A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017-2021.

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (ALRTI) in children under five years of age. Between 2017 and 2021, 396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China. In addition, 151 sequences from China were sourced from GenBank and GISAID, making a total of 549 RSV F gene sequences subjected to analysis. Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved, although some amino acids (AAs) have undergone changes. AA mutations with frequencies ≥ 10% were identified at six sites and the p27 region: V384I (site I), N276S (site II), R213S (site Ø), and K124N (p27) for RSV A; F45L (site I), M152I/L172Q/S173L/I185V/K191R (site V), and R202Q/I206M/Q209R (site Ø) for RSV B. Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A, while the K191R, I206M, and Q209R frequencies increased by over 10% in RSV B. Notably, the nirsevimab-resistant mutation, S211N in RSV B, increased in frequency from 0% to 1.15%. Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations, with low root-mean-square deviation values. These results could provide foundational data from China for the development of RSV mAbs and vaccines.

Epidemiological characteristics of mycoplasma pneumoniae in hospitalized children before, during, and after COVID-19 pandemic restrictions in Chongqing, China.

Background: Mycoplasma pneumoniae (MP) is a significant cause of community-acquired pneumonia with high macrolide resistance rates. Various COVID-19 pandemic restrictions have impacted the prevalence of MP. Objective: To assess the changes in the pattern of MP infections among children before, during, and after the COVID-19 pandemic. Methods: A total of 36685 enrolled patients, aged 0-18 years, diagnosed with pneumonia and admitted to Children's Hospital of Chongqing Medical University from January 2019 to December 2023, were retrospectively reviewed in this study. The epidemiological characteristics of pediatric MP infection were analyzed. Results: Among 36685 patients, 7610 (20.74%) tested positive for MP. The highest positive rate was observed among children aged over 6 years (55.06%). There was no gender disparity in MP infection across the three phases of the COVID-19 pandemic. Hospital stays were longest for children during the COVID-19 pandemic (P <0.001). MP infection was most prevalent in the summer (29.64%). The lowest positive rate was observed during the pandemic, with the highest rate found after easing the measures across all age groups (P <0.001). There was a surge in the positive rate of MP in the third year after the COVID-19 pandemic. Regression analyses demonstrated a shift in the age range susceptible to MP infection, with children aged 3.8 to 13.5 years post-pandemic compared to the pre-pandemic range of 5.3 to 15.5 years old. Additionally, the average macrolide resistance rate was 79.84%. We observed a higher resistance rate during the pandemic than in the pre- and post-pandemic phases (P <0.001). Conclusion: The restrictive measures implemented during the COVID-19 pandemic have influenced the spread of MP to some extent and altered demographic and clinical characteristics, such as age, age group, season, length of stay, and macrolide resistance. We recommend continuous surveillance of the evolving epidemiological characteristics of MP infection in the post-pandemic period when restrictions are no longer necessary.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Azithromycin Effectiveness in Children with Mutated Mycoplasma Pneumoniae Pneumonia.

Objective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation. Methods: This retrospective observational cohort study was conducted at the Children's Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation. Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31-17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively). Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).

The characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria in China between 1965 and 2023: A cross-sectional study.

