E. L. Opie, M.D.; F. G. Blake, M.D.; and T.M. Rivers, M.D. Many observers have described isolated phases of the recent epidemic and of past epidemics of influenza. Few have had an opportunity to follow the pathology of influenza from the onset of an epidemic through a period of several months and to observe the succession of acute and chronic changes which occur in the lungs. Our commission arrived on September 5, 1918, at Camp Pike two weeks before the outbreak of influenza. The commission had previously made a careful study of the clinical course, the bacteriology and to a limited extent the pathology of pneumonia occurring at Camp Funston where there was little if any influenza. Study of the records preserved at the base hospital at Camp Funston had convinced us that this camp had passed through an epidemic of influenza during the spring of 1918, this epidemic being followed by a very severe outbreak of pneumonia. Our investigation at Camp Funston had brought to our attention those phases of pneumonia which with the facilities of a base hospital laboratory could be most profitably studied with a view to determining the causation, the epidemiology and the prevention of the pneumonias prevalent in the American army. Study of pneumonia after death offers the only opportunity of determining the relation of pulmonary lesions to the considerable variety of microorganism associated with them. Clinical diagnosis furnishes no certain criterion for distinguishing lobar and bronchopneumonia; suppurative Study of autopsies following examination of the sputum during life has shown that an individual primarily attacked by influenza may suffer with a succession of pneumonias, one microorganism having prepared the way for another. The complexity of the subject is much increased by the truth that pyogenic microorganisms, like the tubercle bacilli, are capable of producing a considerable variety of pulmonary lesions. Examination of the lungs of a large number of individuals who have died as the result of pneumonia following influenza has disclosed a succession of acute and chronic diseases. Immediately succeeding the height of the epidemic of influenza, death occurred with acute lobar pneumonia or with diffusely distributed hemorrhagic bronchopneumonia caused in the majority of instances by Pneumococcus IV in association with B. influenzÆ. Superimposed infection with hemolytic streptococci increased in frequency and in individuals who had occupied certain wards was almost invariable. At a later period, from one to two months following the maximum incidence of influenza chronic lesions, namely, bronchiectasis, unresolved pneumonia, and chronic empyema were common and often occurred as the result of influenza which had had its onset at the height of the epidemic. When influenza attacked the encampment, about 50,000 troops were quartered in it, and for a considerable period no more troops were brought into the camp and none left Pneumonia of Influenza.—Knowledge concerning the bacteriology of the pneumonia of influenza dates from the study of the epidemic of 1889–90. The frequency with which Diplococcus lanceolatus occurred in association with influenzal pneumonia was well recognized, although several observers, notably Finkler During a subsidiary outbreak of influenza occurring in 1891–92 Pfeiffer Observations upon the pathology of influenzal pneumonia made during the epidemic of 1889–92 have been collected in the monograph of Leichtenstern There appears to be no comprehensive description of the pneumonias of influenza based upon the epidemics of 1889–92. Descriptions dating from this period are much obscured by attempts to separate croupous or fibrinous from catarrhal pneumonias. Croupous lobular pneumonia has been recognized, for example, by Birch-Hirschfeld. Leichtenstern describes a form of pneumonia which he regards as Kuskow Opinions concerning the pathology and bacteriology of the pneumonias of influenza, published since the recent epidemic, have varied almost as much as those just cited. Few observers have had the opportunity of making a considerable number of observations under conditions which determine the relation of the pulmonary lesions to the primary disease. Keegan Symmers Our commission LeCount MacCallum Lyon Goodpasture and Burnett Wolbach Streptococcus Pneumonia.—Finkler emphasized the importance of streptococcus pneumonia as a complication of influenza. In 1888 he described instances of acute primary streptococcus pneumonia observed in 1887 and 1889. This form of pneumonia, Finkler thought, occurred in Bonn in epidemic form before the influenza epidemic of 1889–90 and, he states, exhibited an astonishing similarity to the pneumonia of influenza. He thought that later there was in Bonn a mixed infection of influenza and primary streptococcus pneumonia. In one type of streptococcus pneumonia, described by Finkler, there was lobular consolidation which in multiple patches produced “pseudolobar” consolidation; the consolidated lung was smooth and red, and similar to spleen, rather than hepatized. In another group of instances the lesion merited the name “erysipelas of the lung.” The lesion was an acute interstitial pneumonia in some places, a cellular or occasionally fibrinous pneumonia with involvement of the interstitial tissue in other places. There was edematous swelling and accumulation of leucocytes in the interstices between the alveoli and about The widespread occurrence of streptococcus pneumonia in the army camps in this country attracted attention during the first months of 1918. Cummings, Spruit and Lynch Cole and MacCallum The epidemic of streptococcus pneumonia and empyema occurring at Camp Dodge, Iowa, from March 20 to May 10 is described by Miller and Lusk MacCallum The pneumonia which occurred at Camp Funston is of special interest to our commission because we were for a time stationed at this camp and had the opportunity of following in the excellent records of the hospital the history of the occurrence of pneumonia during the year following the establishment of the camp in September, 1917. Stone, Phillips and Bliss Our commission The foregoing observations are cited to prove that streptococcus pneumonia, which occurred during the spring of 1918 at Camp Funston and doubtless at other camps, had its origin in influenza and did not differ in character from that which occurred on a much larger scale in the fall of 1918. Table of Autopsies.—In order to present as briefly as possible the data upon which the present study has been based, autopsies have been assembled in tabular form in the order of their performance (Table XXVII). During the early period of the epidemic autopsies were performed on all who died with pneumonia, but later, with increase in the number of deaths, this became impossible and autopsies were performed on all those who died in certain wards. Cases of pneumonia following measles have been excluded from the table in order that they may be studied separately and compared with the pneumonias of influenza. It is noteworthy that the lesions of pneumonia following measles have shown a very close resemblance to the pneumonias of influenza, with regard both to pathologic characters and to bacteriology. Five instances of pneumonia following typhoid fever (Autopsies 245 and 329), scarlet fever (Autopsy 311) or mumps (Autopsies 403 and 417) have been excluded from the table. These secondary pneumonias are grouped as an appendix to the section on pneumonia following measles. It is not improbable that individuals with the diseases named are just as susceptible as others to influenza. Included in the table is an instance (Autopsy 487) in which a definite attack of influenza preceded scarlet fever. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
273 | W | 1m | 8 | 4+ | L | + | + | N | E | St. h. B. inf. Staph. | St. h. Pn. IV. Staph. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
274 | W | 2w | 9 | 5 | B | + | N | Pn. IV. | St. h. Staph. | St. h. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
275 | W | 4m | 9 | 4 | L | M | + | + | N | St. h. B. inf. Staph. | St. h. B. inf. Staph. | St. h. Pn. IV. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
W | 1m | 6 | 4+ | L | + | St. h. Staph B. inf. | St. h. Pn. IV. B. inf. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
277 | W | 21d | 10 | 3 | L | + | St. h. Staph | St. h. Staph | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
278 | W | 2m | 16 | 6+ | L | + | E | St. h. B. inf. | St. h. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
279 | W | L | + | Pn. IV | Pn. IV. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
280 | W | 21d | 8 | 8 | L | + | + | + | St. h. B. inf. Staph. | St. h. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
281 | W | 21d | 9 | 5 | L | + | + | h | St. h. B. inf. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
282 | W | 1m | 10 | ? | B | + | + | E | Pn. IV. B. inf. | St. h. B. inf. Pn. II Staph. | St. h. Pn. II. | St. h. Pn. II. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
283 | W | 7d | 19 | 8 | B | P | + | + | + | M | + | 2 | L | + | Pn. IV. B. inf. | Pn. IV. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
318 | W | 2m | 8 | 3 | L | + | Pn. IV. B. inf. | Pn. IV. B. inf. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
319 | W | 1m | 4+ | 4+ | B | P | + | St. h. Staph. | St. h. B. inf. Staph. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
320 | C | 5m | 1+ | 1+ | L | + | Pn. IIa. | Pn. IIa. | Pn. IIa. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
321 | W | 28d | 4+ | 4+ | L | + | E | B. inf. | Pn. IV. B. inf. | Pn. IV. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
322 | W | 10d | 8 | 6 | L | P | + | + | + | Pn. IV. | Pn. III. Staph. aur. | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
323 | W | 2m | 12 | 4 | B | + | Pn. IV. B. inf. Staph. | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
W | 22d | 9 | 6 | B | + | Pn. I. B. inf. | 0 | Pn. I. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
325 | W | 1m | 8 | 8 | B | P | M | N | + | + | St. h. B. inf. Staph. | St. h. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
326 | W | 1m | 5+ | 2 | B | P | + | h | St. h. B. inf. Staph. | St. h. B. inf. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
327 | W | 1m | 4 | ? | B | + | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
328 | W | 5m | 13 | 3+ | L | P | + | + | + | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
399 | W | 1m | 18 | 4 | L | + | Pn. IIa. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
400 | W | 1m | 15 | 11+ | L | + | Pn. IV. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
401 | W | 1m | 13+ | 9 | B | P | + | M | h | + | Pn. IV. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
402 | W | 1m | 14 | 8 | B | P | M | + | + | E | + | + | + | Pn. IV. St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
404 | B | P | + | + | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
405 | W | 21d | 13 | 11+ | B | + | M | Pn. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
406 | C | 2d | 18 | 15? | L | P | + | + | E | Pn. IV. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
408 | C | 1m | 13 | ? | L | P | + | + | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
409 | C | 6d | 12 | 9+ | L | P | + | + | M | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
410 | W | 35d | 13+ | 13+ | L | P | + | + | M | + | E | + | St. h. B. inf. Staph. aur. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
411 | W | 3m | 16 | 2 | B | P | + | + | Pn. IIa. B. inf. | Pn. IIa. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
412 | W | 1m | 15 | 13? | L | + | M | B | P | M | + | E | St. h. B. inf. | St. h. B. inf. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
C | 2m | 7 | 3+ | B | + | E | B. coli. Staph. St. v. | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
455 | C | 26 | 22+ | B | + | + | E | St. h. B. inf. | St. h. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
456 | W | 1m | 23+ | 20+ | L | P | + | E | B. coli. | St. h. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
457 | W | 17m | 17+ | 17+ | B | + | + | + | + | + | Pn. IV. B. inf. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
458 | W | 11m | 10 | 8+? | L | + | + | Pn. IV. B. inf. St. v. | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
459 | C | 10d | 6 | 3 | B | P | + | + | Staph. aur. Pn. IV. | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
460 | W | 1m | 17 | 17 | L | P | + | + | M | + | E | + | St. h. B. inf. Staph. | St. h. B. inf. | St. h. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
461 | C | 5d | 14 | 8+ | L | P | + | M | + | Staph. aur. Pn. I. St. h. | Pn. I. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
462 | C | 5d | 15+ | 12 | B | + | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
463 | W | 3m | 20 | 12 | B | P | + | + | Mh | + | + | B. inf. Staph. | B. inf. Staph. | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
464 | C | 21d | 24 | 17? | L | P | + | Clinical Diagnosis.—The clinical diagnosis recorded upon the clinical history of the patient is given in column 6. Many clinicians have been impressed with the difficulty of determining during life the type of pneumonia associated with influenza. The occurrence of purulent bronchitis, the frequent coexistence of lobar and bronchopneumonia and an atypical onset often make the recognition of lobar pneumonia more difficult than usual. The diffuse consolidation of confluent lobular pneumonia increases the difficulty of recognizing bronchopneumonia. In the table (column 6) lobar pneumonia is indicated by L., bronchopneumonia by B. Among 227 autopsies the clinical diagnosis agreed with the condition found at autopsy in 109 instances (48 per cent); in 35 instances (15.4 per cent) both lobar and bronchopneumonia were found at autopsy and a diagnosis of one or other was made during life. In 83 instances (36.6 per cent) the diagnosis made during life was incorrect. Cases admitted to the base hospital at Camp Pike were as carefully studied as the conditions in a base hospital during an epidemic permitted and diagnosis of pneumonia was doubtless as accurate as in other base hospitals. The inaccuracy of clinical diagnosis of the pneumonia of influenza is further illustrated by a consideration of lobar pneumonia. This diagnosis on the one hand was made 136 times and was correct 67 times and incorrect 69 times; on the other hand, lobar pneumonia was found at autopsy 98 times and had been diagnosed in only 67 of these cases (68.4 per cent). Classification of the Pulmonary Lesions of Influenza.— Influenzal pneumonia exhibits the following noteworthy characters: 1. Acute bronchitis with injury or destruction of lining epithelium and accumulation of inflammatory exudate within the lumen. 2. Hemorrhagic pneumonia with accumulation of blood within the alveoli and within and about the bronchi. 3. Susceptibility of bronchi and pulmonary tissue to secondary pyogenic infection with necrosis and suppuration. 4. Bronchiectasis. 5. Tendency to the occurrence of chronic pneumonia following failure of pneumonia to undergo resolution. All these changes are doubtless referable to the severity of the primary injury to the lower air passages. In the presence of destructive changes in the bronchi many bacterial species, including B. influenzÆ, pneumococci of various types, streptococci (notably hemolytic streptococci) and staphylococci may invade the lungs and produce acute inflammation. The anatomic characters of the pneumonic lesions following influenza are equally varied. In order to obtain insight into the pathogenesis of these lesions, it is desirable to imitate the historical development of knowledge concerning the characters and causes of disease, namely, first to define accurately the lesions concerned In the table of autopsies the following lesions are listed: Column 7. Purulent bronchitis.—“P” indicates that the small bronchi contain mucopurulent fluid. Column 8. Lobar pneumonia.—The occurrence of the lesion is indicated by the plus sign (+). Column 9. Peribronchiolar consolidation.—The presence of nodular patches of consolidation about respiratory bronchioles is indicated by the plus sign (+) when the lesion has been recognized at the time of autopsy. When the lesion has been first recognized by microscopic examination the letter “M” is used. Column 10. Hemorrhagic peribronchiolar consolidation.—The occurrence of this lesion which represents the preceding on a background of hemorrhage is indicated by the plus sign (+). Column 11. Lobular consolidation.—The presence of the lesion is indicated by the plus sign (+). Column 12. Peribronchial consolidation.—Peribronchial pneumonia recognized at the time of autopsy is indicated by the plus sign (+). Peribronchial pneumonia recognized microscopically is indicated by “M.” The presence of peribronchial hemorrhage without consolidation is indicated by “h.” Column 13. Abscess formation with pneumonia.—Suppuration with abscess formation almost invariably just below the pleura is indicated by the plus sign (+). Necrosis of lung tissue recognized microscopically and unaccompanied by suppuration is indicated by “N.” Column 14. Suppurative interstitial pneumonia.—This lesion invariably associated with suppurative lymphangitis is indicated by the plus sign (+). Column 15. Multiple abscess in clusters.—Abscesses in clusters about a bronchus of medium size are indicated by the plus sign (+). Column 16. Empyema.—The presence of the lesion is indicated by “E.” Column 17. Bronchiectasis.—“B” indicates the lesion. Column 18. Unresolved bronchopneumonia.—Presence of the lesion is indicated by the plus sign (+). Column 19. Organizing bronchitis and bronchiolitis.—“O” indicates the lesion. The lesions of columns 7 to 12 are acute inflammatory processes, columns 9 to 12 represent different types The last four columns of the table of autopsies give the bacteriology of the sputum during life and the bacteria found in the bronchi, in the lungs, and in the blood of the heart after death. Mortality of Pneumonia Following Influenza.—From September 6 to December 15, 250 autopsies were performed on patients who had died with pneumonia at the base hospital at Camp Pike, and with few exceptions bacteriologic cultures were made from them. Although it was not possible to perform autopsies on all who died, those which were performed afford a fair index of all deaths, for throughout the epidemic of influenza and its outbreak of pneumonia approximately one half of all who died were examined after death. The relation of autopsies to deaths is shown by a comparison by weeks of the number of deaths and number of autopsies during the months of September and October.
