Autopsy 322.—The patient was admitted with influenza eight days before death; signs of pneumonia appeared two days later, and on the following day Pneumococcus IV was obtained from the sputum. At autopsy there were bronchopneumonia with lobar consolidation, abscesses clustered about a bronchus in the right upper lobe and purulent bronchitis. The blood was sterile; S. aureus was obtained from the consolidated part of the left lung; S. aureus and Pneumococcus III from the abscesses of the right lung. Microscopic examination of sections of abscesses showed the presence of Gram-staining cocci in staphylococcus-like colonies, surrounded by necrotic material and polynuclear leucocytes; Gram-negative bacilli resembling B. influenzæ were seen. (See Fig. 16.)

Autopsy 333.—The onset of influenza was fifteen days before death; a diagnosis of pneumonia was made seven days before death. At autopsy there were confluent bronchopneumonia, clustered abscesses in the right lung and purulent bronchitis (no pleurisy). The blood contained Pneumococcus II atypical. S. aureus and Pneumococcus II atypical were obtained from the abscesses; S. hemolyticus, from the consolidated left lung; S. aureus, B. influenzæ and a few hemolytic streptococci, from the bronchus. (See Fig. 15.)

Autopsy 370.—The patient was admitted seventeen days before death and signs of pneumonia were noted three days after admission. At autopsy there were lobular and confluent bronchopneumonia and small abscesses clustered about bronchi and situated within the gray consolidated lung; purulent bronchitis and patches of atelectasis, with distention of the lungs, so that they failed to collapse on removal. No growth was obtained from the heart’s blood; S. aureus in pure culture was obtained from the abscesses of the right lung; S. aureus, Pneumococcus IV and B. influenzæ were obtained from a small bronchus on the left side.

Autopsy 425.—Illness began with influenza twenty-nine days before death; a diagnosis of pneumonia was made fourteen days before death. At autopsy there were chronic bronchopneumonia with tubercle-like nodules of consolidation with some large patches of consolidation, multiple small abscesses giving a honey-combed appearance to part of the right middle lobe, purulent bronchitis and bronchiectasis. S. hemolyticus was grown from the heart’s blood; S. hemolyticus, B. influenzæ and S. albus from the lung. Sections of an abscess contain clumps of cocci. An abscess cavity has along one side remains of a bronchial wall covered by squamous epithelium; a dilated bronchus, cut longitudinally, terminates in this irregular abscess cavity.

Table XLIX shows the incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzæ in the foregoing autopsies with abscesses clustered about bronchi:

Staphylococcus shows in the lung the same tendency to produce localized abscesses which it exhibits in other tissues of the body; it invades the lung by way of the bronchi, but shows no ability to invade lymphatics, and in the cases we have examined rarely enters the pleura or the blood. In all of these cases B. influenzæ has been found in the bronchi and perhaps precedes the staphylococcus as an invader of the lower respiratory passages. Pneumococci atypical II, Types III and IV have been found in over half of these cases. The significance of this organism is emphasized by the 2 cases in which it has been found in the heart’s blood at autopsy. It appears not improbable that S. aureus has invaded the lung already the site of bronchopneumonia caused by pneumococci.

Notwithstanding the small number of autopsies, the figures in Table XLIX, showing the incidence of pneumococci, streptococci, staphylococci and B. influenzæ, are cited so that they may be compared with the corresponding figures for the usual type of streptococcus abscess (p. 203). The incidence of hemolytic streptococci is relatively low, whereas that of staphylococci approximates 100 per cent. S. aureus was present in great number in the lung of Autopsies 322 and 333 and in pure culture in the abscess of Autopsy 370. Microscopic examination of sections from the abscesses which have been described, demonstrated the presence of Gram-staining cocci in characteristic staphylococcus-like clumps within the exudate of the abscesses; scattered chains of streptococci were not found. In those instances (Autopsies 280 and 286) in which cultures failed to demonstrate staphylococci, microscopic examination demonstrated staphylococcus-like clumps of bacteria within the abscess cavity. Cultures were usually made from the consolidated lung near the abscess where the pleural surface could be seared, rather than from the pus, so that in some instances the microorganism has doubtless escaped detection although present.

