Part 31

A considerable discussion has arisen concerning the proper nomenclature for the pneumonia or pneumonias found in epidemic influenza. From some quarters have come the reports of a true lobar pneumonia, from others a lobular or broncho-pneumonia and others again claim that the reaction is an interstitial pneumonia of varying distribution. It appeared to us that the gross distribution of the lesions is not alone the criterion for a proper appreciation of the inflammatory states which may arise within the lung. I believe it has been amply demonstrated that the pneumonic reactions appearing in different regions of the United States as well as in different countries are not of a constant kind when viewed alone in the light of the gross picture nor are they constant from the standpoint of their bacteriology. We are of the opinion that the earlier phases of the pulmonary reaction are fairly constant in different places and that this constancy is dependent upon the common virus which initiates the respiratory lesion and which then permits a variety of micro-organisms invading as secondary agents. The secondary agents vary with the community and depending upon their nature the character of the reaction differs from that in other places. It has been well demonstrated that in some regions the hemolytic streptococcus is the important organism following the primary injury by the initial virus. In other places the pneumococcus or the staphylococcus or the M. catarrhalis is found to be of primary importance. Up to the present it has not been shown that the influenza bacillus is not the important organism causing the initial reaction and being responsible for the opportunity of secondary invaders leading to such diverse reactions in the lung. In our series we have met with lobar, lobular, interstitial and broncho-pneumonic types. We have not observed a case of the miliary bronchial reaction as described and illustrated by Goodpasture and Burnett and fully investigated by MacCallum. Moreover we have not met with the type of purulent bronchitis as a characteristic lesion preceding pulmonary involvement. The occurrence of pus within the bronchi occurred not early in the pulmonary lesion but later after the bronchi and bronchioles had passed through their stages of acute, serous and hemorrhagic pneumonia and were entering upon their secondary stage with pus production. The pulmonary lesion had long preceded the appearance of pus in the bronchi. We do not hold, however, that such relations between the pulmonary lesion and the purulent bronchitis do not exist for there is evidence that in particular regions this sequence of events was closely observed.

We cannot, however, correlate our findings with the classification of pneumonias as given by MacCallum. His claim for specific types of pneumonia as a sequel to influenza is based upon his statement that “no satisfactory evidence has been brought forward to show that the epidemic influenza is a bacterial infection. It is evidently a general or systematic infection not especially affecting the respiratory tract and analogous in many respects, as Bloomfield has pointed out, to the acute exanthematic diseases.” Thus we are confronted by two schools concerning the nature of influenza. The one claiming that epidemic influenza is essentially a disease of the respiratory system and the other completely denying this.

I am unable to understand the claims which are put forward to substantiate the second view.

The classification of the pneumonias as suggested by MacCallum would be valuable if it could be applied in a practical manner. We find, however, that his description for the pneumococcus-pneumonia hardly coincides with common observations on endemic pneumonia and if the description is to apply only to the pneumonias associated with influenza wherein pneumococcus alone is isolated we find that our own observations do not coincide with this. The picture offered by MacCallum under this heading was reproduced when the bacteriological findings illustrated the presence of organisms other than the pneumococcus or combinations of these. The most characteristic of his description is the one for the streptococcus-pneumonia which when present alone gives quite a unique picture. The picture, however, is to a certain degree modified by the reactions which precede the streptococcus in the lung. Furthermore to offer as a characteristic picture for the influenza infection of the bronchi the presence of a thick yellow pus is hardly complete inasmuch as this exudate appeared only as a stage in the inflammatory process. The intense serous and hemorrhagic response observed early in this type of infection is more unique than the presence of pus which appears somewhat later and which may occur with infections other than the B. influenzæ. It has long been the hope in pathology to be able to establish by the character of the tissue reaction, the nature of the infecting agent. Up to the present this has been possible only with a very few types of bacteria.

_Lung—Stage of Resolution_

The removal of the infection and the inflammatory exudate from the lung tissue is accomplished slowly. Clinically the pulmonary process clears up by lysis, and it is quite unusual to have a crisis with the rapid disappearance of the serious manifestations. It is difficult to obtain a clear conception of what takes place in any individual case recovering from an influenza-pneumonia, but if we have an understanding of what may occur in the inflamed lung tissue in any one of the stages or varieties of kind, we may visualize the changing character of the lung condition tending toward the final restoration.