For most of these autopsies there is a record of the date of onset of the illness, namely, influenza, which finally resulted in pneumonia and death. Comparison of the number of cases of influenza which developed on any day with the number of fatal cases which had their onset on the same Mortality from Pneumococcus and Streptococcus Pneumonias.—By referring fatal cases of streptococcus pneumonia back to their date of origin it is possible to determine what proportion of the cases of influenza, which developed on any day, died with infection by hemolytic streptococcus. The accompanying chart (Chart 1) shows that infection with hemolytic streptococci has been very frequent at the beginning of the epidemic of influenza (shown by area with double hatch in chart) that is, from September 20 to 30 and subsequently has gradually diminished so that few cases have had their onset in the second half of the epidemic from September 30 to October 15. Pneumococcus pneumonia uncomplicated by streptococcus infection (shown by area with single hatch in chart) pursued a course which more closely conformed to the curve representing influenza. The cases of influenza which resulted fatally bore a fairly constant ratio to the total number of cases of influenza from the onset of the epidemic until October 1, but subsequently few cases of influenza developed fatal pneumococcus pneumonia. Chart 1—Showing the relation of (a) onset of cases of pneumonia shown by autopsy to be uncomplicated by secondary infection with hemolytic streptococcus, indicated by upper continuous line with single hatch, and of (b) onset of fatal cases of streptococcus pneumonia, indicated by the lower continuous line with double hatch, to (c) the occurrence of influenza, indicated by the broken line. The onset of each case of fatal pneumonia is represented by a single square. Our study of ward infection in pneumonia furnishes an explanation of the outbreak of fatal streptococcus pneumonia coincident with the initial stage of the influenza epidemic. This outbreak is a true epidemic of streptococcus infection superimposed, in many instances at least, upon preexisting pneumococcus pneumonia, but in some instances, Greater susceptibility to pneumococcus pneumonia in the early than in the late period of the epidemic is perhaps explained by differences in the severity of influenza; the more susceptible individuals were attacked by influenza in the early period, whereas the less susceptible did not acquire the disease until they had been exposed to an immensely increased number of infected individuals. A better explanation is furnished by the greater opportunity at the beginning of the epidemic for the transmission of microorganisms causing pneumonia, for at this time patients with influenza were crowded together and methods to prevent the transmission of infection were little used. BronchitisClinical study has shown that purulent bronchitis (see Fig. 2) occurs in about one-third of the cases of influenza. In a large proportion of cases of bronchitis there is no clinical evidence of pneumonia. The bronchial lesions found in association with the pneumonia of influenza are an index of the ability of the agent, which causes influenza, to injure the bronchi. In those who have died with pneumonia following influenza the large bronchi (with cartilage) are intensely injected, so that the mucosa has a deep red color which on cross section contrasts very sharply with the pearly white of the cartilage. Superficial injury to the bronchi is Purulent bronchitis was noted in 134 autopsies (55.6 per cent of autopsies). From the small bronchi, in many instances, purulent fluid welled up upon the cut surface of the lung, whereas in other instances tenacious mucopurulent fluid could be squeezed from small, cut bronchi by pressure upon lung tissue. The consistency of the material within the bronchi varied greatly, ranging from a viscid and tenacious mucus of creamy, yellow color to a thin, turbid, gray fluid. The coexistence of local inflammatory or of general edema of the lungs modifies the character of the material found in the bronchi at autopsy; with edema the purulent exudate is in some instances diluted so that a thin cloudy fluid flows from the small bronchi. In the presence of advanced edema of the lungs the bronchi rarely if ever contain purulent exudate. The underlying changes in the bronchi are more significant than the character of the exudate found at autopsy. Nevertheless, the group of cases in which the diagnosis of purulent bronchitis has been made, because small and medium sized bronchi have contained purulent or mucopurulent exudate, represents instances of readily recognizable bronchitis of considerable severity. With few exceptions, purulent bronchitis was diffusely distributed in the lungs; occasionally it was observed in one lung alone, and in several instances was limited to the bronchi at the base of a lung, usually of the left lung. In a considerable proportion of instances of purulent bronchitis abnormal distention of the lungs was noted. On removal from the chest the lungs fail to collapse and retain the size and shape of the thorax. Even after section is made through the organ, parts of the lung fail to collapse It is furthermore probable that cyanosis, which is a conspicuous feature of many instances of pneumonia following influenza, is referable, in part at least, to obstruction of the bronchi by mucopurulent exudate. The term pneumonia will refer to those inflammatory changes in the lung which are found within the alveoli; it will include inflammatory changes in the alveoli surrounding the respiratory bronchioles, in the alveolar ducts and infundibula and in their tributary alveoli. Bronchitis will be described by defining the changes which occur (a) in the small bronchi with no cartilage or mucous glands, and (b) in the large bronchi including the primary branches of the trachea. For convenience of description those bronchi may be designated small, which have no cartilaginous plates in their wall. Larger bronchi have cartilage and mucous glands, the latter situated in considerable part outside the cartilaginous plates. These bronchi, of which the largest are the right and left bronchi formed by bifurcation of the trachea, diminish with repeated branching to a caliber of about 1 mm. Small bronchi are lined by columnar ciliated epithelium; their wall consists of very vascular connective Changes in the main bronchi and their primary branches are usually less severe than those in bronchi of smaller size. The epithelium is often intact, the superficial cells being columnar and ciliated, but not infrequently desquamation of superficial cells has occurred and the lower layers alone remain. Occasionally (Autopsy 471) there is necrosis of epithelium with which, although the architecture of cells is preserved, nuclei have disappeared. Accumulation of blood or serum may separate epithelium from the underlying basement membrane (Fig. 1). Complete loss of epithelium occurs, usually in small patches. Fig. 1.—Acute bronchitis showing engorgement of blood vessels of mucosa and elevation of epithelium by serum and blood. Autopsy 352. The blood vessels of the mucosa are engorged. There is sometimes edema or hemorrhage, and in the superficial part of the mucosa polynuclear leucocytes are often fairly abundant. When superficial epithelium has been lost, polynuclears are numerous immediately below the surface of the exposed tissue. Fibrin is often present upon the denuded surface and extends for a short distance into the tissue below. In the deeper part of the mucosa, about the muscularis and especially about and between the acini of the mucous glands, the tissue is infiltrated with lymphoid and plasma cells. Changes in the mucous glands are invariably present. These changes are distention of ducts and acini with mucous, With the bronchitis of influenza the small bronchi (with no cartilage or mucous glands) show every stage of transition from early acute inflammation characterized by accumulation of polynuclear leucocytes within the lumen, engorgement of blood vessels, and infiltration of the wall with polynuclear leucocytes, through various stages of destructive changes to complete disappearance of the bronchial wall and formation of an abscess cavity at the site of the bronchus. In the early stages of acute bronchitis, hemorrhage is frequently associated with the lesion. Blood may be abundant within the lumen of the bronchus, and in the mucosa red blood corpuscles often infiltrate the tissue around greatly distended blood vessels, or accumulating below the epithelium, separate it from its basement membrane. Hemorrhage is not limited to the wall of the bronchus, but frequently occurs into the alveoli in a zone encircling the bronchus. The severity of changes in the bronchial wall is in direct relation to the extent of destruction of the lining epithelium: when the epithelium remains intact polynuclear leucocytes may be found in considerable number immediately below it, but as the lesion progresses, cells in great part mononuclear, namely, lymphoid and plasma cells, accumulate in large number throughout the wall of the bronchus. There is often abundant cellular infiltration within and about the bundles of the muscular coat. The changes assume the character of chronic inflammation. When the lining epithelium of the bronchus is lost, fibrin tends to accumulate over the surface of the defect, to which it is firmly attached. It remains separated by a conspicuous space from adjacent intact epithelium over which it may project. This superficial network of fibrin merges with a similar network, extending to a variable depth within the tissue. What may well be described as coagulative Little patches of fibrin adherent to the inner surface of the bronchus may occur in spots where epithelium has been lost; with uniform loss of epithelium the entire circumference may be lined with fibrin forming a circular zone occasionally quite uniform in thickness. Accumulations of polynuclear leucocytes doubtless bring about conditions which cause solution of fibrin or prevent its formation (when disintegration of leucocytes sets free leucoprotease in abundance). The activity of the infecting microorganisms, usually hemolytic streptococci or staphylococci, may cause complete necrosis of a part or all of the bronchial wall. The cavity which is formed may penetrate into lung tissue that has previously undergone pneumonic consolidation. Further changes caused by the bronchitis of influenza will be considered under peribronchial hemorrhage and edema, peribronchial pneumonia and bronchiogenic abscess. Purulent bronchitis is almost invariably associated with dilatation of the bronchi, the affected bronchi being distended with pus. With increasing dilatation bronchiectasis becomes evident upon gross examination of the tissue, and is much more advanced in the small bronchi than in the larger cartilaginous passages. This subject will be further considered under bronchiectasis. In association with the acute bronchitis of influenza the epithelium of bronchi not infrequently looses its superficial columnar ciliated cells and assumes some of the characters of a squamous epithelium being covered by polygonal or flat cells (Figs. 17 and 18). The condition is often described a “squamous metaplasia,” although it doubtless represents a stage of regeneration following injury rather This change may occur within six days after onset of influenza, though in most instances the duration of illness has been two weeks or more. It may affect either large or small bronchi, but it is more frequently found in the latter. Whenever ciliated columnar cells are lost, superficial cells tend to become flat. Epithelium on one side of a bronchus may have a squamous character, whereas that elsewhere is columnar and ciliated. The flat epithelium may undergo thickening so that it is 0.1 mm. or more in thickness. It is noteworthy that regenerating epithelium growing over a denuded surface has the squamous character which has been described (Plate XIV, Fig. 22). Bacteriology of the Bronchitis of Influenza.—With the pneumonia of influenza, bronchitis is invariably present. Cultures have been made from the right or left main bronchus or from the very small bronchi which contained purulent exudate. A routine method of making the culture has been adopted. The right main bronchus, exposed by drawing the right lung out of the chest and toward the midline, was widely seared with a hot knife; the bronchus was partially cut across through the seared surface with a heated knife and a platinum needle inserted into the lumen. The bacteria obtained named in the approximate order of their relative frequency have been: B. influenzÆ, pneumococci, hemolytic streptococci, staphylococci (aureus and albus), B. coli, S. viridans, M. catarrhalis, and diphthoid bacilli which have not been identified. Mixed infections occurred in most instances. The following list arranged by grouping
B. influenzÆ has been present in the bronchi in 79.3 per cent of instances of pneumonia referable to influenza. Combinations which have been found most frequently are B. influenzÆ and pneumococci (17 instances), B. influenzÆ and hemolytic streptococci (18 instances), or the same combinations with staphylococci, namely, B. influenzÆ, pneumococci and staphylococci (15 instances), and B. influenzÆ, hemolytic streptococci and staphylococci (16 instances). There is little doubt that B. influenzÆ was not identified in some instances in which it was present; when other microorganisms are very numerous its inconspicuous colonies may be overgrown even though the presence of pneumococci, streptococci Table XXVIII represents the incidence of pneumococci, hemolytic streptococci, staphylococci, and B. influenzÆ in the bronchi, lungs and blood of those individuals with pneumonia in whom bacteriologic examination has been made at autopsy. The number of cultures made from the bronchi, lungs or blood of the heart is given in the second column of the table and in other columns are given the incidence in number and percentage of the microorganisms which have been mentioned.
The figures in Table XXVIII are an index of the capacity of the microorganisms which enter the bronchi to invade the lungs and finally the blood. Pneumococci were present in the bronchi in 46.3 per cent of instances, in the lungs in only slightly less, and in approximately 40 per cent of autopsies they had penetrated into the blood. Hemolytic streptococci enter the bronchi with the same frequency and exhibit an equal ability to penetrate into the lungs and blood. Staphylococci enter the bronchi in half of these individuals, but penetrate into the lungs in only a fourth of the instances. They have entered the blood only once (Autopsy 263) in this instance in association with hemolytic streptococci. B. influenzÆ has been present in the bronchi in approximately 80 per cent of autopsies. It is noteworthy that it has been found in the lung in little more than half this percentage of instances and has entered the blood only once (Autopsy 474), in this instance in association with hemolytic streptococci. In a limited number of autopsies there was purulent bronchitis recognized by the presence of mucopurulent exudate in small bronchi. It has been stated that this group of cases is not sharply separable from other instances of bronchitis, because in some cases death has occurred before a purulent exudate has accumulated or in other instances a purulent exudate has been displaced by edema. Table XXIX shows the bacteriology of instances of purulent bronchitis:
The percentages of various bacteria with purulent bronchitis do not differ essentially from those obtained from all autopsies with pneumonia. B. influenzÆ is found in approximately 80 per cent of autopsies. In 16 instances cultures were made from the purulent fluid contained in a small bronchus and the incidence of B. influenzÆ (namely, 81.4 per cent) has not differed from that in the main bronchus. In 7 of 8 instances in which cultures were made, both from the right main bronchus and from the purulent fluid in a small bronchus, B. influenzÆ was found in one or other in all but one autopsy (87.5 per cent); in this instance (Autopsy 472) respiratory disease began thirty-seven days before death and cultures from large and small bronchi at autopsy were overgrown by B. coli. Since observations upon influenza made during life have shown that B. influenzÆ is constantly demonstrable when multiple methods are employed for its detection, the figures just cited give support to the suggestion that B. influenzÆ is constantly present in the bronchi with the bronchitis of influenza. Lobar PneumoniaThe frequency with which the confluent lobular consolidation of bronchopneumonia involving whole lobes or parts of lobes follows influenza has emphasized the desirability of distinguishing carefully between lobar and confluent lobular pneumonia. The pulmonary lesion has been designated lobar pneumonia when it exhibited the well-known characters of this lesion, namely, firm consolidation of large parts of lobes, coarse granulation of the cut surface, Lobar pneumonia occurred in 98 among 241 instances of pneumonia following influenza, namely, in 40.7 per cent of autopsies. The difficulty of separating lobar and bronchopneumonia following influenza has been increased by the frequent combination of the two lesions in the same individual. There were 34 instances in which lobar and bronchopneumonia occurred together. The anatomic diagnosis of lobar pneumonia was made only when lobes or parts of lobes were firmly consolidated and exhibited the characters of the lesion enumerated above; in several instances, in which there was some doubt concerning the nature of the lesion, microscopic examination was decisive. The associated bronchopneumonic lesions represented all the types which have been associated with influenza. In the group of 34 cases of coexisting lobar and bronchopneumonia, lobular consolidation occurred 10 times, peribronchiolar consolidation 14 times (recognized in all but 4 instances by microscopic examination), hemorrhagic peribronchiolar consolidation 9 times, peribronchial pneumonia 4 times. The intimate relation of these lesions to changes in the bronchi is well shown by the frequent presence of purulent bronchitis. The associated lesions of the bronchi in these cases were as follows: purulent bronchitis in 23 instances; peribronchial hemorrhage in 6; bronchiectasis in 11. The frequency of purulent bronchitis and other bronchial lesions in association with coexisting lobar and bronchopneumonia is in sharp contrast with the occurrence of these lesions in association with lobar pneumonia alone; with 69 instances of Lobar pneumonia following influenza passes through the usual stages of red and gray hepatization. Red hepatization was found 16 times, combined red and gray hepatization 28 times, and gray hepatization 20 times. The average duration of pneumonia with red hepatization was 3.7 days, with combined red and gray hepatization 5.1 days and with gray hepatization 7.5 days. These figures, it will be shown later, have some importance in relation to the stage at which hemolytic streptococcus infects lungs the site of lobar pneumonia. Bacteriology of Lobar Pneumonia.—Table XXX is compiled with the purpose of determining the bacteriology of the bronchi, lungs and heart’s blood in autopsies performed on individuals with lobar pneumonia. In some instances bacteriologic examination of one or other of these organs was omitted; the percentage incidence is an index of the presence of pneumococci, hemolytic streptococci, staphylococci or B. influenzÆ in the bronchi, lungs or heart’s blood and measures the invasive power of these microorganisms during the course of lobar pneumonia following influenza.
Pneumococci, the recognized cause of lobar pneumonia, were found in the lungs in 73.3 per cent of autopsies; failure to find the microorganism in all instances is doubtless the result of its disappearance from the lung, which, it is well known, occurs not infrequently particularly during Hemolytic streptococci unlike pneumococci were found more frequently in the bronchi than in the lungs; this microorganism which exhibits little tendency to disappear, once it has established itself within the body, found entrance into the bronchi in 31.8 per cent of instances of lobar pneumonia and in 24.5 per cent entered the lungs. Its invasive power is further illustrated by its penetration into the heart’s blood approximately in half this proportion of autopsies. Staphylococci enter the bronchi in many instances (50 per cent), but relatively seldom (15.1 per cent) invade the lung and rarely if ever penetrate into the blood. The high incidence, namely, 84.1 per cent, of B. influenzÆ in the bronchi is particularly noteworthy; it exceeds that of pneumococci, the well-recognized cause of lobar pneumonia, within the lung. It is found much less frequently within consolidated lung tissue and shows no tendency to invade the heart’s blood. B. influenzÆ finds the most favorable conditions for its multiplication within the bronchi. In view of the frequent occurrence of coexisting lobar and bronchopneumonia it has appeared desirable to determine how far the existence of obvious bronchopneumonia modifies the bacteriology of lobar pneumonia. In Table XXXI the incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzÆ after death with lobar pneumonia on the one hand is compared with their incidence after combined lobar and bronchopneumonia on the other. Pneumococci are found in the lung more frequently with lobar than with combined lobar and bronchopneumonia. The incidence of hemolytic streptococci and of staphylococci in the lung is on the contrary higher when bronchopneumonia is associated with lobar pneumonia. It is not improbable that these microorganisms have a part in the production of associated bronchopneumonia. The frequency with which microorganisms invade the blood is almost identical in the two groups. The relative frequency with which different types of pneumococci produce lobar pneumonia under the conditions existing when Camp Pike was attacked by an epidemic of influenza is indicated by Table XXXII in which instances of lobar pneumonia alone and of combined lobar and bronchopneumonia are listed separately. Pneumococcus I and II, which are found approximately in two-thirds of instances of lobar pneumonia occurring in cities, have an insignificant part in the production of these lesions. Pneumococcus IV and atypical Pneumococcus II, which are commonly found in the mouth, are the predominant cause of these lesions, and with Pneumococcus III, also an inhabitant of the mouths of normal individuals, have been the cause of two-thirds of all instances of lobar pneumonia observed in this camp.
There is no noteworthy difference in the occurrence of these types of pneumococci among instances of lobar pneumonia, on the one hand, and of combined lobar and bronchopneumonia, on the other. Different types exhibit no noteworthy differences in their ability to penetrate into lungs and blood. Hemolytic Streptococcus with Lobar Pneumonia.—There can be no doubt that the concurrent infection with microorganisms other than pneumococcus modifies the progress of lobar pneumonia. With lobar pneumonia alone hemolytic streptococci have entered the bronchi in 30 per cent of instances and have penetrated into the lungs in 20.6 per cent; with associated lobar and bronchopneumonia the same microorganism has entered the bronchi in 34.3 per cent of instances and invaded the lung in 31.6 per cent. Hemolytic streptococci are the only microorganisms other than pneumococci which, in association with lobar pneumonia, Separation of instances of lobar pneumonia into groups on the basis of the occurrence of red or gray hepatization shows that infection with hemolytic streptococcus is more likely to occur during the early stages of the disease. The average duration of lobar pneumonia with red hepatization has been 3.7 days, with red and gray hepatization, 5.1 days, and with gray hepatization, 7.5 days. Infection with hemolytic streptococcus has occurred in association with red or gray hepatization as shown in Table XXXIII.
Notwithstanding the longer duration of the disease and consequent prolongation of exposure to infection, lobar pneumonia, which has reached the stage of gray hepatization, has shown the smallest incidence of infection with hemolytic streptococci. In the stage of gray hepatization there is diminished susceptibility to secondary infection with this microorganism. Characteristic histologic changes have been found in the lungs of those who have died with lobar pneumonia followed by invasion of lungs and blood by hemolytic streptococci (e. g., Autopsies 273, 430), but with no evidence of suppuration found at autopsy. Within the pneumonic lung occur patches of necrosis implicating both exuded cells and alveolar walls; in some places nuclei have disappeared; elsewhere nuclear fragments are abundant. Chart 2.—Showing the relation of (a) date of onset of cases in which autopsy demonstrated lobar pneumonia, indicated by upper continuous line with single hatch, and of (b) date of death of these cases, indicated by lower continuous line with double hatch to (c) the occurrence of influenza, indicated by the broken line, and to (d) the total number of fatal cases of pneumonia, indicated by the broken dotted line. Each case of fatal pneumonia is indicated by one division of the scale as numbered on the left of the chart; cases of influenza are indicated by the numbers on the right of the chart. Relation of Lobar Pneumonia to Influenza.—Some writers have suggested that lobar pneumonia, heretofore observed during the course of epidemics of influenza, is an BronchopneumoniaFor the purpose of the present study it is convenient to group together instances of bronchopneumonia which have Bronchopneumonia unaccompanied by lobar pneumonia or by suppuration occurred in 80 autopsies. Pneumonic consolidation distributed with relation to the bronchi exhibits considerable variety, and an attempt to define a type of bronchopneumonia characteristic of influenza would be futile. Nevertheless, the bronchopneumonia of influenza has in many instances distinctive characters. Lesions of bronchopneumonia which are frequently found in the autopsies under consideration may be conveniently designated by descriptive terms, indicative of their location in the lung tissue. These lesions, of which two or more often occur in the same lung, are: 1. Peribronchiolar consolidation with which the inflammatory exudate is limited to the alveoli in the immediate neighborhood of the bronchioles. 2. Hemorrhagic peribronchiolar consolidation in which gray patches of peribronchiolar pneumonia occur upon a deep red background produced by hemorrhage into alveoli. Pfeiffer believed that this lesion was characteristic of influenza. 3. Lobular consolidation with which consolidation is limited to lobules or groups of lobules. 4. Peribronchial pneumonia with which small bronchi are encircled by pneumonic consolidation. Each one of these lesions will be discussed separately. Following is a list of the bacteria which have been isolated from the consolidated lung of individuals with bronchopneumonia
The similarity of this list to that representing the bacteriology of bronchitis is evident; there is the same multiplicity of microorganisms and the frequent occurrence of mixed infections. B. influenzÆ is much less frequently found in the lung. The relative pathogenicity of the large group of microorganisms enumerated above is better indicated by the following list which shows what microorganisms have penetrated into the blood in autopsies performed on individuals with bronchopneumonia:
Table XXXIV shows the percentage incidence of pneumococcus, hemolytic streptococcus, staphylococcus and
Table XXXIV shows that pneumococci have a less important part in the production of broncho than of lobar pneumonia; with lobar pneumonia this microorganism was found in the lungs in 77.3 per cent of instances and in the blood, in 65.5 per cent, whereas with bronchopneumonia it was found in the lungs in 42.6 per cent and in the blood in 31.4 per cent. Hemolytic streptococci (in lungs and blood) and staphylococci (in lungs), on the contrary, were more common with bronchopneumonia, and doubtless have a part in the production of the lesion. Streptococcus viridans, B. coli and M. catarrhalis, which are not infrequently found in the bronchi (p. 151), occasionally enter the lungs with bronchopneumonia but are rarely found with lobar pneumonia. B. influenzÆ has been found in less than 80 per cent of instances in the bronchi and in about half of the lungs, maintaining an incidence approximately the same as that with lobar pneumonia. Table XXXV shows the types of pneumococci found in association with bronchopneumonia and is inserted for comparison with the similar table (Table XXXII) showing types of pneumococci with lobar pneumonia. With broncho as with lobar pneumonia pneumococci commonly found in the mouth, namely, atypical II, and Types III and IV, have a more important part in production of the lesion than the so-called fixed types, I and II. Atypical Pneumococcus II has been less frequently encountered with broncho than with lobar pneumonia.
