A CLINICAL DESCRIPTION OF INFLUENZA AS IT APPEARED IN THE EPIDEMIC OF 1918–1919

ByJ. A. Lichty, M. D.

The epidemics of influenza which have been recorded from time to time during the past few centuries have always contributed an interesting chapter to the history of medicine. The protean character of the disease with its many complications is always an excuse for another attempt at the description of the clinical manifestations of a recent epidemic. This is not, however, the only incentive at the present time for describing the clinical aspect of the disease as it appeared in the epidemic through which we have just passed. The study of the disease from other aspects, such as the pathological, the bacteriological and the physiological, by well-organized groups of workers has made it necessary to co-ordinate, if possible, the clinical findings in every detail with these apparently basic principles. It would be interesting to review here the peculiarly fortunate circumstances which have led to the investigations. On account of the great war many temporary laboratory organizations which otherwise would not have existed were in operation, and these organizations, moreover, were keen to undertake any laboratory problem which might arise. The present epidemic presented the opportunity, and that the work was taken up with great enthusiasm is evidenced by the reports coming from the various army hospitals, base hospitals and civilian hospitals throughout the world. The permanent laboratories connected with medical schools and with institutions for medical research took up the problems with equal endeavor. This brief reference is made only to call attention to the fact that from such organizations a great mass of information has come which must be critically reviewed and coordinated before it can add to the permanent fund of our knowledge of the disease under consideration.

The material upon which the following clinical observations have been made is peculiarly adapted to review because it consists of two distinct groups of patients which were admitted to the Mercy Hospital. One group of 153 men was composed of soldiers between the ages of 18 and 23, which had been recently inducted into the Student Army Training Corps, and were living in barracks in the immediate vicinity of the hospital. Another group consisted of civilians (394), ranging from youth to old age, which came from various parts of the city and surrounding towns and country. The first group came to the hospital early, or as soon as the disease was recognized; the second group came usually after several days of illness had elapsed, or when a complication had already arisen. Many of this group had been ambulatory cases for the first part of the disease. The entire number of patients admitted to the Mercy Hospital from the first admission, September 21 to December 1, the end of the quarantine, was 547. After December 1 very few simple influenza cases were admitted. These 547 cases form the basis of the observations which will be referred to in this paper.

From the last great epidemic or pandemic of influenza, that of 1889 and 1890, have come clinical descriptions which should be reviewed before speaking of the clinical manifestations which have characterized the present epidemic as shown in the two groups studied.

One of the best descriptions of that epidemic was given by Dr. O. Leichtenstern in Nothnagel’s Encyclopedia of Practical Medicine. This contribution, among many others, describing the epidemic of 1889 and 1890 is one of the first to refer to the Pfeiffer bacillus as being etiologically associated with the disease. It differs, therefore, greatly from descriptions of previous epidemics. Leichtenstern says: “The typical influenza consists of a sudden pyrexia of from one to several days duration, commencing with a rigor, and accompanied by severe headache, generally frontal, with the pains in the back and limbs, by prostration quite out of proportion to other symptoms and marked loss of appetite.” He continues by saying that to these characteristic symptoms may be added the catarrhal phenomena arising from the affection of the respiratory tract, particularly the upper (coryza) and “occasionally” the lower, the trachea and bronchi. This description is so in accord with the symptoms of uncomplicatedinfluenza as found in the present epidemic that very little need be added. Any difference which may occur in the description of the disease is likely to be accounted for by the peculiarity of onset, whether in the upper or lower respiratory tract, and by the different ways of interpreting complications which may have arisen. It is evident from this description that the upper respiratory tract was affected more generally than the lower in the epidemic of 1889 and 1890. In the present epidemic it can safely be said that the reverse was the usual state of affairs. It was a rather unusual occurrence when the affection was limited only to the nose, pharynx, larynx, trachea and larger bronchi. A very large number, no doubt, had a peculiar œdema, a so-called “wet lung,” which we shall discuss later; others went on to a capillary bronchitis or a bronchiolitis, and a large number had broncho-pneumonia. This sequence we shall attempt to show in the statistics at hand. In some cases the lesion in the lower respiratory tract seemed to be primary, there having been no initial coryza. At least none was observed and no history was obtained.

The length of the prodromal stage—the stage from the time of contact to the earliest onset of symptoms—has always led to interesting observations and discussion. In this epidemic we have rather definite information bearing upon this subject.

A young married farmer living in a rural community where no influenza had occurred up to the time of the present experience went to a city about 40 miles distant. On the train he sat in the same seat with a man who was apparently ill, and who was sneezing and coughing. He was in the city only a few hours, and was not in any place of congregation except the railway train. Forty-eight hours after his return to his home he noticed the first symptoms and began a mild course of influenza. About 50 hours later his wife was taken with the same symptoms, and in two days more their only child was afflicted. Other members of the household were also afflicted, and one of them died of pneumonia.

It might be interesting to quote a similar observation made by Macdonald and Lyth, of York, England, published in a recent issue of the British Medical Journal (November 2, 1918, p. 488), which corroborates this experience. They say: “We traveledfrom London together on Thursday, October 3, by train, leaving King’s Cross at 5.30 P. M., arriving in York at 9.30, and as we were leaving the carriage a young flying officer, who had come the whole way with us and was coughing and sneezing at intervals, informed us that he was ill and had had influenza for several days. On Saturday, October 5, we both became ill and had developed typical attacks of influenza. With both of us the illness developed suddenly with laryngitis; in both the first signs were a severe attack of coughing; and in both the time was noted fairly accurately as being between 2 and 2.30 P. M. One case was quite mild, the temperature never over 101. The other was more severe; the temperature arose to 104½ and the catarrh extended to the bronchi. His wife and two children also developed influenza, and in their case the symptoms showed suddenly, about 2 P. M., on Monday, October 7. Now we are convinced that we became infected from our traveling companion during the train journey—more likely toward the end of the journey; and if we take the time of infection as 9.30, this fixes the incubation period for both of us at a minimum of 41 hours, with a maximum margin of error of 4 hours. The three cases developing in the family of one of us point to a similar incubation period, as their illness started almost exactly 48 hours after his, and as it is likely that the infection would not take place until a few hours after the first symptom, the incubation period in these three cases must have been nearly the same as our own two.

