Chapter IV: The Pathology and Bacteriology of Pneumonia Following Influenza (8)

Microscopic examination demonstrates the presence of those changes which have been described in association with chronic bronchitis and bronchiectasis. There is abundant new formation of fibrous tissue about the bronchi of small and medium size, thickening of adjacent interalveolar walls and incorporation of alveoli into the thickened bronchial wall (Figs. 27, 28, 30, and 31). In half of the instances of chronic bronchopneumonia there has been peribronchial fibrinous pneumonia, and organization of fibrin within the alveoli is usually well advanced. In one instance (Autopsy 487; Figs. 27 and 28) after an illness of fifty-five days this process has resulted in the formation of conspicuous patches of firm, grayish white fibrous tissue surrounding dilated bronchi. Organization of fibrinous exudate within the lung has not been limited to the alveoli but has occurred in the bronchioles as well. Organizing bronchiolitis has been present in 5 instances (Autopsies 370, 402, 457 and 473).

Increase of fibrous tissue occurs about the blood vessels and in the septa between the lobules, which are infiltrated with mononuclear wandering cells and fibroblasts. Dilatation and thrombosis of the lymphatic vessels have occurred in both situations, and in 3 instances (Autopsies 283, 425 and 463) organization of these fibrinous thrombi has occurred.

Fig. 27.—Unresolved pneumonia with peribronchial formation of fibrous
tissue; bronchiectasis. Autopsy 487.
]

Fig. 28.—Unresolved pneumonia with bronchiectasis showing new
formation of fibrous tissue about a greatly dilated bronchus of
which the epithelial lining has been lost. Autopsy 487.
]

Thickening, cellular infiltration and fibrosis of the bronchial walls with interstitial inflammation and fibrosis of immediately adjacent alveolar septa are found about the ramifications of the bronchial tree and may be followed to the smallest bronchi. When the respiratory bronchioles are reached it will be found that the alveoli which stud their walls are implicated in the change. The fibrin which they contain is infiltrated with lymphoid and plasma cells, and with progress of the lesion is invaded by fibroblasts and capillaries. Infiltration and fibroid thickening extends from the bronchiolar wall to the alveolar septa continuous with it (Fig. 31 with measles). Similar changes occur about the alveolar ducts, and about the orifices of the tributary infundibula (Fig. 32), peribronchiolar foci of acute inflammation having assumed the characters of a chronic inflammatory process. Fibrin within the alveoli contains round cells and fibroblasts. With thickening of alveolar walls the alveolar lumina may be much diminished in size and often persist as spaces lined by cubical cells. Polynuclear leucocytes are usually numerous within the alveolar duct and in a few alveoli immediately adjacent to it, but elsewhere throughout the focus of inflammation round cells are predominant. The changes which have been described correspond with the transformation of ill-defined, gray or reddish gray spots of consolidation grouped about the terminal bronchi into firm sharply defined grayish white nodules having the consistence and appearance of miliary tubercles.

One of the most constant characters of pneumonia following influenza is its hemorrhagic character. In the earlier stages of pneumonia phagocytosis of red blood corpuscles by large mononuclear cells is frequently seen. In association with the chronic changes which have been described, large mononuclear cells filled with brown pigment, doubtless formed from red corpuscles, are often found within the alveoli. These pigment containing cells are similar to those commonly associated with chronic passive congestion of the lungs.

In one instance (Autopsy 457) hemorrhagic peribronchiolar pneumonia has been found in process of organization. The bronchioles and alveoli adjacent to them contain polynuclear leucocytes, but intervening alveoli almost uniformly contain blood and are the site of new formation of connective tissue. Interalveolar septa are thickened and alveoli which are lined by cubical epithelium are often diminished in size. In many places fibroblasts have penetrated in considerable number into the blood within the alveoli and occasionally newly formed capillaries are found within them.

