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

In successive columns the table gives the autopsy number, race, and length of military service. These factors have had an important influence upon the incidence of influenza and pneumonia and have been discussed in a preliminary report.^[79] The duration of illness (4th column of table), counted from the date of onset of symptoms of influenza or in some instances, when the earliest symptoms were those of pneumonia, from onset of pneumonia, can usually be determined accurately. The duration of pneumonia (5th column of table) is much more uncertain, because its determination dates from the first recognition of the physical signs of pneumonia.

Clinical Diagnosis.—The clinical diagnosis recorded upon the clinical history of the patient is given in column 6. Many clinicians have been impressed with the difficulty of determining during life the type of pneumonia associated with influenza. The occurrence of purulent bronchitis, the frequent coexistence of lobar and bronchopneumonia and an atypical onset often make the recognition of lobar pneumonia more difficult than usual. The diffuse consolidation of confluent lobular pneumonia increases the difficulty of recognizing bronchopneumonia. In the table (column 6) lobar pneumonia is indicated by L., bronchopneumonia by B. Among 227 autopsies the clinical diagnosis agreed with the condition found at autopsy in 109 instances (48 per cent); in 35 instances (15.4 per cent) both lobar and bronchopneumonia were found at autopsy and a diagnosis of one or other was made during life. In 83 instances (36.6 per cent) the diagnosis made during life was incorrect. Cases admitted to the base hospital at Camp Pike were as carefully studied as the conditions in a base hospital during an epidemic permitted and diagnosis of pneumonia was doubtless as accurate as in other base hospitals. Statistics from military and other hospitals based upon clinical diagnosis of the pneumonias of influenza are probably subject to an error of at least 1 in 3 cases, and conclusions based upon them are almost valueless.

The inaccuracy of clinical diagnosis of the pneumonia of influenza is further illustrated by a consideration of lobar pneumonia. This diagnosis on the one hand was made 136 times and was correct 67 times and incorrect 69 times; on the other hand, lobar pneumonia was found at autopsy 98 times and had been diagnosed in only 67 of these cases (68.4 per cent).

Classification of the Pulmonary Lesions of Influenza.— Influenzal pneumonia exhibits the following noteworthy characters:

1. Acute bronchitis with injury or destruction of lining epithelium and accumulation of inflammatory exudate within the lumen.

2. Hemorrhagic pneumonia with accumulation of blood within the alveoli and within and about the bronchi.

3. Susceptibility of bronchi and pulmonary tissue to secondary pyogenic infection with necrosis and suppuration.

4. Bronchiectasis.

5. Tendency to the occurrence of chronic pneumonia following failure of pneumonia to undergo resolution.

All these changes are doubtless referable to the severity of the primary injury to the lower air passages.

In the presence of destructive changes in the bronchi many bacterial species, including B. influenzæ, pneumococci of various types, streptococci (notably hemolytic streptococci) and staphylococci may invade the lungs and produce acute inflammation. The anatomic characters of the pneumonic lesions following influenza are equally varied.

In order to obtain insight into the pathogenesis of these lesions, it is desirable to imitate the historical development of knowledge concerning the characters and causes of disease, namely, first to define accurately the lesions concerned and later to determine with what microorganisms these lesions are associated. The difficulties of this undertaking are increased by the multiplicity of the microorganisms concerned and by the well-known truth that the same microorganism, e. g., the tubercle bacillus, may produce widely different anatomic lesions.

In the table of autopsies the following lesions are listed:

Column 7. Purulent bronchitis.—“P” indicates that the small bronchi contain mucopurulent fluid.

Column 8. Lobar pneumonia.—The occurrence of the lesion is indicated by the plus sign (+).

Column 9. Peribronchiolar consolidation.—The presence of nodular patches of consolidation about respiratory bronchioles is indicated by the plus sign (+) when the lesion has been recognized at the time of autopsy. When the lesion has been first recognized by microscopic examination the letter “M” is used.

