Epidemic Respiratory Disease / The pneumonias and other infections of the repiratory tract accompanying influenza and measles

by Eugene L. Opie; Francis G. Blake; Thomas M. Rivers; James C. Small

Bronchopneumonia

For the purpose of the present study it is convenient to group together instances of bronchopneumonia which have been unaccompanied, on the one hand, by lobar pneumonia (p. [155]) or, on the other hand, by suppuration, which with few exceptions is caused by hemolytic streptococci or by staphylococci. A group of cases in which lobar and bronchopneumonia have occurred in the same individual have already been considered. In many instances, bronchopneumonia is accompanied by abscess formation or by some other form of suppuration; these lesions will be discussed elsewhere.

Bronchopneumonia unaccompanied by lobar pneumonia or by suppuration occurred in 80 autopsies.

Pneumonic consolidation distributed with relation to the bronchi exhibits considerable variety, and an attempt to define a type of bronchopneumonia characteristic of influenza would be futile. Nevertheless, the bronchopneumonia of influenza has in many instances distinctive characters.

Lesions of bronchopneumonia which are frequently found in the autopsies under consideration may be conveniently designated by descriptive terms, indicative of their location in the lung tissue. These lesions, of which two or more often occur in the same lung, are:

1. Peribronchiolar consolidation with which the inflammatory exudate is limited to the alveoli in the immediate neighborhood of the bronchioles.

2. Hemorrhagic peribronchiolar consolidation in which gray patches of peribronchiolar pneumonia occur upon a deep red background produced by hemorrhage into alveoli. Pfeiffer believed that this lesion was characteristic of influenza.

3. Lobular consolidation with which consolidation is limited to lobules or groups of lobules.

4. Peribronchial pneumonia with which small bronchi are encircled by pneumonic consolidation.

Each one of these lesions will be discussed separately.

Following is a list of the bacteria which have been isolated from the consolidated lung of individuals with bronchopneumonia unaccompanied by lobar pneumonia or by suppuration:

B. influenzæ	1
Pneumococci	5
S. hemolyticus	5
S. viridans	1
B. influenzæ, pneumococci	9
B. influenzæ, S. hemolyticus	4
B. influenzæ, staphylococci	4
Pneumococci, S. hemolyticus	1
Pneumococci, staphylococci	2
S. hemolyticus, staphylococci	1
S. hemolyticus, B. coli	1
Staphylococci, S. viridans	1
Staphylococci, B. coli	1
B. influenzæ, pneumococci, staphylococci	1
B. influenzæ, pneumococci, S. viridans	1
B. influenzæ, S. hemolyticus, staphylococci	2
B. influenzæ, pneumococci, staphylococci, S. viridans	1
No microorganisms found	6
	47

The similarity of this list to that representing the bacteriology of bronchitis is evident; there is the same multiplicity of microorganisms and the frequent occurrence of mixed infections. B. influenzæ is much less frequently found in the lung. The relative pathogenicity of the large group of microorganisms enumerated above is better indicated by the following list which shows what microorganisms have penetrated into the blood in autopsies performed on individuals with bronchopneumonia:

Pneumococci	20
S. hemolyticus	23
S. viridans	1
Pneumococci, S. hemolyticus	2
No bacteria found	25
Total	71

Table XXXIV shows the percentage incidence of pneumococcus, hemolytic streptococcus, staphylococcus and B. influenzæ in the bronchi, lungs and blood and is inserted for comparison with the similar table (Table XXX) showing the incidence of these bacteria in lobar pneumonia.

Table XXXIV
	NO. OF CULTURES	PNEUMOCOCCI		HEMOLYTIC STREPTOCOCCI		STAPHYLOCOCCI		B. INFLUENZÆ
		NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE
Bronchus	37	19	48.6	13	35.1	22	59.5	28	75.7
Lung	47	20	42.6	14	29.8	13	27.7	23	48.9
Blood	70	22	31.4	24	34.3

Table XXXIV shows that pneumococci have a less important part in the production of broncho than of lobar pneumonia; with lobar pneumonia this microorganism was found in the lungs in 77.3 per cent of instances and in the blood, in 65.5 per cent, whereas with bronchopneumonia it was found in the lungs in 42.6 per cent and in the blood in 31.4 per cent. Hemolytic streptococci (in lungs and blood) and staphylococci (in lungs), on the contrary, were more common with bronchopneumonia, and doubtless have a part in the production of the lesion. Streptococcus viridans, B. coli and M. catarrhalis, which are not infrequently found in the bronchi (p. [151]), occasionally enter the lungs with bronchopneumonia but are rarely found with lobar pneumonia. B. influenzæ has been found in less than 80 per cent of instances in the bronchi and in about half of the lungs, maintaining an incidence approximately the same as that with lobar pneumonia.

Table XXXV shows the types of pneumococci found in association with bronchopneumonia and is inserted for comparison with the similar table (Table XXXII) showing types of pneumococci with lobar pneumonia.

