[Downloaded free from http://www.cjhr.org on Saturday, August 4, 2018, IP: 189.202.227.

196]

Original Article

Spectrum of Pleural Effusion Etiology Revisited in 18–70 Years of Age

Group: A Tertiary Care Center‑based Study of 1000 Patients

Abstract Rahul Gupta,

Objective: The main objective study was to evaluate the new‑onset cases of pleural effusion with Anchal Gupta1,
respect to etiology/causation. Materials and Methods: A total of 1000 patients were included in the Mohd Ilyas1
study aged between 18 and 70 years. The patients with earlier diagnosis of pleural effusion or those
Departments of Chest
who had undergone thoracocentesis were excluded from the study. All the patients were subjected
Diseases and Tuberculosis and
to thorough clinical examination, chest radiography, chest and abdominal sonography, pleural fluid 1
Radiodiagnosis and Imaging,
analysis, and pleural fluid cytology, and in select cases, pleural biopsy was done. The results were Government Medical College,
assimilated and tabulated, observations thereby drawn by. Results and Observations: Out of total Jammu, Jammu and Kashmir,
1000  patients, 69.5% had tuberculosis followed by malignancy  (16%) with the systemic causes India
forming about 15% bulk of the patients with pleural effusion. It was found more in males, associated
with smoking, and majority of patients had unilateral effusion. Eighty‑nine percent of patients had
exudative effusion. Conclusion: The results of the study revealed that tuberculosis is still the most
common cause of pleural effusion and efforts need to be stepped up to control tuberculosis. The
national programs for control of tuberculosis need to be revisited to assess the magnitude of the
problem, and the patients need to be counseled for the compliance of the therapy. Furthermore,
malignancy is trending upward in the etiology of pleural effusion.

Keywords: Cytology, malignancy, pleural effusion, pleural fluid analysis, tuberculosis

Introduction syndrome, hemothorax  (posttrauma),

The accumulation of fluid in the pleural
cavity  (potential space between the parietal
and visceral pleura) is known as pleural
effusion. The causes may be pleural,
diseased surrounding lung parenchyma,
or systemic. It is one of the major causes
of pulmonary morbidity and mortality.
It can be classified as transudative or
exudative based on the modified Light’s
criteria.[1] Transudative pleural effusion is
commonly due to systemic illnesses, which
results in altered hydrostatic or oncotic
pressures in the pleural space, such as
congestive heart failure, hypoalbuminemia,
nephrotic syndrome, and hepatic
disorders  (cirrhosis). Exudative pleural
effusion commonly occurs due to the local
pleural or lung parenchymal pathology.
The common causes of exudative pleural
effusion include pleural or pulmonary
and asbestosis. Less common causes
of pleural effusion include pulmonary
embolism, drug‑induced  (e.g., amiodarone,
methotrexate), postradiotherapy, esophageal
rupture, and ovarian hyperstimulation
syndrome. In these cases, it may be
transudative or exudative.[2]
Materials and Methods
The prospective, observational study
was carried out in the Department of
Chest Diseases and Tuberculosis of
our institute over a period of 1  year
(April 2016–March 2017). A  total of Address for correspondence:
1000  patients with newly diagnosed pleural Dr. Mohd Ilyas,
effusion were included in the study. Department of Radiodiagnosis
and Imaging, Government
Inclusion criteria Medical College,
Jammu ‑ 180 001,
1. All patients above 18  years and below Jammu and Kashmir, India.
70  years of age with the new‑onset E‑mail: ilyasmir40@gmail.com

tuberculosis, pneumonia, malignancy, and radiographic or sonographic evidence of

inflammatory disorders such as rheumatoid pleural effusion
Access this article online
arthritis, systemic lupus erythematosus, 2. Patients with clinical evidence of pleural
chylothorax  (thoracic duct injury or effusion. In these patients, the clinical Website: www.cjhr.org

lymphatic obstruction), postcardiac injury
This is an open access journal, and articles are distributed
under the terms of the Creative Commons Attribution-
NonCommercial-ShareAlike 4.0 License, which allows others
to remix, tweak, and build upon the work non-commercially,
as long as appropriate credit is given and the new creations
are licensed under the identical terms.
For reprints contact: reprints@medknow.com
suspicion was confirmed by radiography DOI: 10.4103/cjhr.cjhr_109_17
or sonography. Quick Response Code:
How to cite this article: Gupta R, Gupta A, Ilyas M.
Spectrum of pleural effusion etiology revisited in
18–70 years of age group: A tertiary care center-
based study of 1000 patients. CHRISMED J Health
Res 2018;5:110-3.

