Mycoplasma Pneumoniae Pneumonia Research Articles

Novel Functional eQTL-SNPs Associated With Susceptibility to Mycoplasma pneumoniae Pneumonia in Children.

BackgroundThe functional causal single-nucleotide polymorphisms (SNPs) associated with susceptibility to Mycoplasma pneumoniae Pneumonia (MPP) have scarcely been identified. In this study, we aimed to analyze the association between the functional expression quantitative trait locus (eQTL)-SNPs and the risk of MPP.MethodsFirst, we identified reported genes associated with MPP from the human disease database, MalaCards. After investigating multiple databases, we systematically selected seven functional eQTL-SNPs (rs2070874, rs360720, rs8032531, rs4316, rs4353, rs7258241, and rs2250656). Finally, the selected eQTL-SNPs were genotyped using the TaqMan genotyping technology, and compared between 100 children with MPP and 178 healthy controls.ResultsWe found that three eQTL-SNPs (rs8032531 in CD276 and rs4316 and rs4353 in ACE) were significantly associated with susceptibility to MPP. Joint analysis of the three eQTL-SNPs revealed that the risk of MPP increased with an increase in the number of risk alleles present. Plasma protein expression levels of CD276 and ACE were distinctively higher in children with MPP than in healthy children (CD276: P < 0.001; ACE: P = 0.001).ConclusionFunctional eQTL-SNPs in CD276 and ACE may affect the susceptibility to MPP. The risk of developing MPP is higher in patients harboring a greater number of unfavorable alleles of the aforementioned SNPs.

Adoption and Safety Evaluation of Comfortable Nursing by Mobile Internet of Things in Pediatric Outpatient Sedation.

The aim of study was to explore the application effect and safety of comfortable nursing based on optimized mobile Internet of Things (MIoT) in the clinical sedation and diagnosis of mycoplasma pneumoniae pneumonia (MPP) in children. A total of 70 children with MPP admitted to the respiratory clinic of hospital were randomly selected and divided into a control group (comfortable nursing mode) and an observation group (comfortable nursing mode based on optimized MIoT), with 35 cases in each. The nursing effects and safety were compared between groups. The results showed that the node jitter rate, delivery success rate, and congestion times of the multilayered sensing algorithm were better than those of the mobile relay area segmentation algorithm and the wedge merge-energy hole elimination area segmentation algorithm. The CD-RISC resilience score of the observation group ((94.72 ± 1.58) points), the proportion of children with Frankl-3 and 4 points (90%), and the comfort level ((95.01 ± 5.68) points) were higher than those of the control group ((64.12 ± 1.62) points, (33.33%), and (55.23 ± 6.18) points) (P < 0.05). After treatment, the proportion of children with HRCT image lesions in the observation group was lower than that in the control group (P < 0.05). After treatment, the FEV1 ((85.71 ± 5.23) % vs. (68.26 ± 5.90) %) and FEV1/FVC ((74.22 ± 2.12) % vs (64.38 ± 2.34) %) of the observation group were significantly better than those of the control group (P < 0.05). The results showed that the incidence of adverse reactions in the observation group (14%) was significantly lower than that in the control group (46%) (P < 0.05). MIoT-assisted comfort nursing based on multilayer perception region segmentation algorithm can more effectively relieve the emotions of children in MPP outpatient department during sedation and diagnosis and treatment, improve the therapeutic effect and safety, and is worthy of clinical promotion.

Kukoamine A Improves Mycoplasma pneumoniae Pneumonia by Regulating miR-222-3p/Superoxide Dismutase 2.

