Tobacco Documents Online

h QU1950.14 Postgraduate Medicine "Chronic Obstructive Lung Disease Syndrome of Clinical Expediency „ JOHN P. WYMTT, M.D.' AND VERNON W. FISCHER, B.S.t St. Louis University StAool o/ Medicine, St. Louia TeE diHiculiies in de• marrating individual forms of obstructive lung disease by clinical and physiologic meth- ods and the lack of pathologic information on a %+hok-luag basis have led to an irnesti- gational renait•ance in pulmonary disease. De- rangements in the funrr JOHN P. rVYA7°r I Care/ul anlcmortew apprairaf and pathw. logic inueuigorions on a w/wfe,fung basis can bring aboul aigni frcaru advancee in anderstanding o/ chronic pufmonary dia- etue. Fidi rhir approac6, amnibua terms such as "obstructive lung syndrome," "asthmo and onphyrana," and "chronic irreversible hurg dixwe" can be efimo- Ilated and the diobgic and pathogenic lac- mra in tMae disparate Jorxu of diaeare .1" a red tional parameters of the lung encountered in the emphysema complex, such ns resistance to nir flor.. inhomogcaeity of gas distribution, changes in lung volume, and alterations in tbe perfusional-diHusional bed, are also observed in other generalized lung disorders. Cystic fibrosis of the lung. the "honeycomb lung" and genuine asthma rmay, to a greater or lesser degree, manifest one, several or all of rhese derangements. We ahall discass these altered functional parametery, as viewed from patho- •Rolun~ ,.1 PaD.Aat. .n0 ann~w ur arn.nmenr ol hndep: .rkel„n+n. .1 PnMlq. 4 le.r l'el.a,.ry 5r~.y sl tl.Aklee. 1...+ u ... m..rr.n.e er e.me a rrrr. r TI GvTO .~.1 7 1 a c n.. Ihe l e.,M }r1s tillk 6bn! Be.w. \'orrmhrr 068 logic evidence, and unveil the underlying morphodynamic disturbanoea in these duterent forms of obstructive lung disease. Airumy Ileaiqmroe ond Aherat(on in Lrrrrg iroipme Air trapping aud an increase in totaJ lung capacity and in residual volume are fiequent. ly observed in chronic pubnonary emphysema and can be manifested in other loealised or generalized lung diseases as vrel1. In genuine asthma, spirometric analysis conducted short. ly after au acute episode may reveal a aignifi- eant degree of air trapping. In the "boneycomb lung" the major patbologic changes are bron• Brprim.d Imm Cnl 3U. %.. 5. Nmrml.rr 1954 441

F.~,, o ia:) 0 1 5 rna>Re 1. Worrml ouaobhak of tung, otuGnea 1,y connari.e tis eve (CTI. ehove the rtisianoo of nonrrspiramry tmranrl Lronrbi• ok (TB) iato rmpvatory Oronrbi. al® (t1B). Alaen4r dneu and ab saa rnise Som rospirrrnvy broachiolea of tbr ebird order. Aoatomie rite of ecotrilobvler emphre®e tuedceud•  ungk primary tobuk o outlined by a triangte .7luetrating tbe unir eire of poulobalar empbreema lHeorwtos~lu~eae~u 6 p. s L) chiolar dilatation and tortuoRity due to para• tractional fibrosis; thi4 combination delays the expiratory cycle. In the emphysema complex, major allera• tions in total lung volume can be observed particularly in the distinctive type that is cvr• rently labeled, on morphologic gmunda, pan• lobular emphysema. In this variant, eatensive distention and destruction of air ducts and air sacs occur throughout the lung {figure 11. The resultant magnitude of total lung capacity may be a di6ereatial featme in futttrc clinical and physiologic categorization of emphysema' Ifigure 2). la/wmolrPneaty of Cm D1.rri6ution This facet of obtdructive airway disease also can be Sben in several different lung disraws. F7cint 2 fCrrmcl .bnle-lung paprn+rtion (dsrl•.1 superimposed on kotbke panlobular emphsrmetoue long. emphesieinp marked iocrcaac in loul long aprcih in penlobular emphysema. (Pepermunaeefina omlained. 300 r, redund on.+tbfntt 612 .ostce.ornr mronusr