110 © 2018 CHRISMED Journal of Health and Research | Published by Wolters Kluwer ‑ Medknow

[Downloaded free from http://www.cjhr.org on Saturday, August 4, 2018, IP: 189.202.227.196]
Gupta, et al.: Etiological profile of pleural effusion
Exclusion criteria
1. Patients with below 18 years or above 70 years of age
2. Patients already diagnosed with pleural effusion and
patients on the treatment for pleural effusion
3. Patient who already had undergone pleurocentesis.
A detailed history with regard to symptoms, contact
history, travel history, and smoking was elicited followed
by thorough clinical examination involving the general
physical examination and respiratory examination. The
systemic disease component‑related history and clinical
examination were also done.
The clinical component was followed by the
investigations. The investigations included sputum
examination, posteroanterior  (PA) chest radiograph, chest
ultrasonography, abdominal ultrasonography, hemogram,
coagulation profile, liver function tests, and renal function
tests. The effusion was graded as mild, moderate, and
severe based on chest radiographic and sonographic
quantification. The sonographic quantification was done
based on the formula: volume  (mL) = 16  ×  parietal to
visceral pleura distance (mm) at the mid‑diaphragm.[3]
Thoracoscopic‑based pleural biopsy was done in 36 willing
patients.
This was followed by ultrasonography‑guided aspiration
of the pleural effusion. The aspirated fluid was sent for
biochemical and cytological analysis to ascertain the
type of effusion  (exudative versus transudative based on
modified Light’s criteria) and the cause of effusion. The
Adenosine deaminase  (ADA) levels in the pleural fluid
were measured using spectrophotometry with cutoff value
of 36  IU/L. The patients with ADA levels more than this
value were diagnosed to be having tuberculosis if other
criteria were also met.
The diagnosis of tuberculosis was based on the detection
of Mycobacterium tuberculosis in sputum, pleural fluid, and
pleural biopsy specimens along with the demonstration of
high ADA levels in the pleural fluid. It was based on the
demonstration of acid‑fast bacilli  (AFB) on sputum smear in
561 patients. The GeneXpert (CBNAAT) was done in patients
with strong suspicion of tuberculosis who had negative sputum
smear  (134  patients), and it was positive for M. tuberculosis
in 115  patients. The rest of the 19  patients were diagnosed
as having tuberculosis on the basis of AFB demonstration on
thoracoscopic biopsy specimens  (10  patients) and on pleural
fluid smear  (9  patients). The guidelines used were as per the
recommendations of tuberculosis control program‑2016 in
India.
The malignancy was diagnosed based on the demonstration
of malignant cells in the pleural fluid or on the
histopathological examination of pleural biopsy specimens.
The final results were compiled in terms of gender
distribution, age distribution, etiological profile, association
CHRISMED Journal of Health and Research | Volume 5 | Issue 2 | April-June 2018
with smoking, transudative versus exudative type, and
laterality of the effusion.
Observations and Results
The present study revealed that pleural effusion was more
common in males following the earlier described trends
in the literature. It revealed that majority of patients
were between 31 and 40  years of age, there was a strong
association with smoking, and 68% patients of pleural
effusion were smokers. The major presenting symptoms
included fever and dyspnea on exertion, with almost 56%
having moderate effusion. Majority of the patients had
right‑sided effusion. Two most common causes of pleural
effusion included tuberculosis and malignancy.
In patients with tuberculosis, only 10 had transudative
effusion while 685  patients had exudative effusion. In
malignant cases, only two patients had transudative
effusion while 158 had exudative effusion. In cases having
systemic diseases such as liver cirrhosis, congestive
cardiac failure, and renal dysfunction, majority of them
had transudative effusion  (>90%) while those cases having
pleural effusion associated with pancreatitis had exudative
effusion  (approximately 70%). When analyzed with
respect to smoking, it was seen that most of the smokers
had exudative effusion. Of the 70  patients with bilateral
effusion, 56 had tuberculosis as the etiology.
In patients diagnosed as having malignancy on
thoracoscopic biopsy, eight patients had adenocarcinoma,
five had squamous cell carcinoma, and four had small cell
carcinoma. In pleural fluid analysis, about 70% had raised
ADA levels with majority of them having tuberculosis. The
ADA levels were increased predominantly in exudative
effusion  (94.3%) and almost 99% of these patients had
tuberculosis.
Tables  1-13 represent the data acquired in the study and
analysis of the various attributes of the pleural effusion.
Discussion
Pleural effusion is the most common pleural disease
affecting a significant bulk of population in India. It can be
a result of pleural, lung parenchymal, and systemic disease.
The pleural effusion may be benign or malignant.
The pleural cavity is a potential space normally containing
about 0.1–0.3  ml/kg of pleural fluid which is being
exchanged constantly. The pleural fluid is produced by
the parietal pleural vasculature and gets absorbed by the
lymphatics in the mediastinal and diaphragmatic parietal
pleura. If the pleural effusion is due to altered hydrostatic
and oncotic pressures, the resultant is transudates, and if
the effusion is due to increased mesothelial and capillary
permeability, the resultant is exudates.[4]
The pleural fluid is characterized into transudate and
exudate based on the modified Light’s criteria.
111
[Downloaded free from http://www.cjhr.org on Saturday, August 4, 2018, IP: 189.202.227.196]