Mycoplasma pneumoniae pneumonia (MPP) represents a common respiratory disease in children patients. Kukoamine A (KuA) is a spermine alkaloid found in the Chinese herb Cortex Lycii radices, which has a variety of pharmacological properties. However, no study has been reported on the role of KuA in MPP. Exosomes, a type of lipid bilayer-enclosed extracellular vesicles, can be delivered to the target cells, where they regulate function and physiology. With the use of human alveolar basal epithelial cells (HABECs) as an in vitro model, in this study, we sought to characterize the changes in levels of superoxide dismutase 2 (SOD2) and proinflammatory cytokines including IL-6 and TNF-α in HABECs in response to exosomes, which were isolated from peripheral blood serum of MPP patients. We found that, compared to normal, MPP patients exhibited a significant up-regulated miR-222-3p. Further, exosomal miR-222-3p downregulated SOD2 activity but promoted nuclear NF-κB activity and expression of IL-6 and TNF-α in HABECs, ultimately leading to an oxidative stress condition. Interestingly, such stimulating effects were attenuated by the pretreatment of KuA. This study suggests a critical role possessed by KuA in MPP by regulating the miR-222-3p/SOD2 axis, which represents a promising strategy for the treatment of MPP.

Cell damage and neutrophils promote the infection of Mycoplasma pneumoniae and inflammatory response

Mycoplasma pneumoniae (MP) is an important respiratory pathogen of human. The infection of MP can cause direct damage and immune damage in lung, resulting in Mycoplasma pneumoniae pneumonia (MPP). In this study, we aim to investigate the pathogenesis of MPP by detecting the proliferation of MP under conditions of cell damages and neutrophils in vitro. Firstly, we found the supplements of intracellular fluid, protein and RNA derived from intracellular fluid of A549 cells contribute to the survival of MP, thereby promoting the infection of MP. Cell damage can also significantly contribute to the survival of MP without supplements. At the same time, the additions of supplements contribute to apoptosis and the expression of IL-8 and IL-1β. Further, we found live neutrophils show bactericidal activity to MP, and the phagocytosis of MP promotes apoptosis of neutrophils. When co-incubated with MP and A549 cells, the proliferation of MP in the high neutrophils proportion groups were accelerated with functional decline of neutrophils, and the level of extracellular IL-1β showed a time and dose dependent manner to neutrophils. These results suggest that the release of intracellular nutrients by damaged cells and functional decline of neutrophils can promote the infection of MP and play roles in the activation of inflammatory response. Therefore, lung damage and infiltration of neutrophils would be important factors affecting the development of MPP.

High Expression of MUC5AC, MUC5B, and Layilin Plays an Essential Role in Prediction in the Development of Plastic Bronchitis Caused by MPP.

Plastic bronchitis (PB) is a rare respiratory condition which can result in severe respiratory complications such as respiratory failure and death. Mycoplasma pneumoniae infection is a main etiology cause of plastic bronchitis. However, the pathogenesis of plastic bronchitis complicated by Mycoplasma pneumoniae pneumonia (MPP) has not yet been fully elucidated. Our article aims to explore biomarkers for early prediction of MPP cases complicated with plastic bronchitis. We utilized a protein chip to screen for significantly different proteins among the groups of healthy, general Mycoplasma pneumoniae pneumonia (GMPP) and refractory Mycoplasma pneumoniae pneumonia (RMPP) patients, where layilin exhibited a potent change across biology information technology. Next, we demonstrated the high expression of MUC5AC, MUC5B, and layilin in bronchoalveolar lavage fluid (BALF) of MPP cases complicated with plastic bronchitis. Further study suggested that the level of layilin had a positive correlation with both MUC5AC and MUC5B. A receiver operating characteristic (ROC) analysis was performed to assess the diagnostic values of MUC5AC, MUC5B, and layilin in MPP cases with PB. Data show that the three indicators have similar diagnostic ability for MPP children with plastic bronchitis. Then, we used different concentrations of community-acquired respiratory distress syndrome (CARDS) toxin or lipid-associated membrane proteins (LAMPs) to simulate an in vitro experiment. The in vitro assay revealed that CARDS toxin or LAMPs induced A549 cells to secrete MUC5AC, MUC5B, layilin, and proinflammatory factors. These findings suggest that MUC5AC, MUC5B, and layilin are correlated with MPP. The high expression of MUC5AC, MUC5B, and layilin play an essential role in prediction in the development of plastic bronchitis caused by MPP. The high expression of MUC5AC, MUC5B, and layilin may be relevant to the severity of illness.