Column 10. Hemorrhagic peribronchiolar consolidation.—The occurrence of this lesion which represents the preceding on a background of hemorrhage is indicated by the plus sign (+).

Column 11. Lobular consolidation.—The presence of the lesion is indicated by the plus sign (+).

Column 12. Peribronchial consolidation.—Peribronchial pneumonia recognized at the time of autopsy is indicated by the plus sign (+). Peribronchial pneumonia recognized microscopically is indicated by “M.” The presence of peribronchial hemorrhage without consolidation is indicated by “h.”

Column 13. Abscess formation with pneumonia.—Suppuration with abscess formation almost invariably just below the pleura is indicated by the plus sign (+). Necrosis of lung tissue recognized microscopically and unaccompanied by suppuration is indicated by “N.”

Column 14. Suppurative interstitial pneumonia.—This lesion invariably associated with suppurative lymphangitis is indicated by the plus sign (+).

Column 15. Multiple abscess in clusters.—Abscesses in clusters about a bronchus of medium size are indicated by the plus sign (+).

Column 16. Empyema.—The presence of the lesion is indicated by “E.”

Column 17. Bronchiectasis.—“B” indicates the lesion.

Column 18. Unresolved bronchopneumonia.—Presence of the lesion is indicated by the plus sign (+).

Column 19. Organizing bronchitis and bronchiolitis.—“O” indicates the lesion.

The lesions of columns 7 to 12 are acute inflammatory processes, columns 9 to 12 represent different types of bronchopneumonia. Columns 13 to 15 represent suppurative lesions. Columns 17 to 19 represent chronic lesions. A survey of the table shows the predominance of acute lesions in the early period of the study and the gradual increase of chronic lesions.

The last four columns of the table of autopsies give the bacteriology of the sputum during life and the bacteria found in the bronchi, in the lungs, and in the blood of the heart after death.

Mortality of Pneumonia Following Influenza.—From September 6 to December 15, 250 autopsies were performed on patients who had died with pneumonia at the base hospital at Camp Pike, and with few exceptions bacteriologic cultures were made from them. Although it was not possible to perform autopsies on all who died, those which were performed afford a fair index of all deaths, for throughout the epidemic of influenza and its outbreak of pneumonia approximately one half of all who died were examined after death. The relation of autopsies to deaths is shown by a comparison by weeks of the number of deaths and number of autopsies during the months of September and October.

For most of these autopsies there is a record of the date of onset of the illness, namely, influenza, which finally resulted in pneumonia and death. Comparison of the number of cases of influenza which developed on any day with the number of fatal cases which had their onset on the same day will determine the mortality of influenza at different periods of the epidemic. Chart 1 shows the number of cases of influenza which had their onset on each day from September 1 to October 31 and the number of fatal cases with autopsy which had their origin on corresponding days. The comparison by weeks between autopsies and total number of deaths shows that the autopsies represent with considerable accuracy the deaths. If there is any error it occurs at the height of the outbreak of pneumonia from September 29th to October 5th and not at its beginning, or end. The chart shows that the highest mortality occurred among cases of influenza which had their origin at the beginning of the epidemic from September 21 to October 1, whereas after October 1, though the maximum number of cases of influenza occurred on October 3, very few developed fatal pneumonia.

Mortality from Pneumococcus and Streptococcus Pneumonias.—By referring fatal cases of streptococcus pneumonia back to their date of origin it is possible to determine what proportion of the cases of influenza, which developed on any day, died with infection by hemolytic streptococcus. The accompanying chart (Chart 1) shows that infection with hemolytic streptococci has been very frequent at the beginning of the epidemic of influenza (shown by area with double hatch in chart) that is, from September 20 to 30 and subsequently has gradually diminished so that few cases have had their onset in the second half of the epidemic from September 30 to October 15.

Pneumococcus pneumonia uncomplicated by streptococcus infection (shown by area with single hatch in chart) pursued a course which more closely conformed to the curve representing influenza. The cases of influenza which resulted fatally bore a fairly constant ratio to the total number of cases of influenza from the onset of the epidemic until October 1, but subsequently few cases of influenza developed fatal pneumococcus pneumonia.

