Chapter IV: The Pathology and Bacteriology of Pneumonia Following Influenza (7)

=Autopsy 473.=—A. D. P., white, aged twenty-one, a student from
Missouri, had been in military service two weeks. He was admitted to
the hospital with influenza twenty-eight days before his death, and
four days after admission there were signs of pneumonia.
Paracentesis was performed on the right side on the eleventh day
after admission; 4 c.c. of cloudy fluid which contained Pneumococcus
III were obtained at this time and later in the day 800 c.c. were
withdrawn. On the thirteenth day attempted withdrawal of fluid from
both pleural cavities failed. On the eighteenth day aspiration of
the right pleural cavity yielded only 30 c.c. of fluid. On the
nineteenth day 400 c.c. of purulent fluid were withdrawn from the
right pleural cavity. On the twenty-fifth day there was cyanosis and
delirium. Shortly before death aspiration of the right pleural
cavity was attempted, but only 4 c.c. of fluid were obtained.

=Anatomic Diagnosis.=—Chronic bronchopneumonia with lobular and
peribronchiolar consolidation in left lung; fibrinopurulent pleurisy
on both sides; purulent bronchitis and bronchiectasis.

On removal of the sternum, encysted purulent pleurisy is found
between the inner surface of the right lung and the pericardium;
there is here 450 c.c. of very thick creamy, greenish yellow pus
entirely separated from the remainder of pleural cavity. The
external part of the cavity contains 1,450 c.c. of fluid and
voluminous masses of firm fibrin which placed in a measuring
cylinder occupy 450 c.c. The left pleural cavity contains 400 c.c.
of seropurulent fluid in which there is abundant sediment of
fibrinous particles.

The right lung is compressed; the bronchi exude purulent fluid. The
left lung is voluminous; in the upper and lower lobes there are
small yellowish gray nodules of consolidation, grouped in clusters,
and gray patches of lobular consolidation occur. Bronchi are dilated
and filled with purulent fluid.

Bacteriologic examination shows the presence of Pneumococcus III
obtained in pure culture from the blood of the heart and from the
right pleural cavity. S. viridans is grown from the left lung; a
plate from the right bronchus contained B. influenzæ, S. viridans
and a few colonies of staphylococcus and M. catarrhalis.

The foregoing case is particularly noteworthy because aspiration failed repeatedly to yield more than a few cubic centimeters of fluid, doubtless because the voluminous masses of fibrin present in the cavity prevented escape of fluid. Aspiration was attempted shortly before death, but only 4 c. c. of fluid were obtained; nevertheless, at autopsy the right pleural cavity contained 2,350 c.c. of exudate. Another factor of much importance in relation to treatment is the encapsulation of 450 c.c. of purulent fluid between the inner surface of the right lung and the pericardium. It is possible that free drainage might have emptied the main cavity and perhaps even freed the encapsulated fluid.

=Pericarditis.=—Among 241 autopsies on individuals with pneumonia following influenza, pericarditis occurred 23 times; these lesions were classified as follows: Serous pericarditis, 1; serofibrinous pericarditis, 9; seropurulent pericarditis, 1; fibrinopurulent pericarditis, 10; purulent pericarditis, 2.

It is noteworthy that in 12 of 23 instances of pericarditis the lesion was associated with S. hemolyticus infection of the lung and whenever in these instances cultures were made (Autopsies 434, 485, 499 and 504) hemolytic streptococci were obtained from the pericardial exudate in pure culture.

The tendency of interstitial suppurative pneumonia to produce pericarditis is especially evident. Among 21 instances of interstitial suppurative pneumonia pericarditis occurred 6 times (28.6 per cent); among 39 instances of suppurative pneumonia with abscess formation, pericarditis occurred twice (5.1 per cent); whereas among all other autopsies, namely, 181, the lesion occurred 15 times (8.3 per cent).

Pericarditis occurred in association with pneumonia referable to Pneumococcus I, once, (Pneumococcus I isolated from the pericardium); to Pneumococcus II, once; to atypical Pneumococcus II, 5 times (twice isolated from the pericardium); and to Pneumococcus IV, twice (once isolated from the pericardium).

=Peritonitis.=—Purulent peritonitis occurred only twice, in both instances in association with pneumonia caused by hemolytic streptococci. Purulent peritonitis was part of a general serositis involving both pleural cavities, pericardium and peritoneum in 2 noteworthy instances:

=Autopsy 465.=—J. K., white, aged twenty-two, farmer from Oklahoma,
had been in military service one month. He was admitted to the
hospital with influenza, sore throat and bronchitis twenty-four days
before his death. Signs of pneumonia were recognized thirteen days
later and at the same time there was otitis media on the right side.
Empyema and pericarditis were found three days before death and two
days later 1000 c.c. of cloudy fluid were withdrawn from the chest.

=Anatomic Diagnosis.=—Suppurative pneumonia with consolidation and
abscess in right lower lobe below pleura; purulent pleurisy on
right, seropurulent pleurisy on left side; beginning serofibrinous
pericarditis; fibrinopurulent peritonitis; purulent bronchitis.

The body is emaciated. The right pleural cavity contains 350 c.c. of
thick, creamy yellow pus in which are flakes of fibrin; the right
lung is collapsed and lies at the back and inner side of the cavity.
The left pleural cavity contains 500 c.c. of turbid, yellow,
seropurulent fluid in which is soft fibrin. The lower lobe of the
right lung is consolidated throughout, flabby, gray red and finely
granular on section. Below the pleura of the posterior border is a
wedge-shaped cavity with its base 1.5 cm. across, in contact with
the pleural surface. About the cavity consolidated tissue has an
opaque, yellow color. Bronchi in both lungs contain mucopurulent
fluid. The pericardial cavity contains 20 c.c. of turbid fluid; the
left auricular appendage is bound by a thin layer of fibrin to the
parietal pericardium.

The peritoneal cavity contains 100 c.c. of thick, creamy, yellow,
purulent fluid. Between the diaphragm and liver is a layer of
fibrin, in places 1.5 cm. in thickness; fibrin is present upon the
peritoneum overlying the kidneys and base of mesentery.

Bacteriologic examination shows the presence of hemolytic
streptococci, obtained in pure culture from the blood of the heart,
right pleural cavity and peritoneum. From the right bronchus are
grown S. hemolyticus, B. influenzæ and a few colonies of S. viridans
and staphylococcus.

=Autopsy 504.=—G. R. C., white, aged twenty-eight, farmer from
Alabama, had been in military service three months. Onset of illness
occurred six days before death, and two days later he entered the
hospital with fever (103.4° F.), pains in the abdomen and vomiting.
Consolidation at the bases of the lung was recognized on the day
following admission and on the day before death 900 c.c. of greenish
brown fluid were aspirated from the left pleural cavity.

