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Particle size for differentiation between inhalation and injection pulmonary talcosis
ENVIRONMENT.~L
Particle
Drpurimrnr
RESEARCH
21,
94-96
(1980)
Size for Differentiation between Inhalation Injection Pulmonary Talcosis JERROLD L. ABRAHAM
AND CHRISTIANBRAMBILLA
o$ Prrthology.
Scl~oc~l i1.f‘ Mc~dicitw.
M-01 2. UCSD
December
1~ Jo//~/,
C‘trl~fimi~r
and
Y2N3
4. 1978
Light microscopic measurement of the size of birefringent particles in 1 I cases of pulmonary talcosis provides differentiation between injection and inhalation origin, The mean particle diameter (*SD) in inhalation cases was 3.7 i 2.9 /rrn and in injection cases was 14.2 5 9.0 pm (P c 0.001). The finding of a majority of particles too large to be respirable ( a5 pm) should raise the suspicion of injection as the source.
INTRODUCTION
The differentiation between pulmonary diseases caused by inhalation of dust and foreign-particle pulmonary embolism is generally easy. When the lesions are located in the lumen or wall of the blood vessel and/or there is evidence of marked pulmonary arterial hypertension in association with the presence of foreign material, the evidence for vascular origin is strong (Wendt et crl., 1964: Szwed, 1970: Douglas et crl., 1971; Lewman, 1972; Gillett and Ford, 1978). Much of the time the occupational exposure of the patient or the history of drug addiction is the major clue to the diagnosis. However. the exposure to dust may be difticult to document (Nam and Gracey, 1972) and drug abuse histories are not always reliable. Although the histologic lesions may differ considerably from inhalation pneumoconiosis to particle embolism, the pathologist has sometimes to answer on a small sample in which fibrosis may totally obliterate the pulmonary structure. We are particularly interested in lesions due to talcum powders (Kleinfeld rt rrl., 1963: Weiss and Boettner, 1967; Goodwin, 1974: Lead article, 1977). These powders, in addition to their cosmetic properties, are widely used as a lubricating agent in various industries (rubber, painting, rooting, etc.). The heterogeneity of their composition results in different pulmonary responses, depending on the amount of silica, asbestos fibers, different silicates, and true talc. Talc is also used as a filler in oral medications which drug addicts may inject. MATERIALS
AND
METHODS
From the Averill A. Liebow Pulmonary Pathology Collection, we examined 1 I is used in quotation here documented cases diagnosed as “talcosis. ” “Talcosis” as the light microscopic identification of strongly birefringent, plate-like particles and is not specific for talc. Scanning electron microscopy and X-ray microanalytical techniques (Abraham, 1978) have identified many of the particulates in these cases as talc, but several other kinds of silicates are associated with the talc as usually minor or, rarely, major components (Brambilla et ~1.. 1978). Six cases were inhalation pneumoconiosis and 5 were from drug-addicted patients. In all the cases, examination was performed by light microscopy using polarizing filters which revealed numerous plate-like, strongly birefringent crystals. As the crystals 94 0013-9351/80/010094-03$02.00/O Copyright 0 1980 by Academic Press, Inc All right of reproduction in any form reserved.