These charts arranged with reference to the onset of fatal pneumonias dissociate very clearly the outbreak of streptococcus pneumonia, which reached its height at the beginning of the influenza epidemic, from the uncomplicated pneumococcus pneumonia which reached its maximum at the midpart of the influenza epidemic and then abruptly abated.

Our study of ward infection in pneumonia furnishes an explanation of the outbreak of fatal streptococcus pneumonia coincident with the initial stage of the influenza epidemic. This outbreak is a true epidemic of streptococcus infection superimposed, in many instances at least, upon preexisting pneumococcus pneumonia, but in some instances, doubtless, a primary streptococcus pneumonia, following the bronchitis of influenza. In the absence of secondary streptococcus infection a very large proportion of these individuals would have recovered. This epidemic of streptococcus pneumonia, it has been shown, was the result of unfavorable conditions produced by great overcrowding of the hospital and in the early part of the epidemic by inadequate separation of those with streptococcus infection from those with none. With control of these conditions, streptococcus pneumonia rapidly diminished.

Greater susceptibility to pneumococcus pneumonia in the early than in the late period of the epidemic is perhaps explained by differences in the severity of influenza; the more susceptible individuals were attacked by influenza in the early period, whereas the less susceptible did not acquire the disease until they had been exposed to an immensely increased number of infected individuals. A better explanation is furnished by the greater opportunity at the beginning of the epidemic for the transmission of microorganisms causing pneumonia, for at this time patients with influenza were crowded together and methods to prevent the transmission of infection were little used.

Bronchitis

Clinical study has shown that purulent bronchitis (see Fig. 2) occurs in about one-third of the cases of influenza. In a large proportion of cases of bronchitis there is no clinical evidence of pneumonia. The bronchial lesions found in association with the pneumonia of influenza are an index of the ability of the agent, which causes influenza, to injure the bronchi.

In those who have died with pneumonia following influenza the large bronchi (with cartilage) are intensely injected, so that the mucosa has a deep red color which on cross section contrasts very sharply with the pearly white of the cartilage. Superficial injury to the bronchi is not infrequently evident in the larger bronchial branches; superficial loss of epithelium is indicated by erosion of the surface, whereas somewhat deeper destructive changes are occasionally evident. Microscopic examination accurately determines the degree of destructive change.

Purulent bronchitis was noted in 134 autopsies (55.6 per cent of autopsies). From the small bronchi, in many instances, purulent fluid welled up upon the cut surface of the lung, whereas in other instances tenacious mucopurulent fluid could be squeezed from small, cut bronchi by pressure upon lung tissue. The consistency of the material within the bronchi varied greatly, ranging from a viscid and tenacious mucus of creamy, yellow color to a thin, turbid, gray fluid. The coexistence of local inflammatory or of general edema of the lungs modifies the character of the material found in the bronchi at autopsy; with edema the purulent exudate is in some instances diluted so that a thin cloudy fluid flows from the small bronchi. In the presence of advanced edema of the lungs the bronchi rarely if ever contain purulent exudate. The underlying changes in the bronchi are more significant than the character of the exudate found at autopsy. Nevertheless, the group of cases in which the diagnosis of purulent bronchitis has been made, because small and medium sized bronchi have contained purulent or mucopurulent exudate, represents instances of readily recognizable bronchitis of considerable severity.

With few exceptions, purulent bronchitis was diffusely distributed in the lungs; occasionally it was observed in one lung alone, and in several instances was limited to the bronchi at the base of a lung, usually of the left lung.