=Anatomic Diagnosis.=—Interstitial suppurative pneumonia with
consolidation in left lower lobe; purulent pleurisy on both sides;
purulent pericarditis; purulent peritonitis; parenchymatous
degeneration of kidneys; acute splenic tumor.

The body is that of a large well-nourished man. The left pleural
cavity contains 975 c.c. of creamy, yellow fluid; right pleural
cavity contains 425 c.c. of purulent fluid thinner than that on the
left side. The left lung is collapsed; the posterior and lower half
of the lower lobe is consolidated, flabby, deep red and fleshy in
appearance. The interstitial septa are yellow, thickened with
bead-like enlargements and contains creamy purulent fluid which
flows away and leaves small cavities. This interstitial suppuration
is more advanced below the outer surface of the lobe than elsewhere.

The pericardial cavity contains 25 c.c. of creamy, yellow, purulent,
fluid; the epicardium is dull, covered in a few places by a small
amount of fibrin and below it are ecchymoses.

The peritoneal cavity contains 100 c.c. of thick, yellow pus; the
peritoneal surfaces are injected and between the liver and diaphragm
is fibrin.

Bacteriologic examination shows the presence of S. hemolyticus in
pure culture from the blood of the heart, the lower lobe of the left
lung, pericardium and peritoneum. The right main bronchus contains
the same microorganism, B. influenzæ and a few staphylococci.

General serositis has been caused by hemolytic streptococci which in one instance have entered the pleura from a subpleural abscess, and in the other from the suppurating interstitial tissue of the lung. In one of these cases the patient entered the hospital with symptoms suggestive of acute peritonitis.

Bronchiectasis

Acute dilatation of the bronchi is a common result of the bronchitis of influenza, and its frequent occurrence is an index of the severity of the changes in the bronchial wall. In some instances the smaller bronchi in well-localized areas are uniformly dilated; in other instances, large cavities, several centimeters in diameter, are formed and all transitions between the two extremes occur.

The occurrence of bronchiectasis following influenza is mentioned by Leichtenstern[86]. He states that evidence of bronchiectasis can persist for weeks or months and nevertheless end with complete restitution of the lungs to normal. Lord[87] has described instances of bronchiectasis occurring in association with infection by B. influenzæ and Boggs[88] has recorded similar observations.

We have had abundant opportunity to observe early stages in the production of bronchiectasis and to study the much discussed pathogenesis of the condition.

The following figures show the predilection of bronchiectasis for the left lung and for the lower lobes: Bronchiectasis occurred 30 times in the left lung alone, 9 times in the right lung alone and 13 times in both lungs, the total being 52. Among 30 instances in which the lesion occurred only in the left lung, in 24 it was limited to the lower lobe, and in 15 of these 24 instances to the base of the lower lobe. Among 9 instances in which dilatation of bronchi occurred only in the right lung, it was limited to the lower lobe in 4 instances and to the base of the lower lobe in 2 of these 4 instances.

When the lesion is limited to the base of the lower lobes small bronchi with no recognizable cartilage in their wall are dilated to a diameter of from 3 to 6 cm. and are distended with thick mucopurulent fluid. The tenacious character of the bronchial contents and the action of gravity doubtless have a part in the production of the dilatation. In several instances dilatation of the bronchi was limited to the basal parts of both upper and lower lobes.

When bronchiectasis occurs throughout a whole lung, usually the left, or in both lungs, the lesion is more advanced and conspicuous (Fig. 26). There is diffuse dilatation of small and medium-sized bronchi. Dilated bronchi with deeply injected mucosa and filled with yellow mucopurulent fluid, are seen throughout the sectioned lung. A bronchus cut longitudinally may have a nearly uniform diameter of from 5 to 9 mm. for a distance of 5 or 6 cm., maintaining this diameter to within 1 cm. of the pleural surface, where normally only small bronchi occur.

More advanced bronchiectasis is represented by the occurrence of spherical bronchiectatic cavities, having a diameter from 1 to 2.5 cm. In some instances there have been two or three of these cavities but occasionally there may be many. Cylindrical dilatation of the bronchi usually occurs widely distributed in the lungs. In Autopsy 440 a small bronchus, cut longitudinally, was dilated to a diameter of 5 mm. for a distance of 5 cm. and terminated in a spherical cavity 2 cm. in diameter; there was another smaller spherical cavity nearby and dilated bronchi occurred elsewhere. In Autopsy 467, in the upper part of the lower lobe, two spherical cavities 1 and 1.5 cm. in diameter communicated with a bronchus of medium size.

Autopsies with bronchiectasis are listed in the order of the duration of illness to show the parallel increase in the severity of the lesion (Table LI). In 2 instances (Autopsies 244 and 314) bronchiectatic cavities surrounded by firm fibrous tissue have evidently existed before the onset of the fatal illness, which has lasted in one instance approximately four and in the other six days; these autopsies have been omitted from the table.

The table shows that bronchiectasis observed within twelve days after onset of illness with symptoms of influenza is moderately advanced and almost invariably limited to the left lower lobe and usually to the base of the lobe. Advanced dilatation, indicated by the formation of spherical or cylindrical cavities, occurs with increasing frequency as the duration of the respiratory disease increases.

Bronchiectasis has been almost invariably associated with purulent bronchitis. The dilated bronchi contain mucopurulent material and throughout the lungs the same condition is usually widespread. Among 137 instances of purulent bronchitis bronchiectasis consequent upon influenza has been present in 50.