OBJECTIVE: As a large and populous country, China releases a high number of diagnostic criteria. However, the published diagnostic criteria have not yet been systematically analyzed. Therefore, the aim of this study is to investigate the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria published in China. METHODS: We searched five databases for diagnostic criteria from their inception until July 31, 2023. All diagnostic criteria were screened through abstract and full-text reading, and included if satisfying the prespecified criteria. Two researchers independently extracted data on the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria. RESULTS: A total of 143 diagnostic criteria were included. In terms of development methods, the proportions of diagnostic criteria that involved a systematic literature search (n = 2; 1.4%; 95% confidence interval (CI), 0.4% to 5.0%), adoption of formal consensus methods (n = 4; 2.8%; 95% CI, 1.1% to 7.0%), and criteria validation (n = 9; 6.3%; 95% CI, 3.3% to 11.5%) were relatively low. Regarding reporting quality, the average compliance with the ACCORD checklist was 5.1%; none of the diagnostic criteria reported on registration, expert inclusion criteria, expert recruitment process, or consensus results. A majority (58.7%; 95% CI, 50.6% to 66.5%) of criteria did not cite any research, and only one (0.7%; 95% CI, 0.1% to 3.9%) criterion was derived from a systematic review. Moreover, only 16.1% (95% CI, 11.0% to 23.0%) of diagnostic criteria used evidence from the Chinese population. CONCLUSION: The diagnostic criteria developed in China exhibit serious flaws, particularly in evidence retrieval, formation of expert panels, consensus methods, and validation. Additionally, only few diagnostic criteria used a systematic synthesis of the evidence or evidence from the China. There is an urgent need to enhance the methodology for developing diagnostic criteria.

The effects of delayed appropriate antimicrobial therapy on children with Staphylococcus aureus blood infection.

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702-0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227-5.144, P = 0.012) for sepsis, 3.109 (1.166-8.290, P = 0.023) for septic shock.    Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality.

TFEB regulates dendritic cell antigen presentation to modulate immune balance in asthma.

OBJECTIVE: Asthma stands as one of the most prevalent chronic respiratory conditions in children, with its pathogenesis tied to the actived antigen presentation by dendritic cells (DCs) and the imbalance within T cell subgroups. This study seeks to investigate the role of the transcription factor EB (TFEB) in modulating the antigen presentation process of DCs and its impact on the differentiation of T cell subgroups. METHODS: Bone marrow dendritic cells (BMDCs) were activated using house dust mites (HDM) and underwent RNA sequencing (RNA-seq) to pinpoint differentially expressed genes. TFEB mRNA expression levels were assessed in the peripheral blood mononuclear cells (PBMCs) of both healthy children and those diagnosed with asthma. In an asthma mouse model induced by HDM, the TFEB expression in lung tissue DCs was evaluated. Further experiments involved LV-shTFEB BMDCs co-cultured with T cells to explore the influence of TFEB on DCs' antigen presentation, T cell subset differentiation, and cytokine production. RESULTS: Transcriptomic sequencing identified TFEB as a significantly differentially expressed gene associated with immune system pathways and antigen presentation. Notably, TFEB expression showed a significant increase in the PBMCs of children diagnosed with asthma compared to healthy counterparts. Moreover, TFEB exhibited heightened expression in lung tissue DCs of HDM-induced asthmatic mice and HDM-stimulated BMDCs. Silencing TFEB resulted in the downregulation of MHC II, CD80, CD86, and CD40 on DCs. This action reinstated the equilibrium among Th1/Th2 and Th17/Treg cell subgroups, suppressed the expression of pro-inflammatory cytokines like IL-4, IL-5, IL-13, and IL-17, while augmenting the expression of the anti-inflammatory cytokine IL-10. CONCLUSION: TFEB might have a vital role in asthma's development by impacting the antigen presentation of DCs, regulating T cell subgroup differentiation, and influencing cytokine secretion. Its involvement could be pivotal in rebalancing the immune system in asthma. These research findings could potentially unveil novel therapeutic avenues for treating asthma.

Patient and public involvement in systematic reviews: frequency, determinants, stages, barriers, and dissemination.

