Studies on Epidemic Influenza: Comprising Clinical and Laboratory Investigations

by University of Pittsburgh. School of Medicine

It is of importance to appreciate that the deposition of these hyaline structures indicates a severe injury of the alveolar walls not commonly observed in ordinary pneumonias.

In different areas of the same lung these constituents of the early exudate may be observed in all proportions of admixture. Each one of the elements of the exudate may largely overshadow the others and prominently modify the appearance of the lesions. Broadly speaking, however, the inflammatory œdema and hemorrhage occupying the greatest part of the exudate in the lungs and the absence of marked leucocytic response as well as the absence of the characteristic fibrinous meshwork in the alveoli give to the early influenza-pneumonia a character different from those which we ordinarily see.

It is during this early phase of the reaction that the influenza bacilli can be shown within the lung structures. The distribution of bacteria is not uniform. Clusters of these minute bacilli are found in the alveoli at irregular intervals, many of the air sacs containing much exudate being quite free from organisms. When present the bacteria appeared in tightly aggregated schools lying free amongst cells of the exudate, but also certain numbers being incorporated within the large mononuclear cells. In some regions organisms of the type of the influenza bacilli were alone seen, while elsewhere again, and particularly where the exudate was assuming purulent characters other bacteria of the nature of streptococci, staphylococci and micrococcus catarrhalis, were also found.

Lung—Secondary Stage

Following upon the primary reaction in the lung as above described, a secondary reaction makes its appearance at variable periods. This reaction is one in which the inflammatory exudate resembles more closely but is not identical with the responses which are observed in ordinary lobar, lobular and pneumococcus-pneumonia. Whereas in the earlier period, the reaction is largely one of a serous and hemorrhagic exudate accompanied by peculiar hyaline deposits along the inner borders of the alveoli, later there is seen a change in the quality of the exudate with the accumulation of more cellular elements and some fibrin. The naked eye appearance of the involved tissue changes considerably. The lung tissue loses in weight but becomes more solid. The lung contains less fluid and the cut surfaces are drier and the color of the reaction changes from the dark congested appearance to one showing all varieties of red and gray. This change from the flabby and soggy pneumonia to the more definite type of consolidation occurs in the regions which have been previously involved and is not to be found in the lung areas which have escaped the early reaction. The gray consolidation appears to be either a stage of the influenza-pneumonia or is a new reaction superadded to those pulmonary lesions induced by the primary infection.

It is sometimes difficult to recognize the beginning of this pneumonic stage inasmuch as the gray color does not make its appearance even with the presence of fairly large quantities of cellular exudate. The amount of hemorrhage that originally lay in the affected areas for a long time overshadows the presence of the color of the cellular exudate. This is also true of the characters that may be impressed by the presence of fibrin. Small quantities of fibrin scattered through the congested and œdematous lung are not readily recognized and the beginning of this secondary reaction is also easily overlooked if one relies upon evidence of consolidation. More or less solid exudate may occupy a flabby lung without permitting one to appreciate its presence in the gross specimen. When, however, the deposit is of sufficient quantity to change the color of the involved lobe and to alter its consistency, one has little difficulty in recognizing the changes now taking place. The earliest development of this change in the inflammatory reaction was on the fourth day. In the majority of instances the gray color and the consolidation made its appearance about the sixth day. We have, however, on several occasions observed hemorrhagic lesions as late as the seventh and eighth day, at which time it was impossible to recognize a gray hue to the exudate or the character of granular consolidation to the involved lung.

The reaction naturally suggests the stage of gray hepatization as we so well appreciate it in ordinary pneumococcus-pneumonia and from the standpoint of its color and the greater solidification of the lung tissue we might speak of it as such. Here, however, it must be clearly distinguished from the gray hepatization of ordinary pneumonia. This secondary lesion of influenza-pneumonia has but little in common other than its color and the development of a consolidation with true lobar pneumonia. It is never as clear cut as we see it in the latter and the degree of the “gray hepatization” is not uniformly distributed through the involved lobe. One portion of the lobe will show a diffuse gray hue while in other parts more decided lobular or patchy areas are picked out in the advanced reaction. There is not the uniformity of lobar involvement nor is the distribution as regular as one obtains it in broncho-pneumonia. Furthermore, the character of the consolidation differs very decidedly in showing such a variety of hues in reds and grays and the cut surface is not the picture of the dry granular consolidation of our endemic disease. The gray areas are in all states of wetness and ooze a slimy fluid on the cut surface. In the later stages this exudate is most profuse resembling a sticky pus. In its appearance we were reminded of the character seen in unresolved pneumonia as well as in the pneumonias produced by the pneumococcus mucosus, and the B. mucosus capsulatus. We would, therefore, avoid the use of the term gray hepatization and in place of it, as the evidence with the microscope confirms, use the term purulent pneumonia.