TABLE LI

═══════╤════════╤═════════════╤══════════════╤══════════════╤═══════════
NO. OF │DURATION│ TYPE OF │ LOCATION OF │ CHARACTER OF │BACTERIA IN
AUTOPSY│ OF │ PNEUMONIA │BRONCHIECTASIS│BRONCHIECTASIS│ BRONCHUS
│ILLNESS │ │ │ │
│IN DAYS │ │ │ │
───────┼────────┼─────────────┼──────────────┼──────────────┼───────────
394│ 5 ?│Broncho │Rt. base │Dilatation │
359│ 7 +│Lobar and │Lt. lower lobe│Dilatation │
│ │ broncho │ │ │
322│ 8│Abscess │Lt. base │Dilatation │
│ │ (staph.) │ │ │
325│ 8│Interst. │Lt. base │Dilatation │S. hem., B.
│ │ suppuration│ │ │ inf.,
│ │ │ │ │ staph.
352│ 8│Lobar and │Lt. lower lobe│Advanced │
│ │ broncho │ │ dilatation │
429│ 8 ?│Broncho │Rt. base │Dilatation │
288│ 10│Abscess │Lt. base │Dilatation │S. hem., B.
│ │ │ │ │ inf.
374│ 10│Lobar and │Rt. and lt. │Advanced │
│ │ broncho │ lungs │ dilatation │
376│ 10│Abscess │Lt. base │Dilatation │S. hem.
437│ 11│Lobar │Rt. lower lobe│Advanced │
│ │ │ │ dilatation │
482│ 11│Broncho │Lt. base │Dilatation │B. inf.,
│ │ │ │ │ Pneum.
│ │ │ │ │ IV, S.
│ │ │ │ │ hem.
489│ 11│Lobar and │Lt. lung │Dilatation │B. inf.,
│ │ broncho │ │ │ Pneum.
│ │ │ │ │ IV.
287│ 12│Lobar and │Lt. lower lobe│Advanced │Pneum. IV.,
│ │ broncho │ │ dilatation │ B. inf.,
│ │ │ │ │ staph.
289│ 12│Broncho │Lt. lower lobe│Advanced │Pneum. IV.,
│ │ │ │ │ B. inf.
│ │ │ │ │ staph.
295│ 12│Interst. sup.│Rt. lung │Advanced │S. hem., B.
│ │ and abscess│ │ dilatation │ inf.
336│ 12│Broncho │Lt. base │Dilatation │
375│ 12│Broncho │Rt. and lt. │Dilatation │
│ │ │ bases │ │
422│ 12 ?│Lobar and │Lt. base │Dilatation │
│ │ broncho │ │ │
381│ 13│Abscess │Lt. base │Spherical │
391│ 13│Lobar and │Lt. lung │Dilatation │
│ │ broncho │ │ │
401│ 14 ?│Lobar and │Rt. and lt. │Spherical │
│ │ broncho │ lungs │ │
402│ 14│Chronic │Rt. lower lobe│Dilatation │
│ │ broncho │ │ │
410│ 14 ?│Abscess │Rt. upper lobe│Dilatation │
333│ 15│Abscess │Lt. upper lobe│Dilatation │S aur., B.
│ │ (staph.) │ │ │ inf. S.
│ │ │ │ │ hem.
389│ 15│Interst. │Lt. lung │Advanced │
│ │ suppuration│ │ dilation │
412│ 15│Lobar and │Lt. lower lobe│Cylindrical │
│ │ broncho │ │ │
398│ 16│Broncho │Rt. and lt. │Advanced │
│ │ │ lungs │ dilatation │
423│ 16│Broncho │Lt. base │Dilation │
488│ 16│Abscess │Lt. lower lobe│Dilatation │S. hem.,
│ │ │ │ │ Pneum.
│ │ │ │ │ atyp. II.
312│ 17│Broncho │Rt. and lt. │Dilatation │S. hem., B.
│ │ │ lungs │ │ inf.
│ │ │ │ │ staph.
372│ 17│Broncho │Rt. lung │Dilatation │
385 C│ 17│Interst. │Lt. base │Dilatation │
│ │ suppuration│ │ │
448│ 17│Broncho │Lt. lung │Dilatation │
460│ 17│Abscess │Lt. lower lobe│Spherical │S. hem., B.
│ │ │ │ │ inf.,
│ │ │ │ │ staph.
291│ 18│Broncho │Lt. base │Advanced │B. inf.,
│ │ │ │ dilatation │ staph.
296│ 18│Abscess │Lt. base │Dilatation │S. hem., B.
│ │ │ │ │ inf.,
387│ 19│Abscess │Rt. and lt. │Advanced │S. hem., B.
│ │ │ lungs │ dilatation │ inf., S.
│ │ │ │ │ aur.
│ │ │ │ │ Pneum.
│ │ │ │ │ II.
421│ 19│Chronic │Rt. lung │Advanced │
│ │ broncho │ │ dilatation │
440│ 19│Chronic │Rt. and lt. │Spherical │B. inf., S.
│ │ broncho │ lungs │ │ aur.
419│ 20│Broncho │Rt. lung │Dilatation │Pneum. II,
│ │ │ │ │ B. inf.
463│ 20│Chronic │Rt. and lt. │Spherical │B. inf.,
│ │ broncho │ lungs │ │ staph.,
│ │ │ │ │ Pneum. IV
431│ 23│Chronic │Lt. base │Dilatation │
│ │ broncho │ │ │
468│ 23 ?│Lobar and │Lt. lung │Dilatation │S. aur., B.
│ │ broncho │ │ │ inf., S.
│ │ │ │ │ vir.
465│ 25 ?│Broncho │Lt. base │Dilatation │S. hem., B.
│ │ │ │ │ inf.,
│ │ │ │ │ staph.,
│ │ │ │ │ S. vir.
445│ 27│Broncho │Lt. lower lobe│Spherical │S. aur.
449│ 27│Abscess │Rt. and lt. │Spherical │S. hem., B.
│ │ │ lungs │ │ coli.
378│ 28│Abscess │Lt. base │Cylindrical │S. hem., B.
│ │ │ │ │ inf.,
│ │ │ │ │ Pneum.
│ │ │ │ │ atyp. II.
473│ 28│Chronic │Lt. lung │Advanced │B. inf., S.
│ │ broncho │ │ dilatation │ vir.,
│ │ │ │ │ staph.,
│ │ │ │ │ M.
│ │ │ │ │ catarr.
425│ 29│Abscess │Rt. and lt. │Cylindrical │
│ │ (staph.) │ lungs │ │
467│ 30│Abscess │Rt. lower lobe│Spherical │S. hem., B.
│ │ │ │ │ inf.
472│ 37│Chronic │Rt. and lt. │Advanced │B. coli
│ │ broncho │ lungs │ dilatation │
487│ 55│Abscess │Rt. and lt. │Cylindrical │B. inf. S.
│ │ │ lungs │ │ hem.
───────┴────────┴─────────────┴──────────────┴──────────────┴───────────

The bacteriology of autopsies with bronchiectasis is shown in Table LII.

