Document Zn2MXKkX4nRnRJ25LXjB0V9RL

id e n o is My the type of asbestos tar.ty. io'-isiy. we are probably ,;*ing a dose of 20 miliitherefore repeating'this morning, Mr. Shidmore to give a known amount of animals. da, Md. i : We have ob , like to ask Dr. Wagner ioma of the pleura, moment are of the I.C.I. 1,000 animals from the s developed. Among our inimai not injected with Ann. N.Y. Acad. S c i . , 132:507-518, 1965. <;cno.s V I I f . A sbf.stos and N f o plas ia: R p i o e ' iioi.ooy ASBESTOSIS AND PRIMARY IXTRATHORACIC NEOPLASMS William D. Buchanan M inistry of Labour, London, Groat. Britain The purpose of this paper 1- to describe one aspect of a study, which has been continued over many years by the Medical Branch of Her Majes ty's Inspectorate of Factories of the Ministry of Labour, of information on certificates of death relating to certain conditions which although not noti fiable to the Inspectorate, have or may have an occupational causation. Among these conditions is fibrosis of the lung including pneumoconiosis in general and asbestosis in particular. In such cases, note has also been made of any coincident lung pathology. Early References Associating Asbestosis and Malignancy From time to time since a Departmental Committee on Compensation for Industrial Disease' first had the possibility of asbestos causing lung disease brought to its attention in 1906. my Department had shown interest in the matter but with no very definite conclusion emerging. Recognition of sev eral cases of lung fibrosis in asbestos workers, in the late 1920s. however, left little doubt as to the reality of the hazard, and in February' 1928 an enquiry was initiated, the medical aspect being undertaken by my former chief, E. R. A. Merewether. The findings were the subject of an official report2 issued in 1980. in whieh year Merewether1 also published a review of the condition and an account of his investigations. Up to that time there appeared to be nothing to suggest malignant disease as a com plicating factor. Credit for the first published suggestion of such an association is usu ally assigned to Lynch and Smith4 who in 1935 described the case of an asbestos weaver at whose death from asbestosis at the age of 57. a lung cancer was also found. Later that year. Gloyne3 published an account of two cases of squamous cancer of the lung occurring with asbestosis. One was a young woman aged 35, exposed, as a spinner, to asbestos for 8 years: the other, also a woman, aged 71, had. in all. 2 years' exposure in the mat tress and opening department of an asbestos factory, but some 15 years previously. Wood and Gloyne' had. however, reviewed in the Lancet the year before, a series of 100 cases of asbestosis seen since 1928. noting in 2S who had died, two cases of carcinoma of the lung and a third case with a few deposits of growth in the pleura. It is also worth noting that Gloyne2 in 1933. in discussing the complications and sequelae of pulmonary asbes tosis. had included a case of abdominal carcinoma and one of squamous carcinoma of the pleura in a group with other complications, which in the 507 ' 4 m am iitiifiwiiiimwiiiflii 508 Annals New York Academ y of Sciences i light of knowledge then available he considered to be incidental and unretated to the asbestosis. Merewether has informed me that Gloyne had suggested to him the possibility of an association of asbestesis and palmonary malignancy some time before 1935. Certainly in retrospect, our records show that by the end o f 1935. out of just under 100 asbestesis deaths by then recorded, seven had a lung cancer. The first of these cases with malignancy, two in number, were recorded in 1932. one being the young woman described by Gloyne. the other a male asbestos compo mixer and sorter who died, aged 70. after an exposure to asbestos of some 30 years. j j ] ! | jj | Source of Information For many years now, we have enjoyed the cooperation of the Registrars t General for England and Wales and for Scotland, who have supplied, routinely, copies of all death certificates relating to those diseases in which j ' we have an interest. The asfaestosis cases we ourselves have abstracted from the much larger group of certificates recording lung fibrosis due to any cause including pneumoconiosis. We believe, despite the fact that asbestosis is not a formally notifiable industrial disease, that certification of the cause of death where asbestosis was diagnosed during life or found to be present at autopsy, is more ac- ; j curate than for many other diseases. As a result, compilation of all such j K death certificates currently provides a reasonably accurate means of deter- * mining the number of persons dying, in whose lungs asbestosis has been , present and. related to the high proportion of such cases coming to autopsy, other relevant pathological conditions present. 