Progress in gene research and diagnosis and treatment of diffuse panbronchiolitis

Diffuse panbronchiolitis (DPB) was first proposed in 1969 by Japanese scholars Yamanaka, Hiroshi, and Miki, which is different from chronic obstructive pulmonary disease (COPD). It is a chronic inflammatory disease of the airway of diffuse respiratory bronchi of the two lungs. The affected part is mainly the terminal airway at the distal end of the respiratory bronchioles. The inflammatory lesions are diffusely distributed and involve the respiratory bronchioles. The whole layer is called DPB. Prominent clinical manifestations are coughing, coughing, and shortness of breath after activity. Severe cases can cause respiratory dysfunction. Clinically easy to be confused with other chronic airway diseases. The author reviewed the relevant literature in recent years, and summarized the latest research progress on diffuse panbronchiolitis as follows:

Progress in gene research and diagnosis and treatment of diffuse panbronchiolitis

Progress in diagnosis
In 1995 and 1998, the Japanese Ministry of Health and Welfare revised and promulgated the clinical diagnostic criteria for DPB. The current clinical diagnosis in China still refers to this standard. Diagnostic projects include mandatory and reference projects.
Required items:

• Persistent coughing, coughing and difficulty breathing during activities;
• Combined with chronic sinusitis or a past history;
• Chest X-ray see diffuse diffuse distribution of the two lungs in the shape of nodular shadows or chest CT see diffuse lobular central granule-like nodular shadows of the two lungs.

Reference item:

• Chest hearing diagnosis of continuous wet voice;
• One second forced expiratory volume accounted for the predicted value percentage FEV1 <70% predicted value or FEV1/FVC <70%, VC <80% predicted value, RV>150% predicted value, PaO2<80mmHg (under indoor air conditions)
• Serum condensation test (CHA) titer increased (1:64 or more).

Diagnosis: Meet the required items 1, 2, 3, plus more than 2 items in the reference project. General diagnosis: Meets required items 1, 2, and 3. Suspicious diagnosis: Meets required items 1, 2. Typical cases can be diagnosed by X-ray and HRCT; if the clinical and imaging changes are not typical, lung biopsy should be taken. Lung biopsy is best for thoracoscopic or thoracoscopic surgery.

Pathological manifestation
The pathological features of humans have been described very early. Gross anatomy usually over-inflate the lungs and may not collapse after biopsy. Light yellow nodules with a diameter of 2-3 mm are often seen in the central region of the lobules of the lungs. In typical cases, foamy macrophages, lymphocytes, and plasma cells accumulate in the walls of the respiratory bronchioles, alveolar ducts, and alveoli. As the disease progresses, respiratory bronchial lumen stenosis occurs, and foam-like macrophages accumulate in the bronchial wall and tube. Bronchial and bronchiectasis also occur, but the degree of expansion is not as pronounced as idiopathic bronchiectasis. Liu Hongrui et al. performed a pathological section analysis of thoracoscopic or open lung biopsy specimens of DBP patients in China. It was found that there were many fine gray-white nodules distributed on the surface of the lungs, and there were fine sand-like and granular-like unevenness. The extensive bronchioles were observed on the cut surface. Central nodules, sometimes bronchiectasis.
Microscopic histopathological features:

• DPB is localized to the bronchioles and respiratory bronchioles, while other areas of lung tissue can be completely normal;
• The main feature is bronchiolitis;
• Characteristic changes to bronchioles, respiratory bronchiol inflammation stenosis, obstruction of bronchioles; alveolar septum and interstitial visible foam-like cells change. The bronchioles and respiratory bronchiolitis are characterized by thickening of the wall, lymphocytes, plasma cells and histiocytes.

