1150 MICHAELS: LUNG CHANGES IN WOODWORKERS April 22, 1967, v. 96

These findings strengthen further the hypo-thesis of a prolonged tumover time of noradren-aline in the affected skin of patients with atopicdermatitis. All normal skin has sympatheticnerves contributing noradrenaline to a pool. Ina steady state, there is an equivalent rate ofproduction and of loss of this neurohormone. Inatopic dermatitis, it is suggested that the skinis placed under stress so that there is an increasein the size of the noradrenaline pool.

SUMMARYSince the turnover time of administered noradren-

aline in the skin of patients with atopic dermatitishas been shown to be prolonged, it was of interestto demonstrate the site of uptake of noradrenaline-14C in atopic dermatitis as compared with othereczematous and normal skin. Two patients withlong-standing atopic dermatitis, a patient with con-tact dermatitis to nickel, and a patient with normalskin were intradermally injected with DL-nora-

drenaline-7-14C acetate and 8 mm. punch biopsiesof the injected site were performed 24 hours later.Radioautographs were developed. At 199 days, therewas a reaction over arrectores pilorum muscles andthe upper one-third of the epidermis, greater inatopic dermatitic skin than in control sections.Grains in the radioautographs were also visible inproximity to arterolar walls. These results confirmearlier studies suggesting that atopic dermatitic skinretains noradrenaline longer than other dermatoses,concentrating the hormone in arrectores pilorummuscles and upper epidermis.

REFERENCES

1. SOLOMON, L. M., WENTZEL, H. E. AND TULSKY, E.:J. Invest. Derm., 43: 193, 1964.

2. KOPRIWA, B. M. AND LEBLOND, C. P.: J. Histochem.Cytochem., 10: 269, 1962.

3. MOLLER, H.: Acta Dermatovener. (Stockholm), 44(Suppl. 55): 1, 1964.

4. BAER, R. L. AND KOPF, A. W., editors: Year book ofdermatology 1964-65, Year Book Medical Publish-ers, Chicago, 1965, P. 98.

5. VAN SCOTT, E. J. AND EKEL, T. M.: Arch. Derm.(Chicago), 88: 373, 1963.

6. COWAN, M. A.: Ibid., 89: 562, 1964.7. VICKERS, C. F. H.: Ibid., 88: 20, 1963.

Lung Changes in WoodworkersL. MICHAELS, M.D., M.C.Path., F.C.A.P.,* Sudbury, Ont.

Pathological changes were observed in the lungs oftwo workers who had been exposed to wood dustfor many years. The cause of death in each casewas unrelated to the lung condition. The histo-pathological changes in the lung were: (1) centri-lobular fibrosis and emphysema, (2) the presence ofintra-alveolar basophilic particles which had exciteda histiocytic and foreign body reaction. Specialstudies of these bodies tended to confirm the suspi-cion that they were particles of wood dust. Studieshave shown that woodworkers are in an environ-ment heavily saturated with wood dust. The presentstudy suggests that the wood dust is inhaled intothe alveoli and may lead to changes in the lungs.

THE industrial use of wood has greatereconomic importance in Canada than that of

any other product. This industry, comprisingwork involving lumber, furniture, paper and wooditself, employs more than 200,000 people in thiscountry. The sales value of the shipments of pulpand paper alone is higher than that of any othersingle product.' Any illness due to industrialassociation with wood products could, therefore,be of importance to Canada's economy and

The material presented in this paper was demonstratedat the annual meeting of the Ontario Association ofPathologists, Toronto, October 1965.*Pathologist, Sudbury General Hospital, Sudbury, Ontario.

