Chapter XI: Part 11

The varying grades in the intensity of the inflammatory reaction upon the inner surface of the trachea was well illustrated in the microscopic sections. Even with the different degrees of the reaction there was a fairly constant character to the inflammation. In this way the response was found to differ from that commonly observed in ordinary infections of the respiratory tract. The first striking feature is the marked response of the vascular channels, both blood and lymphatic. The vessels lying in the submucosa were found intensely engorged so that their walls were stretched to the point of bursting. In fact, not a few vessels were seen whose walls, probably under the stress of intoxication and dilatation, had given way leading to a flooding of the neighboring tissue with their contents. Where such vessels lay close underneath the surface the hemorrhage escaped into the lumen of the trachea. Accompanying this early vascular response there was found a marked serous exudate leading to a stretching of the submucosal tissues by distention of the interstitial spaces. This reaction resembled an acute inflammatory œdema and occupied the area between the mucosa and the inner border of the cartilage rings. Beyond this region no response was found. Thus in the earliest stages, and where the mucosa was still intact, the main reaction was of the nature of an intense serous inflammation with congestion of the blood vessels and frequent interstitial hemorrhages.

Shortly following the development of the serous exudate in the submucosal tissues, the epithelial lining is found to suffer from the reaction. The serous exudate does not remain confined to the interstitial tissues, but is poured out through the mucosa into the trachea. It would appear that the amount of this clear exudate may become greater than can be dealt with by the mucosa, with the result that an accumulation of this serous fluid takes place between this epithelial layer and its basement membrane. We have repeatedly seen considerable stretches of the mucosa lifted from the basement membrane and shed in large plaques into the lumen. These mucosal cells at the time of their desquamation retain fairly well their morphological characters, and do not show evidence of necrosis prior to their removal. Disintegration of these cells naturally occurs while lying in the secretion of the trachea, and a variable cellular mass in stages of disintegration may often be found both in smears and sections. When the epithelial cells are lifted in wide plates, a type of bleb develops which is easily broken and then disintegrates.

The desquamation of the lining membrane is a fairly constant occurrence in the cases coming to autopsy. In the majority of those which we have examined the greater portion of the trachea was completely denuded, save for small islands lying in the recesses near the mouths of the mucous ducts. In one case this lesion was accompanied by a process of ulceration, due in all probability to the invasion by other micro-organisms. The denuded tracheal surface usually shows a further inflammatory reaction in which a cellular exudate then makes its appearance. This reaction is mainly one in which lymphocytes and plasma cells infiltrate the spaces previously occupied by the serous fluid. The reaction is limited to the submucosa and does not extend into the tissues beyond the cartilages. We have found only occasional polymorphonuclear leucocytes lying close below the surface. During this period, however, varying grades of degeneration may occupy the upper layers. The basement membrane particularly seems to suffer by losing its characteristic outline and staining qualities. This membrane becomes swollen, softened and indefinite. At times a homogeneous precipitate occurs along its free surface giving rise to an appearance resembling a false membrane. This deposit is, however, distinctively different from the diphtheritic membrane of other infections. It is interesting, however, that where such deposits and degeneration occur in the basement membrane more or less degeneration and necrosis also occur in the connective tissues immediately neighboring to it. These tissues show a peculiar granular destruction and alter their staining qualities. Moreover, and what is more important, under these conditions the dilated blood vessels are found to suffer from the injuries taking place in their neighborhood. We have repeatedly found partially or completely thrombosed capillaries, arterioles and venules in these surface layers. These thromboses took place while the vessel was in its distended state and thus produced a mold of the dilated vessel. This observation is of importance in indicating the severity of the effect of the virus and toxin upon the tissues of the trachea, and it is also of importance to appreciate that this damaging influence is very different from that which we encounter in pneumococcus infections, and we shall point out in our discussion on lung a reaction very similar to that which takes place very superficially in the trachea may also occur in the alveolar walls of the lung.

Having referred to the intensity of the responses of the blood vascular system, we must also indicate the part played by the lymphatics. Simultaneously with the reactions taking place about the blood vessels of the trachea we observed similar responses in the lymphatic channels. At first these dilated structures contained only fluid. Later the migration of the lymphocytes took place along these routes, and rarely micro-organisms could be demonstrated either free or within an occasional leucocyte. The sharp response of the lymphatics during the serous inflammation is noteworthy, inasmuch as we have found that the lymph glands lying about the respiratory tubes and lungs were early in their response to the irritating virus.

Bacteria were demonstrated in the secretions lying upon the surface of the trachea. In those specimens in which the mucous membrane was still intact we attempted to demonstrate the clustering of the micro-organisms about the ciliated cells as was described by Mallory in whooping cough. Although the organisms, and particularly small Gram negative bacilli, could be demonstrated lying about these cells no characteristic arrangement was found. Furthermore where the mucosa was still attached to its basement membrane we were never able to demonstrate organisms below the surface of the epithelial layer. In several cases where the mucosa was lifted in bleb-like structures a number of organisms were detected below the epithelial layer and in contact with the basement membrane of the submucosa. We have rarely demonstrated bacteria in the interstitial spaces of the submucosa, even where large numbers of organisms were lying upon the inner denuded surface.