OBJECTIVES: To investigate the frequency, determinants, stages, and barriers of patient and public involvement (PPI) in systematic reviews and to explore its association with the dissemination of reviews. STUDY DESIGN AND SETTING: We examined systematic reviews that required the inclusion of a PPI declaration, published in The BMJ between January 1, 2015, and December 31, 2022. Multivariable analysis was used to assess the association between PPI and key variables. We investigated the association between PPI and the dissemination of reviews using Altmetric scores, citations, and full-text views. RESULTS: A total of 217 systematic reviews were included, of which 56 (25.8%, 95% CI 20.0%-31.6%) included PPI, with a steady increase from 5.9% (1/17) in 2015 to 44.4% (4/35) in 2022. Of the 217 systematic reviews, 160 (73.7%) involved methodologists as co-authors. Factors significantly associated with a higher proportion of PPI included the publication year after 2019 (adjusted odds ratio [aOR] 2.46, 95% CI 1.26-4.83), the involvement of methodologist (aOR 3.08; 95% CI 1.27-7.47), and being led by researchers from high-income countries (aOR 5.47; 95% CI 1.23-24.30). Reviews that included PPI had higher Altmetric scores per month (6.6 vs 3.4, P = .002) and more monthly full-text (1048.6 vs 636.5, P < .001) and PDF (217.7 vs 129.0, P < .001) views than reviews without PPI. However, there was no difference in the monthly citations (2.2 vs 2.0, P = .365) between reviews with and without PPI. CONCLUSION: The proportion of systematic reviews reporting PPI in The BMJ has increased over time, possibly due to journal policies, but it still remains at a low level. Reviews led by researchers from high-income countries or involving methodologists are associated with a higher frequency of PPI within The BMJ. Furthermore, reviews incorporating PPI within The BMJ have a higher potential for broad dissemination.

Long-chain acyl-CoA synthetase 4-mediated mitochondrial fatty acid metabolism and dendritic cell antigen presentation.

OBJECTIVE: This study aims to investigate the role of Acyl-CoA synthetase 4 (ACSL4) in mediating mitochondrial fatty acid metabolism and dendritic cell (DC) antigen presentation in the immune response associated with asthma. METHODS: RNA sequencing was employed to identify key genes associated with mitochondrial function and fatty acid metabolism in DCs. ELISA was employed to assess the levels of fatty acid metabolism in DCs. Mitochondrial morphology was evaluated using laser confocal microscopy, structured illumination microscopy, and transmission electron microscopy. Flow cytometry and immunofluorescence were utilized to detect changes in mitochondrial superoxide generation in DCs, followed by immunofluorescence co-localization analysis of ACSL4 and the mitochondrial marker protein COXIV. Subsequently, pathological changes and immune responses in mouse lung tissue were observed. ELISA was conducted to measure the levels of fatty acid metabolism in lung tissue DCs. qRT-PCR and western blotting were employed to respectively assess the expression levels of mitochondrial-associated genes (ATP5F1A, VDAC1, COXIV, TFAM, iNOS) and proteins (ATP5F1A, VDAC1, COXIV, TOMM20, iNOS) in lung tissue DCs. Flow cytometry was utilized to analyze changes in the expression of surface antigens presented by DCs in lung tissue, specifically the MHCII molecule and the co-stimulatory molecules CD80/86. RESULTS: The sequencing results reveal that ACSL4 is a crucial gene regulating mitochondrial function and fatty acid metabolism in DCs. Inhibiting ACSL4 reduces the levels of fatty acid oxidases in DCs, increases arachidonic acid levels, and decreases A-CoA synthesis. Simultaneously, ACSL4 inhibition leads to an increase in mitochondrial superoxide production (MitoSOX) in DCs, causing mitochondrial rupture, vacuolization, and sparse mitochondrial cristae. In mice, ACSL4 inhibition exacerbates pulmonary pathological changes and immune responses, reducing the fatty acid metabolism levels within lung tissue DCs and the expression of mitochondria-associated genes and proteins. This inhibition induces an increase in the expression of MHCII antigen presentation molecules and co-stimulatory molecules CD80/86 in DCs. CONCLUSIONS: The research findings indicate that ACSL4-mediated mitochondrial fatty acid metabolism and dendritic cell antigen presentation play a crucial regulatory role in the immune response of asthma. This discovery holds promise for enhancing our understanding of the mechanisms underlying asthma pathogenesis and potentially identifying novel targets for its prevention and treatment.