“It can be readily understood that we were in no position to conduct extensive bacteriological examinations, but a culture taken from the posterior nares of one of us on October 10 with a guarded swab showed colonies of Pfeiffer’s bacillus and of micrococcus catarrhalis.”

This observation is so convincing, I have quoted it at length and in full.

The communicability of influenza has been observed by all, and the ease with which it passes from one individual to another noted. One observation made by us was of considerable interest. In a house where a patient lay sick with a severe attack of influenza for nearly three weeks several members of the household passed the door of the sick room a number of times daily, and yet they did not contract the disease. This is in marked contrast with the immediate contact between the two physiciansand the young flying officer, who sat in the same railway carriage compartment for four hours. The same observation was made in the hospital among nurses in direct contact with patients. A large number of these contracted the disease, while those not immediately associated with influenza patients almost invariably escaped. This speaks strongly against the idea that the epidemic was a so-called “plague,” or that it passed without intermediate means through the air and pervaded all places.

From information thus far at hand it seems, therefore, that the prodromal stage, or stage of incubation, is one which covers about 48 hours, and that it is usually without symptoms unless it be a peculiar prostration which had been described by some patients. It would also appear from the experiences just narrated that it was necessary to be in rather close contact with a patient, so that there could be an exchange of respired air before infection could take place.

In all descriptions of the disease the duration is spoken of as “several days, more or less,” “a three-day fever,” or “a seven-day fever.” Because of the careful supervision under which the soldiers were kept while in the barracks an excellent opportunity was afforded to note the duration of uncomplicated cases. The shortest time observed was 1 day, and the longest 10 days. The average duration of temperature among 87 soldiers without inflammation of the lungs or other certain complications was 6⅓ days. Among the civilians the shortest time of pyrexia was a few hours only, while the longest in 73 male patients was 14 days, and in 84 female patients was 16 days. The average length of pyrexia in the males was 4⅝ days, and in the females was 5¼ days.

While the very definite clinical description of the former epidemics of a so-called uncomplicated influenza seems to have served satisfactorily to the present time, the laboratory studies and the possibly more thorough clinical observations which have been carried out recently in this epidemic make it necessary to present anew the whole disease picture of influenza, with the hope of suggesting a classification more in accord with our present knowledge of the disease.

Forms and Varieties of Influenza

A few words as to “forms” or varieties of influenza might be helpful before suggesting a classification of symptoms. In former epidemics of influenza considerable importance was attached to the early manifestations or first symptoms as characterizing the “form” of influenza which was in evidence in the individual patient. These were reported as a “respiratory form,” a “nervous form,” a “gastro-intestinal form,” and other forms—circulatory, renal, psychic, etc. In the epidemic of 1889 and 1890 particularly these types were noted, and they have been described in the subsequent small epidemics, practically characterizing them as being of one or the other, and frequently as being without any respiratory symptoms. In the study of our group of cases in the present epidemic every effort was made to recognize the non-respiratory cases, but we were unable to find a single case which did not have definite respiratory symptoms, either early or late, in addition to any other symptoms present. Only occasionally were nausea, vomiting and diarrhea or tachycardia, or certain neuroses or psychoses, the leading symptoms. The respiratory symptoms in some cases seemed to be at the onset primarily of the lower respiratory system—that is, without the preliminary coryza. These usually ran a rapidly fatal course, characterized by marked cyanosis and confusingly irregular chest signs. We would say, therefore, in so far as our experience goes in this epidemic, we are not justified in speaking of any particular forms except the respiratory form, and whenever pronounced manifestations occurred justifying a characterization of any other form they could more easily be interpreted as a complication, or the manifestation of a coincident disease, or of a severe toxæmia.

The classification of the symptoms, therefore, takes into consideration largely those symptoms arising from the respiratory system. We are of the impression that the pathology demonstrated by Dr. Klotz and described by others justifies the following classification. Clinically we would recognize two distinct groups of epidemic cases.

The first includes thosewithout lung involvementhaving symptoms arising from the upper respiratory tract, including the trachea and the larger bronchi. These were practically without any chest signs except for the rather indefinite signs of an acutebronchitis, and the only symptoms referable to the respiratory tract were a coryza, soreness of the throat, hoarseness and a cough of varying degree and character. If to these symptoms are added those of Leichtenstern just mentioned, one will have a good description of a so-called simple, uncomplicated influenza.

The second includes thosewith lung involvementand associated with physical chest signs, in some indefinite and confusing, while in others definitely conforming with the existing pathology. These symptoms and chest signs were those associated at one time with what appeared to be an acute œdema of the lungs. At another time the physical signs were those of a bronchiolitis (capillary bronchitis), or most frequently of a broncho-pneumonia, of an isolated type or of a massive type. Finally there were some forms of lobar pneumonia which at times we were unable to differentiate from a true lobar (croupous) pneumococcic pneumonia.

Of the group without lung involvement nothing further would seem necessary to be said in addition to what one finds in standard text-books describing the disease picture of former epidemics. The incidence of influenza of this type among our group was as follows: Of 153 soldiers 93, or about 60 per cent., had a so-called simple, uncomplicated influenza, and of the 394 civilians 185, or about 52 per cent., had no lung involvement. There are a few points in which the symptoms of the present epidemic seem to be so peculiar that they merit special consideration.

This can be described as showing a sudden rise to 102–104, at which point it is maintained for a few days, and subsides by lysis in a few days more. A typical chart is as follows:

CHART I

Or the temperature might fall one or two degrees for a day or so after the first rise, and then go up again for one or two more days, and subside by lysis as is shown in Chart II.

CHART II

This would occur without our being able to find any lung lesion unless we accept the acute œdema or wet lung as a complication,and this we were rarely able to recognize by any definite physical signs in the chest. Cyanosis frequently accompanied this second rise of temperature, and was later interpreted as being associated with the so-called wet lung. When the temperature remained up longer than five days it could safely be concluded that lung involvement must be present.