Peribronchiolar Consolidation.—In many instances of bronchopneumonia, usually in association with lobular or confluent consolidation, small firm nodules of consolidation are clustered about the bronchioles (Fig. 2). These nodular foci of consolidation are usually 1.5 to 2 mm. in diameter, being sometimes slightly smaller or slightly larger. They are usually gray and occasionally surrounded by a red halo; sometimes they are yellowish gray. They are clustered about the smallest bronchial tubes to form groups which are from 0.5 to 1 cm. across. A group of nodular foci of consolidation occupies the central part of a lobule of lung tissue. When pneumonia has been of short duration these foci are fairly soft and not sharply defined, and in many instances this form of bronchopneumonia is first recognized by microscopic examination. When the disease has lasted from ten days to two weeks, the consolidated nodules are very firm and sharply circumscribed, closely resembling tubercles. When they have assumed this character, microscopic examination shows that chronic changes indicated by new formation of interstitial tissue have occurred. The lesion may be designated peribronchiolar consolidation. It has occurred usually in association with other types of pneumonic lesion in 61 instances, being recognized at autopsy in 18 and by microscopic examination in 43. Fig. 2.—Acute bronchopneumonia with nodules of peribronchiolar consolidation and purulent bronchitis. Autopsy 429. In association with this peribronchiolar lesion the lung is often voluminous and fails to collapse on removal from the chest. Pressure upon the lung squeezes from the smallest bronchi, both in the neighborhood of the nodular consolidation and elsewhere, a droplet of viscid, semifluid mucopurulent material. The presence of this tenacious material throughout the small bronchi doubtless explains the failure of the lung tissue to collapse. Interstitial emphysema has been present in some of these lungs. A red zone of hemorrhage has occasionally been observed about the foci of peribronchiolar pneumonia. A further stage in the same process is represented by hemorrhage into all of the alveoli separating these patches of consolidation. This hemorrhagic lesion, which will be described in more detail later, has been found repeatedly in the same lung with peribronchiolar pneumonia, being present in 8 among the 61 autopsies cited. Lobular bronchopneumonia accompanied the peribronchiolar lesion 27 times and lobar pneumonia accompanied it 20 times. When an abscess caused by hemolytic streptococcus is associated with peribronchiolar pneumonia, empyema is present, but otherwise pleurisy is absent or limited to a scant fibrinous exudate. Fig. 3.—Acute bronchopneumonia with peribronchiolar consolidation; a respiratory bronchiole partially lined by columnar epithelium passes into alveolar duct and the adjacent alveoli are filled by polynuclear leucocytes. Autopsy 333. Histologic examination demonstrates very clearly the relation of this lesion to the bronchioles (Fig. 3). These passages are filled and distended with an inflammatory exudate consisting almost entirely of polynuclear leucocytes. The respiratory bronchioles are beset with alveoli often limited to one side of the tubule and these alveoli are filled with leucocytes. The alveolar ducts, distinguishable from the bronchioles by the absence of columnar or cubical epithelium and by possession of smooth muscle, are similarly filled with leucocytes; the numerous alveoli which form the walls of the alveolar ducts are distended by an inflammatory exudate. In sections which pass through an alveolar duct and one or more of its infundibula, the further extension of the lesion may be determined (Fig. 4). The infundibulum in proximity with the alveolar duct contains polynuclear leucocytes and the same cells are seen in the alveoli which here form its wall, but the intensity of the inflammatory reaction diminishes toward the periphery, so that the distal part of the infundibulum, which is much distended Fig. 4.—Acute bronchopneumonia with peribronchiolar consolidation; a respiratory bronchiole is in continuity with an alveolar duct and two distended infundibula; alveoli about bronchiole, alveolar duct and proximal part of infundibula contain polynuclear leucocytes, the distal part of the infundibula showing no evidence of inflammation. Autopsy 333. Occasionally there is irregularly distributed hemorrhage and perhaps some edema in the alveoli immediately adjacent to those which form the peribronchiolar focus of inflammation. In such instances small bronchi, that is, air passages, lined by columnar epithelium and devoid of tributary alveoli, may be surrounded by a zone of hemorrhage; immediately surrounding the bronchus, the wall of which shows intense inflammation, alveoli, in a zone of which the radius represents several alveoli, are filled with blood. This hemorrhagic zone is continued from the bronchus over the focus of inflammation which surrounds the bronchiole. The bacteria which have been cultivated from the lung in autopsies with peribronchiolar pneumonia are as follows:
The following list which shows the bacteria found in the blood is an index to the pathogenicity of pneumococci and hemolytic streptococci:
The percentage incidence of pneumococcus, hemolytic streptococcus, staphylococcus and B. influenzÆ in bronchus, lung and blood, given in Table XXXVI, is inserted to indicate with what readiness each one of these microorganisms passes from the bronchus through the lung into the circulating blood.
B. influenzÆ is present in the bronchi in a very large proportion (84.8 per cent) of those in whom this type of bronchopneumonia has been found at autopsy; it is much less frequently recovered from the lungs. Staphylococci, in part S. albus and in part S. aureus, are less frequently found in the bronchi and are recovered from the lungs in a relatively small proportion of autopsies. The percentage incidence of pneumococci and streptococci in lungs and blood demonstrates the pathogenicity of these microorganisms, for whereas pneumococci and hemolytic streptococci are found in the consolidated lungs in 43.9 and 61.0 per cent of instances of the lesion respectively, they make their way into the blood in 40.3 and 36.8 per cent of instances. Coexisting infection with pneumococci and hemolytic streptococci has been not uncommon e. g., Autopsy 275 in which both were in the blood; in 2 instances (Autopsies 333 and 378) in which pneumococci were obtained from the blood, hemolytic streptococci were found in the lungs and bronchi; in 3 instances (Autopsies 258, 273 and 445) in which hemolytic streptococci were present in the blood, pneumococci were obtained from the lungs. In the group of autopsies under consideration, examination of the sputum was made during life and after onset of pneumonia in 11 instances. The microorganisms found in the sputum and at autopsy were as follows:
In 2 instances (Autopsies 285 and 346) among this small group of cases, pneumococci but no hemolytic streptococci were found in the sputum several days before death, whereas death occurred as the result of secondary invasion with hemolytic streptococci and no pneumococci were found at autopsy. It is probable that this sequence of events is not uncommon. B. influenzÆ finds its way into the bronchi and pneumococci follow it; pneumonia limited to peribronchiolar alveoli may occur in consequence of this invasion. Later hemolytic streptococci may follow the same path and cause death with bacteremia. Hemorrhagic Peribronchiolar Consolidation.—Peribronchiolar pneumonia accompanied by diffuse accumulation of blood within the alveoli is one of the most frequent complications of influenza. The lung tissue is laxly consolidated, and on section there is a homogeneous dull deep red background upon which are seen small gray spots (1.5 to 2 mm. in diameter) grouped in clusters about the smallest bronchi (Fig. 5). Wide areas of lung tissue are implicated and the lesion is more common in the dependent parts of the lung than elsewhere. In common with other forms of bronchopneumonia the lesion is in most instances associated with changes in the bronchi; in 55 instances of hemorrhagic bronchiolar pneumonia purulent bronchitis was found in 43 instances; it is noteworthy that purulent bronchitis often is not evident in the presence of pulmonary edema and edema is not infrequent with this pneumonic lesion. Microscopic examination demonstrates the presence of acute bronchitis; the lumina of the small bronchi contain polynuclear leucocytes and red blood corpuscles. Accumulation of blood may separate the epithelium from the basement Fig. 5.—Bronchopneumonia with hemorrhagic peribronchiolar consolidation. In favorable sections it is occasionally possible to follow the bronchiole and alveolar duct, both filled with leucocytes, into an infundibulum. The proximal part of the infundibulum contains polynuclear leucocytes, whereas the distal part and its tributary alveoli are filled with serum and red blood corpuscles. When the lesion has persisted for a short time there is evidence of beginning migration of polynuclear leucocytes from the blood vessels into the alveoli which are filled with Alveolar epithelium in contact with the blood in the lumen is usually swollen and often uniformly nucleated. The inflammatory process is evidently transmitted from the bronchioles and to a less degree from the small bronchi to the adjacent alveoli. Polynuclear leucocytes fill the lumen of the bronchiole and the alveoli immediately adjacent; at the periphery of the focus of pneumonia, the alveoli may contain fibrin. In such instances small bronchi (lined by a continuous layer of columnar epithelial cells) may be surrounded by alveoli containing fibrin. In sections from one part of the lung, the alveoli between the peribronchiolar foci of pneumonia may be uniformly filled with red blood corpuscles, whereas in sections from another part pneumonic foci may be surrounded by a zone of intraalveolar hemorrhage or of hemorrhage and edema outside of which some air-containing tissue occurs. There are transitions between this halo of intraalveolar hemorrhage and edema surrounding each bronchiolar focus and complete hemorrhagic infiltration of all intervening alveoli. Large mononuclear cells are occasionally fairly numerous within the alveoli containing blood. These cells act as phagocytes ingesting red corpuscles, so that at times they are filled with corpuscles. Disintegration of red corpuscles occurs and brown pigment remains within the cell. It is not uncommon to find numerous mononuclear pigment containing cells which resemble those found with chronic passive congestion of the lungs. Lungs, the site of hemorrhagic peribronchiolar pneumonia, may undergo chronic changes which will be described elsewhere. The lesion which has been designated hemorrhagic peribronchiolar pneumonia is that which Pfeiffer regarded as Microorganisms which we have isolated from the lungs of individuals with hemorrhagic peribronchiolar pneumonia are as follows:
With this type of pneumonia B. influenzÆ has not been isolated in pure culture; B. influenzÆ alone is recorded only once (Autopsy 435), but in this instance the culture has been so obscured by contamination that the occurrence of pneumococci or streptococci cannot be excluded; S. hemolyticus has doubtless been present in this lung, for it has been found in the heart’s blood, in the bronchus, and in the peritoneal exudate of the same individual. The incidence of pneumococci and hemolytic streptococci in this list does not differ materially from that with peribronchiolar pneumonia unaccompanied by extensive intraalveolar hemorrhage, though hemolytic streptococci are somewhat more frequent with the hemorrhagic lesion. The following table shows the frequency with which pneumococci and hemolytic streptococci have penetrated into the blood:
Table XXXVII showing the percentage incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzÆ further emphasizes the similarity between the bacteriology of peribronchiolar pneumonia (Table XXXVI) and the closely related hemorrhagic lesion:
Pneumococci have been found in the lungs (31.6 per cent) and blood (25 per cent), somewhat less frequently than with peribronchiolar pneumonia (43.9 and 40.3 per cent respectively), and hemolytic streptococci have been found in the blood more frequently (52.1 per cent) than with the latter (36.8 per cent) but otherwise the bacteriology of the two lesions corresponds closely. The low incidence of B. influenzÆ in the bronchi (72 per cent) with hemorrhagic peribronchiolar pneumonia is perhaps incorrect as the result of the relatively small number of bacteriologic examinations (namely, 25), but the incidence of the same microorganism in the lung has been higher (52.6 per cent) than with nonhemorrhagic peribronchiolar lesion (43.9 per cent). In some instances infection with hemolytic streptococci has occurred after the onset of pneumonia. The following list compares the results of bacteriologic examination of the sputum made after the onset of pneumonia with that of blood, lungs or bronchus after death:
Instances of secondary infection with hemolytic streptococcus occur in the list, namely, Autopsies 346 and 376. From the foregoing studies of the bacteriology of peribronchiolar and hemorrhagic peribronchiolar pneumonia the following conclusions may be drawn: (a) B. influenzÆ is found in most instances of these lesions in the bronchi and in about half of all instances in the lungs, but does not occur unaccompanied by other microorganisms. (b) In a considerable number of autopsies pneumococcus is the only microorganism that accompanies B. influenzÆ; from the lungs it penetrates into the blood from which it is obtained in pure culture. (c) In a considerable number of instances S. hemolyticus accompanies B. influenzÆ, and in some of these instances (representing a large proportion of the relatively small number of cases examined during life), examination of the sputum has demonstrated that infection has been secondary to a pneumonia with which no hemolytic streptococci have been found in the sputum. Lobular Consolidation.—Consolidation of scattered lobules or groups of lobules has occurred in nearly all instances, namely, 71 of 80 autopsies with bronchopneumonia unaccompanied by lobar pneumonia or by suppuration. When death follows shortly after the onset of pneumonia, patches of consolidation have a dull deep red color; blood-tinged fluid escapes from the cut surface which is almost homogeneous or finely granular. The consolidated tissue seen through the pleura, which is raised above the general level, has a bluish red color. Isolated lobules or groups of lobules which have undergone consolidation may be scattered throughout the lungs, but not infrequently there is confluent consolidation of the greater part of lobes, of Lobular pneumonia, which occurred 71 times among 80 cases classified as bronchopneumonia, may be regarded as an almost constant lesion of the disease. It is found not only in association with other lesions of bronchopneumonia, but with lobar pneumonia of influenza as well. The bacteriology of this lesion shows no deviation from that of the slightly larger group of bronchopneumonia (p. 163). All types of pneumococcus have been found in association with the lesion, Pneumococcus I in 2 instances, Pneumococcus II in 1 instance; atypical Pneumococcus II and Pneumococcus IV have been found much more frequently. Pneumococci have been found in more than a third of these autopsies (42.9 per cent in the lungs, 33.3 per cent in the blood); hemolytic streptococci in less than one-third (28.5 per cent in the lungs, 30.2 per cent in the blood). Fig. 6.—Acute bronchopneumonia with confluent gray lobular consolidation in lower part of upper lobe and hemorrhagic peribronchiolar pneumonia in lower lobe; purulent bronchitis.
In one instance of streptococcus pneumonia (Autopsy 274) infection with streptococci occurred subsequent to the examination of the sputum made five days before death; pneumococcus was found in the washed sputum. With lobar pneumonia there was evidence that superimposed infection occurred more frequently during the stage of red than of gray hepatization. With the lobular consolidation of bronchopneumonia this relation has not been found. Among 27 instances of red lobular consolidation, hemolytic streptococcus has occurred 6 times, namely in 22.2 per cent; among 26 instances of red and gray consolidation, 8 times, namely, in 30.7 per cent; among 13 instances of gray consolidation, 5 times, namely, in 38.5 per cent. Infection with hemolytic streptococci is more frequent when the lesion has persisted to the stage of gray hepatization. This difference between lobar and bronchopneumonia is probably dependent in part at least upon the more severe and persistent lesions of the bronchi with bronchopneumonia. The histology of consolidation which is definitely limited to secondary lobules or groups of lobules varies considerably. When death occurs in the early stage of the lesion, When the consolidated lobules have assumed a gray or reddish gray color, polynuclear leucocytes are more abundant and often almost homogeneously pack every alveolus within the boundaries of the lobule. In some instances there is fibrin partially obscured by the presence of leucocytes in great number. Although fibrin is less abundant with bronchopneumonia than with lobar pneumonia, nevertheless in a considerable proportion of instances it is a very conspicuous element of the inflammatory exudate within the bronchioles, alveolar ducts and alveoli. It is unusual to find the alveolar ducts and alveoli uniformly plugged with fibrin containing leucocytes; there is a variegated distribution of exudate which has little resemblance to that of lobar pneumonia. Occasionally (Autopsies 242 and 247) polynuclear leucocytes fill the bronchioles, alveolar ducts and infundibula, whereas the surrounding tributary alveoli contain fibrin In association with lobular pneumonia, fibrin within the lung tissue undergoes certain changes which outline very sharply the alveolar ducts and the other structures usually ill defined in preparations of the lung. A remarkable appearance is produced by the deposit of hyalin fibrin upon the surface of the alveolar ducts and infundibula. This lesion has been described by LeCount. Within the alveolar tissue of the lung, spaces are seen lined by a layer of fibrin which stains homogeneously and very brightly with eosin. They are recognized as alveolar ducts by the presence of scattered bundles of smooth muscle in their wall. The layer of hyaline fibrin overlying the surface of the alveolar duct usually forms a continuous lining and covers over the orifices of the alveoli which surround the alveolar duct. These ducts are rendered still more conspicuous by the character of their contents which exhibits a sharp contrast with that of the surrounding alveoli. The alveoli duct occasionally contains a bubble of air, but more frequently it is filled with serum in which red blood corpuscles are sometimes numerous. There is within the lumen scant fibrin and very few cells, among which polynuclear leucocytes are predominant. In the surrounding alveoli on the contrary leucocytes and fibrin are abundant. A similar change is found in the infundibula very clearly defined by their conical form, which is especially well outlined below the pleura or in contact with interlobular septa. The infundibulum is outlined by hyaline fibrin which passes over the orifices of the tributary alveoli and separates the serous contents of the infundibulum from the cellular fibrinous contents of the alveoli about. The lesion which has been described is often associated with acute bronchitis and bronchiolitis, and the alveoli immediately about the respiratory bronchioles may be filled In association with this fibrinous pneumonia, which has been described, hyaline thrombosis of the capillaries is not uncommon. This hyalin material within the capillaries gives reactions of fibrin, and in sections stained by the Gram-Weigert method for demonstration of fibrin, these thrombosed vessels have the appearance of capillaries irregularly injected with a blue material. The interstitial tissue surrounding consolidated lobules is often edematous; the lymphatics are distended with serum and contain a moderate number of lymphocytes and polynuclear leucocytes. Among the lungs which have been studied histologically, pneumococcus has been almost invariably associated with the lobular lesions which have just been described, whether hemorrhagic, leucocytic or fibrinous; the histologic changes accompanying infection of the lung with streptococcus will be described later. Pneumococcus has been cultivated from the consolidated lung and is found in section of the lung. B. influenzÆ is found in cultures made from the bronchi. Table XXXVIII includes those instances in which the histology of the consolidated lung accords with the description given above.
Another group of cases of lobular pneumonia are important because in association with necrosis of lung tissue recognized by the microscope hemolytic streptococci have been found in the lungs. In such instances serum is abundant and polynuclear leucocytes are relatively scant though their distribution varies considerably; in some places leucocytes are fairly abundant though elsewhere almost absent, but this distribution bears no obvious relation to the bronchioles. In some instances (Autopsies 274 and 487) red blood corpuscles are numerous but in others (Autopsies 275 and 312) they are inconspicuous. The characteristic feature of the lesion is the occurrence of patches of necrosis within which the nuclei both of exudate and of alveolar walls have partially or completely disappeared. In these areas of necrosis short chains of streptococci are found in immense number whereas in living tissue they are present in moderate number. There has been a relatively inactive inflammatory reaction, great proliferation of streptococci and necrosis of invaded tissue. The bacteriology of instances of lobular pneumonia with necrosis is shown in Table XXXIX.
The hemorrhagic and edematous consolidation of the early pulmonary lesions of influenzal pneumonia is their most distinctive feature. Red confluent lobular pneumonia is frequently found in those who have died within the first week following the onset of influenza. The lungs are voluminous and heavy and may weigh as much as 1,500 grams; the pleura which overlies the consolidated area is blue or plum colored and usually shows scant if any evidence of pleurisy. Scattered patches of consolidation are accurately limited to lobules, but in addition there are large areas often involving the greater part of the lobes and not infrequently situated in the lowermost part of the lower lobes. This confluent consolidation may be obviously limited by lobule boundaries. The consolidated tissue is deep red and laxly consolidated; red serous fluid escapes from the cut surface. The lesion not infrequently occurs in association with hemorrhagic peribronchiolar pneumonia. The histology of this confluent lesion has been studied in Autopsies 242, 244, 303, 336, 464, 474 and 506. The histology varies, because, in some instances, leucocytes, in other instances, fibrin, is abundant, but the presence of red blood corpuscles in large number within the alveoli gives a red color to the consolidated tissue. In these cases pneumococci, In the group of autopsies in Table XL there was red confluent lobular pneumonia. These autopsies are separated from those just cited because there was no histologic examination of the tissue.
