Metsovo Lung

Metsovo Lung is a unique epidemic of domestic asbestos exposure where all inhabitants of a village in NW Greece (Metsovo, population: 5.000) had been exposed in the past to a tremolite asbestos-containing whitewash. As a result there has been an epidemic of malignant mesotheliomas (MM) that had reached, in the beginning, (in the 1980s) an incidence 300 higher than expected in non asbestos exposed populations. This was accompanied by pleural calcifications (PCs) in almost half the adult population. Both have declined significantly since the whitewash has not been used after 1980-1985.

History

In the early 1980s when the Medical School of Ioannina was established, a group of Pneumonologists headed by S.H.Constantopoulos started encountering, almost on a daily basis, roentgenograms like this of Figure 1 with extensive PCs. They all belonged to inhabitants of Metsovo. Much to their surprise, nobody was excited with this unusual picture. As a matter of fact they were reasured that this was very common to Metsovites and was the result of old tuberculous pleuricy. Since the picture is not even remotely similar to calcified pleuricy from previous tuberculosis, they started looking into the problem, with the following questions: a) are the PCs really so frequent? b) are they really seen only in Metsovites? and, most importantly, c) if not tuberculosis what is their cause?
The answer to the first two questions came soon, after a field study in Metsovo and other areas around Ioannina. Yes, they were very common among Metsovites, around 50% of adult population, increasing to more than 80% in those above 70. Yes, they were only seen in Metsovo and 3 neightbouring villages.[1]
The answer to the third question became obvious when, a few months later, two consecutive patients appeared with massive pleural effusions that proved to be malignant mesothelioma (Figure 2). Unfortunately, they were only the first of a sad series of mesotheliomas; seven in five years (1981–1985). Seven mesotheliomas in five years in a population of 5.000 are roughly 300 times more than what is expected in a non-asbestos exposed community.[2] As it is well known PCs and MM is a deadly combination that can only be attributed to asbestos exposure,.[3][4]
Thus, the next step was to look for asbestos. Transbronchial lung biopsies from Metsovites with extensive PCs were obtained and sent to Mount Sinai Hospital in New York (Dr. A.Langer and Dr. R.Nolan). Their analysis revealed long thin tremolite asbestos fibers in most biopsies in spite of their minuscule size,[5][6] (Figure 3).
So, asbestos it was, but where was it coming from? There are no asbestos mines or factories near Metsovo. The nearest such mine (active until 1990) is located near Kozani, a city 150 miles east of Metsovo. So the possibility of this exposure being occupational seemed very unlikely.[4][7] However, in the pursuite of the responsible culprit they came across the monumental work of Izzetin Baris dealing with not-occupational (domestic) exposure of vast areas in Anatolya Turkey from erionite and tremolite,.[8][9] Guided by his work, they arranged a meeting with Metsovites where they were told that practically all households in Metsovo were using soil from nearby hills (white soil ="louto" in the local dialect) for whitewashing. The material was applied more often on walls around fireplaces, because it was keeping the walls white, unsoiled from the fire. This was no less than an etymologic diagnosis. Asbestos is called αμίαντος in Greek (amiante in French) and means something that is not soiled (e.g. by fire). This whitewash was used by everybody until 1940-1950 and gradually abandoned, so that in 1980 it was used by only 15% of the households and before 1985 it was completely abandoned,.[10][11]