The pulse was invariably slow, or rather out of proportion to the temperature. Even when the patient seemed very ill the pulse remained from 84 to 96, and of surprisingly good quality. This was noted also when some of the more severe pulmonary involvements or some complications arose. The pulse frequently did not become rapid until shortly before death. The respirations in an uncomplicated case also remained about normal. The rate was not accelerated until lung complications arose, and then a gradually increasing rate was often the first herald of oncoming danger and a sign of grave prognostic import. The relation of the pulse phenomena toward the end of a fatal case was most remarkable. The respiratory rate was accelerated, as has been noted above, but the pulse rate frequently remained unchanged, being characteristically slow. In a patient seen in consultation with Dr. Lester H. Botkin, of Duquesne, Pa., death took place while we were in the sick room. It was a case of apparently uncomplicated influenza of seven days’ duration. The respirations were rapid and the pulse was only 96. In the last five minutes of life the heart beats as observed with the stethoscope never varied, until they suddenly ceased; during the same time the respiratory efforts were only three agonal ones, the last being a minute or so before the last heart beat. There were no physical signs of consolidation at any time recognized in this case, but we feel that the lung, had we seen it at autopsy, would in all likelihood have shown the peculiar hemorrhagic and œdematous character so often observed in the fatal cases.

There were, of course, marked exceptions to the description of slow pulse and later rapid respirations observed. In some the pulse rate and respirations increased, together with or without definite signs of a grave complication.

Cyanosis

This was recognized early in the epidemic. It was sometimes preceded by a peculiar flushing of the face, such as accompanies belladonna poisoning. It might be noticed in the very first days of the attack. The cyanosis was looked upon as being a very early symptom of lung involvement. With our later knowledge from autopsies, and especially as shown by Dr. Klotz, we feel it was surely an accompaniment of, or may even have preceded, the changes in the lung which have been designated as œdematous, “wet” or cyanotic. At the earliest appearance of the cyanosis we were frequently unable to find any change in the physical signs of the chest. Of course, the indefinite signs of an acute bronchitis were present, and in some cases an additional “impaired resonance” was noted over one or both lower lobes, but when this was definitely present other more definite signs soon followed, and our case was shifted suddenly from Group I, i. e., without apparent lung involvement, to Group II, i. e., with definite lung involvement. This cyanosis was noticed first in the face, and frequently was marked on the dorsal surface of the hands. It was not unlike the cyanosis which may sometimes be seen when large doses of certain coal tar derivatives are taken. In fact, the question arose whether in the epidemic of 1889 and 1890, when the coal tar derivatives were prescribed with such freedom and with accompanying cyanosis and apparently such deleterious effects, the cyanosis may not after all have been due more largely to the infection than to the medication. After that epidemic it was said: “Influenza has slain its thousands, but the coal tar products have slain their tens of thousands.” There was no gross hæmaturia or hæmoglobinuria present in these cases, although a few red blood cells were seen microscopically. There was, however, epistaxis, sometimes early in the disease or later associated with the cyanosis. In a few cases there was hæmoptysis, which we regard as always arising in cases where the wet or hemorrhagic lung was present. Cyanosis in disease of the lungs, and especially in the terminal stage of lobar pneumonia, is a familiar and common occurrence, but the cyanosis observed in this epidemic seemed quite different from the ordinary. The points of difference were these: (a) it came early in the disease; (b) it seemed to be more generally present when very little lung involvement could be demonstrated physically, and was just as likely todisappear when more definite chest signs were demonstrable; (c) it was not associated with embarrassment of respiration; (d) it had no relation with a demonstrable circulatory disturbance. The pulse did not become rapid; the quality of the pulse did not change;the right heart was not dilated, as is so frequently the case in the terminal stage of a lobar pneumonia when cyanosis appears; (e) and finally there was no associated œdema of the lungs, or at least that œdema of the lungs which occurs in the later stage of lobar pneumonia, when the pulse becomes rapid, when there is rapid and labored respiration, when the right heart dilates, when there is cold perspiration, and when the signs of impending death are plainly evident. The cyanosis of influenzal pneumonia seemed to be due to an entirely different cause or combination of conditions from those present in lobar or pneumococcic pneumonia. The cyanosis of influenzal pneumonia was, therefore, most confusing, and became all the more so when it was recognized that it did not yield to the respiratory and circulatory stimulants usually employed when cyanosis is present. The inhalation of oxygen was resorted to rather routinely early in the epidemic. It seemed to temporarily influence the cyanosis, but the results were not permanent, and the outcome of the cases did not seem to be different from those in which oxygen inhalations were not used.

The blood pressure in those cases in which cyanosis was observed was invariably low. This seemed to be due to the infection, for in several private patients not belonging to this group of patients with previously known high blood pressures the blood pressure was observed as much lower throughout the course of the infection.

The peculiar behavior of the white blood corpuscles will be discussed more fully in another paper of this series. Our remarks will deal more particularly with the clinical observations and interpretations. The leucocytes fell below the normal from the very onset of the disease; they varied very little regardless of great changes in temperature; they did not always increase, or if they did increase at all it was comparatively little, even in an extensive invasion of the lungs or in severe complications. Concerning the leucopenia we have no explanation to suggest, savethat it is a clinical characteristic of the disease. Our first thought was that the infection came on so suddenly and profoundly there was no time for a leucocyte reaction. But when we recall other diseases associated with a leucopenia, notably typhoid fever, which does not come on with such suddenness, our explanation for the leucopenia of influenza does not seem to hold. The leucopenia must be simply a peculiar toxic blood reaction characteristic of the Pfeiffer bacillus invasion. Such an explanation has long been accepted in the Eberth bacillus infection.

A condition which was frequently noted by the patient was an indescribable weakness and prostration which appeared early, sometimes before any other symptoms were noted or before any elevation of temperature. The young soldier was in apparent perfect condition when he arose in the early morning. During the “setting up” exercises he did not feel so fit, and a few hours later appeared extremely weak. When his condition was called to the attention of the medical officers he was found to have a slight elevation of temperature and was sent to his bed.

In former epidemics, as also in this one, marked prostration was recognized as coming at the height of the disease and remaining persistently during convalescence. But it does not seem to be recorded as among the first symptoms.

Of the group with lung involvement much may be written from a clinical standpoint, and much confusion may be brought about. Especially is this so if one has no definite idea of the pathology present, or if one enters into a discussion of the character of the infection—a point upon which there is as yet no unanimity of opinion. From the many reports which have been put forth from the base hospitals of the various cantonments, and also from the reports coming from civilian practice, it is evident that scarcely any two groups of laboratory men or any two individuals of those separate groups have the same idea as to the bacteriology and the pathology peculiar to this epidemic.

