SECTION I
PATHOLOGY OF THE ACUTE RESPIRATORY DISEASES
INTRODUCTION
Hospital Surgeon, James Mann, introduced his report of the influenza epidemic of 1815-16, with the following significant paragraph: 1
We find diseases at the present day, described under new names, which are calculated to seduce the young practitioner, from a correct and established practice. It is true, that improvements have been made in the science of medicine; but it requires a discriminating mind, and an extensive knowledge of ancient as well as modern authors, so to apply these improvements, as to be able to meet diseases, in all the varying shapes, which they assume in the routine of years.
Few physicians in active practice in 1917 were practising at the time of the pandemic of 1889-92. Perhaps fewer still were familiar with the history of acute epidemic respiratory diseases and the admirable clinical and pathological descriptions which were recorded in medical literature in the nineteenth century. It is thus not surprising that the high morbidity, and more especially the high mortality, of acute respiratory diseases which occured during the World War caused doubts to arise as to the identity of the diseases, and led to differences in opinion as to the proper nomenclature of the pathologic processes. Nevertheless, though the morbidity possibly was higher in 1918 than has been reported for any previous pandemic of this disease, the influence of increase in world population and the greater facility of transportation must be considered.
In the pandemic of 1918 it appeared that, for the first time, the medical profession was prepared to settle the bacteriology of influenza. That it did not do so was to some extent caused by the fact that the entire profession was engaged in the care of the sick. Some groups of medical men were able to investigate the bacteriology of the cases in an intensive manner, but an insufficient number were able to do so; furthermore, there was no opportunity to develop a standard technique for such investigations. While it is probable that the etiologic agent responsible for influenza has been reported and described, there is not sufficient evidence in the form of agreement among workers or verification of bacteriological results to determine that agent beyond doubt. Furthermore, no explanation of the varied bacteriological results that satisfies even the majority of the medical profession has been made.
The influenza bacillus of Pfeiffer still has the greatest claim for consideration as the etiologic agent of epidemic and pandemic influenza. In its favor are its increased prevalence just preceding and in the early part of the influenza epidemics and pandemic; its decrease in prevalence during the latter portion and after the pandemic;2 its presence in culture in the early mild and also fulminant cases; the finding of organisms morphologically and tinctorially identical in tissues from which influenza bacilli were not recovered by cultural methods and the fact that it produces a true toxin, thus accounting for generalized symptoms in the probable absence of general dissemination of the bacteria throughout the body.
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Against the etiologic relationship of this organism to influenza is the failure to find a common strain as shown by serological and immunological reactions, though this is discounted by the fact that there are numerous hemophilic bacteria of similar cultural and staining characteristics frequently found in other conditions, the organism thus apparently being a member of a large group, to be compared with Group IV pneumococci. The failure of many bacteriologists to find the organism in appreciable numbers of cases is in part explained by the demonstration that streptococci and pneumococci growing in the same culture inhibit the growth of the influenza bacillus, also that fresh or unchanged blood inhibits the growth, while blood heated, as in the so-called chocolate plates, favors it. The infrequence of influenza bacilli in blood cultures can be explained at least partly by this inhibitory influence of unchanged blood and also by the fact that in histologic sections the organism is rarely found except on the surface of tissues, apparently having little power to penetrate them. It extends rapidly along air passages, however, producing lesions on the surface and there can generate easily the toxic products which give rise to the general symptoms. A review of published reports of bacteriological investigations does not justify us in saying, on the evidence presented, that the organism was not present even though the cultures were negative.
The fact that suspensions of killed bacteria apparently show no protective influence presents no argument, pro or con, since the method of preparation may have been of such character as to destroy their immunity-producing action; moreover, we are familiar with many organisms, killed suspensions of which do not protect against infection. Failure to produce the disease by inoculation is not a very strong point against the etiological significance of the organism, for, with the widespread dissemination of the disease and the occurrence of mild cases, the presence of immunity or lack of susceptibility can not be ruled out. Certain experiments, particularly those of Cecil and Steffan,3 indicate that, given a virulent strain with which to inoculate, characteristic symptoms can be produced in susceptible persons. The difficulty of determining the pathogenicity of the organism used and the possibility of bacterial variation must be considered in this connection.
