Immunological Features of Pediatric Interstitial Pneumonia Due to Mycoplasma pneumoniae.

Background: Inflammatory response, oxidative stress, and immunologic mechanism are involved in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). However, the role of immune system of pediatric interstitial pneumonia due to M. pneumoniae infections remains poorly understood. The aim of this study was to analyze the immunologic features of pediatric interstitial pneumonia due to Mycoplasma pneumoniae (M. pneumoniae). Methods: A retrospective study was conducted on a primary cohort of children with MPP. Propensity score analysis was performed to match interstitial pneumonia and pulmonary consolidation children. Results: The clinical characteristics strongly associated with the development of interstitial pneumonia were boys, age >5 years, wheezing history, hydrothorax free, lymphocytes (>3.0 × 109/L), CD19+ (>0.9 × 109/L), CD3+ (>2.5 × 109/L), CD4+ (>1.5 × 109/L), CD8+ (>0.9 × 109/L), interleukin-6 (IL-6, <30 pg/ml), IL-10 (<6 pg/ml), and interferon-γ (IFN-γ, <15 pg/ml). After propensity score analysis, children with interstitial pneumonia showed significantly higher CD19+, CD3+, and CD4+ T cell counts, and lower serum IL-6, IL-10, and IFN-γ levels. The final regression model showed that only CD4+ T cells (>1.5 × 109/L, OR = 2.473), IFN-γ (<15 pg/ml, OR = 2.250), and hydrothorax free (OR = 14.454) were correlated with the development of interstitial pneumonia among children with MPP. Conclusions: The M. pneumoniae-induced interstitial pneumonia showed increased CD4+ T cells and lower serum IFN-γ level. Specific immunologic profiles could be involved in the development of pediatric interstitial pneumonia due to M. pneumoniae infections.

Case Report: Activating PIK3CD Mutation in Patients Presenting With Granulomatosis With Polyangiitis.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by gain-of-function (GOF) mutations in PIK3CD or PIK3R1 genes. The phenotypes of APDS are highly variable, ranging from asymptomatic adults to profound immunodeficiency causing early death in childhood. Herein, we reported two pediatric patients with APDS presented with recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA), previously diagnosed as granulomatosis with polyangiitis (GPA). Bronchoscopy showed mucosal nodule lymphoid hyperplasia in the entire airway. Many inflammatory cells infiltrated around the airway and in the lung parenchyma, and numbers of CD3+ T cells and CD20+ B cells were significantly increased, especially CD3+ T cells. Whole exome sequencing showed that they had the E1021K (c.3061 G >A) mutation in the PIK3CD gene. These are the first reported cases of APDS presenting as childhood-onset GPA. Pediatricians should suspect of APDS in the differential diagnosis of children who present with GPA-like symptoms. Additionally, timely and repeated bronchoscopies could contribute to providing an important diagnostic clue for APDS.

Airway microbiota in children with bronchial mucus plugs caused by Mycoplasma pneumoniae pneumonia.

BACKGROUND: There is increasing evidence for a role of lung microbiota in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). However, the alterations of lung microbiota in MPP with bronchial mucus plugs and its role in disease pathogenesis remain poorly understood. METHODS: In this prospective observational study, we performed a longitudinal 16S rRNA-based microbiome survey on bronchoalveolar lavage (BAL) samples collected from 31 MPP with bronchial mucus plugs and 52 MPP without mucus plugs. RESULTS: Our study showed a clear difference in airway microbiota between MPP children with and without bronchial mucus plugs. The MPP children with mucus plugs had lower abundances of Sphingomonas and Elizabethkingia, and a high abundance of Mycoplasma compared with MPP children without mucus plugs, subsequently contributing to increased ratios of Mycoplasma to Sphingomonas and Mycoplasma to Elizabethkingia. Children's age, fever time and serum cytokine levels were associated with airway microbiota alteration. Furthermore, significant correlations between bacterial genus abundances were found in MPP children with mucus plugs. CONCLUSIONS: Our results suggest an impact of airway microbiota on the clinical course of MPP in children, deserving further investigations.

Nomogram for Prediction of Bronchial Mucus Plugs in Children with Mycoplasma pneumoniae Pneumonia.