The whitewash was sent to Mount Sinaii Hospital, NY, NY, and proved to be identical to the material previously obtained from the lungs of Metsovites; fibers of tremolite asbestos,[5][6] (Figures 4, 5).
As mentioned earlier, “luto” was obtained by digging soil from hills 5–10 km far from Metsovo within the “Pindos serpentine zone” (Figure 6). It was shaped like a ball (Figure 7), chushed into powder, boiled and applied on the walls. Crushing the ball released more than 200 fibers/ml of air, when the accepted limits for occupational exposure are lower that one fiber/ml. There were minuscule fiber concentrations during the rest of the process, while no fibers were detected in the ambient atmosphere of Metsovo.[10]
There has never been any commercial use of the soil within this “Pindos serpentine zone” other than that mentioned (asbestos mine in Kozani functioning until the early 1990s), but interestingly, there have been several areas where soil had been used by small populations in the remote past, like in Metsovo, for various domestic uses. In at least two of them there have been small “epidemics” of mesothelioma. The use of this soil has been abandoned at least 50–60 years ago.[12] Outside Greece and of course Turkey,[12][13] similar use with similar results has been reported in other areas of the Mediterranean sea, but also as far as New Caledonia in the Pacific Ocean.[14]
Having found the most likely cause of PCs and mesotheliomas in Metsovo (“luto”) and the temporal course of its use, from 1940-1950 when it was used by all households until 1980-1985 when it was abandoned,[14] it was possible to make an educational guess regarding the end of this epidemic.
First, other sources of asbestos exposure, after the abandonment of “luto”, had to be excluded. Two clinical tools of exposure were use for this purpose. Both had been positive in practically all exposed Metsovites during the peak of “luto” use: chest computed tomography (CT) (Figure 8) [10] and bronchoalveolar lavage (BAL) (Figure 9).[15] All that was required now, was to use these tools in Metsovites born after “luto” use had declined. They had to be over 30, since this is the time needed for PCs to become apparent radiologically.[16] They also had to be and below 50, since older individuals born when “luto” was still used extensively could have been exposed to it, (even if they claimed that they were not using “luto” at home), from the homes of friends and relatives.
The results of this last study confirmed that “luto” was the only source of asbestos exposure in Metsovo as none of the 30- to 50-year-old non-exposed Metsovites examined had PCs or asbestos fibers,.[17][18]
Finally, after thirty years of research it was possible to examine the dynamics of the frequency of PCs among Metsovites between 1980-2010. As expected, their frequency is decreasing and the age when PCs are first seen is increasing,[19][20][21] (Figure 10).
How about mesothelioma? After the first study in the 1980s, two studies have shown that the incidence of mesothelioma is also dropping,[22][23] (Figure 11). Unfortunately however, the end of this“epidemic” cannot be predicted safely. Mesotheliomas appear usually 30–50 years after exposure but this can be prolonged, very rarely, to 70 years. Thus, since “luto's” use has stopped between 1980-1985 mesotheliomas are expected to be seen in fading incidence until 2020-2030. However, there is no way to exclude the possibility of mesothelioma in the unlucky Metsovite born e.g. in 1970, seventy years later, around 2040.[24]
This 30+ year study of “Metsovo Lung” suggests that we are dealing with a unique situation where the whole population (5.000) of a village had been exposed to tremolite asbestos via a traditional material for interior whitewashing (“luto”). After its gradual abandonment, the exposure has ended and young Metsovites present no asbestos related health hazards.