We have previously pointed out that the early stage of influenza-pneumonia is one of congestion, œdema, hemorrhage and more or less leucocytic infiltration, and that this reaction differs materially from that observed in pneumococcus lobar pneumonia. There being no stage of true red hepatization, it has also become apparent that this peculiar primary reaction need not pass into the stage of gray consolidation. Scattered areas in the lung pass from the condition of acute serous and hemorrhagic pneumonia to a type of purulent pneumonia while much of the remaining tissue continues in the state as seen in the early reaction. A certain amount of cellular exudate makes its appearance but not sufficient to lead to a true consolidation. This variety of reaction is present from the fifth day of the pneumonia onwards and may continue with all of its varieties through until the tenth or twelfth day or even longer when recovery from the infection is beginning. Thus the stage of resolution makes its appearance before the inflammatory reaction in the involved lobes has assumed a common character and where we are able to recognize different grades of severity and different stages of inflammation within the same lobe. Resolution taking place in such a lobe has responses occurring in the different parts determined by the nature of the antecedent reaction. We have found that those portions which have not advanced beyond the stage of œdema and hemorrhage may clear up with the disappearance of this early exudate and its infection. In a neighboring portion the purulent inflammation passes through phases differing somewhat from the preceding but also tending toward the restoration of the parenchyma and the disappearance of the inflammation. It would be incorrect to consider the resolution of the early type of inflammatory reaction as an abortive process inasmuch as it is not yet clear whether this serous and hemorrhagic process is not the characteristic inflammation of a peculiar micro-organism or organisms and that when acting alone these bacteria do not in themselves stimulate a further inflammatory response. Hence if it is true that there is a peculiar inflammatory reaction of a non-suppurative and non-fibrinous kind the manner of resolution will differ somewhat from that where these other constituents of the exudate are present. It becomes clear, therefore, that in influenza-pneumonia all of the lung involved in the early peculiar inflammatory reaction need not pass through those stages and reactions as we recognize them in pneumococcus lobar pneumonia.

The resolution taking place in the areas of serous and hemorrhagic pneumonia is accomplished largely by a reabsorption of the fluid, autolytic disintegration of the red blood cells and a certain amount of phagocytosis of red blood cells and their debris. This resolution is quite rapidly accomplished, and the clearing up of such an area may take place in a remarkably short period of time. The leucocytes and endothelial cells which are present with every such reaction become active in phagocytosis of bacteria, and we have repeatedly observed them crowded with small Gram negative bacilli, whose morphology is similar to that of the B. influenzæ. These areas contain but few bacteria of other kinds. The exudate in the alveolar walls is also simple in character and is readily removed. Slight suffusion of blood, serous fluid, and migrating cells may occupy portions of the alveolar walls during the acute reaction, but these, too, are easily removed and the tissue rapidly resumes its normal character. The vascular and lymphatic congestion again disappear and the tissues which once were soggy return to a normal state without leaving behind evidence of the pulmonary incapacity. The lining epithelium of trachea, bronchi and alveoli is restored by proliferation from the neighboring less injured parts.

If this early stage in influenza-pneumonia is to be compared with the early reactions of endemic pneumonia, it is interesting to note with what ease the resolution may be accomplished in the former, whereas in the latter a further sequence of stages must apparently be passed through before the lung is cleared of its inflammatory products. As we have intimated before, the early exudate in these two types of pneumonia differs very essentially, the one being accompanied by much fibrin and leucocytes which are present only in small quantities in the pulmonary lesion of influenza.

Resolution of the other portions of the involved lobes in influenza is not so easily accomplished. Where a progressive lesion with its development of pus occupying both the air sacs and the tissue of the lung, the outcome of attempts at repair are uncertain. Complete resolution with complete disappearance of the purulent exudate may take place as we see it in many other regions occupied by a similar reaction; and where the purulent response is not accompanied by material damage to the tissue the restoration of the lung is so complete that upon its recovery no evidence is left behind of the former injury, but in as much as the presence of a purulent reaction in the lung is often of more severe grade than this, a certain amount of tissue destruction having been accomplished, the repair does not completely restore the tissue to its former normal state. The purulent lesion, however, is not uncommonly accompanied by minute capillary thromboses, tissue derangement, organic destruction, with even tissue alteration amounting to abscess or gangrene, and it is too much to hope that the lung may be completely restored. Minute abscesses varying from microscopic size to large cavities, several centimeters in diameter, were not unusual in the tissues severely involved in the purulent reaction. Thus in these areas, resolution can be accomplished only by a process of slow organization of the damaged parts with the final production of fibrosis. These fibroses are of variable extent depending upon the initial damage. We have been very much struck with the speed with which this process of organization may take place and the extent of the lung tissue which may become involved in this late lesion. In one of our cases we have evidence of marked fibrosis present on the twenty-third day of his illness. Patches of organization varying from one to four centimeters in diameter occupied the different lobes of the lung. The new fibrous tissue was well developed and the purulent reaction had largely disappeared. The fibrosis obliterated the normal architecture of alveoli and bronchioles, leaving only irregular islands of epithelium which assumed grotesque glandular shapes and looked not unlike a new growth. One of the interesting features of these late fibroses which come to occupy various extents of the lung and bronchial tissues is that the individual after recovering from his acute influenzal lesions again passes, in about his third week, into a stage of dyspnœa with manifestations out of proportion to the physical signs or constitutional derangements which can be determined. The dyspnœa is often the outstanding sign and the patient may die in a state of asphyxia.