In a considerable proportion of instances of purulent bronchitis abnormal distention of the lungs was noted. On removal from the chest the lungs fail to collapse and retain the size and shape of the thorax. Even after section is made through the organ, parts of the lung fail to collapse and have a resistant cushion-like consistency. This condition is present where the lung tissue is air containing and dry, and occurs when very small bronchi contain tenacious mucous exudate which becomes apparent upon the cut surface after the sectioned lung is squeezed. Microscopic examination shows that the alveolar ducts and infundibula are distended with air, though the respiratory bronchioles contain inflammatory exudate. Complete obstruction of the bronchi is followed by absorption of air from the tributary pulmonary tissue with atelectasis. It is not improbable that partial obstruction, permitting the penetration of air with inspiration, produces distention of air containing tissue.

It is furthermore probable that cyanosis, which is a conspicuous feature of many instances of pneumonia following influenza, is referable, in part at least, to obstruction of the bronchi by mucopurulent exudate.

The term pneumonia will refer to those inflammatory changes in the lung which are found within the alveoli; it will include inflammatory changes in the alveoli surrounding the respiratory bronchioles, in the alveolar ducts and infundibula and in their tributary alveoli. Bronchitis will be described by defining the changes which occur (a) in the small bronchi with no cartilage or mucous glands, and (b) in the large bronchi including the primary branches of the trachea.

For convenience of description those bronchi may be designated small, which have no cartilaginous plates in their wall. Larger bronchi have cartilage and mucous glands, the latter situated in considerable part outside the cartilaginous plates. These bronchi, of which the largest are the right and left bronchi formed by bifurcation of the trachea, diminish with repeated branching to a caliber of about 1 mm. Small bronchi are lined by columnar ciliated epithelium; their wall consists of very vascular connective tissue containing a layer of smooth muscle and their caliber varies approximately from 1 to 0.5 mm. It is convenient to designate as respiratory bronchioles^[80] the terminal ramifications of the bronchi; they are lined by a single layer of columnar ciliated cells passing over into cuboidal nonciliated epithelium and are beset with small air sacs lined by flat cells or epithelial plates similar to those of the alveoli elsewhere. Not infrequently these alveoli occur along only one side of the bronchiole, the remainder of the circumference being covered by a continuous layer of cubical epithelium. The respiratory bronchiole by branching along its course or at its end is continued into several alveolar ducts which unlike the respiratory bronchioles have no cubical or columnar epithelium but are closely beset by alveoli lined by flat epithelial plates. The alveolar duct is recognized by the absence of cubical epithelium and the presence of bundles of smooth muscle which occur in the wall. The infundibula or alveolar sacs arise as branches from the alveolar ducts and like them are beset with alveoli, but smooth muscle does not occur in their walls. The base of the infundibulum is wider than its orifice, which Miller states is surrounded by a sphincter-like bundle of smooth muscle.

Changes in the main bronchi and their primary branches are usually less severe than those in bronchi of smaller size. The epithelium is often intact, the superficial cells being columnar and ciliated, but not infrequently desquamation of superficial cells has occurred and the lower layers alone remain. Occasionally (Autopsy 471) there is necrosis of epithelium with which, although the architecture of cells is preserved, nuclei have disappeared. Accumulation of blood or serum may separate epithelium from the underlying basement membrane (Fig. 1). Complete loss of epithelium occurs, usually in small patches.

Polynuclear leucocytes are numerous upon the surface of the epithelium and are sometimes fixed in process of migration through epithelium and basement membrane.

The blood vessels of the mucosa are engorged. There is sometimes edema or hemorrhage, and in the superficial part of the mucosa polynuclear leucocytes are often fairly abundant. When superficial epithelium has been lost, polynuclears are numerous immediately below the surface of the exposed tissue. Fibrin is often present upon the denuded surface and extends for a short distance into the tissue below. In the deeper part of the mucosa, about the muscularis and especially about and between the acini of the mucous glands, the tissue is infiltrated with lymphoid and plasma cells.