TABLE LII

════════╤════════╤═════════════════╤═════════════════ │ NO. │ │ │EXAMINED│ PNEUMOCOCCUS │ S. HEMOLYTICUS ────────┼────────┼────────┬────────┼────────┬──────── │ │ NO. │PER CENT│ NO. │PER CENT │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE ────────┼────────┼────────┼────────┼────────┼──────── Bronchus│ 29│ 9│ 31.0│ 15│ 51.7 Lung │ 37│ 16│ 43.2│ 18│ 48.6 Blood │ 50│ 12│ 24.0│ 22│ 44.0 ────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════ │ │ │ STAPHYLOCOCCUS │ B. INFLUENZÆ ────────┼────────┬────────┼────────┬──────── │ NO. │PER CENT│ NO. │PER CENT │POSITIVE│POSITIVE│POSITIVE│POSITIVE ────────┼────────┼────────┼────────┼──────── Bronchus│ 16│ 55.2│ 23│ 79.3 Lung │ 10│ 27.0│ 19│ 51.4 Blood │ │ │ │ ────────┴────────┴────────┴────────┴────────

Comparison of the percentage incidence of the organisms which have to be found associated with bronchiectasis and with purulent bronchitis unaccompanied by bronchiectasis shows that there is no noteworthy difference in the occurrence of pneumococci, hemolytic streptococci or B. influenzæ within the bronchi. When allowance is made for the difficulty of demonstrating B. influenzæ in the presence of a large number of other microorganisms, it is not improbable that this organism has been constantly present in the purulent contents of the bronchi with purulent bronchitis, with and without bronchiectasis. Pneumococci, streptococci and staphylococci are each present in the bronchi in about one-half of the instances of bronchiectasis and mixed infections are very common, S. viridans, B. coli and M. catarrhalis being occasionally found in the bronchi. The table shows that pneumococci, streptococci and staphylococci show no greater tendency to enter the lungs and blood when bronchiectasis and purulent bronchitis coexist than with purulent bronchitis alone.

Moderate dilatation of the small bronchi at the base of the left lung was found in several instances eight days after onset of symptoms referable to the respiratory passages. Advanced, diffuse dilatation of the bronchi was seldom seen before the lapse of two weeks, and bronchiectasis with formation of spherical or cylindrical cavities was found with few exceptions three weeks after onset of the fatal illness. Long continued, purulent bronchitis does not necessarily produce dilatation of the bronchi. It is noteworthy that the average duration of the fatal illness in 137 instances of pneumonia and purulent bronchitis with no bronchiectasis was 12.5 days, whereas the average duration of 49 instances of pneumonia with purulent bronchitis and bronchiectasis was only 16.5 days.

Bronchiectasis is almost invariably associated with purulent bronchitis in which tenacious mucopurulent fluid accumulates in the bronchi. It begins at the bases of the lower lobes and is usually more advanced here than elsewhere. Mechanical distention of the small bronchi by viscid fluid, expelled with difficulty, brings about their dilatation and gravity appears to have a part in accentuating the process. Histologic examination of the changes accompanying bronchitis show that lesions which penetrate into the muscular layer and presumably weaken the bronchial wall are not uncommon and partial or complete destruction of the wall may result. To what extent infiltration of the muscular wall by polynuclear leucocytes or by lymphoid and plasma cells is accompanied by changes which weaken the wall may be questioned. When the epithelial lining of the bronchus is destroyed coagulative necrosis of the underlying tissue occurs and may extend a variable distance into the bronchial wall, not infrequently penetrating into or entirely through the muscular layer. These changes furnish an explanation of the occurrence of bronchiectasis following influenza.

Fig. 17.—Acute bronchiectasis showing fissures penetrating into
bronchial wall and at one place entering surrounding alveolar
tissue; the surrounding alveoli are filled with fibrin. Autopsy 425.
]

Acute bronchiectasis may be found following influenza after the illness has lasted eight or ten days. There is no increase of fibrous tissue. Small bronchi with no cartilage, which in normal lungs have a diameter approximating 1 mm., are dilated to 3 mm. or more. The surface epithelium is wholly or partially lost. Necrosis occurs in places and extends deep into the tissue, destroying muscle and often penetrating the entire thickness of the wall which in these small bronchi consists in large part of fibrous tissue containing greatly engorged blood vessels. In this necrotic material nuclei are absent and the tissue containing fibrin stains deeply with eosin. In it occur fissures or tears which extend from the lumen a variable distance, very frequently penetrating the entire thickness of the wall and entering adjacent alveoli (Figs. 17 and 19). Alveoli thus exposed almost invariably contain plugs of dense fibrin. Where these rents have occurred, adjacent edges of the bronchial wall, held together by underlying lung tissue, have separated from one another, so that the circumference of the bronchus has been increased (Fig. 18). These breaks in the continuity of the wall may occur in several places, so that a fourth or a third of the circumference may be formed by exposed alveolar tissue which has become the site of fibrinous pneumonia (Fig. 20). During life, though the inflamed bronchus is filled by mucopurulent exudate, distention of loose alveolar tissue, uniting the interrupted bronchial wall, is doubtless greater than it appears in the lung fixed by hardening fluids.

Fig. 18.—Acute bronchiectasis showing fissures in the bronchial wall
extending into neighboring alveoli which in zone about are filled
with fibrin; one fissure has separated widely; peribronchial
fibrinous pneumonia (fibrin is black). Autopsy 425.
]

Recently dilated bronchi have an irregularly stellate lumen as the result of clefts penetrating at intervals into or through the bronchial wall (Fig. 26). Longitudinal fissures mark the lining of these dilated bronchial tubes.

When the fatal illness has lasted more than two weeks, abundant new formation of fibrous tissue occurs in a zone surrounding the dilated bronchus. Adjacent alveolar walls are thickened by young fibrous tissue. Alveoli, much diminished in size, are filled by hyaline fibrin into which fibroblasts and newly formed blood vessels have penetrated. These changes are limited to a wide zone in immediate contact with the dilated bronchus, whereas at a greater distance alveolar walls have undergone no thickening and alveoli contain no fibrin.

Fig. 19.—Acute bronchiectasis; the bronchial wall indicated by
engorged mucosa shows a varying degree of destruction, fissures
extending into and through the bronchial wall. Autopsy 352.
]

Fig. 20.—Acute bronchiectasis; with destruction of bronchial wall
exposing alveoli filled with fibrin; peribronchial fibrinous
pneumonia is seen about several bronchi present in the section; Gram
Weigert fibrin stain. Autopsy 425.
]

This stage is well represented by Autopsy 421 after an illness of nineteen days. Bronchiectatic cavities, from 3 to 6 mm. in diameter, are numerous in sections of the lung; their lumina are irregular in outline and often irregularly stellate. Microscopic examination shows the presence of clefts which interrupt the bronchial wall at intervals throughout its entire circumference. The original wall is well indicated by the very richly vascularized connective tissue containing scattered muscle bundles and is infiltrated with lymphoid and plasma cells in great number. Where fissures have occurred the adjacent edges of the interrupted wall have separated from one another, leaving a wide interval where underlying alveolar tissue is exposed. Two changes tend eventually to render the fissures inconspicuous, namely, regeneration of epithelium and new formation of fibrous tissue. Exposed alveoli filled with fibrin are in process of organization and epithelium which has assumed a squamous type has grown down over the exposed surfaces of the interrupted bronchial wall. It has begun to cover or in some instances has completely covered the surface of rents entering alveoli plugged with fibrin (Fig. 21). In the periphery of the bronchus alveolar walls are thickened and infiltrated with lymphoid and plasma cells. The same changes affect bronchi containing cartilage which is undergoing atrophy.