Lobular patches of pneumonia are often found in process of organization (Autopsies 370, 421, 423, 433, 463, 472 and 473). Microscopic examination shows that whole lobules well defined by thickened septa are the site of chronic interalveolar inflammation and intraalveolar organization of exudate, whereas adjacent lobules are air containing and relatively normal. In the earlier stages of the process fibrin present within the alveoli is invaded by fibroblasts, mononuclear wandering cells and blood vessels but in the later stages fibrin has disappeared; the lumina of the alveoli are occupied by cellular fibrous tissue and in places the thickened alveolar walls and intraalveolar fibrous tissue have been fused to form wide patches of new tissue.

With chronic bronchopneumonia confluent lobular consolidation occasionally has a gray ground upon which are scattered small yellow spots clustered about the small bronchi (Autopsies 421, 423 and 431). Microscopic examination has shown that the yellowish spots correspond to dilated bronchioles filled with purulent exudate and surrounded with alveoli containing many polynuclear leucocytes. In the interstitial tissue about the bronchiole and between adjacent alveoli plasma cells are often present in great number. Between these spots of subacute bronchiolar inflammation lung tissue is the site of interalveolar proliferation of fibrous tissue and intraalveolar organization of exudate.

In all instances of chronic bronchopneumonia there has been peribronchial pneumonia in a zone encircling small bronchi with no cartilage and the smallest of the bronchi which have cartilage in their wall; thickening of interalveolar septa, organization of peribronchial fibrinous pneumonia and partial disappearance of alveoli have been described. In the following autopsy peribronchial fibroid pneumonia has been so advanced that conspicuous patches of gray white tissue surrounding bronchi have replaced in some parts of the lung a considerable part of the lung substance.

=Autopsy 487.=—W. C., white, aged twenty-seven years, a farmer from
Mississippi had been in military service twenty-one days. Illness
began on September 17, fifty-five days before death, with chill,
fever, cough, backache, pain in the chest and coryza. The patient
was admitted two weeks after onset with the diagnosis of influenza.
Eight days later his sputum was blood tinged and there were signs of
bronchopneumonia. One month after admission the patient developed a
rash and a diagnosis of scarlet fever was made.

=Anatomic Diagnosis.=—Chronic bronchopneumonia with peribronchial
fibroid induration; bronchiectasis; purulent bronchitis; abscesses
at the bases of both lungs; seropurulent pleurisy on the left side.

The body is much emaciated. The left pleural cavity contains 650
c.c. of opaque, dull yellow, thin, purulent fluid. The surface of
the left lung is covered in spots by white partially organized
fibrin.

On section of the right lung (Fig. 27) the tissue is found in great
part air containing but there are numerous firm, gray patches,
irregular in shape and from 1 to 2 cm. across. In these spots the
tissue is tough and resembles fibrous tissue; within them are much
dilated bronchi. In the central part of the upper lobe is a group of
cavities with smooth wall, the largest of these cavities being 12
mm. in diameter; immediately adjacent are dilated bronchi. Between
and surrounding these cavities is gray tissue, like that described
above. Below the outer surface of the upper lobe is an extensive
area 7 cm. from above downward, thickly studded with bronchiectatic
cavities, in the walls of which there is tough fibrous tissue. In
the middle lobe are several dilated bronchi, the largest of which is
7 mm. in diameter, and elsewhere occur dilated bronchi with
thickened walls. At the base of the lung below the pleura are two
abscesses, which are yellow in the center and surrounded by
hemorrhagic tissue. At the posterior part of the lower lobe there
are numerous firm, nodular, yellowish spots grouped in clusters upon
a background of red, air containing tissue. The bronchi throughout
the lung contain mucopurulent fluid.

In the left lung patches of fibrous tissue are more numerous than on
the right side and are irregular in shape, from 1 to 2 cm. across
and most abundant in the center of the upper lobe. This fibrous
tissue is in great part gray but in places it has a yellowish tinge.
The bronchi everywhere are moderately dilated. At the base of the
lung below the pleura is an abscess.

The other organs show no noteworthy change.

=Bacteriologic Examination.=—The fluid in the left pleura and right
main bronchus contain S. hemolyticus. B. influenzæ is found in the
right lung and right main bronchus.