Clinical Usefulness of Serum Lactate Dehydrogenase Levels in Mycoplasma pneumoniae Pneumonia in Children.

To elucidate the clinical usefulness of lactate dehydrogenase (LDH) levels in children with Mycoplasma pneumoniae(MP) pneumonia and identify cut-off levels in various clinical conditions. The study was retrospectively performed in 145 children who were hospitalized with MP pneumonia. Laboratory findings, including LDH levels at admission and clinical features were retrospectively reviewed from patients' electronic medical records. The mean age of the study population was 5.9 y, and the mean value of LDH was 809.7 U/L. Poor response to treatment for MP pneumonia, respiratory virus coinfection, severe MP pneumonia, development of postinfectious bronchiolitis obliterans (PIBO) after MP pneumonia, pleural effusion, and oxygen need during illness were significantly associated with serum LDH levels. The cutoff levels of LDH for predicting poor response to treatment for MP pneumonia and respiratory virus coinfection were 1058 U/L [area under the curve (AUC), 0.729] and 803 U/L (AUC, 0.682), respectively. Those for pneumonic lesions involving at least one-third of the total lung volume, prediction of PIBO development, and extrapulmonary manifestations were 1098 U/L (AUC, 0.715), 676 U/L (AUC, 0.714), and 859 U/L (AUC, 0.710), respectively. The cutoff levels for pleural effusion during illness and for the prediction of oxygen need were 894 U/L (AUC, 0.699) and 1114 U/L (AUC, 0.771), respectively. LDHlevels areelevatedin diverse clinical conditions in children with MP pneumonia and may be useful in the identification of severe clinical courses of MP pneumonia in children.

Prediction Model for Severe Mycoplasma pneumoniae Pneumonia in Pediatric Patients by Admission Laboratory Indicators.

The purpose of this study was to develop a model for predicting severe Mycoplasma pneumoniae pneumonia (SMPP) in pediatric patients with Mycoplasma pneumoniae pneumonia (MPP) on admission by laboratory indicators. Pediatric patients with MPP from January 2019 to December 2020 in our hospital were enrolled in this study. SMPP was diagnosed according to guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version). Prediction model was developed according to the admission laboratory indicators. Receiver operating characteristic curve and Goodness-of-fit test were analyzed for the predictive value. A total of 233 MPP patients were included in the study, with 121 males and 112 females, aged 4.541 (1-14) years. Among them, 84 (36.1%, 95% CI 29.9-42.6%) pediatric patients were diagnosed as SMPP. Some admission laboratory indicators (immunoglobulins M (IgM), eosinophil proportion, eosinophil count, hemoglobin, erythrocyte sedimentation rate (ESR), total protein, albumin and prealbumin) were found statistically different (p < 0.05) between non-SMPP group and SMPP group. Logistic regress analysis showed IgM, eosinophil proportion, eosinophil count, ESR and prealbumin were independent risk factors for SMPP. According to these five admission laboratory indicators, the prediction model for SMPP in pediatric patients was developed. The area under curve of the prediction model was 0.777, and the goodness-of-fit test showed that the predicted SMPP incidence by the model was consistent with the actual incidence (χ2 = 244.51, p = 0.203). We developed a model for predicting SMPP in pediatric patients by admission laboratory indicators. This model has good discrimination and calibration, which provides a basis for the early identification SMPP on admission. However, this model should be validated by multicenter studies with large sample.

