A THE PATHOLOGY AND PATHOGENESIS OF ...PATHOLOGY AND PATHOGENESIS OFBRONCHIECTASIS BRONCHIAL CASTS Neoprene latex was the most satisfactory of various injection materials used. The

Thurax (1952), 7, 213.

A STUDY OF THE PATHOLOGY AND PATHOGENESIS OFBRONCHIECTASIS *

BY

F. WHITWELLFrom the Departments of' Patlhology, Broadgrcen and Aintree Hospitals, Liverpool

(RECEIVED FOR PUBLICATION FEBRUARY 26, 1952)

Since the first description of bronchiectasis byLaennec in 1819 its pathogenesis has been a con-troversial topic, and although the many theorieshave their recurring moments of popularity, nonehas as yet found general acceptance.One reason for this lies in the widely varying

views of different workers as to the essential natureof the disease. Nowadays the divergence of opinionseems to be occupational, for, while many physi-cians and radiologists think of the bronchialinflammatory changes as mild and the dilatationsof a mechanical nature, most surgeons and patholo-gists regard bronchiectasis as a destructive inflam-matory process.The pathology of bronchiectasis has been

investigated for over a century and the variousaccounts are conflicting. It has been stated thatmany tissue changes described in the earlier literaturecould be attributed to terminal infections andpost-mortem autolysis, and that operation specimensshow less severe lesions which are more consistentwith clinical findings. However, in several recentaccounts the pathological changes described havebeen quite as advanced as those found in post-mortem material, 'but such descriptions have beenfound unacceptable to many clinicians, who regardradiological findings as truer reflections of theunderlying pathology. The popular acceptance ofthis view, with its effect on theories of pathogenesis,has stimulated the present investigation.

It was thought that diversity in the describedlesions of bronchiectasis might be explained by oneor more of the following suppositions. (1) Histo-logical sections may not have been selected (bydifferent investigators) from comparable areas oflung tissue. (2) Variation of histology is due to theseverity, extent, and duration of the illness. (3)Bronchiectasis is not a single pathological entity,but a group of differing conditions having bronchialdilatation as a common factor.-

* Based upon part of an M.D. thesis submitted to the Universityof London in July, 1949.

During a re-examination of histological sectionsof many bronchiectatic lobes most of the describedlesions were seen, but it was impossible to assesstheir frequency, importance, or inter-relationship,or even to locate them. It was thought that themore important features of the disease were beingobscured by detailed histological examination, andthat further knowledge might be gained by adoptingother methods.One difficulty in examining such specimens is

that dissection of the bronchial tree damages thelung tissue and obscures the original shape of thebronchi. Alternatively, to cut the lobes into parallelslices gives more information about bronchialcalibre and peribronchial structures, but less aboutthe bronchial tree as a whole.

In the present investigation the site, shape, andhistology of the lesions of bronchiectasis have beenstudied in 200 consecutive operation specimens bythe following methods: (l) preparation from 70specimens of large histological sections, at varyingdistances from the hilum; (2) detailed dissectionof the bronchial tree of 110 specimens, with histo-logical sections of selected areas; (3) examinationof neoprene casts of the bronchial tree from 20specimens.The object of this work has been to find out

whether any particular types of bronchiectaticlesions are frequently found together, and whethertheir pathology can be correlated to the patients'age, symptoms, duration of disease, or to thenature ofcausative illnesses. The first few specimensexamined all showed widely differing appearances,and, but for the fact that they had been resectedbecause of clinical bronchiectasis, they wouldcertainly not have been considered as examples ofthe same pathological condition. When morespecimens had been studied it was found that abouthalf of them belonged to one or other of fourdistinctive types. The remainder of the specimensformed a heterogeneous group, into which werealso placed those lobes where the original histology

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F. WHITWELL

was obscured by the severity of the disease or bysecondary changes, and those lobes used for neo-prene injections.A large series of specimens has been examined

to provide adequate numbers of each of thesecommon types of bronchiectasis. It was thoughtthat if these were distinct conditions, and not justvariations in a single disease, it might be apparentfrom an examination of the patients' case-notes.When all the specimens had been examined, theessential clinical features of the cases were obtainedfrom the clinical records, and tabulated by. acolleague who was unaware of the pathologicalclassification. These clinical findings have supportedthe opinion that bronchiectasis really consists ofseveral distinct conditions.

Acceptance of this view assists in explaining notonly apparently contradictory accounts of thepathology of bronchiectasis, but also the multiplicityof theories of pathogenesis. These are discussedlater.

MATERIAL AND TECHNIQUE OF THEINVESTIGATION

The material consisted of 200 consecutive operationspecimens removed on account of bronchiectasis or

cystic disease of the lung at the Surgical Chest Centre,Broadgreen Hospital, Liverpool, during the period1946-48. Segmental resections were rarely performedduring this period, and the specimens were nearly allentire lobes and lungs.

FIXATIONThe surgeons fixed the specimens in the operating

theatre by low-pressure injection of 51% formol-saline

corresponded to the observed natural degree of inflation.The specimens were then placed in a large volume of thisfixative for at least two weeks. All specimens weretreated in this manner irrespective of the subsequentmethod of study.

LARGE SECTIONSFixed specimens were immersed in a fresh mixture

of solid carbon dioxide in absolute alcohol for 20minutes to freeze them. They were then sawn intoblocks, 1 cm. thick, with an electric bandsaw, theplane of section being roughly at right angles to thelobar bronchi. The blocks were dehydrated in ethylalcohol, cleared in xylol, and embedded in paraffinwax, the entire process being carried out at reducedpressure (500 mm. Hg.).

Sections 10 tL thick were cut and samples from eachblock stained and examined. In many cases serialsections were taken from the hilum to the periphery,and every fiftieth one was examined. The stains usedon every specimen were Mayer's haemalum and eosin,Weigert's haematoxylin and van Gieson, and Moore'smodification of Weigert's elastic stain (either alone orcounterstained with 1% aqueous pyronin). The sectionswere mounted in balsam on old washed photographichalf- and quarter-plates, and similar glassware was usedfor coverslips. When it was intended to examine thesections with a high power objective they were coveredwith many small thin coverslips.

DISSECTION AND SMALL SECTIONSThe lobes were examined by detailed dissection of the

bronchial tree, using a fine grooved seeker and a razorblade. Histological sections were taken from the areasmost severely and least severely affected, and from theproximal ends of the involved bronchi. The same stainingmethods were used as with the large sections, with theaddition, in some specimen's, of Perl's reaction for freeiron, and frozen sections stained for fat.

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PATHOLOGY AND PATHOGENESIS OF BRONCHIECTASIS

BRONCHIAL CASTSNeoprene latex was the most satisfactory of various

injection materials used. The casts are firm but notbrittle, and they have a flexibility that permits examina-tion of those bronchi which in more rigid materialwould be inaccessible. Another advantage is thatneoprene can be used to fill the alveoli as well as thebronchial tree without the cast fusing into an amorphousmass, for the filled alveoli can be removed in lobules bycutting through the bronchioles.

INJECTION TECHNIQUE.-The injection apparatus con-sisted of a neoprene stock bottle connected to a cannulaby rubber tubing. The pressure of injection, providedby a gas cylinder, was measured with a sphygmomano-meter and regulated with a hand control.

Specimens with adequate hilar bronchi and un-damaged pleural surfaces were selected for injection.These were fixed for a month so that the tissues wouldbe hardened to resist distension from the pressure ofinjections. In each specimen the larger bronchi werecleared of pus with fine Pasteur pipettes attached to asuction pump; a glass cannula was then tiedinto the hilar bronchus and filled with neoprune.After most of the air had been squeezedoutpe.of the specimen and cannula, and all airbubbles had been removed from the injection

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apparatus, the two were connected and injection wasbegun.The injections were originally made at low pressures

(10 mm. Hg.), and were stopped when any alveolarfilling was seen, but this produced incomplete filling ofsome normal bronchi and bronchioles. Later injectionswere made at a pressure of 100 mm. Hg., which wasmaintained until complete alveolar filling of normalsegments had been achieved. No distension of the airpassages was produced by this high pressure, and theknowledge that normal parts of the bronchial tree hadbeen completely filled was of value in assessing theextent of bronchial and bronchiolar obstruction indiseased areas.

After completing an injection the cannula tubing wasclamped and divided, and the specimen with its sealedcannula was immersed in acidified formol saline for afew hours, then in changes of concentrated hydro-chloric acid for a week. By this time all tissues had beendestroyed and a solid cast remained, which was washedin running water.

FOLLICULARBRONCHIECTASIS

ATELECTATICBRONCHIECTASIS

SACCULARBRONCHIECTASIS

FiG. 4.-Ages of patients at time of operation.

After noting the areas of alveolarfilling, the alveoli were removedby cutting through the bron-chioles (Figs. 1-3). As castsbecame brittle when exposed toair for a long time, they werestored in 5%. formol saline.

SOME MACROSCOPIC FEATURESOF THE SPECIMENS' LOBAR

DISTRIBUTIONThe 200 specimens came

from 196 patients, each offour patients having had twoseparate lobectomies. Thelobar distribution of thespecimens can be seen inTable I, and the ages of thepatients in Fig. 4.Few specimens came from

patients older than 40 years,or from those with extensivebilateral disease. The table in-dicates the sites most severelyaffected and most commonlyinvolved, and is consistent withthe findings of larger broncho-graphic surveys, such as thoseof Perry and King (1940) andSchmidt (1947).The left lower lobe was re-

moved over three times asoften as the right lower lobe,and the lingula was resectedin about half the cases wherethe left lower lobe was dis-eased. The right middle lobe

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F. WHITWELL

TABLE ILOBAR DISTRIBUTION OF SPECIMENS

No. %

Left lung .. .. .. .. .. .. 19 9 5Leftupper lobe..6 3Lingula .. 5 2-5Left lower lobe..64 32Base of left lower lobe 2 1Left lower lobe and lingula .. 50 25Base of left lower lobe and lingula 2 1Total left lower lobe involvement 137 68-5Total left-sided involvement .. 148 74Right lung .3 1 5Right upper lobe..6 3Right middle lobe..10 5Right lower lobe..14 7Base of right lower lobe 2 1Right middle lobe and right lower lobe 14 7Right middle lobe and base of right lower lobe 1 0 5Right lower lobe and anterior segment right

upper lobe .. 1 0 5Right lower lobe, right middle lobe, and

anterior segment right upper lobe 1 0-5Total right lower lobe involvement 36 18Total right-sided involvement 52 26

was involved slightly less often thanlobe, and frequently with it.

the right lower

SEGMENTAL DiSTRIBUTIONBronchiectasis has often been described as a

disease affecting the broncho-pulmonary segments,but such a description can be applied to almostany pulmonary disorder. The important fact isthat bronchiectasis involves mainly the smallerbronchi, and both the bronchial and parenchy-matous changes tend to remain localized. Veryoften only small parts of broncho-pulmonarysegments are diseased, and the lesions are betterdescribed as focal. It is the treatment of bron-chiectasis that is segmental, not the disease.