5 . Until the middle 1950s. it was the practice to follow-up such information ! by finding as much detail as possible of the occupational history, but the time involved in doing this has made it impossible to continue the practice ' in all cases and the data in this paper are based therefore, with the excep tion of the very early years, when information came from other sources, on an analysis of the information as recorded on the death certificates. We base this belief on a number of reasons. In Great Britain, pneumo coniosis, including asbestosis. is a condition entitling the victim to indus trial injuries benefits under our National Insurance Act or. where the disease was contracted prior to 1548. the Workmen's Compensation Act, Under the industrial injuries provisions, death benefits, generally in the 1 form of a pension, may be payable to eligible dependents. Payment o f benefits is subject to confirmation that death resulted from the disease, normally based on autopsy findings. Periodic medical examinations are also undertaken by the Pneumoconiosis Medical Panels of workers In many occupations with an asbestosis hazard. Lastly, irrespective of any compen sation aspects, death from asbestosis, being of unnatural causation, is an Hut Italian; t CC V fc. I f- ia -5 S <& * O -< lr' <! r. :x I Y 5 t J: 'i i Sciences >be incidental and unre ad me that Gloyne had n of ashe?to-is and pultainly in retrospect, our ist under 100 a.-bestos is The first of these cases in 1932, one being the -Je asbestos conspo miser to asbestos of some 30 ration of the Registrars who have supplied, routhose diseases in which irselves have abstracted ling lung fibrosis due to not a formally notifiable f death where asbestosis at autopsy, is more ac, compilation of all such accurate means of deterings asbestosis has been cases coming to autopsy, [ow-up such information rational history, but the to continue the practice lerefore, with the excepime from other sources, the death certificates. Great Britain, pneumofing the victim to indusance Act or. where the ten's Compensation Act. enefits. generally in the ependents. Payment of suited from the disease, edical examinations are tnels of workers in many ?spective of any eompentuatural causation, is an j \ ; j j j j 4 41 Buchanan: Asbestosis and Ir.trathoracic Neoplasms 509 !I CO Ci o IO * a & a *x r i* ^ s? s & & 7^ X cXs* xz *x < < X $ < CO CO &o b Z<x &uo X s1 X o^ X *55 b 5 s 33 s 2 i> eg eC*4 <z I 3B 3X <&a oo CO CO CO CM <oS --c 3 ct>s cs MP* V * CM CO m CO t1 kO m mmo CM CO O' t n &4 so 03t h3o* 00 T able 3 I ncidence of Asbestosis and I.unc Cancer 1924-1903 A 1 te 510 Annals New York Academy of Sciences event reportable in England and Wales, to Her Majesty's Coroner who may order an autopsy and hold an inquest. For much the same reasons, it is possible, perhaps likely, that even where of minor degree, the presence of asbestosis has tended to be recorded increasingly on the death certificate. From this, it also follows that the increasing total o f cases thus identified in recent years may include less severely affected persons who in earlier years, when awareness was less, might have gone unrecognized. Even so. our totals of death certificates recording asbestosis probably represent an understatement rather than a maximum total of persons dying with, as distinct from, asbestosis. Previously Published Studies by H.M. Factory Inspectorate Merewether's interest in asbestosis and indeed in the pneumoconioses in general, continued after his original investigations were completed. He was responsible for several publications in the Annual Reports`',', of the Chief Inspector of Factories of data of asbestos deaths with the incidence of carcinoma of the lung in them. The first table is reproduced from the 1947 Annual Report. It is believed that this is the first considerable series suggesting the association to have been analyzed. At that time, an attitude of caution was adopted and no formal claims of any association were made. However, the incidence of 13.2 per cent lung cancers in the total for both sexes of 235 deaths with asbestosis up till then identified, was contrasted with an incidence of lung cancer of 1.32 per cent in 6.884 cases certified at death as having silicosis. References to this apparent association of asbestosis and bronchial can cer were again published by Merewether in the Annual Reports of the Chief Inspector for the years 1954 and 1955 by which time similar obser