Microscopic examination shows that the patches of dense fibrous
tissue seen at autopsy almost invariably surround dilated bronchi
with no cartilage in their walls (Fig. 28) and with a diameter of
from 1 to 2 or more millimeters. These bronchi have lost their
epithelial lining; they contain polynuclear leucocytes, and their
wall in contact with the lumen is infiltrated to a varying distance
with the same cells. Their inner surface is very irregular, and
superficial necrosis occurs. The limits of the preexisting bronchial
wall is no longer recognizable in the dense surrounding fibrous
tissue richly infiltrated with lymphoid and plasma cells. In contact
with the bronchus, often in a wide zone, all traces of alveoli have
been destroyed, but further outward alveoli are represented by
spaces lined by cubical epithelium. At the periphery of the zone of
fibroid induration alveolar walls are much thickened and richly
infiltrated with mononuclear wandering cells; the lumina of the
alveoli contain plugs of organized fibrous tissue often covered by
flat or cubical epithelium. In the surrounding tissue a few small
bronchi are lined by columnar epithelium; there is scant new
formation of fibrous tissue but the alveolar walls are thickened and
infiltrated with cells. Epithelium of the larger bronchi with
cartilage in their walls is usually intact and there is about them
little peribronchial inflammation.

Advanced induration about the bronchioles represents a late stage of chronic peribronchiolar pneumonia. A bronchiole cut transversely is found in the center of a focus of induration situated within relatively normal air containing lung tissue. Next the bronchiole which in some instances has wholly or partly lost its epithelium there is very cellular fibrous tissue; further from the bronchiole alveoli are much diminished in size, lined by flat or cubical epithelium and separated by thick cellular walls. Plugs of cellular fibrous tissue sometimes fill the alveolar duct. In favorable sections, cut in a plane which shows the alveolar duct opening out into infundibula, it is found that newly formed fibrous tissue surrounds the alveolar duct and extends into the walls of its tributary alveoli; alveoli may be obliterated by this fibrous tissue. Induration of alveolar walls is evident along the proximal part of the infundibula which are readily demonstrable because they are much dilated. (See Fig. 32.) The distal parts of the infundibula are surrounded by alveoli with delicate walls.

One bronchus retains along one side part of its epithelium which has assumed a squamous form. In other places the wall has undergone necrosis which at one spot extends deeply into the surrounding tissue. Necrotic tissue in another part of the circumference is infiltrated with polynuclear leucocytes and separated from the surrounding tissue by a space filled with leucocytes. An abscess communicating with the bronchus is thus formed.

The foregoing instance is an example of the chronic fibroid pneumonias with bronchiectasis which occur as sequelæ of the epidemic of influenza. It is not improbable that a considerable number of those who suffer with chronic bronchitis and bronchiectasis following influenza have less extensive lesions similar to those which have been described.

=Bacteriology of Unresolved Bronchopneumonia.=—Bacteria found in the bronchi in 10 instances of chronic bronchopneumonia have been as follows:

BACTERIA IN BRONCHI WITH CHRONIC BRONCHOPNEUMONIA

B. coli 1 B. influenzæ and pneumococcus 1 B. influenzæ and S. hemolyticus 2 B. influenzæ and staphylococcus 1 S. hemolyticus and B. coli 1 B. influenzæ, pneumococcus and staphylococcus 3 B. influenzæ, S. viridans and M. catarrhalis 1

Bacteria found in the lungs in 17 instances of chronic bronchopneumonia were as follows:

BACTERIA IN LUNGS WITH CHRONIC BRONCHOPNEUMONIA

B. influenzæ 1 Staphylococcus 1 S. viridans 1 B. influenzæ and pneumococcus 1 B. influenzæ and S. hemolyticus 3 B. influenzæ and staphylococcus 3 Pneumococcus and S. hemolyticus 1 S. hemolyticus and B. coli 2 B. influenzæ, S. hemolyticus and staphylococcus 3 No organism found 1