Churchill and Belsey (1939) have emphasizedthat bronchiectasis is often multilobar in distri-bution, but within a lobe the disease may beconfjned within one or more broncho-pulmonarysegments. Overholt, Betts, and Woods (1947) havestated that the disease shows a predilection forcertain segments. These and other opinions werebased mainly upon clinical and bronchographicevidence, for there has been little mention of thesubject in pathological accounts. In 1949, Moore,Kobernick, and Wiglesworth studied the pathologyof individual segments in seven operation specimens.They found little correlation between broncho-graphic and histological findings, for all the lowerlobe apical bronchi appeared normal on broncho-graphy and yet showed abnormal histology.

In discussing the segmental distribution of lesionsin the present series there are two types of specimento consider. The small, solid lobes and lungs,which on section showed severely collapsed alveoliwith prominent and often dilated bronchi, nearly

always showed a similar extent of disease in eachsegment. The rest of the specimens, which weremore bulky, at least partially aerated, and withoutconspicuous collapse, contained many normalbronchi and the degree of involvement in affectedsegments was variable. The following remarksabout segmental and intra-segmental distribution oflesions apply only to this second type, whichrepresented nearly 90% of the specimens.Among 114 complete left lower lobes were five

in which the bronchiectasis was of similar extentin all segments, and all these specimens showedsevere alveolar collapse. The segmental distributionof lesions in the remaining 109 specimens is givenin Table II. This shows that the apical segment isnormal in three-quarters of the specimens, theanterior basal segment is normal in a quarter ofthe specimens, and the posterior basal segment isnearly always diseased. This order of frequencyof involvement is also usually the order of severityof the lesions within the segments in a lobe. Eachlower lobe basal bronchus divides into an upperand a lower branch; in most specimens the diseasewas more severe in the lower branches (Fig. 5),while in some instances only these branches wereaffected.

TABLE IISEGMENTAL SITE OF LESIONS IN 109 LEFT LOWER LOBES

Segment Normal Diseased

Apical.78 31Anterior basal.30 79Middle basal.10 99Posterior basal.4 105

Bronchiectasis in the upper lobe also shows apredilection for certain bronchi (Figs. 6, 7, 8, and9). The lingular bronchi are most frequentlyaffected, particularly the lower branch; next infrequency come the anterior and posterior bronchi(particularly their axillary branches), while theapical bronchus is rarely diseased (Fig. 10).A similar kind of distribution is found in right-

sided specimens.

MORPHOLOGY OF BRONCHIAL CASTS

Bronchiectasis is often classified from the shapeof the dilatations, and although the terms cylindricaland saccular are derived from early pathologicaldescriptions, they are now used mainly in reportingbronchographic features.From dissection of the bronchi and a study of

bronchial casts it is difficult usually to see anysimilarity between dilatations and the descriptiveterminology, except in saccular bronchiectasis.Casts prepared from severely bronchiectatic lobes

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Fici. 8X FIG, 9i 8o.X.-Posterior bronchtlst,fromi specititen

in F-ig. 7. [his bronclhLus has onre normalbranich.

. 9 - mnertor bronChLus froml specimenin Fig. 7. There is gross disease otf thetw o axillary branches. the rest of thesegment is normal

14 Bt1i921024, 22;_ ~ ~~~~~FIG. S

5 Neopretie catsts of, twkohi-onchiectaticI eti losser lobes

hle a'Pical brotelclli %\ere noritalc_ ] itn both spcilcimens. andci b1sve

beeti rc\eosed toshiist thbasal hronroehtic more clearly.In bothi SPeCielletis te tppetl-anterior basal bronchi (AR)are normal, and the Lipperbr-onChuLs ill the iiiddiec BR)anid p-iosteiriot- PR) basal seg-ilielnts aite' less se\eielv dis-torltedl tiani the los er bratichles

i 6. -Neoprene cast of broni-ChlieCtatiC right ILITIg. There1 is

g_-oss distortion with flatteningof' the miJiddle ain1d losser lobebroInci The tpper lobe ap;icalbrotiChuis hecatmie detached. bittthe upper lobe is normal exceptftorl brinchiectasis ot the axillarsbraniiiches oft the anterior andposterior bronchii N.eop-rene-hflled alseoli hase becri in-Complrctels renmosed fronti thet1orti-lal bronichli

7-Neopreine eaist ot' bH-oIl-chiectatic ei t ilIug. shoss ing ____fi_gross changes tn the losser lobeand linguLlit. and in thie [ostenor hinchu-01t0nS. iarid axillars IF t. I .-Di)stribUtion of left lotng lesitMIsbranch of the anterior bronchtLis diagrzan' after Brock ).

arc extremely \ariable: often conlstrictiorls are as

prominent as the dilatations, wshich arc flatteniedand irregLilar in shape, e.g., the lowxer lobe in Fig. 6.The mildest lesions produLCe thickeninig aindl

A5W -tiailsxcrseridging for about I cill. in the cast of zat. ' te minal bronchlUus. with n1o obsti-uctioln to the

peripheral bronchioles and alseoli. \x hich fillnormally with neoprene. In the next stage thesebronchial changes are accentuated, with partialobliteration of bronlchiolar connexions. Sexererlesions shiow -more extensive invoolvement withgiceater irregularity of the dilaitations, whlich are

flattencd and have no bronichiolar coninexions(Figs. I1, 12, and 13). In mniany advanced casesthei-e is dilatation of the first and second brtinchingsof the segme-intal bronchi with complete obliterationof the distal bronchial tree.

Casts prepared from aerated lobes, whiere onlya few segments are diseased, sometimqes show

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F. WHITWELL

FIG. 12.-Neoprene casts of terminal bronchiectatic tree; bron-chioles are few and irregular and have no alveolar connexions,and bronchi are thickened.

FIG. 11.-Neoprene cast of terminal part of normal bronchial tree.Upper cast is from a child of 3 years. Lower cast is from a manof 50 years (alveoli removed).

complete neoprene alveolar filling, even aroundthe severely diseased bronchi. These bronchi arefound embedded in alveoli but having no bronchiolarconnexion with them, and there is a complete lossof lobular pattern in these air cells. It is probablethat neoprene has reached these alveoli fromexisting collateral air passages through adjoiningnormal lung tissue.

STRUCTURAL CHANGESIN BRONCHIECTASIS

The variable severity of the lesions of bron-chiectasis in different segments of a lobe was seenin the histological sections as well as in the casts.It is difficult to avoid regarding these differentlesions as stages in the development of bron-chiectasis, for it seems natural to regard grossstructural changes as pointing to the original siteof the disease and the mildly affected bronchi asthe areas of latest extension. As clinical evidence isall against the view that bronchiectasis spreads from FIG. 13.-Neoprene cast of terminal bronchiectatic tree; bronchi

are flattened and irregular and have no bronchiolar connexions.

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one segment to another, a more likelyexplanation is that at the onset of thedisease the bronchi are subjected tovarying degrees of injury.

In areas of gross bronchiectasis itis difficult to distinguish the primaryabnormality from its secondary effects,but in areas of milder bronchiectasisthere are few secondary changes. Thepresent study is based upon theexamination of these milder lesions,which represent the basic pathologyof the disease.The 180 specimens that were ex-

amined microscopically included 22examples of congenital or develop-mental bronchiectasis; these will notbe discussed in the present account.Among the remaining 158 specimensthere were 87 which belonged toone or other of three common typesof acquired bronchiectasis. Thesehave been called follicular, saccular,and atelectatic bronchiectasis, andtheir pathology, pathogenesis, andclinical features will now be discussed.

FOLLICULAR BRONCHIECTASISThe term " follicular " has been

chosen because the most prominentmicroscopic feature is an excessiveformation of lymphoid tissue, occur-ring as follicles and nodes, whichare situated both in the walls ofdiseased bronchi and bronchioles,and among the surrounding alveoli.These lesions are usually associatedenlargement of hilar lymph nodes.The three examples to be describe(

moderate, and severe cases of folliculartasis; in the second and third caseswill be limited to the features not seenspecimens.Reasons will be given for regarding

changes as specific, and the patholofeatures, pathogenesis, and aetiology cdition will be discussed.

MILD FOLLICULAR BRONCHIECTACASE 464.-A 6-year-old girl had suffi

productive cough since the age of 18 noccasional acute pyrexial exacerbations.dyspnoeic on exertion, showed finger-clubbpurulent sputum. At bronchoscopy ptexuding from the left lower lobe bronchus, a

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FIG. 14.-Mild follicular bronchiectasis of left lower lobe (Case 464). Haematoxylinand eosin.

with great grams showed bronchiectasis of the left lower lobe,mainly in the posterior basal segment. This lobe was

i are mild, removed.r bronchiec- Macroscopic Appearance of Specimen.-The lobe isthe account bulky, aerated, moderately pigmented, and covered byin previous shiny pleural membrane, except over the base of the

posterior basal segment, where the membrane isthese tissue thickened. Enlarged lymph nodes are adherent to theogy, clinical lobar bronchus at the hilum.)f this con- Sections made through the lobe show only slightabnormality, and the lesions seen in Fig. 14 are as

extensive as in any area. The disease is limited to thelower part of the posterior basal segment, and,515B although the segmental bronchus appears normal, some

ered from a of its branches are dilated and thickened, and containnonths, with pus.

She was The alveoli around these branches have a grey-white,ing, and had translucent granularity indicating interstitial pneumonia,is was seen and there are some small brown sunken areas of collapseind broncho- under the pleural membrane.

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FIG. 15.-Ulcerated wall of bronchiole. Haematoxylin and eosin x

FIG. 16.-Interruption of bronchiolar elastic tissue near lymph folliElastic stain and pyronin x 256.

Microscopic Features.-The only area to be describedis the posterior basal segment; no other segments showany abnormalities.The only notable features of the posterior basal

bronchus are an excessive vascularity of sub-epithelialtissues, and lymphocytic aggregations around the mouthsof mucous-gland ducts. Elastic tissue, muscle, andcartilage'appear normal.The bronchi of the posterior basal bronchus are filled

with pus, and lined by ciliated columnar epithelium,which has no surface ulceration or squamous metaplasia.The bronchial walls are about three times their normalthickness, because of distension with oedema fluid,dilatation of sub-epithelial capillaries, aggregations oflymphoid cells, and infiltration with chronic inflammatorycells which are mainly plasma cells and lymphocytes.

