Detection And Significance Of HMGB1 In Alveolar Lavage Fluid Of Children With Refractory Pneumonia Mycoplasma Pneumonia

Pneumonia is one of the main causes of death among children under 5 years old in China.The majority of children with pneumonia are Community Acquired Pneumonia（CAP）.Mycoplasma pneumoniae pneumonia（MPP）is a common type of CAP in preschool and school-age children,and it is not uncommon in infants and children aged 1-3 in recent years.^[1]MPP is distributed throughout the year,with different incidence rates in different regions and seasons.There are data showing that the infection rate of MP（Mycoplasma pneumoniae,MP）is higher in the northern part of the winter^[2],while the infection rate in summer and autumn is higher in the southern region^[3].Cough is a prominent clinical manifestation of mycoplasma pneumoniae pneumonia.In the early stage,it is usually irritating dry cough.In addition,it may be accompanied by fever,rash,and difficulty in breathing.Mycoplasma pneumoniae pneumonia is mostly benign and self-limiting,and most of the regular treatment with macrolide antibiotics can be cured^[4].However,in recent years,some patients with MPP have been found to have poor efficacy under routine treatment,rapid progression,relatively severe symptoms,and high incidence of complications.The concept of Refractory Mycoplasma Pneumoniae Pneumonia（RMPP）is proposed.RMPP is more common in older children,heavier illness,longer fever time and longer hospital stay,severe symptoms of systemic poisoning,often manifested as persistent fever,severe cough,difficulty breathing,etc.Chest imaging is progressively aggravated,showing the extent of lung lesions.Large,large area consolidation,atelectasis,pleural effusion,etc.,even with necrotizing pneumonia and lung abscess.RMPP is easy to affect other extrapulmonary systems,and even cause multiple organ failure^[5-7],which greatly threatens children’s life and health,and brings great troubles for clinical diagnosis and treatment.The pathogenesis of RMPP is still unclear^[8],and the following aspects are more concerned:1.MP resistance increased 2.Immune dysfunction 3.Mixed infection 4.The number of infectious agents also affects the prognosis.With the deepening of RMPP research,the immune mechanism of RMPP has been paid more and more attention by the clinic.The research on the immune mechanism of RMPP mainly focuses on cellular immunity,humoral immunity and direct damage of inflammatory factors.After MP invades the body,the immune system can be activated by various means.The immune cells release various inflammatory factors and regulate the immune response to remove the invading MP.Therefore,the role of inflammatory factors in the immune response has become the focus of research.High mobility group box1 protein（HMGB1,HMGB1）is an inflammatory cytokine that is passively released by necrotic cells,or endotoxin,interleukin-1,IL-1.Under the stimulation of tumor necrosis factor alpha（TNF-α）,it is actively secreted by macrophages and monocytes after activation^[9].It has been reported^[10]that the intensity of active secretion of HMGB1 by immune cells is dose-and time-dependent in response to stimulating factors such as lipopolysaccharide（LPS）,TNF-α,IFN-γ,and IL-1β.TNF-αis an early inflammatory factor of inflammatory response,mainly produced by mononuclear-macrophage activation.It is a key protective factor in the fight against inflammatory reactions and enhances the body’s ability to fight infection^[11].The environment stability of the body and the renewal of the body tissues play an important role in regulation.IFN-γcan activate macrophages,help the body to phagocytose infected cells,and can destroy pathogens,but overexpression can trigger the cascade cascade to damage lung tissue,which is not conducive to disease outcome^[12].Kamo et al^[13],purified HMGB1 and TNF-α,IFN-γor IL-1βcan enhance the inflammatory response,while IL-1βneutralizing antibody can completely stop the proinflammatory activity of HMGB1,speculated that HMGB1 may be related to other The combination of immune factors plays an important role in the development of RMPP,and targeted administration of appropriate immunotherapy may be beneficial for the treatment of diseases.At present,the research on HMGB1 at home and abroad mostly focuses on sepsis,asthma,lung injury,Chronic obstructive pulmonary disease（COPD）,lung cancer,etc,and HMGB1 in children with refractory Mycoplasma pneumoniae pneumonia BALF There are few studies on the level and significance of HMGB1,TNF-α,IFN-γand other inflammatory factors,and their relationship in children with refractory mycoplasmal pneumonia is insufficient.The status quo of mycoplasmal pneumonia,it is necessary to further explore the role and mechanism of such cytokines in the pathogenesis of refractory mycoplasmal pneumonia in children,and provide reference for clinical diagnosis and treatment and prognosis evaluation.Objective1.1.To detect whether there are differences in inflammatory factors such as HMGB1,TNF-αand IFN-γin RBPP and Bronchoalveolar lavage fliud（BALF）;2.Study HMGB1 in BALF in children with MPP Relationship between inflammatory factor levels such as TNF-αand IFN-γand severity of the disease;3.To explore the predictive value of HMGB1,TNF-α,IFN-γand other inflammatory factors in BALF on the prognosis and outcome of children with RMPP.Methods1.According to the inclusion criteria,51 patients with MPP who were hospitalized in the Department of Pediatric Respiratory Diseases of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2018and required bronchoscopy and alveolar lavage were included in the study,including26 cases of refractory group.25 cases in the general group,blood samples were taken to detect serum C-reactive protein（CRP）,lactate dehydrogenase（LDH）,ferritin（FER）and D-dimerization.The level of the body.The first group of children underwent the first bronchoscopy in the acute phase（within 2 weeks）,and the refractory group underwent the second bronchoscopy and alveolar lavage in the recovery period（1week after the first lavage）.Alveolar lavage fluid was used to detect the levels of HMGB1,TNF-α,and IFN-γin BALF.The medical records of the included subjects were collected and summarized.The data were collected using SPSS21.0 for statistical analysis.The data were averaged±standard deviation is expressed.The chi-square test was used to compare the age and gender composition.The t-test was used to compare the measurement data.The test value wasα=0.05,and the P value<0.05 was statistically significant.Correlation analysis between variables was performed by Pearson test,α=0.05 was the test standard,and P<0.05 was statistically significant.2.The study has been approved by the ethics committee,and the inclusion of the study subjects have obtained the informed consent of the legal guardian of the child and signed the informed consent form.Results1.The mean values of CRP,LDH,FER and D-dimer in the acute phase of the refractory group were higher than those in the normal group,and the difference was statistically significant（P<0.05）.2.The levels of HMGB1,TNF-αand IFN-γin BALF in the refractory group were significantly higher than those in the normal group（P<0.05）.3.The levels of HMGB1,TNF-αand IFN-γin BALF in the refractory group were significantly lower than those in the acute phase（P<0.05）.4.The level of HMGB1 in BALF of refractory group was positively correlated with serum CRP,LDH,FER and D-dimer levels.Conclusions1.HMGB1,TNF-αand IFN-γparticipate in the immune response and play an important role in the occurrence and development of RMPP.2.The level of HMGB1 in BALF was positively correlated with the change of serum inflammatory index and hypercoagulability in children with RMPP.