PARTICLE
SIZE
IN TALCOSIS
95
seemed qualitatively larger in cases of injection of talcum powder, we measured the maximum diameter to the nearest micrometer of 100 consecutive birefringent particles in each case, using a calibrated ocular measuring grid. RESULTS The results of these measurements are shown in the histogram (Fig. 1). In the injection “talcosis” cases, the particles vary widely in size (up to 50 pm and even more), with a mean of 14.2 pm. In the inhalation “talcosis” cases, on the contrary, the mean size is 3.7 pm; 70% of the particles are less than 5 pm and 98% less than 10 pm (P < 0.001 using the x? test when compared with injection “talcosis”). The only particles between 10 and 1.5pm found in the inhalation “talcosis” cases are very elongated (i.e., fibers), having an aspect ratio (length/width) greater than 10 (usually between 2 and 4 in smaller particles). There is some overlap in the two size distributions but not a single case of inhalation “talcosis” showed less than 50% of particles in the 0 to 5 pm range, nor did a single case of injection “talcosis” have more than 25% of the particles in the 0 to 5 pm range. The sources of injected crystalline material may vary from soil to pharmaceutical tablets. It is possible that on occasion the intravenously injected material may be largely composed of “respirable” (~5 pm) sized particulates. We have not yet recognized such a case. DISCUSSION Little discussion exists on the size of the particles (Alvisatos et (II., 1955) in pulmonary talcosis. It has been claimed (van Wijk and Patterson, 1940) that the inhaled particles larger than 5 pm (aerodynamic diameter) are not harmful to the lung. This is not true in that aerodynamically larger particles which deposit more proximally (Lippmann, 1977) can produce damage to the airways (Abraham, 1978), for example, giving rise to industrial bronchitis (Lapp. 1974). Generally, however, the distal lung parenchyma is protected from the larger particles by the dust deposition characteristics of the upper respiratory tract and major airways (Lippmann, 1977). Owing to their fibrous and plate-like shapes, the inhaled talc particles greater than 5 Frn in maximum diameter may sometimes reach the acinar level and induce parenchymal lung lesions. Some selection of intravenously trans-
Maximum
FIG. talcosis
1. Histogram (600 particles
Dimensmn
showing percentage of particles total) and five cases of injection
( pm)
in each talcosis
size range for six cases of inhalation (500 particles total).
96
ABRAHAM
AND
BRAMBILLA
ported particles must take place in the vascular system, but much larger particles can reach the pulmonary acinar parenchyma via the arterial route than by inhalation, as these results demonstrate. Contrary to in i~itr’o findings (Henderson et rrl., 1975) very large particles of injected talc may be found in giant cells in ~~~Lw. A striking finding in our study is the difference in particle size between inhalation and injection “talcosis.” This should be of interest to pathologists and clinicians. It gives a straightforward and strong suggestion of injection of foreign material when a major fraction of particles are larger than 5 pm (i.e., too large to be “respirable”). Knowledge of dust deposition characteristics is thus of practical diagnostic importance as well as of theoretical interest. ACKNOWLEDGMENTS We thank Mrs. Christina Lloyd for meticulous preparation of the manuscript. This work was supported in part by USPHS Grants HL 19619 and HL 07104. The Averill A. Liebow Pulmonary Pathology Collection is supported in part by the Division of Lung Diseases, NHLBI, NIH. Dr. Christian Brambilla was a recipient of a Fellowship from the Research Council of the Medical University of Grenoble (France).