Gupta, et al.: Etiological profile of pleural effusion

Table 1: Gender distribution of patients (n=1000) Table 7: Pleural fluid analysis (n=1000)

Gender Number of patients (%) Attribute Number of patients (%)
Male 750 (75) Exudative 898 (89.8)
Female 250 (25) Transudative 102 (10.2)

Table 2: Age distribution of patients (n=1000) Table 8: Pleural fluid cytology analysis (n=1000)

Age group (years) Number of patients (%) Attribute Number of patients (%)
18‑30 250 (25) Atypical cells 25 (2.5)
31‑40 290 (29) Malignant cells present 135 (13.5)
41‑50 210 (21) No malignant cells 840 (84)
51‑60 170 (17)
61‑70 80 (8)
Table 9: Thoracoscopic pleural biopsy results (n=36)
Attribute Number of patients
Table 3: Association with smoking (n=1000) Malignancy 17
Attribute Number of males (%) Number of females (%) Tuberculosis 10
Smoker 540 (54) 140 (14) Inconclusive 9
Nonsmoker 210 (21) 110 (11)
Table 10: Etiological distribution of patients based on
Table 4: Symptomology of patients (n=1000) pleural cytology and biopsy (n=1000)
Symptom Number of patients (%) Etiology Number of patients (%)
Fever 720 (72) Tuberculosis 695 (69.5)
Dyspnea on exertion 560 (56) Malignancy 160 (16)
Cough 810 (81) Synpneumonic effusion 45 (4.5)
Chest pain 425 (42.5) Liver cirrhosis 26 (2.6)
Weight loss 490 (49) Congestive cardiac failure 19 (1.9)
Pancreatitis 13 (1.3)
Renal disease (AKI/CKD) 25 (2.5)
Table 5: Distribution based on laterality of Indeterminate/idiopathic 17 (1.7)
involvement (n=1000) AKI: Acute kidney injury, CKD: Chronic kidney disease
Attribute Number of patients (%)
Right‑sided effusion 630 (63)
Table 11: Adenosine deaminase levels in pleural
Left‑sided effusion 300 (30)
fluid (n=1000)
Bilateral effusion 70 (7)
ADA levels Number of patients (%)
Raised 705 (70.5)
Table 6: Severity based on radiographic and sonographic Normal 295 (29.5)
evidence (n=1000) ADA: Adenosine deaminase
Severity Number of patients (%)
Mild 350 (35) Table 12: Adenosine levels with respect to exudative and
Moderate 560 (56) transudative fluid (n=705)
Severe 90 (9) Type of fluid Number of patients with raised ADA levels (%)
Exudative 665 (94.3)
Exudative pleural fluid has at least one of the following Transudative 40 (5.7)
characteristics as per the Light’s criteria:[5] ADA: Adenosine deaminase
1. Pleural fluid protein/serum protein ratio more than 0.5
2. Pleural fluid lactate dehydrogenase  (LDH)/serum LDH presentations are cough, chest pain, and fever. Active
ratio more than 0.6 inflammation may also give the picture of pleurisy.
The clinical examination will be positive for fullness
3. Pleural LDH is more than two‑thirds of the upper limits
of intercostal spaces and dullness on percussion on the
of normal laboratory value for serum LDH.
involved side. The detailed history with regard to the
If these criteria are not met, then the fluid is considered as involvement of pulmonary or systemic disease is important
transudate. in the diagnosis of pleural effusion.[6]
The patients of pleural effusion may be asymptomatic or Chest radiographs are helpful in the confirmation of pleural
may present with exertional dyspnea. The most common effusion. In a standing PA view radiograph, it requires