With broncho as with lobar pneumonia pneumococci commonly found in the mouth, namely, atypical II, and Types III and IV, have a more important part in production of the lesion than the so-called fixed types, I and II. Atypical Pneumococcus II has been less frequently encountered with broncho than with lobar pneumonia.

Table XXXV
	NO. OF CULTURES	PNEUMOCOCCUS I		PNEUMOCOCCUS II		PNEUMOCOCCUS II (Atyp.)		PNEUMOCOCCUS III		PNEUMOCOCCUS IV
		NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE	NO. POSITIVE	PER CENT POSITIVE
Bronchus	37	1	2.7	3	8.1					14	37.8
Lung	47	2	4.3	2	4.3	2	4.3	2	4.3	12	25.2
Blood	70	1	1.4	1	1.4	5	7.1	4	5.7	11	15.9

Peribronchiolar Consolidation.—In many instances of bronchopneumonia, usually in association with lobular or confluent consolidation, small firm nodules of consolidation are clustered about the bronchioles (Fig. 2). These nodular foci of consolidation are usually 1.5 to 2 mm. in diameter, being sometimes slightly smaller or slightly larger. They are usually gray and occasionally surrounded by a red halo; sometimes they are yellowish gray. They are clustered about the smallest bronchial tubes to form groups which are from 0.5 to 1 cm. across. A group of nodular foci of consolidation occupies the central part of a lobule of lung tissue. When pneumonia has been of short duration these foci are fairly soft and not sharply defined, and in many instances this form of bronchopneumonia is first recognized by microscopic examination. When the disease has lasted from ten days to two weeks, the consolidated nodules are very firm and sharply circumscribed, closely resembling tubercles. When they have assumed this character, microscopic examination shows that chronic changes indicated by new formation of interstitial tissue have occurred.

The lesion may be designated peribronchiolar consolidation. It has occurred usually in association with other types of pneumonic lesion in 61 instances, being recognized at autopsy in 18 and by microscopic examination in 43.

Fig. 2.—Acute bronchopneumonia with nodules of peribronchiolar consolidation and purulent bronchitis. Autopsy 429.

In association with this lesion there are almost invariably severe lesions of the bronchi. Purulent bronchitis was noted in 47 of the 61 instances, in which this nodular bronchopneumonia was found at autopsy. An index of the severity of the bronchial injury is the frequency with which bronchiectasis has occurred; dilatation of small bronchi was observed in 24 instances. In 10 instances the bronchi were encircled by conspicuous zones of hemorrhage.

In association with this peribronchiolar lesion the lung is often voluminous and fails to collapse on removal from the chest. Pressure upon the lung squeezes from the smallest bronchi, both in the neighborhood of the nodular consolidation and elsewhere, a droplet of viscid, semifluid mucopurulent material. The presence of this tenacious material throughout the small bronchi doubtless explains the failure of the lung tissue to collapse. Interstitial emphysema has been present in some of these lungs.

A red zone of hemorrhage has occasionally been observed about the foci of peribronchiolar pneumonia. A further stage in the same process is represented by hemorrhage into all of the alveoli separating these patches of consolidation. This hemorrhagic lesion, which will be described in more detail later, has been found repeatedly in the same lung with peribronchiolar pneumonia, being present in 8 among the 61 autopsies cited. Lobular bronchopneumonia accompanied the peribronchiolar lesion 27 times and lobar pneumonia accompanied it 20 times.

When an abscess caused by hemolytic streptococcus is associated with peribronchiolar pneumonia, empyema is present, but otherwise pleurisy is absent or limited to a scant fibrinous exudate.

Fig. 3.—Acute bronchopneumonia with peribronchiolar consolidation; a respiratory bronchiole partially lined by columnar epithelium passes into alveolar duct and the adjacent alveoli are filled by polynuclear leucocytes. Autopsy 333.

Histologic examination demonstrates very clearly the relation of this lesion to the bronchioles (Fig. 3). These passages are filled and distended with an inflammatory exudate consisting almost entirely of polynuclear leucocytes. The respiratory bronchioles are beset with alveoli often limited to one side of the tubule and these alveoli are filled with leucocytes. The alveolar ducts, distinguishable from the bronchioles by the absence of columnar or cubical epithelium and by possession of smooth muscle, are similarly filled with leucocytes; the numerous alveoli which form the walls of the alveolar ducts are distended by an inflammatory exudate. In sections which pass through an alveolar duct and one or more of its infundibula, the further extension of the lesion may be determined (Fig. 4). The infundibulum in proximity with the alveolar duct contains polynuclear leucocytes and the same cells are seen in the alveoli which here form its wall, but the intensity of the inflammatory reaction diminishes toward the periphery, so that the distal part of the infundibulum, which is much distended and in consequence more readily definable than usual, is free from inflammatory exudate.

Fig. 4.—Acute bronchopneumonia with peribronchiolar consolidation; a respiratory bronchiole is in continuity with an alveolar duct and two distended infundibula; alveoli about bronchiole, alveolar duct and proximal part of infundibula contain polynuclear leucocytes, the distal part of the infundibula showing no evidence of inflammation. Autopsy 333.