As long as there is this confusion and element of doubt in the minds of those to whom we are accustomed to look, the clinicianmust necessarily speak with considerable hesitancy, especially when he attempts to interpret the physical signs observed. In our own group the observations of Klotz, Guthrie, Holman and others have given us an interpretation of our clinical findings which, at present at least, is more or less satisfactory. We shall definitely keep in mind their observations and conclusions as we go on with the description of the physical signs of the chest in cases having lung involvement.

In the description of this group it will readily be seen that the lower respiratory tract stood the brunt of the infection. Of the 153 soldiers under our care, 60, or about 40 per cent., were recognized as having pneumonia. Of these, 34 had undoubted demonstrable signs, while 26 were questionable, and yet from the temperature and other symptoms we concluded there was a pneumonia. Of the 394 civilians, 189, or about 50 per cent., had pneumonia. Of this group there were again some 28 or 30 in which the diagnosis was doubtful, according to the ordinary way of making a diagnosis, but we felt sure from the temperature course that more than a simple influenza was present. In the description of the physical findings of the chest in these influenzas with lung involvement it will be readily seen why the diagnosis must sometimes be in doubt.

Before referring to the physical signs it might be well to describe the condition and general appearance of the patient when the lungs became involved. The patient who had been progressing with an apparently simple influenza, with no chest signs except those of bronchitis or tracheitis, occasionally slightly cyanotic, became more cyanotic, the elevation of temperature continued longer than three to seven days, or if it came to the normal began to rise again, his respirations gradually increased and the pain in the chest became well localized. One could safely assume that the patient had developed a lesion in the chest. This could not always be localized during the first few hours or on the first day. The evidence of increased bronchial disturbance was frequently recognized, and later impairment of resonance and diminished breath sounds associated with “a few crackles” were noted. This, so far as we can tell, may have been the only evidence of the stage of œdema or “wet lung.” After this, as the disease advanced, definitely increased vocal fremitus and rather definite tubular breathing with greater impairment of resonancewere noticed. These signs were usually observed first at the apex of the left lower lobe, and from here they extended forward along the inter-lobar sulcus, or downward along the spinal column. If the lesion was noticed first on the left side, in a day or two it was found more or less definitely in the right lower lobe also. It seemed to occur more frequently first in the body of the right lobe, instead of in the apex of the lobe as on the left side. In both lobes it might spread to contiguous areas and form a massive consolidation, or it might be found in small separate areas, some of which would clear up in a day, while others would persist.

The expectoration was frothy, containing either blood or masses of yellowish, greenish purulent material floating in a watery sanguiolent or clear fluid, or enmeshed in frothy mucus. The amount of expectoration in some cases was enormous, but as a rule it was scanty. It was thick and ropy at times and distinctly annoying to the patient.

At this stage the physical signs were very much in accord with those of broncho-pneumonia. In a few hours sometimes, or in a day, the small areas of consolidation became confluent and massive consolidation was formed. It appeared as though the whole lobe would in time become solid, as in a true lobar pneumonia. Or the original areas may apparently have cleared and other areas involved, became the centers of massive consolidations. In many cases both lower lobes were thus similarly affected, and one had the physical signs of a double lobar pneumonia. However, nearly always a small angle of the lobe remained clear, thus differing from the entire lobe involvement characteristic of a true croupous pneumonia. Other signs, such as the absence of vesicular breathing and presence of the crepitant râle, moist râles of all sizes to very coarse râles, could be noted. As in certain stages of a complete consolidation, the lung might be dry; no râles present, but definite tubular breathing present. This in a day or two, or after a longer time, might give the signs of resolution. The stage of resolution, however, was almost invariably prolonged, sometimes extending over weeks. With these variable lung signs were often mingled the signs of a fibrinous or serofibrinous pleurisy, which occasionally but remarkably infrequently went on to effusion or empyæma.

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As stated above, the demonstrable pathology was in the lower lobe, and more frequently in the left than in the right, only occasionally in the middle lobe, and never, we might say, in the upper lobes. The very earliest definite signs were found at the apex of the left lower lobe.

This observation seems to be entirely contradictory to that of the pathologist, who found in 65 per cent. of all cases coming to autopsy a lesion in all the lobes of the lungs (Klotz). The only explanation we can give which seems at all satisfactory to us is that the pathology in the upper and middle lobes must not have been sufficient, or must have been of such a nature that it did not yield the physical signs, i. e., definite impaired percussion resonance, increased vocal fremitus and tubular breathing, with varying shades of moist râles—signs upon which we insisted before we were willing to state definitely that there is a demonstrable pneumonia present.

In this description it has been attempted to follow the order of invasion in a lung which seemed to go through the entire course of the disease. There were, necessarily, all degrees of the process, some cases showing few signs and yet being remarkably ill, and others all of the signs with very little other evidence of serious illness.

We were continually impressed with the notion that the pathology in the lung, at least the pathology demonstrable physically, did not tell the whole story of the case, and that the outcome depended as much or possibly more upon a general infection or toxæmia of which the recognized condition in the respiratory system was only a small part. We were particularly impressed with this in the success or failure following the application of any therapeutic measures. It was quite a common remark, therefore, in the wards of the hospital among those associated in the work that “the patient died too quickly to permit of the succession of the various stages of pneumonia”; or, in the autopsy room, that if the patient had lived long enough he would have had demonstrable, well-recognized pathology of the lung, instead of the cyanotic, wet, spongy lung which was found.

The temperature course in the pulmonary cases was characterized by its irregularities, and by its being entirely out of harmony with the extent and severity of the lung invasion in so far as it could be interpreted by the physical signs. The temperature as described in a simple influenza might not come to the normal in the time of three to seven days, and might even go higher, withno demonstrable chest signs, but with every other evidence of lung involvement. Later the temperature might come down by lysis, which was the usual way, and the chest signs gradually or suddenly become evident. The temperature might remain normal throughout the rest of the course, and a lobe or even both lower lobes of the lungs be as solid as in a true lobar pneumonia. Occasionally the temperature fell by crisis, but there was no associated change in the physical signs of the chest. In short, the temperature seemed to run a course entirely independent of the physical signs in the chest. In two remarkable cases seen in consultation on two consecutive days the physicians in charge declared that no signs of consolidation could be found, though all other evidences of pneumonia were present. In the 12 hours which had elapsed from the time the last examination was made the temperature fell by crisis. At the consultation, to the surprise of the family physicians, we found both lower lobes consolidated, it having occurred apparently with the crisis. Both patients were healthy-looking, robust, young men, and both recovered with delayed resolution. In the convalescence of such cases, if the patient got up too soon or if any other indiscretion took place, a relighting of the lung occurred. From the above description it can be readily seen that a diagnosis of the conditions in the chest in influenzal pneumonia was frequently impossible, because one had to abandon all his previous ideas of pneumonia, in so far as onset, crisis, blood picture, sputum, temperature, respiratory and circulatory phenomena, physical signs and prognosis were concerned.

