Etiology and clinical features of children with bronchiectasis in China: A 10-year multicenter retrospective study.

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Asthma mortality among children and adolescents in China, 2008-2018.

BACKGROUND: Asthma mortality among children and adolescents at the national level in China was unreported. The aim of this study was to analyze the mortality of asthma among children and adolescents in China using a nationally representative database. METHODS: This was a descriptive study using data from the Disease Surveillance Points (DSPs) system. All asthma-related deaths among children and adolescents aged 0-19 years occurring in DSPs across China from 2008 to 2018 were included. Multilevel Poisson regression models were used to compute the total, age-, gender-, region- and residence-specific asthma mortality rates and to investigate the significance of trends and factors associated with asthma mortality. Data from the National Bureau of Statistics were used to estimate the national asthma deaths. RESULTS: Total asthma mortality rate among Chinese children and adolescents fluctuated between 0.020 (0.009, 0.045) and 0.059 (0.025, 0.137) per 100,000 and showed an overall downward trend (RR, 0.909; 95% CI 0.854-0.968) during the study period (2008-2018). Asthma mortality rate was higher in the western China (RR 2.356, 95% CI 1.513, 3.669) and varied over a ninefold range among DSPs in China. The estimated number of deaths decreased by 51.38% from 2008 (n = 148; 95% CI 58,379) to 2018 (n = 71; 95% CI 34, 109). CONCLUSIONS: Asthma mortality rate among children and adolescents in China was at a low level compared to rates worldwide and decreased significantly from 2008 to 2018. Compared with most countries in the world, the number of asthma deaths was higher in China.

Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report.

BACKGROUND: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. CASE PRESENTATION: We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. CONCLUSIONS: To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

Prevention of New Respiratory Episodes in Children with Recurrent Respiratory Infections: An Expert Consensus Statement.

In healthy infants and young children, the development of respiratory tract infections (RTIs) is extremely common. In this paper, we present an international consensus of the available approaches for the prevention of recurrent RTIs in children, including the atopic/allergic ones as well as those with asthma. Few convincing measures for reducing the frequency and clinical relevance of recurrent respiratory episodes in RTI-prone children have been developed until now. Among the most recently suggested measures, immunotherapy is attractive, but only for OM-85 is there a sufficient number of well-conducted clinical trials confirming efficacy in RTIs prevention with an adequate safety profile. In the case of probiotics, it is not clear which bacteria can offer the best results and which dosage and schedule of administration are the most effective. The problems of dosage and the schedule of administration are not solved also for vitamin D, despite some promising efficacy results. While we wait for new knowledge, the elimination or reduction as much as possible of the environmental factors that favor RTIs, vaccination when available and/or indicated, and the systematic application of the traditional methods for infection prevention, such as hand washing, remain the best measures to prevent recurrent infections in RTI-prone children.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

The epidemiology of paediatric Mycoplasma pneumoniae pneumonia in North China: 2006 to 2016.

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2-3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2-3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.

Pertussis detection in children with cough of any duration.

BACKGROUND: The diagnosis of pertussis in clinical practice continues to be a challenge worldwide as the symptoms are variable. We aimed to determine the prevalence of pertussis in Chinese children irrespective of cough duration and explore the clinical characteristics of children with pertussis with different cough durations. METHODS: This was a prospective study of children 1 month to 11 years of age with different cough durations in one large Chinese hospital. Bilateral deep posterior nasopharyngeal swabs and venepuncture for full blood count, CRP and serology and sputum were obtained when possible for investigation. E-test strips were used for testing the susceptibility of the B.pertussis isolates against erythromycin, azithromycin, sulphamethoxazole/trimethoprim, levofloxacin, amoxicillin and doxycycline. Demographic, clinical and laboratory information on culture and antimicrobial susceptibility testing was collected from children, and analyzed using SAS v.10 (SAS Institute Inc., USA). RESULTS: After exclusions we analyzed 312 children. Ninety-seven (31.1%) children had laboratory evidence of pertussis. When grouped by cough duration, few characteristics were significant between children with and without pertussis. Of the 36 isolates, 72.2% (26/36)could not be inhibited by erythromycin and azithromycin at all. The MIC50 and MIC90 to amoxicillin were 0.75 mg/L and 1 mg/L respectively, sensitive to amoxicillin by the EUCAST points. CONCLUSIONS: The "one-size-fits-all" clinical pertussis case definition is no longer optimal to recognize this disease. A large comprehensive study of children with all types of cough is required to make substantial inroads into increasing both the sensitivity and specificity in pertussis diagnosis, which will have a beneficial impact on public health. Amoxicillin maybe an alternative for children with marolide-resistant B.pertussis infection; however, local sensitivities are required to inform clinical practice.

Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disease in China, and very little large-scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. METHODS: Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. RESULTS: A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X-linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment. CONCLUSIONS: Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL-CGD are higher than AR-CGD.

[Prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features].

OBJECTIVE: To investigate the prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features. METHODS: A total of 106 children who were treated at the outpatient service or hospitalized from January 1, 2016 to May 31, 2017 were enrolled. Their nasopharyngeal swabs and venous blood samples were collected for Bordetella pertussis culture, multiple PCR and serum anti-pertussis toxin antibody detection. According to these results, the children were divided into pertussis group with 26 children and control group with 80 children, and clinical features were analyzed for both groups. E-test stripes were used to determine the sensitivity of Bordetella pertussis strains to erythromycin, azithromycin, doxycycline, levofloxacin, sulfamethoxazole/trimethoprim and amoxicillin. RESULTS: Of the 106 children with chronic cough, 26 (24.5%) were found to have Bordetella pertussis infection. There were no significant differences in the incidence rates of typical symptoms of pertussis between the pertussis and control groups (P>0.05). E-test showed that erythromycin and azithromycin had a minimal inhibitory concentration (MIC) of >256 mg/L against five Bordetella pertussis strains, while amoxicillin had an MIC of 0.5-1 mg/L. CONCLUSIONS: The presence of Bordetella pertussis infection in children with chronic cough should be taken seriously by clinicians, and children with chronic cough and Bordetella pertussis infection may not have the typical symptoms of pertussis and are mainly manifested as chronic cough. Amoxicillin may be an alternative drug for macrolide-resistant Bordetella pertussis infection.

[Status of antibiotic use in hospitalized children with community-acquired pneumonia in multiple regions of China].

OBJECTIVE: To investigate the use of antibiotics in children with community-acquired pneumonia (CAP) in multiple regions of China, and to provide a reference for CAP standard treatment and rational antibiotic use in children. METHODS: The medical data of 1 383 children with CAP who were hospitalized in the department of pediatrics in 10 grade A tertiary hospitals from 9 cities between April 14, 2014 and January 1, 2016 were reviewed, to analyze the status of antibiotic use in hospitalized children in North China, Northeast China, East China, and South China. RESULTS: The overall rate of antibiotic use in children with CAP was 89.08%, with 88.7% in North China, 95.5% in Northeast China, 83.3% in East China, and 86.6% in South China. The main types of antibiotics used were cephalosporins, macrolides, compound preparations of ß-lactam antibiotics, polyphosphoric broad-spectrum antibiotics and other ß-lactam antibiotics. The selection of antibiotics was generally rational, but antibiotics were still used in some patients with viral infection alone or a combined use of ≥2 kinds of antibiotics were noted in some patients with infection caused by one kind of pathogen. Irrational antibiotic use was observed in 131 children (10.63%). CONCLUSIONS: There are high rates of antibiotic use and irrational use of antibiotics among children with CAP. Standard management of antibiotic use in children with CAP should be strengthened.

Antibiotic usage in Chinese children: a point prevalence survey.

