Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Objective:To study the clinical characteristics of respiratory syncytial viral pneumonia in children aged 2 to 5 years, and pinpoint the risk factors of severe pneumonia, in order to establish a basis for early diagnosis.Methods:We performed a retrospective investigation of clinical data from 210 children aged 2-5 years, diagnosed with respiratory syncytial virus pneumonia and hospitalized in our institution from December 2017 to June 2023 of New Century International Children′s Hospital, Beijing. According to the severity of their illness, they were divided into mild group and severe group. The aim was to compare their general data and clinical characteristics and to analyze the risk factors of severe respiratory syncytial viral pneumonia.Results:Among 210 children infected with RSV pneumonia, the male to female ratio was 1.26∶1, with a peak body temperature of 39.35±0.68 ℃, an average course of fever was 5.98±2.20 days, and an average hospital stay of 7.16±2.29 days. RSV pneumonia occurred throughout the year, predominantly in spring and winter. Among the children affected, 26.19% had tachypnea, 22.38% had three concave sign, 77.14% had moist rales in the lungs, 42.86% had wheezing sounds, 22.86% had myocardial damage, 15.24% had diffuse panbronchiolitis. The result from the univariate analysis showed that there were statistically significant differences in preterm delivery, peak body temperature, length of hospital stay, tachypnea, wheezing, three concave sign, moist rale, wheezing sound, CRP, X-ray pulmonary shadow and diffuse panbronchiolitis between mild and severe groups ( P<0.05). Multivariate logistic regression analysis showed that moist rales and X-ray lung shadows were risk factors for severe RSV pneumonia. Conclusions:Importantly, certain clinical differences were observed between mild and severe cases of respiratory syncytial virus pneumonia in children aged 2 to 5 years. Moist rales and X-ray lung shadows are independent risk factors for severe respiratory syncytial viral pneumonia in children aged 2 to 5 years.

Objective·To develop physiologically based pharmacokinetic(PBPK)models specifically designed for the Chinese population by utilizing the combination of clozapine and fluvoxamine as a case,and predict the drug-drug interaction(DDI)associated with the combination medication of clozapine,ultimately optimizing the dosage of clozapine.Methods·By obtaining the physicochemical parameters,absorption,distribution,metabolism,excretion(ADME)-related parameters,and physiologically relevant parameters of the Chinese population through literature and pharmacology-related databases,PBPK models for the clozapine and fluvoxamine were constructed by using PK-Sim? software.The models' accuracy was evaluated by comparing predicted values of the area under the curve(AUC)and peak concentration(Cmax)to observed data,using the mean percentage error(MPE)and mean absolute percentage error(MAPE)as evaluation indicators.The models were validated against real-world plasma drug concentration data.Additionally,combining the inhibitory effect of fluvoxamine on clozapine,models for the combination therapy of clozapine and fluvoxamine were developed to predict the pharmacokinetic changes of clozapine.The presence of clinically significant DDI was determined by using the 90%confidence interval of the AUC ratio(AUCR)or Cmax ratio(CmaxR)as evaluation metrics,with a non-effect boundary set at 80%?125%.The pharmacokinetic changes of clozapine upon co-administration with fluvoxamine based on PBPK models were quantified,and a dosage optimization for clozapine was developed.Results·The constructed model of clozapine and fluvoxamine was considered accurate if the absolute value of the MPE was≤10%and the MAPE was<25%during validation,indicating that the predicted concentration-time curves were accurate.The PBPK model for the co-administration of clozapine and fluvoxamine was able to accurately predict pharmacokinetic parameters if the ratio of predicted AUC to observed AUC was within 1.25.The prediction of PBPK model for the co-administration showed that the 90%confidence intervals for AUCR and CmaxR of the combination therapy of clozapine and fluvoxamine were not entirely within the ineffective effect boundary,indicating a clinically significant DDI when these two drugs were used concomitantly.Moreover,the dose optimization according to the PBPK models indicated that when subjects were co-administered with clozapine and fluvoxamine,reducing the dose of clozapine to 50%of the original dose could maintain the exposure levels of clozapine consistent with monotherapy.Conclusion·The established PBPK model can effectively simulate the impact of combination therapy on pharmacokinetic changes of clozapine,providing valuable insights for predicting potential DDI and optimizing dosage regimens.If clozapine needs to be co-administered with fluvoxamine during the treatment,clinicians should remain vigilant for clinically significant DDI and contemplate optimizing the dosage of clozapine accordingly.