Occasionally there is irregularly distributed hemorrhage and perhaps some edema in the alveoli immediately adjacent to those which form the peribronchiolar focus of inflammation. In such instances small bronchi, that is, air passages, lined by columnar epithelium and devoid of tributary alveoli, may be surrounded by a zone of hemorrhage; immediately surrounding the bronchus, the wall of which shows intense inflammation, alveoli, in a zone of which the radius represents several alveoli, are filled with blood. This hemorrhagic zone is continued from the bronchus over the focus of inflammation which surrounds the bronchiole.

Another variation in the character of the lesion is doubtless referable to variation in the severity of primary bronchial injury. Alveoli immediately surrounding small bronchi are filled with dense plugs of fibrin. The alveoli which besot the walls of the bronchioles contain fibrin, but the alveolar duct and its tributary alveoli are filled with polynuclear leucocytes.

The bacteria which have been cultivated from the lung in autopsies with peribronchiolar pneumonia are as follows:

Pneumococcus	5
S. hemolyticus	8
B. influenzæ, pneumococcus	5
B influenzæ, S. hemolyticus	7
B. influenzæ, staphylococcus	1
Pneumococcus, staphylococcus	2
S. hemolyticus, staphylococcus	2
B. influenzæ, pneumococcus, S. hemolyticus	2
B. influenzæ, pneumococcus, staphylococcus	1
B. influenzæ, S. hemolyticus, staphylococcus	2
Pneumococcus, S. hemolyticus, staphylococcus	3
No organism	3
Total	41

The following list which shows the bacteria found in the blood is an index to the pathogenicity of pneumococci and hemolytic streptococci:

Pneumococcus	22
S. hemolyticus	20
Pneumococcus, S. hemolyticus	1
No organism	14
Total	57

The percentage incidence of pneumococcus, hemolytic streptococcus, staphylococcus and B. influenzæ in bronchus, lung and blood, given in Table XXXVI, is inserted to indicate with what readiness each one of these microorganisms passes from the bronchus through the lung into the circulating blood.

Table XXXVI
	PNEUMOCOCCUS	HEMOLYTIC STREPTOCOCCUS	STAPHYLOCOCCUS	B. INFLUENZA
Bronchus	39.4%	57.7%	60.6%	84.8%
Lung	43.9%	61.0%	21.9%	43.9%
Blood	40.3%	36.8%	0. %	0. %

B. influenzæ is present in the bronchi in a very large proportion (84.8 per cent) of those in whom this type of bronchopneumonia has been found at autopsy; it is much less frequently recovered from the lungs. Staphylococci, in part S. albus and in part S. aureus, are less frequently found in the bronchi and are recovered from the lungs in a relatively small proportion of autopsies. The percentage incidence of pneumococci and streptococci in lungs and blood demonstrates the pathogenicity of these microorganisms, for whereas pneumococci and hemolytic streptococci are found in the consolidated lungs in 43.9 and 61.0 per cent of instances of the lesion respectively, they make their way into the blood in 40.3 and 36.8 per cent of instances.

Coexisting infection with pneumococci and hemolytic streptococci has been not uncommon e. g., Autopsy 275 in which both were in the blood; in 2 instances (Autopsies 333 and 378) in which pneumococci were obtained from the blood, hemolytic streptococci were found in the lungs and bronchi; in 3 instances (Autopsies 258, 273 and 445) in which hemolytic streptococci were present in the blood, pneumococci were obtained from the lungs.

In the group of autopsies under consideration, examination of the sputum was made during life and after onset of pneumonia in 11 instances. The microorganisms found in the sputum and at autopsy were as follows:

		SPUTUM	IN BLOOD, LUNGS OR BRONCHUS AT AUTOPSY
Autopsy	240	Pneum. IV	Pneum. IV
	246	Pneum. atyp. II, B. inf.
	247	Pneum. IV, B. inf.	Pneum. IV
	250	Pneum. atyp. II, B. inf.	Pneum. atyp. II
	253	Pneum. atyp. II	Pneum. II
	285	Pneum. atyp. II, B. Inf.	S. hem., B. inf.
	288	S. hem., B. inf.	S. hem., B. inf.
	291	Pneum. IV, B. inf.	Staph., B. inf.
	300	Pneum. atyp. II, B. inf.	Pneum. atyp. II, B. inf.
	312	Pneum. IV, S. hem., B. inf.	S. hem., B. inf.
	346	Pneum. IV, B. inf.	S. hem., B. inf.

In 2 instances (Autopsies 285 and 346) among this small group of cases, pneumococci but no hemolytic streptococci were found in the sputum several days before death, whereas death occurred as the result of secondary invasion with hemolytic streptococci and no pneumococci were found at autopsy. It is probable that this sequence of events is not uncommon. B. influenzæ finds its way into the bronchi and pneumococci follow it; pneumonia limited to peribronchiolar alveoli may occur in consequence of this invasion. Later hemolytic streptococci may follow the same path and cause death with bacteremia.

