According to WHO, there will be 9.87 million new cases of tuberculosis in the world in 2021, and 842,000 new cases of tuberculosis in my country. Tuberculosis seems to be far away, but it is actually close by.
March 24, 2022 is the 27th World Tuberculosis Day, and this year’s WHO campaign theme is: Invest to End TB. Save lives, and my country’s propaganda slogan is: life first, national action, shared health, end tuberculosis.
How to diagnose tuberculosis early? What is the difference and significance of TB-related laboratory tests?
Early detection, standardized treatment, and cure of TB patients are the most important aspects of TB prevention and treatment. How was tuberculosis discovered?
1. See a doctor because of symptoms: People with suspicious symptoms of pulmonary tuberculosis: cough and expectoration of sputum for ≥ 2 weeks, hemoptysis or bloody sputum are the main local symptoms of pulmonary tuberculosis, and those with any of the above symptoms are suspected symptoms of pulmonary tuberculosis By. In addition, chest tightness, chest pain, low-grade fever, night sweats, fatigue, loss of appetite and weight loss are common systemic symptoms in patients with pulmonary tuberculosis.
2. Active screening: people at high risk of developing tuberculosis (such as close contacts of etiologically positive pulmonary tuberculosis patients, HIV-infected patients, and AIDS patients) can carry out active tuberculosis screening; According to the actual situation, active screening of students, supervisors, migrant workers living in a concentrated way, workers of factories and mines, and specific groups in high-incidence areas should be carried out according to local conditions.
3. Health checkup: various health checkup findings (mainly through chest X-ray or chest CT checkup)
So, how should a suspected case of TB be diagnosed?
For those with suspected symptoms of pulmonary tuberculosis or those who need active screening or physical examination, we mainly find patients with suspected pulmonary tuberculosis through chest imaging examination.
The new diagnostic criteria for tuberculosis divides tuberculosis into: 1. Primary tuberculosis; 2. Hematogenous disseminated tuberculosis; 3. Secondary tuberculosis; 4. Tracheal and bronchial tuberculosis; 5 . Tuberculous pleurisy.
One, chest imaging examination
To find pulmonary tuberculosis, it is first necessary to find abnormalities in the lungs through imaging examinations. If there is no abnormality in the lungs, tuberculosis can basically be ruled out. Common chest imaging methods include chest X-ray (chest X-ray), chest CT, etc.
Pros and Cons of Chest X-ray vs. Chest CT:
Chest X-ray: low cost, low radiation dose, convenient (can be bedside), but far less spatial and tissue resolution than chest CT
Chest CT: Compared with chest X-ray, the cost is slightly higher, the radiation dose is slightly higher (but it is a safe dose), and its spatial resolution and tissue resolution are much higher than chest X-ray, especially high-resolution High-rate CT can detect tiny lesions, and the morphological characteristics, density, and relationship with lung tissue and blood vessels of the lesions are very clearly displayed, making the chest CT imaging diagnosis more accurate.
Some studies have shown that the overdiagnosis rate of smear-negative pulmonary tuberculosis by chest X-ray is as high as 21.2% to 45%, indicating that chest X-ray imaging diagnosis has a low diagnostic accuracy for bacterial-negative pulmonary tuberculosis, and the doctor diagnosed Subjective influence is large.
International Tuberculosis Prevention Federation once organized a reading of 1,100 chest radiographs by 90 experts with rich experience in imaging diagnosis from 9 countries. Are there any calcifications on the chest? Do you need treatment? Are there cavities? Could there be tuberculosis? Are the lymph nodes abnormal? Are there any abnormalities on the chest X-ray?) The rate of inconsistency among the responses was 42%, 31%, 28%, 37%, 60%, A surprising 34%.
It can be seen from this that chest X-ray is highly subjective and relatively low in specificity in diagnosing pulmonary tuberculosis. The better spatial and tissue resolution of chest CT greatly improves the accuracy of diagnosis. , but still related to the level of diagnostic physicians’ reading.
1. Primary pulmonary tuberculosis: Mainly manifested as primary lung lesions and intrathoracic lymph node enlargement, or simple intrathoracic lymph node enlargement. Ring enhancement of intrathoracic lymph nodes is a relatively characteristic imaging manifestation of intrathoracic lymph node tuberculosis. Chest CT can find mediastinal lymphadenopathy, but it needs to be differentiated from tumor lymph node metastasis, lymphoma, sarcoidosis, etc.
