Bronchiectasis.—Bronchiectasis has been frequently found as a sequela of the severe bronchitis of influenza and there has been abundant opportunity to study the lesion in process of development. These observations have furnished a satisfactory explanation of its etiology and pathogenesis. Infection of the bronchi by B. influenzæ, accompanied by a variety of other microorganisms, notably hemolytic streptococci and staphylococci, has caused profound changes in the bronchial wall beginning with destruction of the epithelial surface, and followed by necrosis penetrating partially or completely through the wall and occasionally extending into the surrounding alveolar tissue. The difference between the atmospheric pressure within the bronchi and the lower inspiratory pressure within the surrounding alveoli, accentuated by forced inspiration at intervals and by occlusion of the bronchioles with mucopurulent exudate, ruptures the necrotic tissue and produces longitudinal fissures which are recognizable both macroscopically and microscopically. In consequence of the separation of the edges of these fissures by intrabronchial pressure the circumference is increased. These rents in the wall are limited and partially healed by fibrinous pneumonia about them, by new formation of fibrous tissue from the bronchial wall, and adjacent interalveolar septa, by organization of fibrin within adjacent alveoli and finally by growth of epithelium over the denuded surfaces.
Bronchitis caused by B. influenzæ and pyogenic micrococci with necrosis of the bronchi wall is the essential factor in the production of bronchiectasis, but advanced bronchiectasis is found only in those individuals who have survived the onset of illness during several weeks, for dilatation under the influence of positive intrabronchial and negative extra-bronchial pressure occurs slowly.
Unresolved Bronchopneumonia.—Unresolved lobar pneumonia has not been recognized among instances of pneumonia following influenza, but unresolved bronchopneumonia is of frequent occurrence and has well definable gross and microscopic characters. There are purulent bronchitis, bronchiectasis and distention of the lung tissue, so that it fails to collapse; particularly characteristic are the indurated foci of peribronchiolar pneumonia, which being firm and sharply defined, have the appearance of miliary tubercles. When the process is sufficiently long continued there are recognizable patches of fibroid pneumonia. Microscopic examination shows that the lesion is characterized by organization of fibrinous exudate not only within the alveoli but within bronchioles as well, and by thickening of the alveolar walls, thickening of fibrous tissue about the bronchi and blood vessels, and thickening of interstitial septa. These changes may occur as peribronchiolar patches of consolidation, producing tubercle-like nodules, or may involve areas of hemorrhagic peribronchiolar or of lobular consolidation, or may be limited to the immediate neighborhood of bronchi (peribronchial).
No peculiarity of the bacterial flora of the bronchi or of the lung offers a satisfactory explanation of the failure of pneumonic exudate to resolve. Mixed infections have been common and S. hemolyticus, staphylococci, pneumococci, S. viridans, B. coli, etc., have been found in association with B. influenzæ but the incidence of these microorganisms has not been greater than with bronchitis. The lesion has occurred in association with B. influenzæ and pneumococci unassociated with other microorganisms. It seems probable that the severity of injury to the bronchial and alveolar walls accompanied by recurring bacterial invasion or by continued infection with B. influenzæ and one or several cocci, is the factor concerned in the inhibition of resolution and the production of chronic pneumonia. If the disease does not result in early death, chronic pneumonia has an opportunity to manifest itself.
In this investigation of the bacteriology and pathology of influenza and its complications, certain microorganisms have been found so frequently that it is desirable to discuss the pathogenicity of each and to define the character of the lesions which it causes.
Bacillus Influenzæ.—The microorganism has been constantly found in association with influenza when cultures and animal inoculations have been made from various parts of the respiratory tract within from one to five days after the onset of the disease at a time when there have been acute symptoms of the disease.
It is often identified with difficulty in the presence of other microorganisms and may be overlooked when a single culture is made. Repeated cultures from the throat alone made from the fourth to the eighth day after admission to the hospital, at a time when temperature had fallen to normal, have demonstrated the presence of B. influenzæ in 30.5 per cent, whereas the incidence of the microorganism in similar cultures on admission had been 63.4 per cent. The incidence of B. influenzæ in the present epidemic of influenza is not less than that found by Pfeiffer in the epidemic which he studied in 1892.
Nevertheless we have found that B. influenzæ is frequently an inhabitant of the mouth and throat of normal individuals. By inoculation of mice with the saliva or sputum of 76 patients with influenza, the microorganism has been found in 80.3 per cent; by inoculation of mice with the saliva of 185 normal men at army cantonments, it was found in 41.6 per cent; by inoculation of mice with saliva from 50 recruits immediately after they were assembled from isolated farming communities where only a few cases of influenza had occurred, it was found in 22 per cent. Figures for the same groups examined by a single throat culture were as follows: 65.7 per cent, 25.9 per cent and 0 per cent.
Experiments which we have performed on monkeys show that inoculation of the nasopharynx with B. influenzæ obtained from patients with influenza is followed by ill-defined symptoms associated with the presence of B. influenzæ within the throat. After from two to eleven days the symptoms and the microorganism disappear. Injection of B. influenzæ into the trachea causes bronchitis and the microorganism may be recovered from the inflamed bronchi two or three days after inoculation.
The constant association of B. influenzæ with influenza suggests that it is the cause of the disease. Its widespread occurrence in the throats of normal individuals does not contradict this view, since pneumococci long indistinguishable from those which usually cause lobar pneumonia are commonly found in the throats of healthy men. It is possible that B. influenzæ is a secondary invader, entering the respiratory tract when susceptibility is increased by an unknown virus causing influenza; but there is no convincing evidence in favor of this view. It is desirable to determine if microorganisms having the characters of B. influenzæ found with influenza differ in type from those found in the throats of healthy men and if the invasion of the respiratory tract by B. influenzæ is followed by the appearance of immunity reactions in the serum of the patient. Experiments on monkeys demonstrate the pathogenicity of the microorganism.