Discussion
Children afflicted with SMPP have severe clinical symptoms and more complications than those with MPP, including necrotizing pneumonia, atelectasis, bronchiectasis, OB, and permanent airway structural damage. As a result, lung function declines and repeated infections can impact quality of life for these patients. According to previous studies, main clinical manifestations of pediatric SMPP include continuous high fever and the presence of large areas of lung consolidation detected via pulmonary imaging. These findings reflect an overactive immune response that often requires hormone therapy for suppression of harmful inflammatory processes.7-9
The clinicalClinical manifestations of MPP in China differ from those reported in other countries, with symptoms more serious in China, especially in northern areas.4 In recent years, the widespread application of pediatric bronchoscopy for SMPP diagnosis and treatment has led to great progress in treating this disorder in China. Although some practitioners doubt the value of bronchoscopic findings for MPP prognosis, the value of bronchoscopy has been demonstrated for pediatric SMPP prognosis in China. In this study, congestion and swelling of airway mucosa were obvious in acute-stage cases examined via bronchoscopy, with some of these findings accompanied by follicular hyperplasia, a relatively specific MPP-associated manifestation. Meanwhile, during bronchoscopy bronchoalveolar lavage fluid is readily collected for use in MPP pathogen detection as a direct and effective method for achieving differential MPP diagnosis and treatment. Importantly, acute-stage SMMP mucous plug obstructions should be cleared bronchoscopically in a timely manner in order to maintain unobstructed airway subbranches and subsequently control infection. In subacute-stage SMMP, bronchoscopy can be used to monitor recovery from airway inflammation and detect OB sequelae for use in guiding treatment and respiratory rehabilitation planning. Therefore, bronchoscopic examination and intervention can benefit children with SMMP, with no significant adverse effects of bronchoscopy found in this study.
OB, a type of chronic airflow obstruction syndrome, mainly involves small and medium bronchi and is associated with proliferation of fibrous tissue. The main manifestations of OB are atelectasis and lobar collapse. Under bronchoscopic examination, the distal obliterans of some subsegmental and subsubsegmental bronchi of OB patients is accompanied by atrophy of proximal mucosa, appearance of obvious cartilage rings, and lumen expansion. OB often occurs secondary to severe pneumonia and has gradually gained recognition as a common SMPP-associated sequela,10 although few studies in China or abroad have described OB caused by M. pneumoniae infection. With increasing research attention paid to SMPP airway damage, OB detection rates have significantly increased and highlight OB as an urgent clinical problem stemming from processes underlying SMPP development. Meanwhile, studies have shown that MP infection can result in cellular and humoral immune dysfunction and disturbances of cytokine networks. Moreover, an excessive inflammatory reaction causes airway mucosal epithelial damage followed by airway subbranch injury that leads to scar contracture and occlusion. In this study, it was observed that OB caused by SMPP mainly involved grade III bronchi or below. The OB developmental process could be outlined as follows: in acute-stage disease, diseased sub-bronchi begin to erode then mucous plugs develop and blockages form. Next, necrotic epithelium detaches and blocks the airway in the subacute stage. Afterwards, subsegmental bronchi gradually became narrower, leading to poor ventilation, insufficient local blood supply surrounding lesions, then gradual formation of obliterans. The obliterans formation process supports the conclusion that obliterans are caused by airway injury. Meanwhile, initial obliterans lesions first appear as a thin film that is easily reopened using biopsy forceps. Next, the occluded part gradually thickens to form a barrier that biopsy forceps cannot reopen in most cases. It has been suggested that it may be possible to reopen airway branches after choosing the appropriate timing for bronchoscopic intervention, with further study needed to optimize interventional timing for improved treatment outcomes.
In this study, the timing of bronchoalveolar lavage was also investigated to detect correlations with OB incidence during late-stage SMPP. Specifically, the incidence of OB in pediatric patients who received first bronchoalveolar lavage at 10 days post-SMPP onset was significantly higher than that of children receiving their first bronchoscopies within 10 days post-disease onset. It has been suggested that for pediatric patients with persistent fever and large lung consolidations, atelectasis, and other pulmonary pathological changes detected via imaging within 10 days of onset, timely bronchoalveolar lavage is recommended to avoid complications such as OB.