We have observed evidence of organization in its earlier reactions taking place in the patches of gray consolidation. This organization of the lung tissue takes place as an interstitial fibrosis and as an alveolar organization. Masses of granulation tissue grow out into and come to occupy the lumen of the air sacs, while in other instances the new growth of tissue takes place mainly in the alveolar walls converting them from thin partitions to thickened and tough structures. In the cases in which a purulent pneumonia was present for some time, and where some of these tended towards repair, this type of restoration with the new development of connective tissue was found. The amount of fibrosis varied very much, and in many instances there was no evidence that obstruction to the bronchioles occurred to a material degree. Hence, although we believe that more or less organization occurs in all of those cases which have passed through a purulent pneumonia, and that a permanent mark is left upon the lung tissue, it is not probable that the amount of involvement and final damage by fibrosis is sufficient to seriously influence the pulmonary respiration. There is, however, a certain percentage of cases in which this organization and fibrosis does involve sufficient of the lung parenchyma and bronchioles to interfere with the pulmonary ventilation.

Where the purulent pneumonia has markedly involved the parenchyma, and particularly where vascular channels both large and small have suffered, some of them by thrombosis, others by a sclerotic thickening, the circulatory disturbance may be sufficiently interfered with to infarct the area. The infarction usually occupies the purulent area itself, and with the complete occlusion of the circulation the resulting necrosis gives rise to an appearance different from that usually seen in pulmonary infarcts. The area may lie in the peripheral portion of the lobe or may occupy deeper parts. The infarct is of a cream-white color, quite homogeneous, and resembles the appearance of a local area of caseous pneumonia. This appearance is brought about through the local purulent consolidation undergoing necrosis. Some of these areas rapidly develop a cavity through liquefaction of the exudate.

The localization of the inflammatory products not only upon the surface of the air sacs but also in the stroma of the alveoli; the interlobular trabeculæ, and about the vascular channels indicates the intense effect of the virus of this disease. The exudate is largely an indication of the point of action of the irritant upon the tissues, and in influenza with its variety of bacteria in the lung this is not limited to the surface membrane of the air sacs. During this second stage of the reaction the purulent exudate was found occupying all structures of the involved area. Damage upon the component tissues was to be seen in the endothelium of the capillaries, the muscle tissue of the bronchioles and arterioles, the connective tissues and the epithelium. It was seldom that bacteria were demonstrated in the interstitial parts, and it would appear that the damage was the result of their toxins.

Hence, broadly speaking, the end result of the pneumonic process in influenza is far more complex and indefinite than that in lobar pneumonia. Resolution may take place early with the clearing up of the first products of the exudate; or it may be delayed in association with the secondary purulent process which not uncommonly occupies multiple lobes. Where the resolution begins in purulent regions the final outcome is most variable, depending upon the amount of damage which has been imposed upon the lung tissue during the suppurative inflammation, ending either in complete restoration or slight fibrosis of the lung, or passing on to focal scarring of various degrees, sufficient to alter the pulmonary capacity. In other instances the resolution is delayed by the development of abscess, infarct and gangrene. Here the final outcome is determined by the amount of tissue involved in the destructive process, and the persistency with which the infecting micro-organisms attack the local tissues and the constitutional resistance of the individual. Those individuals in whom resolution begins before there is much purulent pneumonia stand the best chance of having the lung return to its normal characteristics.

_Pleura_

Inflammation of the pleura was a complication which varied in its extent and appearance. It appeared to us that a definite interval lapsed between the development of the lesions in the lung and the appearance of an inflammatory reaction upon the pleural surfaces. Although we have recorded evidence of a pleural reaction in 27 cases, this does not indicate that we have met with that number of pleurisies of clinical severity. In this group we include all gradations of pleural reaction from the merest evidence of irritation and slight dulling of the surface to the cases in which definite and marked inflammatory exudate accumulated within the cavity. In many cases we observed a slight increase in the amount of the fluid present in one or other pleural cavity, while there was little or no macroscopic evidence of a cellular or fibrinous exudate. An examination of the fluid showed the presence of lymphocytes and endothelial cells in small numbers, and sections of the pleural surface at points where a slight dulling of the serous membrane was seen at autopsy showed the presence of a very thin layer of a hyaline fibrin. By taking these reactions as indicative of pleurisy we have recorded 6 cases of acute fibrinous pleurisy, 20 of acute serofibrinous pleurisy, and 1 of acute fibrino-purulent pleurisy.