A noteworthy feature of these lists is the multiplicity of microorganism found, namely, B. influenzæ, S. hemolyticus, pneumococcus, staphylococcus, S. viridans, B. coli, and M. catarrhalis. More than one microorganism is usually found in both bronchus and lung. In the one instance (Autopsy 472) in which B. coli alone has been found in the bronchus, B. coli and S. hemolyticus have been found in the lung and hemolytic streptococcus in the blood; it is evident that B. coli alone has not been responsible for the lesion. In one instance (Autopsy 487) B. influenzæ alone has been found in the lung but hemolytic streptococci have been found in the bronchus, pleura and blood of heart; with S. aureus alone in the lung (Autopsy 370), S. aureus, Pneumococcus IV and B. influenzæ have been found in the bronchus. With S. viridans alone in the lung (Autopsy 473), Pneumococcus III has been found in the pleura and in the blood of the heart and has doubtless had an important part in the production of pneumonia; S. viridans, M. catarrhalis and B. influenzæ have been found in the bronchus in this instance.

No single microorganism is associated with the lesions but combinations of B. influenzæ with hemolytic streptococci or staphylococci are common (over 50 per cent). In Autopsy 422 B. influenzæ and Pneumococcus atypical II have been present in the lungs. Among 10 instances in which cultures have been obtained from the bronchus B. influenzæ is found 8 times, and in the 2 instances in which it has not been identified B. coli has been present. B. influenzæ has seldom been found (Table XXVII) in the presence of B. coli, and it is not improbable that B. coli outgrows and obscures the presence of B. influenzæ.

Table LIV shows the per cent incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzæ in the bronchus, lung and heart’s blood with chronic bronchopneumonia and serves as an index of the readiness with which each of these microorganisms passes from bronchus to lung and from lung to the blood in this disease.

TABLE LIV

═══════════╤══════════════╤══════════════╤══════════════╤══════════════ │ PNEUMOCOCCUS │ HEMOLYTIC │STAPHYLOCOCCUS│ B. INFLUENZÆ │ PER CENT │STREPTOCOCCUS │ PER CENT │ PER CENT │ POSITIVE │ PER CENT │ POSITIVE │ POSITIVE │ │ POSITIVE │ │ ───────────┼──────────────┼──────────────┼──────────────┼────────────── Bronchus │ 40.0│ 30.0│ 50.0│ 80.0 Lung │ 12.5│ 56.2│ 37.5│ 68.7 Blood │ 16.6│ 55.6│ 0│ 0 ───────────┴──────────────┴──────────────┴──────────────┴──────────────

Comparison of Table LIV with the analogous figures for acute bronchopneumonia shows little noteworthy difference. Pneumococci are less frequently found in the lung (12.5 per cent) and in the blood (16.6 per cent) with chronic bronchopneumonia than with acute bronchopneumonia (lung 43.9 per cent; blood, 40.3 per cent). Hemolytic streptococci and staphylococci are not more frequently found with unresolved than with acute bronchopneumonia and failure to resolve cannot be referred to either or to both microorganisms, for bronchopneumonia not infrequently remains unresolved in their absence. B. influenzæ is present in the bronchi in at least 80 per cent of instances and perhaps in all; it is usually combined both in the lungs and in the bronchi with one of the pyogenic cocci.

The severity of the injury to the walls of bronchi resulting in continued infection with a variety of bacteria, appears to be the factor determining failure of resolution and the persistence of bronchopneumonia.

=The Relation of Unresolved Bronchopneumonia to Interstitial Suppurative Pneumonia Caused by Hemolytic Streptococci.=—Hemolytic streptococci have been present in a considerable proportion of those who have had unresolved bronchopneumonia and its occurrence in the bronchi, lung and blood of the heart indicates that it has had an important part in causing death. Unresolved bronchopneumonia, following measles, designated by MacCallum “interstitial bronchopneumonia” in a series of autopsies at Fort Sam Houston in the spring of 1918, was constantly associated with hemolytic streptococci. Among the lesions described as interstitial bronchopneumonia was at least one which was evidently what we have designated interstitial suppurative pneumonia. Lymphangitis was not infrequently found with “interstitial bronchopneumonia” following measles. At Camp Lee and Camp Dix, following the epidemic of influenza, MacCallum found “interstitial bronchopneumonia” with no hemolytic streptococci and noted that lymphatics in the interstitial septa were inconspicuous and that none was found distended with exudate; empyema was not present.