Panax notoginseng saponin R1 improves glucocorticoid-inhibited airway epithelium repair via glucocorticoid receptor ß.

BACKGROUND: Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma. OBJECTIVE: This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma. METHODS: In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRß-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRß-siRNA and detected cell proliferation and migration. The expression of GRß and key components of MKP-1 and Erk1/2 were detected by western blotting. RESULTS: In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRß expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair. CONCLUSIONS: Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRß expression and activating the MAPK pathway.

The association between PM2.5 concentration and the severity of acute asthmatic exacerbation in hospitalized children: A retrospective study in Chongqing, China.

BACKGROUND: Ambient PM2.5 is associated with asthma exacerbation. The association between the concentration of PM2.5 and the severity of asthma exacerbation has yet to be thoroughly clarified. The study aims to explore the association between the piror 30 days average concentration of PM2.5 and the severity of acute asthma exacerbation in hospitalized children. METHODS: A total of 269 children with acute exacerbation of asthma were enrolled and divided into three groups according to the PM2.5 exposure concentrations: group 1 (PM2.5: <37.5 µg/m3 ), group 2 (PM2.5: 37.5-75 µg/m3 ), group 3 (PM2.5: ≥75 µg/m3 ), respectively. The ordered logistic regression modeling was conducted to explore the influence of daily PM2.5 concentration on the clinical severity of children's asthma exacerbation. Multiple linear regression was conducted to explore the association between the concentration of PM2.5 and the length of stay in the hospital (LOS). We also conducted a receiver operating characteristic (ROC) curve analysis to explore the cutoff value of PM2.5 to predict the children's asthma exacerbation. RESULTS: There was no statistical difference among the three groups of children in gender, age, body mass index, ethnicity, the first diagnosis of asthma, allergic history, passive smoke exposure, or family history of asthma. There was a statistically significant difference in many hospitalization characteristics (p < 0.05) among the three groups of children. Significant differences were found in terms of accessory muscles of respiration (p = 0.005), respiratory failure (p = 0.012), low respiratory tract infectious (p = 0.020), and the severity of asthma exacerbation (p < 0.001) among the three groups. PM2.5 concentration was primarily positively correlated to neutrophile inflammation. The ordered multivariate logistic regression model showed that higher PM2.5 concentrations were significantly associated with greater odds of more severe asthma exacerbation in one and two-pollutant models. The adjusted odds ratio of severe asthma exacerbation was 1.029 (1.009, 1.049) in the one-pollutant model. The most significant odds ratio of severe asthma exacerbation was 1.050 (1.027, 1.073) when controlling NO2 in the two-pollutant models. Multiple linear regression showed that PM2.5 concentration was significantly associated with longer LOS in both one-pollutant and two-pollutant models. By performing ROC analysis, the average daily concentration of 44.5 µg/m3 of PM2.5 (AUC = 0.622, p = 0.002) provided the best performance to predict severe asthma of children exacerbation with a sensitivity of 59.2% and a specificity of 63.8%. CONCLUSION: The increased prior 30 days average concentration of PM2.5 was associated with greater asthma exacerbation severity and longer length of stay in the hospital of children with asthma exacerbation.

Defining RSV epidemic season in southwest China and assessing the relationship between birth month and RSV infection: A 10-year retrospective study from June 2009 to May 2019.

Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections (LRTI). However, only limited information is available regarding its seasonality and its relationship with birth month. A retrospective hospital-based study was carried out from June 2009 to May 2019 in Chongqing, southwest of China. LRTI cases under 5 years were enrolled in this study and PCR was used to detect 8 respiratory viruses. RSV seasonality was determined using "average annual percentage" (AAP) and "percent positivity" method. A total of 6991 cases were enrolled in this study, with an RSV positivity of 34.5%. From June 2009 to May 2019, we analyzed RSV epidemic season during 10 RSV epidemic years in Chongqing using two methods. The result of AAP method was similar to that of percent positivity method with a 30% threshold, which showed an epidemic season of roughly October to March in the subsequent year, with a small peak in June. On average, the RSV epidemic season in RSV-A dominant years typically started earlier (week 42 for RSV-A vs. week 46 for RSV-B), ended earlier (week 12 for RSV-A vs. week 14 for RSV-B), lasted longer (24 weeks for RSV-A vs. 22 weeks for RSV-B), and reached its peak earlier (week 2 for RSV-A vs. week 3 for RSV-B) than in RSV-B dominant years. The proportion of severe LRTI was higher in cases of single infection with RSV-A compared to those of single infection with RSV-B (26.3% vs. 22.3%, p = 0.024). Among infants under 1 year, those born in May and August through December were more likely to be infected with RSV. Infants born 1-2 months before the epidemic season were relatively more susceptible to RSV infection. In Chongqing, the RSV epidemic was seasonal and usually lasted from October to March of next year with a small peak in summer. Infants born 1-2 months before the epidemic season were relatively more susceptible to RSV infection and this population should be targeted while developing RSV immunization strategies.

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OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS: Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Dysregulation of iron homeostasis in airways associated with persistent preschool wheezing.

BACKGROUND: Currently, there are no reliable clinical tools available to identify persistent asthma symptoms among preschool children with recurrent wheezing. We investigated iron homeostasis in the airways of preschoolers with recurrent wheezing and assessed whether iron homeostasis-related indices may reliably predict persistent wheezing. METHODS: Iron levels and mRNA expression levels of iron homeostasis molecules were examined in bronchoalveolar lavage samples from 89 preschoolers with recurrent wheezing and 56 controls, with a 12-month follow-up conducted. Risk factors for persistent wheezing were identified using least absolute shrinkage and selection operator and multivariate logistic regression. The addition of predictive values of iron indices to the modified Asthma Predictive Index (mAPI) or clinical predictors was determined using area under receiver operating characteristic curves (AUC). RESULTS: Preschoolers with recurrent wheezing had reduced iron levels in their airways, associated with significantly decreased expression of iron export molecule SLC40A1 and increased expression of iron intake factor TFR1 and iron storage factors FTH and FTL. Risk factors for persistent wheezing included mAPI positivity, iron predictors (lower expression of SLC40A1 and higher expression of FTL), and clinical predictors (aeroallergen sensitivity, shorter breastfeeding duration, and earlier age of first wheezing episode). The addition of information on iron predictors significantly enhanced the power of clinical predictors (AUC: 84%, increase of 12%) and mAPI (AUC: 81%, increase of 14%). CONCLUSIONS: Iron homeostasis is altered in the airways of preschoolers with recurrent wheezing. Adding information on iron-related indices to clinical information significantly improves accurate prediction of persistent wheezing in preschool-aged children.

The role of small airway function parameters in preschool asthmatic children.

