Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection. Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir (at a dose of 10 to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms). The intention-to-treat population included all the participants with RSV-confirmed infection who received at least one dose of ziresovir or placebo; the safety population included all the participants who received at least one dose of ziresovir or placebo. RESULTS: The intention-to-treat population included 244 participants, and the safety population included 302. The reduction from baseline in the Wang bronchiolitis clinical score at day 3 was significantly greater with ziresovir than with placebo (-3.4 points [95% confidence interval {CI}, -3.7 to -3.1] vs. -2.7 points [95% CI, -3.1 to -2.2]; difference, -0.8 points [95% CI, -1.3 to -0.3]; P = 0.002). The reduction in the RSV viral load at day 5 was greater in the ziresovir group than in the placebo group (-2.5 vs. -1.9 log10 copies per milliliter; difference, -0.6 log10 copies per milliliter [95% CI, -1.1 to -0.2]). Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months of age or younger. The incidence of adverse events related to the drug or placebo was 16% with ziresovir and 13% with placebo. The most common adverse events that were assessed by the investigator as being related to the drug or placebo were diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1%). Resistance-associated mutations were identified in 15 participants (9%) in the ziresovir group. CONCLUSIONS: Ziresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. (Funded by Shanghai Ark Biopharmaceutical; AIRFLO ClinicalTrials.gov number, NCT04231968.).

Inhibition, transition, and surge: dynamic evolution of pediatric respiratory pathogen trends amid COVID-19 pandemic policy adjustments.

Background: The implementation of a zero-COVID policy for 3 years in China during the COVID-19 pandemic significantly impacted a broad spectrum of acute respiratory tract infections (ARTIs). The epidemiological characteristics of ARTI pathogens in children following the cessation of the zero-COVID policy remain unclear. Methods: Etiologically diagnostic data from 82,708 children with ARTIs at the Children's Hospital of Soochow University during 2016-2023 were analyzed for 8 pathogens (human respiratory syncytial virus [HRSV], influenza A [FluA], FluB, human parainfluenza virus [HPIV], adenovirus [ADV], human rhinovirus [HRV], bocavirus [BoV], and mycoplasma pneumoniae [MP]). The changes in respiratory infections in Suzhou, China during the first year (2020, Phase I) and the second and third years of the pandemic (2021-2022, Phase II) and the first year after the end of zero-COVID policy (2023, Phase III) versus that in the pre-pandemic years (2016-2019) were compared. Results: When compared with the average pre-pandemic levels, the pathogen-positive rate decreased by 19.27% in Phase I (OR: 0.70; 95% CI: 0.67-0.74), increased by 32.87% in Phase II (OR: 1.78; 95% CI: 1.72-1.84), and increased by 79.16% in Phase III (OR: 4.58; 95% CI: 4.37-4.79). In Phase I, the positive rates of HRSV, FluA, ADV, and MP decreased by 26.72, 58.97, 72.85, and 67.87%, respectively, and the positive rates of FluB, HPIV, HRV, and BoV increased by 86.84, 25, 32.37, and 16.94%, respectively. In Phase III, the positive rates of HRSV, FluA, FluB, HPIV, ADV, and HRV increased by 39.74, 1046.15, 118.42, 116.57, 131.13, and 146.40%, respectively, while the positive rate of BoV decreased by 56.12%. MP was inhibited during the epidemic, and MP showed a delayed outbreak after the ending of the zero-COVID policy. Compared with the average pre-pandemic levels, the MP-positive rate in Phase III increased by 116.7% (OR: 2.86; 95% CI: 2.74-2.99), with the highest increase in 0-1-year-old children. Conclusion: The strict and large-scale implementation of the zero-COVID policy in the early stages of the COVID-19 pandemic was the main driving factor for the sharp reduction in the rate of children's respiratory pathogenic infections. The termination of this policy can cause a resurgence or escalation of pathogenic infections.

Changes in the epidemiology of pediatric brain abscesses pre- and post-COVID-19 pandemic: a single-center study.

