ROLE OF PLEURAL FLUID CHOLESTEROL IN DIFFERENTIATING EXUDATIVE AND TRANSUDATIVE PLEURAL EFFUSION

ROLE OF PLEURAL FLUID CHOLESTEROL IN DIFFERENTIATING EXUDATIVE AND TRANSUDATIVE PLEURAL EFFUSION

DISSERTATION SUBMITTED TO THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY, CHENNAI In partial fulfilment of the requirements for the degree of

M.D. BRANCH – XVII

REGISTRATION NUMBER: 201727202

(TUBERCULOSIS AND RESPIRATORY MEDICINE)

DEPARTMENT OF RESPIRATORY MEDICINE

TIRUNELVELI MEDICAL COLLEGE HOSPITAL

TIRUNELVELI – 627011

MAY-2020

CERTIFICATE BY THE DEAN

I hereby certify that this dissertation entitled “ROLE OF PLEURAL FLUID CHOLESTEROL IN DIFFERENTIATING EXUDATIVE AND TRANSUDATIVE PLEURAL EFFUSION” is a record of work done by Dr. P.RAGASUDHA, in the Department of RESPIRATORY MEDICINE, Tirunelveli Medical College, Tirunelveli, during her postgraduate degree course period from 2017- 2020. This work has not formed the basis for previous award of any degree.

Date :

Place : TIRUNELVELI The DEAN

Tirunelveli Medical College,

Tirunelveli - 627011.

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled “ROLE OF PLEURAL FLUID CHOLESTEROL IN DIFFERENTIATING EXUDATIVE AND TRANSUDATIVE PLEURAL EFFUSION” , is a record of work done by Dr. P.RAGASUDHA, in partial fulfilment for the award of the degree of Doctor of Medicine in TUBERCULOSIS AND RESPIRATORY MEDICINE for the May 2020 examination by the Tamilnadu Dr.M.G.R. Medical University, Chennai. This is a bonafide original research work done by her in the department of RESPIRATORY MEDICINE, Tirunelveli Medical College, under my guidance and supervision.

Date :

Place: TIRUNELVELI Dr.E.MATHAN, M.D.

SENIOR ASSISTANT PROFESSOR, DEPARTMENT OF RESPIRATORY MEDICINE,

TIRUNELVELI MEDICAL COLLEGE,

TIRUNELVELI.

DECLARATION BY THE CANDIDATE

I solemnly declare that this dissertation titled “

submitted by me for the degree of M.D., is the record work carried out by me during the period of 2017-2020 under the guidance of Dr.E.MATHAN, M.D, Senior Assistant Professor, Department of Respiratory Medicine, Tirunelveli Medical College, Tirunelveli.

The dissertation is submitted to The Tamilnadu Dr. M.G.R. Medical University, Chennai, towards the partial fulfilment of requirements for the award of M.D.(Branch XVII) Tuberculosis and Respiratory Medicine examination to be held in May 2020.

Place: Tirunelveli Dr. P.RAGASUDHA,

Date Department of Respiratory Medicine,

Tirunelveli Medical College,

Tirunelveli

ACKNOWLEDGEMENT

I wish to thank all the people who helped and supported me in completing this dissertation.

I thank, the DEAN Prof. Dr. S M KANNAN, M.S M.Ch, for permitting me to conduct this study and use the resources of the hospital.

I am greatly thankful to my Head of the Department, Prof. Dr. K KRISHNAMOORTHY, M.D, and Associate Prof.Dr. S MUTHUKUMAR, M.D, who has always provided me the immense help, guidance and support.

I am extremely thankful to my guide, Dr. E MATHAN, M.D, Senior Assistant professor, for his valuable suggestions and concern for successful completion of this dissertation.

I am sincerely thankful to my assistant professors, Dr. O M RAHMAN SHAHUL HAMEEDandDr. P SENTHIL ARASU for their guidance, contribution, support and cooperation for this study.

I wish to express my sincere gratitude to my colleagues,

Dr. GAYATHRI S RAJEEV

I also thank all my senior and junior postgraduate COLLEAGUES, for their cooperation and help for this study. I thank all the PATIENTS, who participated and cooperated in this study. Without their contribution, this study would not have been possible.

CERTIFICATE – II

This is to certify that this dissertation work title “ROLE OF PLEURAL FLUID CHOLESTEROL IN DIFFERENTIATING EXUDATIVE AND TRANSUDATIVE PLEURAL EFFUSION” of the candidate Dr. P.RAGASUDHA with registration Number 201727202 for the award of

in the branch of TUBERCULOSIS AND RESPIRATORY MEDICINE

XVII

. I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion page and result shows 14% percentage of plagiarism in the dissertation.

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CONTENT

SL.NO TITLE PAGE NO

1. INTRODUCTION 1

2. AIM AND OBJECTIVES 4

3. REVIEW OF LITERATURE 5

4. MATERIALS AND METHODS 47

5. RESULTS AND ANALYSIS 52

6. DISCUSSION 73

7. CONCLUSION 76

8. LIMITATION 77

9. BIBLIOGRAPHY

10. ANNEXURE

PROFORMA

CONSENT FORM

MASTER CHART

ABBREVIATIONS

AFB – Acid Fast Bacilli

ADA - Adenosine deaminase

ANA - Anti Nuclear Antibody

ARDS - Acute Respiratory Distress Syndrome

CT – Computed Tomography

CBNAAT – Catridge Based Nucleic Acid AmplificationTtest CKD – Chronic Kidney Disease

CSF – CerebroSpinal Fluid

CCF – Congestive Cardiac Failure HDL – High Density Lipoprotein LDL – Low Density Lipoprotein VLDL – Very Low Density Lipoprotein HIV – Human Immunodeficiency Virus VEGF – Vascular Endothelial Growth Factor TBPE –Ttuberculous pleural effusion

MTB – Mycobacterium tuberculosis

USG - Ultrasonography

SLE – Systemic Lupus Erythematosis

LDH – Lactate dehydrogenase

1

INTRODUCTION

Normally the pleural space contains only a few millilitres of pleural fluid. Pleural fluid accumulates when the rate of formation exceeds the rate of absorption. Pleural effusion is divided into two types depending on pathophysiology. They are Transudate and Exudate[1]. The important step in pleural effusion is to decide whether the effusion is a transudate or exudates by Light’s criteria [2] .

A transudative pleural effusion develops when the systemic factors influencing the formation or absorption of pleural fluid are altered. The fluid may originate in the lung, pleura, or peritoneal cavity [3].

An exudative pleural effusion develops when the pleural surfaces or the capillaries where the fluid originates are altered .If the effusion is a transudate no further diagnostic procedures are necessary and if the effusion is an exudate ,more diagnostic investigation is indicated to delineate the cause of the effusion[4].

Initially a pleural fluid protein level of 3.0g/dl was used to differentiate transudates from exudates [5].

Light et al. in 1972 found criteria to have sensitivity and specificity of 99% and 98%, respectively, for differentiating transudative and exudative pleural effusions.

Exudates meet at least one of the following criteria, whereas transudative pleural effusions meet none [Light’s criteria]:

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1. Ratio of protein in pleural fluid and serum >0.5 2. Ratio of LDH in pleural fluid and serum >0.6

3. Pleural fluid LDH >2/3rd of upper limit of serum LDH [6].

But the other studies only reproduce specificities of 70–86% using Light’s criteria. About 25% of transudates are mistakenly identified as exudates by using Light’s criteria.Acute diuresis in heart failure can elevate protein levels into exudative range [7].