We have shown that interstitial suppurative pneumonia is an acute lesion caused by hemolytic streptococci. Unresolved bronchopneumonia is accompanied by chronic pneumonia and has no necessary relation to this microorganism.

In a foregoing section we have described instances of interstitial suppurative pneumonia unaccompanied by chronic changes, and in the present section we have described instances of unresolved bronchopneumonia with no infection by hemolytic streptococci. We have pointed out that the incidence of streptococcus infection with unresolved bronchopneumonia does not materially differ from that with acute bronchopneumonia even though the greater duration of the disease gives more opportunity for infection. In some of the autopsies made by MacCallum at Fort Sam Houston, lesions of streptococcus infection doubtless coexisted with unresolved bronchopneumonia.

In the 3 autopsies described below, interstitial suppurative pneumonia with empyema caused by hemolytic streptococcus occurs in association with unresolved bronchopneumonia.

=Autopsy 420.=—J. E. S., white, aged thirty-two years, born in
England and resident of Los Angeles, Cal., had been in military
service one month. Onset of illness began on October 3, eleven days
before his death. He was admitted to the hospital on the following
day with the diagnosis of influenza and acute bronchitis. Pneumonia
believed to be lobar was recognized eight days after admission.

=Anatomic Diagnosis.=—Unresolved bronchopneumonia with hemorrhagic
peribronchiolar consolidation in right lung; interstitial
suppurative pneumonia with consolidation in left upper lobe;
fibrinopurulent pleurisy; purulent bronchitis.

The left pleural cavity contains 200 c.c. of turbid yellow fluid in
which are flakes of fibrin. In the inner and upper part of the left
upper lobe there is an area of consolidation where the tissue has a
cloudy, pinkish gray color and is finely granular on section. Here
the interstitial septa are distended by edema, so that they are in
places 0.5 c.c. across; in some spots they have a bright yellow
color. In the posterior parts of the middle and lower lobes there is
flabby consolidation where the tissue has a cloudy, red color with
scattered ill-defined yellow spots.

Bacteriologic examination shows the presence of hemolytic
streptococci in the blood of the heart; hemolytic streptococci with
B. influenzæ and S. aureus in the left lung and S. hemolyticus with
S. aureus in the right lung.

Microscopic examination shows that bronchi, bronchioles, alveolar
ducts and the greater part of the infundibula are filled with
polynuclear leucocytes, whereas the alveoli surrounding these
structures contain fibrin. The walls of the small bronchi are
thickened and contain mononuclear cells; the adjacent alveolar walls
are similarly infiltrated and thickened and the fibrin within them
is undergoing organization, being invaded by plasma cells,
fibroblasts and newly formed blood vessels. In some sections
interstitial septa are distended by edema and contain fibrin in
abundance; in places the tissue contains polynuclear leucocytes
closely packed together. There are lymphatics greatly distended by
polynuclear leucocytes with some fibrin, lymphocytes and red blood
corpuscles.

=Autopsy 428.=—D. B., white, aged twenty-five, a farmer from
Oklahoma, had been in military service three weeks. Onset of illness
was on September 21, twenty-five days before death, with fever,
cough and mucopurulent expectoration. The patient was admitted with
the diagnosis of acute bilateral bronchitis. Four days later
bronchopneumonia was recognized, and subsequently there was otitis
media and empyema; 600 c.c. of thin, purulent fluid were aspirated
from the right chest three days before death.

=Anatomic Diagnosis.=—Unresolved bronchopneumonia; suppuration of
interstitial tissue of upper right and lower left lobes; purulent
bronchitis; fibrinopurulent pleurisy; thoracotomy wound at the base
of the right chest; collapse of both lungs; serofibrinous
pericarditis.

