Andrographolide Attenuates RSV-induced Inflammation by Suppressing Apoptosis and Promoting Pyroptosis after Respiratory Syncytial Virus Infection In Vitro.

BACKGROUND: Respiratory syncytial virus (RSV), which is the predominant viral pathogen responsible for causing acute lower respiratory tract infections in children, currently lacks specific therapeutic drugs. Despite andrographolide's demonstrated effectiveness against various viral infections, its effects on RSV infection remain unclear. METHODS: In this study, RSV infection and andrographolide-intervened A549 cell lines were used. The virus load of RSV and the levels of IL-6 and IL-8 in the cell supernatant were quantified. The potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were analyzed using the Gene Expression Omnibus (GEO) database and the PharmMapper Database, and the changes in mRNA expression of these target genes were measured. To further illustrate the effect of andrographolide on the death pattern of RSV-infected airway epithelial cells, Annexin V-FITC/PI apoptosis assays and Western blotting were conducted. RESULTS: Andrographolide decreased the viral load and attenuated IL-6 and IL-8 levels in cell supernatant post-RSV infection. A total of 25 potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were discovered, and CASP1, CCL5, JAK2, and STAT1 were identified as significant players. Andrographolide noticeably suppressed the increased mRNA expressions of these genes post-RSV infection as well as IL-1ß. The flow cytometry analysis demonstrated that andrographolide alleviated apoptosis in RSV-infected cells. Additionally, RSV infection decreased the protein levels of caspase-1, cleaved caspase-1, cleaved IL-1ß, N-terminal of GSDMD, and Bcl-2. Conversely, andrographolide increased their levels. CONCLUSION: These results suggest that andrographolide may reduce RSV-induced inflammation by suppressing apoptosis and promoting pyroptosis in epithelial cells, leading to effective viral clearance.

Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection: a randomized controlled trial.

BACKGROUND: Saline nasal irrigation is an effective therapy for relieving common cold symptoms. This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation (PSNI) on children with mild and asymptomatic infection with Omicron. METHODS: This randomized controlled trial was conducted in Shanghai, China, and 403 children with mild and asymptomatic infection with Omicron were included. These children were allocated into the PSNI group and the control group. The primary outcome was the duration of viral shedding (DVS), and the secondary outcome was the change in clinical symptoms. RESULTS: The median age of all participants was 5.59 (6.26) years old. The DVS was significantly shorter in the PSNI group [2.40 (1.13)] than in the control group [3.09 (2.14)] (P = 0.014). The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group [hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.04-1.55; P = 0.017]. Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group. The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group, but there was no evidence showing that PSNI contributes to the benefit compared with the control group. CONCLUSION: PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

Vaccination status for mild and asymptomatic infections with SARS-CoV-2 Omicron BA.2 variant in Shanghai.

This study aimed to evaluate the effects of different vaccine regimens on mild and asymptomatic infections with SARS-CoV-2 Omicron BA.2 variant in Shanghai. All asymptomatic patients and those with mild symptoms of Omicron infections were recruited from three major Fangcang shelter hospitals between March 26, 2022 and May 20, 2022. Nucleic acid for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction methods in nasopharyngeal swabs was assessed every day during the hospitalization. The value of cycle threshold lower than 35 was considered as positive result of SARS-CoV-2. A total of 214 592 cases were included in this study. The proportion of the asymptomatic patients was 76.90% and 23.10% of the recruited patients had mild symptoms. The median (interquartile range [IQR]: 25-75) duration of viral shedding (DVS) was 7 (5-10) days among all participants. The DVS varied greatly among different age groups. Children and the elderly had longer DVS compared with the adults. The booster shot of inactivated vaccine contributed to the shorter DVS in patients aged ≥70 years compared with the unvaccinated patients (8 [6-11] vs. 9 [6-12] days, p = 0.002]. Full inactivated vaccine regimen contributed to the shorter DVS in patients aged 3-6 years (7 [5-9] vs. 8 [5-10] days, p = 0.001]. In conclusion, the full inactivated vaccine regimen on children aged 3-6 years and booster inactivated vaccine regimen on the elderly aged ≥70 years appeared to be effective in reducing DVS. The booster vaccine regimen should be rigorously promoted and implemented.