Hemorrhagic Peribronchiolar Consolidation.—Peribronchiolar pneumonia accompanied by diffuse accumulation of blood within the alveoli is one of the most frequent complications of influenza. The lung tissue is laxly consolidated, and on section there is a homogeneous dull deep red background upon which are seen small gray spots (1.5 to 2 mm. in diameter) grouped in clusters about the smallest bronchi (Fig. 5). Wide areas of lung tissue are implicated and the lesion is more common in the dependent parts of the lung than elsewhere. In common with other forms of bronchopneumonia the lesion is in most instances associated with changes in the bronchi; in 55 instances of hemorrhagic bronchiolar pneumonia purulent bronchitis was found in 43 instances; it is noteworthy that purulent bronchitis often is not evident in the presence of pulmonary edema and edema is not infrequent with this pneumonic lesion.

Microscopic examination demonstrates the presence of acute bronchitis; the lumina of the small bronchi contain polynuclear leucocytes and red blood corpuscles. Accumulation of blood may separate the epithelium from the basement membrane. The mucosa immediately below the epithelium contains polynuclear leucocytes in fair abundance and the blood vessels of the bronchial wall are much engorged. Respiratory bronchioles are distended with polynuclear leucocytes and red blood corpuscles. In a zone about each bronchiole, in areas corresponding to the small gray spots seen upon the cut surface of the lung, the alveoli are filled with polynuclear leucocytes. In the lung tissue intervening between these spots of leucocytic pneumonia the alveoli are distended with red blood corpuscles.

Fig. 5.—Bronchopneumonia with hemorrhagic peribronchiolar consolidation.

In favorable sections it is occasionally possible to follow the bronchiole and alveolar duct, both filled with leucocytes, into an infundibulum. The proximal part of the infundibulum contains polynuclear leucocytes, whereas the distal part and its tributary alveoli are filled with serum and red blood corpuscles.

When the lesion has persisted for a short time there is evidence of beginning migration of polynuclear leucocytes from the blood vessels into the alveoli which are filled with blood. The alveolar walls contain numerous polynuclear leucocytes and leucocytes which have entered the intraalveolar blood are numerous in contact with the wall but occur in scant number in the center of the alveolar lumen.

Alveolar epithelium in contact with the blood in the lumen is usually swollen and often uniformly nucleated.

The inflammatory process is evidently transmitted from the bronchioles and to a less degree from the small bronchi to the adjacent alveoli. Polynuclear leucocytes fill the lumen of the bronchiole and the alveoli immediately adjacent; at the periphery of the focus of pneumonia, the alveoli may contain fibrin. In such instances small bronchi (lined by a continuous layer of columnar epithelial cells) may be surrounded by alveoli containing fibrin.

In sections from one part of the lung, the alveoli between the peribronchiolar foci of pneumonia may be uniformly filled with red blood corpuscles, whereas in sections from another part pneumonic foci may be surrounded by a zone of intraalveolar hemorrhage or of hemorrhage and edema outside of which some air-containing tissue occurs. There are transitions between this halo of intraalveolar hemorrhage and edema surrounding each bronchiolar focus and complete hemorrhagic infiltration of all intervening alveoli.

Large mononuclear cells are occasionally fairly numerous within the alveoli containing blood. These cells act as phagocytes ingesting red corpuscles, so that at times they are filled with corpuscles. Disintegration of red corpuscles occurs and brown pigment remains within the cell. It is not uncommon to find numerous mononuclear pigment containing cells which resemble those found with chronic passive congestion of the lungs.

Lungs, the site of hemorrhagic peribronchiolar pneumonia, may undergo chronic changes which will be described elsewhere.

The lesion which has been designated hemorrhagic peribronchiolar pneumonia is that which Pfeiffer regarded as the characteristic type of influenzal pneumonia. In the small bronchi containing pus and in lung tissue, Pfeiffer states, influenza bacilli are predominant and present in astonishing number in smear preparations. The demonstration of B. influenzæ by cultures from pneumonic lung is mentioned by him but its association with other microorganisms in such cultures is not discussed.

Microorganisms which we have isolated from the lungs of individuals with hemorrhagic peribronchiolar pneumonia are as follows:

B. influenzæ	1
Pneumococcus	2
S. hemolyticus	10
B. influenzæ, pneumococcus	7
B. influenzæ, S. hemolyticus	3
B. influenzæ, staphylococcus	2
S. hemolyticus, B. coli	3
B. influenzæ, pneumococcus, staphylococcus	2
B. influenzæ, S. hemolyticus, staphylococcus	5
Pneumococcus, S. hemolyticus, staphylococcus	1
No organisms	2
Total	38

With this type of pneumonia B. influenzæ has not been isolated in pure culture; B. influenzæ alone is recorded only once (Autopsy 435), but in this instance the culture has been so obscured by contamination that the occurrence of pneumococci or streptococci cannot be excluded; S. hemolyticus has doubtless been present in this lung, for it has been found in the heart’s blood, in the bronchus, and in the peritoneal exudate of the same individual.