vations had been recorded by other British observers. Table 2 records the position as published in the Annual Report for 1955 when particulars were T able 2 A sbestosis and Cancer of the Lcxg as at 1955 Males Females Total Diagnosis ' Number Percentage i Number Percentage. NumberT!Percentage Asbestosis I ail cases i 1 Asbestosis j and can- j cer of the 1 lung j ,, 100 1 21.6 143 100 365 5 17 ! i11.9 i 65 100 17.8 Buchan. i b3e 'A :< i % 'vjwin f Sciences lajesty's Coroner who may perhaps likely, that even 5 has tended to he recorded s, it also follows that the nt years may include less when awareness was less, otals of death certificates erstatement rather than a t from, asbestosis. ctory Inspectorate ed in the pneumoconioses itions were completed. He Annual Reports"1" of the deaths with the incidence LE is reproduced from the re first considerable series . At that time, an attitude ny association were made. seers in the total for both identified, was contrasted in 6,884 cases certified at estosis and bronchial cante Annual Reports of the which time similar obserwers. Table 2 records the 155 when particulars were :g as at 1955 .........* Total stage Number Percentage 365 100 ; ; ; I 1 : , j ! < I ?v i f t j{ | \ ! > 9 65 17.8 fc Buchanan; Asbestosis and Intrathoracic Neoplasms 511 ----. Include one caso recorded as "cancer of pleura." tlncludes one case recorded as "sarcoma of pleura." 1Includes four cases recorded as "mesothelioma of pleura.! H T aiii.h 4 Mman Auk at Dkath. 1Q47 Scmi.'s V :... 512 Annals New York Academy of Sciences Buchan held in the Medical Branch of 865 death certificates recording asbestosis. Of these. Go or 17.S per cent referred also to the presence of a lung cancer. It will be noted that the proportion with such a tumor had risen in both sexes as compared with 1947, males from 17.2 per cent to 21.6 per cent; females from S.4 per cent to 11.9 per cent. The Current Position We now have, up to the end of 1963, death certificate information con cerning 5S4 deaths, made up of 392 males and 192 females, in which asbes- tosis has figured. To show the changes over the years more clearly, I have presented in table 3. a complete series of recognized cases in convenient periods of time. This table clearly indicates how, in recent years, asbestosis in males, but not in females, has been more frequently recorded on death certificates and, of particular significance in the context of this paper, how the proportion of these cases, in which a bronchial carcinoma or other form of primary thoracic tumor has been found to be present, is also increasing. This in crease in lung cancer as a complicating feature of asbestosis has occurred in both sexes, although both the actual and the relative incidence of asbes tosis in females, as I have remarked, is falling. In the period 1961-1963, no less than 42 of 77 male asbestosis death certificates also recorded a cancer or mesothelioma, a percentage of 34.5, while the corresponding female \ totals were 4 out of 18. a percentage of 22.2. In the complete series, 30.9 f per cent of males and 13 per cent of females have had a lung tumor. | In the analysis of the information available in 1947, it was noted that j the mean age of death of asbestotics with a lung cancer was 52.1 years, ! whereas those dying from asbestosis without such a complication tended 1 to die earlier at a mean age of 44.2 years <TABLE 4 . By 1954, however, this ' difference was less pronounced. ; T able 5 shows the average age at death of the 584 identified subjects i up to the end of 1963. These are arranged according to sex, in three groups, one in which asbestosis was unaccompanied by either tuberculosis a not uncommon complication in the past or carcinoma; one in which it was complicated by tuberculosis and a third in which a thoracic cancer was the complicating feature. The primary object in doing this was to ascertain whether the interesting observation noted in 1947 was still evident, and in this respect, the complete data are inconclusive. The table does, however, show in both sexes a lengthening span of life in those with uncomplicated asbestosis, perhaps in part due to identification of less severe cases during life and their ultimate inclusion in death records. Although not within the v terms of reference of this paper, I think it is worth remarking that tuber t$i. culosis today r.o longer appears a-: a complication of significance In either t\ sex. There is a .considerable variation in the mean age of death in the ! I i t I `4 f Sciences cates recording ashestonis. presence of a Jung cancer, a tumor had risen in both per cent to 21.6 per cent; rtific-ate information