REFERENCES Abraham, .I. L. ( 1978). Recent advances in pneumoconiosis-The pathologist’s role in etiologic diagnosis. In “The Iung” (W. T. Thurlbeck and M. R. Abell. Eds.). pp. 966137. Williams & Wilkins. Baltimore, Md. Alvisatos, G. P., Pontikakis, A. E.. and Terzis. B. (1955). Talcosis of unusually rapid development. Brit. J. Itrd. MP~. 12, 43-49. Brambilla. C.. Abraham, J. L.. and Liebow. A. A. (1978). Light microscopy. TEM. SEM and x-ray microanalysis of inhalation and intravenous silicate pneumoconiosis. Amer. RcI,. Rasp. Di.\. 117, 221. Douglas, F. G.. Katilmout. K. J.. and Patt. N. L. (1971). Foreign particle embolism in drug addicts: Respiratory pathophysiology. Ann. Int. Med. 75, 865-872. Gillett. D. G., and Ford. G. T. (1978). Drug-induced lung disease. In “The Lung” (W. T. Thurlbeck and M. R. Abell, Eds.). pp. 21-42. Williams & Wilkins, Baltimore, Md. Goodwin. A. (Ed.) (1974). “Proceedings of the Symposium on Talc.” pp. ll102, Washington. D.C. U.S. Bureau of Mines, Information Circular 8639. Washington, D.C.. May 8. 1973. Henderson. W. J.. Blundell. G., and Richards, R. (1975). Ingestion of talc particles by cultured lung libroblasts. Efti,iro,r. MeJ. Res. 2. 173. Kleinfeld, M., Giel. C. P., Majeranowski. J. F.. and Messite. J. (1963). Talc pneumoconiosis. Arc.11. Et~~~iron. Hctrltlr 7, 101 - 115. Lung Diseases” (W. K. C. Morgan and A. Lapp. N. L. (1974). Industrial bronchitis. ln “Occupational Seaton. Eds.). pp. 2655273. Saunders. Philadelphia. Lead article. (1977). Cosmetic talc powder. Ltr/rc,<,( 1. 1348. Lewman. L. V. ( 1972). Fatal pulmonary hypertension from intravenous injection of methylphenidate (ritalin) tablets. H~~mt~n Ptrrh~d. 3. 67-70. Lippmann. M. ( 1977). Regional deposition of particles in the human respiratory tract. In “American Physiological Society Handbook of Physiology. Reactions to Environmental Agents.” pp. 213-232. Bethesda. Md. Nam. K.. and Gracey. D. R. ( 1972). Pulmonary talcosis from cosmetic talcum powder. .I. Arrtc,r. hlc,cl. A.\.\. 221. 492-493. addiction. A/I/I. frrt. hfcd. Szwed, J. J. (1970). Pulmonary angiothrombosis caused by “blue velvet“ 73, 771-774. van Wijk. A. M.. and Patterson. H. S. (1940). The percentage of particles of different sizes removed from dust-laden air by breathing. J. I/td. Hy~g. 22. 31-35. Weiss, B.. and Boettner, E. A. (1967). Commerical talc and talcosis. .4fr,lr. E/ti~irr~~t. H~~~rltl~ 14, 3044308. W.. and Wolf. P. L. (1964). Angiothrombotic Wendt. V. E.. Pure. H. E.. Shapiro. J., Mathews. pulmonary hypertension in addicts. J. Anzcr. Med. A.\.\. 188. 755-757.
Particle
Drpurimrnr
RESEARCH
21,
94-96
(1980)
Size for Differentiation between Inhalation Injection Pulmonary Talcosis JERROLD L. ABRAHAM
AND CHRISTIANBRAMBILLA
o$ Prrthology.
Scl~oc~l i1.f‘ Mc~dicitw.
M-01 2. UCSD
December
1~ Jo//~/,
C‘trl~fimi~r
and
Y2N3
4. 1978
Light microscopic measurement of the size of birefringent particles in 1 I cases of pulmonary talcosis provides differentiation between injection and inhalation origin, The mean particle diameter (*SD) in inhalation cases was 3.7 i 2.9 /rrn and in injection cases was 14.2 5 9.0 pm (P c 0.001). The finding of a majority of particles too large to be respirable ( a5 pm) should raise the suspicion of injection as the source.