Changes in the mucous glands are invariably present. These changes are distention of ducts and acini with mucous, degenerative changes occasionally ending in necrosis of cells, disappearance of acini, dense infiltration of interstitial tissue with lymphoid and plasma cells and finally proliferation of this interstitial tissue. The duct of a mucous gland, dilated and filled with mucus, may be surrounded by lymphoid and plasma cells in great number. Acini, similarly dilated, contain mucus and are composed of cubical cells which have discharged their mucous content. In some instances (e. g., Autopsy 257) the cells of the acini have undergone necrosis; the cytoplasm stains homogeneously and the nuclei have disappeared. Where necrosis has occurred, polynuclear leucocytes may penetrate into the dead cells. In association with degenerative changes in the acini there is abundant infiltration of the interstitial tissue within and about the glands with lymphoid and plasma cells. When the acini have disappeared there is proliferation of fibroblasts and new formation of fibrous tissue, and mucous glands are found in which a few atrophied acini are separated by newly formed fibrous tissue.

With the bronchitis of influenza the small bronchi (with no cartilage or mucous glands) show every stage of transition from early acute inflammation characterized by accumulation of polynuclear leucocytes within the lumen, engorgement of blood vessels, and infiltration of the wall with polynuclear leucocytes, through various stages of destructive changes to complete disappearance of the bronchial wall and formation of an abscess cavity at the site of the bronchus. In the early stages of acute bronchitis, hemorrhage is frequently associated with the lesion. Blood may be abundant within the lumen of the bronchus, and in the mucosa red blood corpuscles often infiltrate the tissue around greatly distended blood vessels, or accumulating below the epithelium, separate it from its basement membrane. Hemorrhage is not limited to the wall of the bronchus, but frequently occurs into the alveoli in a zone encircling the bronchus.

With acute bronchitis there may be desquamation of epithelial cells with partial or complete loss of epithelial lining. In the smallest bronchi the single layer of columnar cells may be separated in places from the underlying tissue, so that intact rows of cells are found within the lumen. In somewhat larger bronchi, lined by epithelium in multiple layers, superficial columnar ciliated cells may be lost. In some instances superficial epithelial cells appear to have lost their cohesion and are separated by narrow spaces; in these instances, polynuclear leucocytes are often numerous between epithelial cells. Epithelium is occasionally separated from its basement membrane by small accumulations of serum or blood. Occasionally necrosis of epithelial cells with disappearance of nuclei is seen and is doubtless caused by the action of bacteria; the affected cells may be raised from the underlying tissue by accumulated serum (Autopsy 253). The changes which have been described bring about partial or complete loss of the ciliated lining of the bronchial tube.

The severity of changes in the bronchial wall is in direct relation to the extent of destruction of the lining epithelium: when the epithelium remains intact polynuclear leucocytes may be found in considerable number immediately below it, but as the lesion progresses, cells in great part mononuclear, namely, lymphoid and plasma cells, accumulate in large number throughout the wall of the bronchus. There is often abundant cellular infiltration within and about the bundles of the muscular coat. The changes assume the character of chronic inflammation.

When the lining epithelium of the bronchus is lost, fibrin tends to accumulate over the surface of the defect, to which it is firmly attached. It remains separated by a conspicuous space from adjacent intact epithelium over which it may project. This superficial network of fibrin merges with a similar network, extending to a variable depth within the tissue. What may well be described as coagulative necrosis has often occurred, and structures, such as white fibrous bundles or wall of blood vessels, are marked out by hyaline material which merges with fibrin. When the walls of the blood vessels which are invariably engorged are involved, the lumen is plugged by a fibrinous thrombus.

Little patches of fibrin adherent to the inner surface of the bronchus may occur in spots where epithelium has been lost; with uniform loss of epithelium the entire circumference may be lined with fibrin forming a circular zone occasionally quite uniform in thickness.

Accumulations of polynuclear leucocytes doubtless bring about conditions which cause solution of fibrin or prevent its formation (when disintegration of leucocytes sets free leucoprotease in abundance). The activity of the infecting microorganisms, usually hemolytic streptococci or staphylococci, may cause complete necrosis of a part or all of the bronchial wall. The cavity which is formed may penetrate into lung tissue that has previously undergone pneumonic consolidation.