con2 females, in which asbesyears more clearly, 1 have rnized cases in convenient s, asbestosis in males, but 1on death certificates and, japer, how the proportion jr other form of primary also increasing. This in>f asbestosis has occurred dative incidence of asbesi the period 1961-1963, no :es also recorded a cancer he corresponding female the complete series, 30.9 e had a lung tumor. i 1947, it was noted that g cancer was 52.1 years, ch a complication tended i. By 1954, however, this e 584 identified subjects ig to sex, in three groups, ither tuberculosis i.a not aa; one in which it was i thoracic cancer was the sg this was to ascertain 7 was still evident, and The table does, however, hose with uncomplicated less severe cases during Although not within the h remarking that ttlberof significance in either an age of death in the f 1 * j j j f * 1 j j i I j j j j ieifcis&aMitielWaf Uak.'iiS".'. Buchanan : Asbestos:s and Intrathoracic Neoplasms 513 1 ' i v imtfit fa? rtehriil 514 i-l s<"t Xa 5< X 1 <X Annate Xew York Academy o f Sciences 8ci s8 l Xy < J2a3 .o3 + *B3 loX i^PO <2 *o6 et <> O OOErt Iog <> o .Q <50 B 35 Oet + trtc 1 - <> J ! <30 *-g Sy Ij Ba Oesaj O ? C03S ea 11 w O 43 ! CO ! 4 1 * 33 i y : o o C4 'J j; 5 'a 1a 1o >' <; ! 33 j i ; i -r i< :i u ' I%* 5 5 .6 i*r1 co io C- ** ITJ o <IO53 4 2 .1 5 5 .3 a IO o 4 IO oio *co* co C-* IO to e* *o3 B B <*) QtO --4 o 73 > -4 ^ < 5 o =5 o . e, c*r3> { *ip r& co 0seo3o o < o 5 Buch female asbestc small. On the been very Uttl this group did tosis only, this Other authoi peritoneum, ar. many instances of asbestosis. . borhood" grouj Mesothelioma h tosis has been < deaths from ca quent but their a percentage of distinguished ii nant disease ex< that, in additio: two examples dt the pleura." If c the proportion t Our records i of cancer of the the suspicion th peritoneum arise The data whic of dying from at erable one and a. be increasing. T there has been i. of statutory prec that the amount years, and we h; of asbestosis are 1 by the statutory there are other it rently dying not 1 suggested that th a greater recogni jgwwiw--yy1 Sciences o IP e* Ip o 4 o w *9 lA ip ft H oo O IP f> ip HCO CO C4 CO <Ipo Ip +tf ) c-a CO tp co ip IP CO H w CO IP 0 CO c o o co o CO aH> Ip o CHO i Buchanan: Asbestosis and Intrathoracic Neoplasms 515 female asbestosis with cancer group, where the totals are mostly relatively small. Or. the other hano. in the large male group with cancer, there has been very little improvement in the average age at death. While initially this group did seem to survive to a greater age than the group with asbes tosis only, this is no longer so, Asbestosis and Mesothelioma Other authors in this Annal have dealt with mesothelioma of pleura and peritoneum, and adduced evidence that this tumor may be one related in many instances to exposure to asbestos with minimal or no obvious evidence of asbestosis. As the population exposed to asbestos dust, including "neigh borhood ' groups is not known, it is impossible to give rates of incidence. s Mesothelioma has also figured in our own series o f deaths in which asbes I tosis has been diagnosed clinically or pathologically. By comparison with deaths from cancer of the lung or bronchi, such deaths have been infre quent but their significance may be better indicated by expressing them as I a percentage of the total number of asbestosis deaths. They have not been distinguished in the tables from the other cases of intrathoracic malig nant disease except in the footnotes to TABLE 3 from which it will be seen that, in addition to four recently diagnosed occurrences there have been two examples described as "cancer of the pleura" and one as "sarcoma of the pleura." If one assumes that all seven cases were in fact mesotheliomas, the proportion turns out to be 1.2 per cent or, in males only, 1.5 per cent. Our records incidentally have also indicated the occasional occurrence of cancer of the ovary, "abdominal" cancer, or "malignant peritonitis" and the suspicion that some such cases may have been mesothelioma of the peritoneum arises. In all, there have been eight such cases. Discussion The data which I have presented suggest that the risk in Great Britain of dying from an intrathoracic tumor if asbestosis is present, is a consid erable one and affects both sexes, although not equally. It also appears to be increasing. This, if true, is a disturbing state of affairs especially as there has been in operation for upwards of 30 years a stringent system of statutory- precautions for the traditional uses of asbestos. It is a fact that the amount of asbestos used annually has increased greatly over the years, and we