Pulmonary tuberculosis is tuberculosis that occurs in the lung tissue, trachea, bronchi, and pleura.
Etiology
The pathogen of tuberculosis is Mycobacterium tuberculosis complex, including Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, and Mycobacterium microti. More than 90% of the pathogens causing human pulmonary tuberculosis are Mycobacterium tuberculosis. Typical Mycobacterium tuberculosis is a slender, slightly curved bacillus with round ends. Mycobacterium tuberculosis in sputum specimens can be T-shaped, V-shaped, and Y-shaped, as well as filamentous, spherical, and clavate. Mycobacterium tuberculosis is red in acid-fast staining and can resist the decolorization effect of acid alcohol, so it is also termed acid-fast bacillus. Mycobacterium tuberculosis has strong resistance to dryness, cold, acid, and alkali. It can survive for several months or years in a dry environment. In dark and humid indoors, Mycobacterium tuberculosis can survive for several months. Mycobacterium tuberculosis is sensitive to ultraviolet rays, and Mycobacterium tuberculosis in sputum can be killed in 2 - 7 hours under direct sunlight. Ultraviolet lamps are often used for disinfection in laboratories or wards. A 10W ultraviolet lamp 0.5 - 1 m from the irradiated object for 30 minutes has a significant bactericidal effect.
Mycobacterium tuberculosis is an obligate aerobe with high nutritional requirements. The generation time of Mycobacterium tuberculosis is 14 - 20 hours, and the culture time is generally 2 - 8 weeks. The composition of Mycobacterium tuberculosis is complex, mainly lipids, proteins, and polysaccharides. Lipids account for 50% - 60% of the total, in which ceroids account for about 50%, which is related to tissue necrosis, caseous liquefaction, cavitation, and tuberculous allergic reactions in tuberculosis. Bacterial protein exists in bound forms and is the main component of tuberculin, inducing skin allergic reactions. Polysaccharides are related to immune responses such as serum reactions.
Figure 1 Natural progression of pulmonary tuberculosis
Pathology
The basic pathological changes of tuberculosis are inflammatory exudation, hyperplasia, and caseous necrosis. The pathological process of tuberculosis is characterized by simultaneous occurrence of destruction and repair. Therefore, the three pathological changes often exist simultaneously, or one of them may be dominant, and they can transform into each other. Lesions dominated by exudation mainly occur in the early stage of tuberculous inflammation or when the lesions deteriorate or relapse, and can be manifested by local infiltration of neutrophils, subsequently replaced by macrophages and lymphocytes. Lesions dominated by hyperplasia are manifested by typical tuberculous nodules with a diameter of about 0.1 mm; after fusion, they can be seen by the naked eye and are composed of lymphocytes, epithelial cells, Langhans cells, and fibroblasts. Caseous necrosis may occur in the middle of tuberculous nodules. Multinucleated giant cells formed by the aggregation and fusion of numerous epithelial cells are termed Langhans giant cells. Lesions dominated by hyperplasia occur when the body has strong resistance and the lesions are recovering. Lesions dominated by caseous necrosis often occur when there are strong virulence of Mycobacterium tuberculosis, excessive bacteria, enhanced hypersensitivity reaction, and low resistance. Caseous necrosis lesions are red-stained, structureless granules with high lipid content in microscopy, and are light yellow and caseous in visual inspection, so they are termed caseous necrosis.
Clinical manifestations
Cough and expectoration for ≥ 2 weeks, bloody sputum, or hemoptysis are the suspected symptoms of pulmonary tuberculosis.
Pulmonary tuberculosis has a slow onset in most patients, and some patients may have no obvious symptoms and are only found during chest imaging examinations. As the lesion progresses, cough, expectoration, bloody sputum, and hemoptysis may occur, and some patients may have symptoms of recurrent upper respiratory tract infection. Pulmonary tuberculosis can also cause systemic symptoms, such as diaphoresis, fatigue, intermittent or continuous low-grade fever in the afternoon, anorexia, and emaciation. Female patients may have menstrual disorders or amenorrhea. Few patients have an acute onset, with moderate to high fever, and some patients have mild or severe dyspnea.
Patients with lesions in the pleura may have symptoms such as irritating cough, thoracodynia, and dyspnea.
Lesions in the trachea and bronchi often present long-term irritating cough. If bronchial lymphatic fistula forms and ruptures into the bronchi or bronchial stenosis, wheezing or dyspnea may occur.