*Primary pulmonary tuberculosis (intrathoracic lymph node tuberculosis): Mediastinal lymphadenopathy characterized by enhanced ring enhancement.
*Lymphoma: Mediastinal lymphadenopathy (“pins and needles” feature)
*Pulmonary sarcoidosis: symmetrical mediastinal and bilateral hilar lymphadenopathy with homogeneous enhancement
2. Hematogenous pulmonary tuberculosis: Acute hematogenous pulmonary tuberculosis manifests as uniformly distributed miliary shadows of the same size and density in both lungs; subacute or chronic Diffuse lesions of hematogenous disseminated pulmonary tuberculosis are mostly distributed in the upper and middle parts of both lungs, with different sizes and densities, and may have fusion. It needs to be differentiated from other diseases such as welder’s pneumoconiosis and lung metastases.
*Hematogenous pulmonary tuberculosis: uniformly distributed miliary nodules of uniform size and density
*Welder’s pneumoconiosis misdiagnosed as blood-spread pulmonary tuberculosis, diffuse lung disease must be asked for occupational history, and blood-disseminated tuberculosis without fever should be diagnosed with caution
*Lung metastases from thyroid cancer: A 27-year-old woman with diffuse miliary shadows in both lungs was misdiagnosed as blood sows. Because of the absence of fever, the diagnosis was questioned, and the final diagnosis was thyroid cancer lung metastases.
3. Secondary pulmonary tuberculosis: The chest imaging manifestations of secondary pulmonary tuberculosis are diverse. Mild cases are mainly manifested as patches, nodules and streak shadows, or tuberculomas or solitary cavities; severe cases can be manifested as lobar infiltration, caseous pneumonia, multiple cavity formation and bronchial dissemination forming tree-in-bud signs, etc. ;
Lung damage may occur in patients with repeated persistent and progressive progress, the volume of the damaged lung tissue is reduced, and there are multiple fibrous thick-walled cavities, secondary bronchiectasis, or multiple calcifications, etc., adjacent to the hilum and The mediastinal structure was pulled and displaced, the thorax was collapsed, the pleura was thickened and adhered, and other lung tissues appeared compensatory emphysema and bronchial disseminated lesions of different old and new ones.
The most common form of pulmonary tuberculosis, it is easily confused with non-tuberculous mycobacterial infection, pneumonia, lung cancer, pulmonary fungal infection, and other lung diseases.
*Typical secondary pulmonary tuberculosis: lesions in the right upper lung (the posterior segment of the upper apex and the dorsal segment of the lower lobe are the predisposing sites for tuberculosis), the proximal end of the lung is cavitated, the draining bronchus can be seen, and the surrounding area can be seen Scattered stove (satellite stove)
*Multiple cavities mainly in the upper lungs, with positive acid-fast sputum staining, it is actually non-tuberculous mycobacterial lung disease (mycobacterial intracellulare lung disease), misdiagnosed as pulmonary tuberculosis
*Typical tree-in-bud sign with bronchial dissemination in the dorsal segment of the right lower lobe confirms pulmonary tuberculosis (but still needs to be differentiated from other mycoplasma pneumonias and nontuberculous mycobacterial lung diseases)
*Left upper lung lesions, polymorphic and multifocal, misdiagnosed as tuberculosis, but mycoplasma pneumonia (tree fog sign)
*Pulmonary tuberculosis manifested as “reverse halo sign”, which was often described as organising pneumonia, vasculitis and other characteristic imaging manifestations, which is not uncommon in tuberculosis at present.
*It is very common for pneumoconiosis to be misdiagnosed as pulmonary tuberculosis in clinical practice. For diffuse lesions, the inquiries about occupational history must be emphasized
*The air crescent sign is often the characteristic imaging finding of Aspergillus, but can also manifest in tuberculosis. This patient had pulmonary tuberculosis.
4. Tracheal and bronchial tuberculosis: tracheal and bronchial tuberculosis is mainly manifested as irregular thickening of the trachea or bronchial wall, stenosis or obstruction of the lumen, and secondary lung tissue at the distal end of the stenotic bronchus may occur Atelectasis or consolidation, bronchiectasis and other bronchial dissemination lesions.
5. Tuberculous pleurisy: chest imaging can only detect pleural effusion for tuberculous pleurisy, and it is difficult to differentiate it from other pleural effusions such as malignant pleural effusion only from imaging. Diagnostic significance is limited. Encapsulated pleural effusion, pleural hypertrophy, and pulmonary tuberculosis lesions suggest diagnostic significance.