INTRODUCTION
The differentiation between pulmonary diseases caused by inhalation of dust and foreign-particle pulmonary embolism is generally easy. When the lesions are located in the lumen or wall of the blood vessel and/or there is evidence of marked pulmonary arterial hypertension in association with the presence of foreign material, the evidence for vascular origin is strong (Wendt et crl., 1964: Szwed, 1970: Douglas et crl., 1971; Lewman, 1972; Gillett and Ford, 1978). Much of the time the occupational exposure of the patient or the history of drug addiction is the major clue to the diagnosis. However. the exposure to dust may be difticult to document (Nam and Gracey, 1972) and drug abuse histories are not always reliable. Although the histologic lesions may differ considerably from inhalation pneumoconiosis to particle embolism, the pathologist has sometimes to answer on a small sample in which fibrosis may totally obliterate the pulmonary structure. We are particularly interested in lesions due to talcum powders (Kleinfeld rt rrl., 1963: Weiss and Boettner, 1967; Goodwin, 1974: Lead article, 1977). These powders, in addition to their cosmetic properties, are widely used as a lubricating agent in various industries (rubber, painting, rooting, etc.). The heterogeneity of their composition results in different pulmonary responses, depending on the amount of silica, asbestos fibers, different silicates, and true talc. Talc is also used as a filler in oral medications which drug addicts may inject. MATERIALS
AND
METHODS
From the Averill A. Liebow Pulmonary Pathology Collection, we examined 1 I is used in quotation here documented cases diagnosed as “talcosis. ” “Talcosis” as the light microscopic identification of strongly birefringent, plate-like particles and is not specific for talc. Scanning electron microscopy and X-ray microanalytical techniques (Abraham, 1978) have identified many of the particulates in these cases as talc, but several other kinds of silicates are associated with the talc as usually minor or, rarely, major components (Brambilla et ~1.. 1978). Six cases were inhalation pneumoconiosis and 5 were from drug-addicted patients. In all the cases, examination was performed by light microscopy using polarizing filters which revealed numerous plate-like, strongly birefringent crystals. As the crystals 94 0013-9351/80/010094-03$02.00/O Copyright 0 1980 by Academic Press, Inc All right of reproduction in any form reserved.
PARTICLE
SIZE
IN TALCOSIS
95
seemed qualitatively larger in cases of injection of talcum powder, we measured the maximum diameter to the nearest micrometer of 100 consecutive birefringent particles in each case, using a calibrated ocular measuring grid. RESULTS The results of these measurements are shown in the histogram (Fig. 1). In the injection “talcosis” cases, the particles vary widely in size (up to 50 pm and even more), with a mean of 14.2 pm. In the inhalation “talcosis” cases, on the contrary, the mean size is 3.7 pm; 70% of the particles are less than 5 pm and 98% less than 10 pm (P < 0.001 using the x? test when compared with injection “talcosis”). The only particles between 10 and 1.5pm found in the inhalation “talcosis” cases are very elongated (i.e., fibers), having an aspect ratio (length/width) greater than 10 (usually between 2 and 4 in smaller particles). There is some overlap in the two size distributions but not a single case of inhalation “talcosis” showed less than 50% of particles in the 0 to 5 pm range, nor did a single case of injection “talcosis” have more than 25% of the particles in the 0 to 5 pm range. The sources of injected crystalline material may vary from soil to pharmaceutical tablets. It is possible that on occasion the intravenously injected material may be largely composed of “respirable” (~5 pm) sized particulates. We have not yet recognized such a case. DISCUSSION Little discussion exists on the size of the particles (Alvisatos et (II., 1955) in pulmonary talcosis. It has been claimed (van Wijk and Patterson, 1940) that the inhaled particles larger than 5 pm (aerodynamic diameter) are not harmful to the lung. This is not true in that aerodynamically larger particles which deposit more proximally (Lippmann, 1977) can produce damage to the airways (Abraham, 1978), for example, giving rise to industrial bronchitis (Lapp. 1974). Generally, however, the distal lung parenchyma is protected from the larger particles by the dust deposition characteristics of the upper respiratory tract and major airways (Lippmann, 1977). Owing to their fibrous and plate-like shapes, the inhaled talc particles greater than 5 Frn in maximum diameter may sometimes reach the acinar level and induce parenchymal lung lesions. Some selection of intravenously trans-
Maximum
FIG. talcosis
1. Histogram (600 particles
Dimensmn
showing percentage of particles total) and five cases of injection
( pm)
in each talcosis
size range for six cases of inhalation (500 particles total).
96
ABRAHAM
AND
BRAMBILLA
ported particles must take place in the vascular system, but much larger particles can reach the pulmonary acinar parenchyma via the arterial route than by inhalation, as these results demonstrate. Contrary to in i~itr’o findings (Henderson et rrl., 1975) very large particles of injected talc may be found in giant cells in ~~~Lw. A striking finding in our study is the difference in particle size between inhalation and injection “talcosis.” This should be of interest to pathologists and clinicians. It gives a straightforward and strong suggestion of injection of foreign material when a major fraction of particles are larger than 5 pm (i.e., too large to be “respirable”). Knowledge of dust deposition characteristics is thus of practical diagnostic importance as well as of theoretical interest. ACKNOWLEDGMENTS We thank Mrs. Christina Lloyd for meticulous preparation of the manuscript. This work was supported in part by USPHS Grants HL 19619 and HL 07104. The Averill A. Liebow Pulmonary Pathology Collection is supported in part by the Division of Lung Diseases, NHLBI, NIH. Dr. Christian Brambilla was a recipient of a Fellowship from the Research Council of the Medical University of Grenoble (France).