Lymphoid aggregations are indistinguishablefrom the follicles and nodes of lymph glands, andthey are situated in sub-epithelial tissues, and indeeper parts of the bronchial walls. In the formersite they cause distortion and partial occlusion ofthe bronchial lumina, while the intra-mural follicles

; produce stenosis of the bronchial branchings.Bronchial supporting tissues are extensively

damaged, particularly near the lymph follicles,where there is no elastic tissue, only a few frag-

t, ments of muscle survive, and even the cartilage ispartly destroyed. Peribronchial fibrous septa arethickened and contain dilated lymphatics.

cAk! The inflammatory reaction seen in the bronchi"r ;^ is also present in the bronchioles, where, because

of their thinner walls and narrower calibre, thet effects are more severe. Though some are dilated,

most of them are compressed and either partlyor completely occluded by the inflammatory

. swelling of their walls.Cuboidal or columnar cells make up the epithe-

lium in which surface erosions occur. Small acute110. ulcers show pus streaming into the lumina from

uncovered areas of vascular granulation tissue inbronchiolar walls (Fig. 15). Where healing hasbegun the granulation tissue is much less inflamedand is covered by layers of flattened cells whichsprout from healthy, adjoining epithelium. Later

~> stages show the replacement of granulation tissueby small areas of fibrosis, and conversion of the

$ layers of cells into a cuboidal epithelium.Some bronchioles have escaped both the

generalized inflammatory thickening and thesurface erosions, and contain normal musclelayers with some lymph follicles and nodes.Elastic stains show, however, that there is des-

. truction of elastic tissue where it lies close to thefollicles, even when there is no diffuse in-flammatory reaction.

While mildly affected bronchioles may be* embedded in normal aerated alveoli, most of those

which are diseased are surrounded by a rim ofchronic interstitial pneumonia, the width of which

icle. is proportional to the severity of the bronchiolarlesions.

In such zones of interstitial pneumonia the alveoliare separated, small, globular, and lined by cuboidalcells, while the interstitial tissues are oedematous andcontain plasma cells and lymphoid tissue. Usuallyalveoli lying outside areas of pneumonia are normal,but in some lobules they are collapsed.Branches of the pulmonary artery accompanying

diseased bronchioles are surrounded by dense fibroustissue. The inter-lobular fibrous septa are thickened.

MODERATE FOLLICULAR BRONCHIECTASTS

CASE 758.-This I -year-old girl had suffered from acough since acquiring measles when 18 months old,and her symptoms increased after whooping cough atthe age of 4 years. On examination she had a productivecough and finger clubbing, and bronchograms showed

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cylindrical bronchiectasis ofthe left lower lobe andlingula, with minimalchanges in the right middlelobe. Left lower lobectomywith removal of the lingulawas performed.

Macroscopic Appearanceof Specimen.-The lingula issmall and firm, and has a Jshiny, thin pleural covering.Sections show the bronchi eto be dilated, thickened,filled with pus, and sur-rounded by interstitial pneu-monia. The microscopicappearance is similar to thatof the posterior basal seg-ment (q .v.). > v,t'-The lower lobe appears

well aerated, though thebasal segments contain some .jfirm areas. The pleuralmembrane is normal: thereare enlarged hilar lymph 4-glands.

Sections of the lobe (Fig.17) show more extensive"disease than in Case 464.There is marked thickeningand dilatation of all branchesof the posterior basal bron-chus, and extensive pneu-monia in this segment.Changes in the middle and 4santerior basal segments areof lesser severity, and are FIG. 17-Moderate follicularcomparable wi.dh those seenin the posterior basal segment of the previous case.No abnormality is to be seen in the more pigmentedapical segment.

Microscopic Features.-The appearance of lesionsin the middle and anterior basal segments is similar tothat of the previous case.

In the posterior basal bronchus there is diffuse infil-tration of chronic inflammatory cells in the sub-epi-thelial tissues The ducts of mucous glands are funnel-shaped instead of being tubular, and lymph folliclessurround their mouths. Bronchial supporting structuresare normal except for loss of elastic tissue near thefollicles.

The branches of the posterior basal bronchus aredilated, thickened, and filled with pus.The epithelium consists of ciliated columnar cells,

with no areas of ulceration or squamous metaplasia.Inflammatory cells are profuse in the oedematous walls;lymph follicles are numerous and often confluent.There is a more complete loss of bronchial supportingtissues than in the previous case, only isolated fragmentsremaining.

bronchiectasis of left lower lobe (Case 758). Iron haematoxylin andvan Gieson.

All bronchioles in the segment are diseased, most ofthem being partly occluded, while some appear almostobliterated. Epithelial changes follow those in the pre-vious specimen, but the inflammatory reaction is moreextensive, lymph follicles are more numerous, and thereis almost total loss of muscle and elastic tissue.

In some fields the zones of interstitial pneumoniaare so wide that they form a confluent mass. As thereis little thickening of interlobular septa, the originallobular pattern is obliterated. No alveolar collapse ispresent.

SEVERE FOLLICULAR BRONCHIECTASISCASE 497.-A 9-year-old girl, who had suffered from

a productive cough since measles in early childhood,was admitted with an acute exacerbation of symptoms.She was dyspnoeic on slight exertion, showed fingerclubbing, and bronchograms revealed bronchiectasis ofthe left lower lobe and lingula. Left lower lobectomywith excision of the lingula was performed.

Microscopic Appearance of Specimen.-The lingulais small and firm, and shows gross bronchiectasis with

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FIG. 18-Severe follicular bronchiectasis of right lower lobe 2 cm. frcHaematoxylin and eosin.

interstitial pneumonia and collapse. The microscopicfeatures do not differ from those at the base of thelower lobe.The lower lobe is quite bulky and firm, and has

enlarged hilar lymph glands. The pleural membrane isthickened over the base of the lob,, but normal at theapex, which is partly aerated.On section (Figs. 18 and 19) there is mild bronchiectasis

with some pneumonia in the partially aerated apicalsegment, while the basal segments all show gross bron-chiectasis with pneumonia, collapse, and some fibrosis.It is mainly in the segmental bronchi and their first andsecond branchings that dilatation is seen: more peri-pheral bronchi look like narrow clefts in solid tissue.The disease is most severe in the lower parts of the basalsegments.

Microscopic Features.-Though the gross appearance

is far removed from that of the previous two specimens

there are no qualitative differences in the histology.Changes in the apical segment are similar to thosedescribed in mild lesions of the previous cases. The

lesions in each basal segment areof equal severity.There is some dilatation but little

thickening of the basal segmentalbronchi, and while epithelial liningsare normal, there is diffuse inflam-matory infiltration of sub-epithelialtissues with some lymph follicle

W. formation. Elastic tissue is exten-sively destroyed, but the loss ofmuscle is only slight and cartilagesare normal. Mucous glands aresmall and scanty; they lie close tothe bronchial epithelium and havevery short ducts.The proximal branches are dilated

and distorted, but more peripheralones are flattened. Their histologyis similar to that described incorresponding bronchi of the

406,01 previous case.In some areas the lesions are

similar to those in severely affectedparts of previous specimens (Fig. 20).

Sometimes, particularly near the4. i~; diaphragmatic surface of the lobe,

it is impossible to define the outerwalls of air passages, or to dis-tinguish bronchi from bronchioles.Granulation tissue in the bronchialand bronchiolar walls merges withthe confluent interstitial pneumoniaforming a granulomatous mass,which contains epithelium-linedclefts and patches of collapse.There are so many lymph folliclesthroughout this granulomatous tissue

om hilum (Case 497). that the pulmonary lobules resemblelymph glands. No bronchial sup-

porting tissues survive; thickened interlobular septa,however, help to identify the original outline of lobules.The close relationship of thickened branches of the

pulmonary artery to the epithelium-lined clefts suggeststhat the latter were originally bronchi and bronchioles,and unlikely to be re-epithelialized pulmonary excava-

tions.

THE PATHOLOGY OFFOLLICULAR BRONCHIECTASIS

These examples demonstrate that lesions mayrange from a relatively minor and inconspicuousfocus in one bronchopulmonary segment of an

otherwise normal lobe, to formation of a more or

less solid lobe which bears little resemblance tothe normal.

In this investigation over a third of the specimensshowed features similar to the illustrated examples,with their typical microscopic lesions, the mostconstant and characteristic of which were the forma-

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tion of lymph follicles and interstitialpneumonia.

LYMPH FOLLICLE FORMATIONSeverely diseased bronchi and bron-

chioles contain many lymph folliclesand nodes within their thickenedwalls, but, although this lymphoidtissue is extremely prominent, itforms only part of an extensivemural inflammation. At this stage of 5*the disease there is widespread des-truction of bronchial elastic tissue,muscle, cartilage, and mucous glands.From the examination of many

specimens it appears that elastic tissueis the first of the supporting tissuesto be destroyed in bronchiectasis,muscle is the next to suffer, and carti-lage survives the longest. Mucousglands are also destroyed, survivingfor about as long as cartilage. It isthought that once any of these FIG. 19.-Same lobe as in Fig. 18, 5specialized tissues has been destroyedit cannot regenerate.

In areas of very mild bronchiectasis theonly abnormalities in the bronchial tree aresub-epithelial accumulations of lymph fol-licles and nodes, and some oedema. Diffuseinflammation is not present and both muscle =and cartilage appear normal; special stains,however, show that there is destruction ofelastic tissue near the lymph follicles (Fig.16). It is considered that this loss of elastictissue is a fundamental lesion in follicularbronchiectasis, for once part of the bronchialtree has been damaged in this manner it ispermanently weakened and incapable ofovercoming secondary infections.Apart from their destructive influence on

elastic tissue, the lymph follicles, merelybecause of their size, distort the affectedbronchial tree. Sub-epithelial follicles pro-ject into the lumina causing partial obstruc-tion, while intramural follicles enlargebronchial walls, compressing the openings Fof peripheral branches of the bronchialtree which enter the diseased bronchi. tSimilar but more severe effects are seen inthe bronchioles, where complete occlusion ; .4is often produced.Lymph follicles and nodes are present in

normal lungs; Miller (1947) and Engel(1947) agree that lymphoid tissue occursat points of bifurcation of bronchi and' FIG. 20.- Follicular broncl

cm. from hilum.

-hiectasis. Haematoxylin and eosin x 10.