Heffner et al. 2002 have identified pleural effusion of exudative type with at least one of the following conditions .

1. Pleural fluid protein >2.9 gm/dL.

2. Pleural fluid cholesterol >45 mg/dL (1.16 mmol/L).

3. Pleural fluid LDH >2/3rd of upper limit of serum [8].

The newer parameters like ADA, cholesterol, interferon gamma assay, ANA, Rheumatoid factor, tumor markers etc. are analysed in the pleural fluid to separate exudates and transudate and they helped to arrive at an etiological diagnosis very easily [9].

Pleural fluid cholesterol can be used to classify exudative and transudative pleural effusion because it misclassifies only a fewer cases than Light’s parameters[10].

The cutoff value of pleural fluid cholesterol as 45mg/dl (1.16 mmol/L) eliminates the possibility of being equivocal to transudates and exudates, and has been used to improve

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the accuracy of differentiating transudative and exudative effusion [11].Present study was conducted to assess the usefulness of pleural fluid cholesterol in differentiating exudative and transudative pleural effusion.

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AIM

To assess the role of pleural fluid cholesterol in differentiating exudative and transudative pleural effusion.

OBJECTIVES

1.To study the diagnostic value of pleural fluid cholesterol in differentiating exudative and transudative pleural effusion.

2.To compare sensitivity and specificity of pleural fluid cholesterol and Light’s criteria in differentiating exudative and transudative pleural effusion.

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REVIEW OF LITERATURE PLEURAL ANATOMY:

Pleura is the serous membrane that covers the mediastinum, the lung parenchyma, the rib cage and the diaphragm.

Pleural cavity is developed from the primitive body cavity [coelomic] , which is derived from primitive mesoderm of embryo. The pleural cavity is lined by a mesothelial membrane, called the pleura[12].

Inner visceral pleura covers the lung surface and inter lobar fissures. Outer parietal pleura which lies outside the visceral pleura and covers the inner surface of the thoracic cavity, diaphragm and mediastinum .

The part of parietal pleura that covers inner surface of the ribs and intercostal muscles is called costal pleura, and the one which covers the convex surface of the diaphragm is called diaphragmatic pleura. Cervical pleura which extends into the neck and the part of the parietal pleura which covers mediastinum is called mediastinal pleura [13].

The Surface of the pleura is glistening and semitransparent. The potential space between these two membranes is named as pleural space.

PLEURAL SPACE:

Pleural space is slit like and it is filled with a thin layer of fluid called pleural fluid. The function of the pleural fluid is mainly lubrication, it reduce and eliminate the friction

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forces, and allows movement of the lung with the chest wall during inspiratory and expiratory movements.

FUNCTIONAL ANATOMY OF PLEURA:

In light microscopy the pleura is found to have five layers.

Five layers of pleura are:

1. Mesothelium

2. Submesothelial connective tissue 3. Layer of elastic tissue

4. Another layer of loose connective tissue which contains blood vessels , lymph vessels and nerves.

5. Deep fibroelastic layer adherent to the underlying tissue.

The connective tissue layer of the visceral pleura has two important functions:

(a) Elastic recoil of the lung in expelling air from the lung.

(b) Restricting the volume of the lungs , to be inflated thereby protecting the lungs from overinflation [14].

MESOTHELIAL CELLS OF PLEURA:

Mesothelial cells covers the surface of both parietal and visceral pleura. These are polygonal in shape, 0.1 micrometer in diameter and 3 micrometer in length. The surface of mesothelial cell is bushy. Mesothelial cells are metabolically active cells.

There exists a tight junction between these mesothelial cells [15].

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BLOOD SUPPLY OF PLEURA:

PARIETAL PLEURA :

Blood supply is very rich and supplied mainly by systemic vessels.

• Costal pleura - Intercostal and internal mammary arteries

• Cervical pleura - Subclavian artery

• Mediastinal pleura - Bronchial, internal mammary and mediastinal vessels

• Diaphragmatic pleura - Superior phrenic branch of internal mammary artery, posterior mediastinal artery which is from aorta in thorax, inferior phrenic artery a branch from abdominal aorta

Venous drainage of parietal pleura is mainly to Azygos vein. From there, it drains into Superior vena cava. Some of the venous blood from diaphragmatic pleura drains Into inferior vena cava also.

VISCERAL PLEURA :

In humans visceral pleura is thick and the main blood supply is from bronchial artery.

Venous blood from visceral pleura is drains into pulmonary veins [16].

LYMPHATICS OF PLEURA :

The lymphatic plexuses present in the costal pleura are confined to the intercostal spaces mainly and are minimal or absent over the ribs. These lymphatic vessels covering the costal surface drain ventrally towards the lymph nodes which are present along the course of internal thoracic vessels and dorsally towards the internal intercostal nodes.

The lymphatic vessels from the mediastinal pleura pass to the tracheobronchial and mediastinal lymph nodes.

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The lymphatic vessels of the pleura that covers the diaphragm, pass to the parasternal nodes, posterior mediastinal and middle phrenic nodes.

The parietal pleural lymphatic drainage plays a vital role in the formation and removal of fluid in pleural space, both in physiological and pathological condition.

There are abundant lymphatic vessels in the visceral pleura. These visceral pleural lymphatics form a plexus that intercommunicate with all vessels that run on the surface of the lung and they run towards the hilum and by penetrating the lung, they join the bronchial lymph vessels, by passing through the interlobular septa[17].

INNERVATION OF THE PLEURA:

PARIETAL PLEURA:

Sensory nerve endings that are present in the diaphragmatic and costal parietal pleura. The somatic intercostal nerves supply the costal pleura and also the peripheral part of the diaphragmatic pleura. When these areas are stimulated, pain is perceived in the adjacent part of the chest wall. Phrenic nerve innervates the central portion of the diaphragm. If the central portion of the diaphragm is stimulated or irritated ,pain will be perceived in the ipsilateral shoulder[18].

VISCERAL PLEURA:

Visceral pleura contains no sensory nerve fibers, so visceral pleura is pain insensitive. It may be manipulated without causing any unpleasant sensation. The visceral pleura also have sensory receptors which are closely related to elastic fibres[19]. Vagus nerve supplies the visceral pleura by its pulmonary branches and sympathetic trunk.

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SURFACE ANATOMY OF PLEURA

At the apices and along the inner margins of the lungs, the pleura lies very close to the lungs. It rises 2-3 cm above the clavicle.

At the lower aspect, pleura extends below the lung 4 to 5 cm anteriorly and 9-10cm posteriorly.

It lies at the level of 8th rib in the mid clavicular line, 10th rib in the mid axillary line, and the 12th rib at the scapular line.

PLEURAL FLUID:

VOLUME:

The pleural fluid normally originates in the capillaries present in the parietal pleura. In physiological state, pleural fluid present in the pleural space is very minimal.

The quantity of fluid is similar in both the pleural spaces. The mean amount of pleural fluid in normal is 8.4 + 4.3 ml[2].