In association with the multiple abscesses which have been described, injury to the bronchi and bronchopneumonia have been invariably present. Purulent bronchitis has been present in all instances of this lesion; in 2 instances there has been dilatation of the bronchi, and in 1 instance in which the onset of influenza was twenty-nine days before death, there has been advanced bronchiectasis.

Microscopic examination shows that the epithelium of the bronchi is partially or completely destroyed and that destruction of the underlying tissue, with acute suppurative inflammation, penetrates to a greater or less depth into the wall. When the epithelium of the bronchus is wholly destroyed and the lumen is filled and distended with polynuclear leucocytes, a cross section of the tube has the appearance of a small abscess; but more careful examination often shows that the engorged mucosa is still intact. Occasionally, a network of fibrin forms a layer covering the denuded mucosa. Disintegration of the superficial tissue may extend to the muscularis or through it, and may penetrate the wall of the bronchus. The tissue in contact with the exposed surface contains many polynuclear leucocytes and blood vessels plugged with fibrinous thrombi, but deeper in the tissue lymphoid and plasma cells are more numerous. In 2 instances (Autopsies 286 and 425) favorable sections have demonstrated that the wall of an abscess on one side consists of the remains of a bronchus, covered by epithelium composed of squamous cells, Whereas the remainder of the wall, here very irregular, is formed by partially destroyed alveoli plugged with fibrin. The suppurative process has penetrated the wall of the bronchus on one side and extended into the surrounding alveolar tissue. In other instances, abscess cavities occur within the alveolar tissue of the lung and their relationship to bronchi is not evident. In the mass of polynuclear leucocytes which fill the abscess cavity, are clumps of staphylococci in great abundance, usually forming characteristic colonies which are conspicuous with the low power of the microscope.

No sharp line can be drawn between nonpurulent and purulent pleurisy. A diagnosis of empyema has been made when the fluid in the chest has become opaque and fibrin has undergone softening or solution. The lesion has been designated seropurulent when there has been abundant thin, opaque, gray fluid. Pleurisy has been designated fibrinopurulent when the cavity has contained opaque fluid and ragged soft white or yellowish fibrin adherent to the chest wall; this fibrin is evidently in process of disintegration and there may be numerous shreds and flakes of fibrin which subside to the bottom of the fluid. The amount of fluid in the cavity may occasionally exceed 1,700 c.c.; that in both pleural cavities may exceed 2,500 c.c. The lesion has been designated purulent when fibrin has almost wholly disappeared and the cavity contains thick yellowish white fluid. In 4 of 5 instances in which thoracotomy had been performed, empyema has assumed this otherwise uncommon type.

Some inflammation of the pleura is almost constantly found in association with all forms of pneumonia, but in many instances is so slight that it has no noteworthy significance. Table L shows the incidence of various types of pleurisy.

Empyema has occurred, on the one hand, in 12.4 per cent of instances of lobar pneumonia and in 9.9 per cent of instances of bronchopneumonia alone. It has occurred, on the other hand, in 87.2 per cent of instances of suppurative pneumonia with abscess formation and in 94.1 per cent instances of interstitial suppurative pneumonia. These suppurative lesions are caused by hemolytic streptococci, and when cultures are made from the pleural exudate this microorganism is isolated.

Of 16 instances in which empyema has occurred in association with lobar pneumonia or bronchopneumonia unaccompanied by suppuration in 6 there has been infection with hemolytic streptococci. Empyema has occurred in the absence of hemolytic streptococci only 10 times.

Empyema Caused by Hemolytic Streptococci.—When necrosis preceding abscess formation has occurred in the lung, streptococci are found in immense numbers in the dead tissue. The pleura overlying the abscess undergoes necrosis and occasionally streptococci are particularly numerous upon the pleural surface of the necrotic tissue. In Autopsy 376 a membrane thin as tissue paper, representing the pleura, separated an abscess containing thick pus from the pleural cavity which was the site of empyema. The abscess may rupture into the pleural cavity and at the same time may be in free communication with a bronchus (Autopsy 480). In one (Autopsy 467) instance an abscess which had ruptured into the pleural cavity had completely discharged its contents and was in process of healing, newly formed fibrous tissue being abundant in its wall.