The main components of bronchial mucous plugs include a mixture of mucin and cellular debris combined with a large number of infiltrating inflammatory cells that make this mixture extremely viscous. At present, it is widely recognized that hyperimmune inflammation is one of the main pathogenic mechanisms underlying SMPP.3,11 MP infection tends to lead to mucosal necrosis and mucus hypersecretion via a mechanism that may involve direct damage and release of infection-triggered toxic metabolites that ultimately damage bronchial epithelial cells and cilia. Such pathological damage may further impair mucociliary system function and weaken ciliary discharge capacity and clearance of secretions. Afterwards, tethered secretions that form within the local airway can trigger airway obstruction, with local obstruction of the proximal bronchus and various sizes of mucous plugs occurring within deep subsegmental bronchi in some serious cases. This study demonstrated that pediatric SMMP patients who also developed OB during late-stage disease exhibited different degrees of mucous plug development during acute-stage SMPP that were detected via bronchoscopy. Therefore, for patients with mixed lesions that are associated mainly with mucous plugs, mucus necrosis, and particularly with successive mucus plug development detected upon bronchoscopic reexamination, localization of mucous plugs should be done as early as possible in conjunction with administration of systemic treatment. Moreover, regular bronchoalveolar lavage treatment would facilitate the timely removal of mucous plugs in order to improve ventilation and secretion clearance at lesion sites and promote inflammatory absorption.
This study demonstrated that the density of large consolidation areas was significantly increased during acute-stage SMPP, suggesting that subbranches can be severely blocked by mucous embolisms. Thus, bronchoscopy should be performed as soon as possible to remove airway secretions that in such cases consist of thick viscous mucus that is difficult to clear away. For conducting a first bronchoscopic examination of patients with this type of lesion, a bronchoscope with a larger diameter (such as 4.0 mm) is recommended; because the diameter of the suction duct is large, it can loosen and brush mucous plugs to the depth of subsegmental bronchi and can effectively remove mucous plugs from deeper airways with the help of a cell brush. Due to acute-stage mucosal damage and congestion, adrenaline can be applied locally to shrink blood vessels while plugs are slowly and gently brushed to minimize bleeding during plug removal. During late-stage SMPP recovery characterized by improved lung imaging findings, the 2.8-mm diameter bronchoscope could be selected for subsequent inspection and clearance of deep subsegmental bronchial mucous plugs.
Due to the risk of pneumothorax that may occur during bronchoscopic examination and treatment of necrotic pediatric SMPP, the use of bronchoscopy for such cases is still controversial at present. However, it is worth noting that of 6 patients with late-stage necrotic pneumonia receiving treatment in this study, all of these patients developed OB even though they had different degrees of bronchoscopically detected airway blockage due to mucous plugs and mucinous necrosis. Notably, no pneumothorax occurred as a result of bronchoscopic treatment. Nevertheless, owing to the small sample size of this study, it is impossible to judge the advantages and disadvantages of bronchoscopy for necrotic SMPP based solely on results of this study.
In summary, pediatric SMPP patients exhibit certain characteristics during different disease stages that can facilitate diagnosis. However, airway mucus and mucosal epithelial necrosis and detachment could lead to clogging of subbranches and subsequent OB. Thus, it is recommended that pediatric SMPP patients with mucous plugs undergo timely bronchoscopy in addition to customary antibiotic treatment. Because this study did not comprehensively summarize and analyze factors associated with OB in pediatric SMPP patients, predictive factors predisposing patients to OB development were not definitively identified. Therefore, collection of additional clinical data is needed to further evaluate possible predictors of later OB occurrence that would be used to inform future clinical practice.
Acknowledgements: We thank the children and families who graciously consented to participate in the bronchoscopy of SMPP children in this study.