There are three other characters which differentiate this gray stage from those of ordinary pneumonias—(1) the irregular distribution, (2) the friability of the involved tissue and (3) the interstitial reaction. We have never observed such an irregularity in the distribution of a gray stage of pneumonia as we have seen it develop in acute influenza-pneumonia. All types of involvement of the lobes are found in different cases and even sometimes in the same case. The least frequent type has been the broncho-pneumonia in its true form. Broncho-pneumonia as we see it in children and the cases following measles is usually fairly uniformly seeded through several lobes and the size of the individual patches is about that of a split pea. The small bronchus can be recognized about the center of the involvement. In those instances one has studded through the lung tissue numerous small swollen areas which are granular, dry and gray. Differing from this the patchy distribution of the gray stage of influenza-pneumonia had no regularity either in the size of the areas nor the distribution. A lobe may show one or more patches. The patches may be distributed toward one portion of the lobe more than another. Furthermore the areas do not always encircle the small bronchi but involve the terminal portion so that an entire lobule is more commonly affected. The lobular type rather than the peribronchial type is most commonly seen and it is often remarkable how sharply the gray lobule is demarcated from the surrounding congested lung tissue. On several occasions we observed a single lobule in the gray stage while the remaining portion of the lobe was in the serous and hemorrhagic condition. However, multiple lobules are commonly seen closely associated in the advancing inflammatory process. Such lobules show peculiar geographical patches or leaflet-like configuration. Varying with the number of lobules involved the extent of the gray change in the lobes assumed more or less a lobar distribution. There was no uniform position to this pneumonic state sometimes appearing in the peripheral tissues of the lung, at other times lying centrally with less involved or less advanced inflammatory reactions surrounding it. Nevertheless, the gray stage made its appearance more rapidly in the lower lobe than the upper and it was not uncommon to find this condition appearing quite early in the upper posterior portion of the lower lobes. This latter position is the one which is recognized during life by the clinician as one of the earliest localizations of the demonstrable pneumonia. It is reported by many that the first physical signs of consolidation are to be obtained close to the lower angles of the scapulae.

There is no doubt that the character of the pneumonic process in the epidemic influenza was not the same in all localities. There have been not a few who have reported a large proportion of their pulmonary lesions as a definite broncho-pneumonia with an interstitial purulent involvement. The prominent reaction was a small circumscribed yellow focus about the bronchioles from which a bead of pus could be expressed. These pea-sized foci were scattered through several or all lobes. It is this type of reaction which appears to develop by a direct extension through the bronchial walls and to remain quite localized in the alveoli about these tubes. This reaction seems to be purulent from its very beginning and does not pass through the stages as we have described them above. There is more or less fibrin present in the exudate, but usually not in the quantity observed in lobar pneumonia. These lesions closely resemble those observed in the post-measles pneumonia, and it is claimed are the result of the same agent; the hemolytic streptococcus. In only one case did we observe a lesion of this kind. The small areas of broncho-pneumonia were confined to the left lower lobe and in the lower portion of the upper lobe. Each area was about the size of a split pea, was quite yellow and in fairly sharp contrast to the background of an acute sero-hemorrhagic pneumonia. The subsequent history of these interstitial purulent broncho-pneumonias is like that in measles, where the tendency toward an organizing pneumonia has been shown. The importance of the hemolytic streptococcus in inducing purulent interstitial lesions of the lung (and also of other organs) cannot be over-impressed. It is not so much the type of the reaction during its acute stage which attracts our attention, but the manner of the healing process. It is more than probable that the organizing pneumonias of influenza, not only of this distinct bronchial type, but also the lobular, confluent and lobar variety have had an associated streptococcus infection. The more intimate discussion of this type of pneumonia has been given by MacCallum.

Our autopsy experience has led us to believe that the definite clinical signs of pneumonia are associated with the development of this gray consolidation of the lung. The lung tissue develops characters which permit the physical signs to be recognized. The tissue is more solid and more readily transmits the bronchial sounds. This is not true of the earlier stages where the inflammatory process is contained within a lung tissue which still is partially crepitant and when the so-called consolidation is due to an inflammatory œdema and not to the more solid fibrinous and cellular exudate. With the protean distribution of the gray lesion one does not wonder at the clinical difficulties in mapping out or even finding the consolidated tissues.