The presence of bronchial mucus plugs (BMP) in children with Mycoplasma pneumoniae pneumonia (MPP) results in delayed clinical and radiographic resolution and long-standing pulmonary sequelae. The predictive factors associated with BMP formation remains poorly defined. Nomograms to predict BMP presence in children with MPP were proposed using a cohort of patients who underwent bronchoscopy intervention at Children's Hospital in Eastern China. Patients with MPP in an earlier period formed the training cohort (n = 872) for nomogram development, and those thereafter formed the validation cohort (n = 399) to confirmed model's performance. BMP in children with MPP were found in 196 (22.5%) and 91(22.8%) patients in the training and validation cohorts, respectively. The independent risk factors associated with BMP were age >5years (OR 2.06; 95% CI 1.43 to 2.98), higher IL-10 level (>10 ng/L, 2.19; 95% CI 1.46 to 3.28), higher IFN-γ level (>30 ng/L, 1.69; 95% CI 1.13 to 2.54), and presence of complication (3.43; 95% CI 1.45 to 8.09). Incorporating these 4 factors, the nomogram achieved good concordance indexes of 0.771(95% CI, 0.734-0.808) and 0.796 (95% CI, 0.744-0.848) in predicting BMP in the training and validation cohorts, respectively. The nomogram achieved an optimal prediction of BMP in children with MPP. Using this model, the risk of BMP formation would be determined, contributing to a rational therapeutic choice.

Flexible Bronchoscopy Combined with Rigid Bronchoscopy for Treatment of Scarring in the Bronchus Caused by a Foreign Body.

Foreign body (FB) aspiration into the tracheobronchial tree is an emergency in the pediatric department, particularly in children aged <3 years. FB granulation tissue is commonly found in children with FB aspiration. However, scarring in the bronchus caused by a FB is rare. We herein report a case involving aspiration of a plastic whistle toy with scarring in the bronchus. The scar tissue was successfully removed by interventional bronchoscopy combined with a flexible electrosurgery probe and carbon dioxide cryotherapy.

MicroRNA-92a inhibits macrophage antiviral response by targeting retinoic acid inducible gene-I.

MicroRNAs are short, non-coding RNAs that have been shown to regulate a wide range of biological processes, including host antiviral immune responses. In the present study, microRNA-92a (miR-92a) was identified as a negative regulator in macrophage-mediated antiviral responses. Overexpression of miR-92a decreases vesicular stomatitis virus (VSV)-induced production of type-I IFNs and facilitates viral replication in macrophages. The mechanism is that miR-92a directly targets RIG-I and reduces its expression, thereby attenuating VSV-triggered activation of TBK-binding kinase 1 and IRF3, both of which are crucial for initiating transcription of type-I IFN genes. Our results demonstrate for the first time the novel role of miR-92a in suppressing antiviral innate immunity.

Low birth weight contributed to increased serum IL-6 levels in infantile respiratory syncytial virus infection.

BACKGROUND: To evaluate the role of serum cytokines in the pathogenesis of respiratory syncytial virus (RSV) infection in infants with low birth weight (LBW). METHODS: A prospective observational study was performed, and hospitalized children with lower respiratory tract infection (LRTI) were recruited. Three hundred fifty-eight patients < 1 year met the inclusion criteria: 116 patients had only RSV infection (RSV group); 242 patients had no RSV or other specific pathogen (non-RSV group). Serum interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were detected through flow cytometry. RESULTS: No significant differences in serum IL-2, 4, 6, 10, and IFN-γ levels were observed between the RSV and non-RSV groups. For RSV infected infants with or without wheezing, delivery mode had no obvious effect on the changes of serum cytokine levels. However, the level of IL-6 in the RSV-infected infants with LBW was significantly higher than that in infants with normal birth weight. CONCLUSIONS: Serum IL-6 level was significantly increased in RSV infected infants with LBW. It is likely that the specific serum cytokine pattern will contribute to our understanding of the pathogenesis of RSV infections, especially in RSV-infected infants with LBW.

Allergic bronchopulmonary aspergillosis in children.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease of the lungs resulting from a hypersensitivity reaction to spores of Aspergillus fumigatus. Here we report the case of a 13-year-old girl with ABPA who presented with productive cough, bronchiectasis and decline in lung function, and review the clinical features and treatment for pediatric ABPA.

Effect of low birth weight on childhood asthma: a meta-analysis.