The reinforcement of the fissured bronchial wall by new formation of fibrous tissue, by thickening of the interalveolar walls and by organization of fibrin within the alveoli is well shown after four weeks (Autopsy 425; Fig. 28). There are spherical bronchiectatic cavities more than a centimeter in diameter surrounded by a dense fibrous wall in which are atrophied alveoli lined by epithelium of cubical form. Occasionally, the fibrous wall is interrupted and alveoli, plugged with organizing fibrin, are in immediate contact with the lumen. When these plugs of fibrin which are slowly absorbed disappear, evidence of preexisting rents in the bronchial wall are lost, and there are in this lung bronchiectatic cavities of which the wall is a continuous circle of dense fibrous tissue.

Fig. 21.—Bronchiectasis with fissures extending through the bronchial
wall into alveolar tissue which is the site of fibrinous pneumonia;
epithelium has grown down into these fissures and has covered the
exposed surfaces. Autopsy 463.
]

Fig. 22.—Regeneration of epithelium over fissures which have been
formed in the wall of a bronchus; the epithelium in the neighborhood
of and within the fissure is squamous.
]

Epithelium lining the dilated bronchi is at times completely destroyed (Fig. 28), but more frequently it persists in part. That which remains has almost constantly the character of squamous epithelium (Figs. 22 and 23). The lowermost cells are cubical; those above them are polygonal, tending to become flatter as the surface is approached; upon the surface are cells often much flattened and occasionally they have lost their nuclei and stain deeply with eosin as the result of superficial necrosis. The change should not be regarded as metaplasia, for the epithelium assumes this squamous type when the superficial columnar cells have been lost. Actual necrosis of superficial ciliated columnar cells is occasionally seen (Autopsy 352); injured cells have separated from one another and desquamated into the lumen of the bronchus. The epithelium which remains after the superficial cells are lost consists of cells which become flatter from base to surface, but the intercellular bridges characteristic of the epithelium of the skin are not found. When epithelium is in process of regeneration, a layer gradually diminishing in thickness extends over the denuded surface, the advancing edge being formed by very flat cells in a single layer. The epithelium growing into fissures which have penetrated the bronchial wall may completely cover the exposed alveolar tissue. The newly formed epithelium may follow a fissure into an alveolus which has been opened and come into contact with the fibrin which fills the alveolus.

Fig. 23.—Squamous epithelium growing over the defect in the bronchial
wall shown in Fig. 22 more highly magnified; squamous epithelium is
present above and columnar epithelium below.
]

Bronchiectasis usually affects the small bronchi with no cartilage. It is not uncommon to find greatly dilated bronchi with no cartilage in close proximity to cartilage containing bronchi of smaller caliber. In one instance (Autopsy 421) a bronchus of medium size with cartilage measured 3 mm. in diameter, whereas two bronchi with no cartilage were dilated to 4 and 6 mm., respectively. Nevertheless, larger bronchi are occasionally the site of superficial loss of epithelium, necrosis extending into the bronchial wall, formation of fissures and stretching of the wall at the spot which is weakened. In association with these changes atrophy of the cartilage may occur (Autopsies 421, 425, 440, 463). Plates of cartilage in process of atrophy are readily recognized by their irregularly indented outline and often by their small size. The fibrous tissue surrounding the cartilage is the site of chronic inflammation and is densely infiltrated with lymphoid and plasma cells among which polynuclear leucocytes are scant. Nevertheless, polynuclear leucocytes are abundant in immediate contact with the cartilage and appear to have an important part in the solution of its matrix, for about them occur indentations of the edge. Leucocytes penetrate into the cartilage.

The necrosis and tears which occur in the wall of the bronchus are not always limited to the bronchus, but may extend deeply into the surrounding tissue. In Autopsies 312 (Fig. 21) and 423 wide areas of necrosis have penetrated deeply into the tissue about the bronchi.

=Autopsy 312.=—Illness began with influenza on September 26,
seventeen days before death; a diagnosis of lobar pneumonia with
consolidation of the right lower lobe was made ten days after onset
and Pneumococcus IV, B. influenzæ and S. hemolyticus were found in
the sputum. At autopsy there was bronchopneumonia with red and gray
lobular and confluent lobular patches of consolidation and right and
left serofibrinous pleurisy; there was purulent bronchitis; no
abscesses were seen. Small bronchi throughout both lungs were
dilated and often surrounded by a zone of hemorrhage.

Hemolytic streptococci were found in the heart’s blood, in the
pleural exudate, consolidated lung and bronchus; B. influenzæ was
found in the lung and in a small bronchus, and staphylococci in the
contents of a small bronchus.

Fig. 24.—Acute bronchiectasis with fissures extending through
bronchial wall which is marked by great engorgement of blood
vessels; at one point a fissure has penetrated deep into the
alveolar tissue and formed a small cavity containing purulent
exudate and surrounded by fibrinous pneumonia. Autopsy 312.
]

Bronchi which are the site of acute inflammation have lost their
epithelium wholly or in part, and deep fissures penetrate the entire
thickness of the bronchial wall, extending into the surrounding lung
tissue which is the site of fibrinous pneumonia. In some instances
plugs of fibrin within the alveoli are bisected by these tears.
There is some superficial necrosis along the edge of each fissure,
in several places extending outward from defects in the walls of
small bronchi dilated to approximately 1.5 mm. There are wide
patches of necrosis affecting both alveolar walls and contents of
alveoli and extending 2 mm. into the lung tissue. When a fissure has
penetrated from the lumen of the bronchus into necrotic tissue (Fig.
21), polynuclear leucocytes have accumulated within the necrotic
tissue, disintegration of tissue occurs, and a small cavity
communicating with the bronchus is formed.

=Autopsy 423.=—C. H., white, aged twenty-five, resident of Oklahoma,
had been in military service one month. Death occurred sixteen days
after onset of influenza.

=Anatomical Diagnosis.=—Chronic bronchopneumonia with
peribronchiolar consolidation throughout right lung and in left
lower lobe; right purulent pleurisy; purulent bronchitis;
bronchiectasis at base of left lung.

The right lung weighs 1,260 grams; in the upper lobe are yellowish
gray nodules having the appearance of tubercles clustered about
small bronchi; in places similar nodules occur upon a background of
pinkish gray consolidation occupying the greater part of the lower
lobe. Bronchi contain purulent fluid. The left lung weighs 760
grams; it is edematous and small, yellowish gray nodules of
consolidation in the lower lobe are clustered about terminal
bronchi. Bronchi at the base of the lower lobe are dilated.

Bacteriologic examination shows the presence of hemolytic
streptococci in the blood of the heart; hemolytic streptococci and
B. influenzæ in the lung.