Objective:To observe the expression of Galectin-7 in the serum and sputum of asthmatic children and to explore its significance in asthmatic children.Methods:The study prospectively case-control selected 183 children diagnosed with bronchial asthma at Department Ⅱ of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children′s Hospital of Capital Medical University. The control group consisted of 41 children with other bronchial diseases and 43 healthy children. Children in the asthma group were divided into acute and non-acute exacerbation groups. Acute exacerbation group was divided as mild acute, moderate acute and severe acute groups; non-acute exacerbation group was divided as mild persistent, moderate persistent and severe persistent groups. Children without acute exacerbation asthma in the asthma group were divided into high and low Galectin-7 groups based on median serum Galectin-7 levels. Serum and sputum were collected, Galectin-7 levels were measured using enzyme-linked immunosorbent assay. The study compared and analyzed the differences in Galectin-7 levels between children with asthma and the control groups using Mann-Whitney U test or the Kruskal-Wallis or the Chi-square test for inter-group comparisons. Results:Among 183 children, 61 cases had acute asthma exacerbation, and 122 cases had persistent asthma without acute exacerbation. The asthma group comprised 110 males and 73 females. The control group consisted of 41 children with other bronchial diseases, including 24 cases of bronchiectasis and 17 cases of obliterans bronchitis. The control group comprised 26 males and 15 females. Forty-three healthy children who underwent physical examination, including 22 males and 21 females. The levels of Galectin-7 in serum were significantly higher in children with an acute asthma exacerbation than that of healthy children (0.1 (0, 0.7) vs. 0 (0, 0.2) μg/L, Z=2.09, P=0.001). Galectin-7 levels in sputum were higher in children with an acute asthma exacerbation than that in children with other bronchial diseases (1.2 (0.1,3.7) vs. 0.4 (0.1, 1.5) μg/L, Z=2.20, P<0.001). Serum Galectin-7 levels were significantly higher in children with persistent asthma compared to children with other bronchial diseases and healthy children (0.6 (0.3, 1.2) vs. 0.1 (0, 0.5) and 0 (0, 0.2) μg/L, Z=-6.12 ,-7.63, both P<0.001), and the levels were significantly and positively correlated with asthma severity ( r=0.77, P<0.001), disease duration ( r=0.34, P=0.001), and number of previous attacks ( r=0.51, P<0.001). There were 61 children in the high-Galectin-7 group and 61 children in the low-Galectin-7 group. Children with high Galectin-7 had more asthma triggers, a greater proportion with a positive family history, more previous asthma attacks, longer duration of asthma, and higher serum total IgE levels compared to those with low Galectin-7 ( χ2=9.30, 22.46, Z=5.06, 3.57, 2.31, all P<0.05). Conclusion:The expression of Galectin-7 is found to be elevated in the serum and sputum of asthmatic children and correlated with asthma conditions.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

In recent years, the number of severe and drug-resistant Mycoplasma pneumoniae pneumonia (MPP) in school-aged children in East Asian countries is on the rise, especially in China.Pediatric MPP is a heterogeneous disease.Some MPP children have a self-limited progression after infection, while some suffer an aggravated and prolonged course of disease.The sequelae of airway occlusion leads to the declines of lung function and quality of life.Although a series of nationally epidemiological data on pediatric MPP in China are scant, pediatric MPP should be regarded as the highly concerned main respiratory disease of school-aged children due to the large population of children in China and the long-term effects of MPP-induced airway occlusion.This article briefly reviews the correlation between Mycoplasma pneumoniae resistance and severe MPP, as well as the classification and treatment of MPP.

Objective:To explore the threshold of tidal breathing nasal nitric oxide (TB-nNO) in diagnosing primary ciliary dyskinesia (PCD) in children aged 3 to 5 years.Methods:Retrospective study.The TB-nNO values were examined of 165 healthy children aged 3-5 in a kindergarten in Xicheng District, Beijing, from March 27 to March 29, 2018, which were also measured in children aged 3-5 years who were diagnosed as PCD, cystic fibrosis, bronchiolitis obliterans, bronchiectasis caused by other diseases and asthma in the Second Department of Pediatric Pneumology, Beijing Children′s Hospital, Capital Medical University from January 2018 to December 2021.Relevant factors associated with TB-nNO in normal children were screened by a multiple linear regression model.The cut-off value of TB-nNO in diagnosing PCD in preschool children aged 3-5 years was determined by calculating the maximum area under the receiver operating characteristic (ROC) curve.Results:TB-nNO value in healthy children aged 3, 4 and 5 years were (94.8±36.4) nL/min, (103.3±50.7) nL/min and (106.9±61.5) nL/min, respectively.The mean TB-nNO value in 9 children with PCD was (18.9±10.8) nL/min.TB-nNO values in 49 children with asthma, 19 children with bronchiolitis obliterans, 17 children with bronchiectasis and 6 children with cystic fibrosis were (97.7±51.1) nL/min, (93.2±49.2) nL/min, (93.7±75.3) nL/min and (45.4±18.2) nL/min, respectively.Using 30 nL/min of TB-nNO as the cut-off point, the sensitivity and specificity of TB-nNO in diagnosing PCD were 88.9% (8/9) and 96.9%, respectively.The area under the ROC curve was 98.3% (95% CI: 95.3%-100.0%). Conclusions:TB-nNO value of 30 nL/min can be used as the cut-off point in the diagnosis screening of PCD in children aged 3-5 years.Its diagnostic value in this age group should be further evaluated.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.
Biomarkers ; Carrier Proteins ; Child ; Humans ; Immunoglobulin Fc Fragments ; Immunoglobulin G ; Macrolides ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma/drug therapy* ; Proteomics

Objective:To investigate the nurse′s knowledge, attitude and practice of sarcopenia and to analyze the related factors.Methods:From November 10th to 22nd in 2020, self-designed questionnaires were used to survey the knowledge, attitude and practice of 1 056 nurses from 139 hospitals in 19 provinces, autonomous regions of China. Multiple stepwise linear regression was used to analyze the main influencing factors of knowledge, attitude and behavior of nurses with sarcopenia.Results:The average knowledge score was (24.25 ± 7.38) points, the attitude score was 63(55, 65) points, the behavioral score was (31.25 ± 13.28) points. Multiple stepwise linear regression results showed that the educational background and professional title of nurses were the maininfluence factors of knowledge score ( t=4.97, 3.35, P<0.05). The nurse′s knowledge score and whether they were teaching nurses or not were the main factors influencing attitude score ( t=9.12, -3.10, P<0.05). Attitude score, working years, and whether a nurse specialist were the main factors influencing behavior score ( t=9.82, 0.77, -5.29, all P<0.05). Conclusions:The nurse′s attitude toward preventing sarcopenia was positive, but their knowledge level was poor, the behavior intervention was insufficient. Nursing managers should carry out training of sarcopenia actively, to improve the screening, evaluation and early intervention ability of nurses for sarcopenia.