Bronchitis
Clinical 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 not infrequently evident in the larger bronchial branches; superficial loss of epithelium is indicated by erosion of the surface, whereas somewhat deeper destructive changes are occasionally evident. Microscopic examination accurately determines the degree of destructive change.
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 and have a resistant cushion-like consistency. This condition is present where the lung tissue is air containing and dry, and occurs when very small bronchi contain tenacious mucous exudate which becomes apparent upon the cut surface after the sectioned lung is squeezed. Microscopic examination shows that the alveolar ducts and infundibula are distended with air, though the respiratory bronchioles contain inflammatory exudate. Complete obstruction of the bronchi is followed by absorption of air from the tributary pulmonary tissue with atelectasis. It is not improbable that partial obstruction, permitting the penetration of air with inspiration, produces distention of air containing tissue.
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 tissue containing a layer of smooth muscle and their caliber varies approximately from 1 to 0.5 mm. It is convenient to designate as respiratory bronchioles[[80]] the terminal ramifications of the bronchi; they are lined by a single layer of columnar ciliated cells passing over into cuboidal nonciliated epithelium and are beset with small air sacs lined by flat cells or epithelial plates similar to those of the alveoli elsewhere. Not infrequently these alveoli occur along only one side of the bronchiole, the remainder of the circumference being covered by a continuous layer of cubical epithelium. The respiratory bronchiole by branching along its course or at its end is continued into several alveolar ducts which unlike the respiratory bronchioles have no cubical or columnar epithelium but are closely beset by alveoli lined by flat epithelial plates. The alveolar duct is recognized by the absence of cubical epithelium and the presence of bundles of smooth muscle which occur in the wall. The infundibula or alveolar sacs arise as branches from the alveolar ducts and like them are beset with alveoli, but smooth muscle does not occur in their walls. The base of the infundibulum is wider than its orifice, which Miller states is surrounded by a sphincter-like bundle of smooth muscle.
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.
Polynuclear leucocytes are numerous upon the surface of the epithelium and are sometimes fixed in process of migration through epithelium and basement membrane.
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, degenerative changes occasionally ending in necrosis of cells, disappearance of acini, dense infiltration of interstitial tissue with lymphoid and plasma cells and finally proliferation of this interstitial tissue. The duct of a mucous gland, dilated and filled with mucus, may be surrounded by lymphoid and plasma cells in great number. Acini, similarly dilated, contain mucus and are composed of cubical cells which have discharged their mucous content. In some instances (e. g., Autopsy 257) the cells of the acini have undergone necrosis; the cytoplasm stains homogeneously and the nuclei have disappeared. Where necrosis has occurred, polynuclear leucocytes may penetrate into the dead cells. In association with degenerative changes in the acini there is abundant infiltration of the interstitial tissue within and about the glands with lymphoid and plasma cells. When the acini have disappeared there is proliferation of fibroblasts and new formation of fibrous tissue, and mucous glands are found in which a few atrophied acini are separated by newly formed fibrous tissue.
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.
With acute bronchitis there may be desquamation of epithelial cells with partial or complete loss of epithelial lining. In the smallest bronchi the single layer of columnar cells may be separated in places from the underlying tissue, so that intact rows of cells are found within the lumen. In somewhat larger bronchi, lined by epithelium in multiple layers, superficial columnar ciliated cells may be lost. In some instances superficial epithelial cells appear to have lost their cohesion and are separated by narrow spaces; in these instances, polynuclear leucocytes are often numerous between epithelial cells. Epithelium is occasionally separated from its basement membrane by small accumulations of serum or blood. Occasionally necrosis of epithelial cells with disappearance of nuclei is seen and is doubtless caused by the action of bacteria; the affected cells may be raised from the underlying tissue by accumulated serum (Autopsy 253). The changes which have been described bring about partial or complete loss of the ciliated lining of the bronchial tube.
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 necrosis has often occurred, and structures, such as white fibrous bundles or wall of blood vessels, are marked out by hyaline material which merges with fibrin. When the walls of the blood vessels which are invariably engorged are involved, the lumen is plugged by a fibrinous thrombus.
