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 traveled from 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
physicians and 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.
_Duration of the Disease_
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 those _without lung involvement_ having 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 acute bronchitis, 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 those _with lung involvement_ and 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.
_Influenza Without Lung Involvement_
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.
_The Temperature_
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:
[Illustration:
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.
[Illustration:
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 and Respirations_
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 to disappear 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.
_Leucopenia_
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, save that 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.
_Asthenia_
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.
_Influenza with Lung Involvement_
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 clinician must 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 resonance were 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.
[Illustration]
[Illustration]
[Illustration]
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, with no 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 disturb them. 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.
_Diagnosis of Influenzal Pneumonia_
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 one suspicious 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.
_Complications_
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 Pfeiffer bacillus 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 be _complications_ of 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 collecting our 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 for a 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.
_Pregnancy_
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 the great 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 48–2/10
per cent. If a pregnant woman miscarries or falls into labor, the
mortality increases to 80–9/10 per 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.
_Sequelæ_
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 symptoms referable 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.
_Prognosis and Mortality of Influenza_
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 in the 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 civilians 157 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.