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May - August 2005: 
Volume 18, Issue 2

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Longitudinal study of pleural plaques in a rural population with environmental exposure to asbestos
Abstract
To follow-up the development of pleural plaques in the rural population of Almopia (a province in Northern Greece) where exposure to asbestos as an environmental pollutant had occurred in the past. In the two years’ period from 1988 through 1990, 1,086 people aged over 5 years, 818 of whom were over 40 years old, were examined with chest radiographs. These people were inhabitants of 7 villages in the province of Almopia with a total population of 3,931 people. Until 1935, the inhabitants of this area had been using rocks containing a high concentration of asbestos fibers as whitewash. Pleural plaques were found in 198 persons over 40 years; malignant lung neoplasm in 9; and malignant mesothelioma in 5 persons. Respiratory function was tested as well in 23 individuals. In 2003 (15 years later), follow-up examinations were performed, including: i) 126 survivors out of the 198 subjects initially presenting pleural plaques, underwent a chest x-ray examination; new radiological findings were compared to the previous ones (1988) using digitalization of radiological films and measurement of the area of shading; ii) respiratory function was re-evaluated in 18 out of the 23 individuals who had been evaluated 15 years ago. In addition, the cause of death of 72 persons who had passed away in the meantime was examined. A) Expansion of radiologically evident lesions was observed, despite the fact that exposure to asbestos had ceased long before. Not only was the area of previous plaques increased, but new plaques had appeared as well (total increase 1,091.1 cm2). B) Total lung capacity declined from 95.6±14.8 to 76.5±9.3 percent of the expected value. C) It was found that, of the 72 deaths in total, 11 people had died of malignant lung neoplasm and 4 of mesothelioma. The radiological appearance of pleural plaques in people with environmental exposure to asbestos in the past gets worse over time; respiratory function is proportionately affected as well. With reference to the total Greek population, prevalence of mesothelioma in the certain area was found to be higher than expected. Pneumon 2005, 18(2): 197-203.
Full text

INTRODUCTION

 

Pleural calcifications in chest radiographs are endemic in various areas of the world where asbestos fibers or other mineral fibers are present in the environment.1 Affected persons present no occupational exposure to asbestos; in addition, no asbestos mines or asbestos processing facilities are sited within a distance that would justify environmental pollution with mineral fibers due to the operation of such facilities. On the contrary, it has been found that mineral fibers contained in traditional whitewash materials used as wall coating are particularly dangerous; initial reports came from Turkey,2 but findings were consequently confirmed by similar reports from the area of Metsovo,3 as well as the province of Almopia in the Prefecture of Pella.4 Apart from pleural calcifications, the incidence of malignant mesothelioma is particularly high in these areas.5-7

 

A 28-month survey conducted in the period 1988-1990 in 7 villages of Almopia province in the Prefecture of Pella with a total population of 3,931 people showed a high prevalence of pleural calcifications ranging from 5.2 to 39.6% in subjects aged over 40 years.4 A very high concentration (50-90%) of asbestos fibers, in particular chrysotile and tremolite, was found in the rocks used by the inhabitants of these areas until 1935 as whitewash. Environmental measurements revealed that the concentration of fibers in the air ranged from 0.01 to 17.9/cm3. Finally, the incidence of malignant mesothelioma was also found to be high among inhabitants of this area.7

 

The present study was designed to: i) reassess the radiographic appearance of pleural calcifications and lung function of those subjects who had been initially evaluated 15 years ago; ii) investigate the cause of death of those persons who had been included in the initial evaluation and died in the meantime.

 

PATIENTS AND METHODS

 

All study subjects gave their informed consent for their participation in the study.

 

i) A normal-size postero-anterior chest radiograph was obtained from the 126 survivors of the 198 subjects who presented pleural calcifications in the 1988-1990 study. The examination was performed in the same radiology department of the Aridea Health Center and radiographs were separately evaluated by two experienced specialists. The CGR-GE triplunix machine (source distance 1.80 m; voltage 110 KV; tension MAS 6) was used. New radiographs were compared to the previous ones that had been obtained from the same persons 15 years ago. Radiographs were digitalized and entered in the computer database using Adobe Photoshop 6 software. Measurements of the area of calcifications were performed using Autodesk Auto CAD 200 software.