Clinical significance of respiratory virus coinfection in children with Mycoplasma pneumoniae pneumonia

BackgroundThe prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia has been increasing. However, few studies have investigated the impact of respiratory virus coinfection in patients with MP pneumonia, and their results have been inconclusive. This study aimed to investigate the impact of respiratory virus coinfection in children hospitalized with MP pneumonia.MethodsThis study enrolled 145 children hospitalized with MP pneumonia between May 2019 and March 2020. The patients were divided into two groups: the respiratory virus coinfection and non-coinfection groups. All the children underwent polymerase chain reaction testing for respiratory virus infection. Information on clinical, laboratory, and radiologic findings were obtained retrospectively via medical chart reviews.ResultsChildren in the respiratory virus coinfection group were younger than those in the non-coinfection group. Respiratory virus coinfection in children hospitalized with MP pneumonia was significantly associated with persistence of fever more than 6 days (adjusted odds ratio [aOR], 2.394; 95% confidence interval [95% CI], 1.172–4.892), severe pneumonia (aOR, 4.602; 95% CI, 1.154–18.353), and poor response to the stepwise approach for MP pneumonia (aOR, 4.354; 95% CI, 1.374–13.800). In addition, higher levels of liver enzymes and lactate dehydrogenase at admission were associated with respiratory virus coinfection in children with MP pneumonia.ConclusionsThe results of this study suggest that respiratory virus coinfection in children hospitalized with MP pneumonia may be associated with refractory MP pneumonia.

Clinical significance of Mycoplasma pneumoniae specific IgM titer in children hospitalized with Mycoplasma pneumoniae pneumonia

BackgroundThe present study aimed to identify the clinical significance of Mycoplasma pneumoniae (MP)-specific immunoglobulin M (IgM) titer, in addition to a diagnosis of MP infection, in children with MP pneumonia.MethodsThis study was performed in 155 children hospitalized with MP pneumonia. The clinical features and laboratory and radiographic findings on admission in children with positive or negative MP-specific IgM titers were retrospectively reviewed from the electronic medical records.ResultsThe mean age of the included children was 6.0 years, and 118 (76.1%) of the children were positive for MP-specific IgM. A longer duration between symptom onset and admission (adjusted odds ratio [aOR] 1.47, 95% confidence interval [CI] 1.24–1.75), longer duration of symptoms during the illness (aOR 1.15, 95% CI 1.02–1.30), and development of extra-pulmonary manifestations (aOR 9.16, 95% CI 1.96–42.81) were significantly associated with a positive MP-specific IgM titer. Serum lactate dehydrogenase levels (aOR 1.00, 95% CI 1.00–1.01) and pneumonic infiltration involving > 50% of the total lung volume on chest radiography (aOR 4.68, 95% CI 1.12–19.55) were associated with positive MP-specific IgM in children with MP pneumonia. A poor response to stepwise treatment for MP pneumonia was more common in children with a positive MP-specific IgM titer than those with a negative MP-specific IgM titer on admission.ConclusionsA positive MP-specific IgM titer at diagnosis of MP pneumonia may partially suggest an exaggerated immune response with a higher disease burden compared to children with MP pneumonia with a negative MP-specific IgM titer.

Investigation of the relationship between community-acquired respiratory distress syndrome toxin and the high-mobility group box protein 1-toll-like receptors-myeloid differentiation factor 88 signaling pathway in Mycoplasma pneumoniae pneumonia

BackgroundIn recent years, reports of refractory Mycoplasma pneumoniae pneumonia (RMPP) have gradually increased, including reports on how these conditions threaten the lives of children. However, the specific mechanism of Mycoplasma pneumoniae pneumonia (MPP) remains unclear. This study aimed to investigate the relationship between community-acquired respiratory distress syndrome toxin (CARDS TX) and High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 (HMGB1-TLRs-MyD88) in MPP and to examine the immune pathogenesis of Mycoplasma pneumoniae infection.MethodsChildren who were diagnosed with MPP and examined by bronchoscopy were included in the MPP group. Additionally, children who underwent bronchoscopy because of bronchial foreign bodies in the same period were included in the control group. Gene expression of CARDS TX, HMGB1, Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), MyD88, and cluster of differentiation 14 (CD14) in bronchoalveolar lavage fluid (BALF) were detected using real-time reverse transcription-polymerase chain reaction. Correlations between CARDS TX and HMGB1-TLRs-MyD88 were analyzed.ResultsCARDS TX, HMGB1, TLR2, MyD88, and CD14 mRNA expression in BALF in the MPP group was significantly higher than that in the control group (all P < 0.05). CARDS TX mRNA expression was positively correlated with HMGB1, TLR2, MyD88, and CD14 mRNA expression (all P < 0.05). Furthermore, HMGB1 mRNA expression was positively correlated with TLR2, MyD88, and CD14 mRNA expression (all P < 0.05).ConclusionsCARDS TX may participate in the immune pathogenesis of MPP through the HMGB1-TLRs/CD14-MyD88 pathway.