ItHo19~016 rrcrne. 1 Lr/r. Papermarrouerion rrvealing numrsoae paothedout empbyeematoor lung toei reptaentati.e of eea• rrrl-Lutar rmphysenu. rUnstained. 300 µ ndneed one.touRh) R,Fhr. Tu,• app,sinnnal confluent air poob leentrilobular emphtsemw) with lolnilar erteriolq (A) centrally eimated anJ r.pnrd r., ,•ompr~,mn by .enWarion. Injected rapillanee at periphery inraeL (Unauioed, 125 µ a 10.) Wulr urajor blockaFes of bronchi by mucus, a:i i: frequentl} oh.rned 'w fibroc,vstic disease or chronic bronchitis, serious hyposentilation Jr%eiops and large segments of the aerating lung units show inequalities in the distribu• lion of gas. This malfunction in gas distribution is founrl in anothrr form of emphrreme whicb is no.% uidei% accepted af distinetive, at least on morphohFic e.'id:nce, namely, centrilobular rmph}sema (figure 1). There are numeroue lndlous areas deep %tithin the lung structure tAth cm,siderable differnnce; in volume . oell a; in anatomic location throughout the lung. Both these features fa%or inequality of gas no% ernenl t figure 3). The magnified pho- tugtaph in figure 3 sho+.s uro closely related centrilobular air pools; the lesion of primacy i- in the respiratory bronchioles which are ccntrally situated in the macrolobule (centri• Inbular emphysema I. The rrcund distinctive fcature of centrilobular emphysema is the uur- cival of structurally intact capillaries at the periphery of the air pools" (figure 3). Recent studies utilizing inhaled and inject- ed radioactive xenon have revealed pro. nounced diHerences between veotilation and perfusion t 1' ,Q 1' owing to these lp•ge con. thient air pools %%ith their intact p ripheral capillaries. This pathophysiologic finding may be an important distinguishing feature in the clinical diagnosis of centrilobular emphysema. Per/rsa7onaf.Dijruionaf Diatr.rberece Aboormalitiees of pub•nonar) perfusion and diffus~'on are highly complex. Both the dual arterial circulation in the pubmonic field and the existence of vascular spasra contribute to this complexity. The pulmonary anerioles, be• cause of their resistence to dissolution in the emphysematous air pool, may be influenced by transmural compression, with resultant hy- posia, or the diffusional capabilities of these vessel may prevent arterial desaturation.' An emensive loss of the microvar,cular bed, as seen in panlobular emphysema, is a significant factor in the high incidence of pulmonary heart •disease which oecurs in this form of emphysema. The triad of hypoventilation, pulmonary hypoxia and pulmonary arterial hypertension may be responsible for the spacm of the pre• eapillary arterioles and lead to cor pulmonale, as in chronic bronchitis' or early phases of eystie fibrosis of the lung." Extensive peribronchial fibrosie in adoles- cent fotras of cystic fibrosis or in pnetunoco- nioris produces bronchopulmonary coremuni- tnrem6er Obr dlo

