There is no detailed information about benign asbestos pleural effusion (BAPE). The aim of the study was to clarify the clinical features of BAPE. The criteria of enrolled patients were as follows: (1) history of asbestos exposure; (2) presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3) the absence of other causes of effusion. Clinical information was retrospectively analysed and the radiological images were reviewed. There were 110 BAPE patients between 1991 and 2012. All were males and the median age at diagnosis was 74 years. The median duration of asbestos exposure and period of latency for disease onset of BAPE were 31 and 48 years, respectively. Mean values of hyaluronic acid, adenosine deaminase, and carcinoembryonic antigen in the pleural fluid were 39,840 ng/mL, 23.9 IU/L, and 1.8 ng/mL, respectively. Pleural plaques were detected in 98 cases (89.1%). Asbestosis was present in 6 (5.5%) cases, rounded atelectasis was detected in 41 (37.3%) cases, and diffuse pleural thickening (DPT) was detected in 30 (27.3%) cases. One case developed lung cancer (LC) before and after BAPE. None of the cases developed malignant pleural mesothelioma (MPM) during the follow-up.
Asbestos-related pathological changes of the pleura include pleural plaques, malignant pleural mesothelioma (MPM), diffuse pleural thickening (DPT), and benign asbestos pleural effusion (BAPE). BAPE is a nonmalignant pleural disease initially described in 1964 [
In the current study, we retrospectively analysed the clinical features of BAPE in patients in Japan. The aim of the study was to clarify the clinical features of BAPE and to suggest more practical diagnostic standard for the disease.
Enrolled patients were referred to Rosai Hospital and affiliated hospitals in Japan for an examination for pleural effusion and were finally diagnosed with BAPE. The criteria of enrolled patients were as follows: (1) previous history of asbestos exposure obtained by an in-person questionnaire or interview; (2) presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3) the absence of other causes of effusion. The pleural fluid was collected by thoracentesis or thoracoscopy, and information on cell classification, cytological analysis, and the biochemical examination was extracted from the medical records. Hyaluronic acid (HA), adenosine deaminase (ADA), and carcinoembryonic antigen (CEA) were included among the clinical laboratory tests. The HA concentration was determined using a latex agglutination turbidimetric immunoassay. ADA was measured using an enzymatic technique. CEA was measured using a chemiluminescent immunoassay.
Clinical and demographic information was obtained from the medical records at each facility. The information included age, gender, smoking status, initial symptoms, and results of laboratory testing of the pleural effusion. The work histories, those of the family members, and residential histories were investigated to assess the patient’s history of asbestos exposure.
The radiological images were sent to Okayama Rosai Hospital for review. Characteristic radiological findings associated with asbestos exposure were assessed as the presence of pleural effusion, asbestosis, rounded atelectasis, pleural plaques, and DPT. Asbestosis was classified on chest X-rays according to perfusion rate (PR) based on the International Labour Organization (ILO) criteria [
Survival data were determined from the day pleural effusion was detected to the day of death or last follow-up and analysed using the Kaplan-Meier method with SPSS 11.0 software (SPSS, Inc., Chicago, IL, USA).
This study was done according to the Ethical Guidelines for Epidemiological Research by the Japanese Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health, Labour, and Welfare. This study was approved by Japan Labour Health and Welfare Organization and the institutional review boards of each institution. Patient confidentiality was strictly maintained. This study was carried out according to the principles set out in the Declaration of Helsinki.
One hundred ten patients from 9 institutions fulfilled the enrolled criteria based on the descriptions in their medical records and review of the radiographs between 1991 and 2012. Characteristics of the patients are shown in Table
Patient characteristics.
Age ( |
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Median (range) | 74 (36–90) |
Gender ( |
|
Male/female | 110/0 |
Smoking history ( |
|
Ever/current | 56 |
Never | 7 |
Symptoms ( |
|
Dyspnea | 34 |
Cough | 15 |
Chest pain | 13 |
Fever | 3 |
Palpitation | 2 |
Sputum | 1 |
Wheezing | 1 |
Back pain | 1 |
Weight loss | 1 |
Fatigue | 1 |
A history of asbestos exposure was reported by 109 patients, with one patient whose detailed information of asbestos exposure was not obtained. Among the 109 patients, 108 patients had a history of occupational asbestos exposure and one patient had a history of environmental asbestos exposure. The occupational categories associated with asbestos exposure are shown in Table
Occupational category related to asbestos exposure.
Shipbuilding | 25 |
Construction | 20 |
Chemical facility | 10 |
Asbestos products manufacturing | 8 |
Electrical work | 8 |
Plumbing | 7 |
Asbestos transportation | 5 |
Moisturizing work | 4 |
Asbestos spraying | 3 |
Steel production | 3 |
Demolition work | 2 |
Automobile manufacturing | 2 |
Heat insulation | 2 |
Firebrick manufacturing | 2 |
Glasswork | 1 |
Metallic product manufacture | 1 |
Furnace installation | 1 |
Coating industry | 1 |
Shipman | 1 |
Others | 2 |
|
|
Total | 108 |
Information regarding the pleural effusion was obtained in 104 cases. The gross impression of the pleural fluid was bloody in 75 cases, light yellow in 27, and light brown and dark red in 1 case each. The effusions were exudative in all cases. A cellular classification of the fluid was obtained in 57 cases and the median proportions of lymphocytes, macrophages, neutrophils, and eosinophils were 77.7%, 9.7%, 8.0%, and 8.0%, respectively. The HA concentration was determined in 106 cases and the mean (standard deviation) concentration was 39,840 (40,228) ng/mL. Mean (standard deviation) values of ADA and CEA were 23.9 (24.9) IU/L and 1.8 (1.3) ng/mL, respectively.