Further changes caused by the bronchitis of influenza will be considered under peribronchial hemorrhage and edema, peribronchial pneumonia and bronchiogenic abscess. Purulent bronchitis is almost invariably associated with dilatation of the bronchi, the affected bronchi being distended with pus. With increasing dilatation bronchiectasis becomes evident upon gross examination of the tissue, and is much more advanced in the small bronchi than in the larger cartilaginous passages. This subject will be further considered under bronchiectasis.

In association with the acute bronchitis of influenza the epithelium of bronchi not infrequently looses its superficial columnar ciliated cells and assumes some of the characters of a squamous epithelium being covered by polygonal or flat cells (Figs. 17 and 18). The condition is often described a “squamous metaplasia,” although it doubtless represents a stage of regeneration following injury rather than a true metaplasia. The basal cells of the epithelium have a cubical or columnar form; above them the cells become polygonal and as the surface is approached, cells are flat and even scale-like. The nuclei of these superficial cells are often lost. There is no close resemblance to the squamous epithelium of the skin, for intercellular bridges are not seen.

This change may occur within six days after onset of influenza, though in most instances the duration of illness has been two weeks or more. It may affect either large or small bronchi, but it is more frequently found in the latter. Whenever ciliated columnar cells are lost, superficial cells tend to become flat. Epithelium on one side of a bronchus may have a squamous character, whereas that elsewhere is columnar and ciliated. The flat epithelium may undergo thickening so that it is 0.1 mm. or more in thickness. It is noteworthy that regenerating epithelium growing over a denuded surface has the squamous character which has been described (Plate XIV, Fig. 22).

Bacteriology of the Bronchitis of Influenza.—With the pneumonia of influenza, bronchitis is invariably present. Cultures have been made from the right or left main bronchus or from the very small bronchi which contained purulent exudate. A routine method of making the culture has been adopted. The right main bronchus, exposed by drawing the right lung out of the chest and toward the midline, was widely seared with a hot knife; the bronchus was partially cut across through the seared surface with a heated knife and a platinum needle inserted into the lumen. The bacteria obtained named in the approximate order of their relative frequency have been: B. influenzæ, pneumococci, hemolytic streptococci, staphylococci (aureus and albus), B. coli, S. viridans, M. catarrhalis, and diphthoid bacilli which have not been identified. Mixed infections occurred in most instances. The following list arranged by grouping bacteria in the order cited above, shows how varied have been the combinations which occur:

B. influenzæ has been present in the bronchi in 79.3 per cent of instances of pneumonia referable to influenza. Combinations which have been found most frequently are B. influenzæ and pneumococci (17 instances), B. influenzæ and hemolytic streptococci (18 instances), or the same combinations with staphylococci, namely, B. influenzæ, pneumococci and staphylococci (15 instances), and B. influenzæ, hemolytic streptococci and staphylococci (16 instances). There is little doubt that B. influenzæ was not identified in some instances in which it was present; when other microorganisms are very numerous its inconspicuous colonies may be overgrown even though the presence of pneumococci, streptococci or staphylococci tends to increase the size of its colonies. Moreover, it is not improbable that the microorganism may disappear from the bronchi. Comparison with observations made upon influenza suggests that multiple methods of examination might have demonstrated a much higher incidence of B. influenzæ. Throat cultures alone made during life demonstrated the presence of B. influenzæ in only 65.7 per cent of patients with acute influenza, whereas when cultures were made from the nose, throat and sputum, and a mouse was inoculated with sputum from each patient, B. influenzæ was found in every instance. After the acute stage of the disease had passed, the number of microorganisms diminished, and in many instances B. influenzæ disappeared from the upper air passages. In some of our autopsies B. influenzæ doubtless present during life has similarly disappeared before death due to pneumonia caused by pneumococci or streptococci. In view of these considerations it is not improbable that B. influenzæ demonstrated by a single culture in 80 per cent of instances has been constantly present.