The distinction which was made by the gross examination of the trachea between the acute tracheitis with serous exudate, subacute tracheitis and mucopurulent tracheitis was not so readily distinguished in the microscopic sections. In the gross the character of the exudate lying upon the surface was the main guide suggesting the nature and intensity of the inflammatory reaction. In the microscopic sections this exudate was largely wanting, or was not sufficiently characteristic to confirm the gross findings. On the other hand, differences in the nature of the injury were to be found mainly in the reaction of the submucosa. As we have indicated above, the early inflammatory reaction of the trachea is mainly evident in an intense congestion accompanied by an inflammatory œdema of the submucosal tissues, hemorrhage sometimes accompanying this response. In the later stages of the reaction a cellular deposit takes the place of the inflammatory œdema and usually consists of lymphocytes and plasma cells. It is only in those cases where the intensity of the irritant continues to act over a longer period of time that a superficial necrosis with leucocytic infiltration makes its appearance. The epithelial layer of the trachea is desquamated early in the acute reaction, and hence a denudation of the surface is to be found in all stages of the acute lesion. The mucous glands have not been found to show any particular involvement in the inflammatory process, and in the majority of instances they were found to have escaped entirely the damaging effect of the virus. Their response in an over-secretion of mucus may be the outcome of a stimulation by toxins or soluble irritants; but on the other hand, may also probably be a reflex response to the injury of the mucosal surface, which being bared of its covering is highly sensitive. The increased discharge of mucus from the deep glands may well be a protective response to such injury.

_Bronchi_

The lesions in the bronchi were in every way comparable to those in the trachea. The main bronchial tubes differ in no material way from the structure of the trachea, and the extension of the inflammatory process from above downwards leads to a reaction in their walls similar to what has been above described. As we follow the subdivisions of the bronchi we gradually lose some of the characteristics contained in the larger tubes. The mucous glands gradually become fewer and eventually disappear. The cartilage rings become smaller and no longer completely encircle the bronchus, and with the further diminution in the size of these structures disappear entirely. A relatively greater amount of muscle tissues takes the place of the cartilage rings. This change in the anatomy of these structures has a certain influence in modifying the character and distribution of the inflammation.

TABLE V

BRONCHITIS AND TRACHEITIS

═════════════════════════════════════
Acute bronchitis and tracheitis 26
Subacute bronchitis and tracheitis 1
Acute mucopurulent tracheitis 5
Acute purulent bronchitis 2
Acute mucopurulent bronchitis 7
Ulcers of trachea 1
Acute bronchiectasis 1
─────────────────────────────────────

Thus whereas we have indicated that the inflammation of the trachea and of the large bronchi is of a peculiar kind and remains confined to the tissue lying inwardly from the cartilage rings, we found that where these structures give place to a loose muscle tissue with a more extensive lymphatic drainage the zone of inflammation is not so limited, but proceeds outwardly into the neighboring tissues. We often use the terms bronchus and bronchioles very freely without clearly distinguishing any real difference. In a study of the inflammatory reactions of the respiratory tubes in epidemic influenza (as well as in other infections) it is best to accept the anatomical definition that the bronchioles not only represent the minute tubules passing to the alveoli, but also those small air passages which devoid of cartilage, mucous glands and heavy connective tissue stroma are in close relation to the parenchymatous tissues of the lung. These soft muscular tubes possess blood and lymphatic vessels which freely communicate with the blood vessels of the lung alveoli. It is in association with these distant tubes that concomitant inflammatory reactions are found in the alveoli and in the bronchial tubes.

Desquamation of the epithelial lining is to be found in every size of bronchial tube where the infection has caused an acute inflammatory reaction. Throughout the pulmonary tissues where the lung is found in some stage of influenzal pneumonia the bronchial tubes, both large and small, are either entirely denuded of the mucosa or show only remnants attached to irregular areas. In the smaller passages dense clusters of desquamated cells are sometimes found within the lumen and indicate the accumulation of a desquamated epithelium obtained from portions of the tubular system in deeper portions of the lung. In the early stages, this desquamation is accompanied by a serous exudate and a certain amount of hemorrhage. Later we find masses of leucocytes which fill up the tube, and though appearing to arise from these structures have in fact largely come from the lung alveoli. Like the larger bronchial tubes the distant ramifications show relatively little cellular reaction in their walls in the early period. It is only when the neighboring lung tissues are extensively implicated in a purulent inflammation that we find a similar exudate occupying the tissues of the bronchioles. Polymorphonuclear leucocytes are equally distributed through the region of the basement membrane, submucosa, muscular coat and outer connective tissue layer. Some grades of degeneration may occupy the inner surface wherein the basement membrane first shows a homogeneous swelling and later a granular degeneration. In a few instances where the small bronchioles have communicated with regions with abscess formation an ulcerating surface occupied the inner boundary.

The evidence in the smaller bronchial tubes, both those with cartilage and those without, that an inflammatory reaction of some degree may occupy the muscular coat is of importance. We have found reactions of inflammation in the muscular coat varying from a mild œdema and cellular exudate to an intense polymorphonuclear leucocyte involvement. In the latter the muscle fibers showed evidence of degenerative change and suggested an acute weakening of this layer. We lay particular importance upon this finding as indicating a causative factor in the development of acute bronchiectasis as was met with in one of our cases. In this particular instance the bronchi passing to the lower lobes of each lung were unusually dilated and could be followed, in the gross, to their distant extremities. The dilatation was more or less uniform and no large pouches or cavities had developed. A mucopurulent exudate was found occupying these dilated tubes. Others have likewise observed the development of acute bronchiectasis under these conditions. Goodpasture and Burnett found that as early as the second to the fourth day one of the striking appearances was the gaping dilated condition of the infundibula, and the tendency to dilatation of the air passages was manifested in a bronchiectasis in 4 out of 30 cases. Boggs as well as Lord have reported upon chronic bronchiectasis associated with the B. influenzæ and there appeared to be evidence that a certain percentage of cases recovering from influenza permanently develop irregular dilatations of the bronchial tubes.