The role of flexible bronchoscopy in children with Mycoplasma pneumoniae pneumonia.

To explore the effectiveness of flexible bronchoscopy in pediatric Mycoplasma pneumoniae pneumonia (MPP). This retrospective cohort study included children with MPP admitted between 2016 and 2019 in Shanghai. Tracheobronchial manifestations, etiologic findings, therapeutic effect, and health-economic indicators were assessed in bronchoscopy (plus bronchoalveolar lavage (BAL)) and non-bronchoscopy group. We used propensity-score matching and multivariable logistic regression to investigate the effect of bronchoscopy and BAL on disease recovery. In 900 children with MPP, 24/278 (8.6%) of those who underwent bronchoscopy had sputum plugs. Coinfection rate was four-fold enhanced by BAL (19.6% vs. 4.5%, p < 0.01) in patients with severe MPP (SMPP) and nearly doubled (10.8% vs. 5.9%, p = 0.03) in those without SMPP, compared with no BAL. Total of 224 (24.9%) patients had multilobar consolidation; after BAL, a significantly shorter lesion-resolution duration was observed on imaging (OR: 0.2, 95% CI: 0.0-0.7). However, longer fever duration (OR: 2.8, 95% CI: 1.7-4.8), hospital stay (OR: 3.1, 95% CI: 1.9-5.1), and higher costs were found in the bronchoscopy group than in the non-bronchoscopy group. Through BAL, coinfection may explain one-fifth of causes for SMPP. Bronchoscopy with BAL may increase the detection rate of pathogen and resolve pulmonary lesions in patients with multilobar consolidation. Flexible bronchoscopy with bronchoalveolar lavage is of great assistance in the timely detection of coinfection, sputum plug and inflammatory polyps in children with Mycoplasma pneumoniae pneumonia (MPP), and improves the recovery of lung damage in MPP patients with multilobar consolidation. This study provides new insights into the indications of flexible bronchoscopy for the diagnosis and treatment of pediatric patients with MPP.

Combined Radiographic Features and Age Can Distinguish Mycoplasma pneumoniae Pneumonia from Other Bacterial Pneumonias: Analysis Using the 16S rRNA Gene Sequencing Data.

The study objective was to evaluate chest radiographic features that distinguish Mycoplasma pneumoniae pneumonia (MPP) from other bacterial pneumonias diagnosed based on the bacterial floral analysis with 16S rRNA gene sequencing, using bronchoalveolar lavage fluid samples directly obtained from pneumonia lesions. Patients were grouped according to the dominant bacterial phenotype; among 120 enrolled patients with CAP, chest CT findings were evaluated in 55 patients diagnosed with a mono-bacterial infection (one bacterial phylotype occupies more than 80% of all phylotypes in a sample) by three authorized respiratory physicians. Among this relatively small sample size of 55 patients with CAP, 10 had MPP, and 45 had other bacterial pneumonia and were categorized into four groups according to their predominant bacterial phylotypes. We created a new scoring system to discriminate MPP from other pneumonias, using a combination of significant CT findings that were observed in the M. pneumoniae group, and age (<60 years) (MPP–CTA scoring system). When the cutoff value was set to 1, this scoring system had a sensitivity of 80%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 95%. Among the CT findings, centrilobular nodules were characteristic findings in patients with MPP, and a combination of chest CT findings and age might distinguish MPP from other bacterial pneumonias.