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F. WHITWELL

bronchioles, and between bronchioles and branchesof pulmonary arteries which accomp.any them. Astudy of normal lung segments has confirmed this,and has shown that this lymphoid tissue is outsidethe bronchial tree, where no alteration of elastictissue is to be seen.Abnormal lymphoid accumulations in the lung

are sometimes seen in other forms of bronchiectasis,around chronic lung abscesses, and in tuberculosis.In these conditions the number of follicles is muchsmaller and they are mostly situated outside thebronchial tree, but local destructive changes dooccur near the occasional ones found in the bronchi.Many authors (Robinson, 1933; Ogilvie, 1941;

Allison, Gordon, and Zinnernann, 1943) havementioned the presence of these bronchial lymphfollicles in bronchiectasis, but their significance hasnot been studied, and only Engel (1947) has notedthe associated loss of elastic tissue. He has calledthis condition " nodal bronchitis and bronchiolitis"and has described thickened collapsed bronchi andbronchioles where the walls contained lymphnodules but no diffuse cellular infiltration. Amarked loss of elastic tissue occurred near the

NORMAL EARLY CHANG

r

A.9 ,

JK3&LATE CHANGES LOBL

FIG. 21.-Development of bronchiolar lesions and secondary lobular cfollicular bronchiectasis.

nodules, and this was noted too often for it to befortuitous. Engel commented that he was unableto decide whether this lesion was caused by avirus. an unusual infection, or some other influence.

INTERSTITIAL PNEUMONIAInterstitial pneumonia is to be seen in other

pulmonary conditions, but it is a constant featureof follicular bronchiectasis. The pneumonia isfound in the parenchyma around affected bron-chioles, and its extent is dependent upon theseverity of the bronchiectasis.

In normal lung tissue the respiratory part of theorgan appears in section as a lace-work of largespaces separated from one another by thin-walledsepta (Maximow and Bloom, 1942). These fineinter-alveolar septa contain capillaries, elasticfibres, and a fine reticulum of connective tissue;and in normal parenchyma such interstitial tissuesare inconspicuous.

In interstitial pneumonia, however, the peri-bronchiolar and inter-alveolar connective tissues areoedematous, and contain infiltrations of plasmacells, mononuclears, and lymphocytes, together

with occasional lymph follicles, dilatedcapillaries and lymphatics. The vastincrease in bulk of interstitial tissues isassociated with a reduction in volumeof the alveoli, and an alteration of theirlining cells.

Cells lining normal alveoli are/- inconspicuous, but in interstitial

pneumonia the alveoli are lined byan epithelium of small cuboidal cells.The origini of this epithelium is obscure;some think it is a down-growth ofbronchiolar epithelium, others regard

Dv. it as a metaplasia of cells normallyfound lining alveoli, while Watts and

___2fistMcDonald (1948) think that both these',4RX, processes occur.

In mild bronchiolar lesions only thosealveoli actually in contact with thebronchiolar walls appear to have under-gone this epithelialization; in fact,in many instances only parts of thesealveoli are affected. As these alteredalveoli are often only found in theperiphery of pulmonary lobules, itseems unlikely that the lining cells area bronchiolar down-growth, and more

ULE probable that local metaplasia hasoccurred as a result of interstitial in-

sollape in flammation.

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PATHOLOG Y AND PA THOGENESIS OF BRONCHIECTASIS

CLINICAL FEATURES OF IFOLLICULAR BRONCHIECTASISThe ages of all the patients were obtained from

the register, but only two-thirds of the case-recordswere available for analysis.The age distribution of all the cases of follicular

bronchiectasis is shown in Fig. 4. Other detailswere obtained from the 28 case-records, and are asfollows:

Under 6 yrs.6-8 yrs. .

9-1l yrs. ..12-14 yrs. .

15-17 yrs. .

18-20 yrs. .

Over 20 yrs.

IUnder 3 yrs.3-6 yrs. . .

7-9 yrs. ..

10-13 yrs. . .

14-18 yrs. . .Over 18 yrs.

AGE AT OPERATION

AGE AT ONSFT OF SYMPTOMS

1 patient9 patients84 ,4 ,,2 ,0 -

1 5 patients7 ,,2 ,,2 ,,2 ,,0 ,,

PRE-OPERATIVE DIURATION OF SYMPTOMSUnder 1 yr. 0 patients1-3 yrs. . 7 ,,4-5 yrs. . 76-10yrs... 10

11 5Iyrs. 2

Over 15 yrs. 2

NATURE OF ILLNESS AT ONSET OF SYMPTOMSMeasles and!or whooping-coughPrimary bronchopneumonia ..Insidious onset ..

Tonsillectomy ..Crush injury of chest ..

PresentDoubtfulAbsentNot noted

PresentDoubtfulAbsentNot noted

13 patients671 patientI ,,

FINGER CLUBBING10 patients4104

PARANASAL SINUS INFECTIONS20 patients43I patient

The severity and extent of the disease appearedto be unrelated to the nature or severity of theinitial illness, or to the duration of the symptoms.

Patients with finger clubbing did not have themore extensive or severe pulmonary lesions; therewas also no correlation between finger clubbingand duration of symptoms.

There was obvious correlation between thenature of the patients' sputa and the degree ofinflammation in the bronchi.

PATHOGENESIS OF FOLLICULAR BRONCHIECTASISThe main lesions occur in smaller bronchi,

bronchioles, and in alveoli, while minor secondarychanges take place in the larger bronchi. The moresevere the involvement of the lobe, the moreproximally does each of these processes extend, withobliteration of the distal bronchial tree. Secondarychanges in the larger bronchi include the destruction

of supporting tissues around the mucous glandducts, which then enlarge and form part of thebronchial wall.

Small bronchi and bronchioles are affectedsimilarly; only the bronchiolar changes will bedescribed as these are more closely associated withthe parenchymal disease. By studying lesions ofdifferent severity it is possible to visualize theevolution of the advanced condition (Fig. 21).The early changes consist of thickening of

bronchiolar walls due to oedema and lymph follicleformation, with destruction of elastic tissue nearthe follicles. These bronchioles are usually ratherflattened, and are surrounded by narrow rims ofinterstitial inflammation.More advanced lesions show a greater number of

follicles and a diffuse mural bronchiolitis, withdestruction of all elastic tissue and most of themuscle. The bronchiolar lumina are reduced andoften appear stellate on cross-section. Interstitialinflammation involves wider areas of the paren-chyma, and there is fibrosis around branches of thepulmonary arteries. Often the interlobular septaand pleural membrane are thickened. ~F

Alveol,ar collapse has been seen only in specimenswhere there was thickening of interlobular septaand pleural membrane. Microscopically this col-lapse is of the type produced by compression, andits distribution is lobular.The cause of the alveolar collapse can be found

in the lobules (Fig. 21). Thickened interlobularsepta and pleural membrane keep the outline of alobule rigid, but as the centre contains an expandinggranulomatous mass (which has arisen from thebronchiole and peribronchiolar tissues) pressurewithin the lobule becomes raised. This tensionproduces both flattening of the weakened bron-chiolar walls, which reduces the lumen to a narrowcleft, and compression collapse of the alveolioutside the area of pneumonia.

THE AETIOLOGY OF FOLLICULAR BRONCHIECTASISThe important clinical facts are that the con-

dition usually begins in early childhood and is asequel to whooping-cough, measles, or primarybronchopneumonia. This bronchiectasis may alsohave an insidious onset.The essential lesions are destructive mural

bronchitis, bronchiolitis, and interstitial inflamma-tion, and the pathology appears very closely relatedto the acute interstitial pneumonias which werereported by MacCallum (1940) in fatal cases ofmeasles and influenza and whooping-cough.MacCallum described the lesions found in servicepersonnel, but Engel (1947) has reported a similar

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FIG. 22.-Saccular bronchiectasis of right lower lobe (Case 395)2.5 cm. from hium. Haematoxylin and eosin >' 1.5.

multifocal condition in children, under the nameof destructive mural bronchiolitis. MacCallum saysthat this condition always follows a virus infectionand haemophilic organisms can usually be grownfrom the lungs, and Engel has suggested a viralorigin for his " nodal bronchiolitis."

Follicular bronchiectasis is very like rodentbronchiectasis (Cruikshank, 1948), which has beenshown by Nelson (1946) to be of viral origin.

Follicular bronchiectasis is probably the sequelof acute viral infection of the lungs contracted inearly childhood. Usually this infection occurs withwhooping-cough or measles, or, when influenzal itis described as primary bronchopneumonia. Insome cases it may be relatively symptomless, likeother virus pneumonias, and pass unnoticed byparents. The original inflammation is probablymultifocal, and normally clears up without anyresidual damage, but in bronchi which are inade-quately drained of secretions the permanent changesof follicular bronchiectasis may arise.

SACCULAR BRONCHIECTASIS"Saccular " is an apt word because it fits both

the anatomical and the bronchographic appearance,though many specimens which did not show this

FIG. 23.-Saccular bronchiectasis of right lower lobe 4 cm. fromhilum (Case 395). Haematoxylin and eosin x 1.5.

type of pathology could have been described assaccular from the bronchograms.

Twenty-three examples of this condition occurredin the present series. Two of them will be describedin some detail, and the pathology, clinical features,and pathogenesis of saccular bronchiectasis will bedi-cussed.CASE 395.-A 33-year-old woman, previously healthy

apart from bad head colds, had suffered from a trouble-some cough for three years, and her symptoms hadbecome more severe recently. Her sputum was copious,purulent, and occasionally blood-stained. She hadfinger clubbing and was dyspnoeic on slight exertion.Bronchograms showed bronchiectasis limited to theright middle and lower lobes. Right lower lobectomywas performed.

Macroscopic Appearance of Specimen.-The specimenis an aerated, pigmented lobe with pleural thickeningover the apical and diaphragmatic surfaces.On section (Figs. 22 and 23) the apical segment shows

some collapse, emphysema, and interstitial pneumoniabut the bronchi appear normal. The base of the lobeshows gross bronchiectasis, with the main bronchi ofnormal calibre, though slightly thickened and occludedby folds of hypertrophic epithelium, while more peri-pheral bronchi form pus-filled cavities. These sacculesare surrounded by aerated alveoli, and there isfibrous thickening of the interlobular septa.

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Microscopic Features.-The lesion in the apicalsegment appearing like pneumonia is a tuberculous 2

infiltration, but there is no bronchial disease in thissegment. No tuberculosis is to be found in thebronchiectatic basal segments, and the two conditionsare thought to be unrelated. v.Most striking is the polypoid appearance of the

epithelial lining of the basal main bronchi, but becauseof tissue shrinkage during processing this is less ,0conspicuous than in the untouched specimen. Thebronchi are partly occluded by these polyps, which con- -isist of vascular granulation tissue covered by columnar iepithelium, the granulation tissue being part of a diffuseinflammatory reaction in the bronchial sub-cpithelial 7tissues. In spite of this bronchial inflammation there is 1:little loss of elastic tissue or muscle in the bronchialwalls, and there is no loss of cartilage.