Assistance from the laboratory was meager, especially in the early days of the epidemic. This was due largely to the inability to get laboratory workers in sufficient numbers to follow the work through, but more largely to the fact that we were unable to interpret the unusual laboratory results which were available. When we were once fully aware of the difficulties in diagnosis which confronted us, we utilized every practical means at our disposal. Among these was an examination of the chest with the X-ray. On account of lack of facilities and of help, it was impossible to make routine X-ray examinations of the chest in all cases. Besides, it was difficult to interpret the X-ray findings, on account of the unusual character of the lesions. Also, many of the patients were so desperately ill one hesitated to disturbthem. We hear that other clinics had similar experiences, and that very little substantial help came from the X-ray, except in cases with complications. Several attempts were made to determine the kind of shadow, if any, the “cyanotic, œdematous, wet” lung would make, but no satisfactory observations have been forthcoming. From our own observations and from the discussions of other observers, it would seem to us that the stereoscopic examination of these chests is the only possible way of getting satisfactory plate readings in these cases where the pathology seems so lawless in its extent and peculiar in its distribution. This method of examination, however, demands facilities convenient at the bedside and perfect co-operation of the patient—difficult conditions to meet under the circumstances. In the acute cases, when the desire to make a diagnosis not only of the presence but of the extent of the disease was keen, X-ray examination was largely impractical. In cases of delayed resolution, or in cases with complications with prolonged convalescence, X-ray examinations were extremely helpful.

In the consideration of any disease the well-trodden path of a painstaking history, a thorough physical examination, and reliable laboratory investigation, together with an intelligent interpretation, will usually lead to a definite diagnosis. In certain diseases, as is well known, the stress must be placed about equally on all of these factors, while in others one or other factor predominates. In influenzal pneumonia, until more is known of the etiology (bacteriology) and of the pathological changes and of the physiological disturbances, the controlling factor in the diagnosis (we feel embarrassed to admit) must be the history. This is true not only of the diagnosis of influenza with or without pulmonary involvement, but is also true of the diagnosis of the various complications, and will be found to be particularly true in the recognition of the bizarre sequelæ, which no doubt in the succeeding months or years will be attributed to or will follow in the train of influenza.

With the knowledge that there is a prevailing epidemic of influenza and that the manifestations are largely in the respiratory tract, any pulmonary disturbance will necessarily make onesuspicious of the presence or the oncoming of an influenzal pneumonia in the patient under consideration. The history of the onset, as of simple influenza, is the greatest factor. This with a continued temperature, cough, cyanosis, slow pulse, continued asthenia, or even an unusual leucopenia, may have a greater weight in determining the diagnosis of lung involvement than will the apparently definite or, as it may happen, the confusing chest signs. To differentiate from ordinary bronchitis, broncho-pneumonia and catarrhal pneumonia, one need only refer additionally to the severity and persistency of the disease when it is of the influenzal type, as compared with the mildness of the ordinary type. To differentiate it from croupous pneumonia, one need only compare the confusing symptom picture of the influenzal pneumonia with the definite, clear picture of ordinary pneumonia; or the confusing kaleidoscopic chest signs of the one with the definite, clear-cut signs of the other. The laboratory thus far has been the smallest factor in making the diagnosis, in that sputum examinations, blood examinations, blood cultures and urine examinations are mostly negative in their results, or at least the findings are not specific. We do not, however, mean to indicate that these tests are not of the greatest value. The leucopenia is the one outstanding feature which seems to have separated this infection from other acute lung infections, excepting miliary tuberculosis. The differentiation of influenzal pneumonia from an acute tuberculous process in the lung may be difficult, especially if there is no reliable history available. However, the fact that pulmonary tuberculosis usually begins at the apices of the lungs and influenzal pneumonia at the bases or at the apices of the lower lobes is quite helpful. Of course, the examination of the sputum for tubercle bacilli will be a deciding factor.

The differentiation between influenzal pneumonia and diseases of the pleura is one which practically rarely needs to be made, for there seem to be very few cases of influenzal infection of the lungs in which the pleura is not also involved to a greater or lesser extent.

In considering the complications of influenza one again comes up squarely against the question: What is influenza and what is the specific micro-organism responsible for it? If the Pfeifferbacillus is the specific cause, what pathology can be attributed to it? It has been an almost universal observation that the lesions in the lungs and pleura which characterized the group of cases with lung involvement rarely yielded a pure culture of the Pfeiffer bacillus, and that secondly in a large percentage of cases the Pfeiffer bacillus apparently was absent, and that other micro-organisms, such as the pneumococcus, streptococcus, micro-organisms commonly found in the pneumonic processes, were present and predominated. The question arises, therefore, may not all the influenzas with lung involvement becomplicationsof influenza? It is our feeling that Pfeiffer bacillus is present throughout the respiratory tract in all cases, and while it may of itself produce a lesion like a broncho-pneumonia or a lobar pneumonia, it chiefly prepares the soil for other germs which may happen to be present, and which are more commonly found in the pneumonias. We, therefore, look upon the lesion commonly found in the lung as being a part of rather than a complication of influenza, and look upon lesions elsewhere, due to the influenzal or other micro-organisms, as a definite complication.