REFERENCES Abraham, .I. L. ( 1978). Recent advances in pneumoconiosis-The pathologist’s role in etiologic diagnosis. In “The Iung” (W. T. Thurlbeck and M. R. Abell. Eds.). pp. 966137. Williams & Wilkins. Baltimore, Md. Alvisatos, G. P., Pontikakis, A. E.. and Terzis. B. (1955). Talcosis of unusually rapid development. Brit. J. Itrd. MP~. 12, 43-49. Brambilla. C.. Abraham, J. L.. and Liebow. A. A. (1978). Light microscopy. TEM. SEM and x-ray microanalysis of inhalation and intravenous silicate pneumoconiosis. Amer. RcI,. Rasp. Di.\. 117, 221. Douglas, F. G.. Katilmout. K. J.. and Patt. N. L. (1971). Foreign particle embolism in drug addicts: Respiratory pathophysiology. Ann. Int. Med. 75, 865-872. Gillett. D. G., and Ford. G. T. (1978). Drug-induced lung disease. In “The Lung” (W. T. Thurlbeck and M. R. Abell, Eds.). pp. 21-42. Williams & Wilkins, Baltimore, Md. Goodwin. A. (Ed.) (1974). “Proceedings of the Symposium on Talc.” pp. ll102, Washington. D.C. U.S. Bureau of Mines, Information Circular 8639. Washington, D.C.. May 8. 1973. Henderson. W. J.. Blundell. G., and Richards, R. (1975). Ingestion of talc particles by cultured lung libroblasts. Efti,iro,r. MeJ. Res. 2. 173. Kleinfeld, M., Giel. C. P., Majeranowski. J. F.. and Messite. J. (1963). Talc pneumoconiosis. Arc.11. Et~~~iron. Hctrltlr 7, 101 - 115. Lung Diseases” (W. K. C. Morgan and A. Lapp. N. L. (1974). Industrial bronchitis. ln “Occupational Seaton. Eds.). pp. 2655273. Saunders. Philadelphia. Lead article. (1977). Cosmetic talc powder. Ltr/rc,<,( 1. 1348. Lewman. L. V. ( 1972). Fatal pulmonary hypertension from intravenous injection of methylphenidate (ritalin) tablets. H~~mt~n Ptrrh~d. 3. 67-70. Lippmann. M. ( 1977). Regional deposition of particles in the human respiratory tract. In “American Physiological Society Handbook of Physiology. Reactions to Environmental Agents.” pp. 213-232. Bethesda. Md. Nam. K.. and Gracey. D. R. ( 1972). Pulmonary talcosis from cosmetic talcum powder. .I. Arrtc,r. hlc,cl. A.\.\. 221. 492-493. addiction. A/I/I. frrt. hfcd. Szwed, J. J. (1970). Pulmonary angiothrombosis caused by “blue velvet“ 73, 771-774. van Wijk. A. M.. and Patterson. H. S. (1940). The percentage of particles of different sizes removed from dust-laden air by breathing. J. I/td. Hy~g. 22. 31-35. Weiss, B.. and Boettner, E. A. (1967). Commerical talc and talcosis. .4fr,lr. E/ti~irr~~t. H~~~rltl~ 14, 3044308. W.. and Wolf. P. L. (1964). Angiothrombotic Wendt. V. E.. Pure. H. E.. Shapiro. J., Mathews. pulmonary hypertension in addicts. J. Anzcr. Med. A.\.\. 188. 755-757.