CHRONIC PULEMPHYSEMABy EARLE B. WEISS, M.D ., SANFORD CHODOSH, M.D.,and MAURICE S . SEGAL, M .D .Tufts University School of Medicine, Boston, Massachuse s

Chronic pulmonary emphysema may be de-fined by many standards but at present is de-monstrable directly by morphologic examina-tion. Clinically, the major complaint is dysp-nea, and this must be associated with increasedexpiratory airway resistance and hyperinflationof the lungs with actual destruction of alveolarwall structure .Pathologically, emphysema is a disease af-

fecting the acinus (basic respiratory unit, in-cluding respiratory bronchioles and alveoli)with the destruction of alveoli forming abnor-mally large air spaces, and resulting in a de-crease in the amount of elastic tissue, and inthe number and size of the capillary bed . Thedistribution of such alveolar destruction maybe (a) centrilobular (centriacinar) or centralacinar destruction, (b) panlobular (panacinar)or generalized acinar disease, and (c) para-septal involving alveoli at the periphery of theacinus. Centrilobular emphysema appears toplay a lesser role than panacinar emphysema,which is of more serious consequence. The latteraffects lung bases and apices with equal sever-ity. For radiological findings to be established,a grade III pathologic severity is usually pres-ent. Patients with chronic bronchitis, in whichthe x-ray film shows widespread emphysema,are subject to a 50 per cent mortality within5 years. Interstitial emphysema and the focalemphysema of coal workers have less clinicalsignificance . Blebs and bullae (large, thin-walled cystic air spaces) may occur in any

M These studies were supported in part by a grantfrom The Council for Tobacco Research-U .S .A .

d from Current Diagnosis 2by Howard F. Conn, M .D. and Rex . Conn, Jr ., M .D .

ished by W. B. Saunders Company, 196

form of emphysema and are referred to as lo-calized or generalized bullous emphysema .The cause and pathogenesis of chronic pul-

monary emphysema are not known . Chronicbronchitis, particularly that occurring withheavy cigaret smoking, appears to be associatedwith emphysema in susceptible individuals.Once the full clinical spectrum develops, it isoften difficult to separate chronic bronchitisfrom emphysema, though the latter may be thedominant component. Radiological and patho-logical studies indicate that while smokersshow more emphysema than nonsmokers (2.5times), the lungs of some nonsmokers revealsignificant degrees of emphysema. Certainly,emphysema is more common in white malesover the age of 40, in whom a history of cough-ing or smoking is present . Experimental studieswith foreign materials (phosgene, nitrogen di-oxide, etc .), epidemiologic analyses of air pol-lution factors, familial emphysema, and anti-trypsin globulin deficiency states suggest thatmany factors may be contributory. The presentexplanations for the development of emphy-sema include : (a) a consequence of chronicbronchial (bronchiolar) obstruction, with airtrapping and alveolar rupture ; (b) direct de-struction of alveoli from chronic inflammationor vascular ischemia; (c) degenerative or im-munologic changes in bronchi or alveoli .

Factors that intensify airways obstructionare important clinically . Thus exacerbations ofinfectious or allergic bronchitis, cigaret smok-

occupational or air pollution irritants, si-and mucoviscidosis may contribute to

ex iratory airways obstruction by hypersecre-

N RY

tion of mucus, inchial edema, brofibrosis, epithelial metaplasia and hyperplasia,or loss of ciliary action . Once emphysemaestablished further dynamic airways obstruc-tion may occur, when high expiratory pressuresare employed to expel air or by the collapse ofbronchi held patent normally by supporting

eolar structures . Associated cough mayuce sudden increases in intrabronchial

pressure, thereby intensifying alveolar damage .It is doubtful whether bronchial. asthma per seleads to chronic pulmonary emphysema, thoughclinically an "asthmatic" component may co-exist .

CLINICAL CRITERIA

The main complaint is dyspnea, intermittentor exertional at the outset because of the largefunctional reserve of the lung, and later con-

ly. Orthopnea is uncommon unless thereis superimposed cardiac failure . Even beforeradiological findings are apparent, the patientwill describe gradual limitation in physical ac-

Many give a history of wheezing oror without significant sputumhe chronic cough often pre-symptoms. Fatigue, anorexic ,

CHRONIC PULMONARY

exudates, bron-and bronchial

EMPHYSEMA-Continued

155

and weight loss are common, Progressive hy-poxemia, and/or respiratory acidosis will causeasterixis and cerebral abnormalities manifested

fusion, agitation, or personality changes .

