Epidemic Respiratory Disease / The pneumonias and other infections of the repiratory tract accompanying influenza and measles

by Eugene L. Opie; Francis G. Blake; Thomas M. Rivers; James C. Small

Unresolved Bronchopneumonia

Chronic 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 instances of the lesion which we have designated interstitial suppurative pneumonia and classifies them as interstitial bronchopneumonia. We have shown that this lesion, which is the result of infection of the lymphatics with S. hemolyticus, bears no necessary relation to the lesion which is characterized in its early stage by peribronchiolar pneumonia and in its later stages by chronic inflammation with mononuclear infiltration and proliferation of the peribronchial, perivascular and interalveolar tissue. At Fort Sam Houston, nearly every patient with measles was infected with hemolytic streptococci; we observed, following influenza, similar prevalence of hemolytic streptococci in certain wards in the base hospital at Camp Pike. Among the cases at Fort Sam Houston there were doubtless instances both of interstitial suppurative pneumonia caused by hemolytic streptococcus and of chronic bronchopneumonia not referable to this microorganism.

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 frequently undergoes partial or complete destruction, and with this severe injury the influence of the inflammatory irritant may extend directly through the wall of the bronchus, for in some instances there is hemorrhage into all the alveoli in a zone encircling the bronchus. Since these alveoli have only indirect communication with the affected bronchus through alveolar tissue not involved in the inflammatory process, it is evident that the surrounding hemorrhage is secondary to the lesion of the bronchus. Fibrinous inflammation in other instances, similarly localized in a zone of alveoli encircling a bronchus, is doubtless the result of direct extension of the inflammatory process through the bronchial wall. After the disease has existed during two or three weeks inflammation is still active immediately below the inner surface of the bronchus; here polynuclear leucocytes are numerous whereas in the deeper parts of the mucosa and about the muscularis leucocytes are scant but lymphoid and plasma cells are very numerous. The severity of the inflammatory reaction may be judged by the abundance and extent of this cellular reaction and is in close relation to the intensity of the changes affecting the mucous membrane of the bronchus. Infiltration of the entire bronchial wall with lymphoid and plasma cells is almost invariable when the primary injury to the bronchus has destroyed the epithelial lining, and this infiltration is not limited to the bronchial wall but extends outward into the contiguous alveolar septa which are thickened by it. The sheath of the pulmonary artery which accompanies the bronchus exhibits a similar change, and the alveolar septa, as a fringe about it, are thickened and infiltrated with mononuclear cells. Interlobular septa continuous with the bronchus often show some infiltration.

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 being abundant (Fig. 28; also Fig. 30). This increase of fibrous tissue is especially noteworthy immediately surrounding the walls of the small bronchi, which are often considerably dilated, and about the smaller of those bronchi which have cartilage; with thickening of alveolar walls immediately adjacent to the bronchus every stage in the obliteration of the alveoli may be found. Their walls are thickened and their lumina are diminished in size and often flattened in a direction concentric with the bronchus. Such atrophied alveoli lined by cubical epithelial cells occurring within the thickened peribronchial fibrous tissue give evidence that this tissue has replaced alveoli. Alveoli surrounding and within the new fibrous tissue are frequently filled with fibrin, and organization indicated by penetration of fibroblasts and capillaries into the fibrin may be far advanced. There is some increase of perivascular and interlobular tissue. The bronchiectasis which is almost invariably found with unresolved bronchopneumonia has been described. Squamous transformation of epithelium (page [251]) is frequently found in association with the chronic bronchitis of unresolved pneumonia.

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 of respiratory disease. In the early stages of the lesion a plug of fibrin within the lumen of the bronchus or bronchiole is invaded by fibroblasts, plasma cells and newly formed capillaries. These capillaries have their origin in the wall of the tube and enter the fibrin at points where in consequence of loss of epithelium fibrin is continuous with the connective tissue. When the bronchiole is cut longitudinally, partially or completely organized fibrin may be found adherent at several places with intact epithelium, sometimes beautifully ciliated, between the sites of attachment. The fibrin is finally replaced completely and the lumen of the bronchiole contains a mass of organized fibrous tissue in which young fibroblasts and plasma cells are numerous.

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.