Table XXVIII represents the incidence of pneumococci, hemolytic streptococci, staphylococci, and B. influenzæ in the bronchi, lungs and blood of those individuals with pneumonia in whom bacteriologic examination has been made at autopsy. The number of cultures made from the bronchi, lungs or blood of the heart is given in the second column of the table and in other columns are given the incidence in number and percentage of the microorganisms which have been mentioned.

Cultures from the bronchus represent the bacteriology of the bronchitis of influenza. Infection of the lung following influenza doubtless occurs by way of the bronchi, so that the bacteria which cause pneumonia are present in the bronchi before they enter the lung tissue. The figures in Table XXVIII, similar to those previously cited, show the high incidence of B. influenzæ, and the occurrence of pneumococci, hemolytic streptococci and staphylococci each present in approximately half of all autopsies.

The figures in Table XXVIII are an index of the capacity of the microorganisms which enter the bronchi to invade the lungs and finally the blood. Pneumococci were present in the bronchi in 46.3 per cent of instances, in the lungs in only slightly less, and in approximately 40 per cent of autopsies they had penetrated into the blood. Hemolytic streptococci enter the bronchi with the same frequency and exhibit an equal ability to penetrate into the lungs and blood. Staphylococci enter the bronchi in half of these individuals, but penetrate into the lungs in only a fourth of the instances. They have entered the blood only once (Autopsy 263) in this instance in association with hemolytic streptococci. B. influenzæ has been present in the bronchi in approximately 80 per cent of autopsies. It is noteworthy that it has been found in the lung in little more than half this percentage of instances and has entered the blood only once (Autopsy 474), in this instance in association with hemolytic streptococci.

In a limited number of autopsies there was purulent bronchitis recognized by the presence of mucopurulent exudate in small bronchi. It has been stated that this group of cases is not sharply separable from other instances of bronchitis, because in some cases death has occurred before a purulent exudate has accumulated or in other instances a purulent exudate has been displaced by edema. Table XXIX shows the bacteriology of instances of purulent bronchitis:

The percentages of various bacteria with purulent bronchitis do not differ essentially from those obtained from all autopsies with pneumonia. B. influenzæ is found in approximately 80 per cent of autopsies. In 16 instances cultures were made from the purulent fluid contained in a small bronchus and the incidence of B. influenzæ (namely, 81.4 per cent) has not differed from that in the main bronchus. In 7 of 8 instances in which cultures were made, both from the right main bronchus and from the purulent fluid in a small bronchus, B. influenzæ was found in one or other in all but one autopsy (87.5 per cent); in this instance (Autopsy 472) respiratory disease began thirty-seven days before death and cultures from large and small bronchi at autopsy were overgrown by B. coli. Since observations upon influenza made during life have shown that B. influenzæ is constantly demonstrable when multiple methods are employed for its detection, the figures just cited give support to the suggestion that B. influenzæ is constantly present in the bronchi with the bronchitis of influenza.

Lobar Pneumonia

The frequency with which the confluent lobular consolidation of bronchopneumonia involving whole lobes or parts of lobes follows influenza has emphasized the desirability of distinguishing carefully between lobar and confluent lobular pneumonia. The pulmonary lesion has been designated lobar pneumonia when it exhibited the well-known characters of this lesion, namely, firm consolidation of large parts of lobes, coarse granulation of the cut surface, fibrinous plugs in the bronchi and, on microscopic examination, homogeneous consolidation and fibrinous plugs within the alveoli. With confluent lobular consolidation of bronchopneumonia the consolidated area is in most cases obviously limited by lobule boundaries, and well-defined lobules of consolidation occur elsewhere in the lungs.

Lobar pneumonia occurred in 98 among 241 instances of pneumonia following influenza, namely, in 40.7 per cent of autopsies.