Intestinal bacteria flora changes in patients with Mycoplasma pneumoniae pneumonia with or without wheezing

Mycoplasma pneumoniae (MP) infection is a common cause of community-acquired pneumonia in children. Furthermore, many children with Mycoplasma pneumoniae pneumonia (MPP) have recurrent wheezing and reduced small airway function after their clinical symptoms have resolved, eventually leading to asthma. MPP can trigger immune disorders and systemic inflammatory responses. Hence, the intestine is the largest immune organ of the body. Therefore, we sought to investigate whether the alteration of intestinal flora is correlated with the development of wheezing in children with MPP. We collected 30 healthy children as group A, 50 children with nonwheezing MPP as group B, and 50 children with wheezing MPP as group C. We found that the percentage of eosinophil cells (EC) was significantly higher in group C than that in group B for routine blood tests and serum inflammatory factors. The serum cytokines, including IL-4, IL-17, TNF-α, and TGF-β, were significantly higher in group C than in group B. In addition, the level of IL-10 was significantly lower in group C than in group B. The distribution characteristics of intestinal flora strains in children with MPP were detected by sequencing of 16S rRNA gene amplicon sequencing. There were differences in the abundance of intestinal flora between children with MPP and healthy children, with lower abundance of Ruminococcus flavefaciens, Clostridium butyricum, Lactobacillus, and Bifidobacterium in the intestine of children with MPP compared to healthy children. The abundance of Ruminococcus flavefaciens and Clostridium butyricum was significantly lower in the intestine of children with wheezing MPP compared to children without wheezing MPP. In the correlation analysis between children with MPP and inflammatory factors, Ruminococcus flavefaciens was found to be negatively correlated with IL-17. Clostridium butyricum was negatively correlated with L-4, IL-17, TNF-α, and TGF-β; however, it positively correlated with IL-10. Thus, it was concluded that alterations in intestinal flora play a crucial role in the immune response to MPP, where a significant decline in intestinal Ruminococcus flavefaciens and Clostridium butyricum leads to an exacerbation of the inflammatory responses, which may promote the development of children with wheezing MPP.

Chest imaging characteristics of mycoplasma pneumoniae pneumonia in children

Mycoplasma pneumoniae pneumonia (MPP) is the most common type of childhood community-acquired pneumonia. MPP is generally mild and self-limiting, but a small percentage of patients still develop a refractory or severe clinical course. Imaging is an important tool for confirmed pneumonia, and it plays an important role in the diagnosis of MPP and assessment of the clinical course. However, imaging features of MPP reported in the literature vary in their patterns to distribution. A comprehensive and deep understanding of imaging findings of MPP in children is beneficial for an accurate diagnosis and guidance of its treatment.

Mycoplasma Pneumoniae Infection and Persistent Wheezing in Young Children: A Retrospective Case-Control Study.

BackgroundTo investigate the clinical characteristics of children with persistent wheezing (PW) with Mycoplasma pneumoniae (MP) DNA in bronchoalveolar lavage fluid (BALF).MethodsThis retrospective case-control study included consecutive admitted children under 3 years of age who were diagnosed with PW and had MP DNA detected in BALF. Patients with mycoplasma pneumoniae pneumonia (MPP) and foreign-body aspiration (FBA) were enrolled as controls. The clinical characteristics of the groups were compared.ResultsDuring the study period, there were 89 patients diagnosed with PW without structural anomalies of the conductive airways, and 30 of these patients (33.7%, 30/89) with MP DNA detected in the BALF were selected as the study group. We included 44 patients with MPP and 44 patients with FBA as controls. Patients with MPP were older and had a higher occurrence of fever and C-reactive protein (CRP) than patients with PW (all P < 0.001). The median MP DNA copy number in patients with MPP was higher than that of patients with PW (P = 0.004). The median level of MP IgG in patients with PW was lower than that of patients with MPP and higher than that of patients with FBA (all P < 0.001). MP DNA copy number positively correlated with age (r = 0.392, P = 0.001) and CRP (r = 0.235, P = 0.048).ConclusionsOur study reveals that MP was highly detected in the BALF of PW patients. In addition, young patients with a low load of MP infection showed lower amounts of antibody, and a weak inflammatory response might be associated with PW.