An increase in the quantity of fluid in the pleural sacs was the most common indication of pleural irritation. The quantity varied from 50 to 500 c.c. of a clear or slightly turbid fluid. Not uncommonly this fluid was blood stained and evidence of superficial extravasation of blood could be recognized directly beneath the pleural membrane. These serous reactions accompanied the early acute stage, while hemorrhage was the accompaniment of the early period of the influenzal pneumonia when similar hemorrhages were found in the lung substance. The pleural reactions were almost entirely confined to the visceral pleura, and only in the very severe responses did we obtain a marked inflammatory reaction with hemorrhage upon the chest wall. Goodpasture and Burnett state that “there is commonly a moderate serous effusion in one or both pleural cavities amounting to 50 or 250 cubic centimeters. The fluid is clear and has the color of blood-stained serum. The pleural surfaces are smooth, shiny and wet, though occasionally a thin, granular fibrinous exudate may be seen by reflected light over limited areas. Often numerous small, red, discrete, or confluent pleural hemorrhages are present over consolidated portions, especially posteriorly on the surface of the lower lobes.” Where organisms other than the influenza bacillus had invaded the pleural sac and had been present for a sufficient time to obtain a reaction, the serous type of exudate observed in the early lesions changed to the turbid type of fluid accompanied by more or less fibrin deposit. There was one case where the intense reaction with fibrin and leucocytes gave rise to a new character to the pleural exudate, a fibrino-purulent pleurisy or empyema.

As we have subsequently learned the pleurisies developing late in the course of the influenza and those which persist after the pulmonary inflammation has passed are prone to be of a purulent kind. There have been a fair number of cases of empyema brought to our attention by the surgical department in the bacteriological laboratory of the hospital, subsequent to the wave of epidemic influenza. If one were to base his finding alone upon observations obtained in the operating room, he would be impressed by the fact that the pleurisy accompanying the epidemic of influenza is of a purulent type. On the other hand, if one were alone to consider the findings at the autopsy table during the five weeks of the epidemic, one would be of the opinion that the pleurisy is of very minor consequence and of a serous type. It is this changing picture which is particularly to be kept in mind. And our experience indicates that during the height of the influenzal lesions of the lung when the pulmonary lesions develop so rapidly that we obtain a pleural reaction closely resembling the inflammatory conditions in the lung and also containing bacteria not unlike the pulmonary flora. Dr. Holman has obtained the influenza bacillus and other varieties from the pleura during these early periods of the pulmonary inflammation. It is more than probable that just as in the infection of the lung tissue where there is a change in the type of the bacteria present, so, too, the flora of the pleura alters in the succeeding stages of the pulmonary reaction. In the late event of empyema we have not observed the influenza bacillus. The majority of the empyemas possess hemolytic streptococci and occasionally pneumococci.

_Heart_

During the acute epidemic and while the disease was at its height it was remarkable how few cases showed involvement of the heart. It was the common observation that even during intense illness the heart action remained fairly stable and did not indicate an effect by intoxication as might be expected from the severity of the illness. In as much as the majority of deaths occurred within relatively few days of the onset of the severe infection, the type of lesion that would be looked for in the heart would be either bacterial inflammatory products within the pericardium, myocardium or endocardium or toxic lesions of musculature alone.

In our series we have encountered no cases of pericarditis. This lesion in the experience of others has also been unusual, and it would appear that bacterial invasion of this sac is accomplished mainly in the presence of secondary infections localizing in the neighboring pleura. It was not uncommon to find a slight increase in the serous fluid in the sac, but this on no occasion amounted to a hydropericardium. The fluid was always clear and with no evidence of fibrin or cellular exudate. Petechial hemorrhages scattered over the epicardium were noted in seven cases. In the majority of instances these minute hemorrhages were scattered in small numbers over the ventricular walls. In one instance these petechial hemorrhages were also present through the myocardium, suggesting the influence of an intoxication not upon the tissues of the heart as much as upon the finer structures of the vascular channels. This is furthermore borne out in the presence of petechial hemorrhages confined not to one organ, but to various tissues and structures in the body.