Severe pneumonia is a common critical emergency in pediatrics. Due to children's underdeveloped immune systems, poor cardiopulmonary function, and generally weaker physical condition, the morbidity and mortality rates of severe pneumonia are higher in children compared to other populations (1), posing a significant threat to their lives. According to World Health Organization statistics (2), severe pneumonia accounts for approximately 7%–13% of all pediatric pneumonia cases and is a major cause of death in children. Studies have shown (3) that patients with severe pneumonia often experience airway clearance dysfunction (ACD), which can exacerbate respiratory dysfunction and even lead to serious complications such as atelectasis and worsened infections, hindering rapid recovery. ACD refers to the inability to clear respiratory secretions or obstructions to maintain airway patency. Without timely and targeted intervention, it may result in hypoxia, respiratory failure, aggravated local ischemia in the heart and brain, and even immediate death (4). Relevant studies have found (5) that airway clearance is closely associated with the mucociliary clearance system and an effective cough mechanism. Cilia facilitate the transport of secretions from central to periphery airways through beating motions, while coughing expels secretions via high- velocity airflow. However, children with severe pneumonia often exhibit intense inflammatory responses that can alter mucus properties, leading to thickened secretions that are difficult to expel. This significantly impairs ciliary clearance and may cause weak or absent cough reflexes, ultimately resulting in secretion retention and an increased incidence of ACD (6, 7).

Currently, there are various clinically observed types of ACD in children with severe pneumonia, among which ineffective cough, thick sputum, and dyspnea are commonly seen, significantly impacting treatment and recovery. Ineffective cough, a major manifestation of ACD in these patients, serves as a clinical predictor of impaired airway clearance. It is often associated with weak cough reflexes or airway narrowing, preventing effective expulsion of secretions. Thick sputum is another contributing factor to ACD; its presence increases the risk of inadequate airway clearance and may even worsen airway secretions, further compromising respiratory function. Dyspnea, also a critical issue in ACD among severe pneumonia patients, may result from multiple factors such as retained airway secretions, airway blockage, and pulmonary infection. Additionally, excessive phlegm or increased mucus secretion in these patients can significantly exacerbate breathing difficulties (8, 9). If not effectively managed during hospitalization, ACD can lead to alveolar damage, atelectasis, pulmonary edema, and in severe cases, may progress to acute respiratory distress syndrome (ARDS) or multiple organ failure. These complications directly delay recovery and may even increase in-hospital mortality (10, 11).

In light of this, the present study was conducted to early identify the types and risk factors of ACD in children with severe pneumonia. The objective is to elucidate the categories and underlying risk factors of ACD in pediatric severe pneumonia, thereby providing a scientific basis for developing more effective treatment strategies.

Studies have indicated (13) that 40%–60% of children with severe pneumonia are prone to producing large amounts of thick sputum, which not only increases the risk of airway obstruction but also elevates the likelihood of ACD. Severe pneumonia in children often involves respiratory system compromise, with clinical manifestations including cough, tachypnea, increased respiratory secretions, and may also be accompanied by severe dyspnea, nasal flaring, and cyanosis (14, 15). Additionally, due to their generally weaker physical condition, respiratory infections can lead to excessive secretions, making it difficult for children to effectively expectorate sputum on their own, thereby increasing the incidence of ACD and posing significant challenges in clinical management.

In this study, the types of ACD observed in children with severe pneumonia primarily included ineffective cough, thick sputum, dyspnea, nasal flaring/increased nasal congestion, tachypnea, and oxygen saturation <93%., Among these, thick sputum was the most common type, and the overall incidence of ACD reached 42.86%, which is consistent with clinical data. Severe pneumonia is often accompanied by varying degrees of inflammatory response, which can directly stimulate goblet cells and submucosal glands to overproduce mucin and alter mucus composition, thereby increasing its viscoelasticity and viscosity. Meanwhile, inflammatory mediators can damage airway ciliated epithelium, reducing the frequency and efficiency of coordinated ciliary beating. Moreover, young patients have underdeveloped organ function, which often leads to weak or ineffective coughing and an inability to generate sufficient airflow shear force to clear secretions, further contributing to the high incidence of ACD. Therefore, early recognition of ACD and implementation of targeted interventions are crucial.