Des modifications pathologiques ont et6 observeesdans le poumons de deux hommes qui, par leurtravail, avaient respir6 pendant des ann6es de lapoussiere de bois. Dans aucun des deux cas, la causele la mort n'a pu etre attribu6 A la pathologiepulmonaire. Les modifications pulmonaires com-prenaient: (1) de la fibrose et de 1'emphyseme dulobe central, (2) la pr6sence de particules alv6o-laires basophiles qui avaient declench6 une r6actiond'histiocytose et de corps 6tranger. L'examen appro-fondi de ces corps e'trangers ont confirm6 le soup-von qu'il s'agissait de particules de poussieres debois. L'etude du milieu a pernis d'indiquer que lestravailleurs du bois vivent dans une atmospherefortement saturee de poussiere de bois. La presente6tude permet de croire que la poussiere de bois estinhal6e dans les alv6oles et peut provoquer deslesions pulmonaires.

could affect the lives of a substantial proportionof the population.Most of the industrial processes in which wood

is handled involve the dissemination of consider-able quantities of fine wood dust into theatmosphere. However, it is stated that pneumo-coniosis does not exist among the workers inthose industries.2 I discovered microscopic intra-alveolar basophilic particles, thought to be wood,in the lungs of two men who had been workingin the wood industry until shortly before their

Canad. Med. Ass. J.April 22, 1967, vol. 96 Michaels: Lung Changes in Woodworkers 1151

deaths; the lungs also showed inflammatory anddegenerative changes. Although the two patientsdied from causes quite unrelated to the lungchanges, these observations should be of interestto Canadian physicians faced with pulmonaryproblems in woodworkers. The purpose of thiscommunication is to describe these changes andto discuss their significance.

Case 1A 40-year-old man was crushed to death in an

elevator accident in a large factory engaged in theproduction of paper from wood pulp. He had workedin most areas of the factory as an odd-job man forabout 10 years. During his life he had not com¬

plained of any significant cough or dyspnea.At autopsy there was a severe crushing injury of

the lower chest and abdomen with extrusion ofabdominal contents into the thoracic cavity througha ruptured diaphragm. There was no hypertrophyor dilatation of the right ventricle or any otherabnormality.

Case 2A 53-year-old man suddenly experienced severe

pain in the mid-chest region. On examination hewas found to be severely shocked and hypotensiveand was admitted to hospital. Morphine, oxygenand heparin were administered, but he died twohours after the onset of his symptoms.He had never complained of cough or dyspnea.

He had worked as a carpenter for 12 years in a

large wood construction company. During the weekbefore his death he had been sawing wood in a

confined space indoors.At autopsy a thrombus completely occluded the

descending branch of the left coronary artery near

its origin. The major coronary arteries showedmarked atherosclerotic narrowing. Patchy fibrosiswas present in the myocardium in the apical regionof the left ventricle. There was no enlargement ofthe right ventricle.

Gross Description of LungsIn Case 1 the lungs were incised at autopsy before

fixation. The cut surfaces of the lungs showedmarked hemorrhage into the lower lobes on eachside. No adhesions were present in the pleuralcavities and bullous emphysema was not seen.

In Case 2 the left lung was examined in the freshstate and the right lung after inflation by the injec¬tion of 10% formalin solution into the main bronchus.No adhesions were present on either side. Thevisceral pleural surfaces of both lungs showednumerous small fibrous nodules, each surrounded bya zone of increased anthracosis. There was no

bullous emphysema, but the cut surfaces of thelungs showed a moderate degree of centrilobularemphysema, which in the fixed inflated right lungwas present mainly in the upper and middle lobes(Fig. 1).

Fig. 1..Close-up of cut surface of the upper lobe ofthe right lung of Case 2 fixed by injection of 10%formalin into the main bronchus. Areas of dilatation ofair spaces associated with increased pigmentation areregularly distributed throughout the tissue. (Specimenwas not photographed under water.)

Microscopic Description of LungsIn both cases histological examination of the lungs

showed areas of peribronchiolar fibrosis and anthra¬cosis with surrounding emphysema of alveolarspaces (Fig. 2). Clusters of foreign-body giant cellsand histiocytes were seen in some alveolar spaces.Within many of these there were one to six particlesof a basophilic material. Each of these particleswas engulfed by a thin rim of the cytoplasm of a

Fig. 2..Microphotograph of Case 1 showing fibrosis,anthracosis and chronic inflammation around terminalbronchioles with emphysematous change in surroundingalveoli (centrilobular emphysema). (Hematoxylin andeosin, X 101.)