The recognition of inflamed bronchi or bronchioles was never difficult. In the gross the presence of the abnormal exudate and the intense injection of the mucosal surfaces always attracted attention to the inflammatory state. Furthermore where the mucosa had been desquamated the surface of these tubes was found to be quite granular if closely observed. With moderate magnification by means of a hand lens the granular appearance was shown to be due to the engorged vessels. Much easier, of course, was the recognition of the inflammatory reaction by the microscope. The importance, however, of the bronchitis and bronchiolitis lay in the amount of involvement which had occurred in the neighboring tissues. As we, however, indicated elsewhere, we do not doubt that many of the cases of three-day fever have a state of tracheitis and bronchitis equal to that which we have observed in many of our cases. Whether the inflammatory reaction progressed beyond the firmer bronchial tubes to the softer and more vascular structures would be difficult to say where our evidence rests upon the clinical findings alone. It is, however, probable that a certain number of the severe and sharp attacks of influenza not only cause a tracheitis and bronchitis of the larger tubes, but also extend more deeply into the smaller ramifications tending to simulate the reactions which we have above described. When we ask ourselves, however, how distantly must the infection invade the smaller bronchial tubes before involving the parenchymatous tissues of the lung we are at a loss to enunciate a general rule. It is more than probable that there are modifying influences which determine whether the bronchitis with a certain amount of its bronchiolitis will progress to a true pneumonia or will remain localized to these tubular systems. I can well appreciate that in the event that a bronchitis has an inflammatory reaction accompanied by much serous exudate there is great danger of flooding the neighboring alveoli with this inflammatory fluid and of carrying the large numbers of the micro-organisms within the tubes to the air sacs of the lung. Under these conditions the virus has an unusual ability to develop the disease from one localized in the air passages to that of a true pneumonia. It is probable that the peculiar early acute reaction which is present in the air passages in epidemic influenza is responsible for the extensive involvement of the lung in the severe and dangerous form of inflammation.

TABLE VI.

EXTENT AND DISTRIBUTION OF PNEUMONIA.

═══════╤════╤════════════════════════════╤════════════╤══════════════════════
AUTOPSY│AGE.│ RIGHT LUNG. │ TYPE OF │ LEFT LUNG.
NUMBER.│ │ │ LESION. │
───────┼────┼──────┬─────────────────────┼────────────┼────────┬─────────────
│ │WEIGHT│INVOLVEMENT OF LOBES.│ │ WEIGHT │ INVOLVEMENT
│ │ OF │ │ │OF LUNG.│ OF LOBES.
│ │LUNG. │ │ │ │
───────┼────┼──────┼──────┬───────┬──────┼────────────┼────────┼──────┬──────
│ │ │UPPER.│MIDDLE.│LOWER.│ │ │UPPER.│LOWER.
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
741│ 18│720 G.│ + │ + │ ++ │Lobar S. & │ 850 G.│ + │ ++
│ │ │ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
743│ 20│825 G.│ + │ + │ + │Lobular S. &│ 1375 G.│ +++ │ +++
│ │ │ │ │ │ H. │ │ │
│ │ │ │ │ │ │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
744│ 30│900 G.│ + │ – │ ++ │Lobar and │ 900 G.│ ++ │ ++
│ │ │ │ │ │ Lobular S.│ │ │
│ │ │ │ │ │ & H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
745│ 18│575 G.│ + │ – │ ++ │Lobular S. &│ 480 G.│ – │ ++
│ │ │ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
746│ 21│900 G.│ + │ ++ │ +++ │Lobar S. & │ 650 G.│ + │ +++
│ │ │ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
747│ 27│ 1510│ +++ │ ++ │ +++ │Lobar S. & │ 1000 G.│ +++ │ +++
│ │ G.│ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
748│ 22│900 G.│ + │ + │ +++ │Lobar and │ 1250 G.│ + │ +++
│ │ │ │ │ │ Lobular S.│ │ │
│ │ │ │ │ │ & H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
749│ 23│ 1480│ ++ │ ++ │ +++ │Lobar S. & │ 1250 G.│ ++ │ +++
│ │ G.│ │ │ │ H. Slight │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
750│ 24│ 1200│ +++ │ + │ +++ │Lobar and │ 825 G.│ + │ +++
│ │ G.│ │ │ │ Lobular. │ │ │
│ │ │ │ │ │ Early │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
751│ 22│ 1250│ – │ – │ +++ │Lobar │ 610 G.│ ± │ ±
│ │ G.│ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
752│ 27│ 1125│ +++ │ + │ +++ │Lobar S. & │ 775 G.│ ± │ +++
│ │ G.│ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
756│ 22│ 1000│ ++ │ ++ │ ++ │Lobar S. & │ 820 G.│ +++ │ ++
│ │ G.│ │ │ │ H. Slight │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
757│ 21│815 G.│ ++ │ – │ ++ │Lobular S. &│ 1075 G.│ +++ │ +++
│ │ │ │ │ │ H. │ │ │
│ │ │ │ │ │ │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
758│ 22│ 1150│ +++ │ + │ + │Lobar │ 1400 G.│ +++ │ +++
│ │ G.│ │ │ │ Purulent │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
761│ 21│ 1250│ +++ │ ++ │ +++ │Lobar S. & │ 550 G.│ + │ +
│ │ G.│ │ │ │ H. and │ │ │
│ │ │ │ │ │ Lobular │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
762│ 21│680 G.│ + │ + │ + │Lobular S. &│ 750 G.│ + │ +++
│ │ │ │ │ │ H. │ │ │
│ │ │ │ │ │ │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
763│ 22│920 G.│ + │ – │ + │B. P. and │ 540 G.│ – │ +
│ │ │ │ │ │ Lobar S. &│ │ │
│ │ │ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
764│ 23│725 G.│ – │ + │ + │Lobular S. &│ 550 G.│ + │ +
│ │ │ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
765│ 25│ 1100│ ++ │ – │ ++ │Lobar S. & │ 1400 G.│ – │ +++
│ │ G.│ │ │ │ H. │ │ │
│ │ │ │ │ │ │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
767│ 25│ 1075│ + │ +++ │ +++ │Lobar and │ 850 G.│ – │ ++
│ │ G.│ │ │ │ Lobular S.│ │ │
│ │ │ │ │ │ & H. and │ │ │
│ │ │ │ │ │ Lobular │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
770│ 21│900 G.│ ++ │ ++ │ ++ │Lobar S. & │ 750 G.│ ++ │ ++
│ │ │ │ │ │ H. and │ │ │
│ │ │ │ │ │ Lobular │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
773│ 22│ 2050│ +++ │ ++ │ +++ │Lobar S. & │ 780 G.│ – │ +++
│ │ G.│ │ │ │ H. and │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
778│ 22│ 1100│ ++ │ + │ ++ │Interstitial│ 975 G.│ ++ │ ++
│ │ G.│ │ │ │ Pneumonia.│ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
781│ 21│ 1000│ +++ │ ++ │ +++ │Lobar S. & │ 540 G.│ + │ +++
│ │ G.│ │ │ │ H. │ │ │
│ │ │ │ │ │ │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
782│ 18│650 G.│ + │ – │ ++ │Lobular S. &│ 875 G.│ ++ │ +++
│ │ │ │ │ │ H. Slight │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
783│ 21│ 1250│ +++ │ +++ │ +++ │Lobar S. & │ 580 G.│ + │ ++
│ │ G.│ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
784│ 21│ 1590│ +++ │ +++ │ +++ │Lobar │ 1400 G.│ +++ │ +++
│ │ G.│ │ │ │ Purulent. │ │ │
│ │ │ │ │ │ │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
786│ 20│ 1100│ ++ │ +++ │ +++ │Lobar S. & │ 700 G.│ – │ ++
│ │ G.│ │ │ │ H. Slight │ │ │
│ │ │ │ │ │ Lobular │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
787│ 21│750 G.│ ++ │ – │ ++ │Lobular S. &│ 1125 G.│ +++ │ +++
│ │ │ │ │ │ H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
791│ 21│775 G.│ + │ ++ │ ++ │Lobular S. &│ 1050 G.│ ++ │ +++
│ │ │ │ │ │ H. and │ │ │
│ │ │ │ │ │ Purulent. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
792│ 21│ 1050│ + │ + │ +++ │Lobar and │ 950 G.│ + │ ++
│ │ G.│ │ │ │ Lobular S.│ │ │
│ │ │ │ │ │ & H. │ │ │
───────┼────┼──────┼──────┼───────┼──────┼────────────┼────────┼──────┼──────
793│ 18│500 G.│ – │ – │ + │Slight │ 435 G.│ - │ +
│ │ │ │ │ │ Lobular S.│ │ │
│ │ │ │ │ │ & H. │ │ │
───────┴────┴──────┴──────┴───────┴──────┴────────────┴────────┴──────┴──────