Microscopic examination shows that the walls of the bronchi are
infiltrated with lymphoid and plasma cells; these cells are very
numerous in peribronchiolar patches of consolidation. A small
bronchus 1 mm. in diameter has squamous epithelium along one side;
on the opposite side, the wall is completely absent and there is
superficial necrosis of exposed alveoli filled with fibrin. A deep
fissure passes from the bronchus into the consolidated tissue; its
edges are necrotic and it is filled with polynuclear leucocytes. A
small cavity in contact with the bronchus has been formed. In
another part of the lung a distended bronchus has lost its
epithelium on one side, and here alveoli filled with fibrin form the
wall of the bronchus which is filled with leucocytes. Extending
outward from the eroded wall is a focus of necrosis where both
alveolar walls and contained exudate have lost their nuclei.

The necrosis which has had its origin in the bronchi is soon followed by accumulation of polynuclear leucocytes, softening and disintegration of tissue. Discharge of the disintegrated tissue through the bronchi results in the formation of a small cavity continuous with the bronchus. These changes are well illustrated by the bronchiogenic abscesses which have been described elsewhere (Autopsies 376, p. 206, and 387, p. 206). When disintegrated tissue is discharged by way of the bronchi no accumulation of pus occurs, but cavities will be formed, in part by dilation of bronchi, in part by erosion of the adjacent lung tissue. Histologic examination shows that these changes have produced the advanced bronchiectasis found in Autopsy 445 (Fig. 25).

=Autopsy 445.=—W. F., white, aged twenty-three, from Mississippi,
had been in military service one month. His illness began September
22, twenty-seven days before death, with severe coryza, weakness,
nausea and vomiting; great pain in bones, cough and sore throat. He
was admitted to the base hospital one week later with diagnosis of
influenza and bronchitis. On October 3, sixteen days before death,
signs of consolidation were found on the left side over the back and
a diagnosis of lobar pneumonia was made. On October 18 there was
severe headache, pupils were dilated, and there was rigidity of
neck; lumbar puncture was made and pneumococci were found in the
fluid obtained. Death occurred on the following day.

=Anatomic Diagnosis.=—Bronchiectasis with unresolved pneumonia
limited to the left lower lobe; acute bronchopneumonia with
peribronchiolar consolidation in right lung; purulent bronchitis,
peribronchial hemorrhage and organizing bronchiolitis in right lung;
adherent pleura on left side; purulent meningitis.

The left upper lobe is crepitant throughout. The outer and posterior
two-thirds of the left lower lobe is riddled with cavities often
rounded and varying in diameter from 0.5 to 3 cm. but not
infrequently irregular in shape and in communication with adjacent
cavities (Fig. 25). In places cavities pass in a tortuous course
from pleura to the midpart of lung. The lining of these cavities is
usually smooth, but in places is covered by gray necrotic material.
Communication between the cavities and medium-sized bronchi is
occasionally found. The lung tissue between the cavities is in part
grayish red and consolidated, in part pink and air containing. The
right lung is edematous throughout; the bronchi in the lower part of
the right lung contain purulent fluid and are in places surrounded
by zones of hemorrhage.

The spleen is very large (14 × 11 × 5 cm.) and firm.

The spinal fluid is cloudy and blood vessels over the lumbar
enlargement and lower thoracic region are congested; in the upper
thoracic region the cord is covered by purulent exudate.

Bacteriologic examination demonstrates the presence of hemolytic
streptococci in the blood of the heart; plates from the left lung
contain a few colonies of S. aureus and Pneumococcus IV; plates from
the right main bronchus contain S. aureus and a large bacillus which
does not stain by Gram’s method. Three plates from the spinal
meninges contain Pneumococcus IV.

Fig. 25.—Advanced bronchiectasis throughout lower left lobe. Autopsy
445.
]

Microscopic examination shows that the cavities which have been
described are lined by very vascular connective tissue containing
many cells; there is no epithelial lining and the surface is in
places covered by fibrin. On the surface polynuclear leucocytes are
numerous, but immediately below, large mononuclear cells occur and
frequently contain one or several ingested polynuclear leucocytes.
None of the structures peculiar to the bronchi can be identified in
the wall of these cavities, and in many places it is evident that
lung tissue has undergone destruction, for in places the lining of
vascular connective tissue is interrupted and an extension of the
cavity penetrating into the lung substance is surrounded by alveoli
filled with fibrin; in contact with the cavity there is some
necrosis.

The cavities communicate with the bronchi and are lined in part by vascular connective tissue which may in part represent preexisting bronchial walls, but no epithelium is present and the relation to the bronchi cannot be established with certainty. These cavities have extended by necrosis which has broken the vascular connective tissue of their wall and penetrated into adjacent lung tissue. Death has been the result of purulent meningitis caused by pneumococcus, and the histologic changes in the walls of the cavities suggest that the activity of the inflammatory reaction here is subsiding, for large mononuclear cells are numerous and are ingesting polynuclear leucocytes. The changes described would, if continued, result in the formation of cavities lined by fibrous tissue and resembling many of those formed as the result of dilatation of the bronchi.

A study of the progress of the changes which result in the formation of bronchiectatic cavities has shown how the inflammatory irritant within the bronchus destroys the epithelium of the bronchus, penetrates into the deeper tissues and produces fissures which extend through the entire thickness of the bronchial wall at one or usually several places. These longitudinal fissures, which at first often give a stellate outline in cross section to the cavity of the affected bronchus, permit the separation of the edges of the fissure, so that an increase in the circumference occurs. The base of the fissure is formed by surrounding alveolar tissue and its edges are the site of necrosis. Tears may extend into the surrounding alveolar tissue, thus permitting further stretching of the bronchial wall. The consequences of rupture of the small bronchi into the adjacent alveoli are to some extent overcome by the inflammatory reaction which plugs the adjacent alveoli with fibrin.

Compression of the lungs by forced expiration, even though the glottis were closed as in coughing, would not dilate the bronchi, because pressure outside and within the bronchi would be equally elevated (Thornton and Pratt[89]). The pressure within the bronchi does not differ greatly from atmospheric pressure, whereas the negative pressure within the pleural cavity may vary from approximately 6 mm. of mercury during quiet inspiration to 30 mm. with forced inspiration. Excess of pressure upon the inner surface of the bronchial walls will vary with coughing and other respiratory efforts, between these limits depending upon the readiness with which pressure is equalized within and without the bronchi by penetration of air into the alveoli. The presence of viscid mucopurulent fluid within bronchioles will obstruct these tubules and retard the entrance of air into alveoli.

