OBJECTIVE: To summarize the clinical data of 7 children with activated phosphoinositide 3-kinase delta syndrome (APDS) and enhance understanding of the disease.
METHODS: A retrospective analysis was conducted on clinical data of 7 APDS children admitted to Hunan Provincial People\'s Hospital from January 2019 to August 2023.
RESULTS: Among the 7 children (4 males, 3 females), the median age of onset was 30 months, and the median age at diagnosis was 101 months. Recurrent respiratory tract infections, hepatosplenomegaly, and multiple lymphadenopathy were observed in all 7 cases. Sepsis was observed in 5 cases, otitis media and multiple caries were observed in 3 cases, and diarrhea and joint pain were observed in 2 cases. Lymphoma and systemic lupus erythematosus were observed in 1 case each. Fiberoptic bronchoscopy was performed in 4 cases, revealing scattered nodular protrusions in the bronchial lumen. The most common respiratory pathogen was Streptococcus pneumoniae (4 cases). Six patients had a p.E1021K missense mutation, and one had a p.434-475del splice site mutation.
CONCLUSIONS: p.E1021K is the most common mutation site in APDS children. Children who present with one or more of the following symptoms: recurrent respiratory tract infections, hepatosplenomegaly, multiple lymphadenopathy, otitis media, and caries, and exhibit scattered nodular protrusions on fiberoptic bronchoscopy, should be vigilant for APDS. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(5): 499-505.
目的: 总结7例PI3Kδ过度活化综合征（activated phosphoinositide 3-kinase delta syndrome, APDS）患儿的临床资料，提高对该病的认识。方法: 回顾性分析2019年1月—2023年8月湖南省人民医院收治的7例APDS患儿的临床资料。结果: 7例患儿（男4例，女3例）中位发病年龄为30个月，中位诊断年龄为101个月。临床表现：反复呼吸道感染、肝脾大及多部位淋巴结肿大7例，脓毒血症5例，中耳炎及多发性龋齿3例，腹泻及关节痛2例，淋巴瘤、系统性红斑狼疮各1例。4例患儿行纤维支气管镜检查，管腔内均可见大量散在的结节样突起。最常见的呼吸道病原为肺炎链球菌（4例）。6例患儿为p.E1021K位点错义突变，1例为p.434-475del位点剪切突变。结论: p.E1021K是APDS患儿最常见的突变位点。对于具有反复呼吸道感染、肝脾大、多部位淋巴结肿大、中耳炎、龋齿等表现1项或多项，且纤维支气管镜下见散在结节样突起的患儿，需警惕APDS。 ［中国当代儿科杂志，2024，26（5）：499-505］.

Polyvalent mechanical bacterial lysate (PMBL) is used for the treatment and prevention of recurrent respiratory tract infections. Although PMBL is an immunostimulant, it remains unknown whether treatment with PMBL influences natural killer cell activity (NKA). Hence, this case-control study compared the changes in IFN-γ levels (surrogate index for NKA) following PMBL treatment or time passing between the PMBL-treated group and controls. The treatment group included adults who had a PMBL prescription for three months against recurrent respiratory tract infection from an outpatient clinic, while the control group had healthy adults visiting the health promotion center for periodic health check-ups. The control group (N = 506) showed no change in IFN-γ levels, while the treatment group (N = 301) showed a significant increase in mean from 462.8 to 749.3 pg/mL after PMBL treatment. In the subgroup with IFN-γ <500 pg/mL, IFN-γ levels significantly increased in both groups. However, the change in the treatment group (287 ± 822 pg/mL) was greater than that in the control group (58 ± 809 pg/mL), and the interaction between the visit and case/control was significant (p = 0.030) in a generalized estimating equation model. In conclusion, NKA increased in the subjects with recurrent respiratory tract infections with PMBL treatment.

BACKGROUND: Acupoint herbal patching (AHP) has been used for recurrent respiratory tract infection (RRTI) in children. This systematic review aimed to analyze the safety and efficacy of AHP in pediatric RRTI.
METHODS: Eleven databases were comprehensively searched up to January 2020. Randomized controlled trials (RCTs) using AHP as a monotherapy or adjunctive therapy in pediatric patients with RRTI were included.
RESULTS: Twenty-two RCTs with 3579 participants were included. Meta-analyses showed that outbreaks and disease duration of respiratory tract infection (RTI) per year significantly decreased in the AHP group compared with the placebo group, when follow-up was conducted after 1, 2, or 3 years. Moreover, AHP as a monotherapy or adjunctive therapy significantly decreased outbreaks and disease duration of RTI without serious adverse events.
CONCLUSIONS: This review provides promising evidence that AHP may reduce the frequency and duration of RTI and improve immune function in pediatric patients with RRTI.