Each basal segmental bronchus divides into two orfour branches which, after a short course, terminate inblind bulbous cavities, or saccules. While the pre-saccular bronchi all show similar microscopic features,an abrupt change is seen as they enter the saccules.

FIG. 24.-Model of basal segmental bronchi of lower lobeThe saccules are large, irregular, somewhat flattened (Case 39:9.

cavities containing pus; most of them are globular orelliptical, but some have an hour-glass

- - ~~~~~~~~~~~~shape.A91 *--K

Their epithelial lining is continuous,exetfor a few small erosions, and is

composed mainly of cuboidal cells. Areasof squamous metaplasia are to be found in

..~~~~~~nearly all the saccules, chiefly at theirbases, but also at places where opposingepithelial surfaces are almost in contact.

Dilated capillaries and chronic inflam-matory cells lie beneath the epithelium,and the saccular walls consist of dense

.;[email protected] tissue which contains no elastictissue, muscle, or cartilage.The saccules represent terminations of

the existing bronchial tree in the diseasedsegments; all more peripheral branches

Z ~~~are either destroyed beyond recognition,t or they are replaced by fibrous bands' containing isolated fragments of cartilage.

X * a! tvo,,,, s^ <; 1<>^ ,-: ME,- ^: ,and epithelium-lined cysts.-@>aZ beb> 9 -a>e tS The gross features of this specimen can

7.

~~~ ~ ~ ~ ~ ~ ~~~~eni temdl(Fig. 24), which hasbeen reconstructed from sections taken250 apart. Parts of the bronchial tree

4 ~ which contain cartilage are represented in

4~~~~~~~~~~~~~~~hite, non-cartilaginous portions are grey,ahond reslwitkh sqtuamous metaplasia are

-~~shown by black dots.~-' Alveoli around the saccules, and in the

#/ basal segments generally, are well aeraIte.

FIG. 25.-Saccular bronchiectasis in left lower lobe 2 cm. from hilum (Case 41).There are no severe inflammatorychanges,Haematoxylin and eosin x 1.5. but the lobular pattern of alveoli is made

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F. WHITWELL~~~~~~~~~~~~~~~~~~~~~~.FIG. 26.-Saccular bronchiectasis 5 cm. from hilum (Case 451). Haematoxylin and eosin x 1.5.

conspicuous by thickening of interlobular fibrous septa. of a distinctive t:Within these lobules there are some respiratory bron- only 17% of s

chioles, but terminal bronchioles are replaced by fibrous some of the uncla

scars. stages of the sCASE 451.-An 18-year-old boy was admitted to features are gross

hospital because of a troublesome cough and a single saccules, normali

slight haemoptysis. Bronchitis had occurred during thes

previous four winters, but there was no history of earlier saccules, andr

respiratory complaint or infectious diseases. He pro- bronchi, whlch r

duced 3 oz. of purulent sputum daily, had marked finger The saccules and

clubbing, and bronchograms showed bronchiectasis considered separallimited to the left lower lobe. This lobe was excised. the primary abno

Macroscopic Appearance of Specimen.-The lobe is SACCULES.-Sacbulky, aerated, slightly pigmented, and has a shiny tures lined by a ci

pleural membrane. elastic tissue, musSections of the lobe (Figs. 25 and 26) show a normal their lining memt

apical segment but severe bronchiectasis in the whole respiratory epithe

of the base. The segmental basal bronchi and their main able tissues in th

branches are not thickened or dilated, but they are about their originpartially occluded by epithelial " polyposis"; more later.distal bronchi are saccular and filled with pus. The la er.

alveoli of the basal segments are aerated, except imme- The constant

diately around the saccules where there is some collapse. metaplasia in the

Microscopic Features.-There is obvious similarity interest as this p]to the previous case, and only points of difference will of the other typesbe stressed. usual distribution

The pre-saccular bronchishow marked polypoid changesin the epithelium. In Fig. 25polyposis of the basal segmentalbronchi can be compared withthe smooth epithelial lining ofthe normal apical bronchus.The epithelial lining of the

saccules is flatter than in theprevious specimen, and areas ofsquamous metaplasia are moreextensive. No connexion wasfound between the saccules andany distal bronchial tree-infact no intact distal bronchi arepresent, though respiratory bron-chioles occur in the parenchyma.The base of the lobe is well

aerated except for a narrow zoneof collapse around and betweenthe saccules. In the areas of col-lapse the alveoli are flattened con-centrically around the saccules.

There is no inflammatoryreaction in the parenchyma, andonly within the peribronchial,perisaccular, and interlobularsepta is an increase of fibroustissue to be found.

THE PATHOLOGY OF SACCULARBRONCHIECTASIS

These two examples arethought to be the end-result

;ype of bronchiectasis. Although,pecimens show these lesions,tssified lobes are probably earliersame condition. Characteristicloss of bronchial structures in theity of the alveoli around thepolyposis" of the pre-saccular*etain normal supporting tissues.the pre-saccular bronchi can be

tely, the former being regarded asirmality.cules are essentially fibrous struc-uboidal epithelium; they have no,cle or cartilage in their walls, andbranes contain no normal ciliatedlium. This absence of recogniz-ie saccules has led to speculationand this subject will be discussed

finding of areas of squamoussaccular epithelium is of specialohenomenon is uncommon in any.of bronchiectasis examined. Theof this metaplasia is shown in the

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two examples (Figs. 24 and 27); sometimes itis less extensive, but in a few specimens thewhole saccular lining is replaced by squamous Iepithelium extending for some distance up thepre-saccular bronchi.Squamous metaplasia is mentioned in most _X

accounts of bronchiectasis in the literature,but its distribution in the diseased lobes has ararely been described. From published illustrationsit is clear that the term has been applied in-discriminately to various epithelial patterns, suchas the layers of heaped-up, flattened cells thatrestore breaches of epithelial continuity, and thetransitional epithelial appearance seen in obliquely -~ rsectioned bronchi (Engel, 1947). In the presentaccount the term is used only when prickle cellsor keratinization have been seen; the latter isextremely rare and was found only in three

FIG. 27.-Model of basal segments of Case 451 (saccularspecimens. bronchiectasis).

Robinson (1933, 1939) des-e i / tt sl{ie§;ev16tt '><e.~., s e X X -wtcribedsquamous metaplasia

of the proximal bronchi in ,a't*\ispecimen of bronchiectasis,i and he thought that it might

XTN. N t ^t, \ s>b6tthavebeen a factor in the9:>'j @ 0 9 _ S "- * . production of the disease by

creating a physiological block; of bronchial ciliary action.~%. ¶ sr-,taNo such distribution was seen

in the present specimens, inwhich the metaplasia wasalways at the distal end ofthe bronchial tree. In dis-

'_ cussing this subject Willis(1948) says:

"Although it has often been£*^. 7 ,^ 1 t;statedthat squamous change

4Wc only occurs in chronicbronchiectasis and bronchitis,

.{ v serthis is an error; except in~~ I ~~~carcinoma squamous meta-

~~~~~~~~~plasia in human bronchialdisease is rare."

.jHowever, metaplasia has been_'&j seen in all specimens of sac-

1cular bronchiectasis (whichform17 of thepresentseres)aswel asinseveral of

;2imens, and bronchiectasis isFIG. 28.-Po'yposis of pre-saccular bronchi (Case 451). Haematoxylin and eosin x almost as common as pul-

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F. WHITWELL

FIG. 29.-Saccules surrounded by rims of compression collapse (CasHaematoxylin and eosin x 7.5.

monary tuberculosis; Willis's statement cannot

therefore be accepted.

THE PRE-SACCULAR BRONCHI.-NO dilatationoccurs in the bronchi and there is little destructionof supporting tissues, despite the severe inflamma-tory reaction in the bronchial walls. The mainabnormality is polyposis of the bronchial epi-thelium, often extensive enough to produce consider-able bronchial obstruction.

In the present material this change has been seen

only in saccular bronchiectasis, but similar lesionsare to be found in the bronchi draining chroniclung abscesses and secondarily infected tuberculouscavities.The bronchoscopic and histological features of

this polypoid change have been described byJackson and Jackson (1932), who thought that itwas an inflammatory reaction produced by con-

tinual irritation from pus, an opinion supported bythe present study. Peroni (1934) considered thatthe polyps occurred first, and then produced

bronchiectasis by obstruction. Samsonj (1940) described a severe case and thought2 the cause was an individual susceptibility

to mucin. Many accounts ofthe pathologyof bronchiectasis mention the hypertrophicbronchial epithelium, but the site andassociation with saccules have not beenstressed.COLLATERAL AIR CIRCULATION IN

. DISEASED SEGMENTS.-Tfle observation thatall bronchi in the diseased segments end inblind saccules, and that these segmentsare well aerated, is considered to be ofsome importance. It provides histologicalconfirnation ofthe existence of a collateralair circulation in bronchiectasis, whichchallenges the validity of certain populartheories of pathogenesis.

iHf Collateral air circulation was originallya theoretical conception based upon a

* belief in the existence of alveolar pores.it, Later this theory was tested and confirmed

by animal experiments (Van Allen andJung, 1931), and more recently by Baarsmaand Dirken (1948) using healthy rabbits,and by Baarsma, Dirken, and Huizinga(1948) in normal human lungs. Theseworkers considered that a collateral aircirculation occurred only in the absence ofinflammatory change in the obstructedsegments.

;e 451). The importance of this mechanism indiseased lungs has only recently received

any attention. Churchill (1949), describing theradiological appearances of isolated bronchiectaticlobes in which the bronchi had been filled withlipiodol, mentioned dilated bronchi extending intoair-containing parenchyma but in no way communi-cating with it. These segments contained trappedair, as they did not deflate when the lobes wereremoved from the body and left the bronchi open.This trapped air serves the function of filling upspace but it has no oxygenating value.

In the two examples of saccular bronchiectasisthe air must have reached the basal parenchymathrough the normal apical segments. This suggeststhat the intersegmental and interlobular fibroussepta are really incomplete fibrous networks whichoffer no barrier to air. Alveolar pores have beenseen in the aerated alveoli of most specimenswhenever sought in thick sections (Fig. 31).Although collateral air circulation is most easily

demonstrated in the saccular cases, it occurs inmost forms of bronchiectasis which do not involveentire lobes.

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PATHOLOGY AND PATHOGENESIS OF BRONCHIECTASIS 231

CLINICAL FEATURES OF SACCULAR BRONCHIECTASISThe age distribution of all these patients is shown

in Fig. 4. Sixteen case-records were available for \\NORMAL APICALSE\.analysis, and the details are tabulated. X

AGE AT OFERATIONUnder 5 yrs. 0 patients 'il15 0yrs. 5 ,\_

21-25yrs.5226-30yrs.7., | 1 9 $ 9 ''_31 35Nrs.. . I

36-40yrs.I patientOver 40 yrs.