═══════╤════════════╤════════════╤════════════╤══════════
AUTOPSY│ TYPE OF │ PLEURA. │ ABSCESS OF │ DAY OF
NUMBER.│ LESION. │ │ LUNG. │ DISEASE.
───────┼────────────┼──────┬─────┼────────────┼──────────
│ │ │ │ │
│ │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
│ │RIGHT.│LEFT.│ │
───────┼────────────┼──────┼─────┼────────────┼──────────
741│Lobar S. & │S.F. │S.F. │ │ 3d.
│ H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
743│Lobar S. & │F. │S.F. │ │ 5th
│ H. Early │ │ │ │
│ P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
744│Lobar S. & │S.F. │S.F. │ │ 7th
│ H. │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
745│B.P. with │S.F. │– │ + │ 10th
│ Necrosis. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
746│Lobar S. & │– │– │ │ 5th
│ H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
747│Lobar S. & │S.F. │– │ │ 6th
│ H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
748│Lobar S. & │– │– │ │ 4th
│ H. and │ │ │ │
│ B.P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
749│Lobar S. & │F. │– │ │ 4th
│ H. Slight │ │ │ │
│ P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
750│Lobar and │F. │F. │ │ 9th
│ Lobular. │ │ │ │
│ Early P. │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
751│B.P. slight.│S.F. │– │ │ 7th
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
752│B.P. and │F. │S.F. │ │ 13th
│ Lobar P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
756│Lobar and │F. │S.F. │ │ 8th
│ Lobular S.│ │ │ │
│ & H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
757│Lobar S. & │F. │F. │ │ 6th
│ H. and │ │ │ │
│ Purulent. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
758│Lobar │F. │F. │ │ 14th
│ Purulent. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
761│Lobular S. &│– │– │ │ 7th
│ H. │ │ │ │
│ │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
762│Lobar S. & │S.F. │S.F. │ │ 10th
│ H. and │ │ │ │
│ Lobular P.│ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
763│B.P. │F.P. │– │ │ 11th
│ │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
764│B.P. │– │– │ │ 9th
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
765│Lobar S. & │– │– │ │ 9th
│ H. and │ │ │ │
│ Early P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
767│Lobar S. & │– │F. │ │ 10th
│ H. Lobular│ │ │ │
│ P. │ │ │ │
│ │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
770│Lobar S. & │S.F. │F. │ + │ 11th
│ H. Lobular│ │ │ │
│ P. │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
773│Lobar S. & │F. │F. │ │ 20th
│ H. Lobular│ │ │ │recurrence
│ P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
778│Interstitial│S.F. │S.F. │ │ 23d
│ Pneumonia.│ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
781│Lobar S. & │S.F. │S.F. │ + │ 5th
│ H. │ │ │ │
│ Purulent. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
782│Lobar S. & │F. │F. │ │ 8th
│ H. and │ │ │ │
│ Early P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
783│Lobar S. & │S.F. │S.F. │ │ 8th
│ H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
784│Lobar S. & │S.F. │S.F. │ │ 8th
│ H. and │ │ │ │
│ Purulent. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
786│Lobar S. & │S.F. │– │ │ 4th
│ H. and │ │ │ │
│ Early P. │ │ │ │
│ │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
787│Lobar S. & │S.F. │S.F. │ │ 8th
│ H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
791│Lobar S. & │F. │S.F. │ │ 6th
│ H. and │ │ │ │
│ Slight P. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
792│Lobar and │S.F. │S.F. │ │ 6th
│ Lobular S.│ │ │ │
│ & H. │ │ │ │
───────┼────────────┼──────┼─────┼────────────┼──────────
793│Slight │– │F. │ Strep. │ 10th
│ Lobular │ │ │Bacteriemia.│
│ Purulent. │ │ │ │
───────┴────────────┴──────┴─────┴────────────┴──────────

