| BackgroundLobar pneumonia is a common lower respiratory tract infectious disease occurringduring childhood. It is also one of the common community-acquired pneumonia(community-acquired pneumonia, CAP). According to the World Health Organization(World Health Organization, the WHO), CAP is the first cause of death in children under5years old around the world, which accounts for about19%of child deaths. In recent years,the obviously upregulated incidence of lobar pneumonia and delayed healing impede theclinical treatment. The main pathogens responsible for CAP consist of bacteria, viruses,mycoplasma, etc. The primary clinical manifestations include high fever, cough, andshortness of breath. It even leads to various extrapulmonary complications in multiplesystems. Although the new powerful antibiotics appear constantly, the morbidity andmortality do not decrease obviously.The pathogenesis of lobar pneumonia in children is so far not very clear, but theimmunological mechanism has attracted extensive attention of many researchers, given that cytokines play important roles during this pathogenesis. On the one hand, the bodyproduces pro-inflammatory factor, such as early pro-inflammatory factor: Tumor necrosisfactor alpha (Tumor necrosis factor alpha, TNF-α), interleukin6(Interleukins-6, IL-6),interleukin8(Interleukins-8, IL-8), High mobility group protein B1(High mobility groupprotein B1, HMGB1), etc., which promote inflammation, and cause tissue damage.Furthermore, the body per se inhibits inflammation and confines the inflammation throughthe release of anti-inflammatory factors, including interleukin4(Interleukins-4, IL-4),interleukin10(Interleukins-10, IL-10). If proinflammatory and anti-inflammatoryreactions reach equilibrium, the homeostasis of the lung will be maintained stable. On thecontrary, in case of disruption of this balance, the body will suffer Compensatoryanti-inflammatory response syndrome (Compensatory anti-inflammatory responsesyndrome, CARS) or Systemic inflammatory response syndrome (Systemic inflammatoryresponse syndrome, SIRS), both of which can further cause the further deleterious effectsto the body. However, the reports on the role of cytokines in lobar pneumonia are scare,and its mechanism is unclear. Therefore, this study is aimed to discuss the changes of thedifferent cytokines in children with lobar pneumonia through the study the changes andcorrelation of cytokines both in serum and in Bronchoalveolar lavage fluid(Bronchoalveolar lavage fluid, BALF) with disease progression, and to evaluate the role ofBronchoalveolar lavage in the treatment of lobar pneumonia in children, thus providingthe theoretical basis for the further understanding of cytokines in the occurrence of lobarpneumonia in children. Meanwhile, we introduce for the first time a new laboratory indexfor the better evaluation of the degree and the curative effect.Experiment objective:1. To observe the serous changes of TNF-α, IL-6, IL-8, IL-10and HMGB1in differentdegrees of lobar pneumonia. Meanwhile, to discuss the relationship between thecytokines and the severity of lobar pneumonia, and to provide a theoretical basis forunderstanding the pathogenesis of lobar pneumonia.2. To observe the expression changes of TNF-α, IL-6, IL-8, IL-10and HMGB1in bothserum and BALF dynamically with the progression of the disease. To analyze the relationship between the level of cytokines in the local or system with the progressionor prognosis of lobar pneumonia, and then to provide a theoretical basis for diseaseprogression, the evaluation of the degree and the curative effect.3. To evaluate the role and safety of bronchoalveolar lavage in the treatment of lobarpneumonia in children by comparing the index (such as clinical signs and symptoms,complications, hospitalization expenses) between the lavaged group and non-lavagedgroup.Experiment methods:In this study,76cases of children with lobar pneumonia from pediatrics of Tangduhospital during October2012-January2014were enrolled, which are identified inaccordance with the diagnostic criteria of lobar pneumonia in the practical pediatrics ofZhuFuTang. The diagnostic criteria contains:(1) There are clinical manifestations such asfever, cough and wheeze;(2) Physical examinations reveal lung breath soundsenlargement, audible wet rale, reduced or disappeared local breath sounds, has dullness orflatness to percussion in lesion sites;(3) Chest X-ray or CT shows a large patch of denseconsolidation shadows in a lung segment or a lung lobe even a whole side lung. Inclusioncriteria:(1) in accordance with the diagnostic criteria for lobar pneumonia, duration lessthan1week prior to admission, and did not have normal use of intravenous antibiotics;(2)have no other diagnosis of respiratory system diseases such as tuberculosis, bronchialasthma, etc.;(3) without symptoms such as fever or joint pain for nearly2months;(4)have no diagnosis of the immune system diseases and did not take corticosteroids,immunoglobulin, interferon, etc.;(5) Subject