post-mortem bronchography andpost-mortem bronchography in the study of bronchitis and emphysema been...

Thorax (1963), 18, 172

Post-mortem bronchography in the study ofbronchitis and emphysemaJ. G. LEOPOLD AND J. GOUGH

From the Welsh National School of Medicine, Cardiff

Many characteristic bronchographic features havebeen recorded in patients with chronic bronchitisbut current interest is focused on the changes atthe periphery of the bronchial tree (Freimanisand Molnar, 1960; Hirschfeld, 1961 ; Hirschfeld,Brantigan, Kress, and Goco, 1962). There are tworeasons for this. Firstly, the small rather than thelarge airways are believed to be of major import-ance in 'obstructive' pulmonary disease. Secondly,some abnormal peripheral patterns described inchronic bronchitis may give a lead to the diagnosisof emphysema, including even the specificanatomical type.

Opportunities of examining lungs pathologicallyshortly after bronchography are rare, hence theneed for a method of post-mortem bronchographywhich can be used to study radiological-patho-logical correlations and assist in interpretingbronchograms produced during life. This paperdescribes a method using airborne lead particles.Although this substance cannot be used in theliving patient we chose it because lead, due to itshigh atomic weight, is sufficiently dense radio-graphically to produce a clear image of the finestair passages when they are merely coated on theirsurfaces. This was preferred to the solid fillingobtained with liquid media, such as Microtrast orthe mixture of Micropaque and gelatin used byReid (1955a). Wyatt, Fischer, and Sweet (1961 and1962) also chose a dry powder Micropaque micro-crystalline barium sulphate. Sills (1962) used iodinevapour but judging from his illustration it isdoubtful whether the peripheral structure is clearlyshown. It is possible by our technique to ascertainaccurately the level at which respiratory structurebegins.

METHOD

CHOICE OF RADIOGRAPHIC CONTRAST MEDIUM Asubstancewas sought which would penetrate along the bronchialpathways to reach and outline the respiratory bronchiolesbut at the same time not produce such a heavy concen-tration in the alveoli as to obscure the anatomical details.Finely powdered metallic lead (2 to 15 microns) in anairborne cloud gives excellent results. The lead is commer-

cially available as a powder, '100 mesh to dust'. Therange of particle sizes in this product varies betweendifferent batches; only those with the f nest dusts havebeen chosen. Finely divided lead is highly toxic ifinhaled. Fortunately it soon settles from the atmosphere.The insufflation is done in a closed room, the operatorwearing a face mask. The Seibe Gorman Mark IV indus-trial respirator holds back particles as small as 0 5 micron.

It is possible that other safer metallic powders couldbe used in place of lead, and current experiments arebeing carried out using precipitated bismuth (B.P.). Thispowder is insoluble in water and has no particles greaterthan 15 microns. The atomic weight is slightly higherthan that of lead: Bi, 209; Pb, 207.

TECHNIQUE The unfixed intact lung is suspended in atransparent negative pressure box (Fig. 1). (A rangeof cannulae is needed for tying into the main bronchiwhich have varied in this series from I to 1-5 cm. indiameter. The left lung is the easier to handle because ofthe greater extrapulmonary length of the left mainbronchus.) Air-tightness of the apparatus and of the lungis important. Results have not been entirely satisfactorywhen a tear in the lung has required repair. The negativepressure applied to produce expansion of the lung has

INSUFFLATOR

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FIG. 1. Transparent negativepressure expansion box.172

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Post-mortem bronchography in the study of bronchitis and emphysema

been of the order of 20 cm. of water, although no harmhas been observed when this figure has been doubled.Generally, pressures in excess of 20 cm. of water arerequired only to overcome the surface tension which ispresent between opposed alveolar walls at the time whenthe first expansion is attempted (Mcllroy, 1952). Thelungs are altemately expanded and then allowed toretract. The lead dust is insufflated into the bronchialcannula during expansion which simulates the inspiratoryphase of respiration and the procedure is repeated over15 to 20 cycles. A volume of approximately 2 to 3 ml. ofdust is used but much is rejected by the lung at eachdeflation. It is important, particularly with emphysema-tous lungs, that adequate time is given between successiveexpansions to allow full collapse of the lung to occur.At the end of the procedure the lung is kept in expansionby plugging the cannula with a rubber bung.