BACKGROUND: Low birth weight is strongly correlated with an increased risk of adult diseases. Additionally, low birth weight might be a risk factor for asthma later in life. METHODS: A systematic literature search of the PubMed database from 1966 to November 2013 was conducted. The criteria for inclusion of papers were as follows: case-control or cohort studies; the odds ratio (OR) or risk ratio (RR) estimates with the corresponding 95% confidence intervals (CIs) were presented, or there were sufficient data for calculation; and studies were published in English up to October 2013. Random-effect and fixed-effect meta-analyses, meta-regression, and cumulative meta-analysis were conducted. RESULTS: Thirteen cohort studies and 1,105,703 subjects were included. The overall pooled RRs (95% CIs) of asthma risk for low birth weight were 1.162 (fixed-effects model, 95% CI, 1.128-1.197) and 1.152 (random-effects model, 95% CI, 1.082-1.222). In stratified analyses, the effect of low birth weight on childhood asthma was strong, particularly in studies conducted in Europe, those with a small sample size, and those published recently. A meta-regression analysis did not find significant determinants. CONCLUSIONS: This meta-analysis shows that low birth weight significantly increases the risk of childhood asthma.

Effects of bronchoalveolar lavage on refractory Mycoplasma pneumoniae pneumonia.

INTRODUCTION: This study prospectively evaluated the effect of early bronchoalveolar lavage (BAL) on refractory Mycoplasma pneumoniae pneumonia with radiologically proven large pulmonary lesions in children. METHODS: A total of 35 children diagnosed as having refractory M. pneumoniae pneumonia with radiologically proven large pulmonary lesions completed the study. According to the time point of BAL, they were divided into 2 groups. In the early BAL group, BAL was performed within 3 d after admission (n = 22); in the late BAL group, BAL was performed 3 d later after admission (n = 13). Clinical effects were compared between these 2 groups. RESULTS: After BAL therapy, improvement in clinical symptoms and laboratory findings as well as resolution of pulmonary lesions on radiography were obtained in all subjects. The median fever duration after admission was 4 (2-7) d and 5 (2-10) d (P < .05), and the median hospitalization duration was 7 (5-10) d and 10 (5-14) d (P < .05), respectively, in the early BAL group and the late BAL group. Approximately 7 d after admission, 67% of subjects in the early BAL group showed resolution of atelectasis on x-ray image versus a corresponding rate of 14% in the late BAL group (P < .05). Furthermore, laboratory indices recovered quicker in the early BAL group than in the late BAL group (P < .01). CONCLUSIONS: BAL appeared to be efficacious and well-tolerated treatment for refractory M. pneumoniae pneumonia with radiologically proven large pulmonary lesions, and early application of BAL may be more beneficial.

More complications occur in macrolide-resistant than in macrolide-sensitive Mycoplasma pneumoniae pneumonia.

We sought to understand the situation of macrolide-resistant genotypes of Mycoplasma pneumoniae, and analyze the relationship between macrolide-resistant genotypes and clinical manifestations of Mycoplasma pneumoniae pneumonia (MPP). Full-length sequencing of the 23S rRNA gene of M. pneumoniae was performed in 235 nasopharyngeal aspirates (NPAs) from children with MPP. We also retrospectively compared the clinical characteristics of macrolide-resistant (MR) M. pneumoniae infections and macrolide-sensitive (MS) M. pneumoniae infections. A total of 206 patients had point mutations in the M. pneumoniae 23S rRNA gene, and these patients are referred to as MR patients. The remaining 29 patients without point mutations are referred to as MS patients. Among 206 MR patients, 199 (96.6%) had A2063G mutations, 6 had A2063T mutations, and the remaining patients had an A2064G mutation. Among the clinical manifestations, we found that the median fever durations were 8 days (range, 0 to 42 days) and 6 days (0 to 14 days) (P < 0.01), the median hospitalization durations were 8 days (2 to 45 days) and 6 days (3 to 16 days) (P < 0.01), and the median fever durations after macrolide therapy were 5 days (0 to 42 days) and 3 days (0 to 10 days) (P < 0.01), respectively, in the MR and MS groups. We also found that the incidence of extrapulmonary complications in the MR group was significantly higher than that in the MS group (P < 0.05). Moreover, the radiological findings were more serious in the MR group than in the MS group (P < 0.05). The increasing prevalence of MR M. pneumoniae has become a significant clinical issue in the pediatric patients, which may lead to more extrapulmonary complications and severe clinical features and radiological manifestations.