There is no doubt that the most frequent complication of influenza, especially in the present epidemic, is in connection with the pleural membranes. When one recalls that pneumonia rarely occurs without there being also a pleuritis, and also when one recognizes that in an influenzal infection of the lungs the specific micro-organism, together with any other micro-organism which may happen to be present, seems to run riot, apparently abandoning its usual mode of invasion, it can be readily understood why this complication is so frequent and so varied. The pleurisy was usually of the fibrinous type, and rarely was accompanied with demonstrable fluid. Of the 153 soldiers in only 3 was fluid detected in the chest, and of the 394 civilians only 10 showed fluid. In many more cases fluid was suspected, but X-ray examinations and free needling of the chest showed that we had misinterpreted the physical signs.

After our experience in the epidemic of pneumonia in the spring of 1918, when the disease was also so prevalent in the cantonments, we of course expected to see many cases of empyæma and lung abscess in the present epidemic. In this we were agreeably disappointed. Only one case of empyæma and only one case with abscess of the lung were found up to the time of collectingour data and the compiling of our statistics. Both of these were among the civilians. From our experience since the compiling of our statistics, we are inclined to believe that this low incidence of empyæma may not altogether represent the real state of affairs, as we have since received in the hospital several cases of empyæma, as well as of abscess of the lung, which seemed to have followed an influenzal infection which had occurred three or four months previously. One of these cases was a particularly remarkable one, in that the patient had already been admitted to the hospital twice since his initial attack of influenza in October for suspected pleurisy with effusion. We were unable to find any fluid with the needle, though we felt certain of having demonstrated it a number of times physically and with the X-ray. About eight weeks after the second admission, however, pus was found after several needlings in the left chest, axillary space, apparently along the inter-lobar sulcus. This case was a good example of many we have seen in which a pneumonia, or possibly, as we see it now, a pleurisy, or even a localized empyæma, seemed to confine itself about the sulcus or fissure between the upper and lower lobes of the lung. Frequently the process began posteriorly, apparently at the apex of the lower lobe, and traveled forward and downward across the axillary space until it appeared in the anterior part of the chest. In most cases we interpreted our signs as those of a consolidated lung, and scarcely knew whether the consolidation was in the upper part of the lower lobe or in the lower part of the upper, or in both. In some cases we suspected a localized empyæma or an abscess in the sulcus, but in none did we find pus after exploring with the needle until this recent case occurred. The passage of the needle in this case, which was done several times before pus was found, always gave the impression that it was going through dense fibrous tissue for some distance before the abscess was finally found. From this experience, and from the extensive and irregular invasion of the pleura which we have seen demonstrated at autopsies, there can be no doubt that the clinical history of the complications of influenza in this epidemic is not a closed chapter.

In six patients there was a purulent inflammation of the pharynx, larynx and trachea. It was extensive and produced profound general symptoms, dyspnœa and profuse purulent expectoration. The lungs were clear, but the patient seemed fora time in danger of death. The condition was considered a grave complication. There was only one case of acute sinusitis, one case of antrum disease, and only four cases of middle ear infection were recognized. This is in marked contrast to other epidemics which have occurred to our knowledge in the past fifteen years or more, and which have been spoken of as influenza or “grippe.” Disease of the tonsils, middle ear disease, mastoid disease and sinus disease occurred with great frequency in those sporadic epidemics. This again seems to show that the deep respiratory tract was more generally and more severely affected in this epidemic than the upper respiratory tract.

With the exception of the pleura, the serous membranes were remarkably free from infection. Only one case of acute endocarditis, three cases of meningitis (all pneumococcic), none of pericarditis, peritonitis or arthritis were recognized among the 547 cases of influenza.

The kidneys did not seem to be involved in the infection. Albumen was present in the urine, as might be expected in febrile conditions, but no evidence of acute clinical nephritis, such as suppression of urine, general œdema or uræmia, was recognized. The condition of the urine in this epidemic will be described more in detail in another paper of this series.

A peculiar pathological process in the muscles was brought to our attention by Dr. Klotz, who demonstrated a myositis or hyaline degeneration of the lower end of the recti abdominalis. This lesion is carefully described in the pathological section. After our attention had been called to this lesion we recognized several cases clinically having the same condition. One was in the right sterno-cleido-mastoid muscle and another was in the left ilio-psoas muscle. This last patient while he was convalescing developed a severe pain in the left hip, extending upward into the lumbar region and downward into the thigh. His decubitus was like that of one suffering with psoas abscess. Every test available was made to confirm this diagnosis, but all the findings were negative. The patient rested in the hospital, in bed, for some time, gradually improved, and eventually made a complete recovery.

In several cases we also detected an osteitis, especially of the bodies of the vertebræ. One was of the cervical vertebræ and the other of the dorsal. The first died after intense suffering.An autopsy was not obtained. The other had a plaster cast applied as in Pott’s disease, and improved sufficiently to leave the hospital in comfort. One hesitates under the circumstances to attribute these bone lesions definitely to the same infecting micro-organism which was responsible for the epidemic of influenza, as it might easily have happened that a coincident quiescent tuberculous lesion was present and relighted during the epidemic. However, in one case from the service of Dr. J. O. Wallace the possibility of the bone lesions being due to the Pfeiffer bacillus was demonstrated. This was a child of 16 months with an epiphysitis of the upper end of the tibia. The inflamed area was incised and pus was found. A smear at the time showed the B. influenzæ, which was grown in pure culture.

A most interesting complication noted in a few of our cases was a transient glycosuria. The first case brought to our attention was a middle-aged female, who complained of failure of vision. Upon making an ophthalmoscopic examination a papillitis of a mild type was noticed. This led to a careful study of the urine, and sugar was found in a small amount for a short period of three days, although the glycosuria readily disappeared by cutting down the carbohydrate intake, the vision came back to normal more slowly. In fact, it was almost one month before the symptoms and signs of the retinal change had entirely disappeared. It is interesting in this connection to recall similar cases referred to in Allbutt’s System of Medicine, vol. vi, on influenza, following the epidemic of 1890 in England. Other transient glycosurias showed no visual changes. We do not consider these to be true cases of diabetes mellitus. In all a transient hyperglycæmia was also noted.

A condition which can scarcely be considered as a complication of influenza, but which, however, was a large factor in increasing the mortality among women, was pregnancy. Among the cases included in this study were five pregnant women, who came to the hospital and were referred to the medical service. As soon as a complication relative to the existing pregnancy arose they were referred to the Obstetrical Department. On account of thegreat amount of work in caring for the influenzal patients, and on account of the scarcity of physicians and nurses, we were unable to follow these cases closely enough to give any such definite data as we wish. Three miscarried or went into premature labor. Happily only one of them died. The two which did not miscarry recovered and left the hospital well.