Mycoplasma pneumoniae Pleural Effusion in Adults.

Parapneumonic effusions often complicate Mycoplasma pneumoniae (MP) pneumonia, contrary to the notion that they are a rare feature of MP infection. Increased research and evidence on MP parapneumonic effusions (MPPE) can help elucidate its clinical significance as one of the variable manifestations of MP infection. This article aims to summarize the existing literature about the clinical characteristics of MPPE in adults and discuss its diagnostic implications from the perspective of pleural fluid analysis. Approximately 20–25% of adult patients with MP pneumonia develop MPPE, and its frequency in children and adults seems to be similar. Although the pathogenesis of MPPE remains to be elucidated, MP-induced cell-mediated immune mechanisms might be partially associated with the development of MPPE. MPPE usually shows mononuclear leukocyte predominance with elevated adenosine deaminase (ADA) activity, similar to tuberculous pleural effusion (TPE). The degree of increase in pleural fluid ADA levels and serum inflammatory biomarkers may help differentiate between MPPE and TPE. During the acute phase, a single positive IgM and positive polymerase chain reaction results allow for a precise and reliable MP infection diagnosis. The mainstay of treatment is the selection of adequate anti-mycoplasma antibiotics with or without corticosteroid, based on the local epidemiologic data on macrolide resistance.

Development of a Nomogram for Predicting Refractory Mycoplasma pneumoniae Pneumonia in Children.

BackgroundIn children, refractory Mycoplasma pneumoniae pneumonia (RMPP) may result in severe complications and high medical costs. There is research on a simple and easy-to-use nomogram for early prediction and timely treatment of RMPP.MethodsFrom December 2018 to June 2021, we retrospectively reviewed medical records of 299 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in Tianjin Children's Hospital. According to their clinical manifestations, patients were divided into the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group. The clinical manifestations, laboratory indicators, and radiological data of the two groups were obtained. Stepwise regression was employed for variable selection of RMPP. The predictive factors selected were used to construct a prediction model which presented with a nomogram. The performance of the prediction model was evaluated by C statistics, calibration curve, and receiver operating characteristic (ROC) curve.ResultsThe RMPP group significantly showed a higher proportion of females, longer fever duration, and longer hospital stay than the GMPP group (P < 0.05). Additionally, the RMPP group revealed severe clinical characteristics, including higher incidences of extrapulmonary complications, decreased breath sounds, unilateral pulmonary consolidation >2/3, and plastic bronchitis than the GMPP group (P < 0.05). The RMPP group had higher neutrophil ratio (N%), C-reactive protein (CRP), interleukin-6 (IL-6), lactic dehydrogenase (LDH), and D-dimer than the GMPP group (P < 0.05). Stepwise regression demonstrated that CRP [OR = 1.075 (95% CI: 1.020–1.133), P < 0.001], LDH [OR = 1.015 (95% CI: 1.010–1.020), P < 0.001], and D-dimer [OR = 70.94 (95% CI: 23.861–210.904), P < 0.001] were predictive factors for RMPP, and developed a prediction model of RMPP, which can be visualized and accurately quantified using a nomogram. The nomogram showed good discrimination and calibration. The area under the ROC curve of the nomogram was 0.881, 95% CI (0.843, 0.918) in training cohorts and 0.777, 95% CI (0.661, 0.893) in validation cohorts, respectively.ConclusionC-reactive protein, LDH, and D-dimer were predictive factors for RMPP. The simple and easy-to-use nomogram assisted us in quantifying the risk for predicting RMPP, and more accurately and conveniently guiding clinicians to recognize RMPP, and contribute to a rational therapeutic choice.

