Pulmonary tuberculosis are traditionally described two different disease syndromes, primary or childhood tuberculosis, and seconds. The age-related terms force because age ;s perhaps the most important factor modifying the clinical manifestations of tuberculous infection The terms primary, secondary. and reinfection type have much less to recommend them because almost all clinical tuberculosis results from the evolution of the initial infection, either promptly or after variable periods of latency but without superimposition of new infection.
CHILDHOOD TUBERCULOSIS
In the majority of both children and adults, tuberculous infection runs its course without producing clinical illness. Infection is more often symptomatic in infants and young children than in adults, because of a tendency in the young to more extensive lymph node involvement and hematogenous spread. At the time at which hypersensitivity develops, a few may show varying degrees of fever and lassitude for a few days. Rarely will development of hypersensitivity be associated with erythema nodosum or symptomatic inflammation of the eye (phlyctenular keratoconjunctivitis), but these are nonspecific allergic reactions, caused more often by hypersensitivity states other than tuberculosis. Hilar lymph node enlargement in the young may partially compress the major bronchi, producing a brassy cough and occasionally sputum and clinical signs of localized bronchial obstruction. The chest roentgenogram will often reveal hilar adenopathy, usually unilateral, and less frequently a small parenchymal infiltrate in the mid or lower lung fields.
Diagnosis OF Pulmonary Tuberculosis
It is based on a positive tuberculin test, which is almost always marked in degree. Occasionally the sputum smear is positive for acid-fast bacilli on microscopy, and tubercle bacilli can probably be cultured from gastric aspirates if several specimens are obtained on different days. Although, as mentioned, symptoms are most often either lacking entirely or else evanescent and subtle, more advanced clinical syndromes based on hilar adenopathy, pleural effusion, and, rarely, direct progression of the initial pulmonary infiltrate may be seen. In the majority in whom tuberculosis produces symptoms, however, these result from either early or late progression of hematogenous foci in the apices of the lungs or elsewhere in the body.
Hilar adenopathy may produce symptoms in the infant and young child owing to a tendency to massive enlargement of lymph nodes and the small size and relative flaccidity of the bronchi, which in combination favor compression and obstruction. Extrinsic compression may produce partial or complete bronchial obstruction, resulting in segmental or lobar collapse and obstructive pneumonitis. Involvement of the bronchial wall from contiguous tuberculous inflammation in the node may progress to produce granulation tissue within-the bronchial lumen and seeding of tuberculous foci in the associated segment or lobe. Prolonged partial bronchial obstruction caused by enlarged nodes, cicatricial changes within the bronchus, or both, may result in bronchiectasis distally. Occasionally a node may dissect into the bronchus, emptying its highly antigenic contents and causing an intense bronchitis and pneumonitis or frank tuberculous pneumonia progressing to caseous necrosis. (At any time the node involvement may become quiescent and in later life dissect into the bronchus and produce symptoms of hemoptysis or segmental tuberculous pneumonitis.)
Tuberculous pleurisy and effusion (see Diseases of the Pleura) is an important and not uncommon complication occurring soon after infection both in children and young adults. A subpleural primary focus may either dissect into the pleural cavity or drain into pleural lymphatics. Less commonly, the hematogenous dissemination associated with the initial infection may produce secondary subpleural foci which dissect into the pleural cavity. Even though the effusion usually subsides spontaneously, a large percentage of patients will subsequently develop progressive pulmonary or extrapulmonary tuberculosis. Idiopathic pleurisy and effusion, especially in children or young adults with a positive tuberculin test, should be treated as active tuberculosis unless another diagnosis is established beyond doubt.
The term progressive primary is usually applied to direct evolution of a poorly contained initial infiltrate into a pneumonic and eventually caseous process. It may be differentiated from the usual case of chronic pulmonary tuberculosis by roentgenologic evidence of hilar adenopathy and by the more frequent nonapical position of the infiltrate. This, term has also been used to describe all forms of pulmonary tuberculosis occurring soon after the initial infection, whether in the area of the initial infiltrate, secondary to lymph node disease, or in apical foci seeded at the time of initial tuberculous bacteremia. This broader definition is less helpful.
It should be emphasized that features characteristic of childhood tuberculosis may also be seen in groups with low genetic resistance to tuberculosis. Thus extensive hilar adenopathy apparently occurs more frequently in young black adults than in whites. Particularly in isolated populations into which tuberculous infection has only recently been introduced, clinical manifestations in adults take on many of the features ordinarily associated with disease in children, except, of course, those related to the size and compressibility of the bronchial tree.