INSUFFLATION OF THE LEAD POWDER The lead is insuf-flated from a small metallic hand insufflator of the typecommonly used for dusting wounds with therapeuticpowders. Replacement of the rubber hand bulb by asupply of pressurized air is more effective in making thelead dust airborne but this has not usually been anadvantage because, early in the procedure, the heavyload of dust clogs the moist bronchial pathway andprevents the finest particles penetrating to the periphery.Dispersion of the lead by a continuous supply of airunder pressure from a pump or cylinder is reserved forcases where, due to tears in the lung or blocking of theair passages by mucus, the method using the handinsufflator has not been effective. Expansion of the lung ina negative pressure container then becomes unnecessary.

RADIOGRAPHY OF THE SPECIMEN For clarity of detail inthe radiograph a fine grain film (Crystallex, a Kodakindustrial x-ray film) has been used and an anode of smelldimension (0-3 mm. focus). The films stand enlargementof five to 10 magnification without loss of detail. Theradiographs have usually been taken with the beam pas-sing coronally through the specimen, i.e., a lateral view.The usual exposure has been 30 mA, 50 Kv at 0-8 sec.

PATHOLOGICAL CORRELATION After radiography thelung is fixed by filling it with 10% formalin solutionrendered neutral or slightly alkaline with sodium bicar-bonate, run into the main bronchus under low pressure,without subsequent clamping of the bronchus. Theaddition of bicarbonate is unnecessary in hard waterareas; it prevents the slight solution of lead that occursin soft water. After one week the lung is cut sagittally.The coating of lead powder on the bronchi and in thelung tissue is clearly visible when the lung is cut. Thelead adheres to surfaces throughout the stages of his-tological preparation, i.e., paraffin embedding, cutting,and staining, aiding the task of relating features seen onthe bronchogram to the anatomy. Slices of lung can beradiographed as a check. The lead does not interferein any of the commonly used staining reactions (Figs. 2and 4) and does not smear as Microtrast does.Gough-Wentworth sections have been cut of the lungs

examined. They provide an accurate record of bronchialN

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FIG. 2. First and second order respiratory bronchiolesseen in histological section with lead dust-coating in situ.Normal lung. Haematoxylin and eosin, x I11.

abnormality and, in particular, of the presence orabsence of emphysema.

RESULTS

More than 30 lungs have been studied by themethod described. Our aim has been solely toperfect the technique and collect for future studycases in which the clinical history enables us tojudge whether the patients had chronic bronchitisas defined in the Ciba Symposium Report (1959).The lungs examined to date include six withemphysema. Three with widespread 'vesicular'emphysema (Heppleston and Leopold, 1961) areincluded and also two further lungs with localdisease of the same type. ('Vesicular' is used todenote emphysema limited to the distal structuresof the acinus, i.e., alveolar ducts and sacs andpossibly distal respiratory bronchioles.) The sixthexample of emphysema is the case of chronicbronchitis with emphysema of centrilobular type(Figs. 3 and 4). It was included so that we couldexamine a known case of clinically severe respira-tory disease.The illustrations show that the me'thod gives

clear definition of the bronchial and bronchiolar

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J. G. Leopold and J. Gough

pathways and, in some parts of the lung at least,respiratory bronchioles. The change in surfacepattern from non-respiratory to respiratory path-ways is striking and accurately depicts the pointwhere alveoli commence. A fine dusting of leadon the surface of respiratory bronchioles resultsin the alveoli becoming discernible in the broncho-grams. In passages heavily dusted with lead, as isoften seen in the proximal respiratory bronchioles,the relatively few alveoli present at this levelappear as domed protrusions from the mainoutline of the passage. In distal respiratorybronchioles, usually only the tissue betweenadjacent alveolar openings is dusted. At this levelalveoli are numerous and the shadow cast in theradiograph can be likened to a piece of wire meshin which the openings represent the alveoli, andthe places where the wire is twisted together repre-sent the lead-dusted surfaces (Figs. 5, 6, and 7).