Racial differences in the associations of urinary phthalate metabolites with depression risk.

OBJECTIVE: This study aimed to investigate the composite effects of different kinds of phthalates on depression risk in the U.S population. METHODS: 11731 participants were included from the National Health and Nutrition Examination Survey (NHANES), a national cross-sectional survey. Twelve urinary phthalate metabolites were used to evaluate the level of phthalates exposure. Phthalates levels were devided into four quartiles. High phthalate was defined as having values in the highest quartile. RESULTS: Urinary mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP) were estimated as the independent risk factors for depression by mutivariate logistic regression analyses. Compared with the lowest quartile group of MiBP or MBzP, an incrementally higher risk of depression and moderate/severe depression was observed in the highest quartile (all Ptrend <0.05). It was observed that incrementally higher risk of depression and moderate/severe depression were associated with more numbers of high phthalates parameter (Ptrend <0.001 and Ptrend = 0.003, respectively). A significant interaction between race (Non-Hispanic Black vs. Mexican American) and 2 parameters (having value in the highest quartile of both MiBP and MBzP) was detected for depression (Pinteraction = 0.023) and moderate/severe depression (Pinteraction = 0.029). CONCLUSION: Individuals with more numbers of high phthalates parameter were at higher risk of depression and moderate/severe depression. Non-Hispanic Black participants were more likely to be affected by high levels of MiBP and MBzP exposure than Mexican American participants.

Huashi baidu granule in the treatment of pediatric patients with mild coronavirus disease 2019: A single-center, open-label, parallel-group randomized controlled clinical trial.

Background: Since late February 2022, a wave of coronavirus disease 2019 (COVID-19) mainly caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China. Traditional Chinese medicine treatment is recommended for pediatric patients; however, the safety and efficacy remain to be confirmed. We conducted a single-center, open-label, parallel-group randomized controlled trial to assess the efficacy and safety of a Chinese herb compound, Huashi Baidu granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19. Methods: 108 recruited children (aged 3-18 years) with laboratory-confirmed mild COVID-19 were randomly allocated 2:1 to receive oral HSBDG for five consecutive days (intervention group) and to receive compound pholcodine oral solution for five consecutive days (control group). The negative conversion time of SARS-CoV-2 nucleic acid and symptom scores were recorded. Results: The median negative conversion time of SARS-CoV-2 nucleic acid was significantly shorter in the intervention group than in the control group (median days [interquartile range (IQR)]: 3 [3-5] vs. 5 [3-6]; p = 0.047). The median total symptom score on day 3 was significantly lower in the intervention group than in the control group (median total symptom score [IQR]: 1 [0-2] vs. 2 [0-3]; p = 0.036). There was no significant differences in the frequency of antibiotic use and side effects between the two groups. Conclusion: HSBDG is a safe, effective oral Chinese herbal compound granule, which shows a good performance within the Omicron wave among pediatric patients.

Vitamin A-regulated ciliated cells promote airway epithelium repair in an asthma mouse model.

BACKGROUND: Asthma is a chronic inflammatory airway disease that causes damage to and exfoliation of the airway epithelium. The continuous damage to the airway epithelium in asthma cannot be repaired quickly and generates irreversible damage, repeated attacks, and aggravation. Vitamin A (VA) has multifarious biological functions that include maintaining membrane stability and integrity of the structure and function of epithelial cells. Our research explored the role of VA in repairing the airway epithelium and provided a novel treatment strategy for asthma. METHODS: A mouse asthma model was established by house dust mite (HDM) and treated with VA by gavage. Human bronchial epithelial (16HBE) cells were treated with HDM and all-trans retinoic acid (ATRA) in vitro. We analyzed the mRNA and protein expression of characteristic markers, such as acetyl-α-tubulin (Ac-TUB) and FOXJ1 in ciliated cells and MUC5AC in secretory cells, mucus secretion, airway inflammation, the morphology of cilia, and the integrity of the airway epithelium. RESULTS: Findings showed destruction of airway epithelial integrity, damaged cilia, high mucus secretion, increased MUC5AC expression, and decreased Ac-TUB and FOXJ1 expression in asthmatic mice. The VA intervention reversed the effect on Ac-TUB and FOXJ1 and promoted ciliated cells to repair the damage and maintain airway epithelial integrity. In 16HBE cells, we could confirm that ATRA promoted the expression of Ac-TUB and FOXJ1. CONCLUSION: These results demonstrated that VA-regulated ciliated cells to repair the damaged airway epithelium caused by asthma and maintain airway epithelial integrity. VA intervention is a potential adjunct to conventional treatment for asthma.