Metabolomic analysis reveals potential biomarkers and the underlying pathogenesis involved in Mycoplasma pneumoniae pneumonia

ABSTRACT Although previous studies have reported the use of metabolomics for infectious diseases, little is known about the potential function of plasma metabolites in children infected with Mycoplasma pneumoniae (MP). Here, a combination of liquid chromatography-quadrupole time-of-flight mass spectrometry and random forest-based classification model was used to provide a broader range of applications in MP diagnosis. In the training cohort, plasma from 63 MP pneumonia children (MPPs), 37 healthy controls (HC) and 29 infectious disease controls (IDC) was collected. After multivariate analyses, 357 metabolites were identified to be differentially expressed among MPP, HC and IDC groups, and 3 metabolites (568.5661, 459.3493 and 411.3208) had high diagnostic values. In an independent cohort with 57 blinded subjects, samples were successfully classified into different groups, demonstrating the reliability of these biomarkers for distinguishing MPPs from controls. A metabolomic signature analysis identified major classes of glycerophospholipids, sphingolipids and fatty acyls were increased in MPPs. These markedly altered metabolites are mainly involved in glycerophospholipid and sphingolipid metabolism. As the ubiquitous building blocks of eukaryotic cell membranes, dysregulated lipid metabolism indicates damage of the cellular membrane and the activation of immunity in MPPs. Moreover, lipid metabolites, differentially expressed between severe and mild MPPs, were correlated with the markers of extrapulmonary complications, suggesting that they may be involved in MPP disease severity. These findings may offer new insights into biomarker selection and the pathogenesis of MPP in children.

Vaccine using community-acquired respiratory distress syndrome toxin as an antigen against Mycoplasma pneumoniae in mice

Mycoplasma pneumoniae (Mp) is one of the most common causes of bacterial community-acquired pneumonia in humans. Because of the frequent epidemics and the emergence of antibiotic-resistant Mp, vaccines for Mp are urgently needed to ameliorate the pneumonia and secondary complications. The community-acquired respiratory distress syndrome (CARDS) toxin produced by Mp is a pathogenic factor that induces severe inflammatory responses in lung. Although blocking CARDS toxin is expected to mitigate the severity of Mp pneumonia, the potential of CARDS toxin as a vaccine antigen has not been assessed. Here, we examined the effectiveness of vaccine using recombinant CARDS toxin (rCARDS toxin) as an antigen in mice. Immunization with rCARDS toxin induced both rCARDS toxin- and Mp-specific antibody responses, indicating that CARDS toxin is located on the surface of Mp. In addition, immunization with rCARDS toxin decreased not only lung injury, neutrophil infiltration, and the production of inflammatory cytokines but also the persistence of Mp in lung after Mp challenge. Furthermore, we elucidated that the CARDS toxin on the surface of Mp facilitates the adherence of Mp to epithelial cells. In conclusion, we have demonstrated the potential of rCARDS toxin as a vaccine antigen to ameliorate Mp pneumonia by suppressing the inflammatory responses induced by Mp and the persistence of Mp in lung. These data support the development of novel vaccines for Mp pneumonia.

Exhausted and Apoptotic BALF T Cells in Proinflammatory Airway Milieu at Acute Phase of Severe Mycoplasma Pneumoniae Pneumonia in Children.

Severe mycoplasma pneumoniae pneumonia (MPP) in children presents with serious clinical complications. Without proper and prompt intervention, it could lead to deadly consequences. Dynamics of the inflammatory airway milieu and activation status of immune cells were believed to be the hallmark of the pathogenesis and progress of the disease. In this study, by employing the T-cell sorting and mRNA microarray, we were able to define the main feature of the chemokine/cytokine expression and the unique characteristics of T cells in the bronchoalveolar lavage fluid (BALF) from severe MPP patients at acute phase. Our study for the first time delineated the molecular changes in isolated BALF T cells in severe MPP children with respect to the cytokine/chemokine expression, cell activation, exhaustion, and apoptosis. By comparing the BALF aqueous expression of cytokines/chemokines with that in sorted T cells, our data give a preliminary clue capable of finishing out the possible cell source of the proinflammatory cytokines/chemokines from the BALF mixture. Meanwhile, our data provide a distinctively pellucid expression profile particularly belonging to the isolated BALF T cells demonstrating that in the inflammatory airway, overactivated T cells were exhausted and on the verge of apoptotic progress.