*For medical professionals only
The blockbuster findings based on clinical data in China may provide an important basis for the typing of MPP in Chinese children
Organize | Yuan Xueqing
Mycoplasma pneumoniae pneumonia (MPP) is the most common community-acquired pneumonia in children aged 5 years and above in mainland China, which can affect the bronchi, bronchioles, alveoli and pulmonary interstitium, and is more harmful to children's health. As a heterogeneous disease, there are differences in the clinical phenotype and prognosis of MPP, which brings certain difficulties to the clinical diagnosis and treatment of MPP in children.
Recently, a study [1] published in Emerging Microbes & Infections (Impact Factor 13.2) preliminarily found that serum IL-17A and IL-6 were associated with the clinical phenotype and prognosis of MPP in children. This may provide a basis for the classification of MPP in Chinese children and the formulation of new treatment strategies for MPP, and facilitate the early prevention and treatment of MPP-induced lower airway occlusion (LAO), which may reduce the heavy burden of residual LAO after Mycoplasma pneumoniae infection in children in mainland China.
The "medical community" is honored to invite the corresponding author of this study: Professor Zhao Shunying from the Respiratory Center of Beijing Children's Hospital Affiliated to Capital Medical University and the first author: Dr. Heng Wang from the Respiratory Center of Beijing Children's Hospital Affiliated to Capital Medical University to make wonderful comments on this study (the comments are attached at the end of the article, don't miss it).
Figure 1 Screenshot of the document
high burden of disease and limited treatment measures,
New treatment strategies are urgently needed
In recent years, there have been increasing reports of severe/refractory MPP cases in children in East Asia, especially in China. Chinese children with MPP are relatively more severe and more prone to LAO, and in the autumn and winter of 2023, Chinese children have ushered in a major outbreak of MPP, and the disease burden is becoming heavier.
At present, the specific pathogenesis of MPP is unknown. It has been found that the differences in the clinical phenotype of MPP may be related to the different immune cell-mediated immune inflammatory responses induced by Mycoplasma pneumoniae infection, as well as the different severity of the responses.
Cytokines are potential clues to the body's immune response and inflammatory status, and can be used as molecular markers for disease assessment.
In fact, there have been numerous studies exploring the cytokine profile of MPP in children. However, these studies have focused on the role of cytokines in differentiating severe and mild MPP and their application value in assisting in the diagnosis of MPP. Few studies have looked at the potential association between cytokine phenotype (endotype) and clinical phenotypic heterogeneity.
In addition, the main treatment options for MPP in children in China are anti-Mycoplasma pneumoniae drugs, different doses of glucocorticoids (GC) and bronchoscopic lavage, but the clinical dilemma of residual LAO in severe MPP remains unresolved, so innovative interventions based on different clinical phenotypes and endotypes may be needed for pediatric MPP.
Based on this, the research team conducted this study to evaluate the cytokine profile of MPP in children and analyze the relationship between dynamic changes in specific cytokine levels and clinical phenotype and prognosis.
MPP clinical phenotype and prognosis
Associated with circulating IL-17A and IL-6 levels
As a prospective longitudinal real-world study, this study included 196 children with acute MPP who were hospitalized in the Second Ward of the Clinical Department of the Respiratory Center of Beijing Children's Hospital and the Second Ward of the Pediatric Respiratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University in Henan Province from June 2021 to March 2023. According to the chest imaging characteristics on days 6-10 of the course of the disease, the 196 children were divided into groups A, B, and C:
- Group A: Lobar consolidation (involving at least half of the lobes). According to the occurrence of pulmonary necrosis in the later stage of the disease, the group was further divided into A1 group (non-necrosis of lung tissue) and group A2 (necrosis of lung tissue).
- Group B: diffuse bronchiolitis with central lobular nodules, thickening of the bronchiole wall, "bud" sign, and ground-glass opacities;
- Group C: patchy opacities/cloud opacities, localized bronchiolitis, or lung consolidation with less than half lobe involvement.
Subsequently, the researchers collected blood samples from the children at multiple time points, and used multiplex cytokine detection to analyze the serum cytokine profile and its dynamic changes after admission, and then performed cluster analysis according to different clinical phenotypes.
The results showed that among the 10 serum cytokines in the 196 children, the levels of IL-17A and IL-6 were the most significantly different (Fig. 2).