Vitamin A–regulated ciliated cells promote airway epithelium repair in an asthma mouse model

Background: Asthma is a chronic inflammatory airway disease that causes damage to and exfoliation of the airway epithelium. The continuous damage to the airway epithelium in asthma cannot be repaired quickly and generates irreversible damage, repeated attacks, and aggravation. Vitamin A (VA) has multifarious biological functions that include maintaining membrane stability and integrity of the structure and function of epithelial cells. Our research explored the role of VA in repairing the airway epithelium and provided a novel treatment strategy for asthma. Methods: A mouse asthma model was established by house dust mite (HDM) and treated with VA by gavage. Human bronchial epithelial (16HBE) cells were treated with HDM and all-trans retinoic acid (ATRA) in vitro. We analyzed the mRNA and protein expression of characteristic markers, such as acetyl-α-tubulin (Ac-TUB) and FOXJ1 in ciliated cells and MUC5AC in secretory cells, mucus secretion, airway inflammation, the morphology of cilia, and the integrity of the airway epithelium. Results: Findings showed destruction of airway epithelial integrity, damaged cilia, high mucus secretion, increased MUC5AC expression, and decreased Ac-TUB and FOXJ1 expression in asthmatic mice. The VA intervention reversed the effect on Ac-TUB and FOXJ1 and promoted ciliated cells to repair the damage and maintain airway epithelial integrity. In 16HBE cells, we could confirm that ATRA promoted the expression of Ac-TUB and FOXJ1. Conclusion: These results demonstrated that VA-regulated ciliated cells to repair the damaged airway epithelium caused by asthma and maintain airway epithelial integrity. VA intervention is a potential adjunct to conventional treatment for asthma (AU)

Allergic diseases aggravate the symptoms of SARS-CoV-2 infection in China.

Background: The relationship between allergic diseases and the adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a subject of controversy. This study aimed to investigate the association between allergic diseases and the incidence and severity of symptoms in SARS-CoV-2 infection. Methods: Clinical data of individuals, including children and their parents, infected with SARS-CoV-2 from December 2022 to January 2023 in China were retrospectively analyzed. The data were collected through questionnaires. Statistical analysis, including chi-squared tests, nonparametric analysis, one-way ANOVA, and logistic regression analysis, was used to examine the relationship between allergic diseases, prior medication, and the symptoms of SARS-CoV-2 infection. Results: There were 3,517 adults and 3,372 children with SARS-CoV-2 infection included in the study. Fever was found to occur at similar rates in children (86.5%) and adults (86.8%). However, other symptoms related to respiratory issues (such as cough and sore throat), neurological symptoms (headache, loss of smell, and loss of taste), and systemic symptoms (muscle soreness and weakness) were observed more frequently in adults (P < 0.001). Additionally, adults exhibited higher overall symptom scores, indicating greater severity. Allergic diseases were found to be associated with the incidence of certain SARS-CoV-2 infection symptoms in both children and adults. Specifically, children with allergic rhinitis (AR) were observed to be more susceptible to upper respiratory symptoms (OR: 1.320, 95% CI: 1.081-1.611, P = 0.006), while asthma patients were found to be more susceptible to severe respiratory symptoms (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). Similar patterns were identified in adults. Furthermore, AR was also suggested to be a risk factor for symptom severity in both children (OR: 1.704, 95% CI: 1.314-2.209, P < 0.001) and adults (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). However, prior medication for allergic diseases did not exhibit a preventive effect on SARS-CoV-2 infection symptoms. Conclusions: Both children and adults with allergic diseases were found to be more prone to experiencing symptoms of SARS-CoV-2 infection, and these symptoms tended to be more severe.