Weakening of the bronchial wall by the changes which have been described will cause lasting dilatation of the bronchi. Whatever increases pressure within the bronchi will increase the tendency to dilatation; the bronchi being filled with mucopurulent exudate dilatation usually appears first at the bases of the lung, since gravity increases intrabronchial pressure here. New formation of fibrous tissue within the wall of the bronchus, thickening of adjacent alveolar walls, and organization of fibrin reinforce the weakened bronchial wall and limit the dilatation which follows injury to the wall. Regeneration of epithelium covering the dilated tube will further obscure the early changes which have made dilatation possible. The changes which weaken the bronchial wall permit dilatation at a time when there is no new formation of fibrous tissue. When the bronchial lesion has persisted several weeks, chronic pneumonia is associated with it. It has been suggested that the contraction of newly formed fibrous tissue within the substance of the lung might cause bronchi to be enlarged by traction upon their walls. Newly formed connective tissue is most abundant in the wall of the bronchiectatic cavity, and here contraction would tend to diminish the size of the cavity.

Unresolved Bronchopneumonia

Chronic bronchopneumonia is characterized by changes similar to those associated with chronic inflammation in other parts of the body, namely, by thickening of the interstitial tissue of the lung, by accumulation of mononuclear cells, by proliferation of fibrous tissue and by organization of exuded fibrin. In a few instances these changes have begun at the end of two weeks after onset of influenza, but they have been little advanced until three weeks has elapsed; advanced chronic inflammation has occurred after from four to eight weeks. Chronic inflammation primarily affects those structures which are most severely injured by the acute lesion and is most conspicuous in immediate proximity to the small bronchi and bronchioles; the perivascular and interlobular connective tissue are secondarily involved. Corresponding to each of the lesions of the alveolar tissue which have been found with bronchopneumonia, namely, peribronchiolar, hemorrhagic peribronchiolar, lobular and peribronchial consolidation, there is a chronic lesion which develops when pneumonia has failed to resolve.

The term interstitial bronchopneumonia has been used by MacCallum to designate a lesion which he has found in association with measles at Fort Sam Houston. This name he states does not describe accurately the early stage of the lesion, for its interstitial character is not evident at first. In his monograph on “Epidemic Pneumonia in the Army Camp,” published in 1919, MacCallum describes and pictures instances of the lesion which we have designated interstitial suppurative pneumonia and classifies them as interstitial bronchopneumonia. We have shown that this lesion, which is the result of infection of the lymphatics with S. hemolyticus, bears no necessary relation to the lesion which is characterized in its early stage by peribronchiolar pneumonia and in its later stages by chronic inflammation with mononuclear infiltration and proliferation of the peribronchial, perivascular and interalveolar tissue. At Fort Sam Houston, nearly every patient with measles was infected with hemolytic streptococci; we observed, following influenza, similar prevalence of hemolytic streptococci in certain wards in the base hospital at Camp Pike. Among the cases at Fort Sam Houston there were doubtless instances both of interstitial suppurative pneumonia caused by hemolytic streptococcus and of chronic bronchopneumonia not referable to this microorganism.

Studying pneumonia following influenza at Camp Lee, Va., and later at Camp Dix, N. J., during the fall of 1918, MacCallum reached the conclusion that “interstitial bronchopneumonia” following influenza was caused by B. influenzæ of Pfeiffer. This lesion attributed to B. influenzæ differed from that previously referred to hemolytic streptococcus in the following characters: the lymphatic channels in the bronchial walls and widened interlobular septa are inconspicuous and none are found distended with exudate; there is no intense infection of the pleura, and polynuclear leucocytes are inconspicuous in the alveolar exudate and in the walls of the bronchi. It seems probable these differences are explained by the absence of hemolytic streptococci which tend to invade lymphatics and produce severe inflammatory changes in the pleura.

=Chronic Bronchitis.=—The earliest changes in the bronchial wall with bronchitis of influenza are hyperemia, leucocytic infiltration and hemorrhage, and they may occur even though the lining epithelium remains intact. Epithelium frequently undergoes partial or complete destruction, and with this severe injury the influence of the inflammatory irritant may extend directly through the wall of the bronchus, for in some instances there is hemorrhage into all the alveoli in a zone encircling the bronchus. Since these alveoli have only indirect communication with the affected bronchus through alveolar tissue not involved in the inflammatory process, it is evident that the surrounding hemorrhage is secondary to the lesion of the bronchus. Fibrinous inflammation in other instances, similarly localized in a zone of alveoli encircling a bronchus, is doubtless the result of direct extension of the inflammatory process through the bronchial wall. After the disease has existed during two or three weeks inflammation is still active immediately below the inner surface of the bronchus; here polynuclear leucocytes are numerous whereas in the deeper parts of the mucosa and about the muscularis leucocytes are scant but lymphoid and plasma cells are very numerous. The severity of the inflammatory reaction may be judged by the abundance and extent of this cellular reaction and is in close relation to the intensity of the changes affecting the mucous membrane of the bronchus. Infiltration of the entire bronchial wall with lymphoid and plasma cells is almost invariable when the primary injury to the bronchus has destroyed the epithelial lining, and this infiltration is not limited to the bronchial wall but extends outward into the contiguous alveolar septa which are thickened by it. The sheath of the pulmonary artery which accompanies the bronchus exhibits a similar change, and the alveolar septa, as a fringe about it, are thickened and infiltrated with mononuclear cells. Interlobular septa continuous with the bronchus often show some infiltration.

A later phase in this series of changes is represented by new formation of fibrous tissue. The bronchial walls and interalveolar septa are thickened by proliferating fibrous tissue, young fibroblasts and newly formed collagen fibrils being abundant (Fig. 28; also Fig. 30). This increase of fibrous tissue is especially noteworthy immediately surrounding the walls of the small bronchi, which are often considerably dilated, and about the smaller of those bronchi which have cartilage; with thickening of alveolar walls immediately adjacent to the bronchus every stage in the obliteration of the alveoli may be found. Their walls are thickened and their lumina are diminished in size and often flattened in a direction concentric with the bronchus. Such atrophied alveoli lined by cubical epithelial cells occurring within the thickened peribronchial fibrous tissue give evidence that this tissue has replaced alveoli. Alveoli surrounding and within the new fibrous tissue are frequently filled with fibrin, and organization indicated by penetration of fibroblasts and capillaries into the fibrin may be far advanced. There is some increase of perivascular and interlobular tissue. The bronchiectasis which is almost invariably found with unresolved bronchopneumonia has been described. Squamous transformation of epithelium (page 251) is frequently found in association with the chronic bronchitis of unresolved pneumonia.

=Organizing Bronchitis and Bronchiolitis.=—When the bronchial epithelium is destroyed, fibrin is deposited upon the denuded surface and may partly or completely fill the lumen of the bronchial tube. The plug of fibrin is adherent to the underlying tissue wherever epithelium is lost but is separated from the bronchial wall by a well-defined space where epithelial lining is still intact. Fibroblasts promptly migrate from the wall of the bronchiole into this fibrin, and fibroblasts, fixed during ameboid movement, are irregularly elongated in a direction toward the fibrin.