This group of autopsies confirms the view that the red confluent lobular pneumonia is caused by pneumococci in association with B. influenzÆ. Hemolytic streptococci may invade secondarily. In Autopsy 297 a few hemolytic streptococci were found in the bronchus but apparently had not entered the lungs. In the absence of histologic examination it is not possible to determine if the invasion of hemolytic streptococcus (in Autopsy 364) has caused necrosis of the pneumonic tissue. Fig. 7.—Bronchopneumonia with purulent bronchitis and peribronchial hemorrhage. Peribronchial Hemorrhage and PneumoniaIn a considerable number of instances, namely, in 19 autopsies, hemorrhage about the small bronchi has been recognizable upon gross examination of the lung. A conspicuous zone of hemorrhage 2 or 3 mm. in thickness surrounds small (with no cartilage) often dilated bronchi and on longitudinal section may be tracted for a considerable distance along the bronchus (Fig. 7). In many additional instances peribronchial hemorrhage has been found by microscopic examination. In some instances the peribronchial zone of hemorrhage is firmer than the tissue elsewhere and it is occasionally difficult to determine whether the lesion is hemorrhage or pneumonia. In 7 instances frank red consolidation of peribronchial tissue was recognized at autopsy; this lesion will be considered later under peribronchial pneumonia. Hemorrhage about bronchi, like other evidences of severe injury to bronchi following influenza, is more frequently found in the lowermost parts of the lungs than elsewhere. It is invariably associated with severe bronchitis; the bronchi have contained purulent Microscopic examination furnishes further evidence of the severity of the bronchial changes which have brought about hemorrhage into the surrounding alveoli. The lumen of the bronchus contains blood and leucocytes; the epithelium is sometimes raised in places from the underlying basement membrane by blood; blood vessels of the bronchial wall are engorged, and there is hemorrhage into the tissue of the bronchus. More frequently the bronchial epithelium is completely lost and the denuded surface is often covered by a layer of fibrin intimately adherent to the inflamed mucosa. Transitions between simple hemorrhage and pneumonia are found, polynuclear leucocytes being mingled with red blood corpuscles. In several instances the alveoli in immediate contact with the bronchial wall have contained fibrin, whereas those in the surrounding zone have contained blood. Bacteria found in the bronchi in 10 instances of peribronchial hemorrhage have been as follows:
The high incidence of B. influenzÆ and the frequent association of B. influenzÆ and hemolytic streptococci are noteworthy. The instance in which no organisms were found is probably due to a defect in media and should perhaps be excluded from the list. The percentage incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzÆ in the bronchus, lungs and blood of the heart is an index of the facility with which these microorganisms penetrate internal organs when the bronchi are the site of this hemorrhagic lesion.
When these figures are compared with those for all forms of bronchitis no very noteworthy differences are found; the incidence of pneumococci here is less and that of hemolytic streptococci greater. In association with the severe changes present in the bronchi, hemolytic streptococci which enter the lungs almost invariably find their way into the blood. In 6 instances there has been frank pneumonic consolidation limited to a zone encircling small and medium-sized bronchi which have often been obviously dilated. On cross section these patches of pneumonia are circular, from 1 to 2 cm. in diameter and each contains a bronchus at its center. When the bronchus is cut longitudinally it is evident that pneumonic consolidation forms a cylindrical sheath about the tube. The consolidation varies in color from red to grayish red. In one instance (Autopsy 253) the consolidated tissue has formed a gray zone in contact with the bronchus and is red in a peripheral zone; microscopic examination shows that the alveoli about the bronchus contain fibrin, whereas those at a greater distance contain red blood corpuscles. In this instance, the associated pneumonia in another part of the lung has been somewhat anomalous and has had characters both of lobar and bronchopneumonia, for scattered in the left lung there have been patches of firm consolidation not more than 2 cm. across. The smaller of these patches are deep red, but the larger are coarsely granular and gray in the center. The patchy The peribronchial pneumonia which has been described occurs in association with evidence of profound injury to the bronchial wall. In 5 of 6 instances purulent bronchitis has been found at autopsy; in half of these instances bronchiectasis has been noted. The epithelium of the bronchus has been found separated from the underlying tissue by serous exudate, blood and leucocytes; epithelial cells undergo necrosis and disappear, the denuded surface being covered by fibrin. Necrosis extends a varying depth into the wall of the bronchus; blood vessels are engorged, and there is in some instances hemorrhage throughout the wall of the bronchus. The character of the exudate in the alveoli surrounding the bronchus differs considerably in different instances. In some instances (Autopsies 374 and 392) red blood corpuscles Peribronchial pneumonia is the result of the direct extension of the inflammatory process through the wall of the bronchus; it occurs when the epithelium of the bronchus is destroyed and the underlying tissues are injured, but may be present in a wide encircling zone even when the lesion has not penetrated the bronchial wall. The distribution of the pneumonia demonstrates very clearly that the inflammatory process does not reach the affected peribronchial alveoli by way of the bronchioles tributary to the bronchus. The bacteriology of these instances of peribronchial pneumonia is noteworthy. (Table XLII.)
Pneumococcus has been found in every instance either in the lungs or blood. Pneumococcus II, which has been uncommon with the pneumonia following influenza at Camp Pike and has occurred only ten times in more than 200 autopsies, has been present in one-half of these cases. The constant association of the lesion with pneumococcus is particularly significant when a comparison is made between the incidence of pneumococcus with peribronchial hemorrhage, on the one hand, and peribronchial pneumonia on the other; pneumococcus has been present in less than a third In addition to the instances in which gross peribronchial consolidation has been noted at autopsy, microscopic examination has demonstrated the presence of fibrinous pneumonia surrounding bronchi in a considerable number of autopsies. In a zone encircling small bronchi (with no cartilage) alveoli are filled by plugs of dense fibrin (Fig. 20) containing in variable number polynuclear leucocytes and mononuclear cells. The width of the zone is often equal or greater than the diameter of the bronchus. Alveoli outside the zone of fibrinous inflammation may contain red blood corpuscles or serum, and desquamated epithelial cells are often abundant. Of 21 instances of peribronchial fibrinous pneumonia 20 were associated with purulent bronchitis. Further evidence of the relation of the lesion to profound injury to the bronchi is its association with bronchiectasis in 17 instances. Peribronchial fibrinous pneumonia, like other lesions encircling the small bronchi, bears a direct relation to the severity of microscopic changes in the bronchus. The epithelium of the bronchus is either partially or completely lost. Occasionally epithelium is raised by hemorrhage or leucocytes from the underlying tissue but more frequently it is wholly lost and the surface is covered by a layer of fibrin. In the early stages of the lesion, polynuclear leucocytes may be numerous throughout the bronchial wall, indicating that the inflammatory irritant within the lumen is affecting the entire wall and extending its influence to the surrounding pulmonary tissue. Later lymphoid and plasma cells are more abundant than polynuclear leucocytes. Coagulative necrosis and disintegration of the bronchial wall, proceeding from the inner surface outward, may extend more or less deeply, and fibrinous inflammation of adjacent alveoli is often more extensive about that segment With this peribronchial pneumonia the smallest bronchi are distended with pus and their walls are infiltrated with polynuclear leucocytes, lymphoid and plasma cells. In a broad zone encircling the bronchus the alveoli are filled with plugs of fibrin. Bronchioles are similarly distended with polynuclear leucocytes; the alveoli which occur upon the wall of the bronchiole are often limited to one side of the wall and are filled with fibrin. This fibrin occasionally projects into the lumen of the bronchiole and forms a continuous layer in contact with the wall on the same side. The alveolar duct and infundibulum are distended with polynuclear leucocytes. The alveoli upon the wall of the alveolar duct and upon the proximal part of the infundibulum are filled with fibrin. The bronchus, bronchiole, alveolar duct and part of the infundibulum are thus surrounded by a continuous zone of alveoli containing fibrin. The alveoli about the distal part of the infundibulum may be filled with polynuclear leucocytes. Lung tissue between adjacent zones of fibrinous pneumonia may contain serum and desquamated epithelial cells. This group of instances of peribronchial fibrinous pneumonia has offered an opportunity to study the bacteriology of pneumonia with organization and to determine if it presents any unusual characters. The bacteriology of autopsies with peribronchial fibrinous pneumonia with no organization is shown in Table XLIII:
B. influenzÆ has been present in the bronchi in every instance save one in which cultures have been made, and it is probable that in this exceptional instance cultures have remained sterile because the media employed have been defective. The incidence of B. influenzÆ in the lung has been unusually high both with and without organization (66.7 per cent with no organization; 77.8 per cent with organization). Streptococci and staphylococci have been found in a considerable proportion of all instances of peribronchial fibrinous pneumonia, but there has been no notable preponderance of these microorganisms when organization has occurred. Organization has been present in instances in which pneumonia is referable to pneumococcus associated with B. influenzÆ and unaccompanied by either streptococci or staphylococci (Autopsies 419 and 422). Wadsworth Injury to bronchi produced in part at least by B. influenzÆ exposes the bronchi and lung tissue to repeated infection with a variety of microorganisms; absorption of Suppurative Pneumonia With Necrosis and Abscess FormationThree varieties of suppurative pneumonia have occurred in association with influenza. A. Necrosis and suppuration with formation of one or several abscesses usually below the pleura and almost invariably caused by hemolytic streptococci. B. Interstitial suppurative pneumonia caused by hemolytic streptococcus. C. Multiple abscesses in clusters caused by staphylococci. Suppurative pneumonia with necrosis and abscess formation will be discussed in this section. Pulmonary abscesses which occurred in 43 autopsies may be included in this group; in 4 of these autopsies abscess and interstitial suppurative pneumonia occurred in the same individual. These abscesses were much more frequently situated in the lower than in the upper lobes and more often in the right than in the left lung. In most instances there was one or several abscesses situated below the pleura of one lobe; occasionally abscesses occurred in two lobes of the same lung or in both lungs. The distribution was as follows: Abscess in only one lung occurred in right upper lobe in 6 autopsies; middle lobe, 3; lower lobe, 15; left upper lobe, 2; lower lobe, 16. Abscesses occurred in both right and left lower lobes, twice. The usual situation was at the lower and posterior part of the lower lobe at or near the basal edge, less frequently below the posterior border or upon the basal surface of the lobe. These abscesses in almost every instance were found immediately below the pleural surface, so that they appeared upon the pleura as opaque yellow spots usually surrounded by narrow zones of hemorrhage. In one instance (Autopsy 376) the In most instances of suppurative pneumonia there have been associated lesions of bronchopneumonia which have been peribronchiolar, hemorrhagic or lobular and have exhibited no unusual characters. The abscess or abscesses are situated within an area of pneumonic consolidation which is not limited by lobule boundaries and has not the characters of bronchopneumonic consolidation. In some instances this consolidation is limited to a zone immediately about the abscess, but often it involves the greater part of a lobe. The tissue is laxly consolidated and flabby; on section it has a dull, conspicuously cloudy appearance and is grayish red, pinkish gray or gray; it is homogeneous or very finely granular. Turbid gray fluid, which sometimes resembles thin pus, oozes from the cut surface. Widespread necrosis of tissue is not infrequently a conspicuous feature of this pyogenic pneumonia (Fig. 8). Upon a cloudy gray background of consolidation are numerous opaque yellowish gray or yellow patches, occasionally 2 or 3 cm. across, giving a mottled character to the cut surface. Upon the pleura these necrotic patches appear as dull opaque yellow spots. They may be surrounded by a zone of hemorrhage. The opaque material is at first firm but may undergo softening, becoming semisolid and finally purulent. Necrotic patches may be scattered throughout a lobe, but fully formed abscesses are with few exceptions immediately below the pleura (Fig. 9). Fig. 8.—Streptococcus pneumonia with massive necrosis. Autopsy 354. Fig. 9.—Abscess below pleura with perforation caused by hemolytic streptococci. Healing suppurative interstitial pneumonia indicated by yellowish gray lines marking interlobular septa at base of lower lobe. Autopsy 474; right lung. (See left lung, Fig. 10.) Table XLV shows the incidence of pneumococcus, S. hemolyticus, staphylococcus and B. influenzÆ in instances of suppurative pneumonia with abscess formation, 4 instances of abscess with interstitial suppurative pneumonia being excluded:
In over 80 per cent of instances of pulmonary abscess hemolytic streptococcus has been found in blood, lungs and bronchus and, when cultures have been made, in the inflamed pleural cavity as well. Streptococci have been found in immense number in sections from the necrotic lung tissue and the abscesses which have been formed. It is evident that hemolytic streptococci have caused suppurative pneumonia and death, being found in the blood of the heart just as frequently as in the lungs (83 per cent). The relative unimportance of pneumococci is indicated by their low incidence in the blood (16.2 per cent) when compared with that of lobar pneumonia (65.5 per cent) or of bronchopneumonia (31.4 per cent). B. influenzÆ has been found in three-fourths of these autopsies in the bronchus, but its incidence in the lungs has been much smaller. In 3 instances of suppurative pneumonia with abscess formation no hemolytic streptococci were found; they are as follows: Autopsy 406.—Acute lobar pneumonia with red hepatization of greater part of right lung; patch of consolidation in lower lobe of left lung containing an abscess cavity 2.5 x 1.5 cm.; localized seropurulent pleurisy (375 c.c.) on left side. Pneumococcus IV was obtained from the blood of the heart; a culture from the lung was contaminated. Tissue from the abscess was not saved for histologic examination. Autopsy 416.—Suppurative pneumonia with necrosis and abscess formation in right lower lobe; fibrinous pleurisy on right side. Pneumococcus IV was obtained from the blood, right lung and right main bronchus. No streptococci were found in sections from the abscess in the right lung. The foregoing observations demonstrate that suppurative pneumonia with abscess formation following influenza is with few exceptions caused by S. hemolyticus. The autopsies (Table XLVI) in which pneumococci have been found in association with hemolytic streptococci in the blood or lungs indicate that pneumococci have had a part in the production of fatal pneumonia.
These autopsies, notably those in which pneumococci have been found in the blood, suggest that infection with
In 2 of these 3 cases infection with hemolytic streptococcus occurred subsequent to the onset of pneumonia. Several observations help to explain the occurrence of abscess in association with the pneumonia of influenza. The fissures which will be described in association with bronchiectasis represent traumatic ruptures of the bronchial wall consequent upon weakening by necrosis and over distention. They expose the injured bronchial wall and the alveolar tissue adjacent to it to infection by the microorganisms contained within the lumen of the inflamed bronchus. Occasionally a favorable microscopic section demonstrates the relation of pulmonary necrosis and consequent suppuration to injuries of the bronchial wall. Peribronchial fibrinous pneumonia occurs about the bronchi of which the epithelial lining has been destroyed, and when a fissure penetrates the bronchial wall fibrinous pneumonia is almost invariably found in a zone about the tear; it doubtless tends to limit the extension of the process. Occasionally, wide areas of necrosis occur within consolidated tissue near the site of the fissure (Autopsy 312 with S. hemolyticus and B. influenzÆ, p. 254). Accumulation of polynuclear leucocytes between living and dead tissue may form a line of demarcation (Autopsy 387); finally, fairly large, irregularly formed, abscess cavities are found. Necrosis and beginning suppuration in contact with the lumen of the bronchus will be described in association with bronchiectasis (Autopsies 312, Fig. 24, and 423, p. 256). In Autopsy 376.—H. M., white, aged twenty-four, a fireman, resident of Oklahoma, had been in military service one month. Onset of illness occurred October 1, ten days before his death; he was admitted to the base hospital on the fourth day of his illness with the diagnosis of bronchopneumonia. Anatomic Diagnosis.—Acute bronchopneumonia with patches of lobular and confluent lobular consolidation in both lungs and hemorrhagic peribronchiolar consolidation in right upper lobe; abscess in right upper lobe below pleura; fibrinopurulent pleurisy on right side; purulent bronchitis; bronchiectasis at base of left lobe. An irregular abscess, 2 x 1 cm., filled with creamy purulent fluid is separated from the interlobular surface of the right upper lobe by a thin membrane representing the pleura. The right pleural cavity contains 200 c.c. of turbid yellow fluid in which is soft fibrin. The bronchi contain purulent fluid in great abundance. The bronchi at the base of the left lower lobe are widely dilated, so that many small bronchi with no cartilage in their wall measure from 3 to 5 mm. in diameter. Cultures show the presence of hemolytic streptococci in the blood of the heart and in three plates from the lung; B. influenzÆ and S. aureus were found in the left bronchus. The bronchi have wholly or partially lost their epithelium and there is deep erosion of the walls. Cavities containing polynuclear leucocytes occur within the alveolar tissue; in some instances pus containing cavities are surrounded by alveolar tissue, but in other places it is evident, that they have had their origin in bronchi. In a short segment of the circumference the wall of the preexisting bronchus is preserved and consists of squamous epithelium, vascular connective tissue and smooth muscle. The remainder of the bronchus has disappeared and a cavity is produced. The very irregular wall of the cavity is formed by partially destroyed alveoli filled with fibrin and leucocytes. Autopsy 387.—C. M., white, aged twenty-one, laborer, resident of Mississippi, had been in military service twenty-one days. Illness began on September 22, nineteen days before death, and the patient was admitted to the hospital on the same day with a diagnosis of bronchitis; a diagnosis of bronchopneumonia was made on October 2, nine days before death. The leucocytes on October 3 numbered 8000 (small mononuclear, 36 per cent; large mononuclear, 5 per cent; polynuclear, 59 per cent). There is advanced bronchiectasis, and bronchi with no visible cartilage are dilated to from 4 to 8 mm. in diameter; they contain purulent fluid which wells up from the cut surface. About dilated bronchi there is in places dull red or grayish red consolidation forming an encircling zone. Situated below the pleural surface within an area of consolidation at the posterior border of the left lower lobe there is a spot 3 cm. across where the tissue is yellow and has in places undergone purulent softening. Several smaller abscesses occur nearby. Cultures from the blood of the heart and from the edematous mediastinum contain hemolytic streptococci. From the abscess are grown S. albus, Pneumococcus II and B. influenzÆ. The purulent contents of a small bronchus contains S. hemolyticus, B. influenzÆ, S. aureus and a few pneumococci. Microscopic examination shows that the epithelium of dilated bronchi has disappeared and the denuded surface is covered by fibrin and polynuclear leucocytes; fissures extend from the lumen through the bronchial wall into the surrounding alveolar tissue. A zone of fibrinous pneumonia surrounds these bronchi and fissures in the bronchial wall penetrate into this zone. One dilated bronchus 2.4 mm. in diameter with no cartilage in its wall has vascular connective tissue covered by epithelium on one side, whereas the remainder of the circumference is formed by exposed alveoli filled with fibrin, the bronchial wall having disappeared. A section through a part of the abscess which has been mentioned shows a very irregularly formed cavity approximately 1 x 0.7 cm. Remains of bronchial wall, consisting of very vascular tissue covered by flat epithelium in several layers, indicate the origin of the cavity. Between these remnants of bronchi deep pockets extend into the pulmonary tissue which in the margin of the cavity is the site of fibrinous pneumonia. In one place, in contact with the cavity, a wide area of consolidated tissue has undergone necrosis and both alveolar walls and their contents have lost their nuclei. Leucocytes which are accumulating at the margin of the necrotic patch form a line of demarcation between living and dead tissue. Abscess may be the result of the profound changes which occur in the bronchi as the result of influenza. Necrosis caused by bacteria within the bronchi weakens and in places destroys the wall. Bacteria penetrate into the surrounding tissue and hemolytic streptococci (or staphylococci) may produce localized abscesses. These abscesses are usually situated near the pleural surface of the lung, because destructive changes causing rupture of the bronchial Healing of Abscess.—The following autopsy is of interest in relation to the treatment of pulmonary abscess and associated empyema. Autopsy 467.—P. C., white, aged twenty-five, a farmer from Missouri, had been in military service three months. Illness began September 27, thirty days before death, and the patient was admitted the day following onset with headache, backache and cough. Pneumonia with consolidation in the right lower lobe was recognized on the sixth day of illness. On the ninth day 500 c.c. of fluid were withdrawn from the right pleural cavity; there were cyanosis and dyspnea. On the eleventh day 700 c.c. of fluid were withdrawn. On the twelfth day thoracotomy was performed and 100 c.c. of greenish fluid were removed. The patient’s condition improved for a time, but on the twenty-sixth day 1,000 c.c. of straw colored fluid were aspirated from the left pleural cavity and on the twenty-eighth day the same amount of seropurulent fluid was withdrawn. Anatomic Diagnosis.—Healing abscess of right lower lobe communicating with the pleural cavity; acute purulent pleurisy with closed thoracotomy wound on the right side; purulent pleurisy on the left side; acute bronchopneumonia with lobular consolidation in the left lung; purulent bronchitis; bronchiectasis with formation of spherical bronchiectatic cavities; acute splenic tumor. At the base of the right chest is a closed thoracotomy wound 2 cm. in length; the right pleural cavity contains 200 c.c. of thick creamy pus and the cavity is lined by a thick tough membrane. The left pleural cavity contains 800 c.c. of white purulent fluid thinner than that on the right side. The right lung is compressed into the posterior and inner part of the chest. The upper lobe is pink and air containing; the posterior and lower part of the lower lobe is red and atelectatic, and fibrous septa are more conspicuous than elsewhere. The pleura of the external surface near the basal edge, in an area 2 cm. across, is depressed and yellowish gray in color. In the center of this area is a small opening communicating with a pocket 0.5 cm. across within the substance of the lung. In the lower lobe beneath the interlobular surface are two spherical bronchiectatic cavities, each about 1.5 cm. across, with smooth lining in continuity with two branches of the same bronchus of medium size. Bacteriologic examination showed the presence of S. hemolyticus in the blood of the heart. No growth was obtained from the left lung; the left pleural cavity contained hemolytic streptococci and S. aureus, the latter in A microscopic section through the abscess and its communication with the pleura shows that its cavity contains polynuclear leucocytes and the wall is formed by granulation tissue covered by fibrin. Some alveoli outside the abscess contain compact balls of fibrin containing a few fibroblasts; this fibrin stains deeply with hematoxylin as if it contained calcium. The surface of the lung is covered by fibrin in process of organization. In the foregoing instance a pulmonary abscess on the right side has ruptured into the pleura and, completely separated from the adjacent lung by a wall of newly formed tissue, is in process of healing. It shows that these pulmonary abscesses below the pleura may heal provided drainage is established by rupture into the pleural cavity and subsequent evacuation of pleural exudate. It is noteworthy that in this instance empyema extended from the right to the left pleural cavity, both S. hemolyticus and S. aureus were found at autopsy. The thoracotomy wound on the right side was closed at autopsy. Interstitial Suppurative PneumoniaA second type of suppurative pneumonia is characterized by acute inflammation of interstitial tissue between the secondary lobules of the lung and by acute lymphangitis; suppuration involves the interstitial septa and the walls of the lymphatics. The lesion is designated by Kaufmann, Acute inflammation and edema of the interlobular septa of the lung with no suppuration is often found with both lobar and bronchopneumonia and is occasionally so far advanced With interstitial suppurative pneumonia, interlobular connective tissue is marked by conspicuous yellow lines, 1 to 3 or even 5 mm. in thickness, forming a network with polygonal meshes which represent secondary lobules (Figs. 10 and 11). The distended septa not infrequently have bead-like enlargements at intervals and from the cut surface it is often possible to scrape away creamy yellow pus. These lines of suppuration invariably extend up to the pleura and are often broadest immediately below it. Adjacent septa which have not undergone suppuration are much thickened and have the yellowish gray appearance produced by edema. Fig. 10.—Interstitial suppurative pneumonia; interstitial septa are the site of suppuration and lymphatics are distended with purulent fluid; empyema. Autopsy 474, left lung. (See right lung) Fig. 9. Fig 11.—Suppurative interstitial pneumonia; the left lower lobe is the site of almost uniform consolidation and here interstitial septa and their lymphatics are distended with pus. There is more extensive interstitial suppuration in the upper lobe where consolidation is absent. The cloudy appearance of the consolidated lung is well shown. Autopsy 452. In approximately half of the cases consolidation, associated with interstitial suppuration, has been lobar in distribution (Fig. 11). The tissue is laxly consolidated, finely granular, and has a cloudy red or gray appearance. The coarsely granular surface of lobar pneumonia is absent. The affected lung may weigh 1,500 or 1,650 grams. Occasionally, interstitial septa of air containing lung tissue is the site of suppurative inflammation or edema. In Autopsy 452 the lower lobe, save a small part at the base, is laxly consolidated; interstitial septa in the consolidated area are yellow, 1.5 to 2 mm. in thickness, beaded and exude purulent fluid on pressure. In the adjacent part of the upper lobe there is a patch of consolidation, and a network of yellow thickened septa extends from it far into the surrounding air containing tissue. The weight of the right lung is 635 grams; of the left, 1,650 grams. The distribution of interstitial suppuration in 21 instances, including 4 in which the lesion has occurred in the same lungs with abscess formation, has been as follows: right upper lobe, 9 instances; middle lobe, 4; lower lobe, 5; left upper lobe, 7; left lower lobe, 6. In 6 of these autopsies more than one lobe of the same lung has been affected by the lesion; in 2 autopsies parts of both lungs have been affected. Localized abscess of the lung is more common in The duration of illness with interstitial suppurative pneumonia has varied from six days to five weeks. In over half of the cases death has occurred during the second week of illness. The bacteriology of these cases is shown in Table XLVIII.