The incidence of pneumococci and hemolytic streptococci in this list does not differ materially from that with peribronchiolar pneumonia unaccompanied by extensive intraalveolar hemorrhage, though hemolytic streptococci are somewhat more frequent with the hemorrhagic lesion. The following table shows the frequency with which pneumococci and hemolytic streptococci have penetrated into the blood:

Pneumococcus	11
S. hemolyticus	24
Pneumococcus, S. hemolyticus	1
No organism	12
Total	48

Table XXXVII showing the percentage incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzæ further emphasizes the similarity between the bacteriology of peribronchiolar pneumonia (Table XXXVI) and the closely related hemorrhagic lesion:

Table XXXVII
	PNEUMOCOCCUS	HEMOLYTIC STREPTOCOCCUS	STAPHYLOCOCCUS	B. INFLUENZÆ
Bronchus	44.0%	64.0%	44.0%	72.0%
Lung	31.6%	57.9%	26.8%	52.6%
Blood of heart	25.0%	52.1%	0%	0%

Pneumococci have been found in the lungs (31.6 per cent) and blood (25 per cent), somewhat less frequently than with peribronchiolar pneumonia (43.9 and 40.3 per cent respectively), and hemolytic streptococci have been found in the blood more frequently (52.1 per cent) than with the latter (36.8 per cent) but otherwise the bacteriology of the two lesions corresponds closely. The low incidence of B. influenzæ in the bronchi (72 per cent) with hemorrhagic peribronchiolar pneumonia is perhaps incorrect as the result of the relatively small number of bacteriologic examinations (namely, 25), but the incidence of the same microorganism in the lung has been higher (52.6 per cent) than with nonhemorrhagic peribronchiolar lesion (43.9 per cent).

In some instances infection with hemolytic streptococci has occurred after the onset of pneumonia. The following list compares the results of bacteriologic examination of the sputum made after the onset of pneumonia with that of blood, lungs or bronchus after death:

		SPUTUM	IN BLOOD, LUNGS OR BRONCHUS AT AUTOPSY
Autopsy	237	S. hem.	S. hem.
	242	Pneum. atyp. II, B. inf.	Pneum. atyp. II
	247	Pneum. IV, B. inf.	Pneum. IV
	266	S. hem.	S. hem., B. inf.
	346	Pneum. IV, B. inf.	S. hem., B. inf.
	376	(No. S. hem.)	S. hem., staph., B. inf.

Instances of secondary infection with hemolytic streptococcus occur in the list, namely, Autopsies 346 and 376.

From the foregoing studies of the bacteriology of peribronchiolar and hemorrhagic peribronchiolar pneumonia the following conclusions may be drawn: (a) B. influenzæ is found in most instances of these lesions in the bronchi and in about half of all instances in the lungs, but does not occur unaccompanied by other microorganisms. (b) In a considerable number of autopsies pneumococcus is the only microorganism that accompanies B. influenzæ; from the lungs it penetrates into the blood from which it is obtained in pure culture. (c) In a considerable number of instances S. hemolyticus accompanies B. influenzæ, and in some of these instances (representing a large proportion of the relatively small number of cases examined during life), examination of the sputum has demonstrated that infection has been secondary to a pneumonia with which no hemolytic streptococci have been found in the sputum.

Lobular Consolidation.—Consolidation of scattered lobules or groups of lobules has occurred in nearly all instances, namely, 71 of 80 autopsies with bronchopneumonia unaccompanied by lobar pneumonia or by suppuration. When death follows shortly after the onset of pneumonia, patches of consolidation have a dull deep red color; blood-tinged fluid escapes from the cut surface which is almost homogeneous or finely granular. The consolidated tissue seen through the pleura, which is raised above the general level, has a bluish red color. Isolated lobules or groups of lobules which have undergone consolidation may be scattered throughout the lungs, but not infrequently there is confluent consolidation of the greater part of lobes, of whole lobes or of almost an entire lung. Such lungs are very heavy and may weigh 1,400 or 1,500 grams; bloody serous fluid exudes from the cut surface. The lesion resembles the red hepatization of lobar pneumonia, but confluent patches of pneumonia are usually well defined by lobule boundaries. The tissue is soft and the granulation of lobar pneumonia is absent. In many instances the lobular or confluent areas of consolidation are reddish gray; in some instances consolidated tissue is in places red and elsewhere gray, and in a smaller group of autopsies there is gray consolidation only (Fig. 6). Red lobular consolidation is often seen in those who have died within the first four days following the onset of pneumonia, but is almost equally frequent after from five to ten days; the average duration of pneumonia in these cases was 5.5 days. Combined red and gray consolidation was more frequently found when pneumonia had lasted more than five days, the average duration of pneumonia being 7.3 days. The greater number of instances of gray consolidation were found after seven days of pneumonia, the average duration of the disease being 10.0 days. These figures are cited to show that lobular, like lobar, consolidation passes gradually from a stage of red to gray hepatization, but the change occurs more slowly and is often long delayed.

