiveA. Simple parapneumonic effusion, Rx with appropriate antibioticsB. Borderline parapneumonic effusion, needs serial thoracentesis plus antibioticsC. Complicated parapneumonic effusion, needs tube thoracostomy plus antibioticsD. Empyema, needs tube thoracostomy plus antibiotics26

Parapneumonic EffusionspH Glucose G.Stain/CultureManagementSimple > 7.2 > 40 mg/dl Negative AntibioticsBorderline 7-7.2 > 40 mg/dl Negative Serial thoracentesisComplicated < 7 < 40 mg/dl Negative Tube thoracostomyEmpyema < 7 < 40 mg/dl Positive Tube thoracostomyWhat About Appearance? Blood-tinged pleural fluid is of little diagnostic value:10,000 RBCs/uL: blood tinged fluid (1ml blood in 500)100,000 RBCs/uL: grossly bloody fluid (1ml in 50) (peripheral blood: 5,000,000RBCs/uL) Causes of 100,000 RBCs/uL: Trauma (will clot) Malignancy Post-cardiac injury Pulmonary embolism Hemothorax is present when the hematocrit of the pleural fluid is >50%of that of the peripheral blood (tube thoracostomy, exploration).27

Pleural Effusions Post-CABG 24% (7/29) CHF 7% (2/29) constrictive pericarditis 3% (1/29)pulmonary embolism 66% (19/29)no discernable cause 42% (8/19) bloody 58% (11/19) nonbloody BloodyPleural Effusions Post-CABG Likely related to bleeding within the pleural space Maximum size within 1 month after CABG Frequently eosinophilic High levels of LDH Resolve after 1-2 thoracenteses Nonbloody Maximum size more than 1 month after surgery Mostly lymphocytic Low LDH Difficult to manage (recur)28

A 35-yr-old male ex-smoker diagnosed with AIDS 4 years ago receivesaerosolized pentamidine for PJP prophylaxis. He is admitted with acuterespiratory failure requiring intubation and mechanical ventilation. You are calledto the bedside because the patient suddenly developed high airway pressureswith a drop in blood pressure and arterial oxygen saturation. When you examinethe patient, you notice decreased air entry on the left side with a deviation of thetrachea to the right. What should you do next:a. Order a CT scan of the chest.b. Add 10 cm H 2 0 of PEEP.c. Insert a chest tube on the right side.d. Insert a large-bore needle in the second intercostal space on the left.e. Place the patient on his side with the left side down. A 35-yr-old male ex-smoker diagnosed with AIDS 4 years ago receivesaerosolized pentamidine for PJP prophylaxis. He is admitted with acuterespiratory failure requiring intubation and mechanical ventilation. You are calledto the bedside because the patient suddenly developed high airway pressureswith a drop in blood pressure and arterial oxygen saturation. When you examinethe patient, you notice decreased air entry on the left side with a deviation of thetrachea to the right. What should you do next:a. Order a CT scan of the chest.b. Add 10 cm H 2 0 of PEEP.c. Insert a chest tube on the right side.d. Insert a large-bore needle in the second intercostal space on the left.e. Place the patient on his side with the left side down.29

Tension Pneumothorax The pressure of air in the pleural space exceeds ambientpressure throughout the respiratory cycle. May result in acute respiratory failure hemodynamic compromise, and cardiopulmonary arrest. If tension pneumothorax is suspected, a large-bore needleshould be inserted immediately in the affected side to allowimmediate relief of the tension until tube thoracostomy can beperformed.30

PNEUMOTHORAX Accumulation of air in the pleural space Primary pneumothorax: without underlying lungdisease Secondary pneumothorax: in association with certainlung diseases IatrogenicKey Points A young woman with a pneumothorax and any patient with parenchymalabnormalities on post drainage CXR should undergo a high-resolutionCT to look for underlying lung disease. Primary pneumothorax (no underlying lung disease) can be managedwith initial simple aspiration. Secondary pneumothorax (underlying lung disease) requires tubethoracostomy. Consider pleurodesis: recurrent pneumothorax: significantly decreases recurrence rate (13% vs. 36%). occupations in which development of pneumothorax may be dangerous (airplanepilots or deep sea divers).31

Estimating The Size of a Pneumothorax 2 vs. 3 dimensions % ptx= (1-D L3 /D H3 )*100 2 cm difference on CXR = 58% ptxsize Lung volume= (6) 3 = 216 cm 3 Hemithorax volume= (8) 3 = 512 cm 3 Lung size=216/512= 42% Pneumothorax size= 58%.32

Pleural Effusion Further pulmonary testing rarely provides moreinformation!N=83; 725 tests: 9 +ve, 7 false +vePeterman TA et al, JAMA 1984;252:1051–1053. Immunocytometry on pleural effusion aids in Dx oflymphomaAm Rev Respir Dis 1992;145:209–211.Trapped Lung: Diagnosis Mechanism: Hydrostatic pressure No active pathology Negative mean pleural pressure which gets worse withfluid removal Chest pain during thoracentesis Hydropneumothorax post-thoracentesis No improvement in SOB/DOE No lung expansion: CT, FB requiredHeldecker J, CHEST 2006; 130:117333