AGE AT ONSET OF SYMPTOMS ORMAL BASAL SEGACough " all life time"...patientsUnder 9 vrs. (except above) 09-12yrs .. .. I patient13-18 yrs. .. 6 patients19-25yrs...Over 25 yrs. ..I patient

PRE-OPERATIVE DURATION OF SYMPTOMSUnder 2 yrs. 3 patien is2-6yrs. 87l1O0rs. 211-15yrs. Ipatient16 20yrs. IOver 20yrs. I

NATURE OF ILLNESS AT ONSET-OF SYMPTOMS )'Measles and, or whooping cough 0 patientsBronchopneumonia .. 9Fairly recent insidious onset 4 -I'Cough all life but no severe childhoodillnesses.3

FINGER CLtJBBINGPresent.10 patients FIG. 30.-Development of collateral air circulation in saccularDoubtful 2 ,. bronchiectasis.Absent. 2Not recorded.2 All patients had copious purulent sputum.

PARANASAL SINUS INFECTIONS No correlation was found between the extent,Present*9 patients severity, and duration of the disease, and theDoubtful .. 2Absent .. 3 " presence of finger clubbing.Not recorded .. 2 It is impossible to correlate theulj|j Adegree of polyposis and squamous

metaplasia to the duration of illness.

PATHOGENESIS OF SACCULARBRONCHIECTASIS

As the changes in pre-saccularbronchi are considered secondaryto the saccular lesions any dis-cussion on pathogenesis amount,tothe question, "From what and howdo the saccules arise?""

SrrE OF THE SACCULES. -Writershave variously suggested that the

W iw ^ wdilatations of bronchiectasis origi-nate from the bronchi (Robinson,1933; Ogilvie, 1941; Mallory, 1947),the bronchioles (Lander and David-son, 1938), and the parenchyma(Opie, 1928; Erb, 1933; McNeil,

~ _ 4 R Macgregor, and Alexander, 1929;FIG. 31.-Alveolar pores seen in thick sections. Elastic stain with pyronin x 600. Lisa and Rosenblatt, 1943).I

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F. WHlTWELL

Neoprene casts, reconstruction models, anddissections of the bronchial tree show that sacculesare the bulbous terminations of the first to thirdbranchings of the segmental bronchi. As adultbronchioles arise only after about 18 branchingsfrom the segmental bronchi (Broman, 1923; Reid,1950). the saccules clearly cannot be of bronchiolarorigin.

Saccules are the direct continuations of largebronchi, they are encased within extension of'theperibronchial fibrous septa, and they are placedclose to and parallel with branches of pulmonaryarteries. Their situation suggests that they wereoriginally bronch:, and not bronchopulmonaryexcavations.

CAUSE OF DILATATION. First, it is possible toeliminate certain of the factors that are oftensuggested as causes of dilatation. Alveolar collapseis negligible in these specimens and cannot beconsidered as a possible cause, in spite of absoluteperipheral bronchial obstruction. Fibrous tissuefound in the saccular walls occurs only as a replace-ment of original bronchial structures. This fibrosisis concentric with the saccules, and not in a planewhere, by contracting, it could exert any dilatingforce on the bronchi. Most writers link togetherfibrosis and contraction, especially when discussingbronchiectasis. However, the behaviour of fibroustissue is perverse, and many examnples occur of itsproperty of ungoverned stretching, e.g., aorticaneurysms and in repaired hernias. Probably thestretching of fibrous tissue in saccular walls is afactor in the production of dilatation.The clinical findings of this group of patients

show that while in many cases the bronchiectasisdated from an attack of bronchopneumonia, innearly half the patients the disease had an insidiousonset which escaped notice.

It is considered that saccular bronchiectasisbegins as a chronic mural inflammation of themedium-sized bronchi. This condition destroysbronchial wall structures and obliterates peripheralbranches (Fig. 30), but is not sufficiently acute ordiffuse to produce parenchymal scarring or tointerfere with the establishment of a collateral air.circulation, provided all segments of a lobe arenot affected.The saccular shape of the diseased brolnchi is

probably produced after the destruction of sup-porting tissues and occlusion of peripheral branches,and results from distension by contained pus, thepressure ofwhich is increased by the partial occlusionof pre-saccular bronchi (see Fig. 28). Support islent to this theory by the compression-collapse

seen in several specimens in perisaccular alveoli(Fig. 29) suggesting that an expansile force iscentred within the saccules.The theory that dilatation is produced through

distension of the bronchi by pus was originally putforward by Laennec, but only a few (Riviere, 1905)have shared his opinion. As early as 1838 Williamsdiscredited Laennec's theory by arguing that mostpatients with copious sputum do not developdilatation, and many patients with bronchiectasishave little sputum. Williams's argument was falsebecause it did not take into account the conditionof the bronchial walls. Andrus (1937) discussedthis subject and said:

" As a problem in physics it is sufficient to noteat this time that in order to exert a dilating force itwould be necessary that the secretion occupy the grosssection of the lumen of the bronchus; such a con-dition would, however, necessarily result in atelectasis,and its possible effects be indistinguishable from thelatter."

His theoretical aerodynamics did not allow forcollateral air circulation, and the illustrated examples.do not support his statement.

ATELECTATIC BRONCHIECTASISIn recent years there have been many accounts

of the association of lobar and segmental collapsewith bronchiectasis, and it has become widelyaccepted that the collapse leads to the bronchiec-tasis. In this condition, which has been calledatelectatic bronchiectasis (although it is recognizedto be an acquired disease), the collapse is usuallythought to be caused by peripheral bronchialobstruction. Many writers have gone even furtherand stated that all bronchiectasis, even whencongenital, is caused in this way.The specimens which have here been classified

as follicular and saccular rarely showed collapse,even on microscopic exa-mination; where collapsewas found it appeared to be consequent to thebronchiectasis. However, some others of thespecimens did show severe alveolar collapse, sathey have been examined as a group in an attemptto find out whether the collapse or the bronchiectasiscomes first, and how this condition arises.The specimens lack homogeneity; in some the

bronchi are collapsed, in others there is grossdilatation, and in most of them the bronchi arethickened but only moderately dilated (Fig. 32).However, the grouping has been of some valuebecause it has shown that " atelectatic bronchiec-tasis" differs from other forms of the disease inits lobar and segmental distribution, and in the

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PATHOLOGY AND PATHOGENESIS OF BRONCHIECTASIS 233

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A 13 FIG. 33.-Atelectatic bronchiectasis with fibrous replacement ofbronchial wall structures. Haematoxylin and eosin x 30.

FIG. 32.-Atelectatic bronchieclasis of two lower lobes. Haema-toxylin and eosin.

histology of the bronchi. Wide variations in thepathology of these specimens makes it impossibleto give typical examples; the pathological findings, t tt - s_,*therefore, will be discussed under headings, andclinical features will be tabulated. .

PATHOLOGY

INCIDENCE AND LOBAR DISTRIBUTION.-The group ! tcontains 21 specimens, about 10% of the whole ;series. 4",The lobes affected are as follows: >-"

R.M.L.+ R.L.L. 1O specimensR.M.L..3 ,R.LL. IspecimenLL.L. 5 specimensILingula I specimen J48Aww ,

wg :nffL. Lung .... .. .. .. 1 ,, > <,t; -d tt'4.**

Middle lobes, and middle with lower lobes, 7represent 15% and 50% respectively of the collapsed rvspecimens, though they form only 4% and 7% of 7% tspecimens in the whole series. While right-sided C ''>*specimens form only a quarter of the whole series, 'they represent three-quarters of the collapsed t

specimens.*Specimens consisting of middle with lower lobes .'-^ .5 *-;>r 3 ido not always show atelectatic bronchiectasis in FIG. 34.-Atelectatic bronchiectasis with intra-bronchiolarboth lobes. The findings are as follows. and intra-alveolar haemorrhage with patent bronchioles.

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Middle Lobe Lower Lobe No. ofSpecimens

Collapse only Atelectatic bronchiectasis 2Atelectatic bronchiectasis Collapse only I

Atelectatic bronchiectasis Atelectatic bronchiectasis 3

Atelectatic bronchiectasis Saccular bronchiectasis I

Collapse only Follicular bronchiectasis 1Atelectatic bronchiectasis Follicular bronchiectasis 1

Collapse only Unclassified bronchiectasis I

SEGMENTAL DISTRIBUTION.-In all segments of an

affected lobe the bronchi show similar histologicalchanges. It is very difficult to assess calibre differ-ences in collapsed specimens, but usually thedegree of dilatation appeared about equal in eachsegment.BRONCHIAL OBSTRUCTION.-The lobar, bronchi

have been examined for stenoses and other lesionsthat might cause bronchial obstruction. None ispresent in lobes showing bronchiectasis, but inspecimens of simple collapse the bronchi are alsocollapsed and therefore obstructed.

Sections have been examined microscopically forobstructing lesions of the peripheral bronchial tree.In contrast to follicular and saccular bronchiectasis,in which peripheral obstruction is invariable, thebronchioles are patent and can be followed into thepulmonary lobules, where the air cells are partlycollapsed (Fig. 34).HILAR LYMPH-GLAND CHANGES.- In many speci-

mens the lymph-glands around the hilar bronchiare greatly enlarged, and on section showed non-specific chronic lymphadenitis, often with fibroticchanges. These glands are indistinguishable fromthe hilar glands in follicular bronchiectasis.

In three of the middle with lower lobe specimensthere are small partly-calcified caseous foci in theperiphery of one lobe (two in middle lobes and onein a lower lobe), and a similar focus is present inthe periphery of a left lower lobe. In two ofthese specimens the hilar lymph-glands containcalcified caseous foci. Except for two specimens oftuberculous bronchiectasis and a saccular bron-chiectasis with tuberculosis in the non-bronchiec-tatic part of the lobe, these are the only tuberculouslesions seen in the whole series.BRONCHIAL TREE.-The bronchi in collapsed

specimens show similar histology throughout alobe. There may be (1) moderate inflammationwithout any destruction of supporting tissues.This was also always seen in specimens of simplecollapse. (2) Slight superficial inflammation, butbronchial walls show dense fibrous thickening, andcontain no elastic tissue, muscle, or cartilage(Fig. 33). (3) Severe inflammatory changes withepithelial ulcerations and destruction of supportingtissues.The bronchioles show similar lesions, but are less

severely affected. In some specimens inflamedbronchial walls contain numerous lymph follicles,but interstitial pneumonia is absent.The type of histological change in the bronchi

appears to be unrelated to the degree of dilatation.ALVEOLI.-In spite of the gross reduction in size

of the lobes, and the apparent total alveolar col-lapse, the microscopic appearances are usuallythose of incomplete absorption collapse.Many lobes seem to be infarcted; in these there

is extravasation of red cells into interstitial tissues,and the partly collapsed alveoli, and some bron-chioles, are distended with blood (Fig. 34). Most

FIG. 35.-Development of atelec-tatic bronchiectasis (a) smallfocus in periphery of middleand lower lobe; (b) enlargedhilar glands and lobar col-

(t 1}~ tlapse; (c) atelectatic bronchi-ectasis with calcified foci inhilar glands.

b c

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of this haemorrhage consists of fresh red cells, but(leposits of haemosiderin in cells of the alveolarwalls and in intra-alveolar heart-failure cells showsthat some bleeding must have occurred beforeoperation. This intra-alveolar haemorrhage wasrarely seen in other forms of bronchiectasis. Theoperative technique was similar in all cases.