 

ii) The lung function of the 18 survivors of the 23 subjects who had their lung function initially evaluated in 1988-1990 was tested in the Lung Function Laboratory of the Pulmonary Medicine Department of the General Hospital "G. Papanikolaou" of the Aristotle University of Thessaloniki. A Jaeger type spirometer was used; flows, lung volumes and capacities were measured using the method of helium closed circuit. The predicted values proposed by Crapo et al were used.8

 

iii) In the meantime between the first and second evaluation by our study group, most subjects with positive radiographic findings had been followed up by the local Health Center. Data on the 72 individuals in total who had passed away in the meantime were obtained from the death certificates kept by the local municipal authorities.

 

RESULTS

 

Radiographic findings

 

Figure 1. Postero-anterior chest radiograph: A, 1988; B, 2003. Female, 79 years old, inhabitant of Megaplatanos village.

The comparative evaluation of chest radiographs from the 126 survivors showed that the area of the old calcifications has increased and additional calcifications have appeared. The total area of pleural calcifications at the initial evaluation was 1,073.4 cm2; upon re-evaluation this area has increased to 2,164.5 cm2. The total area difference in the 15-year period is 1,091.1 cm2 (Figures 1-3). There were no indications of parenchymal lesions.

 

Both at the initial and the repeat evaluation, pleural calcifications were more prominent in the left hemithorax (initial evaluation: total area in the left hemithorax 792.1 cm2 and in the right hemithorax 281.3 cm2; repeat evaluation: total area in the left hemithorax 1,485.6 cm2 and in the right hemithorax 678.9 cm2).

 

Figure 2. Postero-anterior chest radiograph: A, 1989; B, 2003. Female, 60 years old, inhabitant of Promachon village.
Figure 3. Postero-anterior chest radiograph: A, 1989; B, 2003. Female, 66 years old, inhabitant of Promachon village.

 

Lung function testing

 

Eighteen of the twenty-three subjects who had their lung function evaluated in 1988 were re-evaluated in 2003. They included 14 males and 4 females, aged 72.7±6.5 years and 163±8.5 cm in height. The mean area of pleural calcifications was 11.27±12.98 cm2 in 1988 and 18.06±15.71 cm2 in the 18 re-evaluated subjects in 2003 (p<0.001). The results of lung function testing are shown in Table 1.

 

Table 1. Lung function testing    
Lung function
parameters
 1988 2003  P value
TLC
TLC % pred
FVC
FVC % pred
RV
RV % pred
FEV1
FEV1 pred
FEV1/FVC
5.55±1.34
95.65±14.85
3.58±0.93
94.74±17.98
1.95±0.55
98.15±23.85
2.84±0.71
93.43±13.56
79.84±6.81
 
 4.33±0.88
76.48±9.26
2.77±0.65
80.12±13.76
1.52±0.35
66.1±13.48
2.36±0.59
89.1±10.84
84.95±6.48

p<0.001

p<0.001

p<0.001

p<0.01
p<0.01

 

Lung volumes (TLC, FVC, RV, p<0.001) show a significant reduction, whereas the reduction in FEV1 is moderate (p<0.01). On the contrary, there was an increase in FEV1/FVC% ratio (p<0.01). These findings are suggestive of the effect of the asbestos exposure on lung parenchyma, which manifests itself as restrictive pulmonary dysfunction.

 

Thoracic neoplasms

 

In the initial 2-year period of data collection, 5 cases of mesothelioma and 9 cases of malignant neoplasms of the lungs were recorded; all cases were male, smokers and presented pleural calcifications. In the meantime and before repeat evaluation, 4 new cases of mesothelioma and 11 cases of malignant neoplasms of the lungs appeared. With one exception of a female non-smoker, all cases were male smokers.