S—Serous. H—Hemorrhagic. P—Purulent. B.P.—Broncho-pneumonia.
S.F.—Serofibrinous. F.—Fibrinous. F.P.—Fibrinopurulent.

It was very evident that the smaller bronchi and bronchioles were much more readily involved in a severe inflammatory reaction than the larger tubes. A purulent inflammation was not uncommonly found in the bronchioles of the lung when a pneumonic state with leucocytic infiltration was present. Even where such purulent infiltration of the walls of the bronchioles was readily demonstrable the trachea and main bronchi were devoid of this intense reaction. These purulent inflammations were not uniformly distributed in the bronchioles of the lung, but only occurred in those regions where the parenchymatous tissues were in themselves involved in a purulent reaction. It was difficult to find the evidence whether the purulent bronchitis preceded or followed the presence of a purulent pneumonia. The intimacy of the lung tissues with those of the small bronchioles makes it impossible for one or other of these structures to escape when one of them is implicated in a purulent reaction. It is equally important to appreciate that to a considerable extent the lung tissue surrounding the small bronchioles becomes involved by a direct radial extension through the walls of the thin respiratory tubes. Such extension laterally is assisted by the free lymphatic communication lying about the bronchioles and stretching into the lung parenchyma. Purulent processes of the small air tubes always showed a similar reaction in the interstitial tissues of the neighboring air sacs.

Our material did not permit of following the bronchial reactions to their conclusion. In some instances we have found that where abscesses developed within the lung the contiguous bronchi and bronchioles either became eroded or suffered intense suppurative inflammatory lesions on their inner surface. The manner in which repair of the more common inflammatory processes of the bronchi is accomplished could not be demonstrated in the cases dying during the acute stage. In one case an organizing bronchitis was associated with an organizing lobular pneumonia. In this instance the connective tissues were proliferating freely from the inner wall of the bronchi, there being no evidence of a basement membrane at the point where the connective tissue was growing. The development of the connective tissue appeared to be spontaneous and was not taking place within an unresolved fibrinous exudate. In as much as the fibrosing process was largely scattered through all of the lobes, the numerical involvement of the respiratory tubes was quite great. In this instance the amount of obstruction which was imposed upon the respiratory tissues by the fibrosing pneumonia and bronchitis was sufficient to cause considerable distress and dyspnœa during the last few days of the patient’s life. The amount of dyspnœa was out of proportion to the clinical manifestations of pulmonary involvement, and from a clinical point of view it was difficult to arrive at a conclusion of the nature of the lung lesion.

Undoubtedly during the subsidence of the inflammatory process within the bronchi the gradual restitution of the tissues with little or no fibrosis is accompanied by a reproduction of the lining membrane arising from the epithelial remnants in the small mucous crypts. In a few cases lately coming to autopsy where the patients had suffered an influenza five or six weeks previously, the mucosa of the trachea and bronchi had assumed its normal appearance and was fully clothed by a normal epithelial covering.

_Lung—Early Stage_

We have just discussed the importance of the inflammation of the trachea and bronchi in the cases of influenza. It is our belief that every case of influenza has some tracheitis, and a great many have both tracheitis and bronchitis. This is true in the absence of localizing signs and symptoms, as was evident even in these cases in which the simple influenza passed into its more severe type with its pulmonary lesions. In many of these instances clinical evidences of an inflammatory reaction in the respiratory tubes were wanting, while the reactions observed at autopsy were often astounding.

