Protracted bacterial bronchitis (PBB) is a recently defined respiratory disease in children and is described in a recent issue of the Lancet respiratory journal by Dr Chang from the Respiratory and Sleep Unit at the Children’s Medical Research Centre in Queensland, Australia. Teaching you about PBB In Australia, PBB is the most common cause of respiratory outpatient visits for children with chronic wet cough. Because it is a precursor disease to other chronic septic diseases of the respiratory system, such as bronchiectasis, PBB has also been an opportunity to study the early pathological changes in these diseases. Although initially debated as a separate disease, PBB is now included in most national guidelines for pediatric chronic cough, as well as in European textbooks on pediatric respiratory disease. although the concept of PBB is a recent development, visionary physicians have been describing PBB-like abnormalities as a precursor state to bronchiectasis for decades. The diagnosis of PBB is usually based on three clinical criteria: the presence of a chronic wet cough or sputum, evidence of bacterial infection on a Bronchoalveolar lavage (BAL) culture, and significant relief of the cough after two weeks of antibiotic therapy. These criteria are a summary of clinical experience, and all three criteria must be met to diagnose PBB. Since it is nearly impossible to obtain material from the lower airways of every child with chronic wet cough (>4 weeks), the second criterion was changed to exclude other causes of the patient’s wet cough or sputum. On clinical auscultation, croup is rarely heard, and the features of allergy in children with PBB (elevated systemic or airway eosinophils, elevated IgE, or positive RAST test) are similar to those in children without PBB. Because PBB is an airway infection (Figure), children usually do not have sinus or ear disease. Tracheobronchial achalasia usually coexists with PBB (up to 74%), but because chronic inflammation can lead to abnormalities in the airways, it can be difficult to distinguish between the two clinically. In a cohort study of 104 children with PBB, the incidence of tracheobronchomalacia (68%) was comparable to that of a non-PBB control group (53%). Molecular biology tests to aid in the diagnosis of PBB are more often seen in children in kindergarten, which raises the possibility that children with PBB may have a viral predisposition to infection. In fact, several prospective studies have found that type C adenovirus tends to coexist with Streptococcus pneumoniae, Haemophilus influenzae, and Calamotobacter in the bronchoalveolar lavage fluid of children with PBB or bronchiectasis. Pathological studies have found that autoimmune markers are upregulated in children with PBB, unlike in patients with immunodeficiency. Compared to children without PBB, children with PBB showed significant upregulation of TLR-2, relative expression of TLR-4 mRNA, and elevated concentrations of human beta defensin 2 (hBD2) and mannose-associated hemagglutinin (MBL). In contrast, the expression of lipopolysaccharide and cytokines was similar to controls after cell stimulation in the BAL of children with PBB. Inflammation of neutrophils in the lower respiratory tract of patients with PBB was intense and pronounced, as evidenced by a significant upregulation of pro-inflammatory factors (IL-8, MMP-9, IL-1β) and an increased proportion of neutrophils in the BAL. In both basic and clinical cohort studies, we found increased expression of IL-1β, α-defensins, IL-1-associated pathway factors, CXCR2 and other proteins and genes in the BAL of children with PBB compared to children without PBB. There was a significant correlation between the level of IL-1β expression and the duration and severity of the cough. In addition, the expression of Pellino-1 and IL-1 receptor-associated kinase 2, signaling molecules of IL-1β, was significantly higher in patients with frequent recurrences of PBB (>3 times a year) compared to those with infrequent recurrences of PBB (<3 times a year). Depending on the bacteria mentioned above, a 2-week treatment with the relevant antibiotic (amoxicillin - clavulanic acid potassium) is required. If the child's lower respiratory tract is biologically mapped, a longer course of treatment is required to facilitate bacterial clearance. The role of the extracellular network of neutrophils, protective apoptosis or cytosolic burial, and other mechanisms arising from the persistence of neutrophils in PBB is unclear and needs to be further explored. Purging sputum in children is an indication for antibiotic therapy, yet it should be avoided in patients with simple respiratory infections, and physicians should have a clear understanding of the role of antibiotics in patients with chronic wet cough. In patients with PBB with prolonged purulent sputum in the airways, antibiotics should be used prophylactically to avoid the continuation of infection or inflammation that could lead to exacerbation or even development of bronchiectasis. PBB can recur, but the incidence and risk factors for recurrence are not known and further studies are needed to clarify that IL-1 signaling pathway activity is significantly increased when PBB recurs. A preliminary analysis of our ongoing study suggests that patients with recurrent PBB are more likely to be diagnosed with bronchiectasis at 2-year follow-up. Further clinical studies on PBB and its mechanisms need to be explored in depth. Specifically, for diagnostic criterion 3 of PBB, should the duration of antibiotic therapy be changed from 2 weeks to 2-4 weeks, as a small percentage of children do require a longer course of therapy, and the mechanisms of antibiotic resistance should be continuously monitored in the diagnosis and management of patients with PBB.