*Chest CT showed a large amount of pleural effusion on the right side, which could not distinguish tuberculous pleural effusion from malignant pleural effusion or other etiologies. Need to puncture fluid for examination or pleural biopsy to confirm the diagnosis.
The above few cases vividly demonstrate the typical imaging manifestations of pulmonary tuberculosis and the objective phenomenon of the same disease and different shadows of the same disease. Although imaging is not the basis for the diagnosis of pulmonary tuberculosis, accurate analysis of the CT imaging manifestations of pulmonary tuberculosis, grasping the imaging characteristics of pulmonary tuberculosis, and familiarity with the imaging manifestations of atypical pulmonary tuberculosis are important means for us to improve the imaging diagnosis of pulmonary tuberculosis.
II. Etiological examination
How do we diagnose suspected TB in the lungs on a chest X-ray or chest CT? In theory, the detection of TB bacteria is the diagnosis of pulmonary tuberculosis, which is also what we call the etiological examination.
Etiological testing first requires the selection of appropriate test specimens. For pulmonary tuberculosis, the simple and easy specimen is the sputum specimen, which can be a qualified sputum specimen coughed up. If there is no sputum, Sputum can be induced by nebulization of hypertonic saline.
In infants or children, gastric samples are recommended due to the inability to collect sputum or bronchial lavage fluid. For patients who really cannot collect sputum specimens, and given the relatively low positive rate of sputum specimens, invasive collection techniques can be used to obtain specimens from patients with negative sputum specimens, such as bronchoscopy, fine needle aspiration, and lung biopsy tissue specimens. related pathogenic tests.
For tuberculosis other than pulmonary tuberculosis, specimens from corresponding parts can be obtained for etiological testing, such as pleural effusion, ascites, cerebrospinal fluid, purulent secretions, puncture fluid, urine, feces, biopsy tissue Wait.
After obtaining specimens, the main methods of laboratory testing for tuberculosis pathogens are as follows:
1. Sputum smear microscopy: no matter dead bacteria, live bacteria, Mycobacterium tuberculosis (Mtb) and non-tuberculous Mycobacterium (NTM) can be detected. The sensitivity is low, and each milliliter of sputum sample contains at least 5,000 to 10,000 acid-fast bacteria before it can be detected.
2. Mycobacterial culture: higher sensitivity than smear, 10 to 100 Mtb can be detected in sputum samples per milliliter, which is the gold standard for the diagnosis of pulmonary tuberculosis, but it is time-consuming. long, usually 8 weeks. After the culture is positive, strain identification can be done to distinguish Mtb from NTM, and further drug sensitivity tests can be performed to guide clinical medication.
3. Mycobacterium tuberculosis nucleic acid detection (molecular biological detection): take clinical specimens as the detection object, Mtb-related genes as diagnostic markers, complete the detection of whether the specimen contains Mtb nucleic acid or drug resistance A series of detection methods for genes.
Common detection techniques include:
1) Real-time fluorescence quantitative PCR: including Gene Xpert MTB/RIF and MTB complex nucleic acid detection kit, etc.
2) Isothermal (isothermal) amplification technology: including loop-mediated isothermal amplification technology (LAMP), cross-primer detection technology (CPA) and real-time fluorescent nucleic acid isothermal amplification detection technology (SAT) , among which SAT detects Mtb RNA, which is easily degraded in the environment. Generally, it can be regarded as the existence of live bacteria in the specimen after contamination is excluded.
3) Probe reverse hybridization technology: including linear probe (HAIN) and gene chip, mainly used for isoniazid and rifampicin resistance gene detection and bacterial species identification.
4) Probe dissolution curve technology: Currently, it is mainly used for the detection of resistance to isoniazid, rifampicin, ethambutol and quinolones.
5) Gene sequencing technology
The above various molecular detection methods have different detection principles, and the selected target genes are different (part of the detection is for the Mycobacterium tuberculosis complex). Among them, Gene Xpert Mtb/RIF, HAIN , LAMP is recommended by WHO.
Theoretically, positive results are the detection of Mycobacterium tuberculosis nucleic acid, but in practice, the detection of very low or low copy number positive results still needs to be combined with clinical data and immunological examinations. False positives caused by specimen contamination and other factors were excluded.