Just as we feel that simple influenza and inflammation of the respiratory tubes go hand in hand, or better that these respiratory localizations are the all-important ones in every case of simple influenza, so, too, we are of the belief that the pulmonary lesions bear the same relation to all cases of severe and fatal epidemic influenza. We hold that no case comes to his death through acute epidemic influenza without having a lesion in the lung. The pulmonary condition, therefore, is of first importance and its analysis is imperative for a proper understanding of this disease. There has been divided opinion as to the part played by the pulmonary lesion in epidemic influenza, some holding that it is to be looked upon as a part of the disease and others that it must be viewed as a complicating lesion. Complications of various kinds are very common, and there are a number of conditions arising in the lung (abscess, gangrene, necrosis) which must be viewed as complications. There is, however, a type of pneumonia, and here I use the term in its broad sense, which is not in truth a complication but merely a wider extent of involvement of the respiratory tract by the same virus which is always present to cause lesions in the respiratory tubes. The reaction within the lungs is distinctive and differs from the pneumonias which are met with under other conditions and with various bacterial agencies. Nor are our findings in this matter unique for this epidemic. They have been described and discussed in the past. True it is that, like in the epidemic which has just passed us, the incidence of clinical and pathological pneumonia varied quite widely in different communities, so, too, the reports of past epidemics do not give a uniform description of a pulmonary lesion. Where, however, the analysis has been made during the four weeks’ period of the acute epidemic and where the descriptions have been recorded by painstaking observers, the similarity with our present findings is very striking. I would refer in particular to one report made in 1893 in Petrograd by Kuskow. His report deals with 40 carefully studied cases in which records both macroscopic and microscopic were accurately made.

One of the great difficulties in placing an accurate interpretation upon the pulmonary findings lies in the fact that true pneumonia as seen in epidemic influenza in man has not been reproduced in animals. Furthermore, as the majority of the fatal human cases of epidemic influenza with their associated pneumonias present a mixed infection of the lung tissues, it is difficult, if not impossible, to indicate the lesions which have resulted through the activity of one of these as against those induced by the other bacteria present. In our own carefully studied cases wherein bacteriological cultures were taken from every lung there was not a single instance in which the influenza bacillus was present in pure culture. This is more fully commented upon in the studies by Dr. Holman, but the point we wish to make here is the difficulty in arriving at a conclusion in our material as to the actual effects induced by any one type of organism. As it is fully discussed by Dr. Holman we are convinced of the importance of the influenza bacillus in this epidemic. We also appreciate that pneumonia lesions in animals have been induced by a variety of materials gained from influenza patients, but yet in view of the abnormal manner of producing such lesions these are hardly comparable to those in man. We may well expect severe œdema, inflammation and hemorrhage, if in guinea pigs, rabbits and monkeys we introduce by intra-tracheal insufflation large quantities of fluid suspensions of bacteria. And thus we find positive results obtained by the use of a filtrable virus, streptococci, influenza bacilli and other organisms. The lung is a sensitive tissue which quite readily responds to a variety of irritants. In many respects some of these lesions simulate those in influenza, but still we are far from the conclusion that the disease, influenza, with all its manifestations has been actually reproduced.

The pathology of the pulmonary lesions in acute epidemic influenza is so distinctive that except for the late purulent stage which may resemble types of reinfected and unresolved pneumonia the condition cannot be confused with the stages of frank lobar pneumonia. We appreciate that this is a very positive statement, and that opposition will be taken by those who resting their opinion upon individual factors may claim that a clear distinction from other forms of pneumonia is not available. We, however, base our opinion not upon a single feature, but upon the combined pathological complex observed in many individual cases. These features are mainly those seen in the type of the lesion, the character of the distribution, extent of involvement and the multiple stages so commonly present at one time in different portions of the lung. The type lesion that has become so well known in pneumococcus lobar pneumonia has its distinctive stages which for teaching purposes are divided into the stage of (1) congestion, (2) red hepatization, (3) gray hepatization and (4) resolution. In dealing with lobar pneumonia from the standpoint of illustrating these stages the majority of teachers annually confess their inability to present for the student’s study the stage of congestion. The student is impressed that the congestive stage of lobar pneumonia is very transient and rapidly passes into the stage of red hepatization. Patients do not die with pneumococcus pneumonia in the stage of congestion. And this is also largely true of the stage of red hepatization, which is but rarely seen at the autopsy table. This community (Pittsburgh) gives its large quota to the mortality statistics of pneumococcus pneumonia, but it is most unusual to meet with a specimen of red hepatization except for the borders of the advancing gray area. And, furthermore, red hepatization even when found in the unusual cases shows remarkably little of this character when seen under the microscope. True it is that a certain number of red blood cells will be found in the alveoli and a certain degree of congestion will occupy the alveolar walls, but its extent is far less than what we may have hoped to demonstrate to others. So that broadly speaking the intensely congested lung with or without red hepatization is unusual in our frank lobar pneumonia. This was quite the reverse in our cases of acute epidemic influenza-pneumonia. Furthermore lobar pneumonia in the great majority of instances illustrates a distribution distinctive for the name. Massive lobar, or pneumococcus pneumonia is found to occupy one or more lobes or parts of lobes. The involved lobe is fairly uniform in the stage of the inflammatory process. If it is in the early gray stage, this will be seen with equal intensity in the different areas of the lobe. Patches of pneumonia in different stages within the same lobe are not to be found, while this finding is not uncommon in the pneumonias of acute epidemic influenza. And lastly, the frequency with which an inflammatory œdema occupied the lungs in the cases of influenza was in quite striking contrast with the dry fibrinous lesion of common pneumonia. This wet state of the lung was but a stage in the inflammatory process varying in its extent in the different periods, but nevertheless inducing a character in the early pulmonary lesions which was quite foreign to our usual finding. This wet state also assisted in modifying the subsequent picture so that when the lung assumed its gray appearance it was rather of a slimy character than of the firm dry nature. In this late gray stage the slimy lung somewhat resembled the appearance of unresolved pneumonia where this condition had been brought about by a new infection upon the original cause of the pneumonia.