No other organism, isolated from the pandemic, appears to deserve much consideration as an etiologic factor of influenza. Bacterium pneumosintes 4 was isolated from cases after the peak of the pandemic had passed and its status can not be determined until the occurrence of another similar outbreak of the disease.
While it is not appropriate here to discuss the history of acute respiratory disease, certain lessons are taught by the experience of the armies of the United States in previous wars which should be reviewed in connection with the consideration of such diseases during the World War.
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WAR OF 1812 1
During the winter of 1812-13, there was a high incidence of acute respiratory disease among the troops stationed on the northern frontier. Measles was epidemic among the troops from September to December, 1812. As the epidemic continued the symptoms increased in severity and pneumonic complications became more frequent. Beginning in October, 1812, acute respiratory disease independent of measles assumed epidemic proportions and replaced the diarrheas, dysenteries and "intermittents" (malaria) of the summer. It was noted that the morbidity and mortality was greater among troops from south of the Delaware River. Morbidity and mortality were less in the next winter for the Army as a whole, as it consisted for the most part of seasoned troops, yet it was noted that troops joining at that time were as severely affected as were the men mobilized the preceding year.
The clinical features and the pathological anatomy of the cases were identical with those of the epidemics of the fall of 1917 and the spring of 1918; the pathology of which, as is now realized, is not to be differentiated from that of the influenza pandemic of the fall of 1918.
This influenzal disease attacked the troops of 1812 throughout the various Army stations but showed varied clinical pictures in different stations. A catarrhal affection was universal among the men at all stations at the time of the epidemic.
In many of the early cases death occurred within one to four days of the onset of severe symptoms and appeared to be from suffocation rather than from that group of symptoms usually associated with pneumonia. The labored respirations were not from pain but from a sense of suffocation. Mann considered that the lung, by reason of engorgement of the bronchi, excluded air from the smaller ramifications and thus was "incapable of absorbing or transmitting through its membrane the vital principle of the atmospheric air." The lungs were filled with blood, were dense and heavy and frequently sank in water. Empyema was apparently frequent in cases surviving sufficiently long. The clinical picture varied as did the pathology not only as between stations but also at the same station. Repeated removal of small amounts of blood was found an efficacious method of treatment. The explanation of the efficacy of bleeding is somewhat obscure but it is noteworthy that during the last pandemic the blood was found to be concentrated and the removal of small amounts of blood and forcing fluids appeared to be an efficacious treatment in the early stages of the disease.5
Acute respiratory diseases were not as prevalent in the winter season of 1813-14 but in the fall of 1815-16, epidemic influenza spread over the eastern United States and Brazil.6
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Mann described the clinical course and pathology of this epidemic in the civil population of Sharon, Mass., in considerable detail and stated that they were identical with that seen in the troops of the northern frontier during the two preceding seasons.a
CIVIL WAR (1861-1865)
Acute respiratory diseases were an important cause of morbidity and mortality throughout the entire period of the Civil War. 7
There was no such epidemic as the one of the fall of 1918 in the World War, but there were excessive seasonal variations in the respiratory disease rates with a curve for "catarrh" in the winter of 1862, resembling that for the influenza epidemic of 1918. The percentage of fatal cases of pneumonia for the five years 1861 to 1866, inclusive, was 24.08 for white troops, and during the last three years it was 32.44 for colored troops. The rates were higher during the first year, decreasing rather slowly in the white troops and more rapidly in the colored. In the Confederate troops the acute diseases of the respiratory tract are represented as being of more serious import than among the Federal troops. In one hospital 37.18 percent of the cases of pneumonia and pleurisy proved fatal. A comparison table shows an annual death rate per thousand for pneumonia of the Confederate armies as 20.6 and of the Union troops 7.8. The influence of measles in epidemic form was recognized as a predisposing factor to a marked increase in the bronchitis and pneumonia rate accompanied by an increase in mortality.