Lobular pneumonia, which occurred 71 times among 80 cases classified as bronchopneumonia, may be regarded as an almost constant lesion of the disease. It is found not only in association with other lesions of bronchopneumonia, but with lobar pneumonia of influenza as well.

The bacteriology of this lesion shows no deviation from that of the slightly larger group of bronchopneumonia (p. [163]). All types of pneumococcus have been found in association with the lesion, Pneumococcus I in 2 instances, Pneumococcus II in 1 instance; atypical Pneumococcus II and Pneumococcus IV have been found much more frequently. Pneumococci have been found in more than a third of these autopsies (42.9 per cent in the lungs, 33.3 per cent in the blood); hemolytic streptococci in less than one-third (28.5 per cent in the lungs, 30.2 per cent in the blood).

Fig. 6.—Acute bronchopneumonia with confluent gray lobular consolidation in lower part of upper lobe and hemorrhagic peribronchiolar pneumonia in lower lobe; purulent bronchitis.

The following list shows the bacteriology of a small group of autopsies in which the sputum was examined after onset of pneumonia:

		SPUTUM	BLOOD, LUNGS OR BRONCHUS AT AUTOPSY
Autopsy	233	Pneum. atyp. II	Pneum.
	237	S. hem.	S. hem.
	242	Pneum. atyp. II, B. inf.	Pneum. atyp. II
	250	Pneum. atyp. II, B. inf.	Pneum. atyp. II
	253	Pneum. atyp. II	Pneum. atyp. II, staph., B. inf.
	266	S. hem.	S. hem., B. inf.
	274	Pneum. IV	S. hem.
	291	Pneum. IV, B. inf.	Staph., B. inf.
	312	Pneum. IV, S. hem., B. inf.	S. hem., staph., B. inf.

In one instance of streptococcus pneumonia (Autopsy 274) infection with streptococci occurred subsequent to the examination of the sputum made five days before death; pneumococcus was found in the washed sputum.

With lobar pneumonia there was evidence that superimposed infection occurred more frequently during the stage of red than of gray hepatization. With the lobular consolidation of bronchopneumonia this relation has not been found. Among 27 instances of red lobular consolidation, hemolytic streptococcus has occurred 6 times, namely in 22.2 per cent; among 26 instances of red and gray consolidation, 8 times, namely, in 30.7 per cent; among 13 instances of gray consolidation, 5 times, namely, in 38.5 per cent. Infection with hemolytic streptococci is more frequent when the lesion has persisted to the stage of gray hepatization. This difference between lobar and bronchopneumonia is probably dependent in part at least upon the more severe and persistent lesions of the bronchi with bronchopneumonia.

The histology of consolidation which is definitely limited to secondary lobules or groups of lobules varies considerably. When death occurs in the early stage of the lesion, consolidated patches are deep red and somewhat edematous, so that bloody serous fluid escapes from the cut surface of the lung and red blood corpuscles are present in the alveoli in great abundance together with polynuclear leucocytes, fibrin and serum in varying quantity. It is not uncommon to find evidence that the lesion has had its origin in the bronchioles and extended from them to other parts of the lobule. Polynuclear leucocytes may be relatively abundant within and immediately about the bronchioles and alveolar ducts, whereas the intervening alveoli and infundibula are filled with red blood corpuscles among which are polynuclear leucocytes and perhaps some fibrin. It may be evident that bronchiolar pneumonia with hemorrhage into intervening alveoli is in process of transformation into a more diffuse leucocytic pneumonia, for polynuclear leucocytes are making their way from the alveolar wall into the blood-filled lumen and, as the result of the presence of blood, remain for a time close to the lining of the alveolus.

When the consolidated lobules have assumed a gray or reddish gray color, polynuclear leucocytes are more abundant and often almost homogeneously pack every alveolus within the boundaries of the lobule. In some instances there is fibrin partially obscured by the presence of leucocytes in great number.

Although fibrin is less abundant with bronchopneumonia than with lobar pneumonia, nevertheless in a considerable proportion of instances it is a very conspicuous element of the inflammatory exudate within the bronchioles, alveolar ducts and alveoli. It is unusual to find the alveolar ducts and alveoli uniformly plugged with fibrin containing leucocytes; there is a variegated distribution of exudate which has little resemblance to that of lobar pneumonia. Occasionally (Autopsies 242 and 247) polynuclear leucocytes fill the bronchioles, alveolar ducts and infundibula, whereas the surrounding tributary alveoli contain fibrin and polynuclear leucocytes in moderate number; red blood corpuscles may be present in sufficient number to give a homogeneously red color to the lobular consolidation.

In association with lobular pneumonia, fibrin within the lung tissue undergoes certain changes which outline very sharply the alveolar ducts and the other structures usually ill defined in preparations of the lung. A remarkable appearance is produced by the deposit of hyalin fibrin upon the surface of the alveolar ducts and infundibula. This lesion has been described by LeCount.