As shown in Table
Concomitant asbestos-related radiological findings.
Findings |
|
% | |
---|---|---|---|
Pleural plaques | 98 | 89.1 | |
Calcified | 76 | ||
Asbestosis | 6 | 5.7 | |
PR† | 1 | 3 | |
2 | 2 | ||
3 | 1 | ||
Rounded atelectasis | 41 | 37.3 | |
DPT‡ | 30 | 27.3 |
In most of the cases, thoracentesis and/or thoracotomy were done to collect the fluid and drain the pleural effusion. Oral steroids were prescribed in 5 cases and one of them demonstrated temporal decrease of the effusion. Survival data was obtained in 70 cases from Okayama Rosai Hospital. As shown in Figure
Overall survival of patients with benign asbestos-related pleural effusions at Okayama Rosai Hospital.
In the current study, we examined the clinical features of BAPE and demonstrated that BAPE developed after long-term asbestos exposure. In a previous report, BAPE occurred 15–20 years after exposure and was more common in younger patients aged 21–40 years [
The diagnosis of BAPE should be based on a history of asbestos exposure and an exclusion of other causes of effusion such as tuberculous pleuritis, bacterial pleuritis, collagen diseases, heart failure, and malignant conditions such as MPM and LC. In our analysis, the gross impression of the pleural fluid was bloody in 72% of the cases, and cellular classification of the fluid demonstrated lymphocyte dominancy. These results are similar to those of a previous report showing that the effusion was exudative and could be hemorrhagic, as well as predominantly eosinophilic [
In cases of LC, tumor cells are detected in the fluid in more than 60% of cases [
In addition, we analysed some markers such as HA concentration, ADA, and CEA. Recently, we reported the clinical usefulness of HA for the differential diagnosis of MPM and BAPE [
Based on the findings in the current study and previous reports, we propose more practical diagnostic standard for the diagnosis of BAPE including (1) asbestos exposure history, (2) exudative effusion, and (3) exclusion of other pleuritides such as LC, MPM, and tuberculous pleuritis by radiological examination and pleural biopsy via thoracoscopy. Additional diagnostic information is as follows: (1) in cases thoracoscopy could not be undergone, the diagnosis should be discussed based on the bacteriological examination and biochemical markers such as CEA, ADA, and HA; in cases with elevated CEA (>5 ng/mL), ADA (>35 IU/L), or HA (>100,000 ng/dL), carcinomatous pleuritis, tuberculous pleuritis, or MPM is more likely, respectively; and (2) in cases with some concomitant medical problem such as autoimmune diseases, the activity of the disease should be carefully evaluated, because autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis could involve the pleura and cause pleural effusion (Table
Proposed diagnostic criteria of benign asbestos pleural effusion.
Diagnostic criteria | |
|
|
(1) Asbestos exposure history. | |
(2) Exudative effusion. | |
(3) Exclusion of other pleuritides such as lung cancer, MPM†, and tuberculous pleuritis by radiological examination and pleural biopsy via thoracoscopy. | |
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|
Additional diagnostic information | |
|
|
(1) In cases thoracoscopy could not be undergone, the diagnosis should be discussed based on the bacteriological examination and biochemical markers below. | |
(a) Elevated carcinoembryonic antigen (>5 ng/mL) suggests carcinomatous pleuritis. | |
(b) Elevated adenosine deaminase (>35 IU/L) suggests tuberculous pleuritis. | |
(c) Elevated hyaluronic acid (>100,000 ng/dL) suggests MPM. | |
(2) In cases with some concomitant medical problem such as autoimmune diseases, the activity of the disease should be carefully evaluated. |
“Benign” is meant to refer to a nonmalignant process, but these effusions can be associated with significant morbidity [
There are a few limitations to the current study. First, this was a retrospective study. Second, pathological analyses including immunohistochemistry were not reviewed. In addition, there are recent reports that increased uptake of fluorodeoxyglucose (FDG) by positron emission tomography (PET) may be a useful marker to distinguish MPM from benign pleural disease [
BAPE develops after a long latency period after past asbestos exposure. The diagnosis of BAPE should be based on the exclusion of other pleural diseases. A thorough evaluation, including diagnostic thoracentesis and cytological and bacterial analysis, must be performed. Clinical markers such as HA, ADA, and CEA might help with the differential diagnosis. However, thoracoscopic exploration and pleural biopsy should be performed to confirm a diagnosis of BAPE.
This study is a part of “the research and development and the dissemination projects related to the 9 fields of occupational injuries and illnesses” of Japan Labour Health and Welfare Organization. This organization had no involvement in the study design, collection, analysis, and interpretation of the data, writing of the paper, or decision to submit the paper for publication.
The authors declare that there is no conflict of interests in their submitted paper.