Treatment of childhood tuberculosis varies little from treatment in the adult, except that isoniazid dosage is larger (10 to 15 mg. per kilogram). The risk of induction of pyridoxine deficiency and peripheral neuritis is negligible in the young. An identified but uncomplicated infection is usually’ treated with isoniazid alone, except when drug resistance seems likely on epidemiologic grounds (contact with a known drug-resistant patient). Limitation of activity and provision for added sleep and rest during the day are advisable for the first few weeks. Patients symptomatic because of bronchial compression by enlarged nodes may be benefited by a short course of corticosteroids- (in dosage equivalent to prednisone, 20 to 40 mg. per day).
It must be recognized that resolution of a tuberculous process under therapy may proceed less rapidly in a lymph node than in lung parenchyma. Hence, the roentgenologic density, which is due to lymph node compression and not to intrinsic disease, may not recede rapidly with drug therapy (see Extrapulmonary Tuberculosis). Treatment of progressive, caseous pulmonary parenchymal disease is the same for children as for adults, except for the higher isoniazid dosage.
CHRONIC PULMONARY TUBERCULOSIS
In contrast to that in children, tuberculosis in adults is predominantly a disease of the pulmonary parenchyma. As mentioned, most if not all chronic pulmonary tuberculosis in the adult is due to the evolution of foci seeded during the preallergic bacteremic phase of the initial infect: :r. This evolution may occur either fairly promptly or after long periods of quiescence when subtle changes in the host resistance or other factors produce conditions favorable for this to occur Whether or not a latent period intervenes, these fee: gain largest size and, therefore, are most prone to reactivation in the apical posterior aspects of the lung, in which local factors are most favorable to bacterial growth.
The earliest infiltrate in chronic pulmonary tuberculosis appears most commonly in the posterior or apical segment of an upper lobe or the apical segment of a lower lobe, beginning as a small patch of bronchopneumonia surrounding a growing colony of tubercle bacilli. This inflammatory reaction in the hypersensitive host produces an alveolar exudate containing fibrin-rich fluid and a mixture of inflammatory cells. With increasing intensity of the inflammatory reaction, tissue necrosis of a type quite characteristic of tuberculosis and termed caseous (of a cheesy consistency) develops. As long as it persists intact, caseous necrosis :s an effective mechanism of host defense, inhibiting bacterial growth and causing the death of mos: organisms, presumably because of low oxygen tension and probably other factors as well. (Invariably, however, a few metabolically dormant organisms persist.)
The critical factors reversing this favorable trend are the tendency of the caseous material eventually to liquefy and the access of liquefied material to the bronchial tree. Bronchial drainage of liquefied material produces a ccv::\ in open communication with inspired air. in which high oxygen tension enhances bacteria, multiplication and from which secretions rich in bacteria are spread via the bronchi to other areas of the lung and to the outside environment. Once reactivation occurs, the progressive nature of tuberculosis in the hypersensitive has: is largely due to the combination of these three factors: the tendency of caseous necrosis to liquefy, the access of liquefied and infectious material to the bronchial tree, and the aerobic nature of the organisms, resulting in huge bacterial populations within open cavities.
Organisms delivered to the draining bronchus expose other areas of the lung to infection. Bronchogenic spread may take place by simple spillage, but is enhanced by the cough mechanisms which, because of explosive expiration followed by deep inspiration, aerosolize infectious material and then distribute it -videly throughout the lung. Sooner or later new foci of disease develop. Each in turn may undergo caseous necrosis and then heal, or liquefy, slough, and produce another cavity. New lesions usually appear first within other portions of the segment or lobe initially involved. Although contiguous spread may occur, bronchial spread is more frequent, producing scattered, patchy disease. The apical posterior areas of the contralateral lung are apt to become diseased, presumably again because of local factors intrinsic to these areas favoring growth of organisms spread via the bronchi. In addition to the exudative tissue response characteristic of progressive disease, there is usually also a productive tissue reaction characterized by giant cells and epithelioid cells forming tubercles and leading eventually to fibrosis and healing. This is particularly true in the anterior and basal portions of the lung which have a remarkable capacity to resist progressive infection. Continuing, heavy exposure to these areas from cavities above usu-lally produces gradual destruction by scarring and fibrosis rather than new necrotic areas.