In this study, it was observed that the children in the ACD group were younger than those in the non-ACD group, suggesting that younger children are more susceptible to ACD. This is primarily due to their immature respiratory system, relatively narrow airways, poor ciliary motility, and underdeveloped cough reflex, all of which increase the risk of ACD. Additionally, the nutritional status of ACD group was poorer than that of the non-ACD group. Malnutrition can compromise immune function, weaken respiratory muscle strength, impair mucosal repair capacity, adversely affect mucus composition and quality, and even lead to deteriorated pulmonary function and impaired respiratory muscle contraction. These factors can exacerbate infection and thereby increase the risk of ACD manifestations such as ineffective cough and thick sputum. The incidence of comorbid respiratory failure, heart failure, pulmonary rales, and pulmonary rhonchi was significantly higher in the ACD group than in the non-ACD group. This indicates that children with severe pneumonia who present with these complications are at a markedly elevated risk of developing ACD. Respiratory failure significantly impairs lung function, directly hinders gas exchange, and reduces cough efficacy, thereby compromising airway clearance. Heart failure can cause pulmonary congestion and edema, increasing the likelihood of lung pathology and ACD. Pulmonary rales and rhonchi are both signs of accumulated airway secretions, suggesting either excessive airway secretions or airway narrowing, which further raises the risk of impaired airway clearance.

Studies have shown that mechanical ventilation, an invasive procedure used to support respiratory function through an artificial airway, can disrupt the natural defense mechanisms of the respiratory tract. It impedes ciliary movement, reduces mucus clearance, and promotes the accumulation of airway secretions, thereby worsening ACD (16, 17). Consistent with this, the current study found a significantly higher rate of mechanical ventilation in the ACD group, confirming it as a risk factor for ACD in children with severe pneumonia. Analysis indicates that mechanical ventilation requires endotracheal intubation or tracheotomy, reflecting the critical condition of the children and pronounced respiratory symptoms. Prolonged mechanical ventilation can impair spontaneous breathing, promote excessive secretions retention, weaken the cough reflex, and diminish the autonomous cleaning ability of the airways, ultimately increasing the incidence of ACD (18, 19). In light of these findings, clinical practice should emphasize enhanced airway management for mechanically ventilated children with severe pneumonia, including timely clearance of respiratory secretions, to maintain airway patency.

Typically, children with severe pneumonia release large amounts of inflammatory mediators and cytokines, making them highly significant in assessing the severity of the disease (20). Changes in PLT often reflect the intensity of the inflammatory response. An elevated PLT level indicates a serious inflammatory reaction or abnormal coagulation, which is commonly observed in children with severe pneumonia. CRP, a nonspecific acute-phase inflammatory marker, is associated with the degree of systemic inflammation and tissue damage. Its elevated expression in children with severe pneumonia suggests active inflammation and a higher risk of pulmonary complications. PCT, a prohormone of calcitonin without hormonal activity, increases significantly in response to severe stimuli such as bacterial infection, making it a key indicator for clinical identification of bacterial infections. IL-6, secreted by various cells including T lymphocytes, fibroblasts, B lymphocytes, and monocytes/macrophages, plays a critical role in inflammatory and immune responses, serving as an important marker for early diagnosis and warning of infectious diseases (21). In this study, the ACD group exhibited lower PLT levels but significantly higher CRP, PCT, and IL-6 levels compared to the non-ACD group. This suggests that PLT and CRP expression may influence the occurrence of ACD, with CRP, PCT, and IL-6 being particularly significant factors contributing to ACD in children with severe pneumonia. Although PLT was significantly lower in the ACD group, it was not selected in the final LASSO model, possibly due to its complex relationship with inflammation and coagulation, which may have been overshadowed by more direct inflammatory markers such as CRP and PCT, or due to multicollinearity. Elevated CRP levels are closely related to airway mucosal damage and impaired mucociliary clearance. As CRP increases, severe damage to the airway mucosa, dysfunction of ciliary clearance, and epithelial cell shedding may occur, leading to the formation of mucus plugs that obstruct the airways. Additionally, elevated CRP can contribute to the formation of plastic mucus, further increasing the risk of airway obstruction and ACD. Similarly, elevated PCT levels in children with severe pneumonia often indicate severe infection, which may be accompanied by intense inflammatory responses and tissue damage, resulting in increased mucus secretion, impaired mucociliary function, and ultimately ACD. As a pro-inflammatory cytokine, IL-6 is often elevated in severe pneumonia, reflecting exacerbated airway inflammation, increased mucus production, and impaired ciliary function, all of which significantly raise the incidence of ACD (22, 23). Therefore, close clinical monitoring of CRP, PCT, and IL-6 levels is essential. Regular assessment of these markers can help identify the risk of ACD in children with severe pneumonia at an early stage, enabling timely intervention.