We very soon recognized in consultation with the obstetricians that the pregnant woman was in a really dangerous condition if she contracted influenza. She was likely to have a termination of her pregnancy in the height of the infection, no matter how recent or how remote pregnancy had taken place. If pregnancy did not terminate, the chances of recovery were less than those of the non-pregnant woman; if it did terminate, the chances for recovery were still less. To the pregnant woman with pneumonia very little hope of recovery could be offered. I am indebted to Dr. Paul Titus, of the Obstetrical Department of the School of Medicine, University of Pittsburgh, for a report which includes the cases seen by himself and his assistant, Dr. J. M. Jamison, during this epidemic. Dr. Titus was kind enough to include in his report certain conclusions which merit consideration. The report is as follows: “A series of 50 cases, at all stages of gestation. Interruption of pregnancy occurred in 21, or 42 per cent., of the cases; 29, or 58 per cent., in which pregnancy was uninterrupted. Mortality of pregnant women developing epidemic influenza is higher than that of ordinary individuals, even though their pregnancy is undisturbed, since 14 of the 29 in whom pregnancy was not interrupted died, an incidence of 48210per cent. If a pregnant woman miscarries or falls into labor, the mortality increases to 80910per cent. (17 of the 21 in whom pregnancy was interrupted died). The period of gestation has less influence on the outcome than the interruption itself. Of 10 at term, 3 lived and 7 died after delivery.

“Two main features of this condition as a complication of pregnancy are: First, pregnant women developing epidemic influenza are liable to an interruption of their pregnancy (42 per cent. aborted, miscarried or fell into labor); second, the prognosis, which is already grave on account of the existence of pregnancy, becomes more grave if interruption of pregnancy occurs.

“The cause of the frequency of interruption of pregnancy is probably a combination of factors: (1) The theory of Brown-Sequard that a lowering of the carbon-dioxid content of the blood causes strong uterine contractions sufficient to induce labor. (2) The toxæmia causes the death of the fœtus, particularly if not mature, when it acts as a foreign body and is extruded (10 premature fœtuses were born dead, while 1 was born alive, although 9 out of 10 at full term were born alive and survived).

“The cause of the frequency of death following interruption of pregnancy is also due in all probability to a combination of factors: (1) Shock incident to labor. (2) Increase from muscular labor of carbon-dioxid in blood already overloaded by the deficiency of the diseased respiratory organs. (3) Sudden lowering of intra-abdominal pressure by the delivery. (4) Lowering of blood pressure by the hemorrhage of the delivery. (5) Strain of labor on an already impaired myocardium.”

If one had been told a year ago that an epidemic could occur which would result in the death of 60 per cent. of all pregnant women affected, it would have been thought too unlikely to warrant any consideration. Though the effect upon pregnancy of the acute infectious diseases forms an important chapter in the pathology of pregnancy, it seems that the profession, and in this the obstetrician is no exception, has never realized how pernicious and tragic the results of an influenzal epidemic can be in a community. From the experience in previous epidemics we cannot but feel that the infection in the present epidemic was unusually fatal. Whitridge Williams (“Text-book of Obstetrics”) speaks of the interruption of pregnancy as having occurred in 6 out of 7 cases with one observer, and in 16 out of 21 in another, while a third has found it only twice in 41 cases. However, none of these writers speaks of having had a death.

In referring to some of the associated conditions of influenza one scarcely knows whether to consider them as complications or sequelæ. The pathological process certainly had its origin from the influenzal attack, but at times apparently assumed an inactive stage. The patient is usually free from any specific influenzal symptoms, but retains for a long time other symptomsreferable to various organs, or he may have been normal for a shorter or a longer period and then suddenly develop symptoms apparently independent of the previous infection. It may be well to consider all such conditions which followed the febrile attack, whether immediately or more remotely, as sequelæ, and I shall therefore speak of them as such.

The first and probably the most interesting and confusing are the conditions found in the lungs following influenza. A chronic bronchitis, an old bronchiectasis, or a previous tuberculous lesion in whatsoever stage, may present acute symptoms and signs which are difficult to interpret. The question always arises in the individual case—is this a process due to the recent influenzal attack, or was it there before the attack? Is it of streptococcic, pneumococcic, or tuberculous origin? The history of previous diseases of the lungs may help to arrive at a diagnosis. The history of the severity of the influenzal attack is of very little help, because the apparently mildest attack may be followed by the most profound changes in the lungs, and the gravest attack with a history of definite lung infection may leave the lungs without a trace of the previous pathology. The physical examination is helpful, of course, in determining whether the lesion is at the apices or at the bases, and from this a reasonably safe inference may be drawn as to whether it is from a previous tuberculous lesion or a recent influenzal infection. The Roentgenologist depends almost entirely upon this localization. If the linear striæ are only at the apex, it is probably tuberculous; but if they are only at the base, or also at the base, it is likely to be an influenzal lung. In fact, the Roentgenologist with his present information is ready to admit that it is most difficult to speak definitely of the lungs in these cases. The possibility of confusing the post-influenzal lung with a tuberculous lesion is not peculiar to this epidemic. After the epidemic of 1889 and 1890 the same condition was observed by clinicians. Dr. Roland G. Curtin, of Philadelphia, in 1892 and 1893 conducted a series of clinics at the Philadelphia Hospital, in which he spoke of the “non-bacillary form of phthisis,” and showed case after case which he said might be diagnosed as pulmonary tuberculosis, but because of the recent epidemic and the absence of the tubercle bacillus he diagnosed them as post-influenzal lung.

In the present stage of our knowledge, many of these post-influenzal lungs will not be diagnosed properly until sufficient time is given for either the lung to clear up or the tubercle bacillus to appear in the sputum. We would emphasize the importance at the present time of finding the tubercle bacillus in all suspicious lung lesions before giving a positive opinion as to the tuberculous nature, even though the physical signs are very definite.

Another group of sequelæ is that due to thyroid disturbance, or disturbance of the endocrin system in general. Since the epidemic a number of patients have been seen who noticed an enlargement of a previously normal thyroid gland or greater enlargement of a previously hypertrophied gland. In the same way the symptoms of hyperthyroidism appeared, new in some or a recrudescence in others.