c,itions and contributes to the difficulties in clinical studies of obstructive lung disearr-.. °iFnifieant degrees of alveolar wall thiebeainr in the "hooeyootnb lung" also impair diEu- sion. This factor and the acquired maUorma• lions of the periusional paths resulting from frbrosiis probably account for the frequency or cor pulmotiale in thi.a distinctive pulmonan• dtsnhilitv. txo.c a Le/g. Postmonem histomechattieol etndier rbo.ing tugh reei6l ance to air and 6ea.r gas. SF.; ctaisreoee lo.ered ith rapidlf di9oeing gaE brUom. Riehr. Pspamuroeeetias ehoxing 6eedom of Isnp bom destruetive emph. e®n. (Umriainrd. 300 u. mdorvd one-third I IaderJerenre If'itR ConlraclPle Porrera Witluo the palmonic field, alterations in two contractile foras have received ronsider able attention in recent yeam Quantitatite los,% of eLnaticily in the emphytuma comple. La probably a secondary phenomenon; recent electron microscopic mudies have not re%ealed any qualitative chaogea.' The other force nctnr 5. Left. Sr.rrr 4roncho eotntrittionr in pnatmsnrm bron• rLogram It3anum fulfate. artual siis t RrpAr Goblet r.11 mrrraee and prrath thirlrnrd lu.rmrnt mem hrane. htPhl. chatartrrnt,r ~I senuinr osthma 1 Prn•~dte artd %rhdi ruta 0 /. 1 35 1

, i;P 0 1.9 5, 0 1 S I 1 r161 R[ b. LrII. pu/tIDOnCm 'rtebfue .ohlme 6{udl~ r!• •eaLnr costrol inAation ar•- deaariuoar1 el clr -ehaded- and• in emphy- .ens„ a nhrft to the nght .uh great adrnmg ol loop t b5rtaeeu eRea t rn• druuve of iQpaired viato- elasnc lung propenies Crruer aad ry[hr. loereoeed reeutaore in emphroeme cuntraeted silh coerrol lung tehadedl aad modest d.rreae! in rspirerorr dor ra1C compared w lrh eonG01 Hnr tihsdedl. wrv 4t I 0 0 0 s e a l•1l.p.e.r nmw taapi r OAas' . Yr /sd .4 1r r ~ wu .•m. yi•.vnr r l.rirn.. 9 I uhich influences the opening and closing of air sacs ie related to the surface tension of the alveolar linieg fluid. lnvestigations of this aspect have been largely confined to the nor• mal lung. but the possibility that hypoxic state_• within the lung field could interfere utth this alveolar unit membrane and influ• ence air•sac size and gas diffusion is. worthy of speculation. Illuarrorioe Cases rour clinicopathologic case reports will illustrate some of the morphologic features that separate the different typei of chronic obstructire lung disease. Case I-A 50 year old Negro woman had a 15 .ear history of asthma and was known to be allergic to pine and other tree pollens. A physician specializing in chest diseases noted that she had a ventilatory impairment t.hich t.•as partially relined by steroids. The patient died during an nttack of asthma. Post- nt~ Rt C. Poslmorrrm F~aph .~f hNVmrrh~mr~ •ho..mF r.rrl.+nprd dega• innan thmr• nbsrned m r~ph.rrma eonvarred wuh ncrma. 11dewr mortem pulmonary analysis revealed that the inflationary pressure was higher than normal and was slightly lower with belittm, which diffuses readily through mucus plugs. There aas no alteration in the viscoclastie proper- tics. Total lung sun ey did not reveal evidence of emphysema Ifigure 4). The bronchogram presented the radiologic markings of "broken bough," produced by blockage of subsegmen- tal bronchi with mucus. Histologic examiua• lion showed the thickening of the basement membrane that is highly characteristic of genuine asthma I figure 51. Comment-The pathologic findings are those of classic asthma. 7•his ease chailengea the textbook rubric that chronic pubnonary emphysema is always an aftermath of pure bronchial asthma and poses the question nhether the clinical disclosure of funetional ventilatory impairment necessarily warranLs the conclusion of the presence of destrnctive pulmonary emphysema.