BACKGROUND: An increased incidence of brain abscesses was observed post-COVID-19 pandemic. However, it remains unclear how the COVID-19 pandemic influenced the epidemiology of brain abscesses. This study aimed to investigate changes in the epidemiology of brain abscesses pre- and post-COVID-19 pandemic. METHODS: A retrospective study of demographic, clinical, radiological, and laboratory characteristics of patients with brain abscesses in Children's Hospital of Soochow University from 2015-2023 was performed. RESULTS: A total of 34 patients were admitted to the hospital during the study. The post-COVID-19 cohort had an average of 5.5 cases/year, which is a 129.2% increase compared to the pre-COVID-19 cohort's average of 2.4 cases/year. Additionally, the rates of fever upon admission (86.36% vs 50%, p = 0.04) and experiencing high-grade fever within 6 weeks before admission (40.91% vs 8.33%, p = 0.044) were significantly increased. A potential rise in the rate of intensive care unit admission was observed (36.36% vs 8.33%, p = 0.113). The average value of globulin in the post-COVID cohort was significantly higher compared to the pre-COVID cohort (31.60 ± 5.97 vs 25.50 ± 5.08, p = 0.009). Streptococcal infections were the predominant cause of brain abscesses in both cohorts (40% vs 43.75%, p = 0.57). CONCLUSIONS: There was a significant increase in the number of brain abscess patients after the COVID-19 pandemic. This underscores the importance of children receiving the streptococcal vaccine.

Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid.

Background: This study aimed to investigate the clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia (CAP) and concomitant cytomegalovirus (CMV) infection. Methods: This cross-sectional study enrolled consecutive pediatric patients admitted with CAP who tested positive for CMV DNA in bronchoalveolar lavage fluid (BALF). Flexible fiberoptic bronchoscopy was performed when routine treatment for CAP proved ineffective. The study participants were further stratified into two groups based on CMV serological test results: recent CMV infection group and CMV replication group. Clinical characteristics were compared between these two groups. Results: Among 124 patients aged 1-11 months included in this study, 80 (64.5%) patients were categorized as having recent CMV infection, and 44 (35.5%) tested positive for CMV replication. Co-infection with other pathogens was detected more frequently in the CMV replication group (n = 29, 65.9%) than in the recent CMV infection group (n = 35, 43.7%; P = 0.018). Patients with recent CMV infection were younger and exhibited higher levels of alanine transaminase (ALT) and aspartate aminotransferase compared to those with CMV replication (all P < 0.05). Multivariable regression analysis showed age was independently associated with recent CMV infection (odds ratio [OR], 0.707; 95% confidence interval [CI], 0.586-0.853; P < 0.001). Notably, receiver operating characteristic curve analysis showed that a CMV PCR level of 3,840 copies/ml in blood samples had a sensitivity of 34.7% and specificity of 90.0% for diagnosis of recent CMV infection with an area under the curve (AUC) of 0.625 (95% CI: 0.513-0.736, P = 0.048). A CMV PCR level of 6,375 copies/ml in urine samples had a sensitivity of 77.1% and specificity of 61.5% for diagnosis of recent CMV infection with an AUC of 0.695 (95% CI: 0.531-0.858, P = 0.04). Furthermore, multivariate linear regression analysis revealed that the blood CMV DNA copy number was associated with ALT (B = 0.001; P < 0.001). Conclusions: The CMV DNA copy numbers in blood and urine could serve as discriminatory markers between recent CMV infection and CMV replication. Measuring CMV DNA levels in blood may be an effective method for monitoring liver function impairment in pediatric patients presenting with CAP and concurrent CMV infection.

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.

Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling.