have some evidence from other sources that the victims of asbestosis are to a greater extent in those industries not directly affected by the statutory precautions. It is well therefore, to consider whether there are other important iniluences operating which result in those cur rently dying not being comparable to those of earlier years. I have already suggested that the increasing totals of recent years may in part be due to a greater recognition of cases which might truly be described as dying i ' J \( i i '* 3 *!' I J1 ' ^` I* 4"* 5* t 't 516 Annals New* York Academy o f Sciences "with"' in contrast to `from" asbestosis. There may be a tendency to perform an autopsy examination of anyone dying from any chest complaint who. in the past, had worked in an asbestos factory. Certainly by now there must be a general awareness of asbestosis as an occupational hazard in the neighborhood areas of the principal asbestos-using factories. By such a means, in view of current compensation policies, a lung cancer might become related in death certification to a relatively minor degree o f asbestosis without the latter necessarily being in any way causal. Study of information on death certificates relating to a particular disease cannot, in the absence of information concerning the size of the population at risk, give any worthwhile information on attack rates. There is also an increasing incidence of lung cancer in the population as a whole, and other influences, such as cigarette smoking, no doubt also operate in asbestotics. Nevertheless, the proportion of males in the whole series in whom lung cancer was present amounted to 30.9 per cent, and of females, to 13.0 per cent, whereas by contrast, in 1962,u which year represents the highest incidence yet published, in the general population 7.5 per cent of deaths in males of 20 years and upwards were due to primary lung or bronchial can cer and 1.4 per cent in the case of females. It is also worth noting that the ratio of the percentage of male asbestotics dying with a lung tumor to the corresponding female series is only 2.4 to 1 compared with a correspending ratio in the general population in 1962 of 5.4 to 1. The data suggest that in contrast to the improving longevity of those with asbestosis alone, there is little improvement in the age at death of those also affected with a cancer. This would suggest that cancer is a complication usually, although by no means always, of long latent period, greater on average than the mean period of survival from first exposure of those severely affected by the asbestosis of earlier years but within the normal period of survival of the less severely affected of today. This might be a further explanation of the growing proportion of such cases dying of lung neoplasm. All said, it seems beyond dispute that in Great Britain, there is a greater risk of dying'from intrathotacie rumor if asbestosis of the lungs is present. Summary The findings of a continuing study by the Medical Branch of H.M. Fac- f tory Inspectorate. Ministry of Labour, of information recorded on death certificates of persons dying with asbestosis are presented. Arrangements are in force whereby copies of all such certificates are received routinely by the Medical Branch. It is considered, for reasons outlined, including the high proportion of such cases coming to autopsy, that this method is a reasonably accurate one of assessing both the incidence of all recognized cases as asbestosis and of complications ensuing. | j f j j } | j g j j j ; j i j j j j ; : ; j , : , ; Bueh A review of the lungs or l Nevertheless, lung carcinoni was that publ: Factories. Sir Up to the et asbestosis have currently inert in both s^xes c<. so that current have also a neo of time of male where the astx where eomplica yearly increasii The conclusion < rising incidence little doubt that tosis is also prest I would like tt over the years, h on which the dat for helpful criti? spector of Factoi this paper. 1 . Departments 1907. P .ep o r 2. Merewether. D u st on. th e S tatio n ery C 9 Mep-ewether, O th e r ptiin-.o 1 2 : !9 c --222; 4. Lynch. K. M. o f th e Iunsr ir 5. (jtISjYSE, R . in asf/e*toSiS. 