BACKGROUND: Small airways are the major sites of inflammation and airway remodeling in all severities of asthma patients. However, whether small airway function parameters could reflect the airway dysfunction feature in preschool asthmatic children remain unclear. We aim to investigate the role of small airway function parameters in evaluating airway dysfunction, airflow limitation and airway hyperresponsiveness (AHR). METHODS: Eight hundred and fifty-one preschool children diagnosed with asthma were enrolled retrospectively to investigate the characteristics of small airway function parameters. Curve estimation analysis was applied to clarify the correlation between small and large airway dysfunction. Spearman's correlation and receiver-operating characteristic (ROC) curves were employed to evaluate the relationship between small airway dysfunction (SAD) and AHR. RESULTS: The prevalence of SAD was 19.5% (166 of 851) in this cross-sectional cohort study. Small airway function parameters (FEF25-75%, FEF50%, FEF75%) showed strong correlations with FEV1% (r = 0.670, 0.658, 0.609, p<0.001, respectively), FEV1/FVC% (r = 0.812, 0.751, 0.871, p<0.001, respectively) and PEF% (r = 0.626, 0.635, 0.530, p<0.01, respectively). Moreover, small airway function parameters and large airway function parameters (FEV1%, FEV1/FVC%, PEF%) were curve-associated rather than linear-related (p<0.001). FEF25-75%, FEF50%, FEF75% and FEV1% demonstrated a positive correlation with PC20 (r = 0.282, 0.291, 0.251, 0.224, p<0.001, respectively). Interestingly, FEF25-75% and FEF50% exhibited a higher correlation coefficient with PC20 than FEV1% (0.282 vs. 0.224, p = 0.031 and 0.291 vs. 0.224, p = 0.014, respectively). ROC curve analysis for predicting moderate to severe AHR showed that the area under the curve (AUC) was 0.796, 0.783, 0.738, and 0.802 for FEF25-75%, FEF50%, FEF75%, and the combination of FEF25-75% and FEF75%, respectively. When Compared to children with normal lung function, patients with SAD were slightly older, more likely to have a family history of asthma and airflow obstruction with lower FEV1% and FEV1/FVC%, lower PEF% and more severe AHR with lower PC20 ( all p<0.05). CONCLUSION: Small airway dysfunction is highly correlated with large airway function impairment, severe airflow obstruction and AHR in preschool asthmatic children. Small airway function parameters should be utilized in the management of preschool asthma.

Effect of Acute PM2.5 Exposure on Lung Function in Children: A Systematic Review and Meta-Analysis.

Objective: The objective of this study was to conduct a systematic review and meta-analysis to identify the adverse effects of acute PM2.5 exposure on lung function in children. Design: Systematic review and meta-analysis. Setting, participants and measures: Eligible studies analyzing PM2.5 level and lung function in children were screened out. Effect estimates of PM2.5 measurements were quantified using random effect models. Heterogeneity was investigated with Q-test and I2 statistics. We also conducted meta-regression and sensitivity analysis to explore the sources of heterogeneity, such as different countries and asthmatic status. Subgroup analyses were conducted to determine the effects of acute PM2.5 exposure on children of different asthmatic status and in different countries. Results: A total of 11 studies with 4314 participants from Brazil, China and Japan were included finally. A 10 µg/m3 increase of PM2.5 was associated with a 1.74L/min (95% CI: -2.68, -0.90) decrease in peak expiratory flow (PEF). Since the asthmatic status and country could partly explain the heterogeneity, we conducted the subgroup analysis. Children with severe asthma were more susceptible to PM2.5 exposure (-3.11 L/min per 10 µg/m3 increase, 95% CI -4.54, -1.67) than healthy children (-1.61 L/min per 10 µg/m3 increase, 95% CI -2.34, -0.91). In the children of China, PEF decreased by 1.54 L/min (95% CI -2.33, -0.75) with a 10 µg/m3 increase in PM2.5 exposure. In the children of Japan, PEF decreased by 2.65 L/min (95% CI -3.82, -1.48) with a 10 µg/m3 increase of PM2.5 exposure. In contrast, no statistic association was found between every 10 µg/m3 increase of PM2.5 and lung function in children of Brazil (-0.38 L/min, 95% CI -0.91, 0.15). Conclusion: Our results demonstrated that the acute PM2.5 exposure exerted adverse impacts on children's lung function, and children with severe asthma were more susceptible to the increase of PM2.5 exposure. The impacts of acute PM2.5 exposure varied across different countries.

Transcriptomic analysis identified SLC40A1 as a key iron metabolism-related gene in airway macrophages in childhood allergic asthma.