Trapped Lung Persistent unilateral effusion Result of fibrinous or granulomatous pleuritis Dysfunctional resolution of pleural inflammation Inability of a portion of the lung to re-expand Fluid fills the space to maintain hydrostatic equilibriumTrapped Lung: Clinical Features Diagnostic dilemma Chronic, asymptomatic pleural effusion Large effusion: SOB/DOE H/O Remote infection, pleurisy, trauma, surgery Restrictive physiology Rapid re accumulation Time to Dx: 40 months (12-144)Huggins JT, CHEST 2007;131:20634

All of the following are the features of Trapped lung except?A: Remote history of Rheumatoid PleuritisB: Rapid reaccumulation of fluid postthoracentesisC: Pleural Fluid LDH of >210 IU/LD: Chest pain during thoracentesisE: Decortication is the treatmentTrapped Lung: Etiology S/P CABG: IMA (non-hemorrhagic) Empyema Post-cardiotomy syndrome Uremic pleuritis Rheumatoid pleurisy TB effusion Hemothorax35

Trapped Lung: Pleural Fluid Appearance: Serous Total proteins: 2.9 g/dl (2-4.2) LDH: 124 IU/L (99-170) pH: 7.37 Nucleated Cells: 415/ul (21-1837) Differential: Mononuclear Cells 78%(63-96)CHEST 2007; 131:206Lung EntrapmentTrapped LungPathogenesisCXRInflammation, infection,CaContralateral mediastinalshiftHydrostatic ForcesNo shiftFluid Exudate TransudateDiscordant ExudatePpl Positive NegativePleural spaceElastanceNormalHighHighRx Rx the cause DecorticationSeminars Respir Criti Care Med 2002; 22:63136

Pleural EffusionThoracic US is being used frequently: By internists Quick, safe, bedside Solid vs Liquid Subpulmonic vs subdiapragmetic pathology Loculated vs free fluidCT scan is a must: Empyema (split pleura sign) vs Lung abscess Loculation Mesothelioma/plaques Chylous effusionPleural Effusion Further pulmonary testing rarely provides moreinformation!N=83; 725 tests: 9 +ve, 7 false +vePeterman TA et al, JAMA 1984;252:1051–1053. Immunocytometry on pleural effusion aids in Dx oflymphomaAm Rev Respir Dis 1992;145:209–211.37

Categorizing Risk for Poor Outcome in Patients withParapneumonic EffusionPleural Fl. Anatomy GS and Cx pH Risk DrainageMinimal (< 10 mm)Free-flowing ? ? V. low NoSmall to moderate(>10 mm to 7.2 Low NoFree-FlowingLarge (> 1/2 chest)Loculated Positive 7.0 - 7.2 Moderate YesThickened pleura Pus < 7.0High YesColice, et al. Chest, 2000:118:1158-71.Effusions of Indeterminate Etiology About half will resolve spontaneously and no disease will beapparent on long-term follow-up (e.g. BAPE) The other half: carcinoma, mesothelioma, lymphoma, TB,con. tissue dis., PE, drug-induced. Many are caused by malignant disease which is eitherobvious or incurable anyway The most likely treatable or curable diagnosis is TB.38

Effusions of Indeterminate Etiology Observe the patient (no systemic or constitutionalsymptoms)Or Proceed with thoracoscopy or thoracotomy (fever, wt loss,large effusion) Thoracoscopy (medical-VATS) Direct visualization of the pleura Sampling Therapy (pleurodesis)Benign Asbestos Pleural Effusion (BAPE) Nonspecific exudate, often bloody Peak incidence is about 10 to 15 years after onset of asbestosexposure (before other pleural complications of asbestos). Persists for a mean of 4 months and then resolvesspontaneously in most patients. Does not seem to be an indicator for increased risk ofmesothelioma. Diagnosis is by history of asbestos exposure and exclusion ofother causes.39

PleurodesisAgent and Dose Success Rate Adverse EffectsTalc2.5 to 10 GmDoxycycline500 mgTetracycline (NA)500 mg to 20 mg/KgBleomycin15 to 240 Units153/165 (93%) Pain: 9/131 (7%)Fever: 21/131 (16%)43/60 (72%) Pain: 24/60 (40%)240/359 (67%) Pain: 51/359 (14%)Fever: 36/359 (10%)108/199 (54%) Pain: 56/199 (28%)Fever: 48/199 (24%)Nausea: 21/199 (11%)Walker-Renard et al. Ann Int Med 1994;120:56.40

Pleural Diseases Effusions: Fluid Transudates Exudates Pus Empyema Blood Hemothorax Chyle: Chylothorax Pneumothorax (air) Malignancy (cells) Mesothelioma Secondary41

Key Points Transudates are usually due to a systemic problem outside thelung-pleura Exceptions: early atelectasis, PE Exudates are usually due to direct lung-pleural involvement. Exceptions: pancreatitis, subphrenic abscess PE can be associated with a transudate (atelectasis) or anexudate (infarction) Measurement of pleural fluid LDH, cholesterol and proteinconcentrations can differentiate a transudate from an exudatewithout phlebotomy.42