PHYSICAL EXAMINATION

Early in the disease, general health appearsgood and the physical findings may be subtle .Later, evidence of tissue wasting and tachyp-

ith pursed lip breathing and excessivework of breathing will be observed. With es-tablished disease, the rib interspaces are wid-ened and the thorax is hyperinflated (barrel-chested) and fixed, moving as a unit in inspira-tion with striking use of accessory respiratorymuscles. A dorsal kyphosis is often present .The diaphragms are low and relatively im-mobile. Percussion note is hyperresonant andbreath sounds are distinct with a prolongedexpiratory phase . The presence of rhonchi andwheezing will depend upon local factors, withposttussive rales occurring frequently . Exami-nation of the heart may reveal an ill-definedcardiac border, distant cardiac tones (oftenheard best in the epigastrium), and in the pres-ence of pulmonary hypertension and right ver-

largement, a sternal lift, S2P beinggreater than S-,A, prominent A wave, (--,stclic

156 CHRONIC PULMONARY EMPHYSEMA-Continued

Figure 2 .

ram showing large bulla

leftlung and issal

scular pattern .

gallop (RV), or tricuspid insufficiency mur-mur. The usual peripheral signs of congestiveheart failure will be present in advanced stagesassociated with cor pulmonale . Clubbing, cya-nosis, or edema may be noted. Profuse diapho-resis often accompanies states of decompen-sated respiratory acidosis .

LABORATORY STUDY

Routine laboratory data are of limited value .Secondary polycythemia may be present withhypoxemia. The white blood cell count mayrise during infection, however, often one seesonly a shift to immature polymorphonuclearforms with a mild elevation in white count .Plasma chloride may fall and serum bicarbon-ate rise (> 25 mEq . per liter) with respiratoryacidosis. The sputum may be mucoid at first,becoming purulent during infectious episodes .Sputum cytologic pattern is that seen inchronic bronchitis with polymorphonuclearcells, macrophages, bronchial epithelial cells,and background debris with pneumococci andHemophilus influenzae in culture. (See sec-tion on chronic bronchitis .) The electrocardio-gram demonstrates a pattern of right heartstrain and systolic overload . The usual rightaxis deviation may be replaced by a left axiswith overinflation and cardiac rotation .

RADIOLOGIC CRITERIA

Correlation between symptoms and radio-logic findings is often poor in emphysema . In-spiratory and expiratory posteroanterior (A)and lateral (B) chest films are useful in deter-

air trapping and diaphragmatic move-' 1) . A single midsagittal tomograme pulmonary vasculature patterns,

while full tomography may delineate bullae(Fig. 2) . Overpenetration producing fictitiousloss of normal vascular markings is to beavoided. In diffuse emphysema, the follow-ing may be observed :

1. Hyperradiolucency of lung parenchymaand widened intercostal spaces,

2. Elongate, narrow vertical heart, andprominent pulmonary artery trunk (1 .5 cm.)with accentuated hilar and tapered peripherallung vessels (i .e . loss and distortion of the finebranching pattern of the vascular tree) .

3. Low (seventh anterior interspace) andabsolutely flat diaphragms .4. Increased retrosternal (lateral) and retro-

cardiac air.5. Bullae, which are avascular and of va .i-

able definition .A mild degree of panlobular emphysema will

not be seen radiologically and once the abovecriteria are observed, fairly extensive anatomicchanges will be present.Fluoroscopy may be employed to assess

diaphragmatic motion, air trapping phenome-non, or gross patterns of regional ventilation .

Bronchography may reveal distortion bybullae, or the changes of chronic bronchitis(if present) with elongation, cutoffs, beading,and diverticula .

PHYSIOLOGY

The physiological findings will vary with thestage of disease, in particular the degree ofairways obstruction, and the total amount ofreduced ventilated lung volume, in relation tothe effective pulmonary vascular perfusion .Recent bronchodynamic studies indicate thatair flow limiting segments occur between seg-mental and mainstem bronchi .Mechanics of Breathing . The slow or

forced vital capacity may be normal, increased,or decreased, and thus of limited value alone .However, the forced expiratory volume willshow reduction of first (FEV1_()) and thirdsecond parameters (Fig . 3) . The maximumvoluntary ventilation (MVV) and expiratoryflow rates (MMEFR, MEFR) are reduced .

FORCEDNRATORYVOLUME

arterial CODistribution .

inert gas distributthat the gas motributed to the alveoli .