1152 Michaels: Lung Changes in Woodworkers Canad. Med. Ass. J.April 22, 1967, vol. 96

Fig. 3..Low-power view of section of lung in Case 2showing intra-alveolar foreign-body giant cell and histi-ocytic infiltrate and basophilic particles. Arrows indicatesome of the basophilic particles. (Hematoxylin and eosin,X 300.)

foreign-body giant cell or surrounded by histiocytes.The basophilic foreign particles are difficult toillustrate adequately in black-and-white photographsowing to their tinctorial similarity to cell nuclei.They were irregular in shape, often roughly sphericaland measured 10 to 15 fi. in maximum diameter.Smaller fragments were also present (Figs. 3 and4). Some of the particles showed as many as fourconcentric laminations of darker blue stainingmaterial alternating with lighter zones (Fig. 5). InCase 1 only three or four particles with theirsurrounding cellular reaction were seen in any singlesection of lung tissue. In Case 2, in which the wholeof the fixed inflated right lung was available forstudy, many such structures were found in some

sections, particularly in those taken from the middlelobe or the posterior portion of the upper lobe,where numbers of basophilic bodies were presentin most random low-power fields. Occasional groupsof basophilic particles engulfed by histiocytes or

giant cells were seen in the lumen of bronchioles.In Case 2 occasional basophilic particles were seen

surrounded by histiocytes, lymphocytes, fibroblastsand collagen in the thickened walls of alveoli andalveolar ducts (Fig. 6). It may be presumed thatthese lesions would become areas of peribronchiolarfibrosis similar to those shown in Fig. 2.

Basophilic Intra-Alveolar ParticlesCompared with Wood DustBecause of the occupational involvement with

wood in each of these two cases it was suspected

Fig. 4..High-power photograph of basophilic particles,intra-alveolar histiocytes and giant cells in Case 2. Someof the phagocytosed basophilic particles are marked byarrows. (Hematoxylin and eosin, X 978.)

that the basophilic intra-alveolar particles were

products of wood dust inhaled by the patientsin the course of their work. The microscopicalstructure of wood dust is that of fragments com¬

posed of variable numbers of narrow hollowspindle-shaped fibres called tracheides. In sec¬

tion these tracheides appear as polygonal struc¬tures, forming a honeycomb of spaces lined bywalls composed mainly of cellulose. A resinoussubstance, lignin, is present mainly between thecellulose walls. The tracheides are stronglybirefringent (Fig. 7).A comparison of the properties of the baso¬

philic particles with tracheides from wood dustwas undertaken. To obtain samples of the latterin histological section, portions of dust from thefloor of the factory in which Case 1 worked were

dehydrated, embedded in paraffin wax cut andmounted like tissue. The staining reactionscarried out are shown in Table I. It will be seen

TABLE I..Comparison of Staining Properties of Basophilic Intra-Alveolar Particles with Tracheides from Wood Dust

Canad. Med. Ass. J.April 22, 1967, vol. 96 Michaels: Lung Changes in Woodworkers 1153

Fig. 5..A single basophilic body showing (just below and to right of centre)concentric laminations in Case 2. Below and to the left of it the nuclei of the foreignbody giant cell which has engulfed it are visible. (Hematoxylin and eosin, X 2875.)

that the particles resemble tracheides of wooddust in most of their reactions. The phlorglucinoltest for lignin was negative, however. This testgave a positive reaction in the fine cement layersof the wood-dust tracheides although the

Fig. 6..Giant cell and inflammatory infiltrate in alveo¬lar wall around the basophilic particle are shown by thearrow. (Hematoxylin and eosin, X 443.)