BACKGROUND: The impact of the gut microbiota on recurrent respiratory tract infection (RRTI) remains to be fully elucidated.
METHODS: To characterize the gut microbiota in patients with RRTI, fecal samples from 26 patients with RRTI and 23 healthy volunteers were profiled using the Illumina MiSeq platform. Beta diversity (Principal Component Analysis (PCA), Principal Co-ordinates Analysis (PCoA), Non-metric multidimensional scaling (NMDS)) analysis showed that the bacterial community structure segregated differently between the RRTI and control groups.
RESULTS: Results from alpha diversity analysis revealed lower microbiota diversity in samples from RRTI patients than in normal controls. Taxonomic analysis illustrated that the abundance of six phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Verrucomicrobia, Tenericutes) and four genera (Enterococcus, Faecalibacterium, Bifidobacterium, Eubacterium were significantly different between these two groups. In addition, Enterococcus (P < 0.001) was more enriched in the RRTI group, whereas the abundances of Eubacterium (P < 0.001), Faecalibacterium (0.01 < P < 0.05) and Bifidobacterium (0.01 < P < 0.05) were reduced in the RRTI group compared to those in the normal control group. The performance of the model was assessed using ROC analysis, and Enterococcus, Eubacterium and Bifidobacterium achieved AUC values of 0.860, 0.820, and 0.689, respectively.
CONCLUSIONS: These results provide fundamental evidence in support of intestinal microbiota dysbiosis in children with RRTI.

Over many years, OM-85, a lysate of 21 common bacterial respiratory pathogens, has been demonstrated to prevent respiratory recurrences in children. However, further studies are needed to explore the true importance of OM-85 in the prevention of respiratory tract infections (RTIs) in children. This study was planned to further contribute to the evaluation of the role played by OM-85 in prevention of recurrent RTIs in children.
This study was a randomized (3:3:1), placebo-controlled, double-blind, single-centre, phase IV trial carried out in Italy to assess the efficacy of OM-85 (Broncho-Vaxom®; Vifor Pharma; Meyrin 2/Geneva, Switzerland) in reducing the number of new RTI episodes in 288 children aged 1 to 6 years with a history of recurrent RTIs and to compare the efficacy of the standard 3-month regimen with that of administration of OM-85 for 6 months during a 6-month study period.
The number of RTIs and of children who experienced at least one RTI were significantly lower among patients receiving OM-85 for 3 months than among those given placebo (33% vs 65.1%, p < 0.0001). Differences were statistically significant for upper RTIs (i.e., common cold/viral pharyngitis and acute otitis media; p < 0.0001 and p = 0.006, respectively). Days of absence from day-care for children and working days lost by parents were significantly lower in the group with children treated with OM-85 for 3 months than in the placebo group (p = 0.007 and p = 0.004, respectively). No difference was seen between children who received OM-85 for 3 and those who received OM-85 for 6 months. The prevalence of atopy as well as the history of recurrent wheezing and age of the study child did not influence the results. Benefit was maximally evident among children with a history of frequent recurrences. OM-85 was well tolerated and safe, even in children who received an influenza vaccination.
The use of OM-85 for 3 months in 3 series of 10 consecutive days each time reduces the risk of recurrent RTIs in children, with a favourable safety profile. The greater effect observed in children prone to several respiratory episodes than in non-prone children seems to indicate that this lysate should be administered especially to children with a proven high susceptibility to RTIs.

UNASSIGNED: To observe the clinical efficacy of pidotimod in the treatment of recurrent respiratory tract infection in children.
UNASSIGNED: One hundred thirty-two patients with recurrent respiratory tract infection who received treatment in Tianan City Central Hospital were selected and divided into an observation group and a control group using random number table, 66 in each group. Patients in the control group were given conventional treatment, while patients in the observation group were given conventional treatment and pidotimod treatment; the clinical efficacy of the two therapies was compared. The levels of IgG and IgM were measured after treatment.
UNASSIGNED: The vital signs and the content of inflammatory mediator and Th1/Th2 in serum before and after treatment were compared, and the clinical efficacy of the two groups was evaluated. The fever, pulmonary rale, cough and antiadoncus of patients in the observation group disappeared earlier than those in the control group (P<0.05). The onset duration of respiratory tract infection and days of antibiotic application of the observation group were shorter than those of the control group after treatment (P<0.05). The times of infection of the observation group were less than that of the control group (P<0.05). Before treatment, the two groups had no significant difference in the content of inflammatory mediators and Th1/Th2 in the serum (P>0.05). The serum content of tumor necrosis factor (TNF)-α and interleukin (IL)-4 of the two groups one week after treatment was lower than that before treatment, and the content of interferon (IFN)-γ and IFN-γ/IL-4 were higher than that before treatment; moreover the observation group had lower serum content of TFN-α and IL-4 and lower content of IFN-γ and IFN-γ/IL-4 compared to the control group (P<0.05). The overall response rate of the observation group was 92.4%, much higher than 81.8% in the control group (P<0.05).
UNASSIGNED: Pidotimod has a remarkable efficacy in the treatment of pediatric recurrent respiratory tract infection because it can effectively inhibit the infection and optimize Th1/Th2 immune function.