Within the alveolar tissue of the lung, spaces are seen lined by a layer of fibrin which stains homogeneously and very brightly with eosin. They are recognized as alveolar ducts by the presence of scattered bundles of smooth muscle in their wall. The layer of hyaline fibrin overlying the surface of the alveolar duct usually forms a continuous lining and covers over the orifices of the alveoli which surround the alveolar duct. These ducts are rendered still more conspicuous by the character of their contents which exhibits a sharp contrast with that of the surrounding alveoli. The alveoli duct occasionally contains a bubble of air, but more frequently it is filled with serum in which red blood corpuscles are sometimes numerous. There is within the lumen scant fibrin and very few cells, among which polynuclear leucocytes are predominant. In the surrounding alveoli on the contrary leucocytes and fibrin are abundant. A similar change is found in the infundibula very clearly defined by their conical form, which is especially well outlined below the pleura or in contact with interlobular septa. The infundibulum is outlined by hyaline fibrin which passes over the orifices of the tributary alveoli and separates the serous contents of the infundibulum from the cellular fibrinous contents of the alveoli about.

The lesion which has been described is often associated with acute bronchitis and bronchiolitis, and the alveoli immediately about the respiratory bronchioles may be filled with polynuclear leucocytes. It is very common to find large bubbles of air sharply defined within the purulent contents of the bronchiole. In some lobules the alveolar ducts, infundibula and alveoli intervening between these foci of leucocytic pneumonia are almost uniformly filled with fibrin and polynuclear leucocytes, but in other places the formation of complete layers of hyaline fibrin is in process. Bubbles of air are often seen within the alveolar ducts, and about them is an irregular layer of fibrin formed by the penetration of air into a channel previously filled with a loose network of fibrin containing serum in its meshes. The fibrin compressed against the walls of alveolar duct and infundibulum remains as a compact layer separating these structures from the alveoli which project from their walls. The bubble of air is doubtless later absorbed and replaced by serum, so that many alveolar ducts are filled with serum almost wholly free from cells, whereas alveoli outside the fibrinous membrane contain a network of fibrin with leucocytes in greater or less abundance.

In association with this fibrinous pneumonia, which has been described, hyaline thrombosis of the capillaries is not uncommon. This hyalin material within the capillaries gives reactions of fibrin, and in sections stained by the Gram-Weigert method for demonstration of fibrin, these thrombosed vessels have the appearance of capillaries irregularly injected with a blue material.

The interstitial tissue surrounding consolidated lobules is often edematous; the lymphatics are distended with serum and contain a moderate number of lymphocytes and polynuclear leucocytes.

Among the lungs which have been studied histologically, pneumococcus has been almost invariably associated with the lobular lesions which have just been described, whether hemorrhagic, leucocytic or fibrinous; the histologic changes accompanying infection of the lung with streptococcus will be described later. Pneumococcus has been cultivated from the consolidated lung and is found in section of the lung. B. influenzæ is found in cultures made from the bronchi. Table XXXVIII includes those instances in which the histology of the consolidated lung accords with the description given above.

Table XXXVIII
NO. OF AUTOPSY	CHARACTER OF LOBULAR CONSOLIDATION	PREDOMINANT TYPE OF INFLAMMATORY EXUDATE	CULTURE FROM HEART’S BLOOD	CULTURE FROM LUNG	CULTURE FROM BRONCHUS
242	Red	Fibrinous	Pneum. atyp. II
244	Red	Leucocytic and hemorrhagic		Pneum. IV B. inf.	Pneum. IV, B. inf.
247	Red and gray	Fibrinous	Pneum. IV
249	Red and gray	Fibrinous	Pneum. III
252	Red and gray	Fibrinous		Pneum. II B. inf.	Pneum. II, B. inf., S. vir.
257	Red and gray	Leucocytic	Pneum. I		B. inf., staph.
303	Red	Fibrinous		Pneum. IV B. inf.	Pneum. IV, B. inf., staph.
314	?	Fibrinous	Pneum. IV	Pneum. IV	Pneum. IV, B. inf., staph.
336	Red	Fibrinous
395	Red and gray	Leucocytic	Pneum. atyp. II	Pneum. atyp. II
464	Red	Leucocytic and hemorrhagic		Pneum. I B. inf.	Pneum. I, B. inf., staph.
476	Red	Leucocytic and hemorrhagic
498	Red and gray	Fibrinous		S. aur.
506	Red	Fibrinous	Pneum. IV	Pneum. IV S. aur.	Pneum. IV, B. inf., S. aur., M. catarrh

Pneumococcus was found in all but 2 instances, and in one of these (Autopsy 336) the only culture was from the heart’s blood and in the other (Autopsy 498) cultures were unsatisfactory because proper media were not obtainable. Pneumococci of Types I, II, II atypical, III and IV are represented in the list. B. influenzæ has been found in a considerable number of instances in which cultures have been made from the lung and in every instance in which cultures have been made from the bronchi. Staphylococci are often found in the bronchi, but in most instances they do not penetrate into the lung.