In the lobes showing simple collapse elastictissue in alveolar walls appears to be thickened,probably because of its relaxed state. In atelectaticbronchiectasis the alveolar wall elastic tissue iseither represented by a few short thick curls, or itis completely absent. A variable amount ofinter-alveolar fibrosis is seen but there are noother signs of inflammation.

CLINICAL FEATURES OF ATELECTATICBRONCHIECTASIS

The age distribution of all cases is shown inFig. 4. The case-records of 15 patients wereavailable for analysis, and provided the followingdetails.

AGE AT OPERATIONUnder 5 yrs.5-10 yrs.11-1 5 yrs.16-20yrs.21-25yrs.

26-30yrs.

Over 30 yrs.

AGE AT ONSET OF SYMPTOMSUnder 3 yrs.3-6yrs.

15yrs.

21-23yrs.Not stated

0 patients633

2 -

I patient0 ,

3 patients7

I patient2 patients2

PRE-OPERATIVE DURATION OF SYMPTOMSUnder I yr. 0 patients1-3 yrs. 54-5 yrs. 36-10 yrs. 3II-I 5 yrs. 2Not stated 2

NATURE OF ILLNESS AT ONSET OF SYMPTOMSMeasles and/or whooping cough 7 patientsPrimary bronchopneumonia 3

Insidious onset .. 2Pleurisy .. I patientNotstated. 2 patients

FINGER CLUBBINGPresent (recorded as mild)Absent . .Not stated

PARANASAL SINUS INFECTIONSPresentDoubtfulAbsent

5 patients9 .,I patient

3 patients48

Three patients who had tuberculous foci in thelobes and hilar lymph-glands dated their symptomsfrom whooping-cough or measles in early childhood.

There was a close correlation between the amountof inflammatory change seen in the bronchi and

the quantity and nature of the sputa; in manycases there was a complete absence of sputum.

PATHOGENESIS OF ATELECTATIC BRONCHIECTASISThe following features, which are characteristic of

atelectatic bronchiectasis and not of other forms ofthe disease, suggest how atelectatic bronchiectasismay arise: (1) the generalized distribution ofcollapse and bronchiectasis in the lobes; (2) theabsence of central or peripheral bronchial obstruc-tion in the lobes at the time of operation; (3) thepresence of tuberculous foci in some lobes andhilar lymph-glands; (4) the frequency of involve-ment of the right middle lobe, either alone or withthe lower lobe; (5) the variability of bronchialchanges, and the absence of inflammation in thecollapsed parenchyma; (6) the absence of fingerclubbing, sinus infections, and foul sputum inmany patients.The bronchiectasis must either be the cause, or

the result, of collapse. If collapse were secondaryto bronchiectasis one would expect the segmentaldistribution of the lesions, and their histology, tobe the same as in aerated forms of the disease.This was not so, so the collapse is probablythe primary condition. There were a few excep-tions to this generalization; they may have beensecondarily-collapsed follicular bronchiectases.

If the theory that collapse is caused by peripheralbronchial obstruction is accepted, in these casesone is forced to conclude that simultaneous obstruc-tions occurred in all peripheral bronchi; otherwisethe bronchiectasis could not affect all branches,and collateral air circulation would prevent alveolarcollapse. The improbability of such an occurrence,and the complete absence of peripheral obstructioni most of the specimens, suggests that there is nosound basis for this theory.There is far more evidence supporting the view

that collapse is caused by obstruction of lobarbronchi. Although no obstructive lesions of theproximal bronchi were found in these specimens, orseen in pre-operative bronchograms, the frequentfinding of enlarged, fibrotic, or caseous hilar lymph-glands suggests that collapse arose from occlusionby these glands of the lobar bronchi. This theoryreceives further support from the high incidence ofright middle lobe specimens in atelectatic bron-chiectasis, for Brock (1946) has demonstrated thepeculiar vulnerability of the middle lobe bronchusto compression from enlargement of the surroundinglymph glands.

Recently Brock (1950) has described suppurativechanges, bronchiectasis, and collapse in middlelobes as a sequel to tuberculous hilar adenitis. He

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states that in some cases this glandular enlargementmay be non-tuberculous, and that similar changesmay occur in other lobes. Specimens in this groupwere not examined for calcified foci radiologically,but they were dissected carefully and all hilarlymph glands were examined.Some specimens in this group showed absorption

collapse without bronchiectasis. In these lobes thebronchi were collapsed with their walls in apposition,and no irreversible histological changes werepresent, either in the bronchi or alveoli.

It is thought that this is similar to the state of alobe when its hilar bronchus had been occludedby lymph gland enlargement. When these glandsshrink the lobar bronchus becomes patent and aircan again enter the bronchial tree. In many casesthis is followed by aeration of the collapsed alveoliand the restoration of the lobe to normal, but ifsevere inflammatory changes have occurred in thebronchi, or if fibrosis has taken place in the paren-chyma, the lobe is unable to expand again. Insuch a case (Fig. 35), permanently collapsed alveolisurround aerated bronchi, which dilate because of*destruction of their supporting tissues and accumula-tion of bronchial secretions. The slight reductionin intra-pleural pressure, which might occur aftercollapse of a middle lobe, could exert little dilatingforce on its bronchi.

Bronchial dilatation in these cases may beexplained on mechanical grounds without thenecessity of there being severe inflammatorychanges, though the initial cause of the hilarlymphadenopathy is usually inflammatory. Theabsence of finger clubbing, sinus infections, andpurulent sputum in many of this group of patientssupports this theory of a mechanical disorder.

DISCUSSIONAlthough in this investigation a great variety of

bronchiectatic lesions has been found, the accounthas been limited to a. description of three commonforms which were seen in operation specimens. Inno instance could the bronchial dilatation havebeen considered to be reversible; it was always theresult of destructive inflammatory processes, per-manent alveolar collapse, or abnormal developmentresulting in bronchi of wide calibre.

Follicular and saccular bronchiectasis havedistinctive lesions and natural histories. Atelectaticbronchiectasis is a less specific and largely amechanical disorder, which usually follows occlusionby hilar adenitis of a lobar brorchus. The causesof lymphadenopathy are not restricted to anyperiod of life, neither are the specimens from

patients of any particular age, though they aremostly from young children. It is natural that thehilar adenitis seen in follicular bronchiectasisshould, in some instances, produce total obstructionof lobar bronchi, and result in specimens whichshow a mixture of follicular and atelectatic lesions.

All these lesions have been described previouslyon many occasions, but in the literature they haveusually been regarded as variations in a singledisease entity. it is not intended to review thisliterature; excellent summaries can be found inthe works of Ewart (1900), Ballon, Singer, andGraham (1931), Ogilvie (1941), and Lisa andRosenblatt (1943). It is sufficient to remark thatonly three accounts appear to be inconsistent withthe present study. Lander and Davidson (1938),reporting on 140 operation specimens, found littledestruction of bronchial wall structures, and inmany cases only slight indications of inflammation.Specimens such as these were extremely rare in thepresent series; they were not considered to be truebronchiectasis, and their removal had been dueto misinterpretation of radiological and clinicalfeatures. Lisa and Rosenblatt (1943), reporting on110 post-mortem specimens, remarked that thebronchial elastic tissues were relatively unimpaired.In the present study one of the earliest and mostconstant features of affected bronchi and bronchioleshas been the destruction of elastic tissue. Moore,Kobernick, and Wiglesworth (1949) have statedthat there is little correlation between the broncho-graphic appearances of a lobe and the condition ofthe bronchi; in fact, their work suggests thatsegmental resections can be of little value. Theopposite conclusion has been reached from thepresent study.

Literature on the pathogenesis of bronchiectasisis even more voluminous than that on its pathology;and it is much more confusing. One reason is,perhaps, that many theories are based on pathologywhich is inferred rather than observed. For example,similar radiological appearances are described ascollapse, fibrosis, and pneumonia, by differentwriters who deduce that these various conditionsare the cause of bronchiectasis. Another sourceof confusion is the vague use of the word " bron-chiectasis." For example, it is used in describingsome histological findings in fatal cases of pneumonia(Opie, 1928; McNeil et al., 1929), the gross lesionsproduced in animals by experimental methods(Weinberg, 1937; Tannenberg and Pinner, 1942),and the temporary bronchographic changes foundin 90% of university students who suffer fromrecurrent bronchitis (Ochsner, 1930). From studiesin similar rather restricted fields many writers have

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generalized about the pathogenesis of clinicalbronchiectasis.

Fortunately, the number of theories of patho-genesis is limited; in fact, apart from the possibleinfluence of allergy and sinus infections, no newtheory has been propounded in the last hundredyears. Nearly all writers are agreed that normalbronchi do not dilate when subjected to variousmechanical stresses, and most theories accept aprimary basis of bronchial weakness, due either toinflammation or developmental defects.Developmental abnormalities and the most

commonly suggested secondary causes of dilatationare discussed below.

DEVELOPMENTAL ABNORMALITIESAbout 10% of the specimens were examples of

congenital cystic lung, which is a developmentalabnormality. In five other specimens the bronchiwere thin-walled, and the calibre of the smallbranches was unduly wide, often, indeed, muchwider than the proximal bronchi. No inflammatory,fibrotic, or destructive lesions were present, and theparenchyma was entirely normal. In three of thesespecimens, however, the bronchial supportingtissues seemed to be underdeveloped. The widecalibre appeared to be their natural condition andnot due to dilatation.

Apart from these few specimens no evidence wasfound of any developmental abnormalities; norwas it necessary to postulate any such defects inorder to explain the bronchiectasis.

PRESSURE OF SECRETION IN BRONCHIThis theory, and the objections to it, have been

discussed on page 232. The terminal dilatationsin saccular bronchiectasis probably result fromdistension of weakened bronchi by their containedsecretions. The same mechanism may account formany of the dilatations of follicular and atelectaticbronchiectasis, though this is more difficult tosubstantiate.