BACKGROUND: Paediatric respiratory tract infections are among the most common reasons for preschool and school absences and visits to physicians. The disease mainly involves the upper respiratory tract and is associated with fever, cough, sore throat, and running nose. Children with recurrent respiratory infections (RRI), which are defined as more than six serious diseases a year, are a difficult diagnostic challenge. The aim of this study was to assess immunological deviations in laboratory tests performed in children with RRI.
METHODS: In the retrospective study 25 children suffering from recurrent respiratory tract infection, aged 4.1 ±2.3 years, 13 boys and 12 girls, were involved. For all children chemiluminescence of granulocytes and immunophenotyping of lymphocytes from peripheral blood were examined. An immunophenotype of peripheral blood lymphocytes involved evaluation of T cell, B cells, and NK cells, examined with flow cytometry.
RESULTS: Eleven of the studied children had decreased chemiluminescent response to stimulants, normal response was found for nine children, and five children had an increased result of the test. Five of the 25 children had decreased B cells number, and five had decreased number of T cells including decrease of CD4, as well as CD8 positive cells. Children with decreased chemiluminescence had more frequent neutropaenia than children with normal or increased chemiluminescent response, p < 0.05 (exact Fisher test).
CONCLUSIONS: Recurrent respiratory tract infection could be associated with improper neutrophils response to pathogens, and immunological examination should be performed to find the reason for the increased number of infections in a year.

Trace elements play an important role in maintaining the normal metabolic and immune function. The onset of recurrent respiratory tract infection (RRI) is associated with the immune function, genetic factors and nutritional status. However, the association between the levels of trace elements and RRI remains inconclusive. We aimed to investigate the alterations of hair levels of zinc (Zn), copper (Cu) and iron (Fe) in Chinese children with RRI by performing a meta-analysis. A predefined electronic databases search was performed to identify eligible studies for the analysis of hair Zn, Cu or Fe levels in Chinese children with RRI. Thirteen studies were included. RRI patients displayed significantly lower levels of hair Zn (13 studies, random effects SMD: - 1.215, 95% CI: - 1.704 to - 0.725, p < 0.0001), Cu (11 studies, random effects SMD: - 0.384, 95% CI: - 0.717 to - 0.052, p = 0.023) and Fe (12 studies, random effects SMD: - 0.569, 95% CI: - 0.827 to - 0.312, p < 0.0001) compared with controls. No evidence of publication bias was observed. Sensitivity analysis did not change the results significantly. In conclusion, the deficiency of Zn, Cu and Fe may be contributing factors for the susceptibility of RRI in Chinese children. However, more studies in different ethnicities should be performed in the future.

It is known that the immunogenicity and efficacy of conventional inactivated influenza vaccines (IIVs) are not completely satisfactory in children. The aim of this prospective, randomised, single-blind study was to compare the immune response to, and the effectiveness and safety of, an IIV (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) administered to 68 children aged 36-59 months affected by recurrent respiratory tract infections (RRTIs) who were vaccinated with (n=33) or without (n=35) the mixed bacterial lysate OM-85 BV (Broncho-vaxom, Vifor Pharma, Geneva, Switzerland). OM-85 BV had no effect on seroconversion or seroprotection rates, geometric mean titres, or dendritic cells, which were not significantly different between the two groups. Moreover, OM-85 BV did not significantly increase the pool of the memory B cells that produce IgG and IgM antibodies against the influenza antigens. However, respiratory morbidity was significantly lower in the children treated with OM-85 BV (p<0.05), thus confirming its positive effect on the incidence of RRTIs. There was no difference in the incidence of adverse events between the two groups. These findings show that the immune response of children to influenza vaccine is not significantly influenced by the administration of OM-85 BV. However, the use of OM-85 before and at the same time as IIV seems to reduce respiratory morbidity, and seems to be safe and well tolerated.

The present single-centered randomized control trial (RCT) was carried out with the prime aim of assessing the effect of Kasahara Dashemani Vati (trial drug) on Kasa and Vyadhikshamatva in the children suffering from recurrent respiratory tract infections and comparing it with the efficacy of Indukanta Vati. The clinical trial included 40 patients belonging to age group of 3-12 years. The drugs were administered in a daily dose fixed as per \"Clark\'s Rule\" along with honey for duration of 60 days. The effect of treatment on the signs and symptoms of Kasa was assessed on the 15(th) day, whereas the effect on Vyadhikshamatva was assessed on the 60(th) day. The patients were under follow-up for a period of 60 days after completing the treatment course for evaluation of any recurrence. Effect of the therapy on the individual signs and symptoms of Kasa, laboratory parameters, immunoglobulin (Ig) biomarkers, status of Atura Bala, and prevention of recurrence during follow-up period were the parameters used to assess the overall effect of therapy. The observed data were subjected to appropriate statistical analysis for testing the statistical significance. Kasahara Dashemani provided relief in all symptoms of Kasa irrespective of Doshic involvement and on the parameters of Atura Bala. All the changes were statistically highly significant. The control group also showed similar effects which were statistically highly significant. The trial group was found to have a direct influence on serum Ig status. No patient has reported any adverse drug reactions during the treatment and follow-up periods.