This report is of a preliminary nature but thereare already noteworthy findings related to theperipheral parts of the bronchogram. A closesimilarity has been noted between in vivo 'peri-pheral pooling' and the circular shadows at theperiphery of the post-mortem bronchogram in the

only case of centrilobular emphysema occurringin this series (Figs. 3 and 4). Furthermore,bronchograms of normal lungs show that thecentral tissue of the lung contains fewer branchesbetween the main bronchus and the first order ofrespiratory bronchiole than has been previouslyrecognized. There may be only six branches (Fig.7). This contrasts with the estimate of Reid(1958), who stated 'the shortest pathway whichsupplies the lung close to the hilum of the seg-ment may have as few as eight'. Hayek (1960),quoting from two different sources, gives figuresof nine and 11.

DISCUSSION

Bronchography has been used to demonstrateabnormalities in persons with chronic bronchitisbut the pathological basis for some of theseabnormalities has not been adequately studied.There is agreement among bronchographists con-cerning the changes at bronchial level which canbe attributed directly to chronic bronchitis.Dilatation of small bronchi which may be local orgeneralized and sometimes apparent only in thefilms taken on inspiration has been described by

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FIG. 3. Part of bronchogram of a slice of lung showing 'pools'. Male, 65 years, with bronchitis, clinical emphysema,and right heart failure. iThe circular expansions, terminating the branchev of the bronchial tree, arefinely dusted by leadpowder. These expansions are centrilobular (respiratory bronchiolar) spaces of emphysema, x 3.

FIG. 4. Histological preparation of lung depicted in Fig. 3. Two small centrilobular spaces. The supplying bronchioleand periphery ofright-hand space are outlined by lead particles. Near right edge is a lobular septum. H. and E., x 11.

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i Distal Respiratory-_t Bronchioles

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FIG. 5. 'Positive' and 'negative' re-presentations of alveoli in lead dustbronchograms.

FIG. 6. Low-power magnification of the peripheralpattern in a broncho-gram using lead powder, to show the distinction between respiratory andnon-respiratory structure. Respiratory structures have a feathery orbossed outline because of the alveoli projecting from the walls, x 3.

FIG. 7. Upper anterior andlingular segmental bronchi oflung shown in Fig. 9. A centralbranch ofthe anterior bronchusdivides only three times beforerespiratory bronchioles areoutlined, i.e., six branchesfromthe main bronchus, x 3.

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FIG. 8. Normal post-mortem bronchogram, left lung.Male 30 years. Accidental electrocution, x T.

FIG. 10. Post-mortem bronchogram. Left lung with earlywidespread 'vesicular' emphysema (panacinar, CibaSymposium, 1959). Male, 56 years. Note the large lungsize, diverticulosis of the stem ofthe lingular bronchus, andthe outlining of respiratory bronchioles in the lingula, x i.

FIG. 9. Post-mortem bronchogram, left lung. Woman of56 years with chronic bronchitis. Widespread tubularbronchial ectasia. Compare with Fig. 8. x j.

t / -.-FIG. 11. Left lower lobe. Apical bronchus showing 'diver-ticulosis', x 2.



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Bonnamour and Badolle (1929), Spark and Wood(1932), Christopherson (1933), and Simon andGalbraith (1953) (Figs. 8 and 9). 'Diverticula' ofthe bronchi were reported by Duprez and Mam-puys (1953) and by Simon and Galbraith (1953)(Figs. 10 and 11). The difficulty of filling thesmaller branches of the bronchial tree due to thepresence of secretions gives the so-called 'brokenbough' appearance.Christopherson's (1933) publication, which was

early in the application of bronchography to thestudy of bronchitis, showed changes in the peri-pheral part of the bronchogram. Interest in thechanges at this level has increased within recentyears and a variety of terms is used to describethe appearance, e.g., peripheral pooling, mimosaor lily of the valley patterns, and spider-likeformations.