A prediction model for the efficacy of continuous positive airway pressure on bronchiolitis.

Objectives: Prediction of the efficacy of continuous positive airway pressure (CPAP) on bronchiolitis is necessary for timely treatment. This study aims to establish a nomogram for efficacy of CPAP on bronchiolitis, and compares accuracy with Pediatric Risk of Mortality III (PRISM III), Brighton Pediatric Early Warning Score (Brighton PEWS) and Pediatric Critical Illness Score (PCIS). Methods: From February 2014 to December 2020, data on children diagnosed with bronchiolitis and treated with CPAP in Chongqing was collected. The nomogram was evaluated by using multivariate logistic regression analysis. We compared the predictive value of model with PRISM III, PEWS and PCIS. Results: A total of 510 children were included. The nomogram prediction model including fever, APTT, white blood cells, serum potassium concentration, lactic acid, immunodeficiency, atelectasis, lung consolidation, congenital airway dysplasia and congenital heart disease was established. The AUC of the nomogram was 0.919 in the training set and 0.947 in the validating set. The model fitted well, as evidenced by the calibration curve and Hosmer-Lemeshow goodness-of-fit test. We discovered that the nomogram significantly performed better than PRISM III, PCIS and PEWS. Conclusions: A nomogram including ten factors for predicting the efficacy of CPAP on bronchiolitis was established. It had higher performance than the PRISM III, PCIS, and PEWS in terms of clinical benefits.

The Relationship Between Daily Dietary Intake of Fiber and Short Sleep Duration in the Presence of Di(2-Ethylhexyl) Phthalate: A Population-Based Study.

Objective: This study aimed to evaluate the relationship between daily dietary intake of fiber (DDIF) and short sleep duration (SSD) in the presence of di(2-ethylhexyl) phthalate. Methods: Data of 13,634 participants in this study were collected from the National Health and Nutrition Examination Survey (NHANES). The sum of urinary mono-2-ethyl-5-carboxypentyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl)-hexyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate was used to evaluate the level of di(2-ethylhexyl) phthalate (DEHP) exposure. The ln-transformed urinary creatinine-corrected DEHP [ln(DEHP/UCr)] level was used in the statistical models. DDIF was divided into tertiles (<5.77 g/1,000 kcal, 5.77-9.04 g/1,000 kcal, and ≥9.04 g/1,000 kcal). Results: The 13,634 participants included in this study were classified into two groups according to sleep duration. The dose response analysis showed that higher ln(DEHP/UCr) was related to a higher risk of SSD (<7 h and <6 h). Participants in the highest vs. the lowest quartile of DEHP were found to be at increased risk of SSD (<7 h, <6 h, and <5 h). The result of risk of SSD <7 h was OR 1.57, 95% CI, 1.40-1.76; Ptrend <0.001, of SSD <6 h was OR 1.38, 95% CI, 1.18-1.61; Ptrend <0.001, and of SSD <5 h was OR 1.45, 95% CI, 1.13-1.86; Ptrend <0.001. DEHP exposure was found to be associated with SSD <7 h in a sex-specific manner (Pinteraction = 0.033). A significant interaction between ln(DEHP/UCr) and DDIF(tertiles1 vs. tertiles2) (Pinteraction = 0.02) was detected for SSD <7 h. Conclusion: Our results showed that there was a harmful association between DEHP exposure and SSD (<7 h, <6 h, and <5 h). The ameliorative effects of median level of DDIF on SSD <7 h in the presence of DEHP exposure were observed in this study.

Establishment of a Simple Pediatric Lower Respiratory Tract Infections Database Based on the Structured Electronic Medical Records.