In some of these there was a disturbance of carbohydrate metabolism, as shown by an occasional glycosuria and an increase in the blood sugar, or by a possible disturbance of the suprarenals, as brought out by the administration of adrenalin hypodermatically (Goetsch test). In the application of this test in post-influenzal patients it appeared that the whole endocrin system was in a state of imbalance.

It appears to us not at all improbable that the so-called psychoneuroses of which fatigue, nervousness, irritability and tachycardia play such an important part might also be explained in the same way. These constitute a group of sequelæ which were frequently recognized after previous epidemics, and which are again coming to the foreground.

We are of the opinion, on account of the apparent absence of any specific pathology of the gastro-intestinal tract and its appendages during the attack of influenza, that the sequelæ referred to the digestive system are largely due to exacerbations of previous physiological disturbances or pathological processes. The patient with a previous peptic ulcer has a recurrence of his ulcer. The patient with an infection of the biliary tract has an acute exacerbation, or may have an attack of biliary colic. In fact, there seem to have been many more cases of this kind since the epidemic than before, and most of the patients date the time of the onset from a period soon after recovering from influenza.

Very few, if any, patients in our experience have exhibited sequelæ due to disease of the cardio-vascular or genito-urinary systems. It may be that these will appear later when the more remote effects of an acute infection are recorded.

A very commonplace sequel, but of more or less interest, is the tendency to furunculosis. Our attention was particularly called to the associated hyperglycæmia. The blood sugar readings varied from 0.2 to 0.41. There was no glycosuria, acetone or diacetic acid. We have no explanation to offer for this, although one might dilate readily on many attractive theories. The hyperglycæmia, one may add, was readily reduced by a lowered carbohydrate intake, which also had a curative action on the furunculosis.

Finally we would mention the peculiar epidemic which has been observed apparently over the world, encephalitis lethargica. We do not for a moment put ourselves on record as regarding this disease as a post-influenzal affair, but no one will deny that it has a peculiar time relation to the epidemic; and further, that its distribution is apparently identical. Its bacteriology seems to be unknown. Its local pathology in the mid-brain is not peculiar or at variance with encephalitis produced by known organisms. We have seen five cases; three of whom had had undoubted influenza, while the other two were entirely free from even the slightest suggestion of any type of illness previous to the attack. All of these cases recovered. It has been stated that following the 1890 epidemic a clinical condition was observed in Europe which bears a close resemblance to what has been termed at the present time encephalitis lethargica.

In giving a prognosis of influenza one has to take into consideration the peculiar manifestations of the disease, especially the possible and sudden changes which are liable to take place in the lungs. The points which lead one to feel that the outlook is grave occur in about the following order, which is also about the order of the severity of the symptoms. First,cyanosis. This usually appeared quite early and was considered a forerunner of definite lung infection. It may have been a symptom only of the “wet lung,” to which reference has been made, but it was usually followed with definitely recognized pathology inthe chest, and it immediately made the outlook unfavorable. Second,continuation of elevated temperature. If the temperature fell to normal in three or four days, the outlook was, of course, good; but if it went up again, or if the temperature did not fall in that time, the chances were that there was a lung involvement, even though the chest signs were negative or only those of an acute bronchitis. Strange to say, however, when definite chest signs were once recognized, the height of the temperature or the continuation of fever was not so important a prognostic factor. Third,increase in pulse rate. The pulse, as was noted before, was unusually slow, even though the patient seemed desperately ill; when, however, it began to increase in rate the condition was usually very grave. Fourth,the extent of lung involvement. This was of very little prognostic value. Both lower lobes might be solid, and yet if there was no cyanosis and the pulse and respirations were satisfactory, the outlook was rather good. On the other hand, there might be the slightest involvement of the lung, and if the pulse were rapid and cyanosis present the outlook was grave. Fifth,depression and stupor, or loss of so-called “morale.” If the patient remained clear in his mind, bright and hopeful, no difference how extensive the involvement or how grave the symptoms, the prospect of recovery was better. This is, of course, not peculiar to influenza, but it seemed particularly striking during the epidemic. Sixth,a gradually rising rate in respiration, which often was not more than two per minute per day, if progressive, even in the absence of other untoward signs, conveyed a serious prognosis.

Our mortality among the civilians in comparison with the soldiers was exceedingly high. The first cases seen by us were among the soldier patients sent to the hospital. These were as fine a lot of healthy young men as one can well imagine. They came to the hospital comparatively early in the infection. After the first week it appeared as though our experience would be entirely different from those in other localities, for we had very few deaths. In another week our mortality began to rise, but never as high as among the civilians, as will be seen by the following figures.

Of the 153 soldiers 87 were without lung involvement, and of these none died; 66 had lung involvement, and of these 16 died. Mortality among the 153 was 10 per cent. Of the 394 civilians157 were without lung involvement, and of these 1 died; 237 had lung involvement, or some other complication, and of these 93 died. Mortality among the 394 was 23.6 per cent.

It will be seen that the mortality in the civilians was more than twice as high as in the soldiers. It has already been mentioned that the soldiers were ordered to the hospital promptly. The civilian patients, on the other hand, were later in coming to the hospital, some of them appearing when they had already developed serious complications. Another factor in determining the mortality were the ages of the patients. The soldiers ranged from 18 to 34 years, with an average of 20 years. The civilians ranged from 6 months to 73 years, with an average of 30 years. Generally speaking, the greater the age the higher was the mortality.

A third factor which should be considered in determining the actual mortality is the result of later complications and sequelæ. The figures as given are those of 547 patients, 110 of whom had died in the Mercy Hospital and 437 of whom had been discharged therefrom between September 22 and November 30, 1918, the length of the quarantine. Those who were discharged had been up and about for a week or 10 days before leaving the hospital. From our experience with post-influenzal patients admitted to the Mercy Hospital since November 30, we are of the opinion that some of the patients discharged before November 30 as recovered may have later developed sequelæ which might have proved fatal. No follow-up system has been pursued as yet which enables us to speak definitely and statistically of the present condition of those discharged.

This compilation does not readily lend itself to drawing any more specific conclusions, but we cannot desist from expressing our opinion that in the clinical study of this recent epidemic we find very little that may not have been observed by clinicians in previous epidemics.

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