Studies on Epidemic Influenza: Comprising Clinical and Laboratory Investigations

by University of Pittsburgh. School of Medicine

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.