Asian Cardiovasc Thorac Ann 2002;10:43-46
© 2002 Asia Publishing EXchange Pte Ltd
Common Causes of Pleural Effusion in Referral Hospital in Isfahan, Iran 1997-1998
Mohammad Golshan, MD,
Mehri Faghihi, MD,
Khadijeh Ghanbarian, MD,
Mustafa Ghanei, MD
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Department of Medicine Al-Zahra Medical Center Isfahan University of Medical Sciences Isfahan, Iran
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Mohammad Golshan, MD Tel: 98 311 627 6101 Fax: 98 311 222 8204 email: golshan{at}medscape.com Department of Medicine, Al-Zahra Medical Center, Isfahan University of Medical Sciences, P.O. Box 81655/755, Isfahan, Iran.
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ABSTRACT
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During a one-year period to September 1998, data were collected from all 213 patients referred with pleural effusion. There were 132 males and 81 females; their ages ranged from 18 to 85 years. The most common etiologies of effusion were congestive heart failure (39.4%), malignancy (27.2%), pneumonia (8%), empyema (5.2%), and tuberculosis (5.2%). Pleural effusions are frequent in Iran, and the causes are fairly similar to those reported by European authors, but with slightly more tuberculosis cases, mostly among Afghan refugees.
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INTRODUCTION
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Accumulation of fluid in the pleural space, in excess of the normal small amounts, and sufficient to be detected radiographically, is defined as pleural effusion (PE).1,2 It can be caused by a wide variety of intrathoracic and systemic diseases ranging from banal viral infections to serious conditions such as congestive heart failure (CHF) or metastatic carcinomas.1,3–8 In some cases, the etiology of PE will be disclosed by history and physical examination alone, whereas in others, the cause and clinical significance may not be obvious.1,7 In the latter group, a definitive or presumptive identification of the cause may be determined through analysis of pleural fluid obtained by thoracentesis.1,9 However, invasive approaches such as percutaneous needle biopsy of the parietal pleura, thoracoscopy, or thoracotomy and open biopsy often become necessary for accurate diagnosis.7,10 In some instances, the etiology may remain unknown even after an exhaustive work-up.11 The most serious concern in a patient with PE is the possibility of malignancy or tuberculosis (TB).12 In developed countries, CHF, pneumonia, and malignancies are the most common causes of PE.1,13 In developing countries, the problem of TB is still unresolved and this may affect the diagnostic approach to PE.12,14–17 Iran has been host to millions of Afghan refugees in the past two decades, many of whom suffer from TB as a result of poor nutrition and unhygienic conditions. This could potentially affect the Persian tables of differential diagnosis for PE. The purpose of this study was to determine the causes of PE observed in a referral center in Isfahan.
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PATIENTS AND METHODS
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A prospective study of 213 consecutive cases of PE was carried out during a 12-month period from October 1997 to September 1998. Most patients (202) were admitted to medical wards in Al-Zahra Medical Center of Isfahan University with PE on admission or developing during the hospital stay. Eleven patients with primary or postoperative empyema, who had been admitted to surgical wards, were included. The patients were systematically assessed with a meticulous interview and physical examination. Lateral decubitus radiographs and ultrasound scans were carried out when the volume of fluid was minimal or localization was suspected. Computed tomography of the chest was performed if parenchymal involvement was expected. Pleural paracentesis was undertaken in all cases to observe the color and determine the exudative or transudative nature of the fluid using Light's criteria.1 Cytology of the fluid, direct smears, and cultures for pyogenic organisms and Mycobacterium tuberculosis were routinely carried out. All patients with exudative effusions underwent percutaneous needle biopsy using a Cope's needle. Additional tests including amylase and second biopsies were applied when necessary. Thoracotomy and open biopsy were performed in 8 patients suspected to have malignant disease, in whom needle biopsy did not confirm the diagnosis.