K~~~)ft?~~~)iy wsIar a Paperuaaermruou of lung m ehrou ic bumclvus thn.,ng ahtence of deawrb•e empbneuw (Loaiainrd. 300 ~ reduerd one. Ihvd 1 Case 2-A 59 year old w•hile man, a dia- belic, was hospitalized because of cheat pain and deep cyanosis. He died in the hospital. n0 ae 9. I'; pe. NormaL Bn.nrhlel nnunu rith rar hlagmous platm iblarki aed a lew widrlr nranrrrd vueua glande. L..ner. Chronir bronchiiis. 5rgni6ranr mrreane m mueur Flanda -am+a' .nh some narromg ol lumen of IoonrhLL r1 dmsu,nal pomt. -Aldrh.de lurham elain. Autopsy revealed that the immediate eause of death w•as thrombosis of the right descending coronary- arlery. Six months before death, his total lung capacity had tK,en 7.8 liters ( 151 per cent), residual solume 5.3 Gters (39 per eent ), vital capacity 2.6 liters (70 per cent 1. and alveolar nitrogen 3.2 per cent (normal. h~,- than 2.5 per cent). Postmortem pulmo- oary "function" €tudie€ revealed marked widening of the inflationary-deflationar) curve (figure 61. an indicant of sesere impairmenl of the intrin-ic ci"-elastic properlie= of thr lung: increased resistann• to expir:rtory air flos; and Fignificantlc delayed deflation. the latter feature indicating postmorlem air tralw ping due to the abnormally flaccid bronchi and in part to the lo« of suatentacutar ti«ue- (figure : 1; and enryrhs€em.ataue change affect- ing about 70 per cent of the lung 1 r%hole•lunF papenection 1. Both patterns of emphy€ema were present. Centrilobular ernphysema was noted in the upper lobe, anJ panlobular em• physema in the losuer half. Coexistence of both forma has been found in approcimatPls one•third of our cases. Comment-Thir case dernonstrate- that siF• nificant correlation with anlemorlem function atudica. e.g.. total lung eafraeits and residual .•olume. can b: obtained if multiple morphn• an.J%.tie procedures are applied post mortem. The greatly increased lung capacity ano the limited retention of alveolar nitrogen indicate that the panlohular de•truction of the lower bt6 roafcn4oi +r[ nrmrIIL

0 © 0 0 1 1'dasa :I) hupmo 1®WV.e! ~ r-r...r tl a r hl[apnnrr h.nm tm e~) hn ..rp. {Mo-hr h plnrh ncime 10. Fibrot}e "boaeteomb" luag re.eala nstricra.e roluma opene with difficulry at -12 em naru, end offers iacreaeed r.maranre (right 1 m inAaril.n. h31f of thO lung was Ihe ominous component in thi, Fatient's disease. Case 3-A 63 year old white mao com• plained of chronic cough. sputum production and shortness of breath of tao years' duration. He had smoked one package of cigarettes per day for 47 years. Pulmonary function studies in 1960 anll in 1962 yielded the following results: total lung r.apacity 2.1 liter, (50 per cent 1 and 1.9 liters (58 per cent 1 rrspective• ly. residual volume 2.0 liters (2) per centl and 2.0 Glers ('.'.0 per centl, alveolar nitrogen 2.0 per cent and 5.1 per cent, and oxygen consumption 29 cc. and 42 cc. (normal, 45 ce per liter). The eliniral diagnosis in 1962 w,as "secere impairment of ventilatory func• tion with severe degree of emphy.emalous change." The patient was eomatose at the time of his final admission to the hospital. At the time of death the carbon dioxide level wk 33.8 mEq. and the Mood urea nitrogen wa~ elevated. Aulopay revealed pure right aentricular hy. I('k-'1.11 ~ o1(P) U ncrmr IL Putawnem bronrbogre® .itL aUau.tabde tpisud garled "Fnach loaP' appeaeoes fu .'nunsr) comb" lung IBarivm uillate, reduce~ ame•third.l ruralt 12 Papermaeroeeerion ipwtnring omltifoal "bonerrnmb" ereas rhnw`hout lang 5eld with iata• .enieg lun tlaoe hee of emphr.emeton dhmptlon (Unnafned. redoeed onr.tbLd) Nmrmber 1960 40