The left pleural cavity contains 550 c.c. of turbid seropurulent
fluid in which are numerous flakes of soft fibrin. The right pleural
cavity contains 150 c.c. of similar fluid. The mediastinum is
edematous. The pericardial cavity contains 50 c.c. of yellow fluid.

The right lung is moderately collapsed. In the upper and lower lobes
are small patches of red, lobular consolidation. The upper third of
the upper lobe is laxly consolidated and near its inner surface the
interstitial septa are thickened to from 1 to 1.5 mm. in width, and
at intervals occur bead-like swellings from which creamy purulent
fluid exudes upon the cut surface. In the left lung small patches of
gray consolidation occur throughout the lower lobe and here the
interstitial septa are thickened, beaded and contain purulent fluid.

Bacteriologic examination shows that the blood contains S.
hemolyticus; from the right lung and from the right main bronchus
hemolytic streptococci and B. influenzæ are grown.

Microscopic examination shows that the epithelium of the bronchi has
undergone hypertrophy; the wall is infiltrated with lymphoid and
plasma cells and thickened by new formation of fibrous tissue; there
is similar thickening of adjacent alveolar septa and alveoli, often
lined by cubical cells, are diminished in size. Connective tissue
about the blood vessels and the interstitial septa are thickened and
infiltrated with mononuclear cells. In parts of the lung the
interstitial septa are edematous and contain polynuclear leucocytes,
in some places in great number. Lymphatics are greatly dilated and
filled with polynuclear leucocytes which in the center of some
lymphatics have undergone necrosis. In one place a small abscess is
in contact with a distended lymphatic. Lymphatics contain
Gram-staining cocci in pairs and short chains, present in immense
number where necrosis has occurred.

=Autopsy 433.=—B. J., white, aged twenty-seven, from Arkansas, has
been in military service one month. Onset of illness was on
September 28, nineteen days before death, with cough and
expectoration. Pneumonic consolidation was recognized two days later
and 20 c.c. of cloudy fluid were aspirated from the left chest on
the same day. Hemolytic streptococci were found in a culture from
the throat nine days before death.

=Anatomic Diagnosis.=—Unresolved bronchopneumonia with
peribronchiolar and confluent lobular consolidation; interstitial
suppuration of the right lower lobe; purulent bronchitis;
fibrinopurulent pleurisy.

The right pleural cavity contains 700 c.c. of yellowish gray
purulent fluid containing flakes of fibrin. The left pleural cavity
contains seropurulent fluid localized over the external part of the
lung.

The right lung is voluminous and free from consolidation save at the
lower and posterior part of the lower lobe where the tissue is deep
red and studded with firmer spots of yellow color clustered about
the bronchi. In places the interstitial septa are thickened and
yellow. Surrounding some of the bronchi near the apex of the left
lung are red patches of consolidation.

Culture from heart’s blood remained sterile. S. hemolyticus was
grown from right pleural cavity, and S. hemolyticus and B. influenzæ
were grown from the right lung. Culture from the left lung contained
S. aureus and contaminating microorganisms.

Microscopic examination shows the presence of peribronchiolar
patches of pneumonia in which there are few polynuclear leucocytes
and many lymphoid and plasma cells; the alveolar walls are thickened
and infiltrated with mononuclear cells. In some sections the tissue
is wholly consolidated and the site of advanced organizing
pneumonia. Interlobular septa and connective tissue about blood
vessels are thickened and cellular. Small bronchi have lost their
epithelial lining, their walls are thickened and there is
peribronchial organizing pneumonia. In some sections the lymphatics
are immensely dilated and distended with polynuclear leucocytes.
There is necrosis of the walls of the lymphatics and of the
polynuclear leucocytes within the lumen.

In the discussion of acute bronchopneumonia it has been shown that S. hemolyticus is not infrequently a secondary invader of a pneumonic lesion perhaps caused by pneumococci. With progress of the disease hemolytic streptococci persist. In the autopsies with unresolved pneumonia just described, hemolytic streptococci have found their way into the lymphatics and produced suppurative lymphangitis with inflammation of the interstitial septa of the lung.