The criteria for diagnosis of CHF was an enlarged heart with clinical or echocardiographic evidence of cardiac dysfunction, and one or more of the following: lung congestion on a chest radiograph, peripheral edema, optimal response to treatment, and exclusion of other causes of effusion such as pneumonia, malignancy, or pulmonary thromboembolism (PTE). Nephrotic syndrome was diagnosed by proteinuria above 3.5 g•day-1, edema, and hypoalbuminemia of less than 35 g•L-1. Liver cirrhosis was determined by clinical and laboratory evidence of liver damage; a liver biopsy had already been performed in 5 patients. Malignant effusions were identified by pleural cytology in 48 cases and confirmed in 40 by percutaneous biopsy. Open biopsy in 6 cases confirmed a malignant etiology in 5. Patients with PE and negative findings from cytology and percutaneous biopsy, who were known to have a primary malignancy and showed computed tomographic evidence of lung involvement, were considered to have malignant effusions (after exclusion of associated infections or emboli), and no further evaluation was undertaken. Tuberculosis was diagnosed either by typical caseating granulomas in pleural biopsy or by isolation of Mycobacterium tuberculosis in pleural fluid or tissue. Parapneumonic effusions were diagnosed by: a history of acute febrile illness with purulent sputum; radiographic pulmonary infiltrates compatible with pneumonia, which responded favorably to antibiotic therapy; or isolation of organisms in the pleural fluid. Empyema was diagnosed when thick purulent-appearing fluid with a specific gravity exceeding 1.018 was found in the pleura.1 Pulmonary emboli were confirmed by a suggestive clinical picture and multiple segmental perfusion defects not matching the chest radiograph; most patients in this group had risk factors for PTE. Miscellaneous exudates were PE that was clearly secondary to chronic renal failure, collagen vascular disorders, or lung atelectasis due to endobronchial tumor mass.
Continuous data were calculated as mean ± standard deviation. Discrete variables were calculated as per-centages. The Student's t test was used to compare differences between subgroups. A p value < 0.05 was considered statistically significant.
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RESULTS
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The 213 patients studied consisted of 132 males and 81 females, ranging from 18 to 85 years of age (mean, 61 ± 13 years). Only 21 patients were younger than 40 years old. Transudates were more prevalent among patients in medical wards (106, 49.8%); however, when 11 patients in surgical wards with empyema were added, exudates predominated (107, 50.2%). The various etiologies of the transudates are summarized in Table 1
. The underlying disorders in patients with exudative effusions are listed in Table 2. Patients with transudative effusions were older than the exudative group (69 ± 12 versus 58 ± 15 years; p < 0.05). There were 7 patients diagnosed with PTE without a serious underlying chronic illness; the pleural fluid was transudative in 5, and exudative in 2. Thus, PTE has been included in both tables. Seven patients with CHF and 4 with malignant pleural involvement were found to have associated PTE; all 7 were older than the average for their disease categories. These complicated cases have been included only in the CHF and malignancy categories. The protein content of the pleural fluid in 5 of the patients with CHF complicated by PTE was in the borderline exudative range. One case of empyema was secondary to infection of a ruptured hydatid cyst in a 32-year-old man. The most common primary malignancies were lung and breast adenocarcinomas, followed by carcinomas of uncertain origin, and one case of lymphoma. Small-cell and squamous cell bronchogenic carcinomas were responsible for malignant pleural involvement in 2 and 1 patients, respectively. Bloody effusions were observed exclusively in malignant effusions.
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DISCUSSION
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It has been estimated that CHF might be responsible for more than one-third of all pleural effusions in the United States, followed by pneumonia, malignancy, and PTE.1 An epidemiologic study from the Czech Republic reported the 4 main etiologies of PE to be CHF, malignancy, pneumonia, and PTE, in order of frequency.13 The data in our series are closer to those from the Czech Republic, with CHF and malignancy as the 2 main causes of PE, comprising the etiology in approximately two-thirds of the cases. CHF is the most common cause of PE in many parts of the world.1 However, the prevalence of CHF in our series was higher than expected, probably because of the hospital being a referral center known for cardiac and pulmonary services. The same explanation could be true for the high prevalence of malignant effusions. Parapneumonic effusions, usually the most common cause of exudative PE, were diagnosed in a small proportion; this can be partly explained by the fact that pulmonary infections have the highest diagnostic priority for local physicians, and are rapidly diagnosed and managed without the need for referral. In fact, only complicated cases unresponsive to early treatment were referred. This explanation is further supported by the fact that 14 of the 17 parapneumonic effusions were loculated.