Objective: This study aimed to establish a pediatric lower respiratory tract infections (PLRTIs) database based on the structured electronic medical records (SEMRs), to provide a brief overview and the usage process of the SEMRs and the database. Methods: All the medical information is recorded by a clinical information system developed by Eureka Systems Company. A plugin of the software was used to set the properties of items of the SEMR. Children with lower respiratory tract infections (LRTIs) who were admitted to the department of respiratory medicine of our hospital from May 2020 were included. PostgreSQL 13.1 software was used to construct the PLRTIs database. Results: Seven kinds of SEMRs were established, and the admission record was the most important and complex among them. It was mainly composed of 10 parts, i.e., basic information, history of present illness, past history (without respiratory disease), past history of respiratory diseases, personal history, family history, physical examination, the score of LRTIs, auxiliary examination, and diagnosis. With the three-level doctor ward round, the recorded information of the SEMR would be checked repeatedly, thus guaranteeing the correctness of the information. The data of the SEMR and laboratory tests could be extracted directly from the hospital information system (HIS) by PostgreSQL 13.1 software with the specific structured query language (SQL) code. After manually checking the original records, the datasets were imported into PostgreSQL 13.1 software, and a simple PLRTIs database was constructed. According to the inclusion criteria of this study, a total of 1,184 children with LRTIs were included in this database from 1 May 2020 to 30 April 2021. Conclusion: A series of SEMRs for PLRTIs were designed and used during the hospitalization. A simple PLRTIs database was established based on the SEMR. The SEMRs will provide complete and high-quality data on LRTIs in children.

Comparison of Pulmonary Function and Inflammation in Children/Adolescents with New-Onset Asthma with Different Adiposity Statuses.

(1) Background: The relationship between obesity and asthma is still uncertain. This study aimed to investigate the effect of overweight/obesity on the pulmonary function of patients with new-onset pediatric asthma and explore the possible causative factors related to concomitant obesity and asthma. (2) Methods: Patients aged 5 to 17 years old with newly diagnosed mild to moderate asthma were recruited from June 2018 to May 2019, from a respiratory clinic in Shanghai, China. Participants were categorized into three groups: normal weight, overweight, and obese asthma. A family history of atopy and patients' personal allergic diseases were recorded. Pulmonary function, fractional exhaled nitric oxide (FeNO), eosinophils, serum-specific immunoglobulins E (sIgE), serum total IgE (tIgE), and serum inflammatory biomarkers (adiponectin, leptin, Type 1 helper T, and Type 2 helper T cytokines) were tested in all participants. (3) Results: A total of 407 asthma patients (197 normal weight, 92 overweight, and 118 obese) were enrolled. There was a reduction in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), FEV1/FVC%, and FEF25-75% in the overweight/obese groups. No difference was found between the study groups in the main allergy characteristics. Leptin levels were higher while adiponectin was lower in asthmatics with obesity. Higher levels of IL-16 were found in overweight/obese asthmatic individuals than in normal-weight individuals. (4) Conclusions: Obesity may have an effect on impaired pulmonary function. While atopic inflammation plays an important role in the onset of asthma, nonatopic inflammation (including leptin and adiponectin) increases the severity of asthma in overweight/obese patients. The significance of different levels of IL-16 between groups needs to be further studied.

The Association between Daily Dietary Intake of Riboflavin and Lung Function Impairment Related with Dibutyl Phthalate Exposure and the Possible Mechanism.

This study aimed to evaluate the relationship between the daily dietary intake of riboflavin (DDIR) and impaired lung function associated with dibutyl phthalate (DBP) exposure. Data of 4631 adults in this national cross-sectional survey were included. Urinary mono-benzyl phthalate (MBP) was used to evaluate the level of DBP exposure. The ln-transformed urinary creatinine-corrected MBP (ln(MBP/UCr)) level was used in the statistical models. High DDIR was defined as the DDIR ≥1.8 mg per day. The results of lung function impairment and high monocytes were significantly higher in the highest MBP group compared with the lowest MBP group. A significant interaction between ln(MBP/UCr) and DDIR (Pinteraction = 0.029) was detected for the risk of lung function impairment. The risk of lung function impairment (ORquartiles4 vs. 1 1.85, 95% CI, 1.27-2.71; Ptrend = 0.018) and high neutrophils (ORquartiles4 vs. 1 1.45, 95% CI, 1.06-1.97; Ptrend = 0.018) was significantly higher in the highest vs. the lowest quartile of MBP in participants with low/normal DDIR but not in in participants with high DDIR. The results of this study showed that high DDIR was associated with less lung function impairment related with DBP exposure, and the inhibiting of the neutrophil recruitment might be the potential mechanism.