Asthma is the most prevalent chronic inflammatory disease of the airways in children. The most prevalent phenotype of asthma is eosinophilic asthma, which is driven by a Th2 immune response and can be effectively managed by inhaled corticosteroid therapy. However, there are phenotypes of asthma with Th17 immune response that are insensitive to corticosteroid therapy and manifest a more severe phenotype. The treatment of this corticosteroid-insensitive asthma is currently immature and requires further attention. The objective of this study is to elucidate the regulation of the Hedgehog signaling pathway in Th17 cell differentiation in asthma. The study demonstrated that both Smo and Gli3, key components of the Hedgehog signaling pathway, were upregulated in Th17 polarization in vitro and in a Th17-dominant asthma model in vivo. Inhibiting Smo with a small molecule inhibitor or genetically knocking down Gli3 was found to suppress Th17 polarization. Smo was found to increase in Th1, Th2, Th17 and Treg polarization, while Gli3 specifically increased in Th17 polarization. ChIP-qPCR analyses indicated that Gli3 can directly interact with IL-6 in T cells, inducing STAT3 phosphorylation and promoting Th17 cell differentiation. Furthermore, the study demonstrated a correlation between elevated Gli3 expression and IL-17A and IL-6 expression in children with asthma. In conclusion, the study demonstrated that the Hedgehog signaling pathway plays an important role in the pathogenesis of asthma, as it regulates the differentiation of Th17 cells through the IL-6/STAT3 signaling. This may provide a potential therapeutic target for corticosteroid-insensitive asthma driven by Th17 cells.

S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice.

Background: Allergic asthma is the most prevalent asthma phenotype and is associated with the disorders of immune cells and glycolysis. Macrophages are the most common type of immune cells in the lungs. Calprotectin (S100A8 and S100A9) are two pro-inflammatory molecules that target the Toll-like receptor 4 (TLR4) and are substantially increased in the serum of patients with severe asthma. This study aimed to determine the effects of S100A8/A9 on macrophage polarization and glycolysis associated with allergic asthma. Methods: To better understand the roles of S100A8 and S100A9 in the pathogenesis of allergic asthma, we used ovalbumin (OVA)-induced MH-S cells, and OVA-sensitized and challenged mouse models (wild-type male BALB/c mice). Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, flow cytometry, hematoxylin-eosin staining, and western blotting were performed. The glycolysis inhibitor 3-bromopyruvate (3-BP) was used to observe changes in glycolysis in mice. Results: We found knockdown of S100A8 or S100A9 in OVA-induced MH-S cells inhibited inflammatory cytokines, macrophage polarization biomarker expression, and pyroptosis cell proportion, but increased anti-inflammatory cytokine interleukin (IL)-10 mRNA; also, glycolysis was inhibited, as evidenced by decreased lactate and key enzyme expression; especially, knockdown of S100A8 or S100A9 inhibited the activity of TLR4/myeloid differentiation primary response gene 88 (MyD88)/Nuclear factor kappa-B (NF-κB) signaling pathway. Intervention with lipopolysaccharides (LPS) abolished the beneficial effects of S100A8 and S100A9 knockdown. The observation of OVA-sensitized and challenged mice showed that S100A8 or S100A9 knockdown promoted respiratory function, improved lung injury, and inhibited inflammation; knockdown of S100A8 or S100A9 also suppressed macrophage polarization, glycolysis levels, and activation of the TLR4/MyD88/NF-κB signaling pathway in the lung. Conversely, S100A9 overexpression exacerbated lung injury and inflammation, promoting macrophage polarization and glycolysis, which were antagonized by the glycolysis inhibitor 3-BP. Conclusion: S100A8 and S100A9 play critical roles in allergic asthma pathogenesis by promoting macrophage perturbation and glycolysis through the TLR4/MyD88/NF-κB signaling pathway. Inhibition of S100A8 and S100A9 may be a potential therapeutic strategy for allergic asthma.

Clinical characteristics of persistent or recurrent pneumonia combined with airway malacia in children.