BACKGROUND: Children as a population have high antimicrobial prescribing rates which may lead to high resistance of bacteria according to data from some single-center surveys of antibiotic prescribing rates in China. The acquirement of baseline data of antibiotic prescribing is the basis of developing intervention strategies on inappropriate antimicrobial prescriptions. Few studies show clearly the pattern and detailed information on classes of antibiotics and distribution of indications of antibiotic prescriptions in children in China. This study aims to assess the antibiotic prescribing patterns among children and neonates hospitalized in 18 hospitals in China. METHODS: A 24-hour point prevalence survey on antimicrobial prescribing was conducted in hospitalized neonates and children in China from December 1st, 2016 to February 28th, 2017. Information on the antibiotic use of patients under 18 years of age who were administered one or more on-going antibiotics in the selected wards over a 24-hour period was collected. These data were submitted to the GARPEC (Global Antimicrobial Resistance, Prescribing and Efficacy in Children and Neonates) web-based application ( https://pidrg-database.sgul.ac.uk/redcap/ ). For statistical analysis, Microsoft Excel 2007 and SPSS 22.0 were used. RESULTS: The antibiotic data were collected in 35 wards in 18 hospitals from 9 provinces. In total, 67.76% (975/1439) of the patients (n = 1439) were given at least one antibiotic, including 58.1% (173/298) of neonates (n = 298) and 70.3% (802/1141) of children (n = 1141). In neonates, the three most frequently prescribed antibiotics were third-generation cephalosporins (41.7%), penicillins plus enzyme inhibitor (23.8%), and carbapenems (11.2%). In children, the three most frequently prescribed antibiotics were third-generation cephalosporins (35.5%), macrolides (23.2%), and penicillins plus enzyme inhibitors (15.9%). The most common indication for antibiotics was proven or probable bacterial lower respiratory tract infection (30.9% in neonates and 66.6% in children). CONCLUSIONS: Antibiotics are commonly prescribed in the Chinese children population. It is likely that the third-generation cephalosporins and macrolides are currently overused in Chinese children. Efforts must be made to ensure safe and appropriate antibiotic prescribing to reduce and prevent the future development of antibiotic resistance.

Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence.

PURPOSE OF REVIEW: To provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis. RECENT FINDINGS: Nonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population. Orally administered immunomodulators result in the mounting of innate and adaptive immune responses to infection in the respiratory mucosa and anti-inflammatory effects in proinflammatory environments. Clinical data reflect these mechanistic effects in reductions in the recurrence of respiratory infections and wheezing events in high-risk paediatric populations. A new generation of clinical studies is currently underway with the power to position the nonspecific bacterial lysate immunomodulator OM-85 as a potential antiasthma prophylactic. SUMMARY: An established mechanistic and clinical role for prophylaxis against paediatric respiratory infections by nonspecific immunomodulators exists. Clinical trials underway promise to provide high-quality data to establish whether a similar role exists in wheezing/asthma prevention.

Pediatric allergy and immunology in China.

Over the past 30 years, China has enjoyed rapid economic development along with urbanization at a massive scale that the world has not experienced before. Such development has also been associated with a rapid rise in the prevalence of allergic disorders. Because of the large childhood population in the country, the burden of childhood allergic disorders has become one of the major challenges in the healthcare system. Among the Chinese centers participating in the International Study of Asthma and Allergies in Childhood, the data clearly showed a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic eczema. However, the discipline of pediatric allergy in mainland China is still in its infancy due to the lack of formal training program and subspecialty certification. Clinicians and researchers are increasingly interested in providing better care for patients with allergies by establishing pediatric allergy centers in different regions of the country. Many of them have also participated in national or international collaborative projects hoping to answer the various research questions related to the discipline of pediatric allergy and immunology. It is our hope that the research findings from China will not only improve the quality of care of affected children within this country but also the millions of patients with allergies worldwide.