Few patients may be accompanied by tuberculous hypersensitivity syndrome, including erythema nodosum, herpetic conjunctivitis, and keratitis.
Pulmonary tuberculosis in children may also present developmental delay. In primary pulmonary tuberculosis of children, the trachea or bronchi may be compressed by enlarged tracheal or parabronchial lymph nodes, or bronchial tuberculosis of lymphatic fistula may occur, and patients often have wheezing.
When complicated by extrapulmonary tuberculosis, symptoms of the involved organ may occur.
In the early stage, the pulmonary signs are not obvious. When the lesion enlarges, local percussion reveals dullness, and tubular breath sounds can be heard on auscultation. When complicated by infection or bronchiectasis, moist crackles can be heard.
When the lesion involves the trachea and bronchi and causes local stenosis, fixed and localized wheezing can be heard on auscultation. When atelectasis occurs, the trachea may shift to the involved side, the involved thorax may collapse, the intercostal space may narrow, percussion may reveal dullness or flatness, and breath sounds may weaken or disappear on auscultation.
When the lesion involves the pleura, pleural friction rub can be heard on the affected side in the early stage. As the pleural effusion increases, the affected thorax is full, the intercostal space widens, the trachea shifts to the healthy side, percussion reveals dullness to flatness, and breath sounds weakens or disappear on auscultation. After the effusion decreases or disappears, pleural thickening and adhesion can occur, the trachea may shift to the involved side, the involved thorax may collapse, the intercostal space may narrow, respiratory movement may be restricted, percussion may reveal dullness, and breath sounds may weaken on auscultation.
Primary pulmonary tuberculosis may be accompanied by superficial lymphadenopathy. Hematogenous disseminated pulmonary tuberculosis may be accompanied by hepatosplenomegaly and choroidal nodules in the fundus. Children patients can have miliaria on the skin.
Classification and imaging examination
Pulmonary tuberculosis can occur in the lungs, trachea, bronchi, pleura, and other parts. According to the lesion site, it is divided into 5 types.
Primary pulmonary tuberculosis
Primary pulmonary tuberculosis includes primary complex and intrathoracic lymph node tuberculosis, mostly in children and adolescents, with no symptoms or mild symptoms. Most patients have a history of tuberculosis contact. The tuberculin test is mostly strongly positive. The chest x-ray film shows doughnut opacity shadow; that is, the primary lesion, involvement of draining lymph nodes (lymphangitis), and enlarged hilar lymph nodes form typical primary complex. The primary lesion can generally subside quickly and may not leave any traces. If chest x-ray film only shows hilar lymph node enlargement, it is diagnosed as intrathoracic lymph node tuberculosis. Hilar lymph node tuberculosis can be mass with clear edges and high density or inflammation with unclear edges and infiltration.
Figure 2 Schematic diagram of primary complex
Hematogenous disseminated pulmonary tuberculosis
Hematogenous disseminated pulmonary tuberculosis can be divided into acute, subacute, and chronic hematogenous disseminated pulmonary tuberculosis. Acute hematogenous disseminated pulmonary tuberculosis (acute miliary pulmonary tuberculosis) is more common in infants, young children, and adolescents, especially children with significantly decreased immunity resulting from malnutrition, infectious diseases, and long-term use of immunosuppressants. It is often accompanied by primary pulmonary tuberculosis. Acute miliary pulmonary tuberculosis can also occur in adults, with acute onset, continuous high fever, and severe symptoms. Generalized enlarged superficial lymph nodes, hepatosplenomegaly, and sometimes pale red miliary rashes on the skin can be found. Meningeal irritation symptoms such as nuchal rigidity can occur. About 1/3 of patients have choroidal nodules on fundus examination. Acute hematogenous disseminated pulmonary tuberculosis is manifested by homogeneous miliary opacities of the same size and density in both lungs. Subacute and chronic hematogenous disseminated pulmonary tuberculosis have slow onset and mild symptoms; imaging shows diffuse lesions in both lungs, mostly in the upper and middle parts of both lungs, with different sizes and densities, and may have fusion; and fresh exudation coexists with old induration and calcified lesions.
Figure 3 Acute miliary pulmonary tuberculosis on CT
Miliary opacities of the same size and density are homogeneously distributed in both lungs.