OBJECTIVE: The aim of this study is to investigate the clinical characteristics and pathogens involved in persistent or recurrent pneumonia combined with airway malacia in children. METHODS: We retrospectively reviewed the information of children hospitalised with persistent or recurrent pneumonia, including clinical presentations, laboratory examination results and pathogens. RESULTS: A total of 554 patients were admitted, 285 (51.44%) of whom were found to have airway malacia. There were 78 (27.37%), 166 (58.25%) and 41 (14.39%) patients with mild, moderate and severe malacia, respectively. Patients with airway malacia were younger than those without malacia (6.0 vs. 12.0 months, p < 0.01) and were more likely to present with wheezing (75.07%), fever (34.39%), dyspnoea (28.77%), cyanosis (13.68%) and wheezing in the lungs (78.95%). The incidence of preterm delivery, oxygen therapy, paediatric intensive care unit (PICU) admission and mechanical ventilation was higher, and the hospital stay (11.0 vs. 10.0 days, p = 0.04) was longer in these patients than in those without malacia. Patients with severe airway malacia were more likely to undergo oxygen therapy, PICU admission, mechanical ventilation and have multiple malacia than were those with mild or moderate malacia. Mycoplasma pneumoniae (30.18%) was the most common pathogen. CONCLUSION: Severe airway malacia likely aggravates conditions combined with pneumonia. The proportion of multisite malacia was greater in severe airway malacia patients.

Intervention with ICOSL Antibodies Alleviates Inflammatory Infiltrations in Mice with Neutrophilic Asthma.

Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation. Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma. Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically. Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice. Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.

miR-130b regulates B cell proliferation via CYLD-mediated NF-κB signaling.

Previous studies have revealed that B cell activation is regulated by various microRNAs(miRNAs). However, the role of microRNA-130b regulating B cell activation and apoptosis is still unclear. In the present study, we first found that the expression of miR-130b was the lowest in Pro/Pre-B cells and the highest in immature B cells. Besides, the expression of miR-130b decreased after activation in B cells. Through the immuno-phenotypic analysis of miR-130b transgenic and knockout mice, we found that miR-130b mainly promoted the proliferation of B cells and inhibited B cell apoptosis. Furthermore, we identified that Cyld, a tumor suppressor gene was the target gene of miR-130b in B cells. Besides, the Cyld-mediated NF-κB signaling was increased in miR-130b overexpressed B cells, which further explains the enhanced proliferation of B cells. In conclusion, we propose that miR-130b promotes B cell proliferation via Cyld-mediated NF-κB signaling, which provides a new theoretical basis for the molecular regulation of B cell activation.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Developing and validating clinical models to identify candidates for allergic rhinitis pre-exposure prophylaxis.

PURPOSE: Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire. METHODS: This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively. RESULTS: This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models. CONCLUSION: Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Are we ready to face the next wave of RSV surge after the COVID-19 Omicron pandemic in China?

Background: China had its first wave of COVID-19 in 2020 and second wave of COVID-19 Omicron in 2022. The number of RSV cases decreased sharply in 2020 and 2022. Investigation of the resurge of RSV infections after the first wave of COVID-19 will guide us to take preventive actions before the resurge of RSV infections after the second wave of COVID-19 Omicron. Methods: We analysed epidemiological and clinical data of 59934 patients with lower respiratory tract infections (LRTI) from a prospective long-term cohort surveillance programme in Suzhou, China, collected from February 2016 to January 2022. The annual incidence of RSV infection in children aged<16 years in 2020 and 2021 was compared with the pre-pandemic years 2016 to 2019. We also compared the clinical characteristics, and RSV-related ICU admissions between pre-pandemic years and 2021. Results: Among children with LRTI, the positive rate of RSV increased by 70.7% in 2021 compared to the average level in the pre-pandemic years. The RSV resurge in 2021 was most prominently in children aged 2-4 years (a significant rise compared with the expected value 149.1%; 95%CI, 67.7% to 378%, P<.01). The percentage of RSV-related ICU admissions decreased in 2021 (3.2% vs 6.7%, P<0.01). The death rate of RSV infections in 2021 was 0.2%, while that in pre-pandemic years was only 0.02%. RSV-associated death in immunocompetent children (complicated by necrotizing encephalitis) was firstly occurred in 2021. Conclusions: Our findings raise concerns for RSV control in Southeast China after the COVID-19 pandemic especially for children aged 2-4 years. Although ICU admissions were significantly reduced in this resurgence, we could not ignore the increase of RSV-associated death.