Fig. 7..Section of wood dust from shop floor of factorywhere Case 1 worked, showing fragments of birefringenttracheides. (Unstained section photographed betweencrossed polaroids, X 300.)

1154 Michaels: Lung Changes in Woodworkers Canad. Med. Ass. J.April 22, 1967, vol. 96

Fig. 8..Section of lung of Case 2 showing intra-alveolarparticle with non-birefringent centre surrounded bystrongly birefringent wall. (Unstained section photo-graphed between crossed polaroids, X 1150.)

tracheide structures themselves were negative.The structure of the intra-alveolar particles wasseen most clearly when unstained sections wereviewed between crossed polaroids. Many of theparticles showed a dark, non-birefringent centresurrounded by a brightly birefringent wall(Fig. 8). The birefringence of the lung particles,although not of the tracheides from wood dust,was masked by hematoxylin but, like the wooddust, was enhanced by toluidine blue staining,which gave an alcohol-sensitive metachromasiato both. The lung bodies were easily detectedby observation of unstained sections betweencrossed polaroids using the scanning lens of themieroscope. Particularly large numbers were ob¬served in this way after making scrapings of thecut surface of fixed (formalin) lung tissue,smearing them on to a mieroscope slide, dryingthem in air and then covering them with a layerof immersion oil.

Investigation of Pulmonary Changesin Patients Employed in Wood IndustryParaffin blocks of the autopsied lungs of a

further 21 patients who had worked in the timberindustry in various parts of Northern Ontariowere obtained through the files of the SudburyGeneral Hospital. In none of these subjects wasa detailed history obtainable regarding the lengthand type of exposure to wood dust.

Sections were cut, mounted unstained on

mieroscope slides and examined between crossedpolaroids for birefringent bodies typical of the

structures described here. In none of thesesections were such structures observed.A review of the autopsy reports and the

routinely stained histological material from the21 patients showed severe emphysema in three,squamous carcinoma of a lung in one and numer¬ous pulmonary corpora amylacea in one.

Discussion

Basophilic intra-alveolar particles of the typedescribed here are unlike any normal structuresfound in the lungs* Pulmonary corpora amylaceamight be considered to have some resemblanceto these structures in their intra-alveolar position,their concentric lamination and their close asso¬ciation with histiocytes and giant cells. Butcorpora amylacea are always larger, uniformlyrounded and usually eosinophilic.5 There islittle doubt that the structures described hereoriginated outside the body.These foreign particles, identical in appear¬

ance in both cases, were found in persons whoseoccupations brought them into an atmospherecontaminated with wood dust. The particlesshow the staining reactions of a polysaccharidematerial, for the most part similar to the re¬action of tracheides from wood dust. Physicaland chemical differences due to electric chargephenomena between minute and larger particlesof wood dust probably exist,6 and these mayexplain the slight differences in staining re¬actions between the intra-alveolar particles andfactory wood dust described in this work. Itseems reasonable to assume that the intra-alveolar particles originated from inhaled wooddust.Very few studies of the public health aspects

of the wood industry are available in the Eng¬lish language. Hanslian and Kadlec7 of Czecho-slovakia have devoted much attention to thissubject, mainly from the point of view of derma¬tological lesions in woodworkers. They contendthat respiratory as well as skin disturbances mayresult in this industry from the very high con¬centrations of wood dust to which woodworkersare exposed.8 They have shown that during themanufacture of furniture a concentration ofwood dust as high as 200 mg./cu.m of air maydevelop; the average level of 40 mg./cu.m. ofwood dust in the air found in this work was farabove the maximum level which they stateshould be allowed.10 mg./cu.m. of air. Theseauthors found that at high concentrations ofwood dust 90% of the wood particles weresmaller than 5 /x. In the lungs of the two patientsdescribed in this communication the particleswere mostly about 10 /*. in diameter, althoughsmaller particles were also observed.