CELLS IN PLEURAL FLUID:

Normally pleural fluid contains

 75% - macrophages

 25% - lymphocytes.

 < 2% - mesothelial cells, neutrophils and eosinophils.

BIOCHEMICAL FACTORS:

• In humans normally pleural fluid contains 1 to 2 gm /dl of protein.

• K+ level is identical to plasma.

• Hco3+ level is 20 -25% higher than plasma.

• Na+ level is 3-5% less than plasma.

• Glucose level is identical to plasma [20].

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These electrolyte gradients suggest that an active process is involved in formation of pleural fluid.

PLEURAL FLUID PRESSURE AND DYNAMICS :

The movement of fluid within pleural membranes is based on the balance between the hydrostatic and oncotic pressure exists between the microvasculature and the pleural space. It is governed by Starling‘s Law[21].

FORMATION OF PLEURAL FLUID:

Pleural fluid that enters the pleural space originated either from

• The pleural capillaries

• The interstitial spaces of the lung

• The intrathoracic lymphatics

• The intrathoracic blood vessels

• The peritoneal cavity PLEURAL CAPILLARIES:

Normally a gradient for fluid formation is present in the parietal pleura. The hydrostatic pressure in the parietal pleura is nearly 30 cm H2O. The pleural pressure is 5 cm H2O approximately. The net hydrostatic pressure is 30 - (-5) = 35 cm H2O. It favours the movement of fluid from the pleural capillaries to the pleural space. oncotic pressure of the plasma is nearly 34 cm H2O. Pleural fluid normally contains only a small amount of protein. It’s oncotic pressure is approximately 5 cm H2O. So the net oncotic pressure gradient of 34-5 = 29 cm H2O. So the net gradient of 6 cm H2O [ 35- 29 ] favours the movement of fluid to the pleural space from the pleural capillaries[22].

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PLEURAL FLUID FROM INTERSTITIUM :

In diseased conditions like CHF, the most of pleural fluid originated from the interstitial spaces of the lungs. The volume of pleural fluid collected is directly proportional to increased wedge pressure.

So increase in interstitial fluid leads to increase in the subpleural interstitial pressure and the fluid will move through thick visceral pleura to the pleural space[23].

FROM PERITONEAL CAVITY :

If there is free fluid in the peritoneal cavity and there are openings in the

diaphragm, pleural fluid accumulation can occur. In this conditions, the pressure in the pleural cavity is less than the pressure in the peritoneal cavity, so the fluid will move from the peritoneal space to the pleural space.

No direct lymphatic connections between the pleural and peritoneal cavities[24].

THORACIC DUCT INJURY:

Disruption of thoracic duct results in accumulation of lymph, producing a chylothorax. The rate of pleural fluid accumulation with chylothorax may be more than 1,000 mL/day.

PLEURAL FLUID ABSORPTION:

• Lymphatic clearance

• Clearance via capillaries in visceral pleura.

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LYMPHATIC CLEARANCE :

The amount of fluid that can be cleared through these lymphatics is substantial.

The pleural space is in communication with the lymphatic vessels in the parietal pleura by means of stomas.Stomas are not seen in the visceral pleura.

From the pleural space Cells, proteins and particulate matters are removed by pleural lymphatics. Lymphatic clearance is 28 times as high as the normal rate of pleural fluid formation[25].

PATHOGENESIS OF PLEURAL EFFUSION FORMATION:

The basic pathogenesis leads to the formation of the pleural effusion are:

• Formation of increased pleural fluid.

• Decreased absorption of the pleural fluid.

FORMATION OF INCREASED PLEURAL FLUID:

1]. Increased interstitial fluid in the lungs

• Pneumonia

• Left ventricular failure

• Pulmonary embolism

• ARDS

• Post lung transplantation

2]. Increased pressure in intrapleural vessels:

 Right or left ventricular failure.

 Superior vena caval syndrome.

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3]. Increased permeability of pleural capillaries:

• Pleural Inflammation

• Increased levels of VEGF.

4]. Increased protein level in pleural fluid:

 Increased permeability pulmonary edema

 hemothorax

5]. Decreased pleural pressure :

 Atelectasis of lung

 Increased elastic recoil of the lung.

6]. Increased fluid in peritoneal cavity:

 Peritoneal dialysis.

 Ascites

7]. Thoracic duct disruption

8]. Disruption of thoracic blood vessels

DECREASED ABSORPTION OF PLEURAL FLUID:

1]. Obstruction of the lymphatics draining the parietal pleura 2]. Increased systemic vascular pressure

• Superior venacava syndrome.

• Right heart failure.

3]. Disruption of the aquaporin system in the pleura[1].

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DIFFERENTIAL DIAGNOSIS OF PLEURAL EFFUSION:

TRANSUDATIVE PLEURAL EFFUSION 1. Congestive heart failure

2. Nephrotic syndrome.

3. Hepatic hydrothorax.

4. Pulmonary embolism 5. Peritoneal dialysis

6. Superior vena cava obstruction 7. Myxedema

8. Urinothorax 9. Sarcoidosis 10. Amyloidosis

11. Leakage of CSF into pleural space 12. Atelectasis [26].

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EXUDATIVE PLEURAL EFFUSION 1. Malignant causes

 Mesothelioma

 Body cavity Lymphoma

 Metastastic disease

 Pyothorax associated lymphoma 2. Infectious diseases

 Tuberculosis

 Bacterial pneumonia

 Invasive fungal diseases

 Viral infections

 Parasitic disease 3. Pulmonary embolization.

4. Abdominal conditions

 Oesophageal perforation

 Acute and chronic pancreatitis

 Abdominal abscesses

 Diaphragmatic hernia

 Post abdominal surgery

 Hepatic transplantation

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5. Collagen vascular diseases

 Rheumatoid pleuritis

 SLE

 Wegener‘s granulomatosis

 Churg-Strauss syndrome

 Drug induced lupus

 Sjogren syndrome

6. Heart diseases:

 Postcoronary artery bypass graft surgery

 Dressler’ syndrome

 Pericardial disease

 Post –Fontan procedure 7. Asbestos related lung diseases 8. Yellow nail syndrome

9. Uremic pleural disease 10. Sarcoid lung

11. obstetric and gynaecological disease

 Ovarian hyperstimulation syndrome

 Meig’s syndrome

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12. Drug induced

 Nitrofurantoin

 Clozapine

 Methotrexate

 Interleukin

 Dantrolene

 Methysergide

 Bromocriptine

 Procarbazine

 Minoxidil

 Amiodarone.

 Interferons.

13. Trapped lung syndrome.

14. Radiation exposure 15. Hemothorax

16. Iatrogenic injury

17. Ovarian hyperstimulation syndrome 18. Diseases of pericardium

19. Chylothorax [27].

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TUBERCULOUS PLEURAL EFFUSION [TBPE]:

Pathogenesis :

 Subpleural caseous focus in the lungs [less commonly lymphnodes] ruptures into the pleural space which results in the entry of tuberculous proteins into the pleural space that initiates a hypersensitivity reaction.

Other possible mechanisms:

 Direct infectious invasion of pleural space

 Tuberculous osteitis of the rib

 Paravertebral cold abscess resulting from vertebral TB

 Hematogenous spread to the pleura.

MALIGNANT EFFUSION:

Several different mechanisms are responsible for the development of effusion in patients with malignancy.