Insights into the Role of Na+ on the Transformation of Gypsum into α-Hemihydrate Whiskers in Alcohol-Water Systems.

Alcohol-water solution-mediated transformation of gypsum into α-hemihydrate (α-HH) whiskers provides a green alternative for the high-value-added recycling of flue gas desulfurization (FGD) gypsum. However, the role of non-lattice cations during the transformation is still unclear. We report an evolution from "boosting-retarding" to "boosting-retarding-boosting" and finally to "boosting only" effect of non-lattice Na+ functioned by the concentration of ethylene glycol (EG) in water solutions. The driving force increased almost linearly upon the introduction of Na+ through the formation of ion pairs, and a higher slope was obtained at a higher EG concentration. Adsorption of Na+ ions and solidification of eugsterite on gypsum surfaces blocked the nucleation sites of α-HH. The retarding effect first rapidly increased and gradually approached a limit, following a parabolic trend after Na+ ions were introduced. Pentasalt, with a structure similar to that of α-HH, precipitated on the gypsum surface at higher c(Na+). The interaction of the driving force and the structural evolution of calcium sulfate ionic clusters accounts for the evolution of transformation kinetics. The retardation zone was compressed with the increase in EG volume ratios, and a monotonic boosting effect upon Na+ was observed at a 35.0 vol % of EG. Nucleation kinetics dominates the aspect ratio of α-HH whiskers. This study may provide a significant guidance for the utilization of FGD gypsum.

Evaluation of the Clinical Effectiveness of Oseltamivir for Influenza Treatment in Children.

Objective: To estimate the clinical effectiveness of oseltamivir in children with different subtypes of influenza virus infection. Methods: A total of 998 children with acute respiratory infection were enrolled from January to March 2018, and were divided into influenza A, influenza B, influenza A + B, and non-influenza infection (IV-negative) groups. Influenza-like symptoms and duration of fever were evaluated and compared between oseltamivir-treated and non-treated groups. Results: There were no significant differences in the reduction in total febrile period and duration of fever from the onset of therapy between the oseltamivir treated and non-treated children infected with influenza A (p = 0.6885 for total febrile period and 0.7904 for the duration of fever from the onset of treatment), influenza B (p = 0.1462 and 0.1966), influenza A + B (p = 0.5568 and 0.9320), and IV-negative (p = 0.7631 and 0.4655). The duration of fever in children received oseltamivir therapy within 48 h was not significantly shorter than that beyond 48 h (p > 0.05). Additionally, percentages and severities of influenza-like symptoms, including headache, myalgia, fatigue, bellyache, vomiting, diarrhea, sore throat, cough, and coryza were not decreased and alleviated after treatment of oseltamivir. Conclusion: Oseltamivir treatment does not significantly shorten the duration of fever, nor does it significantly relieve influenza-like symptoms in children with infection of influenza.

Exploring the appropriate dose of nebulized hypertonic saline for bronchiolitis: a dose-response meta-analysis.

Nebulized hypertonic saline (HS) has gathered increasing attention in bronchiolitis. This study aims to evaluate the relationship between the dose of nebulized HS and the effects on bronchiolitis. Five electronic databases-PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and ISRCTN-were searched until May 2021. Randomized controlled trials (RCTs) that investigated the effect of HS on bronchiolitis were included. A total of 35 RCTs met the eligibility criteria. HS nebulization may shorten the length of stay (LOS) in hospital (mean difference -0.47, 95% CI -0.71 to -0.23) and improve the 24-hour, 48-hour, and 72-hour Clinical Severe Score (CSS) in children with bronchiolitis. The results showed that there was no significant difference between 3% HS and the higher doses (>3%) of HS in LOS and 24-hour CSS. Although the dose-response meta-analysis found that there may be a linear relationship between different doses and effects, the slope of the linear model changed with different included studies. Besides, HS nebulization could reduce the rate of hospitalization of children with bronchiolitis (risk ratio 0.88, 95% CI 0.78 to 0.98), while the trial sequential analysis indicated the evidence may be insufficient and potentially false positive. This study showed that nebulized HS is an effective and safe therapy for bronchiolitis. More studies are necessary to be conducted to evaluate the effects of different doses of HS on bronchiolitis.