S. hemolyticus has been almost invariably present in lungs, heart’s blood and bronchi. In 16 of 21 autopsies hemolytic streptococci have been obtained from the blood in pure cultures, in one instance associated with pneumococcus. With associated empyema, pericarditis or peritonitis, the same microorganism has been found in the pleural cavities, pericardium or peritoneum. Furthermore, microscopic examination has demonstrated the presence of chains of streptococci in the affected interlobular tissue and in much greater abundance in the distended lymphatics. Nevertheless in 2 instances no streptococci have been found. These cases are as follows: Autopsy 330.—Illness began with symptoms of influenza ten days before death; signs of pneumonia were recognized three days before death. There is firm, gray red consolidation of the entire left upper lobe; the interlobular septa are here indicated by yellow lines of obvious suppuration and thick puslike fluid exudes from the cut surface of the consolidated tissue. The upper half of the left lower lobe has undergone gray hepatization, but here there is no distention of the interlobular septa. There is fibrinopurulent pleurisy on the left side with accumulation of 400 c.c. of fluid. Pneumococcus IV is Autopsy 379.—Illness began seven days before death with influenza; signs of pneumonia were first recognized the day before death. The middle lobe of the right lung is firmly consolidated; on section there is mottling of deep red and pinkish red and the cut surface is coarsely granular. The interstitial septa are distended by fluid and are grayish yellow. There is fibrinopurulent pleurisy on the right side with accumulation of 600 c.c. of fluid. Pneumococcus atypical II is obtained from the blood of the heart. A large bacillus unstained by Gram’s method is obtained from the right lung and from the right main bronchus. In the bronchus are a few influenza bacilli. In the suppurating and necrotic tissue of the interstitial septa are found diplococci and chains of 4 to 6 cocci in great number; a few large Gram-negative bacilli are found. In both these autopsies consolidation had the characters of lobar pneumonia, and pneumococci were obtained from the blood of the heart. It is possible that streptococci failed to grow or while present elsewhere were absent at the spot where cultures were made. It is noteworthy that B. influenzÆ was found in the bronchi in every instance (10) in which cultures were made, but was obtained much less frequently from the lung. In one instance (Autopsy 474) this microorganism was found in the blood in association with hemolytic streptococci. There was suppurative interstitial pneumonia in the left lung and abscess in the right lower lobe with rupture into the cavity and empyema. Hemolytic streptococci and B. influenzÆ were found in the bronchus, right pleural cavity and blood of the heart. In 4 instances (Autopsies 251, 259, 295 and 474) interstitial suppurative pneumonia has been associated with abscess formation. In one instance (Autopsy 251) the right middle lobe has been the site of interstitial suppuration and abscess formation; in another (Autopsy 295) the left lower lobe has been the site of both lesions, but in the other 2 instances suppurative interstitial pneumonia and abscess formation have occurred in opposite lungs. In all Empyema has been present in all but 3 of 21 instances of interstitial suppurative pneumonia. Fig. 12.—Suppurative interstitial pneumonia, showing an immensely dilated lymphatic containing purulent exudate, a short distance below the pleura. Autopsy 474. Histologic examination of lungs with interstitial suppuration shows that the interlobular septa are distended by serum and contain a conspicuous network of fibrin. Polynuclear leucocytes are present in varying number, and at times densely infiltrate the distended tissue; it is not uncommon to find a zone of densely crowded polynuclear leucocytes along each edge of the septum, whereas the central part contains comparatively few. Occasionally, there is hemorrhage into the distended connective tissue. Fig. 13.—Suppurative interstitial pneumonia showing a dilated lymphatic. Autopsy 428. Necrosis of the cells which fill the lymphatics occurs in spots, usually in the center of the thrombus, and occasionally affects the entire contents of the lymphatic; polynuclear leucocytes have lost their nuclei or in some the nucleus has undergone fragmentation. In these spots the network of fibrin has disappeared. Not infrequently the wall of the lymphatic in a small sector or throughout the circumference Accumulation of polynuclear leucocytes, necrosis of these cells, solution of fibrin at first in the centers of the lymphatic thrombus and later throughout, occasionally with necrosis of the wall of the vessel, result in the formation of an abscess at the site of the distended lymphatic. These lymphatics, dilated by purulent fluid, may have a diameter from 2 to 3 mm. and may cause considerable compression and collapse of immediately adjacent alveoli. Lymphangitis, distention of lymphatics, thrombosis and finally suppuration may occur in the lymphatic vessels encircling the blood vessels and in those situated in the adventitia of the bronchi of medium size. The alveoli adjacent to the distended septa are filled by inflammatory products; edema is almost invariably present and the alveoli may contain serum and desquamated epithelial cells; fibrin is often present, but more frequently polynuclear leucocytes are predominant. Not infrequently, abscess formation, recognized microscopically, has occurred in contact with septa most often immediately below the pleura. Polynuclear leucocytes are present in immense number and alveolar septa have disappeared; occasionally, with abscess formation there is more or less widespread necrosis of tissue, cells both of the exudate and of the alveolar walls having lost their nuclei. Lymphatics in many places are distended and plugged by fibrinous thrombi, whereas elsewhere softening of the thrombus has been brought about by suppuration. Suppuration, both within the lymphatic and in adjacent alveoli, appears to be secondary to lymphatic obstruction. In some instances the lymphatic appears to have undergone distention after the thrombus has formed, for between the Fig. 14.—Endophlebitis occurring in association with suppurative pneumonia; the intima contains lymphoid cells in great number; at one spot there is a small thrombus adherent to the intima. Autopsy 325. Acute endophlebitis has been repeatedly observed in association with interstitial suppurative pneumonia (Fig. 14). The lesion usually occurs in veins situated within the septa which are the site of intensely acute inflammation associated with necrosis. The wall of the vein appears to be so injured by the surrounding changes that polynuclear leucocytes and small mononuclear cells accumulate below the endothelium. Throughout the circumference of the veins, often 0.5 to 1 mm. in diameter, the endothelium is separated from the underlying media by polynuclear leucocytes which form a conspicuous zone encircling the lumen. Some cells of lymphoid type are usually present among the polynuclear leucocytes. Polynuclear leucocytes In other instances the accumulation of cells below the endothelium is almost wholly mononuclear. Cells of the type of lymphocytes occur, but more abundant are slightly larger cells with more abundant cytoplasm. These cells may form a thick zone below the intima throughout the entire circumference of the lesion. It seems probable that these cells, like the polynuclear leucocytes, are derived from circulating blood within the lumen of the vessel, for small cells of the type of lymphocytes are not infrequently found adherent to the lumen and occasionally one is fixed in process of passing through the endothelium. This endophlebitis appears to be the result of changes outside the vessel; there is usually necrosis of the adjacent tissue and the production of the lesion is favored by lymph stasis; as the result of injury to the vessel wall, polynuclear leucocytes in response to chemotaxis, or with milder irritation, mononuclear cells, wander through the endothelium and accumulate below it perhaps on account of the greater impermeability of the middle coat to the passage of cells. The lesion described does not occur exclusively with interstitial suppurative pneumonia caused by hemolytic streptococci, but has been found in association with abscess formation (Autopsies 354 and 383) caused by hemolytic streptococci or (Autopsy 322) caused by staphylococci. In 1 instance it has been found with lobar pneumonia (Autopsy 320) caused by atypical Pneumococcus II and in 2 Interstitial suppurative pneumonia of long standing may occasionally be accompanied by chronic changes which bring about thickening of the interlobular tissue. In the following autopsy acute suppurative inflammation in the left lung has been associated with conspicuous thickening of interlobular septa in the right lung. Autopsy 474.—I. H., white, aged twenty-one, was a native of Oklahoma and had been in military service one month. His illness began with influenza thirty-six days before death; he was admitted to the base hospital thirty-one days before his death with signs of pneumonic consolidation of the right lower lobe. Evidence of fluid in the right pleural cavity was obtained two weeks before death, and from 100 to 700 c.c. of thick purulent fluid were aspirated on five occasions. Hemolytic streptococci were found in the aspirated fluid. Anatomic Diagnosis.—Interstitial suppurative pneumonia in left lung; abscess of right lower lobe with rupture into pleural cavity; thickening of interlobular septa of right lower lobe; double purulent pleurisy with thoracotomy on right side; serofibrinous pericarditis. The right pleural cavity contains 85 c.c. of thick purulent fluid; the right lung (Fig. 9) is collapsed and pushed to the median line, being bound by firm adhesions to the pericardium. Over the external and basal surfaces is a localized cavity walled off by adhesions. An abscess cavity in the lower part of the lower lobe communicates through a perforation in the basal surface of the lung with the pleural cavity and is in free communication with a small bronchus. About the abscess the lung is red and laxly consolidated, but elsewhere air containing; throughout the lower half of the lower lobe, the interlobular septa are marked by conspicuous yellowish gray lines about 1 mm. in thickness. Between these thickened septa the lung tissue contains air. The lung weighs 600 grams. The left lung (Fig. 10) is voluminous and heavy, weighing 1,320 grams. The surface is Bacteriologic examination has shown hemolytic streptococci in the blood, left lung, right and left pleural cavities, and right bronchus. B. influenzÆ has been found in the bronchus, in the right pleura and in the heart’s blood. A few colonies of S. aureus have been found on the plate from the right pleural cavity (site of thoracotomy). Microscopic examination of the right lower lobe shows that the interstitial septa are much thickened by young fibrous tissue infiltrated with lymphoid and a few plasma cells. Large mononuclear cells with granular cytoplasm are very numerous. A lymphatic is much distended and contains a few polynuclear leucocytes and many lymphoid and large mononuclear cells. There is no suppuration. Sections from the right lung show suppurative lymphangitis with suppurative inflammation of interstitial tissue. The right lung is the site of a healing lesion of the interstitial tissue which has developed simultaneously with acute interstitial suppurative pneumonia in the left lung. Both lesions are doubtless caused by S. hemolyticus. This healing lesion exhibits little similarity to the interstitial bronchopneumonia described by several observers with both measles and influenza. The following autopsy furnishes further evidence that interstitial suppurative pneumonia exhibits a tendency to heal. Proliferation of endothelial cells lining the inflamed lymphatics gives rise to phagocytic cells which aid in removing the accumulated leucocytes. Anatomic Diagnosis.—Interstitial suppurative pneumonia in left upper lobe; acute bronchopneumonia with lobular consolidation in right upper lobe; localized purulent pleurisy on left side with compression and atelectasis of left lung; compensatory emphysema of right lung; purulent bronchitis; beginning serofibrinous pericarditis; chronic passive congestion of liver, spleen and kidneys. The right lung is very voluminous, free from coal pigment and bright pink save over lobular patches of consolidation which have a bluish red color; the bronchi contain mucopurulent material. The anterior surface of the left lung is bound to the chest wall by firm adhesions, but over the external and posterior surfaces of the lung there is a localized cavity containing 1,100 c.c. of turbid fluid. The left lung is collapsed and airless with deep fleshy red color. In the upper lobe there are scattered patches of consolidation 1.5 to 2.5 cm. across where the tissue is grayish red and coarsely granular. In the adjacent tissue interstitial septa are thickened to 1 or 2 mm. and are conspicuous as gray bands. Along their course occur bead-like swellings from which purulent fluid can be scraped. These septa at one point reach the anterior surface of the lung where the pleural cavity is in large part obliterated by adhesions; here there is an encapsulated pocket 4 x 1.5 cm. containing thick creamy pus. Bacteriologic examination of the blood shows the presence of hemolytic streptococci; cultures from the lungs contain hemolytic streptococci and B. influenzÆ. Microscopic examination shows that interlobular septa are thickened and infiltrated with plasma cells in large number. Leucocytes in the center of much dilated lymphatics have undergone necrosis and have lost their nuclear stain. About the periphery of the lumen and evidently derived from the swollen endothelial cells which surround it, are numerous large mononuclear cells. They act as phagocytes and ingest polynuclear leucocytes. Multinucleated giant cells, derived from these cells, occur. In several places thrombosed lymphatics in process of organization occur; the lumen is filled with compact fibrin which is invaded by fibroblasts and newly formed capillaries. The process just described is analogous to that which occurs whenever an unopened abscess heals; mononuclear cells accumulate and act as phagocytes ingesting polynuclear leucocytes. Autopsy 499.—J. H. M., white, aged twenty-four, a farmer from Arkansas, had been in military service five months. Onset of illness began two weeks before his admission to the hospital on November 15 with cough, fever, headache and malaise; on admission there was acute bronchitis. Thirteen days after admission the patient developed parotitis (mumps?); five days later and five days before death pleurisy was recognized on the right side and pneumonia was suspected. Death occurred thirty-six days after onset. The temperature on admission was 103.2° F. and remained elevated during one week falling by lysis; from this time until the pleurisy was recognized it was normal and later it remained approximately 103° F. Anatomic Diagnosis.—Fibrinopurulent pleurisy on right side; fibrinous pleurisy on left side; fibrinopurulent pericarditis; chronic interstitial (interlobular) pneumonia in process of healing; purulent bronchitis; acute splenic tumor; parenchymatous degeneration of kidneys. The right pleural cavity contains 1,650 c.c. of grayish yellow fluid containing an abundant sediment of softened fibrin. Part of this fluid, more opaque than the remainder is confined in a localized pocket between the inner surface of the lung and the pericardium. The apex and anterior surface of the right upper lobe, over an area about 7 cm. across, is held by fibrinous adhesions to the chest wall; when this adhesion is broken a pocket is exposed 6.5 x 2.5 cm. containing fibrin and fluid. The pericardial cavity is distended by 350 c.c. of turbid yellow seropurulent fluid. The pericardial surfaces are covered by shaggy, tough gray fibrin. The right lung is collapsed; the lower and posterior part of the upper lobe is deep red and atelectatic. Throughout the upper lobe the interlobular septa are thickened, often 1 mm. across and very conspicuous; in the lower and anterior tip of the lobe is an area where tissue is firm grayish red and heavier than water. The lower and posterior half of the right lower lobe is firm and airless, and the tissue is reddish gray or gray and in places finely granular on section; interlobular septa are conspicuous. Although the lung is cut into thin sections, no abscesses are found. Bronchi throughout the lung contain mucopurulent fluid. The left lung over its lower half is covered by a thin layer of fibrin. The tissue is crepitant throughout and moderately edematous. Bronchi contain mucopurulent fluid. Hemolytic streptococci in pure culture are obtained from the blood of the heart, right pleural cavity and pericardium. No growth is obtained on a plate inoculated with material from the right lower lobe. The right bronchus contains hemolytic streptococci and B. influenzÆ. In association with hemolytic streptococci in the blood, pleura and pericardium, there has been inflammation of the interlobular septa of the lungs with acute lymphangitis; there has been no suppuration and the lesion is in process of healing with new formation of fibrous tissue. It is evident that this lesion, as well as pleurisy with advanced organization, preceded the exacerbation of the patient’s illness which occurred five days before death. The advanced chronic changes found at autopsy indicate that the pulmonary and pleural lesions had their origin during the illness which was present at the time of admission to the hospital. Interstitial pneumonia caused by hemolytic streptococci was of mild character and did not produce suppuration within the lung; nevertheless, hemolytic streptococci which reached the pleura caused empyema. Suppurative Pneumonia with Multiple Clustered Abscesses Caused by StaphylococciIn the preliminary report of this commission published in The Journal of the American Medical Association, loc. cit., pg. 111, we described suppurative pneumonia with multiple abscesses caused by staphylococci and cited 4 instances of the lesion which followed influenza. Chickering and Park In a small group of cases abscesses in the lungs have had characters which serve to distinguish them from the abscesses previously described. Small, sharply circumscribed yellow nodules, which in their centers have undergone suppurative softening, form a cluster upon a red, airless background (Figs. 15 and 16). One or more of these groups several centimeters across, occur in the lungs. It is usually evident that the abscesses are clustered about a medium-sized bronchus, but occasionally with increase in the size of the small cavities the lung tissue assumes a honey-combed appearance. These clustered abscesses occur in association with bronchopneumonia and have been in all instances associated with purulent bronchitis. The mucosa of the small bronchi may be destroyed so that the surface is eroded. These small clustered abscesses are seen as conspicuous yellow spots immediately below the pleura, but there has been no associated empyema. In 2 instances these abscesses were accompanied by fibrinous pleurisy, but in the remaining autopsies the pleura has been normal. The infrequency of empyema is in contrast with its almost invariable presence when a streptococcus abscess is found below the pleura. Autopsy 280.—Onset of illness with malaise, headache, cough and fever was on September 24, eight days before death. At autopsy there were hemorrhagic peribronchiolar and lobular bronchopneumonia, clustered foci of suppuration in right lung, purulent bronchitis and fibrinous pleurisy. Hemolytic streptococci were obtained from the consolidated lung and from a bronchus. A culture from the right lung was contaminated. In the bronchus were found B. influenzÆ and a few staphylococci. Microscopic examination of the abscesses shows that they contain Gram-staining cocci grouped into staphylococcus-like colonies. Autopsy 286.—Duration of illness, which began September 25 with symptoms of influenza, was nine days. At autopsy there were lobular and confluent patches of bronchopneumonia, clustered abscesses in the right lung below the pleura, purulent bronchitis, and serofibrinous pleurisy localized in the neighborhood of the abscesses. Pneumococcus IV was obtained from the blood of the heart, and Pneumococcus IV, staphylococci and B. influenzÆ from the right main bronchus; growth failed to occur on plates from right and left lungs. Microscopic examination shows the presence of clumps of cocci with staphylococcus grouping in the centers of the small abscesses. Section through one abscess shows its continuity with the wall of a bronchus; along one side of the abscess is epithelium composed of flattened epithelial cells in multiple layers continuous with that of the bronchus; the remainder of the abscess wall is formed by disintegrated lung tissue. Fig. 15.—Abscesses in two clusters caused by S. aureus in upper part of right upper lobe; confluent lobular consolidation in lower part of lobe. Autopsy 333. Fig. 16.—Abscesses in cluster caused by S. aureus at apex of right upper lobe. Autopsy 322. Autopsy 322.—The patient was admitted with influenza eight days before death; signs of pneumonia appeared two days later, and on the following day Pneumococcus IV was obtained from the sputum. At autopsy there were bronchopneumonia with lobar consolidation, abscesses clustered about a bronchus in the right upper lobe and purulent bronchitis. The blood was sterile; S. aureus was obtained from the consolidated part of the left lung; S. aureus and Pneumococcus III from the abscesses of the right lung. Microscopic examination of sections of abscesses showed the presence of Gram-staining cocci in staphylococcus-like colonies, surrounded by necrotic material and polynuclear leucocytes; Gram-negative bacilli resembling B. influenzÆ were seen. (See Fig. 16.) Autopsy 370.—The patient was admitted seventeen days before death and signs of pneumonia were noted three days after admission. At autopsy there were lobular and confluent bronchopneumonia and small abscesses clustered about bronchi and situated within the gray consolidated lung; purulent bronchitis and patches of atelectasis, with distention of the lungs, so that they failed to collapse on removal. No growth was obtained from the heart’s blood; S. aureus in pure culture was obtained from the abscesses of the right lung; S. aureus, Pneumococcus IV and B. influenzÆ were obtained from a small bronchus on the left side. Autopsy 425.—Illness began with influenza twenty-nine days before death; a diagnosis of pneumonia was made fourteen days before death. At autopsy there were chronic bronchopneumonia with tubercle-like nodules of consolidation with some large patches of consolidation, multiple small abscesses giving a honey-combed appearance to part of the right middle lobe, purulent bronchitis and bronchiectasis. S. hemolyticus was grown from the heart’s blood; S. hemolyticus, B. influenzÆ and S. albus from the lung. Sections of an abscess contain clumps of cocci. An abscess cavity has along one side remains of a bronchial wall covered by squamous epithelium; a dilated bronchus, cut longitudinally, terminates in this irregular abscess cavity. Table XLIX shows the incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzÆ in the foregoing autopsies with abscesses clustered about bronchi:
Staphylococcus shows in the lung the same tendency to produce localized abscesses which it exhibits in other tissues of the body; it invades the lung by way of the bronchi, Notwithstanding the small number of autopsies, the figures in Table XLIX, showing the incidence of pneumococci, streptococci, staphylococci and B. influenzÆ, are cited so that they may be compared with the corresponding figures for the usual type of streptococcus abscess (p. 203). The incidence of hemolytic streptococci is relatively low, whereas that of staphylococci approximates 100 per cent. S. aureus was present in great number in the lung of Autopsies 322 and 333 and in pure culture in the abscess of Autopsy 370. Microscopic examination of sections from the abscesses which have been described, demonstrated the presence of Gram-staining cocci in characteristic staphylococcus-like clumps within the exudate of the abscesses; scattered chains of streptococci were not found. In those instances (Autopsies 280 and 286) in which cultures failed to demonstrate staphylococci, microscopic examination demonstrated staphylococcus-like clumps of bacteria within the abscess cavity. Cultures were usually made from the consolidated lung near the abscess where the pleural surface could be seared, rather than from the pus, so that in some instances the microorganism has doubtless escaped detection although present. In association with the multiple abscesses which have been described, injury to the bronchi and bronchopneumonia have been invariably present. Purulent bronchitis Microscopic examination shows that the epithelium of the bronchi is partially or completely destroyed and that destruction of the underlying tissue, with acute suppurative inflammation, penetrates to a greater or less depth into the wall. When the epithelium of the bronchus is wholly destroyed and the lumen is filled and distended with polynuclear leucocytes, a cross section of the tube has the appearance of a small abscess; but more careful examination often shows that the engorged mucosa is still intact. Occasionally, a network of fibrin forms a layer covering the denuded mucosa. Disintegration of the superficial tissue may extend to the muscularis or through it, and may penetrate the wall of the bronchus. The tissue in contact with the exposed surface contains many polynuclear leucocytes and blood vessels plugged with fibrinous thrombi, but deeper in the tissue lymphoid and plasma cells are more numerous. In 2 instances (Autopsies 286 and 425) favorable sections have demonstrated that the wall of an abscess on one side consists of the remains of a bronchus, covered by epithelium composed of squamous cells, Whereas the remainder of the wall, here very irregular, is formed by partially destroyed alveoli plugged with fibrin. The suppurative process has penetrated the wall of the bronchus on one side and extended into the surrounding alveolar tissue. In other instances, abscess cavities occur within the alveolar tissue of the lung and their relationship to bronchi is not evident. In the mass of polynuclear leucocytes which fill the abscess cavity, are clumps of staphylococci in great abundance, usually forming characteristic colonies which are conspicuous with the low power of the microscope. Empyema, Pericarditis and PeritonitisNo sharp line can be drawn between nonpurulent and purulent pleurisy. A diagnosis of empyema has been made when the fluid in the chest has become opaque and fibrin has undergone softening or solution. The lesion has been designated seropurulent when there has been abundant thin, opaque, gray fluid. Pleurisy has been designated fibrinopurulent when the cavity has contained opaque fluid and ragged soft white or yellowish fibrin adherent to the chest wall; this fibrin is evidently in process of disintegration and there may be numerous shreds and flakes of fibrin which subside to the bottom of the fluid. The amount of fluid in the cavity may occasionally exceed 1,700 c.c.; that in both pleural cavities may exceed 2,500 c.c. The lesion has been designated purulent when fibrin has almost wholly disappeared and the cavity contains thick yellowish white fluid. In 4 of 5 instances in which thoracotomy had been performed, empyema has assumed this otherwise uncommon type. Some inflammation of the pleura is almost constantly found in association with all forms of pneumonia, but in many instances is so slight that it has no noteworthy significance. Table L shows the incidence of various types of pleurisy.
Of 16 instances in which empyema has occurred in association with lobar pneumonia or bronchopneumonia unaccompanied by suppuration in 6 there has been infection with hemolytic streptococci. Empyema has occurred in the absence of hemolytic streptococci only 10 times. Empyema Caused by Hemolytic Streptococci.—When necrosis preceding abscess formation has occurred in the lung, streptococci are found in immense numbers in the dead tissue. The pleura overlying the abscess undergoes necrosis and occasionally streptococci are particularly numerous upon the pleural surface of the necrotic tissue. In Autopsy 376 a membrane thin as tissue paper, representing the pleura, separated an abscess containing thick pus from the pleural cavity which was the site of empyema. The abscess may rupture into the pleural cavity and at the same time may be in free communication with a bronchus (Autopsy 480). In one (Autopsy 467) instance an abscess which had ruptured into the pleural cavity had completely discharged its contents and was in process of healing, newly formed fibrous tissue being abundant in its wall. With few exceptions empyema has accompanied subpleural abscess caused by hemolytic streptococci, being found on the side corresponding to the abscess. Among 39 instances of pulmonary abscess, empyema has been limited to the side of the abscess in 23; it has been present on the opposite side as well in 10 instances. In 2 instances there have been abscesses in both lungs; in one (Autopsy Empyema has been almost invariably found in association with interstitial suppurative pneumonia. This lesion extends by way of the lymphatics up to the pleural surface and is often more conspicuous just below the pleura than elsewhere. Empyema has been absent in only 3 of 21 examples of the lesion and in one of these there has been serous effusion. In 12 instances interstitial suppuration has occurred only on one side and empyema has been limited to this side; in 5 instances with interstitial suppuration on one side there has been empyema on both sides; in 2 instances with interstitial suppuration in both lungs there has been double empyema. The amount of fluid in the pleural cavity has varied from less than 100 to 1,500 c.c. The fluid has occasionally been seropurulent or yellow, thick and purulent, but in most instances the exudate is best described as fibrinopurulent. There is yellow or yellowish gray purulent fluid containing flakes of soft ragged fibrin. The foregoing study has shown, on the one hand, that empyema is a frequent complication of streptococcus pneumonia and, on the other hand, that empyema following influenza with relatively few exceptions is caused by hemolytic streptococci. Empyema caused by this microorganism exhibits in some instances characters not seen with other varieties of pleural inflammation. The tissue between sternum and pericardium is often edematous and the adjacent fat has a firm brawny consistence. In some instances the exudate contains blood, and hemolysis has occurred Stone, Bliss and Phillips Autopsy 473.—A. D. P., white, aged twenty-one, a student from Missouri, had been in military service two weeks. He was admitted to the hospital with influenza twenty-eight days before his death, and four days after admission there were signs of pneumonia. Paracentesis was performed on the right side on the eleventh day after admission; 4 c.c. of cloudy fluid which contained Pneumococcus III were obtained at this time and later in the day 800 c.c. were withdrawn. On the thirteenth day attempted withdrawal of fluid from both pleural cavities failed. On the eighteenth day aspiration of the right pleural cavity yielded only 30 c.c. of fluid. On the nineteenth day 400 c.c. of purulent fluid were withdrawn from the right pleural cavity. On the twenty-fifth day there was cyanosis and delirium. Shortly before death aspiration of the right pleural cavity was attempted, but only 4 c.c. of fluid were obtained. Anatomic Diagnosis.—Chronic bronchopneumonia with lobular and peribronchiolar consolidation in left lung; fibrinopurulent pleurisy on both sides; purulent bronchitis and bronchiectasis. On removal of the sternum, encysted purulent pleurisy is found between the inner surface of the right lung and the pericardium; there is here 450 c.c. of very thick creamy, greenish yellow pus entirely separated from the remainder of pleural cavity. The external part of the cavity contains 1,450 c.c. of fluid and voluminous masses of firm fibrin which placed in a measuring cylinder occupy 450 c.c. The left pleural cavity contains 400 c.c. of seropurulent fluid in which there is abundant sediment of fibrinous particles. The right lung is compressed; the bronchi exude purulent fluid. The left lung is voluminous; in the upper and lower lobes there are small yellowish gray nodules of consolidation, grouped in clusters, and gray patches of lobular consolidation occur. Bronchi are dilated and filled with purulent fluid. Bacteriologic examination shows the presence of Pneumococcus III obtained in pure culture from the blood of the heart and from the right pleural cavity. S. viridans is grown from the left lung; a plate from the right bronchus contained B. influenzÆ, S. viridans and a few colonies of staphylococcus and M. catarrhalis. Pericarditis.—Among 241 autopsies on individuals with pneumonia following influenza, pericarditis occurred 23 times; these lesions were classified as follows: Serous pericarditis, 1; serofibrinous pericarditis, 9; seropurulent pericarditis, 1; fibrinopurulent pericarditis, 10; purulent pericarditis, 2. It is noteworthy that in 12 of 23 instances of pericarditis the lesion was associated with S. hemolyticus infection of the lung and whenever in these instances cultures were made (Autopsies 434, 485, 499 and 504) hemolytic streptococci were obtained from the pericardial exudate in pure culture. The tendency of interstitial suppurative pneumonia to produce pericarditis is especially evident. Among 21 instances of interstitial suppurative pneumonia pericarditis occurred 6 times (28.6 per cent); among 39 instances of suppurative pneumonia with abscess formation, pericarditis occurred twice (5.1 per cent); whereas among all other autopsies, namely, 181, the lesion occurred 15 times (8.3 per cent). Pericarditis occurred in association with pneumonia referable to Pneumococcus I, once, (Pneumococcus I isolated from the pericardium); to Pneumococcus II, once; to atypical Pneumococcus II, 5 times (twice isolated from the pericardium); Peritonitis.—Purulent peritonitis occurred only twice, in both instances in association with pneumonia caused by hemolytic streptococci. Purulent peritonitis was part of a general serositis involving both pleural cavities, pericardium and peritoneum in 2 noteworthy instances: Autopsy 465.—J. K., white, aged twenty-two, farmer from Oklahoma, had been in military service one month. He was admitted to the hospital with influenza, sore throat and bronchitis twenty-four days before his death. Signs of pneumonia were recognized thirteen days later and at the same time there was otitis media on the right side. Empyema and pericarditis were found three days before death and two days later 1000 c.c. of cloudy fluid were withdrawn from the chest. Anatomic Diagnosis.—Suppurative pneumonia with consolidation and abscess in right lower lobe below pleura; purulent pleurisy on right, seropurulent pleurisy on left side; beginning serofibrinous pericarditis; fibrinopurulent peritonitis; purulent bronchitis. The body is emaciated. The right pleural cavity contains 350 c.c. of thick, creamy yellow pus in which are flakes of fibrin; the right lung is collapsed and lies at the back and inner side of the cavity. The left pleural cavity contains 500 c.c. of turbid, yellow, seropurulent fluid in which is soft fibrin. The lower lobe of the right lung is consolidated throughout, flabby, gray red and finely granular on section. Below the pleura of the posterior border is a wedge-shaped cavity with its base 1.5 cm. across, in contact with the pleural surface. About the cavity consolidated tissue has an opaque, yellow color. Bronchi in both lungs contain mucopurulent fluid. The pericardial cavity contains 20 c.c. of turbid fluid; the left auricular appendage is bound by a thin layer of fibrin to the parietal pericardium. The peritoneal cavity contains 100 c.c. of thick, creamy, yellow, purulent fluid. Between the diaphragm and liver is a layer of fibrin, in places 1.5 cm. in thickness; fibrin is present upon the peritoneum overlying the kidneys and base of mesentery. Bacteriologic examination shows the presence of hemolytic streptococci, obtained in pure culture from the blood of the heart, right pleural cavity and peritoneum. From the right bronchus are grown S. hemolyticus, B. influenzÆ and a few colonies of S. viridans and staphylococcus. Autopsy 504.—G. R. C., white, aged twenty-eight, farmer from Alabama, had been in military service three months. Onset of illness occurred six days before death, and two days later he entered the hospital with fever (103.4° F.), pains in the abdomen and vomiting. Consolidation at the bases of the lung was recognized on the day following admission and on the day before death 900 c.c. of greenish brown fluid were aspirated from the left pleural cavity. The body is that of a large well-nourished man. The left pleural cavity contains 975 c.c. of creamy, yellow fluid; right pleural cavity contains 425 c.c. of purulent fluid thinner than that on the left side. The left lung is collapsed; the posterior and lower half of the lower lobe is consolidated, flabby, deep red and fleshy in appearance. The interstitial septa are yellow, thickened with bead-like enlargements and contains creamy purulent fluid which flows away and leaves small cavities. This interstitial suppuration is more advanced below the outer surface of the lobe than elsewhere. The pericardial cavity contains 25 c.c. of creamy, yellow, purulent, fluid; the epicardium is dull, covered in a few places by a small amount of fibrin and below it are ecchymoses. The peritoneal cavity contains 100 c.c. of thick, yellow pus; the peritoneal surfaces are injected and between the liver and diaphragm is fibrin. Bacteriologic examination shows the presence of S. hemolyticus in pure culture from the blood of the heart, the lower lobe of the left lung, pericardium and peritoneum. The right main bronchus contains the same microorganism, B. influenzÆ and a few staphylococci. General serositis has been caused by hemolytic streptococci which in one instance have entered the pleura from a subpleural abscess, and in the other from the suppurating interstitial tissue of the lung. In one of these cases the patient entered the hospital with symptoms suggestive of acute peritonitis. BronchiectasisAcute dilatation of the bronchi is a common result of the bronchitis of influenza, and its frequent occurrence is an index of the severity of the changes in the bronchial wall. In some instances the smaller bronchi in well-localized areas are uniformly dilated; in other instances, large cavities, several centimeters in diameter, are formed and all transitions between the two extremes occur. The occurrence of bronchiectasis following influenza is mentioned by Leichtenstern We have had abundant opportunity to observe early stages in the production of bronchiectasis and to study the much discussed pathogenesis of the condition. The following figures show the predilection of bronchiectasis for the left lung and for the lower lobes: Bronchiectasis occurred 30 times in the left lung alone, 9 times in the right lung alone and 13 times in both lungs, the total being 52. Among 30 instances in which the lesion occurred only in the left lung, in 24 it was limited to the lower lobe, and in 15 of these 24 instances to the base of the lower lobe. Among 9 instances in which dilatation of bronchi occurred only in the right lung, it was limited to the lower lobe in 4 instances and to the base of the lower lobe in 2 of these 4 instances. When the lesion is limited to the base of the lower lobes small bronchi with no recognizable cartilage in their wall are dilated to a diameter of from 3 to 6 cm. and are distended with thick mucopurulent fluid. The tenacious character of the bronchial contents and the action of gravity doubtless have a part in the production of the dilatation. In several instances dilatation of the bronchi was limited to the basal parts of both upper and lower lobes. When bronchiectasis occurs throughout a whole lung, usually the left, or in both lungs, the lesion is more advanced and conspicuous (Fig. 26). There is diffuse dilatation of small and medium-sized bronchi. Dilated bronchi with deeply injected mucosa and filled with yellow mucopurulent fluid, are seen throughout the sectioned lung. A bronchus cut longitudinally may have a nearly uniform More advanced bronchiectasis is represented by the occurrence of spherical bronchiectatic cavities, having a diameter from 1 to 2.5 cm. In some instances there have been two or three of these cavities but occasionally there may be many. Cylindrical dilatation of the bronchi usually occurs widely distributed in the lungs. In Autopsy 440 a small bronchus, cut longitudinally, was dilated to a diameter of 5 mm. for a distance of 5 cm. and terminated in a spherical cavity 2 cm. in diameter; there was another smaller spherical cavity nearby and dilated bronchi occurred elsewhere. In Autopsy 467, in the upper part of the lower lobe, two spherical cavities 1 and 1.5 cm. in diameter communicated with a bronchus of medium size. Autopsies with bronchiectasis are listed in the order of the duration of illness to show the parallel increase in the severity of the lesion (Table LI). In 2 instances (Autopsies 244 and 314) bronchiectatic cavities surrounded by firm fibrous tissue have evidently existed before the onset of the fatal illness, which has lasted in one instance approximately four and in the other six days; these autopsies have been omitted from the table. The table shows that bronchiectasis observed within twelve days after onset of illness with symptoms of influenza is moderately advanced and almost invariably limited to the left lower lobe and usually to the base of the lobe. Advanced dilatation, indicated by the formation of spherical or cylindrical cavities, occurs with increasing frequency as the duration of the respiratory disease increases. Bronchiectasis has been almost invariably associated with purulent bronchitis. The dilated bronchi contain mucopurulent material and throughout the lungs the same condition is usually widespread. Among 137 instances of purulent bronchitis bronchiectasis consequent upon influenza has been present in 50.