It is incorrect in influenza pneumonia to speak of the lesions as lobar pneumonia or broncho-pneumonia if by these terms we have in mind the pathological characters observed in the pneumococcic pneumonia with its lobar or bronchial distribution. Influenza-pneumonia appeared with both lobar and lobular characteristics. Nearly every case had both types of lesions present, but the nature of the inflammatory process is so decidedly different from that of the ordinary endemic pneumonia that a confusion in the interpretation is likely to arise and in fact has already raised a considerable polemic. Influenza-pneumonia is commonly lobar, lobular or bronchial in distribution. It is, however, not of the characters that are associated with the lesions designated under these terms. When, therefore, we here use the word “lobar” we mean lobar _in distribution_ but not lobar in type. As will be seen from our table, it was usual to have multiple lobes involved. But the lesions, not only in the different lobes varied in their character and distribution, but even within the same lobe a variety of types was present.

TABLE VII

═══════════════════════════════════════════════╤═══════════════════════ Day of Pneumonia on Which Death Occurred │ No. of Cases ───────────────────────────────────────────────┼─────────────────────── Second │ 2 Third │ 4 Fourth │ 7 Fifth │ 6 Sixth │ 7 Seventh │ 3 Eighth │ 1 Tenth │ 1 Twentieth │ 1 ───────────────────────────────────────────────┴───────────────────────

To a certain degree we were able to analyze the types of the lesions as they occurred in the different stages and progress of the pulmonary inflammation. Briefly, these were as follows: the earliest stage of congestion following rapidly upon the infection from the bronchi was followed by (1) inflammatory œdema, (2) hemorrhage, (3) cellular exudate (a. mononuclear cells, b. leucocytes, c. interstitial infiltration) and (4) resolution or organization, abscess, infarct and gangrene. The majority of our cases died during the stages of congestion, hemorrhage or early purulent infiltration. In the early stages the amount of fibrin was small or entirely absent, later, with the appearance of leucocytes, some fibrin was present.

For the estimation of the time elapsing between the onset of the pneumonia and death we are dependent upon the clinician. This is often quite difficult to do, in as much as with a primary respiratory disease, such as epidemic influenza represents, it is very difficult to determine the time when there is a transition from the inflammatory process of the upper respiratory tubes to that of the pulmonary tissue. In many of the cases where from the onset there was intense prostration and every evidence of marked intoxication the clinical manifestations of localized processes taking place in the respiratory system were very much in the background and often of insidious progress. In four of our cases it appeared as if the pulmonary manifestations had made their appearance with the first sudden and severe onset of the influenza. On the other hand, also, the clinical signs and symptoms of lung involvement were different from those of frank lobar pneumonia. We would, from our experience at the autopsy table, say that where in the cases of epidemic pneumonia there are present the signs of pulmonary consolidation like those of true lobar pneumonia, that there has been an antecedent period of a pulmonary lesion which passed unrecognized by the clinician. To more clearly state the case, whereas in lobar pneumonia the stage of congestion preceding the stage of red hepatization gives rise to no signs whereby the clinician can indicate the time of its onset or determine the time when it has passed into the succeeding stage, and moreover, the stage of congestion is of short duration to be measured in a period of a few hours, this stage in epidemic influenza though equally indefinite in its clinical manifestations is much prolonged, lasting not only a period of hours but even a period of several days. It is this pulmonary state which is difficult or even impossible to recognize in the living. All gradations of it occur and the clinician can only broadly suggest from all the evidence at hand, the period when inflammation with definite exudate began in the lung. In as much as the total length of illness of a number of cases was only three, four and five days, whereas there was nothing at the onset to suggest pulmonary involvement, we can estimate approximately, at least, the duration of the lung condition. This makes it possible to give a relative estimate of the character of the lesions present at different periods of time. The outstanding finding, as we will discuss again, was that a distinct and peculiar pulmonary reaction was primarily imposed upon the lung, which made its appearance at periods different from those of frank lobar pneumonia.

We were repeatedly surprised at finding death to have occurred during the stage of acute congestion with some hemorrhage and inflammatory œdema of lung and in the absence of any sign of grey hepatization or purulent infiltration. In many of these cases the involved areas of lung though heavy and œdematous, were still partly air-containing and the amount of lung involvement was insufficient, on the basis of mechanical interference, in accounting for the severity of the clinical symptoms and the fatal outcome. This must have impressed everyone dealing with the autopsies during the acute epidemic. It immediately suggests that in some cases at least the pulmonary lesion, in as far as incapacitating the external respiratory system, was not the sole or even the important cause of death, but that a condition of intoxication, borne out by the evidence of damage in muscles, blood and kidney is a large factor of danger in this disease.

We shall briefly describe the important pulmonary findings as we have met with them in the successive stages of influenza-pneumonia. This, we hope, will make clear the interpretation of the pathology of the lung lesion of the epidemic as it came under our observation.

The earliest pulmonary lesion which we encountered was one of congestion, inflammatory œdema and hemorrhage. These three conditions were usually present at the same time and were found in the height of intensity in all of the cases dying within the first four days of illness. During this early period these manifestations of inflammation were not accompanied by definite red or grey hepatization as might ordinarily be expected. The lesions varied greatly in their intensity, the œdema always being very prominent, while the hemorrhage varied from a diffuse infiltration of the involved lobe or added to this, was localized in massive collections four or five cm. in diameter and commonly occupying the central portions of the lobes. We have seen several hemorrhages lying in close proximity to each other with their borders coalescing and leading to a larger central involvement. In the regions where the hemorrhage and inflammatory œdema were diffuse, air was still present within the lung tissue, sometimes to an extent permitting the lung tissue to float on water but more often in quantity sufficient only to suspend the tissue at various depths. On pressure the fine air bubbles were recognized amidst the blood-stained fluid. Acute compensatory emphysema often occupied the anterior borders of the lobes or formed interstitial blebs beneath the pleura. The quantity of fluid, inflammatory œdema and hemorrhage, contained within these bulky lobes was often very surprising. A lobe when compressed would leak fluid with the ease that it could be obtained from a sponge. Out of the lower lobe on one occasion we pressed 700 c.c. of limpid blood-stained exudate. The acute emphysema which may make its appearance suddenly, is