6. Wood, V,'. B. & cases. L ancet 1. (tlj/: ^ J>. b e r c i e 1 1 : .7.7' H, A nneal Repos 1919. : 79--ii. .... a, ^ n ,u i^TiC6S be &tendency to per il ar.y chest complaint ,ry. Certainly by now an occupational hazard js-using factories. By policies, a lung cancer -.lively minor degree of -.ny way causal. z to a particular disease ,e size of the population rates. There is also an ;.n as a whole, and other -j operate in asbestotics. le series in whom lung i of females, to 13.0 per represents the highest 7.5 per cent of deaths in v lung or bronchial can ; also worth noting that ving with a lung tumor compared with a corref 5.4 to 1. oving longevity of those t in the age at death of jest that cancer is a eoms, of long latent period, rival from first exposure -Her years but within the jted of today. This might -tion of such cases dying Britain, there is a greater sis of the lungs is present. ti I i t dical Branch of H.M. Facmation recorded on death presented. Arrangements ites are received routinely ns outlined, including the isy, that this method is a incidence of all recognized t Buchanan: Asbc-stosis and Ir.trathoracic Neoplasms 517 A review of the literature indicates that the possibility of carcinoma of the lung?, or bronchi as a complication hau been expressed prior to 1947. Nevertheless, it is believed that the first series in which the incidence of iung carcinoma had been related to a sizeable group of asbestosis deaths was that published in the 1P47 Annual Report of the Chief Inspector of Factories. Similar reports followed in 3954 and 1955. Up to the end of 1953. 584 death certificates recording the presence of asbestosis have been obtained and the annual totals of such certificates are currently increasing. The proportion recording a thoracic tumor is also in both sexes continuing to increase disproportionately to the total number, so that currently over 3('> per cent of males dying with asbestosis present have also a neoplasm. Data on the mean age at death over various periods of time of male and femaie asbestosis cases indicate an improving prognosis where the asbestosis is uncomplicated but no significant improvement where complicated by cancer. Suggestions to account for this and also the yearly increasing total of recorded cases of asbestosis are put forward. The conclusion of the study is that even when viewed against the steadily rising incidence of lung cancer in the population as a whole, there seems little doubt that there is a special risk of an intrathoracic tumor if asbes tosis is also present in the lungs. Acknowledgments I would like to record the debt due to my colleague G. O. Williams who, over the years, has been responsible for the abstraction of the information on which the data preserved are based. I wish also to thank Dr. Williams for helpful critism and Dr. T. A. Lloyd Davies, H.M. Senior Medical In spector of Factories and the Ministry of Labour for permission to present this paper. References 1. Departmental Committee on Compensation for I ndustrial Diseases. 1907. Report. H. M. Stationery 0tfi.ee. London, England. 2. Merewcther. E. R. A. & C. *V. Price. 19$ . Report on Effects of Asbestos Dust on the Lungs and Bur. Suppression in the Asbestos Industry. H. M. Stationery Office, London. England. " 3. Merewethek. E. E. A. 19-3.'. The occurrence of pulmonary fibrosis and Other pulmonary affections in asbestos workers. J. Indus. Hvg. Toxicol. 12:198-222; 239-257. ' 4. Lynch, K. M. & W. A. Sm ith. 1935. Pulmonary asbestosis III; Carcinoma of the lung in asbesto-siiieesis. Am. J. Cancer 24: 56. 5. Gloyne. S. R. 1935. Two cases of squamous carcinoma of the iung occurring in asbestosis. Tubercle 17:5. " 6. Wood. W. B. & S. R. Gloyne. 1934. Pulmonary asbestosis. A review of 100 cases. Lancet 2: 13SS. 7. Gloyne. S. R. 1933. The morbid anatomy and histology of asbestosis. Tu bercle 14: 550. ' 8. A n n e a l Report of th e Ch ief I nspector of F actories for t h e year 1947. 1949. : 79-Sl. H. M. Stationery Office London, England. """"'MJWB!WH|.|ilHMHt.Wwwmwwpwj. J, wiwuww i 518 Annals New York Academy o f Sciences 9. a n n e a l Report of t h e Ch ief I nspector of F actories for t h e Year 1954. 1955. : 199-198. H. M. Stationery Office. London. England. 10. A n n e a l Repost of th e Ch ief I nspector of F actories for t h e year 1955. 1956. ; 296. H.M. Stationers- Office. London, England. 11, The R egistrar General's Statistical Review of E ngland and Wales for the year 1962. 1964. Part. I. Tables, Medical. H. M. Stationery Office. London, England. XEOPLASI UNITED 3 Before present would like to dis important. Malignant neoj ing radiation typ a long delay betv In the case of c; peated contacts o the case of agen" continuous from will occur and ho exposure. Now let us con; duce neoplasia bt Here we are deal results in death fi because of the loi result from such e In these situatu to produce the otl veiopment of neop posure. Of equal ; cured, or death del An historical re interesting. All of the early heavily exposed to of the sulfa drugs c-ulosis and pr.eum' pectar.ey in the ger relatively small pe.of cancer become;-, r In 1506, Auribai study of mortality