Comparison of the percentage incidence of the organisms which have to be found associated with bronchiectasis and with purulent bronchitis unaccompanied by bronchiectasis shows that there is no noteworthy difference in the occurrence of pneumococci, hemolytic streptococci or B. influenzÆ within the bronchi. When allowance is made for the difficulty of demonstrating B. influenzÆ in the presence of a large number of other microorganisms, it is not improbable that this organism has been constantly present in the purulent contents of the bronchi with purulent bronchitis, with and without bronchiectasis. Pneumococci, streptococci and staphylococci are each present in the bronchi in about one-half of the instances of bronchiectasis and mixed infections are very common, S. viridans, B. coli and M. catarrhalis being occasionally found in the bronchi. The table shows that pneumococci, streptococci and staphylococci show no greater tendency to enter the lungs and blood when bronchiectasis and purulent bronchitis coexist than with purulent bronchitis alone. Moderate dilatation of the small bronchi at the base of the left lung was found in several instances eight days after onset of symptoms referable to the respiratory passages. Advanced, diffuse dilatation of the bronchi was seldom seen before the lapse of two weeks, and bronchiectasis with formation of spherical or cylindrical cavities Bronchiectasis is almost invariably associated with purulent bronchitis in which tenacious mucopurulent fluid accumulates in the bronchi. It begins at the bases of the lower lobes and is usually more advanced here than elsewhere. Mechanical distention of the small bronchi by viscid fluid, expelled with difficulty, brings about their dilatation and gravity appears to have a part in accentuating the process. Histologic examination of the changes accompanying bronchitis show that lesions which penetrate into the muscular layer and presumably weaken the bronchial wall are not uncommon and partial or complete destruction of the wall may result. To what extent infiltration of the muscular wall by polynuclear leucocytes or by lymphoid and plasma cells is accompanied by changes which weaken the wall may be questioned. When the epithelial lining of the bronchus is destroyed coagulative necrosis of the underlying tissue occurs and may extend a variable distance into the bronchial wall, not infrequently penetrating into or entirely through the muscular layer. These changes furnish an explanation of the occurrence of bronchiectasis following influenza. Fig. 17.—Acute bronchiectasis showing fissures penetrating into bronchial wall and at one place entering surrounding alveolar tissue; the surrounding alveoli are filled with fibrin. Autopsy 425. Acute bronchiectasis may be found following influenza after the illness has lasted eight or ten days. There is no increase of fibrous tissue. Small bronchi with no cartilage, which in normal lungs have a diameter approximating 1 mm., are dilated to 3 mm. or more. The surface epithelium is wholly or partially lost. Necrosis occurs in places and extends deep into the tissue, destroying muscle and often penetrating the entire thickness of the wall which in these small bronchi consists in large part of fibrous tissue containing greatly engorged blood vessels. In this necrotic material nuclei are absent and the tissue containing fibrin stains deeply with eosin. In it occur fissures or tears which extend from the lumen a variable distance, very frequently penetrating the entire thickness of the wall and entering adjacent alveoli (Figs. 17 and 19). Alveoli thus exposed almost invariably contain plugs of dense fibrin. Where these rents have occurred, adjacent edges of the bronchial wall, held together by underlying lung tissue, have separated from one another, so that the circumference of the bronchus has been increased (Fig. 18). These breaks in the continuity of the wall may occur in several places, so that a fourth or a third of the circumference may be formed Fig. 18.—Acute bronchiectasis showing fissures in the bronchial wall extending into neighboring alveoli which in zone about are filled with fibrin; one fissure has separated widely; peribronchial fibrinous pneumonia (fibrin is black). Autopsy 425. Recently dilated bronchi have an irregularly stellate lumen as the result of clefts penetrating at intervals into or through the bronchial wall (Fig. 26). Longitudinal fissures mark the lining of these dilated bronchial tubes. When the fatal illness has lasted more than two weeks, abundant new formation of fibrous tissue occurs in a zone surrounding the dilated bronchus. Adjacent alveolar walls are thickened by young fibrous tissue. Alveoli, much diminished in size, are filled by hyaline fibrin into which fibroblasts Fig. 19.—Acute bronchiectasis; the bronchial wall indicated by engorged mucosa shows a varying degree of destruction, fissures extending into and through the bronchial wall. Autopsy 352. Fig. 20.—Acute bronchiectasis; with destruction of bronchial wall exposing alveoli filled with fibrin; peribronchial fibrinous pneumonia is seen about several bronchi present in the section; Gram Weigert fibrin stain. Autopsy 425. This stage is well represented by Autopsy 421 after an illness of nineteen days. Bronchiectatic cavities, from 3 to 6 mm. in diameter, are numerous in sections of the lung; their lumina are irregular in outline and often irregularly stellate. Microscopic examination shows the presence of The reinforcement of the fissured bronchial wall by new formation of fibrous tissue, by thickening of the interalveolar walls and by organization of fibrin within the alveoli is well shown after four weeks (Autopsy 425; Fig. 28). There are spherical bronchiectatic cavities more than a centimeter in diameter surrounded by a dense fibrous wall in which are atrophied alveoli lined by epithelium of cubical form. Occasionally, the fibrous wall is interrupted and alveoli, plugged with organizing fibrin, are in immediate contact with the lumen. When these plugs of fibrin which are slowly absorbed disappear, evidence of preexisting rents in the bronchial wall are lost, and there are in this lung bronchiectatic cavities of which the wall is a continuous circle of dense fibrous tissue. Fig. 21.—Bronchiectasis with fissures extending through the bronchial wall into alveolar tissue which is the site of fibrinous pneumonia; epithelium has grown down into these fissures and has covered the exposed surfaces. Autopsy 463. Fig. 22.—Regeneration of epithelium over fissures which have been formed in the wall of a bronchus; the epithelium in the neighborhood of and within the fissure is squamous. Epithelium lining the dilated bronchi is at times completely destroyed (Fig. 28), but more frequently it persists in part. That which remains has almost constantly the character of squamous epithelium (Figs. 22 and 23). The lowermost cells are cubical; those above them are polygonal, tending to become flatter as the surface is approached; upon the surface are cells often much flattened and occasionally they have lost their nuclei and stain deeply with eosin as the result of superficial necrosis. The change should not be regarded as metaplasia, for the epithelium assumes this squamous type when the superficial columnar cells have been lost. Actual necrosis of superficial ciliated columnar cells is occasionally seen (Autopsy 352); injured cells have separated from one another and desquamated Fig. 23.—Squamous epithelium growing over the defect in the bronchial wall shown in Fig. 22 more highly magnified; squamous epithelium is present above and columnar epithelium below. The necrosis and tears which occur in the wall of the bronchus are not always limited to the bronchus, but may extend deeply into the surrounding tissue. In Autopsies 312 (Fig. 21) and 423 wide areas of necrosis have penetrated deeply into the tissue about the bronchi. Autopsy 312.—Illness began with influenza on September 26, seventeen days before death; a diagnosis of lobar pneumonia with consolidation of Hemolytic streptococci were found in the heart’s blood, in the pleural exudate, consolidated lung and bronchus; B. influenzÆ was found in the lung and in a small bronchus, and staphylococci in the contents of a small bronchus. Fig. 24.—Acute bronchiectasis with fissures extending through bronchial wall which is marked by great engorgement of blood vessels; at one point a fissure has penetrated deep into the alveolar tissue and formed a small cavity containing purulent exudate and surrounded by fibrinous pneumonia. Autopsy 312. Bronchi which are the site of acute inflammation have lost their epithelium wholly or in part, and deep fissures penetrate the entire thickness of the bronchial wall, extending into the surrounding lung tissue which is the site of fibrinous pneumonia. In some instances plugs of fibrin within the alveoli are bisected by these tears. There is some superficial necrosis along the edge of each fissure, in several places extending outward from defects in the walls of small bronchi dilated to approximately 1.5 mm. There are wide patches of necrosis affecting both alveolar walls and contents Autopsy 423.—C. H., white, aged twenty-five, resident of Oklahoma, had been in military service one month. Death occurred sixteen days after onset of influenza. Anatomical Diagnosis.—Chronic bronchopneumonia with peribronchiolar consolidation throughout right lung and in left lower lobe; right purulent pleurisy; purulent bronchitis; bronchiectasis at base of left lung. The right lung weighs 1,260 grams; in the upper lobe are yellowish gray nodules having the appearance of tubercles clustered about small bronchi; in places similar nodules occur upon a background of pinkish gray consolidation occupying the greater part of the lower lobe. Bronchi contain purulent fluid. The left lung weighs 760 grams; it is edematous and small, yellowish gray nodules of consolidation in the lower lobe are clustered about terminal bronchi. Bronchi at the base of the lower lobe are dilated. Bacteriologic examination shows the presence of hemolytic streptococci in the blood of the heart; hemolytic streptococci and B. influenzÆ in the lung. Microscopic examination shows that the walls of the bronchi are infiltrated with lymphoid and plasma cells; these cells are very numerous in peribronchiolar patches of consolidation. A small bronchus 1 mm. in diameter has squamous epithelium along one side; on the opposite side, the wall is completely absent and there is superficial necrosis of exposed alveoli filled with fibrin. A deep fissure passes from the bronchus into the consolidated tissue; its edges are necrotic and it is filled with polynuclear leucocytes. A small cavity in contact with the bronchus has been formed. In another part of the lung a distended bronchus has lost its epithelium on one side, and here alveoli filled with fibrin form the wall of the bronchus which is filled with leucocytes. Extending outward from the eroded wall is a focus of necrosis where both alveolar walls and contained exudate have lost their nuclei. The necrosis which has had its origin in the bronchi is soon followed by accumulation of polynuclear leucocytes, softening and disintegration of tissue. Discharge of the disintegrated tissue through the bronchi results in the formation of a small cavity continuous with the bronchus. These changes are well illustrated by the bronchiogenic abscesses which have been described elsewhere (Autopsies 376, p. 206, and 387, p. 206). When disintegrated tissue Autopsy 445.—W. F., white, aged twenty-three, from Mississippi, had been in military service one month. His illness began September 22, twenty-seven days before death, with severe coryza, weakness, nausea and vomiting; great pain in bones, cough and sore throat. He was admitted to the base hospital one week later with diagnosis of influenza and bronchitis. On October 3, sixteen days before death, signs of consolidation were found on the left side over the back and a diagnosis of lobar pneumonia was made. On October 18 there was severe headache, pupils were dilated, and there was rigidity of neck; lumbar puncture was made and pneumococci were found in the fluid obtained. Death occurred on the following day. Anatomic Diagnosis.—Bronchiectasis with unresolved pneumonia limited to the left lower lobe; acute bronchopneumonia with peribronchiolar consolidation in right lung; purulent bronchitis, peribronchial hemorrhage and organizing bronchiolitis in right lung; adherent pleura on left side; purulent meningitis. The left upper lobe is crepitant throughout. The outer and posterior two-thirds of the left lower lobe is riddled with cavities often rounded and varying in diameter from 0.5 to 3 cm. but not infrequently irregular in shape and in communication with adjacent cavities (Fig. 25). In places cavities pass in a tortuous course from pleura to the midpart of lung. The lining of these cavities is usually smooth, but in places is covered by gray necrotic material. Communication between the cavities and medium-sized bronchi is occasionally found. The lung tissue between the cavities is in part grayish red and consolidated, in part pink and air containing. The right lung is edematous throughout; the bronchi in the lower part of the right lung contain purulent fluid and are in places surrounded by zones of hemorrhage. The spleen is very large (14 × 11 × 5 cm.) and firm. The spinal fluid is cloudy and blood vessels over the lumbar enlargement and lower thoracic region are congested; in the upper thoracic region the cord is covered by purulent exudate. Bacteriologic examination demonstrates the presence of hemolytic streptococci in the blood of the heart; plates from the left lung contain a few colonies of S. aureus and Pneumococcus IV; plates from the right main bronchus contain S. aureus and a large bacillus which does not stain by Gram’s method. Three plates from the spinal meninges contain Pneumococcus IV. Fig. 25.—Advanced bronchiectasis throughout lower left lobe. Autopsy 445. The cavities communicate with the bronchi and are lined in part by vascular connective tissue which may in part represent preexisting bronchial walls, but no epithelium is present and the relation to the bronchi cannot be established with certainty. These cavities have extended by necrosis which has broken the vascular connective tissue of their wall and penetrated into adjacent lung tissue. Death has been the result of purulent meningitis caused by pneumococcus, and the histologic changes in the walls of the cavities suggest that the activity of the inflammatory reaction here is subsiding, for large mononuclear cells are numerous and are ingesting polynuclear leucocytes. The changes described would, if continued, result in the formation of cavities lined by fibrous tissue and resembling many of those formed as the result of dilatation of the bronchi. A study of the progress of the changes which result in the formation of bronchiectatic cavities has shown how the inflammatory irritant within the bronchus destroys the epithelium of the bronchus, penetrates into the deeper tissues and produces fissures which extend through the entire thickness of the bronchial wall at one or usually several places. These longitudinal fissures, which at first often give a stellate outline in cross section to the cavity of the affected bronchus, permit the separation of the edges of the fissure, so that an increase in the circumference occurs. The base of the fissure is formed by surrounding alveolar tissue and its edges are the site of necrosis. Tears may extend into the surrounding alveolar tissue, thus permitting further stretching of the bronchial wall. The consequences Compression of the lungs by forced expiration, even though the glottis were closed as in coughing, would not dilate the bronchi, because pressure outside and within the bronchi would be equally elevated (Thornton and Pratt Weakening of the bronchial wall by the changes which have been described will cause lasting dilatation of the bronchi. Whatever increases pressure within the bronchi will increase the tendency to dilatation; the bronchi being filled with mucopurulent exudate dilatation usually appears first at the bases of the lung, since gravity increases intrabronchial pressure here. New formation of fibrous tissue within the wall of the bronchus, thickening of adjacent alveolar walls, and organization of fibrin reinforce the weakened bronchial wall and limit the dilatation which follows injury to the wall. Regeneration of epithelium covering the dilated tube will further obscure the early changes which have made dilatation possible. The changes which weaken the bronchial wall permit dilatation at a time when there is no new formation of fibrous tissue. When the bronchial lesion has persisted several weeks, Unresolved BronchopneumoniaChronic bronchopneumonia is characterized by changes similar to those associated with chronic inflammation in other parts of the body, namely, by thickening of the interstitial tissue of the lung, by accumulation of mononuclear cells, by proliferation of fibrous tissue and by organization of exuded fibrin. In a few instances these changes have begun at the end of two weeks after onset of influenza, but they have been little advanced until three weeks has elapsed; advanced chronic inflammation has occurred after from four to eight weeks. Chronic inflammation primarily affects those structures which are most severely injured by the acute lesion and is most conspicuous in immediate proximity to the small bronchi and bronchioles; the perivascular and interlobular connective tissue are secondarily involved. Corresponding to each of the lesions of the alveolar tissue which have been found with bronchopneumonia, namely, peribronchiolar, hemorrhagic peribronchiolar, lobular and peribronchial consolidation, there is a chronic lesion which develops when pneumonia has failed to resolve. The term interstitial bronchopneumonia has been used by MacCallum to designate a lesion which he has found in association with measles at Fort Sam Houston. This name he states does not describe accurately the early stage of the lesion, for its interstitial character is not evident at first. In his monograph on “Epidemic Pneumonia in the Army Camp,” published in 1919, MacCallum describes and pictures Studying pneumonia following influenza at Camp Lee, Va., and later at Camp Dix, N. J., during the fall of 1918, MacCallum reached the conclusion that “interstitial bronchopneumonia” following influenza was caused by B. influenzÆ of Pfeiffer. This lesion attributed to B. influenzÆ differed from that previously referred to hemolytic streptococcus in the following characters: the lymphatic channels in the bronchial walls and widened interlobular septa are inconspicuous and none are found distended with exudate; there is no intense infection of the pleura, and polynuclear leucocytes are inconspicuous in the alveolar exudate and in the walls of the bronchi. It seems probable these differences are explained by the absence of hemolytic streptococci which tend to invade lymphatics and produce severe inflammatory changes in the pleura. Chronic Bronchitis.—The earliest changes in the bronchial wall with bronchitis of influenza are hyperemia, leucocytic infiltration and hemorrhage, and they may occur even though the lining epithelium remains intact. Epithelium A later phase in this series of changes is represented by new formation of fibrous tissue. The bronchial walls and interalveolar septa are thickened by proliferating fibrous tissue, young fibroblasts and newly formed collagen fibrils Organizing Bronchitis and Bronchiolitis.—When the bronchial epithelium is destroyed, fibrin is deposited upon the denuded surface and may partly or completely fill the lumen of the bronchial tube. The plug of fibrin is adherent to the underlying tissue wherever epithelium is lost but is separated from the bronchial wall by a well-defined space where epithelial lining is still intact. Fibroblasts promptly migrate from the wall of the bronchiole into this fibrin, and fibroblasts, fixed during ameboid movement, are irregularly elongated in a direction toward the fibrin. Organization of fibrin occurs within the smallest bronchi (diameter 0.3 to 0.5 mm.) or within respiratory bronchioles. It has been found in 8 autopsies. In one instance it has been present eleven days after the onset of influenza, but usually it is seen three or four weeks after onset of symptoms The lesion has been associated with chronic bronchopneumonia in 6 of 8 instances. In Autopsy 445, p. 257, organizing bronchitis and bronchiolitis occurred in the right lung unassociated with other chronic lesion, although there was advanced bronchiectasis with fibrous induration in the left lung. In Autopsy 499 (p. 224) organizing bronchiolitis occurred in association with chronic changes which appear to have followed interstitial suppurative pneumonia caused by S. hemolyticus. Other severe lesions of the bronchi have accompanied organizing bronchitis and bronchiolitis. Purulent bronchitis has been present in 7 of 8 instances; bronchiectasis in 5 of 8 instances. The bacteriology of autopsies with organizing bronchitis and bronchiolitis is shown in Table LIII. The bacteriology of these cases presents no constant feature. Invasion of the blood by S. hemolyticus has been present in a large proportion of cultures, namely, in 5 of 7 (71.4 per cent). In one of the 2 instances in which hemolytic streptococci have been found, neither in the blood nor lungs, Pneumococcus III has been found in the blood and S. viridans in the lungs and bronchus; in the other, S. aureus has been found in the lung and bronchus. Staphylococci have been found frequently in the bronchi (60 per cent) and in the lungs (50 per cent). B. influenzÆ has been present in the bronchi in the usual proportion of instances (80 per cent). The lesion has occurred in the presence of B. influenzÆ combined with streptococci or staphylococci.