References

  1. ↑ Constantopoulos SH, Goudevenos JA, Saratzis NA, Langer AE, Selikoff IJ, Moutsopoulos HM. Metsovo Lung: pleural calcifications and restrictive lung function in North-Western Greece; environmental exposure to mineral fiber as etiology. Environmental Research , 1985; 38(2): 319-331
  2. ↑ Constantopoulos SH, Malamou-Mitsi V, Goudevenos JA, Papathanasiou MP, Pavlidis NA, Papadimitriou CS. High incidence of malignant pleural mesothelioma in neighbouring villages of Northwest Greece. Respiration, 1987; 51: 266-271
  3. ↑ Selikoff IJ, Churg J, Hammond EC. Asbestos exposure and neoplasia. JAMA 1964; 188: 142-146
  4. 1 2 Dennis J. Darcey and Tony Alleman. Occupational and environmental exposure to asbestos. In: Victor L. Roggli, Tim D. Oury and Thomas A. Sporn (Eds). Pathology of asbestos-associated diseases. 2nd edition, Springer Verlag 1992; p. 17-33
  5. 1 2 Langer AM, Nolan RP, Constantopoulos SH, Moutsopoulos HM. Association of Metsovo Lung and pleural mesothelioma with exposure to tremolite-containing whitewash. Lancet i, 1987; April 25: 965-967
  6. 1 2 Constantopoulos SH, Langer AM, Saratzis N, Nolan RP. Regional findings in Metsovo Lung. Lancet ii, 1987; 452-453
  7. ↑ Constantopoulos SH. Environmental mesothelioma associated with tremolite asbestos: Lessons from the experiences of Turkey, Greece, Corsica, New Caledonia and Cyprus. Regulatory Toxicology and Pharmacology, 2008; 52: S110-S115
  8. ↑ Baris YI, Saracci R, Simonato L, Skidmore JW, Artvinli M. Malignant mesothelioma and radiological chest abnormalities in two villages in central Turkey. Lancet 1981; 1: 984-987
  9. ↑ Baris ΥΙ, Sahin AA, Ozesmi M, Kerse I, Ozen E, Kolacan B, Altinorrs M, Goktepeli A. An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urug in Anatolia. Thorax 1978; 33: 181-192
  10. 1 2 3 10. Constantopoulos SH, Saratzis NA, Goudevenos JA, Kontogiannis D, Karantanas A. Katsiotis P. Tremolite white-washing and pleural calcifications . Chest 1987; 92: 709-712
  11. ↑ 11. Constantopoulos SH, Theodoracopoulos P, Dascalopoulos G, Saratzis N, Sideris K. Metsovo Lung outside Metsovo. Chest, 1991; 99: 1158-61
  12. 1 2 8. Baris YI, Saracci R, Simonato L, Skidmore JW, Artvinli M. Malignant mesothelioma and radiological chest abnormalities in two villages in central Turkey. Lancet 1981; 1: 984-987
  13. ↑ 9. Baris ΥΙ, Sahin AA, Ozesmi M, Kerse I, Ozen E, Kolacan B, Altinorrs M, Goktepeli A. An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urug in Anatolia. Thorax 1978; 33: 181-192
  14. 1 2 7. Constantopoulos SH. Environmental mesothelioma associated with tremolite asbestos: Lessons from the experiences of Turkey, Greece, Corsica, New Caledonia and Cyprus. Regulatory Toxicology and Pharmacology, 2008; 52: S110-S115
  15. ↑ 12. Constantopoulos SH, Dalavanga YA, Sakellariou K, Goudevenos J, Kotoulas OB. Lymphocytic alveolitis and pleural calcifications in non-occupational asbestos exposure. Protection against neoplasia? American Review of Respiratory Diseases, 1992; 146: 1565-1570
  16. ↑ 13. Hillerdal G. Malignant mesothelioma 198: review of 4.710 published cases. Brit J Dis Chest 1983; 77: 321-328
  17. ↑ 14. Gogali A, Ntzani E, Peristeri S, Tzarouchi L, Manda-Stachouli C, Vadivoulis Th, Dascalopoulos G, Tsampoulas K, Constantopoulos S, and Dalavanga Y. End of domestic asbestos exposure epidemic in Metsovo; N.W. Greece European Respiratory Society, Annual Congress 2012
  18. ↑ 15. Gogali A, Ntzani E, Konstantinidis A, Peristeri S, Tzarouchi L, Manda-Stachouli C, Daskalopoulos G, Constantopoulos SH, Dalavanga YA. Assessment of an isolated environmental and domestic asbestos exposure in Metsovo NW Greece: evidence of containment (Submitted)
  19. ↑ 14. Gogali A, Ntzani E, Peristeri S, Tzarouchi L, Manda-Stachouli C, Vadivoulis Th, Dascalopoulos G, Tsampoulas K, Constantopoulos S, and Dalavanga Y. End of domestic asbestos exposure epidemic in Metsovo; N.W. Greece European Respiratory Society, Annual Congress 2012
  20. ↑ 15. Gogali A, Ntzani E, Konstantinidis A, Peristeri S, Tzarouchi L, Manda-Stachouli C, Daskalopoulos G, Constantopoulos SH, Dalavanga YA. Assessment of an isolated environmental and domestic asbestos exposure in Metsovo NW Greece: evidence of containment (Submitted)
  21. ↑ 16. Manda-Stachouli C, Dalavanga Y, Dascalopoulos G, Leontaridi Ch, Vassiliou M, Constantopoulos SH. Decreasing prevalence of pleural calcifications among Metsovites with non-occupational asbestos exposure. Chest, 2004; 126: 617-621
  22. ↑ 17.17. Sakellariou K, Malamou-Mitsi V, Haritou A, Koumpaniou Ch, Stachouli C, Dimoliatis ID, Constantopoulos SH. Malignant pleural mesothelioma from non-occupational asbestos exposure in Metsovo (North West Greece); slow end of an epidemic? Εuropean Respiratory Journal, 1996; 9: 1206-1210
  23. ↑ 18. Gogali A, Manda-Stachouli C, Ntzani EE, Matthaiou M, Konstantinidis AK, Zampira I, Koubaniou Ch, Dalavanga Y, Stefanou D, Constantopoulos SH and Daskalopoulos G. Malignant mesothelioma in Metsovo, Greece, from domestic use of asbestos: 30 years later. Εuropean Respiratory Journal,2012; 39: 1-2
  24. ↑ 19. Constantopoulos S. Metsovo Lung. A detective story with a happy ending. PNEUMON Supplement 1, Vol 27, 2014
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