participation was voluntary, as indicated byfree and informed consent from their parents. Exclusion criteria: do not meet the aboveinclusion criteria. The involved children are all graded according to the ClinicalPulmonary Infection Score (Clinical Pulmonary Infection Score, CPIS) rating standards onthe day of admission. The41cases of CPIS Score>6points are designated into severegroup (CPIS high group). The35cases of CPIS Score≤6points are designated into mildgroup (CPIS low group). The enrolled children are randomly divided into lavaged group(46cases) and non-lavaged group (30cases) according to the attitude towards bronchoalveolar lavage of parents. The CPIS high score children of the lavaged group aredivided into two groups (recovery group of18cases, deterioration group of7cases) after10days of comprehensive treatment. The concentration of TNF-α, IL-6, IL-8, IL-10andHMGB1in serum and BALF are measured using double antibody sandwichenzyme-linked immunosorbent assay (enzyme-linked-immunosorbent serologic assay,ELISA).Results:1. The serous levels of TNF-α, IL-6, IL-8, IL-10and HMGB1in severe group and mildgroup are obviously significantly higher than those of healthy controls (P <0.05). Theserous levels of TNF-α, IL-6, IL-8, IL-10and HMGB1in severe group aresignificantly higher than those of the mild group. The serous levels of TNF-α, IL-6andIL-8have moderate positive correlations with HMGB1(P <0.05), and the correlationcoefficient are0.05,0.365and0.466, respectively. The serous level of IL-10has amoderate negative correlation with that of HMGB1(P <0.05), with the correlationcoefficient being-0.485.2. The serous levels of TNF-α, IL-6, IL-8, IL-10and HMGB1in lavaged group andnon-lavaged group are downregulated along with the progression of the disease, andthe serous levels of cytokines in the lavaged group decreased faster than those of thenon-lavaged group during the progression of the disease. The level changes of IL-6, IL8, IL-10and HMGB1in the two groups are all statistically significant (P <0.05). Thelevels of TNF-α, IL-6, IL-8, IL-10and HMGB1in BALF increased more significantlythan those in serum (P <0.05). The levels of TNF-α、IL-6、IL-8、IL-10and HMGB1in serum have positive correlations with those in BALF (P <0.05), with the correlationcoefficient being0.05,0.805,0.900,0.908,0.921, respectively. The levels of TNF-α,IL-6,IL-8, IL-10and HMGB1in BALF increased more significantly than those inserum both in the high score group of CPIS and low score group of CPIS (P <0.05).As for the comparison in the group of serum or BALF, the levels of TNF-α, IL-6, IL-8,IL-10and HMGB1in the high score group of CPIS are obviously higher than those oflow score group of CPIS (P <0.05). The serous and BALF levels of TNF-α, IL-8, IL-10and HMGB1in deterioration group are significantly higher than thosein recover group (P <0.05). The serous and BALF levels of IL-6in recovery group arehigher than those in deterioration group along the extension of the course, but thedifference has no statistical significant (P>0.05). The serous and BALF levels ofHMGB1have a downward trend both in the recovery group and in thedeterioration group with the progression of the disease, but there was no statisticallysignificant difference between the two groups (P>0.05).3. The body temperature recovery time, lung rale disappearing time, length of hospitalstay were all shorter in lavaged group than those in the non-lavaged group, and thedifferences between the two groups appeared statistically significant (P <0.05). Thehospitalization cost was lower in lavaged group than that in non-lavaged group, but thedifference has no statistical significant (P>0.05). The differences of recovery time ofchest CT were not statistically significant (P>0.05).8out of46cases occurredintraoperative hemorrhage in lavage group (17.39%),10out of46cases occurredpostoperative fever again (21.73%),46cases (100%) had the transient cough and1outof46cases appeared intraoperative cyanosis (2.17%). Occurrences of pulmonaryhemorrhage, pneumothorax, cardiopulmonary arrest, anesthetic accident were notobserved.Conclusion:1. The TNF-α, IL-6, IL-8, IL-10of early inflammatory factors and HMGB1of the lateinflammatory factor are involved in the onset of children lobar pneumonia. HMGB1,as a late inflammatory factor, may serve as a new reference index for the evaluation ofthe degree of the lobar pneumonia.2. The expression levels of TNF-α, IL-6, IL-8, IL-10and HMGB1in serum and BALFare all closely associated with the severity of lobar pneumonia. The higher the levels ofTNF-α, IL-6, IL-8, IL-10and HMGB1are, the more severe the pneumonia appear tobe. The relationship between the condition and the level of cytokines in BALF is moreobvious than that in serum. The level changes of TNF-α, IL-8and IL-10can be used tomonitor the prognosis of disease. 3. Bronchoalveolar lavage is not only an easy way to treat fewer complications, but alsois helpful to promote the recovery of lobar pneumonia. |
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