Thrombosis of lymphatics in the wall of bronchi adjacent to blood vessels and in interlobular septa occurs, and occasionally organization of the fibrinous plug within the lymphatic is in progress (Autopsies 283, 425 and 463). Fibroblasts and capillaries penetrate from the wall of the lymphatic into a mass of hyaline fibrin which fills the lumen. Unresolved Bronchopneumonia.—The most common type of pneumonic lesion following influenza is characterized by acute inflammation of the alveoli immediately adjacent to the bronchioles and the lesion is associated in many instances with hemorrhage or edema. If this lesion persists unresolved during several weeks, evidences of chronic inflammation are found. Peribronchial, perivascular and interlobular connective tissue is thickened and richly infiltrated with lymphoid and plasma cells, large mononuclear cells and many young fibroblasts. Interalveolar septa adjacent to the walls of bronchi and between alveoli surrounding inflamed bronchioles are implicated in the process. Chronic bronchopneumonia is often overlooked at autopsy because newly formed connective tissue is not present in sufficient quantity to attract attention (Fig. 26). When the lesion is advanced conspicuous gray white patches of fibrous tissue may be seen about the bronchi (Autopsy 487; Fig. 27) and interlobular septa may be obviously thickened (Autopsy 472). The most distinctive feature of the lungs is the presence of small, firm, gray or yellowish gray nodules of consolidation which resemble miliary tubercles. They represent the peribronchiolar patches of bronchopneumonia present during the acute stage and have assumed the well-defined outline and firm consistence of tubercles because polynuclear leucocytes and red blood corpuscles have in large part disappeared, interstitial tissue is increased, and exudate is in process of organization. These nodules are grouped in clusters about the small bronchi. With unresolved bronchopneumonia the lungs are very voluminous and fail to collapse after they are removed from the chest and in some instances even after incision. The air containing tissue is usually dry. In our autopsies the lungs have been pink in color and often free from coal pigment, because those suffering with pneumonia have been in considerable part men from rural districts. Thick mucopurulent material exudes from the small bronchi which have been cut across; purulent bronchitis has been present in 20 of 21 instances of chronic bronchopneumonia. Bronchiectasis has been present in 13 instances; dilatation is often advanced, so that throughout the lungs are found bronchi with no cartilage distended to a diameter of 0.5 cm. In addition to the firm peribronchiolar tubercle-like nodules of consolidation there are scattered patches of gray lobular or confluent lobular consolidation. Yellowish nodules, grouped about bronchi and resembling those found elsewhere in air containing tissue, are occasionally seen scattered upon the cut surface of a patch of gray, confluent lobular consolidation (Autopsies 421, 423, 431). Fig. 26.—Unresolved bronchopneumonia with tubercle-like nodules of peribronchiolar consolidation best seen in lower lobe; bronchiectasis. Autopsy 425. Increase of fibrous tissue occurs about the blood vessels and in the septa between the lobules, which are infiltrated with mononuclear wandering cells and fibroblasts. Dilatation and thrombosis of the lymphatic vessels have occurred in both situations, and in 3 instances (Autopsies 283, 425 and 463) organization of these fibrinous thrombi has occurred. Fig. 27.—Unresolved pneumonia with peribronchial formation of fibrous tissue; bronchiectasis. Autopsy 487. Fig. 28.—Unresolved pneumonia with bronchiectasis showing new formation of fibrous tissue about a greatly dilated bronchus of which the epithelial lining has been lost. Autopsy 487. Thickening, cellular infiltration and fibrosis of the bronchial walls with interstitial inflammation and fibrosis of immediately adjacent alveolar septa are found about the ramifications of the bronchial tree and may be followed to the smallest bronchi. When the respiratory bronchioles are reached it will be found that the alveoli which stud their walls are implicated in the change. The fibrin which they contain is infiltrated with lymphoid and plasma cells, and with progress of the lesion is invaded by fibroblasts and capillaries. Infiltration and fibroid thickening extends from the bronchiolar wall to the alveolar septa continuous with it (Fig. 31 with measles). Similar changes occur about the alveolar ducts, and about the orifices of the tributary infundibula (Fig. 32), peribronchiolar foci of acute inflammation having assumed the characters of a chronic inflammatory process. Fibrin within the alveoli contains round cells and fibroblasts. With thickening of alveolar walls the alveolar lumina may be much diminished in size and often persist as spaces lined by cubical cells. Polynuclear leucocytes are usually numerous within the alveolar duct and One of the most constant characters of pneumonia following influenza is its hemorrhagic character. In the earlier stages of pneumonia phagocytosis of red blood corpuscles by large mononuclear cells is frequently seen. In association with the chronic changes which have been described, large mononuclear cells filled with brown pigment, doubtless formed from red corpuscles, are often found within the alveoli. These pigment containing cells are similar to those commonly associated with chronic passive congestion of the lungs. In one instance (Autopsy 457) hemorrhagic peribronchiolar pneumonia has been found in process of organization. The bronchioles and alveoli adjacent to them contain polynuclear leucocytes, but intervening alveoli almost uniformly contain blood and are the site of new formation of connective tissue. Interalveolar septa are thickened and alveoli which are lined by cubical epithelium are often diminished in size. In many places fibroblasts have penetrated in considerable number into the blood within the alveoli and occasionally newly formed capillaries are found within them. Lobular patches of pneumonia are often found in process of organization (Autopsies 370, 421, 423, 433, 463, 472 and 473). Microscopic examination shows that whole lobules well defined by thickened septa are the site of chronic interalveolar inflammation and intraalveolar organization of exudate, whereas adjacent lobules are air containing and relatively normal. In the earlier stages of the process fibrin present within the alveoli is invaded by fibroblasts, With chronic bronchopneumonia confluent lobular consolidation occasionally has a gray ground upon which are scattered small yellow spots clustered about the small bronchi (Autopsies 421, 423 and 431). Microscopic examination has shown that the yellowish spots correspond to dilated bronchioles filled with purulent exudate and surrounded with alveoli containing many polynuclear leucocytes. In the interstitial tissue about the bronchiole and between adjacent alveoli plasma cells are often present in great number. Between these spots of subacute bronchiolar inflammation lung tissue is the site of interalveolar proliferation of fibrous tissue and intraalveolar organization of exudate. In all instances of chronic bronchopneumonia there has been peribronchial pneumonia in a zone encircling small bronchi with no cartilage and the smallest of the bronchi which have cartilage in their wall; thickening of interalveolar septa, organization of peribronchial fibrinous pneumonia and partial disappearance of alveoli have been described. In the following autopsy peribronchial fibroid pneumonia has been so advanced that conspicuous patches of gray white tissue surrounding bronchi have replaced in some parts of the lung a considerable part of the lung substance. Autopsy 487.—W. C., white, aged twenty-seven years, a farmer from Mississippi had been in military service twenty-one days. Illness began on September 17, fifty-five days before death, with chill, fever, cough, backache, pain in the chest and coryza. The patient was admitted two weeks after onset with the diagnosis of influenza. Eight days later his sputum was blood tinged and there were signs of bronchopneumonia. One month after admission the patient developed a rash and a diagnosis of scarlet fever was made. The body is much emaciated. The left pleural cavity contains 650 c.c. of opaque, dull yellow, thin, purulent fluid. The surface of the left lung is covered in spots by white partially organized fibrin. On section of the right lung (Fig. 27) the tissue is found in great part air containing but there are numerous firm, gray patches, irregular in shape and from 1 to 2 cm. across. In these spots the tissue is tough and resembles fibrous tissue; within them are much dilated bronchi. In the central part of the upper lobe is a group of cavities with smooth wall, the largest of these cavities being 12 mm. in diameter; immediately adjacent are dilated bronchi. Between and surrounding these cavities is gray tissue, like that described above. Below the outer surface of the upper lobe is an extensive area 7 cm. from above downward, thickly studded with bronchiectatic cavities, in the walls of which there is tough fibrous tissue. In the middle lobe are several dilated bronchi, the largest of which is 7 mm. in diameter, and elsewhere occur dilated bronchi with thickened walls. At the base of the lung below the pleura are two abscesses, which are yellow in the center and surrounded by hemorrhagic tissue. At the posterior part of the lower lobe there are numerous firm, nodular, yellowish spots grouped in clusters upon a background of red, air containing tissue. The bronchi throughout the lung contain mucopurulent fluid. In the left lung patches of fibrous tissue are more numerous than on the right side and are irregular in shape, from 1 to 2 cm. across and most abundant in the center of the upper lobe. This fibrous tissue is in great part gray but in places it has a yellowish tinge. The bronchi everywhere are moderately dilated. At the base of the lung below the pleura is an abscess. The other organs show no noteworthy change. Bacteriologic Examination.—The fluid in the left pleura and right main bronchus contain S. hemolyticus. B. influenzÆ is found in the right lung and right main bronchus. Microscopic examination shows that the patches of dense fibrous tissue seen at autopsy almost invariably surround dilated bronchi with no cartilage in their walls (Fig. 28) and with a diameter of from 1 to 2 or more millimeters. These bronchi have lost their epithelial lining; they contain polynuclear leucocytes, and their wall in contact with the lumen is infiltrated to a varying distance with the same cells. Their inner surface is very irregular, and superficial necrosis occurs. The limits of the preexisting bronchial wall is no longer recognizable in the dense surrounding fibrous tissue richly infiltrated with lymphoid and plasma cells. In contact with the bronchus, often in a wide zone, all traces of alveoli have been destroyed, but further outward alveoli are represented by spaces lined by cubical epithelium. At the periphery of the zone of fibroid induration alveolar walls are much thickened and richly infiltrated with mononuclear wandering cells; the lumina of the alveoli contain plugs of organized fibrous tissue often covered by flat or cubical epithelium. In the surrounding tissue a few small bronchi are lined by columnar Advanced induration about the bronchioles represents a late stage of chronic peribronchiolar pneumonia. A bronchiole cut transversely is found in the center of a focus of induration situated within relatively normal air containing lung tissue. Next the bronchiole which in some instances has wholly or partly lost its epithelium there is very cellular fibrous tissue; further from the bronchiole alveoli are much diminished in size, lined by flat or cubical epithelium and separated by thick cellular walls. Plugs of cellular fibrous tissue sometimes fill the alveolar duct. In favorable sections, cut in a plane which shows the alveolar duct opening out into infundibula, it is found that newly formed fibrous tissue surrounds the alveolar duct and extends into the walls of its tributary alveoli; alveoli may be obliterated by this fibrous tissue. Induration of alveolar walls is evident along the proximal part of the infundibula which are readily demonstrable because they are much dilated. (See Fig. 32.) The distal parts of the infundibula are surrounded by alveoli with delicate walls. One bronchus retains along one side part of its epithelium which has assumed a squamous form. In other places the wall has undergone necrosis which at one spot extends deeply into the surrounding tissue. Necrotic tissue in another part of the circumference is infiltrated with polynuclear leucocytes and separated from the surrounding tissue by a space filled with leucocytes. An abscess communicating with the bronchus is thus formed. The foregoing instance is an example of the chronic fibroid pneumonias with bronchiectasis which occur as sequelÆ of the epidemic of influenza. It is not improbable that a considerable number of those who suffer with chronic bronchitis and bronchiectasis following influenza have less extensive lesions similar to those which have been described.
Bacteria found in the lungs in 17 instances of chronic bronchopneumonia were as follows:
A noteworthy feature of these lists is the multiplicity of microorganism found, namely, B. influenzÆ, S. hemolyticus, pneumococcus, staphylococcus, S. viridans, B. coli, and M. catarrhalis. More than one microorganism is usually found in both bronchus and lung. In the one instance (Autopsy 472) in which B. coli alone has been found in the bronchus, B. coli and S. hemolyticus have been found in the lung and hemolytic streptococcus in the blood; it is evident that B. coli alone has not been responsible for the lesion. In one instance (Autopsy 487) B. influenzÆ alone has been found in the lung but hemolytic streptococci have been found in the bronchus, pleura and blood of heart; with S. aureus alone in the lung (Autopsy 370), S. aureus, Pneumococcus IV and B. influenzÆ have been found in the bronchus. With S. viridans alone in the lung (Autopsy 473), No single microorganism is associated with the lesions but combinations of B. influenzÆ with hemolytic streptococci or staphylococci are common (over 50 per cent). In Autopsy 422 B. influenzÆ and Pneumococcus atypical II have been present in the lungs. Among 10 instances in which cultures have been obtained from the bronchus B. influenzÆ is found 8 times, and in the 2 instances in which it has not been identified B. coli has been present. B. influenzÆ has seldom been found (Table XXVII) in the presence of B. coli, and it is not improbable that B. coli outgrows and obscures the presence of B. influenzÆ. Table LIV shows the per cent incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzÆ in the bronchus, lung and heart’s blood with chronic bronchopneumonia and serves as an index of the readiness with which each of these microorganisms passes from bronchus to lung and from lung to the blood in this disease.
Comparison of Table LIV with the analogous figures for acute bronchopneumonia shows little noteworthy difference. Pneumococci are less frequently found in the lung (12.5 per cent) and in the blood (16.6 per cent) with chronic bronchopneumonia than with acute bronchopneumonia (lung 43.9 per cent; blood, 40.3 per cent). Hemolytic streptococci and staphylococci are not more frequently The severity of the injury to the walls of bronchi resulting in continued infection with a variety of bacteria, appears to be the factor determining failure of resolution and the persistence of bronchopneumonia. The Relation of Unresolved Bronchopneumonia to Interstitial Suppurative Pneumonia Caused by Hemolytic Streptococci.—Hemolytic streptococci have been present in a considerable proportion of those who have had unresolved bronchopneumonia and its occurrence in the bronchi, lung and blood of the heart indicates that it has had an important part in causing death. Unresolved bronchopneumonia, following measles, designated by MacCallum “interstitial bronchopneumonia” in a series of autopsies at Fort Sam Houston in the spring of 1918, was constantly associated with hemolytic streptococci. Among the lesions described as interstitial bronchopneumonia was at least one which was evidently what we have designated interstitial suppurative pneumonia. Lymphangitis was not infrequently found with “interstitial bronchopneumonia” following measles. At Camp Lee and Camp Dix, following the epidemic of influenza, MacCallum found “interstitial bronchopneumonia” with no hemolytic streptococci and noted that lymphatics in the interstitial septa were inconspicuous and that none was found distended with exudate; empyema was not present. We have shown that interstitial suppurative pneumonia is an acute lesion caused by hemolytic streptococci. Unresolved bronchopneumonia is accompanied by chronic pneumonia and has no necessary relation to this microorganism. In the 3 autopsies described below, interstitial suppurative pneumonia with empyema caused by hemolytic streptococcus occurs in association with unresolved bronchopneumonia. Autopsy 420.—J. E. S., white, aged thirty-two years, born in England and resident of Los Angeles, Cal., had been in military service one month. Onset of illness began on October 3, eleven days before his death. He was admitted to the hospital on the following day with the diagnosis of influenza and acute bronchitis. Pneumonia believed to be lobar was recognized eight days after admission. Anatomic Diagnosis.—Unresolved bronchopneumonia with hemorrhagic peribronchiolar consolidation in right lung; interstitial suppurative pneumonia with consolidation in left upper lobe; fibrinopurulent pleurisy; purulent bronchitis. The left pleural cavity contains 200 c.c. of turbid yellow fluid in which are flakes of fibrin. In the inner and upper part of the left upper lobe there is an area of consolidation where the tissue has a cloudy, pinkish gray color and is finely granular on section. Here the interstitial septa are distended by edema, so that they are in places 0.5 c.c. across; in some spots they have a bright yellow color. In the posterior parts of the middle and lower lobes there is flabby consolidation where the tissue has a cloudy, red color with scattered ill-defined yellow spots. Bacteriologic examination shows the presence of hemolytic streptococci in the blood of the heart; hemolytic streptococci with B. influenzÆ and S. aureus in the left lung and S. hemolyticus with S. aureus in the right lung. Microscopic examination shows that bronchi, bronchioles, alveolar ducts and the greater part of the infundibula are filled with polynuclear leucocytes, whereas the alveoli surrounding these structures contain fibrin. The walls of the small bronchi are thickened and contain mononuclear cells; the adjacent Autopsy 428.—D. B., white, aged twenty-five, a farmer from Oklahoma, had been in military service three weeks. Onset of illness was on September 21, twenty-five days before death, with fever, cough and mucopurulent expectoration. The patient was admitted with the diagnosis of acute bilateral bronchitis. Four days later bronchopneumonia was recognized, and subsequently there was otitis media and empyema; 600 c.c. of thin, purulent fluid were aspirated from the right chest three days before death. Anatomic Diagnosis.—Unresolved bronchopneumonia; suppuration of interstitial tissue of upper right and lower left lobes; purulent bronchitis; fibrinopurulent pleurisy; thoracotomy wound at the base of the right chest; collapse of both lungs; serofibrinous pericarditis. The left pleural cavity contains 550 c.c. of turbid seropurulent fluid in which are numerous flakes of soft fibrin. The right pleural cavity contains 150 c.c. of similar fluid. The mediastinum is edematous. The pericardial cavity contains 50 c.c. of yellow fluid. The right lung is moderately collapsed. In the upper and lower lobes are small patches of red, lobular consolidation. The upper third of the upper lobe is laxly consolidated and near its inner surface the interstitial septa are thickened to from 1 to 1.5 mm. in width, and at intervals occur bead-like swellings from which creamy purulent fluid exudes upon the cut surface. In the left lung small patches of gray consolidation occur throughout the lower lobe and here the interstitial septa are thickened, beaded and contain purulent fluid. Bacteriologic examination shows that the blood contains S. hemolyticus; from the right lung and from the right main bronchus hemolytic streptococci and B. influenzÆ are grown. Microscopic examination shows that the epithelium of the bronchi has undergone hypertrophy; the wall is infiltrated with lymphoid and plasma cells and thickened by new formation of fibrous tissue; there is similar thickening of adjacent alveolar septa and alveoli, often lined by cubical cells, are diminished in size. Connective tissue about the blood vessels and the interstitial septa are thickened and infiltrated with mononuclear cells. In parts of the lung the interstitial septa are edematous and contain polynuclear leucocytes, in some places in great number. Lymphatics are greatly dilated and filled with polynuclear leucocytes which in the center of some lymphatics have undergone necrosis. In one place a small abscess is in contact with a distended lymphatic. Lymphatics contain Gram-staining cocci in pairs and short chains, present in immense number where necrosis has occurred. Autopsy 433.—B. J., white, aged twenty-seven, from Arkansas, has been in military service one month. Onset of illness was on September 28, nineteen Anatomic Diagnosis.—Unresolved bronchopneumonia with peribronchiolar and confluent lobular consolidation; interstitial suppuration of the right lower lobe; purulent bronchitis; fibrinopurulent pleurisy. The right pleural cavity contains 700 c.c. of yellowish gray purulent fluid containing flakes of fibrin. The left pleural cavity contains seropurulent fluid localized over the external part of the lung. The right lung is voluminous and free from consolidation save at the lower and posterior part of the lower lobe where the tissue is deep red and studded with firmer spots of yellow color clustered about the bronchi. In places the interstitial septa are thickened and yellow. Surrounding some of the bronchi near the apex of the left lung are red patches of consolidation. Culture from heart’s blood remained sterile. S. hemolyticus was grown from right pleural cavity, and S. hemolyticus and B. influenzÆ were grown from the right lung. Culture from the left lung contained S. aureus and contaminating microorganisms. Microscopic examination shows the presence of peribronchiolar patches of pneumonia in which there are few polynuclear leucocytes and many lymphoid and plasma cells; the alveolar walls are thickened and infiltrated with mononuclear cells. In some sections the tissue is wholly consolidated and the site of advanced organizing pneumonia. Interlobular septa and connective tissue about blood vessels are thickened and cellular. Small bronchi have lost their epithelial lining, their walls are thickened and there is peribronchial organizing pneumonia. In some sections the lymphatics are immensely dilated and distended with polynuclear leucocytes. There is necrosis of the walls of the lymphatics and of the polynuclear leucocytes within the lumen. In the discussion of acute bronchopneumonia it has been shown that S. hemolyticus is not infrequently a secondary invader of a pneumonic lesion perhaps caused by pneumococci. With progress of the disease hemolytic streptococci persist. In the autopsies with unresolved pneumonia just described, hemolytic streptococci have found their way into the lymphatics and produced suppurative lymphangitis with inflammation of the interstitial septa of the lung. |