Secondary pulmonary tuberculosis
Secondary pulmonary tuberculosis is the most common pulmonary tuberculosis in adults. The chest imaging manifestations are diverse, including infiltrative pulmonary tuberculosis, caseous pneumonia, tuberculoma, chronic fibrocavitary pulmonary tuberculosis, and destroyed lung.
Infiltrative pulmonary tuberculosis
Infiltrative exudative tuberculosis lesions and fibrocaseous proliferative lesions often occur in the apex of the lung and under the clavicle. Imaging shows small patchy or punctate opacities, which can fuse and form cavities. Exudative lesions are easilyresorbed, while fibrocaseous proliferative lesions are resorbed very slowly and may remain unchanged for a long time.
Figure 4 Infiltrative pulmonary tuberculosis on CT
Exudative opacities in both upper lungs running along the bronchi and cavities with smooth inner walls can be seen.
Caseous pneumonia
Caseous pneumonia often occurs in patients with weakened immunity and weak constitution and infection with Mycobacterium tuberculosis or lymph node-bronchial fistula, and is caused by entry of large amounts of caseous substances in the lymph nodes to the lungs through the bronchi. The imaging of lobar caseous pneumonia shows lobar homogeneous ground-glass opacity, the dissolution areas appear gradually and are manifested by mottled cavities, disseminated lesions can occur, and mycobacterium tuberculosis can be detected in the sputum. Lobular caseous pneumonia have milder symptoms than lobar caseous pneumonia; chest x-ray shows lobular patchy disseminated lesions, mostly in the middle and lower parts of both lungs.
Figure 5 Caseous pneumonia on CT
A large patchy consolidation in the upper right lung, bronchial inflation sign, and local calcification can be seen.
Tuberculoma
Tuberculoma is mostly formed by the resorption of caseous lesions and the encapsulation by the surrounding fibrous membrane or the healing of caseous cavities, with a diameter of 2 - 4 cm, mostly less than 3 cm. There are calcification or cavities formed by liquefactive necrosis in tuberculoma. More than 80% of tuberculomas have satellite lesions, which can be used for diagnosis and differential diagnosis.
Chronic fibrocavitary pulmonary tuberculosis and destroyed lung
The characteristics of chronic fibrocavitary pulmonary tuberculosis and destroyed lung are long course of disease, recurrent progression and deterioration, severe damage to lung tissue, severely impaired lung function, bilateral or unilateral fibrous thick-walled cavities and extensive fibrous hyperplasia, reduced volume of the affected lung tissue, traction and displacement of adjacent hilar and mediastinal structures, chest collapse, pleural thickening and adhesion, compensatory emphysema in other lung tissues, and bronchial disseminated lesions.
Tracheobronchial tuberculosis
Tracheobronchial tuberculosis is mainly manifested by irregular thickening of the tracheal or bronchial wall and stenosis or obstruction of the lumen. Secondary pulmonary atelectasis or consolidation in distal stenotic bronchus, bronchiectasis, and bronchial disseminated lesions in other parts may occur.
Tuberculous pleurisy
Tuberculous pleurisy is divided into dry pleurisy and exudative pleurisy. Dry pleurisy is an early pleural inflammatory reaction and usually has no obvious imaging manifestations. Exudative pleurisy is mainly manifested by pleural effusion that can present little or excessive free effusion or localized effusion in any part of the pleural cavity; in patients with slow resorption, pleural thickening and adhesion are often accompanied, and exudative pleurisy can also evolve into pleural tuberculoma and empyema.
Laboratory examination
Bacteriological examination
Smear microscopy is positive, Mycobacterium culture is positive, and the strain is identified as Mycobacterium tuberculosis complex.
Molecular biological examination
Mycobacterium tuberculosis nucleic acid test is positive.
Pathological examination
Pathological changes are manifested by epithelioid granulomatous inflammation, and necrotic and non-necrotic granulomas of varying sizes and numbers can be seen in optical microscopy. Granulomas are formed by the fusion of epithelioid nodules. Typical tuberculosis lesions are composed of fused epithelioid nodules, caseous necrosis is in the center, peripheral Langhans multinucleated giant cells can be seen, and the outer layer is lymphocyte infiltration and proliferated fibrous connective tissue. In order to prove tuberculous lesions, it is necessary to find pathogens in the lesions. Histopathology can usually use acid-fast staining. After the section is stained, red-stained, clavate bacilli with blunt and slightly curved ends can often be found in the center of the necrotic area or at the junction of the necrotic area and the epithelioid granuloma in microscopy; in Auramine-Rhodamine fluorescent staining, the bacilli can also be found in fluorescent microscopy. The polymerase chain reaction (PCR) can be used to detect the DNA of Mycobacterium tuberculosis in paraffin-embedded tissues and differentiate it from other acid-fast bacilli. In some old tuberculosis lesions, there are only coagulative necrosis and fibrotic lesions; when the Mycobacterium tuberculosis is not found in acid-fast staining, PCR can be used to detect the DNA of Mycobacterium tuberculosis. PCR has high sensitivity and specificity and is helpful for confirmation of the diagnosis.