Canad. Med. Ass. J.April 22, 1967, vol. 96 MMICAE ES: LUNG CHANGES IN WOODWORKERS 1155

Hanslian and Kadlec8 have, moreover, carriedout chemical and biological studies on differenttypes of wood and have divided wood into threegroups depending on the degree of toxicity oftheir component substances: (a) woods with lowbiological activity (relatively non-toxic), e.g. oak,beech, maple and ash; (b) woods with high bio-logical activity (relatively toxic), e.g. pine, larchand mahogany, and (c) strongly allergenicwoods, e.g. yew, mansonia. Case 1 in the presentstudy worked in a paper mill where softwoodmainly of the active, second group was used.Case 2 was employed in a general wood con-struction plant and was involved in working withall three types of wood. Thus both men inhaledlarge amounts of a type of wood dust which, ac-cording to Hanslian and Kadlec, could haveharmful effects on human tissues.A brisk foreign-body giant cell and histiocytic

reaction had taken place around all of the intra-alveolar basophilic particles in each case. Thiscould indicate a simple reaction to a foreign sub-stance, similar to the cellular exudate seenaround a splinter of wood embedded in the skin,and does not necessarily have the pathologicalimplication of toxicity. It seems possible, how-ever, that large numbers of particles, even if non-toxic, inhaled into the alveoli could over theyears lead to a degree of fibrosis of the lungs, andstages possibly intermediate to parenchymalfibrosis were seen in Case 2 (Fig. 6).

Centrilobular fibrosis and emphysema werepresent in both cases and may have been theresult of this repeated insult to the lungs over theyears. However, neither patient reported anyrespiratory symptoms and it must be admittedthat centrilobular emphysema is sometimes seenin the lungs of urban residents in the absence ofany relevant industrial history. Whether theemphysematous lesions described in these twopatients are the direct result of the repeated pre-vious aspiration of wood dust cannot be deter-mined in the light of our present knowledge.

I suggest that because of the observations pre-sented here more attention should be directed topossible respiratory changes in woodworkers andto investigation of their clinical, physiologicaland immunological conditions. From the largeconcentration of basophilic bodies in the lungsof Case 2, basophilic bodies might well be ex-creted in the sputum of affected patients and thestrongly birefringent properties of these particlescould be of value in screening unstained slidesof smeared sputum. The environmental condi-tions of woodworkers at work merit further at-tention, and additional pathological studies ofthese people would be of interest.

SUMMARYTwo woodworkers in whom basophilic intra-

alveolar particles were seen at autopsy are described.Both died from non-respiratory causes. Theparticles excited a foreign-body and histiocytic re-action, and centrilobular fibrosis, anthracosis andemphysema were present in both cases. A comparisonof the microscopical features of these bodies withthose of wood dust is presented. Recommendationsfor further study of the possibility of a woodworkers'pneumoconiosis are put forward.

I wish to thank Mrs. Anita Belfry, R.T., and Mr.James Mason, A.I.M.L.T., for technical assistance in thiswork, and Mr. Gerry Hess, Medical Photographer,Sudbury Hospitals, for the photographs.

REFERENCES

1. Canada. Dominion Bureau of Statistics: Canada yearbook, 1963, Queen's Printer, Ottawa, 1964.

2. HINSHAW, H. C. AND GARLAND, L. H.: Diseases ofthe chest, 2nd ed., W. B. Saunders Company, Phila-delphia, 1963, p. 762.

3. BARKA, T. AND ANDERSON, P. J.: Histochemistry,theory, practice and bibliography, Harper & RowPublishers, Inc., New York, 1963, p. 85.

4. GATENBY, J. B. AND BEAMS, H. W., editors: Themicrotomist's vade-mecum (Bolles Lee), 11th ed.,J. & A. Churchill Ltd., London, 1950.

5. MICHAELS, L. AND LEVENE, C.: J. Path. Bact., 74: 49,1957.

6. HANSLIAN. L. AND KADLEC, K.: Personal communica-tion, 1966.

7. Idem: Berufsdermatosen, 14: 41, 1966.8. Idem: Prac. Lec., 16: 276, 1964.