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Ribosomal RNA‑depleted RNA sequencing reveals the pathogenesis of refractory Mycoplasma pneumoniae pneumonia in children.

ABSTRACT: Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae) is a major cause of community‑acquired pneumonia in children. In some cases, M. pneumoniae pneumonia (MPP) can develop into refractory MPP (RMPP), which shows no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. However, the pathogenesis of RMPP remains poorly understood. The present study aimed to identify target genes that could be used as biomarkers for the clinical diagnosis of early‑stage RMPP through high‑throughput sequencing technology. The differences in long non‑coding (lnc)RNAs, mRNAs and circular (circ)RNAs were examined between whole‑blood samples from two patients with non‑refractory MPP (NRMPP), two patients with RMPP and three healthy children using ribosomal (r)RNA‑depleted RNA‑sequencing techniques and an integrated mRNA/circRNA analysis. A total of 17 lncRNAs (four upregulated and 13 downregulated), 18 mRNAs (six upregulated and 12 downregulated) and 24 circRNAs (12 upregulated and 12 downregulated) were the most significantly differentially expressed (P<0.05) between the NRMPP and RMPP groups. Upon functional analysis, the significantly differentially expressed genes encoded by the targeting mRNAs (prostaglandin‑endoperoxide synthase 2, IL‑8 and fos‑like antigen 1) were screened and identified to be enriched in the 'IL‑17 signaling pathway'. Furthermore, the key circRNAs in the NRMPP and RMPP comparative groups were primarily enriched in 'herpes simplex virus 1 infection', 'viral carcinogenesis' and 'RNA transport'. In the present study, a comprehensive analysis of the differences between the NRMPP and RMPP cases was performed based on rRNA‑depleted RNA‑sequencing techniques, and the selected genes and circRNAs may be closely associated with the complex pathogenesis of RMPP.

SUBMITTER: Huang F

PROVIDER: S-EPMC8436218 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroudThe current diagnostic criteria for refractory Mycoplasma pneumoniae pneumonia (RMPP) among Mycoplasma pneumoniae Pneumonia (MPP) are insufficient for early identification, and potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP.MethodsA total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA).ResultsMultivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08-1.33, P = 0.038), fever duration (HR 1.34, 95%CI 1.20-1.50, P < 0.001), lymphocyte count (HR 0.45, 95%CI 0.23-0.89, P = 0.021), serum D-dimer (D-d) level (HR 1.70, 95%CI 1.16-2.49, P = 0.006), and pulmonary imaging score (HR 5.16, 95%CI 2.38-11.21, P < 0.001). The area under the ROC curve was 90.7% for the development cohort and 96.36% for the validation cohort. The internal and external verification calibration curves were almost linear with slopes of 1, and the DCA curve revealed a net benefit with the final predictive nomogram.ConclusionThis study proposes a predictive nomogram only based on five variables. The nomogram can be used for early identification of RMPP among pediatric patients with MPP, thereby facilitating more timely and effective intervention.

Project description:Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Project description:BackgroundRefractory Mycoplasma pneumoniae pneumonia (RMPP) has a serious, rapid progression that can easily cause a variety of extra-pulmonary complications. Therefore, the early identification of RMPP is crucial. This study aimed to construct and validate a risk prediction model based on clinical manifestations, laboratory blood indicators, and radiological findings to help clinicians identify patients who are at high risk of RMPP.MethodsWe retrospectively analyzed the medical records of 369 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to Xi'an Children's Hospital, China. The demographics, clinical features, laboratory data, and radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and subjected to univariate and multivariate logistic regression analyses.ResultsThe fever peak and duration of the children in the RMPP group (n=86) were higher and longer compared with those in the GMPP group (n=283) (P<0.05). There was a significant difference in the incidence of lobar pneumonia and pleural effusion in pulmonary imaging between the two groups (P<0.05). Laboratory tests showed that the children with RMPP had lower serum uric acid (SUA) and albumin (ALB) as compared with the GMPP group (P<0.05). White blood cells (WBCs), neutrophil count (NEP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were higher in the RMPP group (P<0.05). Binary logistic regression analysis showed that the fever duration, pleural effusion, WBC, NEP, lactate dehydrogenase (LDH), CRP, NLR, and SUA levels were independent predictors of RMPP (P<0.05). The receiver operator characteristic (ROC) curve results showed fever duration, WBC, NEP, CRP, LDH, SUA, and NLR had good predictive value. The areas under the curve (AUCs) were 0.861, 0.730, 0.758, 0.837, 0.868, 0.744, and 0.713 and the best cutoff values were 10.50, 10.13, 6.43, 29.45, 370.50, 170.50, and 3.47, respectively. Finally, fever duration of more than 10.5 days, pleural effusion, WBC >10.13×109/L, NEP >6.43×109/L, CRP >29.45 mg/L, LDH >370.50 U/L, NLR >3.47, and SUA <170.5 µmol/mL constructed a prediction model of RMPP. According to internal validation, the mean AUC of the nomogram based on the development dataset was 0.956 [95% confidence interval (CI): 0.937-0.974] with good discrimination ability for predicting RMPP patients. The calibration plot and Hosmer-Lemeshow test (P=0.70) of the prediction model showed good consistency between the predicted probability and actual probability. Decision curve analysis (DCA) showed that the nomogram is clinically useful.ConclusionsThe simple and easy-to-use nomogram can help clinicians, especially primary doctors, to make early diagnoses of RMPP.

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Ribosomal RNA‑depleted RNA sequencing reveals the pathogenesis of refractory Mycoplasma pneumoniae pneumonia in children.

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