KR11195E1?1 pertrophy (80 gm.; control, 45 gm.) without evidence of valvular malformations or signifi• cant coronary artery disease. A total lung survey ahowed no evidence of emphysema Ifigure 8). A bronchogram revealed the changes of widespread chronic bronchitis.' Hielologic examination confirmed the extent and degree of chronic bronchitis. Contider• able increase of mucus glands and goblet cel1• was observed (figrne 91 in eddition to vascu• lar thickening of the precapillary pulmonary arterioles. Comment-This case illustrates the clinical precept that chronic bronchitis without evi• dence of emphysema can produce cor puG monate and metabolic acidosis. Confirmation cf this clinical viewpoint is possible only by pathologic investigation aa a whole-lung basie. Tile pulmonary heart disease and arteriolar thickening probably were related to continuinF bouts of bronchial obstruction which produced alveolar hypoventilation with hypoxia and hypercapnie. Case 4-A 69 year old white man who was exposed to silver compotlndo- for many years in his work af a chemist suffered from dyspnea and nonproductive eough for five yeare. For tw•o years nrior to his death he wae bedridden because o( cor puhnonale. Two years before death. pulmonary function studies revealed a restrictive form of ventilatory disease: total lung rapacitp 2.51itera (50 per cent), residual volume 1.2 liters (48 per cent), alveolar nitro• gen 1.2 per cent, and oxygen consumption 26 cc. Electrocardiographic study revealed marked right ventricular hypertrophy. X-ray examination showed extensive linear shadows throughout both lungs. The clinical diagnosis Tcas obstructive emphysema secondary to fibrosis. When admitted to the hospital for the last time, the patient had eyanosia of the face and clulrbed fingera, and the carbon dioxide level was 38.7 mF.q. He died of right hearl failure. Postmortem studies disclosed art elevated resiatcnce to inflation of the lung. an increased flow rate, a decreased volume, and e=uperim• posltion of the deflationary curve on the in• flationary curve. Thes<e histomechanical find. ings are indicative of exlensive fibro=ia within the lung (figure 10). Marked dilatation of the bronchial arterial pattern suggested bron- chial-pulmonary communications. Purc right ventricular hypertropby was present (78 gm.; wntroL 45 gm. ). A broncbogram revealed a gnarled, twisted "French loaf" appearance that ie highly cbaraeteristic of the "honey- comb lange^ (figure 11). Papenection showed multifocal distribution of e'eyatie" nonrespira- tory bronchioles due to a peribronchial fibros- ing condition: "honeycomb lung" (figure 12). Comment-Thia condition has bem mis- takenly labeled "broncbiolar emphyaerm." AO the features separating this restrictive veatil.a- tory disease from chronic pulmonary emphy seme are demonstrated here. The impaired ventilatory capacity eod marked decrease in total lung capacity, the prominence of cor pulmonale, the altered bronchial arteriogram and the bronchopulmonary shunts, the charac- teri•tic bronehogram. and the distinctive ana- tomic portrait set this condition apart from chronic pulmonary emphysema. AIXNOW'LEDG11fMT We wir,h to aekno.ledre Ihe valoable reehniul aNieunlr of Mr Eorl C \irchrenlmer. \t.':.H.A. REFERE!•CES I. a+Arr. J. P_ Facnoi V. W. and Sm.n. H. C• Panlohulur empblaema: Aoetcvrc end pallxd. namica Dla. llnr 41:739. 1962 Y _: l,enlnlohutar emphyeenTa lab. Inveat. 10• Ib9 19b1 1 DG+mocun. L B.. Bm+n.. 1:. 5rcwaxT, P. B_ BaT,a..A.C.Bau,W.G•Je.mdB.raD.V. .Rudiee of rcglonal ventilation and perfurioo in pulnwnary emphrrema udng aeaon°. Am Re. Reapu. Dia BB:S1S 1463. 4. Jaaryo%. A. G.: Di9uaon nf paera from alreolur to prempiUarv aneeee Science 139:B24 19fiS S FLtTenma. C 11_ Hlee•)oM P_ McNlcoI~ a1 W. aad Paut6 N B.: The diatploau of pulmonsn emphyeema m Iha prtaence of eJnonic bmnchhiw (luarn J. Med. 32:3119t.1 6. Gormrwa. IL ILL. 11mso. G. A1_ Almasal. D H and Flaeuan. A. P.. Cot palmoode io enUc Bbroaio of the panenu Cirrularion $4:942 1961. 7. WTan. J. P_ Fn~arx V. W. and cw¢T• tL C- The pu6omerphologl of the emphyxma awmpler. Am Bev. Reap.r. Dn.89:583 (Aptill 196t. R Hmaaann. 1. It. Ba.nrrcaM. 0. G. ICanl. M B and Goco• R. V.: Bronelx•aeopr and brrmehogiaph. In emph.eerna tad chronie broor6itiL Dia Chesr ;1:2YL 1%2 448 eOreT6p.ol'ATE V6ulrlIr