Mechanisms:

Direct results:

 Pleural metastases with increased permeability

 Mediastinal node involvement with diminished pleural lymphatic drainage

 Pleural metastases with obstruction of lymphatic vessels.

 Bronchial obstruction that leads to decreased pleural pressure

 Thoracic duct disruption

 Pericardial involvement

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Indirect results:

 Post obstructive pneumonitis

 Hypoproteinemia

 Pulmonary embolism

 Postradiation therapy[1].

CONGESTIVE CARDIAC FAILURE:

CCF is the most common cause of transudative pleural effusion. Previously it was thought to be due to increased pressure in the pleural capillaries which result in an increased movement of fluid from pleura into the pleural space, and decreased removal of pleural fluid via visceral pleura according to Starling’s law.

Current theories states that the fluid which enters the pleural space is from alveolar capillaries rather than capillaries in the pleura

Pleural effusion in CCF is more related to the left ventricular failure,and also occurs in some patients with right ventricular failure[28].

HEPATIC HYDROTHORAX:

Pleural effusion occasionally occurs as a complication of hepatic cirrhosis.

It usually occurs ony when ascitic fluid is there.patients with cirrhosis have decreased plasma oncotic pressure that leads to accumulation of fluid in pleural space.

Rarely the effusion occurs as a result of movement of ascitic fluid into pleural space from peritoneal cavity[29].

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EVALUATION OF THE PATIENT WITH PLEURAL EFFUSION:

Patients with pleural effusion may be symptomatic or asymptomatic. Following details are needed

for proper evaluation of the causes for pleural effusion.

• Detailed history

• Physical examination

• Diagnostic radiology

• Pleural fluid analysis HISTORY

The common symptoms of patients with pleural effusion are cough, chest pain and breathlessness. The patient will complaint of fever and productive cough, if there is any underlying parenchymal involvement.

Pleuritic type of chest pain is described by the patient as stabbing pain which is aggravated on deep inspiration and coughing . The pain may radiates to the shoulder if the central portion of the diaphragmatic pleura is inflamed. Localized pain occurs If the costal pleura is involved.

BREATHLESSNESS:

Dyspnea in patients with pleural effusion is mainly due to decreased movement of the chest wall due to chest pain or due to underlying parenchymal disease or due to collapse of the underlying lung.

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DRY COUGH:

Dry cough is due to inflammation of pleura or the compression of the lung by the fluid will bring the opposing bronchial walls into contact so that stimulating cough reflex.

ASYMPTOMATIC PATIENTS WITH PLEURAL EFFUSION a. Nephrotic syndrome

b. Rheumatoid pleurisy c. Yellow nail syndrome d. Trapped lung

e. Urinothorax f. Peritoneal dialysis

g. Benign asbestos related pleural effusion

PATIENTS PRESENTING WITH TYPICAL SYMPTOMS a. Bacterial pneumonia

b. Lupus pleuritis c. Pulmonary embolism d. Malignant pleural effusion e. Malignant mesothelioma [30].

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PHYSICAL EXAMINATION :

On examination, the physical signs of pleural effusion will depends on

a) Volume of the pleural fluid b) Underlying lung compression c) Patency of bronchus

Whenever about 500ml of pleural fluid is present, the findings will be

a) Percussion – stony dullness

b) Decreased intensity of breath sounds c) Decreased vocal fremitus.

When more than 1000ml is there

a) Bulging of the intercostal spaces.

b) Diminished expansion of the chest wall c) Percussion- stony dullness upto scapula d) Absent or decreased breath sounds

e) Egophony above the upper level of pleural effusion.

f) Absent vocal fremitus

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With massive pleural effusion

a) Bronchial breath sounds at the apex.

b) Liver and Spleen palpable due to depressed diaphragm.

c) Absent or decreased breath sounds in entire hemithorax.

d) Egophony above the level of pleural effusion.

e) Bulging of intercostal spaces[31].

DIAGNOSIS OF PLEURAL EFFUSION BY RADIOLOGY

a) Chest x ray

b) Ultrasonogram chest c) CT-Chest.

CHEST X RAY:

The postero-anterior view, Lateral view and lateral decubitus view are used to find out pleural effusion.

• In upright position small amount of fluid [ approximately 75 ml ] accumulates between diaphragm and the inferior surface of the lower lobe, without

silhouetting the diaphragm.

• When more fluid accumulates it obliterates the posterior costophrenic angle.

• Increasing amounts of fluid blunt the lateral CP angle.

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MENISCUS SIGN :

In chest x ray postero anterior view, when more fluid accumulates the entire outline of the diaphragm is lost on the affected side, and the fluid extends upward around the anterior, lateral, posterior thoracic walls. It produces homogenous opacification of the lung base with concave upward sloping produces the typical meniscus shape of the fluid[Figure1].

Figure. 1[Meniscus sign]

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LOCULATED EFFUSION:

In loculated type, the effusion is D shaped along lateral chest wall, without obliterating costophrenic angle[32].Figure .2

Figure. 2 [Loulated pleural effusion]

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SUBPULMONIC EFFUSION:

Some times Pleural fluid will accumulated in an infrapulmonary location without extending up the chestwall or spilling into the costophrenic sulci and it is called as subpulmonic effusion. Figure.3

Chest x ray features:

• Apparent elevation of the ipsilateral hemidiaphragm

• Lateral peaking of the hemidiaphragm

• On the left the distance between the lower border of the lung and gastric bubble is greater than 2cm[33].

Figure.3[Subpulmonic effusion]

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ULTRASONOGRAM CHEST:

In USG chest pleural fluid appears as is seen as anechoic[ echo free] or hypoechoic [reduced echogenicity relative to the liver][34].Figure. 4

Figure. 4[USG Chest showing pleural effusion]

 Ultrasound is useful to determine whether pleural fluid is present or not.

 To detect the loculated effusions .

 To identify the appropriate location for thoracentesis,chest tube placement,and pleural biopsy.

 In diagnosing effusions in bedridden patients

 To differentiate the pyopneumothorax from lung abscess.

 To distinct the pleural fluid from pleural thickening[1].

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CT-THORAX:

CT thorax detect even very small effusion.

Identify the presence of inflammation by the presence of pleural thickening and enhancement after injection of the contrast [35] .

Find out underlying lung parenchymal lesions.

Free flowing pleural fluid on CT produces a sickle-shaped opacity[36]. Figure. 5

Figure.5[CT Chest showing sickle shaped pleural effusion]

Loculated pleural effusions - lenticular in shape , smooth margins and displacement of adjacent parenchyma.

CT chest also helpful in detecting mass lesion when it is associated with pleural effusion .

Pleural enhancement in Contrast enhanced CT is more than 80% sensitive and highly specific in evaluation of malignant pleural effusion.

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RIGHT SIDED PLEURAL EFFUSION:

1. Congestive cardiac failure

2. Liver cirhosis with portal hypertension 3. Meig’s syndrome

4. Subphrenic abscess 5. Ruptured Liver abscess

6. Thoracic duct injury below the level of D5.

Figure.6[Right sided pleural effusion]

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LEFT SIDED PLEURAL EFFUSION:

1. Pancreatitis.

2. Thoracic duct injury above the level of D5.

3. Dressler’s syndrome.

4. Left sub diaphragmatic abscess.

5. Esophageal rupture[37].

Figure.7[Left sided pleural effusion]

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BILATERAL PLEURAL EFFUSION:

 Congestive cardiac failure

 Malignancy.