2. The value of HRCT in the diagnosis of diffuse panbronchiolitis
HRCT showed that DBP showed a small-leaf central distribution of granular nodules with tree buds. The nodule size was generally 2-5 cm, no fusion tendency, and the nodules were not connected to the pleura. You Zhengqian found that the tree buds and the diffuse fine miliary granules appeared together, and the distribution range was relatively diffuse, often involving multiple lung lobes on both sides, mostly in the middle, lower, and lower lung fields. But less common. Wide range of lesions is a major feature of this disease. Even if other pulmonary infectious diseases have tree buds, the scope is far less than the disease.
Gu Yu and other HRCT with ventral HRCT scan also found that 2 cases were distributed in the two lungs with a diameter of 2mm micro-nodules, the following lungs are more, small and blurred edges, located in the center of the leaflet Inside, around the lobular center of the bronchioles and arteries, near the pleura, they reflect inflammation around the bronchioles, which is a typical lobular central air cavity nodule. In one case, bronchiectasis and thickening of the bronchioles were seen. The use of expiratory scanning is because the gas content in the lungs is significantly reduced during exhalation, and the transmittance of the normal lung field is uniform or stepwise. When the small airway lumen is narrowed or occluded, the gas in the corresponding alveoli cannot be exhaled. The flaky low density is called air retention. Therefore, the HRCT in diffuse panbronchiolitis reflects the local ventilation function of the lung to some extent by expiratory scanning.
According to the classification of Akfia et al, the nodule central nodule and tree bud sign belong to type 1 and type 2, suggesting that after treatment, some lesions are still reversible. Studies have shown that in patients treated with low-dose erythromycin, the number and extent of lobular central nodules and "tree buds" are significantly reduced. Zhang Hong et al. reviewed the 6 cases after treatment, which confirmed this conclusion. When the small annular shadow of bronchiectasis and wall thickening appeared, it further developed into cystic and columnar expansion of the proximal bronchus, indicating that the lung lesion has been Enter the irreversible stage.

Progress in treatment
Since l984, Kudo has obtained a positive therapeutic effect since the use of erythromycin (ETM) low-dose, long-term dosing therapy. 14-membered macrolides led by erythromycin mainly inhibit the secretion of water by inhibiting mucin and blocking chloride channels, thereby reducing excess secretion of airways; by inhibiting neutrophils and vascular endothelium and airway epithelium Adhesion, and block cytokines such as interleukin-8 (IL-8) secreted by airway epithelial cells, alveolar macrophages, and neutrophils, thereby inhibiting local aggregation of neutrophils to inflammation; The activity of granulocytes itself, thereby reducing the production of airway epithelial damage factors such as peroxides and elastase. It is now clear that erythromycin inhibits the expression of neutrophil migration factors such as IL-8 in mRNA expression levels. It also has an inhibitory effect on the activity of the transcriptional regulator AP-1, which is involved in mRNA expression. Except for some cases of bronchodilation, almost all cases have different degrees of improvement in various clinical symptoms after 4 to 3 months of treatment. Relapsed cases after withdrawal of the drug are still effective. The amount of new macrolides per administration is small, and the number of daily administrations is also reduced (1-2 times a day), so the adverse reaction rate is significantly lower than that of ETM. Other l4-membered ring macrolides such as erythromycin (CTM) and roxithromycin (RTM) have the same efficacy as ETM. Relapsed cases after withdrawal of the drug are still effective. The 16-membered ring macrolides are ineffective against DPB, and the a5-membered ring azithromycin (ATM) has also achieved good results.
It is still unclear how long the best course of treatment is appropriate. In Japan, the general course of treatment is more than 2 years. A small-scale study of some Japanese patients shows that patients with severe conditions, especially those with concurrent bronchiectasis, should be appropriately extended. A study in Chinese patients found that most patients experienced more symptoms within a few weeks after taking the drug, including sputum volume, difficulty breathing, and asthma. The following indicators that can confirm the improvement of lung function can be detected within 4 weeks, including one-second forced expiratory volume (FEV1), forced vital capacity (FVC), residual gas volume (RV), and arterial oxygenation, but excluding carbon monoxide diffusion. Quantitative (DLCO) (this indicator is normal in most patients). After 8.6 months of mean treatment (erythromycin 250 mg, 2/day), the above indicators increased by 59.2%, 47%, 17%, 16.7% and 21%, respectively.