Etiology and clinical features of infection-associated plastic bronchitis in children.

OBJECTIVE: To investigate the etiological characteristics of plastic bronchitis (PB) caused by pulmonary infections in children and to identify any differences in the clinical features of PB cases caused by different pathogens. METHOD: We collected data on children diagnosed with PB and admitted to the Respiratory Department at Soochow University Children's Hospital between July 2021 and March 2023 utilizing electronic bronchoscopy. We analyzed clinical characteristics and the species of pathogens causing the illness in these children. RESULT: A total of 45 children were enrolled. The main clinical symptoms observed were cough (100%), fever (80%), shortness of breath (28.9%), and wheezing (20.0%). Pathogens were identified in 38 (84.4%) patients. Mycoplasma pneumoniae (MP) had the highest detection rate at 53.3%, followed by the Boca virus at 26.7%. MP-induced PB typically occurs in older children with an average age of 7.46 ± 2.36 years, with the main symptoms including high fever (85.7%) and local hyporespiration (42.9%). In contrast, Boca virus-induced PB tends to occur in younger children, with the main symptoms of moderate fever (54.5%), and wheezing (54.5%). The MP group exhibited a higher incidence of both internal and external pulmonary complications, including pleural effusion (42.9%), elevated aspartate aminotransferase (52.4%), lactic dehydrogenase (76.2%), and D-D dimer (90.5%). Conversely, the Boca virus group primarily showed pulmonary imaging of atelectasis (81.8%), with no pleural effusion. The average number of bronchoscopic interventions in the MP group was 2.24 ± 0.62, which was significantly higher than that required in the Boca virus group (1.55 ± 0.52). During the second bronchoscopy, 57.1% of children in the MP group still had visible mucus plugs, while none were observed in the Boca virus group. CONCLUSION: MP and Boca virus are the primary pathogens responsible for PB among children. The clinical manifestations of PB typically vary significantly based on the pathogen causing the condition.

Patterns of aeroallergen sensitization in asthma patients identified by latent class analysis: A cross-sectional study in China.

BACKGROUND: This cross-sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. METHODS: 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. RESULTS: Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: "High weed pollen and house dust mites (HDMs) sensitization" (8.87%), Class 2: "HDMs dominated sensitization" (38.38%), Class 3: "High HDMs and animal dander sensitization" (6.95%), Class 4: "Low/no aeroallergen sensitization" (45.80%). Western cohort: Class 1: "High weed pollen sensitization" (26.14%), Class 2: "High multi-pollen sensitization" (15.02%), Class 3: "HDMs-dominated sensitization" (10.33%), Class 4: "Low/no aeroallergen sensitization" (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. CONCLUSIONS: Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

DTX3L Enhances Type I Interferon Antiviral Response by Promoting the Ubiquitination and Phosphorylation of TBK1.

Studies already revealed that some E3 ubiquitin ligases participated in the immune response after viral infection by regulating the type I interferon (IFN) pathway. Here, we demonstrated that type I interferon signaling enhanced the translocation of ETS1 to the nucleus and the promoter activity of E3 ubiquitin ligase DTX3L (deltex E3 ubiquitin ligase 3L) after virus infection and thus increased the expression of DTX3L. Further experiments suggested that DTX3L ubiquitinated TBK1 at K30 and K401 sites on K63-linked ubiquitination pathway. DTX3L was also necessary for mediating the phosphorylation of TBK1 through binding with the tyrosine kinase SRC: both together enhanced the activation of TBK1. Therefore, DTX3L, being an important positive-feedback regulator of type I interferon, exerted a key role in antiviral response. IMPORTANCE Our present study evaluated DTX3L as an antiviral molecule by promoting IFN production and establishing an IFN-ß-ETS1-DTX3L-TBK1 positive-feedback loop as a novel immunomodulatory step to enhance interferon signaling and inhibit respiratory syncytial virus (RSV) infection. Our finding enriches and complements the biological function of DTX3L and provides a new strategy to protect against lung diseases such as bronchiolitis and pneumonia that develop with RSV.