Organization of fibrin occurs within the smallest bronchi (diameter 0.3 to 0.5 mm.) or within respiratory bronchioles. It has been found in 8 autopsies. In one instance it has been present eleven days after the onset of influenza, but usually it is seen three or four weeks after onset of symptoms of respiratory disease. In the early stages of the lesion a plug of fibrin within the lumen of the bronchus or bronchiole is invaded by fibroblasts, plasma cells and newly formed capillaries. These capillaries have their origin in the wall of the tube and enter the fibrin at points where in consequence of loss of epithelium fibrin is continuous with the connective tissue. When the bronchiole is cut longitudinally, partially or completely organized fibrin may be found adherent at several places with intact epithelium, sometimes beautifully ciliated, between the sites of attachment. The fibrin is finally replaced completely and the lumen of the bronchiole contains a mass of organized fibrous tissue in which young fibroblasts and plasma cells are numerous.

The lesion has been associated with chronic bronchopneumonia in 6 of 8 instances. In Autopsy 445, p. 257, organizing bronchitis and bronchiolitis occurred in the right lung unassociated with other chronic lesion, although there was advanced bronchiectasis with fibrous induration in the left lung. In Autopsy 499 (p. 224) organizing bronchiolitis occurred in association with chronic changes which appear to have followed interstitial suppurative pneumonia caused by S. hemolyticus. Other severe lesions of the bronchi have accompanied organizing bronchitis and bronchiolitis. Purulent bronchitis has been present in 7 of 8 instances; bronchiectasis in 5 of 8 instances.

The bacteriology of autopsies with organizing bronchitis and bronchiolitis is shown in Table LIII.

The bacteriology of these cases presents no constant feature. Invasion of the blood by S. hemolyticus has been present in a large proportion of cultures, namely, in 5 of 7 (71.4 per cent). In one of the 2 instances in which hemolytic streptococci have been found, neither in the blood nor lungs, Pneumococcus III has been found in the blood and S. viridans in the lungs and bronchus; in the other, S. aureus has been found in the lung and bronchus. Staphylococci have been found frequently in the bronchi (60 per cent) and in the lungs (50 per cent). B. influenzæ has been present in the bronchi in the usual proportion of instances (80 per cent). The lesion has occurred in the presence of B. influenzæ combined with streptococci or staphylococci.

TABLE LIII

═══════════╤══════════════╤══════════════╤══════════════╤══════════════
AUTOPSY │ DURATION OF │ BLOOD │ LUNGS │ BRONCHUS
│ ILLNESS │ │ │
───────────┼──────────────┼──────────────┼──────────────┼──────────────
420 │11 days │S. hem. │S. hem., B. │
│ │ │ inf., S. │
│ │ │ aur. │
402 │14 days │Pneum. IV, │ │
│ │ S.hem. │ │
370 │17 days │ │S. aur. │S. aur.,
│ │ │ │ Pneum. IV,
│ │ │ │ B. inf.
457 │17+ days │ │ │Pneum. IV, B.
│ │ │ │ inf.
421 │19 days │S. hem. │Pneum. IV, S. │
│ │ │ hem. │
445 │27 days │S. hem. │Pneum. IV, S. │S. aur.
│ │ │ aur. │
473 │28+ days │Pneum. III │S. vir. │B. inf., S.
│ │ │ │ vir.,
│ │ │ │ staph., M.
│ │ │ │ catarr.
499 │36 days │S. hem. │ │S. hem. B.
│ │ │ │ inf.
───────────┴──────────────┴──────────────┴──────────────┴──────────────

Thrombosis of lymphatics in the wall of bronchi adjacent to blood vessels and in interlobular septa occurs, and occasionally organization of the fibrinous plug within the lymphatic is in progress (Autopsies 283, 425 and 463). Fibroblasts and capillaries penetrate from the wall of the lymphatic into a mass of hyaline fibrin which fills the lumen.

=Unresolved Bronchopneumonia.=—The most common type of pneumonic lesion following influenza is characterized by acute inflammation of the alveoli immediately adjacent to the bronchioles and the lesion is associated in many instances with hemorrhage or edema. If this lesion persists unresolved during several weeks, evidences of chronic inflammation are found. Peribronchial, perivascular and interlobular connective tissue is thickened and richly infiltrated with lymphoid and plasma cells, large mononuclear cells and many young fibroblasts. Interalveolar septa adjacent to the walls of bronchi and between alveoli surrounding inflamed bronchioles are implicated in the process. Interstitial changes characterize the lesion only in its late stage. It appears undesirable to give the name “interstitial pneumonia” to the early stage of a lesion which begins and in most instances terminates as an acute relatively superficial inflammation of the bronchi, bronchioles and peribronchiolar alveoli.

Chronic bronchopneumonia is often overlooked at autopsy because newly formed connective tissue is not present in sufficient quantity to attract attention (Fig. 26). When the lesion is advanced conspicuous gray white patches of fibrous tissue may be seen about the bronchi (Autopsy 487; Fig. 27) and interlobular septa may be obviously thickened (Autopsy 472). The most distinctive feature of the lungs is the presence of small, firm, gray or yellowish gray nodules of consolidation which resemble miliary tubercles. They represent the peribronchiolar patches of bronchopneumonia present during the acute stage and have assumed the well-defined outline and firm consistence of tubercles because polynuclear leucocytes and red blood corpuscles have in large part disappeared, interstitial tissue is increased, and exudate is in process of organization. These nodules are grouped in clusters about the small bronchi.

With unresolved bronchopneumonia the lungs are very voluminous and fail to collapse after they are removed from the chest and in some instances even after incision. The air containing tissue is usually dry. In our autopsies the lungs have been pink in color and often free from coal pigment, because those suffering with pneumonia have been in considerable part men from rural districts. Thick mucopurulent material exudes from the small bronchi which have been cut across; purulent bronchitis has been present in 20 of 21 instances of chronic bronchopneumonia. Bronchiectasis has been present in 13 instances; dilatation is often advanced, so that throughout the lungs are found bronchi with no cartilage distended to a diameter of 0.5 cm. In addition to the firm peribronchiolar tubercle-like nodules of consolidation there are scattered patches of gray lobular or confluent lobular consolidation. Yellowish nodules, grouped about bronchi and resembling those found elsewhere in air containing tissue, are occasionally seen scattered upon the cut surface of a patch of gray, confluent lobular consolidation (Autopsies 421, 423, 431).

Fig. 26.—Unresolved bronchopneumonia with tubercle-like nodules of
peribronchiolar consolidation best seen in lower lobe;
bronchiectasis. Autopsy 425.
]