 Viral infections.

 Nephrotic syndrome.

 Pulmonary Embolism.

 Eosinophilic pneumonias.

 Cirrhosis of liver.

 Amyloidosis [38].

Figure.8 Bilateral pleural effusion

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MASSIVE PLEURAL EFFUSION^:

When the Pleural effusion occupies entire hemithorax, it is called massive pleural effusion.

Figure.9 Massive pleural effusion

CAUSES:

 Malignancy.

 Hepatic hydrothorax

 Meig's syndrome

 Hepatic hydrothorax.

 Chylothorax[39].

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THORACENTESIS:

Thoracentesis is a procedure in which needle is inserted into the pleural space, to remove the pleural fluid. It can be done after explaining about the procedure to the patient. It should be done under strict aseptic precautions. It is an important diagnostic procedure in pleural effusion. Pleural fluid analysis will help us to categorize the pleural effusion as either transudate or exudates .

COMPLICATIONS OF THORACENTESIS:

1. Iatrogenic pneumothorax 2. Infections.

3. Hemothorax.

4. Injury to the neurovascular bundle 5. Pain shock[1].

DIAGNOSIS OF PROBABLE ETIOLOGY OF PLEURAL EFFUSION BY GROSS APPEARANCE:

 Transudative effusion - clear and straw coloured, odorless and nonviscid.

 Exudative effusion - amber like, appears cloudy [On prolonged standing exudative effusion clots,and the transudates which has less fibrin content, so remains in a fluid state].

 Bloody effusion –due to damage of a vessel during thoracentesis and during pleural or lung biopsy.

34

[If the fluid is uniformly red , the most probable cause of effusion is malignancy. Other conditions like TB, pulmonary infarction, rheumatoid pleuritis will also leads to a hemorrhagic effusion].

 Hemothorax - seen in trauma, invasive procedures, pleural metastasis and catamenial hemothorax.

 Aspiration of white or milk like fluid - due to chylothorax or cholesterol effusion.

 Brown colored fluid - due to long standing bloody fluid and amoebic liver abscess.

CHARACTER OF PLEURAL FLUID:

 Frank empyema - Purulent fluid or gross pus.

 Mesothelioma - Viscous fluid .

 Ruptured amoebic live abscess - Anchovy sauce like.

 Inflammatory exudates -Turbid fluid character.

ODOUR OF FLUID:

Ammonia odour - urinothorax.

Putrid odour - anaerobic empyema.

Therefore by doing thoracentesis, observation of the fluid color,odour, character, the probable diagnosis of pleural effusion and the possible cause can be ascertained. But further biochemical tests will be needed to confirm etiology.

35

PLEURAL FLUID pH:

Normally the pleural fluid is alkaline in character. high metabolic activity in pleural space decreases the pH level in pleural fluid .it is considered low if the pH value is <

7.3. Most of the transudative effusion will have pH betweeen 7.45 to 7.55. But pH of most exudative effusion will range from 7.30-7.45.

CAUSES OF pH less than 7.2

1. Complicated parapneumonic effusion 2. Oesophageal rupture.

3. Tuberculous pleuritis..

4. Rheumatoid pleuritis 5. Malignancy

6. Hemothorax 7. Systemic acidosis.

8. Lupus pleuritis 9. Paragonimiasis 10. Urinothorax

Pleural fluid pH measurement is useful in deciding management of complicated parapneumonic effusion. If the pH is <7.2 it is an indication for intercostal tube drainage. With pleural fluid pH one can determine whether invasive pleural procedures are required or not[40]..

36

MESOTHELIAL CELLS

Mesothelial cells lines the pleural cavity. They are present in minimal amount in normal pleural fluid. These cells are uncommon in tuberculous pleural effusion. But AIDS patients with Tuberculous effusion usually have increased amount of

mesothelial cells.

Mesothelial cells paucity is seen in:

1. Empyema

2. Chemical pleurodesis

3. Rheumatoid pleuritis

4. Chronic malignant effusion.

37

PLEURAL FLUID GLUCOSE:

Low pleural fluid glucose :

 Pleural fluid glucose level of <60 mg/dl or

 pleural fluid to serum glucose less than 0.5 Causes of low pleural fluid glucose:

1. Tuberculosis

2. Parapneumonic effusion 3. Rheumatoid pleural effusion.

Rare causes :

1. Parasitic infections [ paragonimiasis infection]

2. Hemothorax

3. Churg-Strauss syndrome.

Low pleural fluid glucose in parapneumonic effusion is associated with poor prognosis and it is an indication for intercostal tube drainage as the prime line of treatment[41].

PLEURAL FLUID PROTEIN:

Previously the amount of pleural fluid protein was used to differentiate the transudates and exudates. By comparing pleural fluid protein with serum protein we can diagnose transudative and exudative pleural effusion.

Tubercular effusion – the protein level is almost always more than 4 g/dl.

38

Parapneumonic effusion and malignant effusion – the pleural fluid protein level is usually wide range.

More than 7gm/dl of total protein in pleural fluid usually indicates Waldenstroms macroglobulinemia and multiple myeloma.

Light‘s criteria uses pleural fluid protein to serum protein ratio as one of its criteria to differentiate transudate and exudate effusion.

PLEURAL FLUID LDH :

Pleural fluid LDH is used to differentiate the pleural effusion into exudates and transudates. LDH level is increased in pleural fluid whenever the effusion is due to an inflammatory process. It is included as one of the pleural fluid parameters in Light‘s criteria.

Conditions in which Pleural fluid LDH level of more than 1000 IU/L seen in :

 Complicated parapneumonic effusion

 Empyema

 Pleural paragonimiasis.

 Malignancy.

PLEURAL FLUID CELL COUNT:

Analysis of pleural fluid cell count is very useful in differentiating the causes of pleural effusion. If the total cell count in pleural effusion is >1000/ µL it is more in favour of exudates and if less than 1000 cells/ µL it is more likely of transudates.

39

Pleural fluid cell count more than 10000/ µL is seen in parapneumonic effusion, sub diaphragmatic abscess and acute pancreatitis.

The predominant cell type in transudative effusion are mononuclear cell, macrophages, lymphocytes and mesothelial cells[42].

PLEURAL FLUID EOSINOPHILIA:

When the pleural fluid eosinophil count is > 10% of the total nucleated cells, it is called eosinophilic pleural effusion.

Causes of increased pleural fluid eosinophils with peripheral eosinophilia : 1. Hodgkin disease

2. Fungal infection 3. Paragonimiasis

4. Benign asbestos pleural effusion 5. Churg Strauss syndrome

6. Tropical eosinophilia

7. Drugs –Dantrolene, Nitrofurantoin.

Causes of pleural fluid eosinophilia without peripheral eosinophilia:

1. Trauma

2. Pulmonary infraction 3. Pneumothorax

4. Hemothorax

40

Causes of pleural fluid neutrophilia : 1. Pulmonary infections

2. Acute pulmonary embolism

3. Very early stage of pleural effusion[43].

CYTOLOGICAL EXAMINATION OF PLEURAL FLUID:

Cytological examination of pleural fluid is most informative in the diagnosis of pleural effusion.