Almost all lesions will show some mixture of exudative and productive tissue responses, with progressive disease in one area coexisting with regression in another. Moreover, the pace and tempo of progressive disease is highly variable from one patient to the next and in the same individual at different times. Lowered host resistance, owing to either intercurrent or genetic factors, vigorous hypersensitivity reactions, and large numbers of organisms favor acute inflammatory reactions and rapid progression, which may produce the clinical and roentgenographic picture of acute, confluent, bacterial pneumonia (tuberculous pneumonia or phthisis florida).
At the other end of the spectrum, relatively effective immunity, limited hypersensitivity, and a low bacterial population favor predominantly productive lesions, slow progression, and a greater tendency to spontaneous healing. Large, thick-walled cavities in a shrunken, extensively carnified lobe (chronic fibroid tuberculosis) may persist for years without causing symptoms but serving as a constant source of contagion for susceptible persons in the environment.
Mechanisms of healing are basically the same whether they occur spontaneously, under the influence of rest therapy, or after drug treatment. The exudative component of the early broncho-pneumonic infiltrate may resolve with preservation of normal lung architecture and function. More often the exudate organizes and is replaced with fibrous tissue. Caseous foci may remain solid and become encapsulated by fibrosis. The bronchus draining an open cavity occasionally becomes obstructed by granulation tissue and debris at the bronchocavitary junction. Such blocked cavities may become inspissated and encapsulated with fibrotic tissue and result in a tenuous form of healing. A cavity that remains open probably always remains infectious except under the influence of antimicrobial therapy of prolonged duration, which may produce elimination of all necrotic and infectious tissue and a clean fibrotic cavity wall. It must be remembered, however, that regardless of the type and extent of healing, viable though dormant organisms persist, which in favorable circumstances are capable of renewed growth and reactivation of disease.
Clinical Manifestations
Symptoms OF Pulmonary Tuberculosis.
Pulmonary tuberculosis in its incipiency is most often asymptomatic. Small apical infiltrates may persist for months or even years in tenuous balance, undergoing minor extensions and regressions and producing no indication by which their presence might be known unless fortuitously discovered by chest roentgenogram. When sufficient in amount, however, absorption of tuberculoprotein and other antigenic substances results in constitutional or general symptoms such as anorexia, weight loss, asthenia, lassitude and fatigue, fever, chilliness, rarely frank rigors, night sWeats, and wasting.
These are in no way specific, being produced in indistinguishable fashion by a wide variety of chronic, progressive in-infectious and neoplastic processes. However, in earlier years tuberculosis so greatly, overshadowed all other causes alone or in combination of these constitutional symptoms that they were taken, with justification, as indicative of phthisis. In the majority, constitutional symptoms begin insidiously and progress gradually over so protracted a period that the patient may not realize that he is ill. Not infrequently the magnitude of the illness is recognized with surprise only when viewed retrospectively in comparison with the state of restored health affected by drug therapy. Weight loss and fatigue are more likely to lead to medical attention than is fever, which is often unappreciated by the patient although usually present in the later course of the illness, characteristically in the afternoon.
Symptoms related specifically to the local inflammatory reaction in the lung are alfeo variable in degree and in time of onset, and although they tend to appear somewhat later, do in general parallel constitutional symptoms in onset and degree. Cough and sputum are the most consistent and predictable local symptoms. Both are due to bronchial involvement, which usually does not occur until parenchymal cavitation develops. Accordingly, their presence indicates an already advanced extent of disease. Bronchial irritation in the path of draining cavities with or without actual tuberculous bronchitis stimulates the cough reflex. Cavity drainage, together with bronchial secretions, results in sputum production. Depending upon the degree of bronchial reaction, the size of cavities, and the quantity of drainage, cough may vary from mild and unnoticed to paroxysmal and severe, and sputum may be scant and mucoid or copious and purulent. Usually cough and sputum appear gradually and progress slowly over months or years, varying with the tempo and destructiveness of the pulmonary process. Temporary improvement may dissuade the patient from seeking diagnostic attention, with tragic and, in earlier years, often mortal consequences.