The difficulty of separating lobar and bronchopneumonia following influenza has been increased by the frequent combination of the two lesions in the same individual. There were 34 instances in which lobar and bronchopneumonia occurred together. The anatomic diagnosis of lobar pneumonia was made only when lobes or parts of lobes were firmly consolidated and exhibited the characters of the lesion enumerated above; in several instances, in which there was some doubt concerning the nature of the lesion, microscopic examination was decisive. The associated bronchopneumonic lesions represented all the types which have been associated with influenza. In the group of 34 cases of coexisting lobar and bronchopneumonia, lobular consolidation occurred 10 times, peribronchiolar consolidation 14 times (recognized in all but 4 instances by microscopic examination), hemorrhagic peribronchiolar consolidation 9 times, peribronchial pneumonia 4 times. The intimate relation of these lesions to changes in the bronchi is well shown by the frequent presence of purulent bronchitis. The associated lesions of the bronchi in these cases were as follows: purulent bronchitis in 23 instances; peribronchial hemorrhage in 6; bronchiectasis in 11. The frequency of purulent bronchitis and other bronchial lesions in association with coexisting lobar and bronchopneumonia is in sharp contrast with the occurrence of these lesions in association with lobar pneumonia alone; with 69 instances of lobar pneumonia alone purulent bronchitis occurred 17 times and bronchiectasis once.

Lobar pneumonia following influenza passes through the usual stages of red and gray hepatization. Red hepatization was found 16 times, combined red and gray hepatization 28 times, and gray hepatization 20 times. The average duration of pneumonia with red hepatization was 3.7 days, with combined red and gray hepatization 5.1 days and with gray hepatization 7.5 days. These figures, it will be shown later, have some importance in relation to the stage at which hemolytic streptococcus infects lungs the site of lobar pneumonia.

Bacteriology of Lobar Pneumonia.—Table XXX is compiled with the purpose of determining the bacteriology of the bronchi, lungs and heart’s blood in autopsies performed on individuals with lobar pneumonia. In some instances bacteriologic examination of one or other of these organs was omitted; the percentage incidence is an index of the presence of pneumococci, hemolytic streptococci, staphylococci or B. influenzæ in the bronchi, lungs or heart’s blood and measures the invasive power of these microorganisms during the course of lobar pneumonia following influenza.

Pneumococci, the recognized cause of lobar pneumonia, were found in the lungs in 73.3 per cent of autopsies; failure to find the microorganism in all instances is doubtless the result of its disappearance from the lung, which, it is well known, occurs not infrequently particularly during the later stages of the disease. In 65.5 per cent of instances of fatal lobar pneumonia pneumococci have entered the heart’s blood.

Hemolytic streptococci unlike pneumococci were found more frequently in the bronchi than in the lungs; this microorganism which exhibits little tendency to disappear, once it has established itself within the body, found entrance into the bronchi in 31.8 per cent of instances of lobar pneumonia and in 24.5 per cent entered the lungs. Its invasive power is further illustrated by its penetration into the heart’s blood approximately in half this proportion of autopsies.

Staphylococci enter the bronchi in many instances (50 per cent), but relatively seldom (15.1 per cent) invade the lung and rarely if ever penetrate into the blood.

The high incidence, namely, 84.1 per cent, of B. influenzæ in the bronchi is particularly noteworthy; it exceeds that of pneumococci, the well-recognized cause of lobar pneumonia, within the lung. It is found much less frequently within consolidated lung tissue and shows no tendency to invade the heart’s blood. B. influenzæ finds the most favorable conditions for its multiplication within the bronchi.

In view of the frequent occurrence of coexisting lobar and bronchopneumonia it has appeared desirable to determine how far the existence of obvious bronchopneumonia modifies the bacteriology of lobar pneumonia. In Table XXXI the incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzæ after death with lobar pneumonia on the one hand is compared with their incidence after combined lobar and bronchopneumonia on the other.

Pneumococci are found in the lung more frequently with lobar than with combined lobar and bronchopneumonia. The incidence of hemolytic streptococci and of staphylococci in the lung is on the contrary higher when bronchopneumonia is associated with lobar pneumonia. It is not improbable that these microorganisms have a part in the production of associated bronchopneumonia. The frequency with which microorganisms invade the blood is almost identical in the two groups.