With few exceptions empyema has accompanied subpleural abscess caused by hemolytic streptococci, being found on the side corresponding to the abscess. Among 39 instances of pulmonary abscess, empyema has been limited to the side of the abscess in 23; it has been present on the opposite side as well in 10 instances. In 2 instances there have been abscesses in both lungs; in one (Autopsy 385 A) there has been double empyema, and in the other (Autopsy 487) empyema only on the left side. In one instance abscess has been recognized by microscopic examination and its location is not recorded. In 5 instances of abscess formation there has been no empyema. In Autopsy 383 there has been no pleurisy noted; in Autopsy 416 there has been fibrinous pleurisy and in Autopsies 277, 290 and 380, serofibrinous pleurisy.

Empyema has been almost invariably found in association with interstitial suppurative pneumonia. This lesion extends by way of the lymphatics up to the pleural surface and is often more conspicuous just below the pleura than elsewhere. Empyema has been absent in only 3 of 21 examples of the lesion and in one of these there has been serous effusion. In 12 instances interstitial suppuration has occurred only on one side and empyema has been limited to this side; in 5 instances with interstitial suppuration on one side there has been empyema on both sides; in 2 instances with interstitial suppuration in both lungs there has been double empyema.

The amount of fluid in the pleural cavity has varied from less than 100 to 1,500 c.c. The fluid has occasionally been seropurulent or yellow, thick and purulent, but in most instances the exudate is best described as fibrinopurulent. There is yellow or yellowish gray purulent fluid containing flakes of soft ragged fibrin.

The foregoing study has shown, on the one hand, that empyema is a frequent complication of streptococcus pneumonia and, on the other hand, that empyema following influenza with relatively few exceptions is caused by hemolytic streptococci. Empyema caused by this microorganism exhibits in some instances characters not seen with other varieties of pleural inflammation. The tissue between sternum and pericardium is often edematous and the adjacent fat has a firm brawny consistence. In some instances the exudate contains blood, and hemolysis has occurred so that the fluid has a diffuse red color. The occurrence of multiple pocketed collections of purulent fluid within the pleural cavity is peculiar to streptococcus empyema. These pockets have been found 6 times in association with abscess and 5 times with interstitial suppurative pneumonia. In the presence of an exudate within the pleural cavity, some part of the lung, usually the anterior surface behind the sternum and costal cartilages, is glued by fibrinous adhesions to the parietal pleura. Here occur pockets containing thin purulent fluid and softened fibrin or thicker creamy pus walled off by fibrin about the edges of the pocket. At the site of the lesion the lung, after it is separated from the chest wall, is marked by a shallow depression surrounded by the fibrin which has walled in the pocket. The little cavity thus formed, varying much in size, is usually oval, the long diameter being from 1 to 3 cm. These pleural pockets may occur over the external surface of the lung (Autopsies 452, 455, and 472) or between the internal surface and pericardium (Autopsy 452). Occasionally with partial fibrinous adhesion between the pleural surfaces there are both scattered pockets containing purulent fluid and a larger encapsulated collection of fluid; in Autopsy 455 the pleural surfaces were adherent and there was 100 c.c. of purulent fluid encapsulated in a space over the external surface of the lung, 12 × 8 cm. In Autopsy 452 the lower part of the pleural cavity was encapsulated and contained 650 c.c. of fluid. This tendency of empyema caused by S. hemolyticus to form encapsulated pockets is doubtless of considerable importance in the treatment of the condition.

Stone, Bliss and Phillips^[85] have described these encapsulated pockets as “subcostosternal pus pockets” and have maintained that they are formed about the sternal lymphatic nodes. We have found them so widely scattered that this relation seems improbable.

Pneumococcus Empyema.—Empyema occurred in association with pneumonia referable to pneumococci 10 times, once with Pneumococcus II; 6 times with Pneumococcus atypical II; once with Pneumococcus III and twice with Pneumococcus IV. The lesion was seropurulent once; fibrinopurulent 8 times and purulent once. Fibrin in several instances was somewhat voluminous. In the following instance voluminous masses of fibrin had an important influence upon the attempted treatment.

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.

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