L YMPHOCYTIC PLEURAL EFFUSION:

If lymphocytes in pleural fluid are > 80% of total cells it is called lymphocytic effusion.

Causes:

1. Tuberculosis – most common cause.

2. Malignancy 3. Chylothorax.

4. Lymphoma.

5. Yellow nail syndrome 6. Sarcoidosis

7. Rheumatoid disease [44].

41

MALIGNANT EFFUSION:

Characteristic features:

 Malignant cells are large

 The nuclei may exceed 50 µm in diameter

 The nucleoli are large and and exceed 5 µm in diameter

 The malignant cells often have a high nucleocytoplasmic ratio [ the mean nuclear diameter/ cytoplasmic diameter > 0.74 ,the patient had malignant effusion].

The accuracy of cytology has been reported to be 40-87% by various studies [45-47].

PLEURAL FLUID ADA :

Adenosine deaminase is an important enzyme in the degradation of purine and lymphocyte differentiation. It is involved in maturation of monocyte-macrophage lineage. ADA levels tend to be higher in tuberculous pleural effusions than in other exudative pleural effusion.

A cut off level between 40 to 45 U/L is used with levels above this being indicative of tuberculous pleural effusion. The sensitivity and specificity of pleural fluid ADA is 90% for the diagnosis of tuberculous pleural effusion.

42

CAUSES OF ELEVATED ADA : 1. Tuberculous pleurisy

2. Rheumatoid pleurisy

3. Empyema 4. Q fever 5. Malignancy

6. Brucellosis

7. After coronary bypass surgery [48].

PLEURAL FLUID CHOLESTEROL:

Pleural fluid Cholesterol level is studied to differentiate exudative and transudative pleural effusion. pleural fluid cholesterol is derived from

1. Degenerating cells

2. Vascular leakage from increased permeability

Cholesterol is synthesized by the cells lining the pleura themselves and it is depends on metabolic activity and needs[49] . Pleural fluid cholesterol also increased by degenerated leucocytes and erythrocytes [ which contains large quantities].

Pleural cholesterol also derives from plasma. 70% of plasma cholesterol is bound LDL and the remaining cholesterol to HDL or VLDL[50].

Increased permeability of pleural capillaries also leads to increased pleural fluid cholesterol levels.

43

Hamm et al. studied about the cholesterol in differentiating transudative and exudative pleural fluid and found it to be simple and cost effective[51].

Cholesterol cut off value of > 45mg/dl is taken in studies to differentiate exudative and transudative effusion. Pleural fluid cholesterol level of >200mg/dl suggests chyliform effusion.

PLEURAL FLUID AMYLASE:

The amylase rich pleural effusion:

 Pleural fluid to serum amylase ratio > 1 or

 Pleural fluid amylase level above the upper limit of normal serum amylase.

COMMON CAUSES:

Pancreatic disease malignancy

Esophageal rupture[52].

LIPID ANALYSIS

pleural fluid triglyceride is indicated in patients with suspected chylothorax.

Pleural fluid triglyceride level of > 110mg/dl strongly supports the diagnosis of chylothorax. If triglyceride level is < 50mg/dl, chances of chylothorax is less.

If triglyceride level between 50-110mg/dl, do lipoprotein electrophoresis to detect the presence of chylomicrons. Presence of chylomicrons in lipoprotein electrophoresis is diagnostic of chylothorax.

44

INTERFERON –GAMMA:

CD4+ T cells produce Interferon –gamma that migrates into the pleural cavity. It is used in the diagnosis of tuberculous pleural effusion. Interferon-gamma increases polymyristate acetate which induces the hydrogen peroxide production in macrophages, and facilitates the elimination of intracellular parasites. It also inhibits mycobacterial growth in monocytes. Interferon gamma >140pg/ml is significant in diagnosis of tuberculous pleural effusion[53].

IMMUNOLOGICAL TESTS:

The immunological tests are useful for the diagnosis of SLE and Rheumatoid arthritis.

Anti-nuclear antibody (ANA) ,Rheumatoid factor (RF) are assessed in pleural fluid.

ANA IN PLEURAL FLUID

Pleural fluid ANA of >1: 160 or pleural fluid to serum ANA > 1 is suggestive of systemic lupus erythematosis.

Rh FACTOR IN PLEURAL FLUID

When Rh factor in pleural fluid is > 1:320 and greater than serum rheumatoid factor[54,55]

DIFFERENTIATION OF EXUDATIVE AND TRANSUDATIVE EFFUSION:

After complete analysis of pleural fluid the most important step is to differentiate the effusion into exudates and transudates, based on the multiple parameters tested in the pleural fluid.

Initially the pleural fluid protein level was taken as an important parameter for differentiation of exudative and transudative effusion.

45

Later it was found that the pleural fluid protein alone was not quite sensitive to differentiate exudates and transudates and may leads to misclassification[56,57].

Light‘s et al. suggests that pleural fluid protein and LDH levels are to be measured and compare it with serum protein and LDH values in a combination test, used an ‘or’ diagnostic test.

EVALUATION OF PATIENTS WITH PLEURAL EFFUSION

46

Chakko et al. observed that transudative effusions due to congestive heart failure, after treating with diuretics, light‘s criteria will classify it as exudate. This is due to rapid fluid absorption from pleural space[58].

To overcome these pitfall of Light‘s criteria, Roth et al. suggested to do serum and pleural effusion albumin gradient, that also needs blood sampling.

PLEURAL FLUID CHOLESTEROL TO DIFFERENTIATE EXUDATE AND TRANSUDATE :

Pleural fluid cholesterol is studied to separate the exudative and transudative effusion.

A.B. Hamal et al. studied about pleural fluid cholester and found that pleural fluid cholesterol with cut off value of > 45mg/dl has higher sensitivity and specificity in differentiating exudates and transudates than the parameters of Light’s criteria[59].

So this study ‘ROLE OF PLEURAL FLUID CHOLESTEROL IN

DIFFERENTIATING EXUDATIVE AND TRANSUDATIVE PLEURAL

EFFUSION’ was taken to assess the diagnostic utility of this test, in separation of pleural effusion to exudate and transudate in comparison with Light‘s criteria.

47

MATERIALS AND METHODS:

The present study ‘Role of pleural fluid cholesterol in differentiating exudative and transudative pleural effusion’ was conducted in Department of Respiratory Medicine, Tirunelveli Medical College Hospital, Tirunelveli after obtaining approval from Tirunelveli Medical College Institutional Ethical Committee[TIREC].

STUDY DESIGN:

Cross sectional study STUDY DURATION:

The study was carried out during the period of January 2018 to June 2019.

STUDY POPULATION:

Patients were selected from outpatient and inpatient Departments of Tirunelveli Medical College Hospital.