Figure 2: Box plot of the overall distribution of serum cytokine levels of 10 serum cytokines on days 6-10 of the course of illness (n=196)
In addition, different clinical phenotypes were associated with different serum levels of IL-17A and IL-6: the significant increase in IL-17A was mainly related to consolidation-atelectasis and diffuse bronchiolitis caused by mucus hypersecretion, while the significant increase in IL-6 was mainly related to lung tissue necrosis secondary to consolidation-atelectasis.
Further analysis of the serum levels and prognosis of IL-17A and IL-6 after admission with different phenotypes showed that GC could not effectively inhibit the expression of IL-17A in children with lung consolidation-atelectasis and diffuse bronchiolitis caused by mucus hypersecretion. In addition, persistently elevated IL-17A may be associated with LAO.
To discover the association of cytokines with the clinical phenotype of MPP in children,
It may provide a basis for future MPP typing and new treatment strategies for children
This study focused on cytokines that are relatively readily available in routine clinical diagnosis and treatment, and found that a significant increase in IL-17A was associated with lung consolidation-atelectasis and diffuse bronchiolitis caused by mucus hypersecretion, while the increase in IL-6 was more common in patients with lung tissue necrosis secondary to lung consolidation-atelectasis, and persistently elevated IL-17A may be associated with LAO.
It is worth mentioning that epithelial damage and airway remodeling caused by long-term mucus hypersecretion may be one of the reasons for the occurrence of LAO. Therefore, circulating IL-17A levels may not only be used to assess the severity of MPP in children, but also may be a potential prognostic indicator for children with consolidation-atelectasis and diffuse bronchiolitis.
In addition, this study found that GC was ineffective in inhibiting the expression of IL-17A, suggesting that targeted therapy measures for IL-17A may be needed in children with severe MPP with lung consolidation-atelectasis and diffuse bronchiolitis in the future.
Expert Comments:
The clinical diversity of MPP in children in mainland China is diverse, and the incidence of LAO in different phenotypes is different, which means that different treatment regimens need to be adopted for different phenotypes. Therefore, it is necessary to summarize the different performance characteristics of MPP in children, and individualize the classification according to the clinical characteristics to guide future precision treatment, so as to effectively avoid residual LAO. In this study, based on the clustering and summarizing of different clinical phenotypes of MPP in children, we further explored the circulating cytokine profile (molecular phenotype/endotype) in the acute stage, and found the relationship between circulating IL-17A and IL-6 and the clinical phenotype and prognosis of MPP in children, and hormone therapy may not be able to effectively inhibit the secretion of IL-17A. Given the strong association between IL-17A and mucus hypersecretion and fibrosis, this suggests that the addition of IL-17A-targeted agents may be required in children with the specific clinical phenotypes described above.
In conclusion, this study may provide a molecular basis for the classification of MPP in Chinese children in the future, and may promote the innovation of MPP treatment strategies.
Expert Profile
Professor Zhao Shunying
- Chief Physician, Professor, Doctoral Supervisor.
- Honorary Director of the Respiratory Center of Beijing Children's Hospital Affiliated to Capital Medical University, under the supervision of Professor Jiang Zaifang.
- He specializes in the diagnosis and treatment of difficult and rare diseases of the respiratory system in children.
- As the first author and corresponding author, he has published more than 100 articles in core journals and SCI magazines, undertaken a number of fund projects such as the National Natural Science Foundation of China and the Beijing Natural Science Foundation, and wrote and participated in a number of expert consensus and guidelines for the diagnosis and treatment of children's respiratory diseases.
Click to read the original article and download the Doctor Station App to view~
参考文献：[1]Wang H, Zhang Y, Zhao C, Peng Y, Song W, Xu W, Wen X, Liu J, Yang H, Shi R, Zhao S. Serum IL-17A and IL-6 in paediatric Mycoplasma pneumoniae pneumonia: implications for different endotypes. Emerg Microbes Infect. 2024 Dec; 13(1):2324078. doi: 10.1080/22221751.2024.2324078. Epub 2024 Apr 4. PMID: 38407218; PMCID: PMC10997354.
Source of this article: Medical Infection Channel Reviewer: Dr. Wang Heng of Beijing Children's Hospital Affiliated to Capital Medical University
Editor in charge: Xiang Yu
*The Medical Community strives to be professional and reliable in its published content, but does not make any commitment to the accuracy of the content.
to learn more clinical skills