In this study, we summarized the etiology, clinical manifestations, and treatment of 68 children with PB. We found that children with airway abnormalities or right ventricular dysfunction after CHS were prone to PB. Anti-infection, corticosteroids, or improving right ventricular function are helpful in treating PB, and FOB is an essential tool for diagnosing and treating PB. For recurrent critically ill PB patients, ECMO assistance is a vital salvage treatment.
During the research span of more than 5 years, we screened 13752 children with CHD. Of the 68 children with PB, 32 had airway abnormalities and 38 had right heart dysfunction, so we should be alert to PB for children with these abnormalities after CHS. The pathology of PB in the airway abnormalities group was characterized by neutrophil infiltration surrounded by fibrin, which is consistent with the performance of type 1 in the PB classification (7). Studies have shown that infection and allergy are the main factors related to the pathogenesis of PB in type 1. Inflammatory stimulation causes tracheal mucosa injury, necrosis, increased mucus secretion, and easily forms mucus plugs to block the airway and accelerate cast formation (8). In addition, normal respiratory flora are generally not pathogenic. However, in the absence of good clearance mechanisms and effective innate or acquired immune responses, these normal airway flora can invade the lower respiratory tract and cause disease (9). In this study, the BALF of all children was sent for pathogenic examination and the incidence of infection was up to 100% in the airway abnormality group. The reason for this may be the combination of the airway abnormalities group with tracheal stenosis, tracheomalacia or tracheospasm, which interferes with normal airway clearance and immune function. Airway surgery can disrupt the airway's filtering and cleaning ability, and pathogens may be more likely to cause airway inflammation and promote the development of PB. Therefore, we believe that, especially in children with airway abnormalities after CHS, more attention should be paid to the prevention and treatment of infections to avoid or improve the occurrence and development of PB. In addition, there were 7 children with a special allergic constitution, which may be a risk factor of type 1 PB in these children.
The present study found that the pathology of PB with right ventricular dysfunction showed a small number of neutrophils and fibrin infiltration, which was consistent with the pathology of type 2 PB (7). Studies have shown that the occurrence and development of type 2 PB are related to abnormal lymphatic circulation (10–11). Children after Fontan or Glenn surgery may be due to the high flow of pulmonary blood vessels or increased pulmonary vascular resistance, which leads to the increase of intrapulmonary vascular exudation and the aggravation of a load of intrapulmonary lymphatic circulation (12–13). Our study also confirmed that some children with right ventricular dysfunction were treated by reducing pulmonary vascular resistance and improving right ventricular function, and their clinical symptoms improved and they were discharged from the hospital. Normally, lymphatic flow is centered and regulated by valves, but dysfunction of lymphatic vessels or injury to the thoracic duct can lead to abnormal blood flow patterns (14–16). In our study, there were 3 cases of chylothorax in the right ventricular dysfunction group, and 2 cases of children with thoracic duct dilatation and valvular insufficiency were caused by increased flow in the thoracic duct after Fontan and PA/VSD correction surgery, respectively. The other patient had chylothorax after Glenn's operation.
Pharmacological treatment is an important treatment for PB. Several studies have pointed out that respiratory infection is closely related to the occurrence of PB (17–18). In this study, the BALF of all children was sent for pathogenic examination, and different pathogens were detected in 41 children. The incidence of infection up to about 60%. Antibiotics is the primary treatment, and should be adjusted in time according to the pathogenic examination results of BALF. Another study pointed out that corticosteroids are therapeutic in PB by mediating the anti-inflammatory effect on eosinophil infiltration (19). In this study, all children were treated with intravenous or oral corticosteroids, combined with budesonide suspension for aerosol inhalation, and most children achieved good treatment results. Additionally, studies suggested that inhaled tissue prothrombin activator (tPA) and uPA can be used to treat PB (20–21). In this study, 18 children with recurrent casts were treated with uPA combined with chymotrypsin inhalation, all of them were relieved, and no side effects were found. In addition to symptomatic treatment, active treatment of the primary disease also needs to be strengthened. For patients with right ventricular dysfunction, reducing pulmonary vascular resistance and increasing ventricular filling pressure may help prevent PB (22–23).
Nonpharmacological treatment includes postural drainage, pulmonary physiotherapy, mechanical ventilation. Among them, FOB to remove foreign bodies and plaster in the bronchi is the most common and effective treatment method (24). All children in this study underwent FOB and BAL to suck the casts causing trachea and bronchi obstruction. Meanwhile, the pathogen test results of BALF can help target the application of antibiotics. In our study, 18 children received two FOBs and 8 received more than two. After FOB, the clinical symptoms of these children were significantly relieved.
Two patients in this study were supported by V-A ECMO after PAS correction and tracheoplasty due to continuous deterioration of the trachea and bronchi with repeated casts. During ECMO assistance, we used anti-infection, nebulized inhalation of acetylcysteine, budesonide, uPA, and chymotrypsin, combined with fiberoptic bronchoscopy, and finally, the two patients were successfully weaned from ECMO. This confirms the effectiveness of pharmacological and nonpharmacological treatment combinations in critically ill children with PB.
Limitations
There were several limitations to this study. Firstly, the retrospective nature of our study suggests that our findings may be subject to selection bias. Moreover, due to the limited number of cases, the number and types of diseases included in this study are limited. Finally, Since the patients in this study were children after CHS, the results cannot be extrapolated to children with other diseases.