It has been found (24) that children with severe pneumonia are often associated with immune dysfunction, while the immune function of children directly affects the severity of this disease. Immune dysfunction is manifested as abnormalities in cellular and humoral immunity, and several studies have shown that compared with children with simple pneumonia, children with severe pneumonia have relatively lower levels of IgA and IgM, with their condition worsening as the levels of indicators decrease (25). Among them, IgM is the earliest type of antibody produced in the immune response, which activates the complement system and enhances phagocytosis of pathogens, and in children with severe pneumonia, the changes of its level mainly reflect the acute phase characteristics of pathogen infection; while IgA, as a key factor of mucosal local immunity, tends to be distributed on the mucosal surfaces of respiratory and digestive tracts, which can play the role of anti-infection and protective barrier. The reduced IgA expression in children with severe pneumonia indicates that their respiratory mucosal defense ability is attenuated, and children are highly susceptible to the attack of pathogens (26, 27). From the results of this study, the levels of IgA and IgM were significantly lower in ACD group than in non-ACD group, and especially IgA as a key factor in the development of ACD in children with severe pneumonia. It has been reported (28) that IgA is the main protective antibodies of respiratory mucosa, which can directly inhibit the adhesion of pathogens on respiratory epithelial cells, thus avoiding pathogens from colonizing and infecting. When the level of its expression decreases, the ability of body to resist the pathogens is clearly weakened and even results in recurrent infections and intensification of inflammatory reactions, which in turn causes ACD. In addition, reduced IgA levels are closely related to immune dysfunction in children with severe pneumonia, and once their IgA expression is abnormal, their respiratory mucosal barrier function is directly affected (29, 30) In response, clinical attention should be paid to the monitoring of IgA levels in children with severe pneumonia, with timely and effective measures been taken for intervention to improve airway clearance in children with severe pneumonia.

However, this study has certain limitations. For instance, as a single-center study with a small sample size, the limited number of participants may introduce selection bias, potentially affecting the representativeness and reliability of the findings. Additionally, the classification of ACD types in this study may differ from criteria used in other research, leading to limited comparability across studies. Therefore, future clinical efforts should focus on conducting multicenter, large-sample prospective studies to comprehensively understand the epidemiological characteristics, risk factors and prognosis of ACD in children with severe pneumonia. It is also essential to establish a unified and quantifiable classification standard for ACD types in this population to enhance the comparability and scientific rigor of research outcomes.

In summary, children with severe pneumonia are at risk of developing ACD, which may be influenced by factors such as mechanical ventilation, CRP, PCT, IL-6, and IgA levels. These five factors can be used to assess the risk of ACD in this population. If ACD is confirmed early through evaluation of these markers, clinical management should be promptly adjusted. Treatment strategies may include nebulized inhalation of mucolytic agents such as N-acetylcysteine to reduce sputum viscosity, supplementation with immunonutrients or intravenous immunoglobulin for children with low IgA levels, enhanced airway humidification, high-frequency oscillatory sputum expulsion, and daily assessment of weaning criteria to shorten mechanical ventilation duration, thereby reducing ventilator-induced lung injury.