 

DISCUSSION

 

Following environmental exposure to asbestos quite a long time (over 40 years) is required for pleural calcifications to become clinically evident.4,9 Pleural calcifications may occur even after exposure to low concentrations of asbestos fibers.10 In addition, it seems that the specific type of asbestos fibers determines whether pleural calcifications will occur; it has been suggested that calcifications are caused by exposure to amphibole fibers, primarily tremolite.4,10-12

 

The findings of the present study indicate that the radiographic appearance of pleural calcifications following environmental exposure to asbestos deteriorates over time despite cessation of exposure long time ago. Longitudinal studies on workers with occupational exposure to asbestos have also shown radiographic progression of calcifications and continuing deterioration for many years (over 20 years) after the initial exposure.13,14 It is likely that the initial exposure to asbestos fibers may cause lesions that have the ability to progress inevitably and irrespective of whether exposure continues or has stopped. Another study that included 1,454 workers in asbestos mines in South Africa, 691 of whom retired, also concluded that cessation of exposure has no effect on either the expected change in the size of the calcifications or the occurrence of new shadings on repeat examination.15 Hence, it seems that pleural calcifications due to environmental exposure to asbestos behave the same as those that appear due to occupational exposure to this agent.

 

Furthermore, pleural calcifications were found to be significantly more prominent in the left hemithorax. Similar findings have been reported by other study groups.16,17 To date, no satisfactory explanation has been proposed for this differential appearance of the lesions. Moreover, the left-sided predominance of pleural lesions has recently been questioned.18

 

As regards lung function, a considerable reduction in lung volumes (TLC, FVC, RV), a moderate reduction in FEV1 and an increase in FEV1/FVC ratio were observed. Chest radiographs of the subjects of the present study showed no signs of pulmonary fibrosis (asbestosis); nevertheless, the presence of parenchymal lesions not evident on chest radiograph that cause a reduction in lung volumes cannot be excluded. Therefore, future studies should use high-resolution computer tomography scanning to exclude parenchymal involvement, since simple chest radiographs lack adequate sensitivity for such evaluations.

 

Lung function testing of individuals with pleural calcifications has yielded conflicting results. Some studies have failed to show a significant association between pleural calcifications and lung function.19,20 In an asbestos-cement factory in Belgium, there was no relationship between either the presence or the extent of pleural calcifications and lung function parameters in 73 workers who were exposed for 23-27 years.20 In other studies, the effect of calcifications on lung function was small;21,22 however, some studies have shown a significant decline in lung function manifested primarily as a reduction in lung volumes.23,24 In 155 non-smoking workers with pleural calcifications, FEV1 and FVC were significantly reduced compared to non-exposed subjects.23 Nevertheless, in 202 non-smoking workers in shipyards, with varying levels of exposure to asbestos and the presence of pleural calcifications as the single abnormality, FVC was reduced by 6.9% to those workers who had calcifications compared to those who did not.24 The presence of profound pleural thickening appears to be more aggravating than pleural calcifications,25,26 since it usually affects both hemithoraxes.27

 

The expansion of pleural calcification over time has caused restrictive pulmonary dysfunction in our patients. The involvement of parenchymal lesions in the development of this disorder cannot be excluded based solely on plain chest radiographs.

 

The number of mesothelioma cases in the study population (9 cases in 3,931 persons followed up for 15 years) is 75 times higher than the expected rate, which is 1 case/1,000,000 population/year;28 the true incidence of malignant mesothelioma is even lower in populations not exposed to asbestos.29 The presence of pleural calcifications has already been associated with increased risk of mesothelioma in the past.30 A study of 1,596 men with pleural calcifications in Uppsala, Sweden, in the period 1963-1985 showed a relative risk for bronchogenic cancer 1.4; in addition, 9 cases of mesothelioma were diagnosed whereas the expected number was 0.8.31 The type of asbestos fibers (amphibole group, mainly tremolite) has a key role in the development of both pleural calcifications and mesothelioma following environmental pollution with asbestos.7,32

 

In contrast to mesothelioma, the risk of bronchogenic cancer shows only a moderate increase;31 chrysotile fibers have been implicated in the development of this malignancy,33 although it is not always easy to separate the carcinogenic effect of smoking. The number of malignant neoplasms of the lungs in the examined population was lower than the expected in the general Greek population.34

 

CONCLUSIONS

 

The radiographic appearance of pleural calcifications following environmental pollution with asbestos deteriorates over time with a pattern similar to that reported for lesions caused by occupational exposure to this agent. Pleural calcifications have a moderate effect on lung function leading to restrictive pulmonary dysfunction. The incidence of malignant mesothelioma is exceedingly high in the studied population and is primarily attributable to the high tremolite content of the asbestos-containing rocks found in the area.

 

REFERENCES

 

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References