The diseases recorded were catarrh, epidemic catarrh, acute and chronic bronchitis, pneumonia, and acute diseases of the upper respiratory tract. After 1862, catarrh disappears from the record, practically the entire rate of which in subsequent reports appears to have been included in that for acute bronchitis. Many cases of "epidemic catarrh" were reported but there was no spread of this condition as a general epidemic. The increased incidencies were local in character and occurred independently in different camps throughout the course of the war. New levies and organizations new to field service appeared to be most liable to this condition.
Acute bronchitis had a low death rate. Many of the deaths, however, followed attacks of measles. The pathological findings reported in the fatal cases were in part those of intense bronchitis, while a few showed the pathological
a At Sharon, the peripneumonia notha made its first attack, with symptoms of uncomnmon coldness and torpor, which pervaded the whole system, without those strong rigors observed in pleurisy, and intermittent fever; the heat of the body at the same time, to the touch, much below the standard of health. * * * There was a remarkable pale pink coloured suffusion over the whole face, distinct from the usual febrile blush in the cheeks; the appearance was similar to the sudden flush colour, produced by sitting before a fire, after having been exposed to cold. This appearance was most conspicuous on persons having fair and light complexions. This was accompanied with a bloated countenance, which gave to the spare and pale-faced patient, additional beauty to the general features. This rouge-like appearance, was less conspicuous on the body, than the face. It is to be noticed, that during the cold stage, the patients suffered from pain throughout the muscles of the body, in one case similar to rheumatism. In four or five instances, this epidemic made its assault upon the head; which bleeding immediately relieved; upon enquiry, I found there was here no complaint whatever within the chest. It was then prognosticated, that in 24 hours, more or less disease would exhibit itself on the lungs. This prediction, which was presumed upon former experience, on the northern frontiers, was fulfilled in every instance where made; while the pneumonic symptoms which followed, were not eventually less severe, than in those cases, where the first symptoms of disease showed themselves, within the breast. The appearances were engorgements, congestions, and inflammations, even where there was previous to death no increase of heat. The bronchiae were charged with a mixture of blood, and mucus. Where the disease had been of some duration, adhesions of the lungs to the circumjacent parts were noticed. The spongy mixture of this viscus was lost; while it assumed in some measure, the solid and compact state of the liver. It was sometimes covered with a yellowish, glutinous, extravasated fluid, which adhered with some force to its surface.
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lesions of a hemorrhagic pneumonitis without definite foci of consolidation, a pathology with which we became familiar during the epidemics of 1918. Some cases described clinically as bronchitis were found at necropsy to have a lobular pneumonia which was considered to have supervened on the attack of bronchitis.
"Chronic bronchitis" gave rise to a moderate discharge rate for disability and to a certain number of deaths. It appeared to follow "acute bronchitis" and to represent those cases not infrequently observed during the last war of the failure of the bronchopneumonia to clear up, or to those cases of bronchiectasis following influenza which have given rise to some degree of invalidism among the veterans. The necropsy reports are not sufficiently definite to enable one to judge of the pathologic condition present.
Under "pneumonia" it is stated that many diseases were of more frequent occurrence than pneumonia, but only diarrhea and dysentery and the continued fevers furnished a larger death list. It was shown, however, in the discussion of the points of interest connected with these grave camp diseases, that pneumonia was present, and caused or hastened the fatal issue in 21.6 percent of the deaths from diarrhea and dysentery and in 68.3 per cent of those attributed to the continued fevers; the mortality from measles also resulted largely from inflammatory processes in the lungs.
Under the title of pneumonia are described many cases of the various forms including the unfavorable terminations of abscess of the lung, gangrene, unresolved pneumonia and bronchiectasis. Some of these cases the physical signs of which indicated a persistence of consolidation were termed "chronic pneumonia" or "chronic interstitial pneumonia."