It is uncertain whether these terms describeappearances of identical or different pathology.However, Duinker and Huizinga (1962) suggestthat the 'mimosa', 'lily of the valley' and 'spider'patterns are one entity, for which they now

advocate the term of 'the flowers'. 'Pools' theybelieve are different. Proof of the correct interpre-tation of these patterns is awaited. Nevertheless,we firmly believe that all these changes in theperipheral bronchogram are more relevant tochanges in the respiratory rather than in the non-

respiratory structure because, in a lung whichdeveloped granulomata after bronchography withdionosil, the peripheral pools were shown to bedue to the filling of centrilobular emphysematousspaces (Leopold and Seal, 1961). Reid (1955b)explained pools on the basis of saccularbronchiolar ectasia occurring proximal to theterminal bronchiole. Israels and Warringa (1961)called this type of disease 'gallnut' bronchiectasis.There are therefore two quite contradictory viewsregarding the significance of pools. Our viewplaces their origin more distally in the bronchialtree than the view of Reid. Theoretically it mightbe considered of fundamental importance to notehow many bronchial branchings occur proximal tothe pools. The bronchogram showing peripheral'pooling' published by Leopold and Seal (1961)has raised the question whether the pools couldrepresent emphysematous spaces because theywere entered by contrast medium after as few as

six branchings beyond the main bronchus.Our post-mortem bronchograms of normal lungs

provide a satisfactory reply. They show that theremay be as few as six branches from the mainbronchus to the first respiratory bronchiole alongthe non-axial pathways which supply the centre ofthe lung. We doubt that careful noting of the

number of branchings proximal to the pools willnecessarily be of help in distinguishing peripheralsaccular bronchiectasis from centrilobularemphysema. Instead, in patients showing poolingwe suggest the radiographs should be repeated fivedays to one week later. One can expect the usualmechanisms of bronchial clearance to remove theradio-opaque medium from ectatic non-respiratorybronchioles because ectatic changes at this levelare rarely associated with metaplasia of the liningepithelium to a non-ciliated pattern. On the otherhand, opaque medium, lying within centrilobularspaces, depends for its removal on mobilization byalveolar macrophages which will be slower andmay be incomplete.

SUMMARY

Airborne lead particles were used to produce post-mortem bronchograms. The method has thespecial merit of outlining the bronchial tree torespiratory bronchiole level where the presence ofalveoli projecting from the walls results in adistinctive change of outline.The in vivo appearance of 'peripheral pooling'

has been duplicated in the post-mortem broncho-grams of a case of centrilobular emphysema.Bronchograms of normal lungs have shown farfewer branchings of the bronchial tree leading torespiratory bronchiole level in the central tissue ofthe lungs than has previously been recognized.There may be as few as six branches from themain bronchus to the first respiratory bronchiole.

We wish to thank Dr. E. H. Hanson and the staff ofthe Radiology Department of the Cardiff Royal Infirmaryfor their co-operation.

REFERENCES

Bonnamour, S., and Badolle, A. (1929). Presse mid., 37, 173.Christopherson, J. B. (1933). Amer. J. med. Sci., 186, 504.Ciba Symposium Report (1959). Thorax, 14, 286.Duinker, N. W., and Huizinga, E. (1962). Ibid., 17, 175.Duprez, A., and Mampuys, R. (1953). Ibid., 8, 141.Freimanis, A. K., and Molnar, W. (1960). Radiology, 74, 194.Hayek, H. von (1960). The Human Lung, trans. V. E. Krahl, p. 86.

Hafner Publishing Co., New York.Heppleston, A. G., and Leopold, J. G. (1961). Amer. J. Med., 31, 279.Hirschfeld, J. H. (1961). Amer. Rev. resp. Dis., 83, 16.

Brantigan, 0. C., Kress, M. B., and Goco, R. V. (1962). Dis.Chest, 41, 291.

Israels, A. A., and Warringa, R. 3. (1961). In Bronchitis. An inter-national symposium, 1960, Groningen. p. 160, ed. N. G. M. Orieand H. J. Sluiter. Royal Van Gorcum, Assen, Netherlands.

Leopold, J. G., and Seal, R. M. (1961). Thorax, 16, 70.Mcllroy, M. B. (1952). Ibid., 7, 285.Reid, L. M. (1955a). Ibid., 10, 197.

(1955b). Ibid., 10, 199.- (1958). Recent Trends in Chronic Bronchitis, ed. N. C. Oswald

p. 29. Lloyd-Luke, London.Sills, B. (1962). Amer. Rev. resp. Dis., 86, 238.Simon, G., and Galbraith, H. J. B. (1953). Lancet, 2, 850.Spark, J. V., and Wood, F. G. (1932). Ibid., 2, 1419.Wyatt, J. P., Fischer, V. W., and Sweet, H. (1961). Lab. Invest., 10, 159.--- - (1962). Dis. Chest, 41, 239.

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