Immunological examination
Tuberculin skin test is moderately positive or strongly positive, interferon-γ release test is positive, and Mycobacterium tuberculosis antibody is positive.
Electronic bronchoscopy
Electronic bronchoscopy is often used in the diagnosis of bronchial tuberculosis and lymph node-bronchial fistula. Bronchial tuberculosis is manifested by mucosal hyperemia, ulcers, erosions, hyperplasia, scar formation, and bronchial stenosis. Tissues can be obtained at the lesion site for pathological examination and Mycobacterium tuberculosis culture. For pulmonary tuberculosis lesions, secretions or lavage fluid can be collected for pathogen examination, and specimens can also be obtained through transbronchial lung biopsy for examination.
Diagnosis
The diagnosis of pulmonary tuberculosis is mainly based on etiological examination, including bacteriology and molecular biology, in combination with epidemiology, clinical manifestations, chest imaging, auxiliary examinations, and differential diagnosis. The etiological and pathological results are the basis for definite diagnosis.
In the diagnosis of pulmonary tuberculosis in children, in addition to sputum pathogen examination, gastric juice pathogen examination should also be emphasized.
Differential diagnosis
Infiltrative pulmonary tuberculosis should be differentiated from infectious lung diseases such as bacterial pneumonia, pulmonary mycosis, and pulmonary parasitosis. Further differentiation can be achieved through detailed medical history data, etiological examination, and treatment response.
Tuberculoma should be differentiated from peripheral lung cancer, inflammatory pseudotumor, pulmonary hamartoma, and pulmonary sequestration. Peripheral lung cancer can often be diagnosed by percutaneous lung biopsy or transbronchial lung biopsy and pathological examination. Inflammatory pseudotumor is an inflammatory granulomatous lesion with unknown etiology, often has a history of chronic pulmonary infection, and the lesion can gradually shrink after anti-infection treatment. Pulmonary hamartoma is often an isolated lesion, and shows a popcorn opacity. Pulmonary sequestration is more common in young individuals, and can be asymptomatic for a long time without pulmonary infection; the lesion is prone to occur in the posterior basal segment of the lower lobe of the lung, and is more common in the lower left lung; contrast-enhanced CT can show separate blood supply.
Hematogenous disseminated pulmonary tuberculosis should be differentiated from bronchoalveolar carcinoma, pulmonary hemosiderosis, and diffuse interstitial lung disease.
Bronchial lymph node tuberculosis should be differentiated from central lung cancer, lymphoma, and sarcoidosis. Usually, it is necessary to take a biopsy through bronchoscopy or endoscopic ultrasound for a definite diagnosis.
Tuberculosis cavity should be differentiated from cancerous cavity, pulmonary cyst, and cystic bronchiectasis. The wall of cancerous cavity is mostly irregular, and nodular protrusions can be seen in the cavity; there are no satellite lesions around the cavity, and the cavity increase rapidly in size. Pulmonary cyst is congenital abnormalities of lung tissue, mostly in the upper lung field; when complicated with infection, a fluid level can be seen in the cavity, and there are no satellite lesions; when not complicated with infection, it can be asymptomatic for many years, and the lesion remains unchanged for many years. Cystic bronchiectasis mostly occurs in the middle and lower lung fields of both lungs; patients often have a history of excessive purulent expectoration and hemoptysis; thin-section CT is helpful for diagnosis.
Treatment
Treatment of newly diagnosed active pulmonary tuberculosis (including smear-positive and smear-negative pulmonary tuberculosis)
Daily regimen is isoniazid, rifampicin, pyrazinamide, or ethambutol once a day for 2 months in the intensive phage, followed by isoniazid or rifampicin once a day for 4 months in the continuation phase.