Wc expiratory spirogi ow .to -rep

c

In the airways obstruc ~ ,, ,, nFEV3,O) s

nes (compared to the observed total FEV) are Iper cs

sd respectively Some impi( , N, ,rnent is noted incentage of -V1.0 and FEV3 .0 of the observed total FEV is normal in pulmonarthough the total FEV is reduced,

cotatic conn

piratorwork of breathing is efollowing use of bronchomay indicate asthmatic orPortents .Lung Volume. The

crease in residual volumthe total lung volume.

Ventilation . Tidal volume, respiratory fre-quency, and minute ventilations may benormal or increased initially . Later in thecourse, this compensating mechanism will failand the total ventilation will be decreased . Hy-perventilation (VE/VO2 > 35) is often associ-ated with a large o.\,gen cost of treatbing .Physiologic dead s,,rice may be in aywd asthe result of local iw 1 J auce hi pW n R or thepresence of bullae . Alveolar ventilation (VA)may be reduced, relative to total ventilation bythe presence of increased dead space,effective VA should be compared with

for

in is an in-clative to

ficance .- nitrogen studies of

abnormal, indicatings are not equally dis-

Gas02 gradiing capaci(DLf,,oSS) reveal a reduction in effective sur-face area. This may be due to ventilation/per-fusion imbalance or direct changes in the pul-

I Blood Gases and pH. Hypoxemia(P02 < 85 mm. Hg) with or without hyper-capnernia (PCO2 > 45 to 50 mm. Hg) andvariable degrees of respiratory acidosis (pH

I and tissuef dis-ronicis for

< 7.35) dependingbuffering capacities, relate to leveease and the presence of compheatibronchitis . In chronic respiratory aeach 10 mm . rise in P aCO2 the

,appropriate"

rise in pH should to 3.2nM (H+)/l, indi-c~itTng the absenceAwd"s; such asencu as the

way redt:that pat

reveWa~r, , atbing for 30 riiinution from chronic b

ith ii

S inued

The A-aed. Studies

for carbon monoxide

Is

1 57

d compared

cent and 90 to 95odilators . The per-ictive pattern) even

inplicating metabolickalosis which is

therapy .evi-

1 5 8

may show : (1) more rapid and shallowrespiratory pattern ; (2) reduced compliance ;(3) greater dead space ventilation ; (4) earlierdevelopment of hypoxemia and hypercapnia ;(5) earlier development of cor pulmonale ; (6)normal DLco .

SPECIAL DIAGNOSTIC TESTS

Differential Bronchospirometry . May beof use in preoperative evaluation, particularlyif unilateral lesion is present (viz., carcinoma,bullae),

Radioactive Isotopic Scan . Both perfusionand ventilation may be evaluated more com-pletely by regional isotope scan studies, wheretechnically available . Angiography may assesspulmonary vascular distribution .

Bronchoscopy . Findings during bronchos-copy are primarily those of bronchitis, if pres-ent. Bronchial collapse with expiration may beobserved .

COMPLICATIONS

The nature of the pathologic process sug-gests that the physiological impairment in thedisease is relatively fixed . However, acuteintercurrent insults may precipitate ventila-tory failure and C02 narcosis . Since this stateis potentially reversible, their diagnosis be-comes mandatory, e .g . exacerbation of in-

fectious or allergic bronchitis, inspissation ofsecretions (sputum volume low, hard to raiseand progressive dyspnea), bronchospasm, corpulmonale, pneumonitis, pneumothorax, gas-trointestinal bleeding, pulmonary thrombo-embolism, drug or 0 2 depression of ventilationor pleural effusion. Inguinal hernia and pepticulcer disease also occur as complications inemphysema.

COURSE

Interestingly, many patients manage to func-tion for many years after emphysema is firstdocumented. However, the general course forsuch patients is a variable but definite dete-rioration and limitation in physical function .There is a tendency to worsen during thewinter months with frequent episodes of in-fectious bronchitis . Pulmonary hypertensionand cor pulmonale (see section on cor pul-monale) usually occur late in the course, as theresult of a decreased pulmonary capillary bed,plus functional and organic pulmonary vascularchanges due to hypoxia, acidosis, and poly-cythemia. Alterations in blood gases, reductionin ventilatory ability, age of onset of disease,etc., are poor prognostic signs . However, clin-ical evidence indicates that careful supportivemedical care and physical and inhalation ther-apy may help maintain the patient with lessmorbidity and greater productiveness .