Two symptoms which are fortuitous and unpredictable are hemoptysis and chest pain. Hemoptysis may be associated with rapid slough of a caseous lesion or may be due to ulceration in a draining bronchus. It usually presents as blood-streaking or a small amount of fresh blood. It can occur early, but is usually a manifestation of advanced disease. Particularly in late chronic disease, bleeding may be copious and sudden, owing to involvement and necrosis of an artery within the fibrous wall of a cavity (Rasmussen aneurysm).
Exsanguination is unusual, but particularly in advanced disease with compromised pulmonary function there’ may be a real threat of drowning, which requires prompt positioning for drainage (prone or Trendelenburg) and avoidance of reflex-dulling drugs. Hemoptysis of almost any degree is attended by great concern. Prior to the availability of effective chemotherapy, a large hemoptysis was often associated with extensive bronchogenic spread of infectious material. However, at present the fever and new basilar infiltrates caused by aspirated blood do not result in new tuberculous foci, being rapidly responsive to chemotherapy, and clearing in a few days or a week is the rule. A less startling symptom, but one also meriting concern, is pleural pain.
This is usually due to extension of inflammation to the pleural surface with involvement of the parietal pleura without production of pleural fluid i dry pleurisy). Much less commonly, pleural pain will be associated with serofibrinous pleurisy with effusion (which ordinarily occurs earlier in the course of the infection than does established apical pulmonary tuberculosis), and rarely tuberculous empyema will be discovered. Like hemoptysis, chest pain is a seldom ignored symptom, and these two are the symptoms most likely to lead to a diagnosis of tuberculosis. Rarely, medical attention is not sought until manifestations of very advanced illness occur. These may be due to disease in other tissues bathed in the highly infectious pulmonary secretions. Painful mouth ulcers, hoarseness and dysphagia owing to laryngeal involvement, tuberculous otitis media, or anal pain caused by a tuberculous perirectal abscess may first bring the patient to the physician. Shortness of breath may accompany acute tuberculous pneumonia or indicate impending pulmonary insufficiency following extensive destructive disease.
Lower and Middle Lobe Tuberculosis in Older Persons.
As the frequency of chronic pulmonary tuberculosis in young adults recedes, certain atypical presentations in older persons are being recognized with some frequency. A chronic and progressive infiltrate in the lower or mid lung field may be due to a recently acquired primary infection, with direct progression in an older person with the weakened immunologic responsiveness attendant on old age. Also, long quiescent tuberculous hilar lymph nodes may dissect into a bfonchus, release infectious material into it. and cause tuberculous pneumonia in the associated lobe or segment. Particularly m older women, some instances of the “middle lobe syndrome,! ordinarily caused by nontuberculous infection in an obstructed lobe, will be found to be due t: tuberculosis activated in this manner.
Physical Examination of Pulmonary Tuberculosis.
A complete physical examination is essential to the proper assessment it” individuals with pulmonary tuberculosis art: will provide valuable information regarding the ‘degree of illness, the patient’s tolerance to it. the presence of associated diseases, and the anatomii functional changes in the lung.
Other Laboratory Findings.
The normocytic, normochromic anemia of chronic infection is usually present and may be severe. The white blood count is usually within normal limits; marked leukocytosis should suggest a complicating bacterial infection. A monocytosis of 8 to 15 per cent may be seen. The erythrocyte sedimentation rate is usually elevated. In prolonged and severe infection, hyperglobulinemia and hypoalbuminemia in some combination may be seen. Hematuria or pyuria may direct attention to coexisting renal tuberculosis. Marked albuminuria should suggest complicating amyloidosis. A low serum sodium is sometimes found in extensive chronic pulmonary tuberculosis owing to abnormal retention of water and is attributed to inappropriate secretion of antidiuretic hormone. Treatment is water restriction, and the problem disappears as the infection responds to drug therapy. It is important to exclude diabetes because of the higher incidence of tuberculosis in this disease.
other Diagnosis of Pulmonary Tuberculosis.
The diagnosis of tuberculosis is usually suggested by the clinical picture and roent-genographic findings. A strong presumptive diagnosis may often be made on the basis of roent-genographic characteristics alone. A direct sputum smear positive for acid-fast bacteria on microscopy will in the proper setting provide nearly conclusive evidence, and positive findings on microscopy are the rule in extensive or cavitary disease (see Bacteriology in previous article). However, even in advanced disease, failure to demonstrate bacilli on microscopy cannot be used as evidence excluding a diagnosis of tuberculosis.