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 than a true metaplasia. The basal cells of the epithelium have a cubical or columnar form; above them the cells become polygonal and as the surface is approached, cells are flat and even scale-like. The nuclei of these superficial cells are often lost. There is no close resemblance to the squamous epithelium of the skin, for intercellular bridges are not seen.
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 bacteria in the order cited above, shows how varied have been the combinations which occur:
| B. influenzæ | 3 |
| Pneumococci | 5 |
| S. hemolyticus | 3 |
| Staphylococci | 3 |
| B. coli | 3 |
| S. viridans | 1 |
| B. influenzæ, pneumococci | 17 |
| B. influenzæ, S. hemolyticus | 18 |
| B. influenzæ, staphylococci | 4 |
| Pneumococci, S. hemolyticus | 1 |
| Pneumococci, staphylococci | 3 |
| S. hemolyticus, staphylococci | 4 |
| S. hemolyticus, B. coli | 2 |
| Staphylococci, S. viridans | 1 |
| B. influenzæ, pneumococci, S. hemolyticus | 6 |
| B. influenzæ, pneumococci, staphylococci | 15 |
| B. influenzæ, pneumococci, S. viridans | 2 |
| B. influenzæ, S. hemolyticus, staphylococci | 16 |
| B. influenzæ, S. hemolyticus, M. catarrhalis | 1 |
| B. influenzæ, staphylococci, S. viridans | 1 |
| Pneumococci, S. hemolyticus, staphylococci | 3 |
| Staphylococci, B. coli, S. viridans | 1 |
| B. influenzæ, pneumococci, S. hemolyticus, staphylococci | 7 |
| B. influenzæ, pneumococci, staphylococci, M. catarrhalis | 1 |
| B. influenzæ, S. hemolyticus, staphylococci, B. coli | 1 |
| B. influenzæ, S. hemolyticus, staphylococci, S. viridans | 1 |
| B. influenzæ, S. hemolyticus, staphylococci, M. catarrhalis | 1 |
| B. influenzæ, staphylococci, S. viridans, M. catarrhalis | 1 |
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 or staphylococci tends to increase the size of its colonies. Moreover, it is not improbable that the microorganism may disappear from the bronchi. Comparison with observations made upon influenza suggests that multiple methods of examination might have demonstrated a much higher incidence of B. influenzæ. Throat cultures alone made during life demonstrated the presence of B. influenzæ in only 65.7 per cent of patients with acute influenza, whereas when cultures were made from the nose, throat and sputum, and a mouse was inoculated with sputum from each patient, B. influenzæ was found in every instance. After the acute stage of the disease had passed, the number of microorganisms diminished, and in many instances B. influenzæ disappeared from the upper air passages. In some of our autopsies B. influenzæ doubtless present during life has similarly disappeared before death due to pneumonia caused by pneumococci or streptococci. In view of these considerations it is not improbable that B. influenzæ demonstrated by a single culture in 80 per cent of instances has been constantly present.
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.
| Table XXVIII | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| NO. OF CULTURES | PNEUMOCOCCI | HEMOLYTIC STREPTOCOCCI | STAPHYLOCOCCI | B. INFLUENZÆ | |||||
| NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | ||
| Bronchus | 121 | 56 | 46.3 | 58 | 47.9 | 61 | 50.4 | 96 | 79.3 |
| Lung | 153 | 68 | 44.4 | 77 | 50.3 | 37 | 24.2 | 70 | 45.7 |
| Blood | 218 | 87 | 39.9 | 85 | 39.0 | 1 | 0.5 | 1 | 0.5 |
Cultures from the bronchus represent the bacteriology of the bronchitis of influenza. Infection of the lung following influenza doubtless occurs by way of the bronchi, so that the bacteria which cause pneumonia are present in the bronchi before they enter the lung tissue. The figures in Table XXVIII, similar to those previously cited, show the high incidence of B. influenzæ, and the occurrence of pneumococci, hemolytic streptococci and staphylococci each present in approximately half of all autopsies.
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:
| Table XXIX | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| NO. OF CULTURES | PNEUMOCOCCI | HEMOLYTIC STREPTOCOCCI | STAPHYLOCOCCI | B. INFLUENZÆ | |||||
| NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | ||
| Bronchus | 66 | 33 | 50.0 | 32 | 48.5 | 36 | 54.5 | 53 | 80.3 |
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.