112 CHRISMED Journal of Health and Research | Volume 5 | Issue 2 | April-June 2018

[Downloaded free from http://www.cjhr.org on Saturday, August 4, 2018, IP: 189.202.227.196]
Gupta, et al.: Etiological profile of pleural effusion
Table 13: Relationship of smoking to type of
fluid (exudate vs. transudate)
Attribute Transudate Exudate
Smoking 198 700
Nonsmoking 90 12
200  ml to obscure the costophrenic angle displaying the
meniscus sign, while on a lateral radiograph, 50  ml fluid
can be appreciated. Sonography of the chest is more
sensitive in the diagnosis of pleural effusion and also helps
in the guidance of thoracentesis.[7]
Pleural fluid cytology is also important. It has 60%
sensitivity in the detection of malignant cells with increase
in yield by three attempts on different days to almost 95%.
Pleural fluid can also be used for ADA levels  (specific
for tuberculosis), amylase levels  (in esophageal rupture),
NT‑pro‑BNP levels  (heart failure), and triglyceride
levels (>110 mg/dl in chylothorax).[8]
Once the diagnosis is made, the main aim of the treatment
strategy is to treat the underlying cause. In India, the
tuberculosis is treated as per the guidelines issued via the
revised national tuberculosis program and WHO guidelines
which are modified from time to time.
In a study by Mohan and Ravindran, they found tuberculosis
as the most common cause of exudative pleural effusion
followed by malignancy.[9] The same results are reflected in
the present study.
The present study revealed that malignancy as a cause
of pleural effusion has taken the second seat following
tuberculosis. The pleural fluid analysis, pleural biopsy, and
radiographic and sonographic analysis were used in the
accurate diagnosis of these cases.
The results were also in conformity with the study done
by Raghavan et  al., who concluded that tuberculosis and
malignancy form the bulk of the patients with pleural
effusion.[10]
Malignant pleural effusion indicates an advanced
malignancy as described by Dixit et al.[11] The similar results
were obtained in the present study where almost 65% of
patients with malignant effusion had advanced/unresectable
malignancy.
Dhital et  al., in their study, concluded that tuberculosis
is the most common cause of unilateral effusions
followed by synpneumonic effusions.[12] The present study
revealed that tuberculosis as the most common cause of
pleural effusion  (unilateral as well as bilateral), but in
contradiction, the second most common cause was found
to be malignancy.
CHRISMED Journal of Health and Research | Volume 5 | Issue 2 | April-June 2018
Conclusion
The present study concludes that despite the revised
national tuberculosis control program in India, the
tubercular effusions are still at large. The cause is
usually the noncompliance with antitubercular therapy.
The malignant pleural effusion cases are far less than
tuberculosis, but their incidence is rising as compared
to previous studies. While evaluating a case of pleural
effusion, a combined approach, involving clinical
evaluation, radiographic and sonographic evaluation,
pleural fluid analysis, pleural fluid cytology, and in cases
where possible thoracoscopic pleural biopsy, must be
utilized to fruitful and accurate diagnosis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Akulian  J, Feller‑Kopman  D. The past, current and future of
diagnosis and management of pleural disease. J  Thorac Dis
2015;7:S329‑38.
2. Yalcin  NG, Choong  CK, Eizenberg  N. Anatomy and
pathophysiology of the pleura and pleural space. Thorac Surg
Clin 2013;23:1‑10, v.
3. Usta  E, Mustafi  M, Ziemer  G. Ultrasound estimation of volume
of postoperative pleural effusion in cardiac surgery patients.
Interact Cardiovasc Thorac Surg 2010;10:204‑7.
4. Charalampidis  C, Youroukou  A, Lazaridis  G, Baka  S,
Mpoukovinas  I, Karavasilis  V, et al. Physiology of the pleural
space. J Thorac Dis 2015;7:S33‑7.
5. Light  RW. The light criteria: The beginning and why they are
useful 40 years later. Clin Chest Med 2013;34:21‑6.
6. Karkhanis  VS, Joshi  JM. Pleural effusion: Diagnosis, treatment,
and management. Open Access Emerg Med 2012;4:31‑52.
7. Prina  E, Torres  A, Carvalho  CR. Lung ultrasound in the
evaluation of pleural effusion. J Bras Pneumol 2014;40:1‑5.
8. Ferreiro  L, Toubes  ME, Valdés L. Contribution of pleural fluid
analysis to the diagnosis of pleural effusion. Med Clin  (Barc)
2015;145:171‑7.
9. Mohan KM, Ravindran C. Etiology and clinical profile of pleural
effusion in a teaching hospital of South India: A  descriptive
study. Pulmon 2012;14:89‑96.
10. Raghavan S, Jayachandran R, Mosses  S. Clinical and etiological
profile of patients with pleural effusion in a tertiary care centre.
J Med Sci Clin Res 2017;5:23553‑8.
11. Dixit R, Agarwal KC, Gokhroo A, Patil CB, Meena M, Shah NS,
et al. Diagnosis and management options in malignant pleural
effusions. Lung India 2017;34:160‑6.
12. Dhital  KR, Acharya  R, Bhandari  R, Kharel  P, Giri  KP,
Tamrakar  R, et al. Clinical profile of patients with pleural
effusion admitted to KMCTH. Kathmandu Univ Med J  (KUMJ)
2009;7:438‑44.
113