Acute hemorrhagic pneumonitis does not appear as such under the heading pneumonia but under that of fatal acute bronchitis, and it is quite clear that the pathological entity is that seen during the epidemic of September and October, 1918, in the United States, and in a lesser number of cases in the high respiratory incidence of the spring of the same year.
The high fatality in cases in which the pleura and pericardium were involved is noted in the general discussion. Practically every type of lesion seen during the World War is described in these protocols of the necropsies of the Civil War. Under secondary pneumonia are included a large proportion of those pulmonary inflammations which appeared at the time to be entirely secondary, in fact the descriptions of the clinical course indicate the presence of an acute respiratory infection without severe embarrassment of respiration and no physical signs of pneumonia preceding the increased symptoms due to consolidation. The clinical descriptions of these cases correspond with those recorded during both the spring and fall epidemics of 1918. The clinicians and pathologists of that time considered that a primary bronchitis was followed by a distinct and separate disease, namely, pneumonia, and believed that the first made the patient more susceptible to the second rather than that they were definite manifestations of the same disease either in character or extent.
Under pleurisy are recorded numerous fatal cases in most of which there was general involvement of the chest cavity. The records showed that no definite differentiation was made between mild pleuritic involvement and frank empyema.
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MEXICAN BORDER MOBILIZATION (1915-16)
During the mobilization on the Mexican border of 1915-16, an epidemic of about 400 cases of pneumonia occurred among 40,000 troops with a 20 percent case fatality. The epidemiological and bacteriological characteristics of this outbreak were described by Nichols.8 Pneumococci and streptococci were cultivated from the sputum. Type determinations showed pneumococcus Type I in 56 percent, Type II in 22 percent, Type III in 2 percent and Group IV in 20 percent. Many of the troops were from Northern States where Type I was prevalent in the pneumonia of the camps in 1917. In view of our experience during 1917 and 1918, it is probable that an acute respiratory infection preceded the pneumonia. Had this not been so, a greater proportion of the pneumonic lesions should have been caused by a single type of organism, though ill the present state of our knowledge, bacterial variation must be considered. The lack of all pathologic description prevents us from making a definite decision as to the character of the pulmonary inflammation which was recorded as lobar on the basis of clinical observation. Direct evidence of tent, company and regimental contagion was obtained. In reporting the epidemic Nichols made the following prophecy which was overlooked in the rush of war preparation taking place at the time of publication: "Epidemic lobar pneumonia is to be expected in large camps in the winter months."
REFERENCES
(1) Mann, James: Medical Sketches of the Campaigns of 1812, 13, 14. Dedham, 1816, p. 306.
(2) Zinsser, Hans: The Etiology and Epidemiology of Influenza. Medicine, Baltimore, Vol. 1, No. 2, 1922, 213-309.
(3) Cecil, R. L., and Steffan, G. I.: Acute Respiratory Infection in Man Following Inoculation With Purulent Bacillus Influenza. Journal of Infectious Diseases, Chicago, 1921, xxviii, 201-225.
(4) Olitsky, P. K., and Gales: F. L.: Experimental Studies of the Nasopharyngeal Secretions from Influenza Patients. Journal of Experimental Medicine, Baltimore, 1921, xxxiii, 125, 361, 375, and 713; ibid., 1921, xxxiv. 1; ibid., 1922, xxxv, 1, 553 and 813; 1922, xxxvi, 685.
(5) Underhill, F. P., and Ringer, M.: Blood-concentration Changes in Influenza, with Suggestions for Treatment. Journal of the American Medical Association, Chicago, 1920, 1xxv, 1531.
(6) Hirsch, August: Handbook of Geographical and Historical Pathology. The New Sydenham Society, London, 1883, i, 12, 17, 23.
(7) Medical and Surgical History of the War of the Rebellion. Part 3, Medical, 719.
(8) Nichols, Henry J., Maj., M. C.: The Lobar Pneumonia Problem in the Army From the Viewpoint of the Recent Differentiation of Types of Pneumococci. The Military Surgeon, Washington, D. C., 1917, xli, 149-161.