Three, immunological examination
It is mainly used to detect whether there is tuberculosis infection in the body, and it is impossible to distinguish whether it is sick or not. It can be used for the diagnosis of latent tuberculosis infection and the differential diagnosis of tuberculosis.
1. Tuberculosis cell immunology examination, including:
1) Tuberculin skin test (TST, the current PPD test), which is simple and inexpensive, but can be affected by BCG vaccination and non-tuberculous mycobacteria infection resulting in false positives .
2) Tuberculosis gamma interferon release assay (IGRA): QFT-G and T-SPOT kits are commonly used internationally. At present, there are many IGRA kits on the market in China. IGRA has better sensitivity and specificity than PPD, is not affected by BCG vaccination, and only has cross-antigens with 5 non-tuberculous mycobacteria, but it is more expensive. Regardless of the IGRA kit, laboratory quality control is very important to avoid false negative results.
3) Recombinant Mycobacterium tuberculosis fusion protein (EC) skin test: ESAT-6 and CFP-10 (same specific antigens as IGRA) were used as specific antigens for skin test, which were similar to T -SPOT has high consistency.
2. Tuberculosis humoral immunological examination: tuberculosis antibodies, etc.
On the whole, the TB immunology test mainly uses in vitro antigen and antibody tests to determine whether the body is infected with TB, and cannot distinguish whether it has TB.
In general, a positive sign of tuberculosis infection, a negative sign of no tuberculosis infection, but it is affected by the immunity of the body and the influence of the test kit and laboratory quality control, especially the clinical false negative and false positive of the tuberculosis antibody At present, the WHO does not recommend TB antibodies as TB infection and auxiliary diagnosis.
PPD and IGRA can be used as auxiliary diagnostic tools for tuberculosis infection and tuberculosis. It should be noted that positive results do not mean disease. Laboratory quality control effects lead to false negatives.
4. Pathological examination
If the diagnosis is still not clear by the above methods, it is necessary to obtain tissue specimens through percutaneous lung biopsy, transbronchoscopy lung biopsy or surgical biopsy, and diagnose by pathology.
In general, for most diseases, pathological diagnosis is the gold standard, but for infectious diseases, etiology is the gold standard for diagnosis. The typical pathological manifestations of tuberculosis are granulomas with caseous necrosis.
Pathology often needs to be differentiated from other granulomatous diseases, such as other infectious granulomatous nontuberculous mycobacterial infections, fungal diseases (Cryptococcus, Aspergillus, Mucor, Histoplasma etc.), parasitic diseases, leprosy, etc.; and other non-infectious granulomatous diseases such as sarcoidosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, Crohn’s disease, foreign body granuloma, etc. identify.
Special staining (note that positive acid-fast staining still cannot differentiate tuberculosis from nontuberculous mycobacteria), and molecular pathology can help in the differential diagnosis.
V. Others: Adenosine Dehydrogenase (ADA)
Elevated pleural effusion adenosine dehydrogenase (ADA) (usually ≥ 40U/L as the diagnostic standard, and the cut off points reported in different literatures are different) is sensitive and specific for the diagnosis of tuberculous pleurisy Both sexes are high and can be used as an indicator for the clinical diagnosis of tuberculous pleurisy.
Six. Diagnostic anti-tuberculosis therapy
Because the positive rate of tuberculosis etiology is less than 50% (the positive rate of sputum smear is less than 30%), and the acceptance of invasive tests such as lung biopsy is not high, the clinical Commonly, a clinical diagnosis is given after a comprehensive discussion of clinical symptoms + chest imaging manifestations + tuberculosis immunological examination and exclusion of other diseases, and the diagnosis of pulmonary tuberculosis can be confirmed by diagnostic anti-tuberculosis treatment.
The author of this article: Yang Chengcheng, Deputy Chief Physician, Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital
Typesetting: Meichao
Image source: Author provided
Title image: Zhanku Hailuo
References:
1.Global tuberculosis report 2021
2. Diagnosis of Pulmonary Tuberculosis-Health Industry Standard of the People’s Republic of China, WS288-2017
3. TuberculosisClassification of Diseases – Health Industry Standard of the People’s Republic of China, WS196-2017
4. Expert consensus on pathological diagnosis of tuberculosis in China-2017
5. Expert consensus on molecular diagnosis of tuberculosis etiology-2018
6. Technical Guidelines for Tuberculosis Prevention and Control in China-2021
7. Pay attention to the imaging characteristics and key points of bacterial-negative pulmonary tuberculosis-2018