Malignant PE usually signifies incurable disease with considerable morbidity and a dismal mean survival of less than 1 year. Malignant effusions should be suspected in patients with known cancer or with lymphocytic exudative effusions, especially when effusions are bloody. Direct tumor involvement of the pleura is most effectively diagnosed by pleural fluid cytology. A single pleural fluid cytologic study can detect 54% to 63% of malignancies; the yield increases to 77% when serial samples are processed.7 In our series, serial cytologic examinations detected tumor cells in 48 cases (83%). Percutaneous needle biopsy of the pleura is a bedside procedure that can increase the detection of malignancy, and also disclose the tumor cell type to elucidate the therapeutic plan.7 Percutaneous pleural biopsy confirmed the diagnosis in 40 of our patients (69%) at first trial, and a second biopsy detected adenocarcinoma in one other. Open biopsy was necessary to confirm the malignancy in 5 cases including the patient with lymphoma.
Tuberculous pleuritis is another diagnostic consideration in exudative PE. Although classically associated with primary TB infection, these effusions have been increasingly associated with reactivation of TB.12,18 Tuberculous pleuritis is usually found in younger adults.12,16 This type of pleuritis should be suspected in patients with a history of exposure to TB or with a positive purified protein derivative test. It should also be considered when exudative effusions are predominantly lymphocytic, especially if fewer than 5% mesothelial cells are detected in differential cell counts; however, in patients with human immunodeficiency virus infection whose immune responses are altered, the cytologic profile of the tuberculous effusion may be affected, and this change might not be observed.1,12,19 Because PE results from a hypersensitivity to TB proteins and lipopolysaccharides rather than microbial invasion of the pleura, acid-fast bacillus stains of pleural fluid are rarely diagnostic.1 In contrast, histologic examination and culture of pleural tissue obtained by closed-needle pleural biopsy increase the diagnostic yield to 80% to 90%.1 Eleven patients (5.2%) in this series were diagnosed to have TB, which is well above the rates reported from the United States, but much lower then those from Saudi Arabia and Lebanon.1,16,17 Eight of the 11 patients (73%) with tuberculous PE were Afghan refugees. Our TB patients were considerably younger than the average patient with an exudate. None of the TB effusions were bilateral. The underlying lung showed parenchymal infiltration in 5 cases. The pleural fluid contained more than 50 g•L-1 protein in 9 cases. Pleural biopsy was the most useful diagnostic test, showing caseating granulomas in 10 of the 11 patients. However, it was necessary to perform the biopsy more than once for final diagnosis in 4 cases; culture of the biopsy sample confirmed the diagnosis in the 11th case.
There was an interesting case of a patient who was referred for evaluation of a lung abscess and empyema. Computed tomography of the chest in this 44-year-old farmer showed an infected hydatid cyst. The diagnosis was confirmed at thoracotomy. In most of the patients with transudates, a firm clinical diagnosis could be established, but we were unable to detect reliable clues in the history or physical examinations to discriminate the various causes of exudates. Eleven patients with serious underlying conditions such as CHF or malignant disorders, also had associated PTE, which can result in a fatal outcome. Therefore, it should be noted that confirmation of a primary underlying disease dose not exclude additional PTE and/or infection, and such a combination should always be kept in mind, especially when the profile of the pleural fluid tends towards the exudative range in a patient with CHF or chronic renal failure.
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Acknowledgments
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The research department of Isfahan University of Medical Sciences financially supported the study.
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ABSTRACT
INTRODUCTION