Another group of cases of lobular pneumonia are important because in association with necrosis of lung tissue recognized by the microscope hemolytic streptococci have been found in the lungs. In such instances serum is abundant and polynuclear leucocytes are relatively scant though their distribution varies considerably; in some places leucocytes are fairly abundant though elsewhere almost absent, but this distribution bears no obvious relation to the bronchioles. In some instances (Autopsies 274 and 487) red blood corpuscles are numerous but in others (Autopsies 275 and 312) they are inconspicuous. The characteristic feature of the lesion is the occurrence of patches of necrosis within which the nuclei both of exudate and of alveolar walls have partially or completely disappeared. In these areas of necrosis short chains of streptococci are found in immense number whereas in living tissue they are present in moderate number. There has been a relatively inactive inflammatory reaction, great proliferation of streptococci and necrosis of invaded tissue. The bacteriology of instances of lobular pneumonia with necrosis is shown in Table XXXIX.

Table XXXIX
NO. OF AUTOPSY	CHARACTER OF LOBULAR CONSOLIDATION	PREDOMINANT TYPE OF INFLAMMATORY EXUDATE	CULTURE FROM HEART’S BLOOD	CULTURE FROM LUNG	CULTURE FROM BRONCHUS
274	Red	Leucocytic and hemorrhagic	S. hem.	S. hem.	S. hem., staph.
275	Red and gray	Leucocytic	Pneum. IV S. hem.	S. hem., B. inf., staph.	S. hem., B. inf., staph.
312	Red and gray	Leucocytic	S. hem.	S. hem., B. inf.	S. hem., B. inf., staph.
478	Red	Leucocytic and hemorrhagic	S. hem.	S. hem.

Lobular pneumonia, in some of these instances at least, has been caused primarily by pneumococci; necrosis has been the result of secondary invasion by streptococci. In Autopsy 275 Pneumococcus IV has been obtained from the blood, but in the presence of streptococci has presumably disappeared from the lung and bronchus. In the case represented by Autopsy 274, Pneumococcus IV has been found in the sputum five days before death at the onset of pneumonia, but at this time no hemolytic streptococci have been found. In the case represented by Autopsy 312, Pneumococcus IV, B. influenzæ and a few colonies of hemolytic streptococci have been obtained from the sputum two days after recognition of pneumonia and five days before death.

The hemorrhagic and edematous consolidation of the early pulmonary lesions of influenzal pneumonia is their most distinctive feature. Red confluent lobular pneumonia is frequently found in those who have died within the first week following the onset of influenza. The lungs are voluminous and heavy and may weigh as much as 1,500 grams; the pleura which overlies the consolidated area is blue or plum colored and usually shows scant if any evidence of pleurisy. Scattered patches of consolidation are accurately limited to lobules, but in addition there are large areas often involving the greater part of the lobes and not infrequently situated in the lowermost part of the lower lobes. This confluent consolidation may be obviously limited by lobule boundaries. The consolidated tissue is deep red and laxly consolidated; red serous fluid escapes from the cut surface. The lesion not infrequently occurs in association with hemorrhagic peribronchiolar pneumonia.

The histology of this confluent lesion has been studied in Autopsies 242, 244, 303, 336, 464, 474 and 506. The histology varies, because, in some instances, leucocytes, in other instances, fibrin, is abundant, but the presence of red blood corpuscles in large number within the alveoli gives a red color to the consolidated tissue. In these cases pneumococci, associated in the lungs or in the bronchi with B. influenzæ, have been the cause of pneumonia. In two autopsies studied histologically (Autopsies 274 and 478) there was red lobular and confluent pneumonia and the blood and lungs contain hemolytic streptococci demonstrated by cultures; microscopic examination showed the presence of a widespread necrosis of the lung tissue.

In the group of autopsies in Table XL there was red confluent lobular pneumonia. These autopsies are separated from those just cited because there was no histologic examination of the tissue.

Table XL
NO. OF AUTOPSY	BACTERIOLOGY OF HEART’S BLOOD	BACTERIOLOGY OF LUNGS	BACTERIOLOGY OF BRONCHUS
289	Pneum. IV	Pneum. IV	Pneum. IV, B. inf., staph.
297		Pneum. IV, B. inf.	Pneum. IV, B. inf., S. hem. (a few)
306
339	Pneum. IV
364	S. hem.
418	Pneum. atyp. II	Pneum. atyp. II, B. inf., S. vir.
424		Pneum. IV.

This group of autopsies confirms the view that the red confluent lobular pneumonia is caused by pneumococci in association with B. influenzæ. Hemolytic streptococci may invade secondarily. In Autopsy 297 a few hemolytic streptococci were found in the bronchus but apparently had not entered the lungs. In the absence of histologic examination it is not possible to determine if the invasion of hemolytic streptococcus (in Autopsy 364) has caused necrosis of the pneumonic tissue.

Fig. 7.—Bronchopneumonia with purulent bronchitis and peribronchial hemorrhage.