SAMPLE SIZE : 100 INCLUSION CRITERIA:

1. Age > 18 years

2. Patients with definite clinical diagnosis and pleural effusion evidenced by radiological imaging.

48

EXCLUSION CRITERIA:

1. Age <18 years

2. Patients who are not willing for informed consent /thoracentesis.

3. Patients previously diagnosed and treated.

4. Pleural effusion with multiple etiology.

5. CKD

6. Pulmonary embolism METHODOLOGY:

After obtaining informed written consent, detailed history, and clinical examination, chest X ray was done to localise pleural effusion. Diagnostic thoracentesis was performed in every case and the help of Ultrasonography of chest to localise the fluid was taken in some cases. About 50ml of pleural fluid was aspirated with 16 gauge needle. All pleural fluid samples were tested for Cell count,Protein,Sugar,Lactate dehydrogenase, Cholesterol, ADA, CBNAAT, Gramstain, Culture and Sensitivity.

Routine blood investigations were sent for sugar, Urea, Creatinine, Albumin, Protein, Lactate dehydrogenase, HIV testing. Sputum was sent for AFB and CBNAAT[if necessary].

Further investigations , such as CT Chest, Bronchoscopy were also done to determine the etiology of pleural effusion when needed.

49

Pleural fluid protein was measured by the Biuret method. Cholesterol measured by enzymatic method.

Pleural fluid cholesterol of more than 45mg/dl is taken as cut off value.

Radiological findings:

Side involved and the amount of pleural fluid were noted. Amount of pleural fluid present in chest radiography was classified into

1. Minimal - below the level of anterior end of 4^th rib.

2. Moderate - between anterior end of 4^th to 2^nd rib.

3. Massive - above the level of 2^nd anterior rib.

Clinical diagnosis was made and pleural fluid parameters were analyzed with it.

TUBERCULOUS PLEURAL EFFUSION:

Patients were diagnosed as tuberculous pleural effusion by one and /or more of the following criteria:

1. Sputum AFB smear positive

2. Sputum CBNAAT showing the result of MTB detected.

3. Pleural fluid AFB smear positive

4. Pleural fluid CBNAAT showing the result of MTB detected.

5. Pleural fluid ADA levels more than 70 U/L.

6. Pleural fluid ADA levels between 40-70 U/L and lymphocyte rich effusion.

7. ADA levels more than 40 U/L ,strong clinical suspicion,no other alternative diagnosis was made.

50

PARAPNEUMONIC EFFUSION:

Parapneumonic effusion was diagnosed by associated clinical features, radiological findings, pleural fluid cytology showing predominant neutrophils in an exudative pleural effusion, positive microbiologic culture, Gramstain.

MALIGNANT EFFUSION :

Malignant pleural effusion was diagnosed by positive pleural fluid cytology in pulmonary and an extrapulmonary malignancy.

Negative pleural fluid cytology in a pulmonary malignancy when the malignancy is proved by fine needle aspiration cytology or by means of bronchoscopy.

CONGESTIVE CARDIAC FAILURE [CCF] :

CCF was diagnosed by presence of clinical features [ increased jugular venous pulse, tachycardia] with cardiomegaly or echocardiography evidence of cardiac dysfunction.

HEPATIC HYDROTHORAX :

Hepatic hydrothorax was diagnosed by positive ultrasonography or CT findings with clinical and labarotory evidence of hepatic derangements and portal hypertension.

Pleural effusions associated with congestive cardiac failure, hepatic hydrothorax were classified as transudates and all others[ Malinancy,Parapneumonic,Tuberculous pleural effusions] as exudates.

51

Pleural fluid was categorized as transudative and exudative pleural effusion on the basis of etiology which was contributed by clinical ,imaging, pathological evaluations. Thus the pleural effusions were classified as exudative andf transudative on the basis of etiological diagnosis, Light’s criteria ,pleural fluid cholesterol [taken a cutoff value of 45mg/dl].

52

OBSERVATION AND RESULTS AGE AND SEX DISTRIBUTION:

Among 100 patients studied 61% were males [n=61] ,39% were females [n=39%].

The mean age group of the patients was 44.86 years.

AGE IN YEARS MALES FEMALES

< 20 5 1

21-40 20 12

41-60 30 13

61-80 6 13

Age group in years 5

20

30

6 1

12 13 13

0 5 10 15 20 25 30 35

< 20 21-40 41-60 61-80

Males Females

53

DISTRIBUTION OF TYPE OF PLEURAL EFFUSION [FINAL DIAGNOSIS]:

A total of 100 patients with definite final diagnosis, eligible for the study were included in which 27% [n=27] cases were transudates, and 73% [n=73] cases were exudates.

27

73

0 10 20 30 40 50 60 70 80

Transudate Exudate

Distribution of type of pleural effusion [final diagnosis]

Distribution of type of pleural effusion

54

Among 73 patients with exudative pleural effusion 57.5% [n=42] were males, 42.5%

[n=31] were females. Mean age group was 42.23 years.

Among 27 patients with transudative pleural effusion 70.4% [n=19] were males,29.6%

[n=8] were females. Mean age group was 51.96 years.

SEX DISTRUBUTION IN TYPE OF PLEURAL EFFUSION

19

42

8

31

0 5 10 15 20 25 30 35 40 45

Transudate Exudate

Males Females

55

Among 73 patients with exudates , 8.2% [n=6] of cases were <20 years in age, 39.72%

[n=29] of cases were between 21 – 40 years,34.24% [n=25] of cases were between 41 – 60 years and 17.8%[n=13] of cases were 61-80 years.

Among 27 patients with transudates 11.1% [n=3] of cases were between 21 – 40 years in age,66.67% [n=18] of cases were between 41 – 60 years and 22.2%[n=6] of cases were above 60 years.

AGE IN YEARS EXUDATES TRANSUDATES

<20 6 0

21-40 29 3

41-60 25 18

61-80 13 6

AGE DISTRUBUTION IN TYPE OF PLEURAL EFFUSION

Age group in years 6

29

25

13

0 3

18

6 0

5 10 15 20 25 30 35

< 20 21-40 41-60 61-80

Exudates Transudates

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DISTRIBUTION OF CAUSES [FINAL CAUSES] OF PLEURAL EFFUSION Among 73 patients with exudative pleural effusion, tuberculous pleural effusion was the most common pleural effusion in the study. It counted 48 cases out of 73 cases [65.8%].

Carcinoma lung was the second most common cause accounting for 20.5% [n=15].

Parapneumonic effusion accounting for 13.7% [n=10].

No of pleural effusion Mean age group of study patients :

1 . Tuberculous pleural effusion : 37.04 years 2. Parapneumonic effusion : 41.7 years 3. Malignant effusion : 60.66 years 4. Transudative effeusion : 51.96 years

4

10 15

23

48

0 10 20 30 40 50 60

Hepatic hydrothorax parapneumonic effusion Malignancy CCF Tuberculous effusion

57

SMOKING AND ALCOHOLISM IN STUDY POPULATION :

TRANSUDATE EXUDATE

Number % Number %

Smoking Smoker 18 66.7 27 37

Nonsmoker 9 33.3 46 63

Alcoholic Alcoholic 16 59.25 21 28.77

Non alcoholic 11 40.75 52 71.23

TRANSUDATIVE PLEURAL EFFUSION:

About 66.7% had history of smoking and 59.25% were alcoholics.

EXUDATIVE PLEURAL EFFUSION:

About 37% had history of smoking and 28.77% were alcoholics.

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DIABETES MELLITUS AND HIV IN STUDY POPULATION :

Diabetes mellitus was present in 48.15% [n=13] of the patients with transudative pleural effusion and in 16.44% [n=12] of the patients with exudative pleural effusion.