Introduction: Asthma is the most common chronic condition in children, with allergic asthma being the most common phenotype, accounting for approximately 80% of cases. Growing evidence suggests that disruption of iron homeostasis and iron regulatory molecules may be associated with childhood allergic asthma. However, the underlying molecular mechanism remains unclear. Methods: Three childhood asthma gene expression datasets were analyzed to detect aberrant expression profiles of iron metabolism-related genes in the airways of children with allergic asthma. Common iron metabolism-related differentially expressed genes (DEGs) across the three datasets were identified and were subjected to functional enrichment analysis. Possible correlations between key iron metabolism-related DEGs and type 2 airway inflammatory genes were investigated. Single-cell transcriptome analysis further identified major airway cell subpopulations driving key gene expression. Key iron metabolism-related gene SLC40A1 was validated in bronchoalveolar lavage (BAL) cells from childhood asthmatics with control individuals by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence. The intracellular iron content in BAL cells was assessed by Perls iron staining and the iron levels in BAL supernatant was measured by iron assay to assess airway iron metabolism status in childhood asthmatics. Results: Five common iron metabolism-related DEGs were identified, which were functionally related to iron homeostasis. Among these genes, downregulated SLC40A1 was strongly correlated with type 2 airway inflammatory markers and the gene signature of SLC40A1 could potentially be used to determine type 2-high and type 2-low subsets in childhood allergic asthmatics. Further single-cell transcriptomic analysis identified airway macrophages driving SLC40A1 expression. Immunofluorescence staining revealed colocalization of FPN (encoded by SLC40A1) and macrophage marker CD68. Down-regulation of SLC40A1 (FPN) was validated by qRT-PCR and immunofluorescence analysis. Results further indicated reduced iron levels in the BAL fluid, but increased iron accumulation in BAL cells in childhood allergic asthma patients. Furthermore, decreased expression of SLC40A1 was closely correlated with reduced iron levels in the airways of children with allergic asthma. Discussion: Overall, these findings reveal the potential role of the iron metabolism-related gene SLC40A1 in the pathogenesis of childhood allergic asthma.

Vancomycin efficiency and safety of a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis.

Background: Optimal vancomycin trough concentrations and dosages remain controversial in sepsis children. We aim to investigate vancomycin treatment outcomes with a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis from a clinical perspective. Methods: Children diagnosed with Gram-positive bacterial sepsis and received intravenous vancomycin therapy between January 2017 and June 2020 were enrolled retrospectively. Patients were categorized as success and failure groups according to treatment outcomes. Laboratory, microbiological, and clinical data were collected. The risk factors for treatment failure were analyzed by logistic regression. Results: In total, 186 children were included, of whom 167 (89.8%) were enrolled in the success group and 19 (10.2%) in the failure group. The initial and mean vancomycin daily doses in failure group were significantly higher than those in success group [56.9 (IQR =42.1-60.0) vs. 40.5 (IQR =40.0-57.1), P=0.016; 57.0 (IQR =45.8-60.0) vs. 50.0 (IQR =40.0-57.6) mg/kg/d, P=0.012, respectively] and median vancomycin trough concentrations were similar between two groups [6.9 (4.0-12.1) vs.7.3 (4.5-10.6) mg/L, P=0.568)]. Moreover, there was no significant differences in treatment success rate between vancomycin trough concentrations ≤15 mg/L and >15 mg/L (91.2% vs. 75.0%, P=0.064). No vancomycin-related nephrotoxicity adverse effects occurred among all enrolled patients. Multivariate analysis revealed that a PRISM III score ≥10 (OR =15.011; 95% CI: 3.937-57.230; P<0.001) was the only independent clinical factor associated with increased incidence of treatment failure. Conclusions: Vancomycin dosages of 40-60 mg/kg/d are effective and have no vancomycin-related nephrotoxicity adverse effects in children with Gram-positive bacterial sepsis. Vancomycin trough concentrations >15 mg/L are not an essential target for these Gram-positive bacterial sepsis patients. PRISM III scores ≥10 may serve as an independent risk factor for vancomycin treatment failure in these patients.

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OBJECTIVES: To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis. METHODS: The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB. RESULTS: A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%. CONCLUSIONS: The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.