FIBROSISThe usual theory supposes that bronchi become

dilated by the contraction of bands of fibroustissue running between them, but no such arrange-ment of fibrous tissue was seen in the specimens.Fibrosis occurred as a thickening of the normalfibrous structures in the peribronchial, perivascular,interlobular, and pleural connective tissues. Occa-sionally concentric fibrosis was seen in the walls ofdiseased bronchi, and it was always present in thewalls of saccules. Inter-alveolar fibrosis was

Q

found in some areas of chronic interstitial pneu-monia, and in absorption collapse.

In most forms of bronchiectasis fibrosis is a latedevelopment. It is the stretching of fibrous bron-chial walls in saccular bronchiectasis that leads todilatation; it is the parenchymal fibrosis ofatelectatic bronchiectasis which prevents re-aeration.

BRONCHO-PULMONARY EXCAVATIONIn a few lobes the dilatations appeared to be

re-epithelialized abscess cavities, which had origin-ated in the parenchyma. However, these lesionswere uncommon and not seen in the three typesof bronchiectasis described.

PERIPHERAL BRONCHIAL OBSTRUCTION ANDALVEOLAR ABSORPTION COLLAPSE

These two lesions are linked in most recentdiscussion on pathogenesis (Warner and Graham,1933; Boyd, 1935; Andrus, 1937, 1940; Landerand Davidson, 1938; Fleischner, 1940; Lander,1946; Coope, 1948). It is argued that collapsefollows obstruction, and dilatation occurs inbronchi proximal to the obstruction. These bronchiare subjected to a great dilating stress, which iscaused by the difference in pressure between thepleural space and the atmosphere in the bronchi.From the present study there appears to be no

sound basis for this theory. Obstruction of peri-pheral bronchi was always present in follicular andsaccular bronchiectasis, but absorption collapsewas absent, probably because of adequate collateralair circulation. Absorption collapse was found in10% of the specimens but it affected whole lobes,not lobules or segments. No peripheral bronchialor bronchiolar obstruction was present in theselobes, and the collapse had probably been causedby proximal bronchial obstruction.Many other arguments can be raised against this

theory. In cases where only a few small bronchiin one segment are affected there could be nosignificant alteration of pleural pressure to create adilating force, even if collapse occurred distal tothe bronchiectasis. The absence of radiologicalcollapse in many cases has been explained in manyunconvincing ways. Andrus (1940) states thatpatchy collapse is diagnosed as pneumonia, thatcollapse is concealed by the heart shadow, and thatcollapse may cause lung injury " and then bedissipated." Perry and King (1940) think thatcollapse can "lie dormant" for many years untilpurulent bronchitis supervenes. These reasons forthe absence ofradiological collapse, even if accepted,do not explain the normal aeration of so many

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TABLE IIIPATHOLOGY OF BRONCHIECTASIS

Follicular I Saccular Atelectatic

84% left-sided 72% left-sided 36% left-sided

Iso'ated bronchi affected Isolated bronchi affected All bronchi involved

Chronic inflammatory changes in bronchi Chronic inflammatory changes in bronchi Variable degree of inflammatory change,and bronchioles, with formation of lymph and saccules, no lymph follicle formation lymph follicles sometimes seenfollicles

Destruction of elastic tissue and muscle, some Little destruction of supporting tissues except Variable amount of destruction, sometimesdestruction of cartilage and mucous glands within saccules, where none remain very little

Bronchial epithelium intact and smooth, Bronchial epithelium intact but polypoid. Bronchial epithelium usually intact andsmall ulcerations in bronchioles. No Some ulcerations in saccules and promi- smooth. Few ulcerations, no squamoussquamous metaplasia nent squamous metaplasia metaplasia

Bronchio'es narrowed or obliterated Bronchioles obliterated Bronchioles patent

Alveoli mostly well aerated, but some inter- Alveoli well aerated, no chronic interstitial Marked alveolar collapse, uniform through-stitial pneumonia around affected bronchi pneumonia. Some compression collapse out lobe. Little inflammatory change inand bronchioles. Some compression around saccules collapsed alveoli, but some fibrosiscollapse around areas of pneumonia

TABLE IVCLINICAL ASPECTS OF DIFFERENT TYPES OF BRONCHIECTASIS

Clinical Findings

Age at onset of symptoms

Duration of symptoms

Age at time of operation

Illness at onset of symptoms

Bronchograms

Nasal sinus involvement

Clubbing

Follicular Saccular

53% under 3 yrs. 78% under 7 25% complained of symptoms allyrs. their lives. 70% began symp-

toms between 13 and 25 yrs.

1-15 yrs. 50%for 1-5 yrs. 22-20yrs. 50%for2-6yrs.

Mainly 6-11 yrs. old, with gradual None under 15 yrs., mostly be-decrease up to 20 yrs. None tween 15 and 25 yrs., with a fewover 20 yrs. cases in older groups

Vague onset in 25%. Measles andyor whooping-cough in 45%.Primary bronchopneumonia in20%

Usually cylindrical, sometimesatelectatic

Over 70%

Under 50%

Vague onset in 45% (including25% who had symptoms alltheir lives). Unspecified pneu-monia in 56%. No associationwith measles or whooping-cough

Saccular

Over 70()

75%

Atelectatic

20% under 3 yrs. 70, under 7yrs.

1-15 yrs. 33% for 1-3 yrs.

Mostly between 5 and 10 yrs.,but no sudden fall-off of olderpatients

Vague onset rare. Measles orwhooping-cough in 50%/; pri-mary bronchopneumonia in 25%

Atelectatic

Infrequent

Infrequent

operation specimens, such as has been seen in thepresent series, and which has frequently beendescribed in the literature.

SUMMARYThe investigation has consisted of the examination

of 200 consecutively removed bronchiectatic lungsand lobes. Methods used consisted of neopreneinjection casts of bronchial trees, large histologicalsections of entire lobes, and detailed dissections ofbronchial trees with histological examinations ofselected areas.The lobar, segmental, and intra-segmental distri-

bution of the lesions have been described (seeTables I and 11, and Fig. 10).More than half the specimens belonged to one

or other of three rather distinctive types of bron-

chiectasis, which have been called follicular,saccular, and atelectatic bronchiectasis, and theirpathology, clinical features, and pathogenesis hasbeen discussed (see Figs. 21, 30, and 35, andTables I II and IV).

Finally, current theories of pathogenesis havebeen criticized in the light of the present enquiry.

This work has been only made possible through theco-operation of the staff of the Surgical Chest Centre,Broadgreen Hospital. In addition I would like to thankMr. H. Morriston Davies, Mr. F. R. Edwards, and Dr.Robert Coope for many valuable discussions on medicaland surgical aspects of bronchiectasis. I wish also toacknowledge my indebtedness to Dr. Rachel M. Raw-cliffe for her assistance in the preparation of neoprenecasts and in the tabulation of case-records, and toDr. P. J. Taylor for correction of the MS.

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REFERENCES

Allison, P. R., Gordon, J., and Zinnemann, K. (1943). J. Path. Ba t.,55, 465.

Andrus, P. M. (1937). Amer. Rev. Tuberc., 36, 46.(1940). Ibid., 41, 87.

Baarsma, P. R., and Dirken, M. N. J. (1948). J. thorac. Surg., 17,238.- and Huizinga, E. (1948). Ibid., 17, 252.

Ballon; H., Singer, J. J., and Graham, E. A. (1931). Ibid., 1, 154.Boyd, G. L. (1935). J. Amer. med Ass., 105, 1832.Brock, R. C. (1946). The Anatomy of the Bronchial Tree. London.-(1950). Thorax, 5, 5.Broman, 1. (1923). Anat. Anz., 57, Suppl. (Verh. anat. Ges.), p. 83.

Quoted by Engel.Churchill, E. D. (1949). J. thorac. Surg., 18, 279.-and Belsey, R. (1939). Ann. Surg., 109, 481.Coope, R. (1948). Diseases of the Chest, 2nd ed. Edinburgh.Cruikshank, A. H. (1948). J. Path. Bact., 60, 520.Engel, S. (1947). The Child's Lung. London.Erb, I. H. (1933). Arch. Path., 15, 357.Ewart. W. (1900), Allbutt and Rolleston's System of Medicine, 2nd

ed., vol. 5, p. 127 seq. London.Fleischner, F. (1940). Amer. Rev. Tuberc., 42, 297.Jackson, C., and Jackson, C. L. (1932). J. Amer med. Ass., 99, 1747.Laennec, R. T. H. (1819). Dc L'Auscultation Mediate. Paris.Lander, F. P. L. (1946). Thorax, 1, 198.

and Davidson, M. (1938). Brit. J. Radiol., 11, 65.

Lisa, J. R., and Rosenblatt, M. B. (1943). Bronchiectasis. London.MacCallum, W. G. (1940). Textbook of Pathology, 7th ed. Phila-

delphia.

McNeil, C., Macgregor, A. R., and Alexander, W. A. (1929). Arch.Dis. Childh., 4, 170.

Mallory, T. B. (1947). New Engi. J. Med., 237, 795.Maximow, A. A., and Bloom, W. (1942). Textbook of Histology,

4th ed. Philadelphia.Miller, W. S. (1947). The Lung, 2nd ed. Springfield, Illinois.Moore, J. R., Kobernick, S. D., and Wiglesworth, F. W. (1949).

Suirg. Gynec. Obstet., 89, 145.Nelson, J. B. (1946). J. exp. Med., 84, 7 and 15.Ochsner, A. (1930). Amer. J. med. Sci., 179, 388.Ogilvie, A. G. (1941). Arch. intern. Med., 68, 395.Opie, E. L. (1928). Arch. Path., Chwago, 5, 285.Overholt, R. H., Betts, R. H., and tods F. M. (1947). Dir. Chest,

13, 583.Peroni A. (1934). Arch. Otolaryng., 19, 1. Quoted by Samson.Perry, K. M. A., and King, D. S. (1940). Amer. Rev. Tuberc., 41,

531.Reid, L. McA. (1950). Thorax, 5, 233.Riviere, C. (1905). St. Bart's Hosp. Rep., 41, 123.Robinson, W. L. (1933). Brit. J. Surg., 21, 302.

(1939). Amer. J. Path., 15, 638.Samson, P. C. (1940). J. thorac. Surg., 9, 679.Schmidt, H. W. (1947). Ann. Otol., St. Louis, 56, 793.Tannenberg, J., and Pinner, M. (1942). J. thorac. Surg., 11, 571.Van Allen, C. M., and Jung, T. S. (1931). Ibid., 1, 3.Warner, W. P., and Graham, D. (1933). Arch. intern. Med., 52, 888.Watts, C. F., and McDonald, J. R. (1948). Arch. Path., Chicago,

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