HIV was present in 3.7% [n=1] of cases with transudative pleural effusions and 5.48%

[n=4] of cases with exudative pleural effusion.

13

12

11.4 11.6 11.8 12 12.2 12.4 12.6 12.8 13 13.2

TRANSUDATIVE EXUDATIVE

DIABETES MELLITUS

DIABETES MELLITUS

4

1

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5

EXUDATIVE TRANSUDATE

HIV

HIV

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RADIOLOGICAL FINDINGS :

Among 100 patients screened 54 cases had right sided pleural effusion ,39 cases had left sided pleural effusion and 7 cases had bilateral pleural effusion.

SIDE TRANSUDATIVE EXUDATIVE

Number % Number %

Right 18 66.67 36 49.31

Left 2 7.41 37 50.68

Bilateral 7 25.92 0 0

0 5 10 15 20 25 30 35 40

TRANSUDATE EXUDATE

18

36

2

37

7

0

RIGHT LEFT BILATERAL

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Amount of pleural fluid was recorded radiologically 21% [n=21] of the patients had mild pleural effusion, 52% [n=52] of the patients had moderate pleural effusion, 22%

[n=22] of patients had massive pleural effusion and 5% [n=5] of the patients had loculated pleural effusion.

0 5 10 15 20 25 30 35

Mild Moderate Massive loculated

20

33

15

5 1

19

7

0

Exudative Transudative

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PLEURAL FLUID CYTOLOGY

Lymphocytic pleural effusion was 41 % [n=41] out of 100 cases . All the lymphocytic cases were tuberculous in etiology.

18 % [ n=18] of pleural effusions were Inflammatory in nature, of which 9 % [n=9] of the effusions were parapneumonic and 6% [n=6] of the cases were tuberculous,3%

[n=3] of the cases were malignancy.

7% [n=7] of the cases were positive for malignant cells.

4% [n=4] of pleural effusions were acellular .

30% [n=23] of pleural effusions were reactive in nature.

All the acellular and reactive pleural effusions were transudative in nature.

41

30

18

7

4

0 5 10 15 20 25 30 35 40 45

LYMPHOCYTIC REACTIVE INFLAMMATORY MALIGNANT ACELLULAR

62

LIGHT’S CRITERIA:

Out of 100 cases, Light‘s criteria diagnosed 95% [n =95] cases as exudates and 5%[n=5] of cases as transudates.

5

95

TRANSUDATIVE EXUDATIVE

63

MEAN PLEURAL FLUID PROTEIN :

Mean pleural fluid protein level in transudative pleural effusion was 3.46gm/dl.

Mean pleural fluid protein level in exudative pleural effusion was 4.91gm/dl.

 Tuberculous effusion : 4.82gm/dl.

• Para pneumonic effusion : 5.42gm/dl.

• Malignant effusion : 4.85gm/dl

FINAL DIAGNOSIS NUMBER MEAN STD.DEVIATION

Tuberculous 48 4.82 0.96

Malignancy 15 4.85 1.33

Parapneumonic 10 5.42 1.49

FINAL DIAGNOSIS NUMBER MEAN STD.

DEVIATION

P VALUE

Pleural fluid Protein

Exudative 73 4.91 1.13

0.0001

Transudative 27 3.46 0.95

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MEAN PLEURAL FLUID LDH:

• The mean pleural fluid LDH value in transudative effusion cases was 230.48 IU/L.

• In exudative effusions the mean level was 970.30 IU/L FINAL

DIAGNOSIS

NUMBER MEAN STD.DEVIATION P VALUE

LDH Exudative 73 970.30 804.99 <0.0001

Transudative 27 230.48 86.85

• Tuberculous effusion : 939.17 IU/L

• Parapneumonic effusion : 716.2 IU/L

• Malignant effusion :1500 IU/L

FINAL DIAGNOSIS NUMBER MEAN STD.DEVIATION

Tuberculous 48 939.17 689.81

Parapneumonic 15 716.20 510.11

Malignant 10 1500.90 1367.01

65

PLEURAL FLUID CHOLESTEROL:

Out of 100 cases pleural fluid cholesterol identifies 25% [n=25] of cases as transudates and 75% [n=75] of cases as exudates.

75 25

type of pleural effusion

Exudates Transudates

66

MEAN PLEURAL FLUID CHOLESTEROL:

• The mean pleural fluid cholesterol level in exudative pleural effusion cases was 83.92mg/dl

• In transudative pleural effusion 24.44mg/dl.

FINAL DIAGNOSIS N MEAN STD. DEVIATION P VALUE Pleural Fluid

cholesterol

Exudate 73 83.92 24.72 <0.0001

Transudate 27 24.44 10.28

• Tuberculous effusion : 82.21mg/dl

• Parapneumonic effusion : 105.2mg/dl

• Malignant effusion : 75.2mg/dl

FINAL DIAGNOSIS NUMBER MEAN STD.DEVIATION

Tuberculous 48 82.21 17.94

Malignancy 15 75.20 23.47

Parapneumonic 10 105.20 41.32

67

LIGHT’S CRITERIA VS FINAL DIAGNOSIS:

Out of 100 total cases as per final diagnosis, 73 cases were exudates and Light‘s criteria diagnosed 72 cases correctly as exudates, misclassified 1 exudate as transudate.

Out of 27 transudate cases as per final diagnosis, Light‘s criteria diagnosed only 5 cases as transudates.

Final diagnosis Total P value Exudative Transudative

Light’s Criteria

Exudative Count 72 22 94 0.001

% within Light's criteria

76.6% 23.4% 100.0%

Transudative Count 1 5 6

% within Light's criteria

16.7% 83.3% 100.0%

Total

Count 73 27 100

% within Light's criteria

73.0% 27.0% 100.0%

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PLEURAL FLUID CHOLESTEROL VS CLINICAL DIAGNOSIS

Pleural fluid cholesterol diagnosed all 73 cases correctly as exudates.

Pleural fluid cholesterol diagnosed 25 cases correctly as transudates and misclassified 2 transudates as exudates .

fInal diagnosis Total P value Exudative Transudative

PF

Cholesterol

> 45 Count 73 2 75 <0.0001

% within Cholesterol

97.3% 2.7% 100%

<45 Count 0 25 25

% within Cholesterol

0.0% 100.0% 100%

Total Count 73 27 100

% within Cholesterol

73.0% 27.0% 100%

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LIGHT’S CRITERIA VS PLEURAL FLUID CHOLESTEROL VS FINAL DIAGNOSIS

73

95

75 27

5

25

0 20 40 60 80 100 120

FINAL DIAGNOSIS LIGHT'CRITERIA CHOLESTEROL

TRANSUDATE EXUDATE

70

PLEURAL FLUID TO SERUM PROTEIN RATIO

Pleural fluid to serum protein ratio identifies 75% [n=69]of cases of exudates correctly but only 50% [n=4] of cases of Transudates are identified correctly.

final diagnosis Total P value Exudative Transudative

Protein ratio

> 0.5 Count 69 23 92 0.127

% within Protein ratio

75.0% 25.0% 100.0%

<0.5 Count 4 4 8

% within Protein ratio

50.0% 50.0% 100.0%

Total Count 73 27 100

% within Protein ratio

73.0% 27.0% 100.0%