Intermittent regimen is isoniazid, rifampicin, pyrazinamide, or ethambutol once every other day or 3 times a week for 2 months in the intensive phase, followed by isoniazid or rifampicin once every other day or 3 times a week for 4 months in the continuation phase.
Retreatment of smear-positive pulmonary tuberculosis
Daily regimen is isoniazid, rifampicin, pyrazinamide, streptomycin, or ethambutol once a day for 2 months in the intensive phase, followed by isoniazid, rifampicin, or ethambutol once a day for 6 - 10 months in the continuation phase.
Intermittent regimen is isoniazid, rifampicin, pyraclostrobin, streptomycin, or ethambutol once every other day or 3 times a week for 2 months in the intensive phase, followed by isoniazid, rifampicin, or ethambutol once every other day or 3 times a week for 6 months in the continuation phase.
Treatment of multiple drug resistant pulmonary tuberculosis
Group 1 medications are first-line oral anti-tuberculosis drugs, including Isoniazid, rifampicin, ethambutol, pyrazinamide, and rifabutin.
Group 2 medications are anti-tuberculosis injections, including kanamycin, amikacin, capreomycin, and streptomycin.
Group 3 medications are fluoroquinolones, including moxifloxacin, levofloxacin, and ofloxacin.
Group 4 medications are oral antibacterial second-line anti-tuberculosis drugs, including ethionamide, prothionamide, cycloserine, terizidone, and para-aminosalicylic acid.
Symptomatic treatment
The general symptoms of pulmonary tuberculosis quickly relieve and subside in medication therapy, and no special treatment is required. Hemoptysis is a common symptom of pulmonary tuberculosis. Generally, in mild hemoptysis, bed rest is needed, and medications such as aminocaproic acid, aminomethylbenzoic acid, etamsylate, and carbazochrome can be used. In severe hemoptysis, the treatment regimen is posterior pituitary hormone intravenously 5 - 10U diluted with 40ml of 25% glucose solution for 15 - 20 minutes, followed by posterior pituitary hormone diluted with 5% glucose solution intravenously at a rate of 0.1U/(kg.h). Posterior pituitary hormone constricts arterioles, and reduces the amount of blood in the pulmonary circulation, thereby achieving a good hemostatic effect. Posterior pituitary hormone is contraindicated in patients with hypertension, coronary atherosclerotic heart disease, or heart failure, and in pregnant women. Bronchial artery embolization can be used for massive hemoptysis caused by bronchial artery damage.
Glucocorticoids
Glucocorticoids are only used for patients with severe tuberculosis, and must be used under effective anti-tuberculosis treatment. The dose depends on the condition. The general regimen is prednisone orally 20 mg per day once a day for 1 - 2 weeks, then the dose is gradually reduced by 5 mg per week, and the course of treatment is 4 - 8 weeks.
Immunotherapy
Immune preparations can be used to regulate the immune status of the body, so that the body can generate an appropriate immune response to the disease, thereby preventing and treating the disease. Currently, common immunotherapies and immune preparations include Mycobacterium vaccae for injection, cytokines (IL-2, γ-interferon), and active thymus extracts (thymosin or thymopentin).
Surgical treatment
Surgical treatment is indicated in patients with ineffective medication treatment, multidrug-resistant thick-walled cavities, large caseous lesions, tuberculous empyema, bronchopleural fistulas, or massive hemoptysis.
Prevention
BCG vaccination
It is generally believed that BCG vaccination has a poor effect on preventing pulmonary tuberculosis in adults, but it has a good effect on preventing tuberculous meningitis and miliary tuberculosis that often occur in children. After BCG vaccination, newborns still need to be isolated from patients with pulmonary tuberculosis.
Prophylactic treatment
Prophylactic treatment is mainly used in high-risk populations susceptible to Mycobacterium tuberculosis infection, including HIV-infected patients; close contacts of smear-positive pulmonary tuberculosis patients; patients with untreated pulmonary fibrous lesions, silicosis, diabetes, or long-term use of glucocorticoids or immunosuppressants; drug addicts, malnourished individuals; and children and adolescents with nodules ≥15mm in diameter in tuberculin test. The treatment plan is isoniazid 300mg in adults, 4 - 8mg/kg in children, once a day for 6 - 9 months; rifampicin plus isoniazid once a day for 3 months; or rifapentine plus isoniazid 3 times a week for 3 months.