TABLE VIII

DISTRIBUTION OF PNEUMONIC LESIONS AND GRADES OF SEVERITY

═════════════════════════════════════
DEGREE OF INVOLVEMENT + ++ +++ Total
Left upper lobe 10 6 7 23
Left lower lobe 4 10 17 31
Right upper lobe 12 8 9 29
Right middle lobe 10 9 4 23
Right lower lobe 5 9 18 3
─────────────────────────────────────

All lobes were simultaneously
involved in some grade of pneumonia
in 18 cases—56 per cent.

at times quite remarkable. It may appear very early in disease. We have not met with a single case where the emphysema of the lung led to a rupture of the air sacs and an interstitial infiltration of air through lung, mediastinum, neck and subcutaneous tissues. Some very remarkable cases are reported by different authors where this emphysema was of astounding grade leading to a crepitating infiltration throughout the mediastinum, neck and the subcutaneous tissues over the thorax and abdomen as low as the pubis. The milder grade of emphysema consisted mainly of an abnormal expansion of the air sacs which were not infiltrated by exudate and which probably had some effect in preventing the diffusion of the inflammatory fluid from entering certain regions. These emphysematous areas could be readily recognized by the naked eye along the anterior borders of the lung as well as between the involved pneumonic patches within the lung.

These lungs, involved in this early serous and hemorrhagic exudate varied considerably in their appearance according to the regional and quantitative involvement. As is seen from Table viii, the lower lobes were more commonly occupied by massive exudate than the upper, and the involvement of multiple lobes was the usual. Still more remarkable is the fact that all lobes were simultaneously involved in some grade of reaction (pneumonia) in 56 per cent. of cases. In complicated influenza-pneumonia Goodpasture and Burnett found the inflammatory reaction in both lungs and involving to a greater or less degree the lobes on each side. Most commonly this involvement consisted of a lobar distribution in one or two lobes with a lobular or patchy disposition of exudate in one or more of the remaining lobes. Where the distribution was lobar the involved lobe was distended to its fullest and the pleura tightly stretched over the lung tissue which, heavy with fluid, was not solid but flabby. The lung could be moulded under the finger and could be compressed into various shapes. At first sight this flabby, heavy lung tissue suggested the appearance of the waterlogged lung which one encounters in renal disease or failing circulation. A closer analysis, and particularly when the lung was sliced, showed an entirely different character.

Where the inflammatory œdema was accompanied by much focal hemorrhage the distribution was nodular and suggested the appearance of the hemorrhagic lung of plague pneumonia. It was this appearance which led to the suggestion that the pandemic was not one of influenza but possibly of an infection related to the eastern plague. The nodular masses of hemorrhage at times occupied areas varying from the size of a walnut to that of a golf ball and were localized amidst a relatively mildly involved lung tissue making a sharp contrast between the involved and relatively normal tissue. With the removal of the lung from the body and the partial collapse of the aerated tissues these nodules became still more prominent. The greater the amount of hemorrhage within these areas the more solid became the occupied tissue. Such sporadic distribution of hemorrhagic lesions occurred in the two most intense and rapidly fatal cases. Both of these individuals died within 48 hours of the time of onset of the lung conditions. In these two cases we do not believe that the pulmonary lesions had been prolonged over a time even as long as 36 hours but with the difficulty of estimating the onset of the lung involvement we are giving a liberal estimate of this time.

Besides meeting with the stages of congestion, œdema and hemorrhage during the earliest days of the pulmonary lesions we have found that they are to be encountered virtually through all the stages of the fatal cases either as remnants of the original reactions which had not been entirely obliterated by the succeeding purulent process or as was so commonly found, new reactions occurred in other regions of the lung so that, in the same individual, inflammatory reactions of different stages of development could be defined. I do not recollect a single autopsy of a case dying during the acute period which did not show evidence of some areas in the stages of this early acute reaction. Naturally where resolution is well advanced within the lung all trace of inflammatory exudate of various kinds is removed and where such individuals with their resolved pneumonia are brought to death through succeeding complications the above finding will not be borne out. We limit, however, our statement to the findings in the acute deaths.

We have previously intimated that the œdema present in the early stages of the reaction is to be looked upon as an inflammatory œdema or better as a true serous exudate, and must not be confused with the transudation of fluids in non-inflammatory conditions. We have on several occasions collected the fluid expressed from the soggy lungs and have made some determinations of their chemical qualities. The difficulty immediately arises in separating the materials arising from cellular degeneration from the natural constituents of the serous exudate. We were unable to obtain specimens in which laked blood was not present, so that even though the cellular constituents and fibrin were removed, decomposition products could not be separated. The analyses, however, gave a differentiation from the transudate seen in renal and cardiac conditions.

During the period of the accumulation of this inflammatory fluid the clinician could often recognize a profuse watery exudate within the lung or even observed an abundant serous discharge arising in bronchi and trachea. At times the quantity of expectoration was great. Frothy serous fluid accumulated in the air passages and would periodically be expectorated. At other times the hemorrhage was of quite serious extent and the patient would suddenly bring up several mouthfuls or more of bright blood. This pulmonary hemorrhage was without manifestations different from the acute illness with cyanosis of other individuals. The two most acute cases, which we have referred to above, were of this kind, both of them having marked hæmoptysis with the loss of upwards of a pint of blood at a time.