Prognosis of bronchial asthma in children with different pulmonary function phenotypes: A real-world retrospective observational study.

Objective: To follow up on the changes in pulmonary function phenotypes in children with asthma in the first year after diagnosis, and explore the risk factors of poor control in children with good treatment compliance. Methods: Children who were diagnosed with asthma in the Respiratory Department of Shanghai Children's Medical Center from January 1, 2019 to December 31, 2020 and were re-examined every 3 months after diagnosis for 1 year were continuously included, regardless of gender. We collected the clinical data, analyzed clinical characteristics of the different pulmonary function phenotypes at baseline and explored risk factors of poor asthma control after 1 year of standardized treatment. Results: A total of 142 children with asthma were included in this study, including 54 (38.0%) with normal pulmonary function phenotype (NPF), 75 (52.8%) with ventilation dysfunction phenotype (VD), and 13 (9.2%) with small airway dysfunction phenotype (SAD) in the baseline. Among them, there were statistically significant differences in all spirometry parameters, age, and course of disease before diagnosis (P < 0.05), and a negative correlation between age (r 2 = -0.33, P < 0.001), course of disease before diagnosis (r 2 = -0.23, P = 0.006) and FEV1/FVC. After 1-year follow-up, large airway function parameters and small airway function parameters were increased, fractional exhaled nitric oxide (FeNO) was decreased, the proportion of NPF was increased, the proportion of VD was decreased (P < 0.05), while there was no significant difference in the proportion of SAD. After 1 year of standardized treatment, 21 patients (14.8%) still had partly controlled or uncontrolled asthma. Our results showed that the more asthma attacks occurred within 1 year (OR = 6.249, 95% CI, 1.711-22.818, P = 0.006), the more times SAD presented at baseline and Assessment 1-4 (OR = 3.092, 95% CI, 1.222-7.825, P = 0.017), the higher the possibility of incomplete control of asthma. Conclusion: About 15% of the children with good treatment compliance were still not completely controlled after 1 year of treatment, which is closely associated with persistent small airway dysfunction.

The Associations of Caesarean Delivery With Risk of Wheezing Diseases and Changes of T Cells in Children.

Objectives: This study aimed to assess the associations of caesarean delivery (CD) with risk of wheezing diseases and changes of immune cells in children. Design: The cross-sectional study was conducted between May, 2020 and April, 2021. Setting and participants: The study was conducted in Shanghai Children's Medical Center, Shanghai, China. A total of 2079 children with a mean age of 36.97 ± 40.27 months and their guardians were included in the present study via face-to-face inquiry and physical examination by clinicians. Methods: Logistic regression was applied to estimate odds ratio (ORs) and 95% confidence intervals (CIs) for the association between CD and first episode of wheezing (FEW) or asthma. Models were adjusted for premature or full-term delivery, exclusive breastfeeding (at least 4 months) or not. Results: Among the 2079 children, 987 children (47.47%) were born by CD and 1092 (52.53%) by vaginal delivery (VD). Children delivered by caesarean had significantly lower gestational age (P<0.01) compared with those who delivered vaginally. Our results also showed that CD was related to increased risk of FEW by the age of 3(adjusted OR 1.50, 95%CI 1.06, 2.12) and increased tendency to develop asthma by the age of 4 (adjusted OR 3.16, 95%CI 1.25, 9.01). The subgroup analysis revealed that the negative effects of CD on asthma were more obvious in children without exclusive breastfeeding (adjusted OR 4.93, 95%CI 1.53, 21.96) or without postnatal smoking exposure (adjusted OR 3.58, 95%CI 1.20, 13.13). Furthermore, compared with children born through VD, a significant change of the T cells (increased proportion of CD4+ T cells and decreased number and proportion of CD8+ T cells) were observed before the age of one in the CD group. However, the changes were insignificant in children over 1 year old. Conclusions: This study showed age-dependent associations of CD with asthma and FEW in offspring. Moreover, CD appeared to have an effect on the cellular immunity in infants, the disorder of which may contribute to the development of asthma in children.