Changes in coagulation markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for Mycoplasma severity

Patients

A total of 170 children with MPP who received treatment at Luoyang Maternal and Child Health Hospital between June 2021 and February 2022 were consecutively selected as the study population. The patients were diagnosed with MPP according to the ‘Expert Consensus on the Diagnosis and Management of Mycoplasma pneumoniae Pneumonia in Children’ (2015 version), [11] as developed by the Respiratory Group of the Paediatrics Branch of the Chinese Medical Association. Briefly, the diagnostic criteria of MPP are as follows: (1) cough, with or without fever and other respiratory manifestations, and double lung auscultation can be heard along with dry and wet rales or signs of solid changes; (2) imaging suggests that the lungs present lobar infiltration or staged solid changes, lobular punctate infiltration or interstitial changes; and (3) MP infection: a single serum MP antibody titre of > 1:160, or twice 4-fold rise in titer in serum MP antibody, or a positive MP-polymerase chain reaction in a throat swab or alveolar lavage fluid.

For the present study, the diagnostic criteria for MPP combined with NP were observed as follows: (1) Previous lung imaging was normal, and, based on a definite diagnosis of MPP, an early computed tomography (CT) scan of the lungs suggested solid lung changes or combined pleural effusion. (2) As the disease progressed, liquefied necrosis of the lung tissue was observed in the original solid lung area, with multiple small, thin-walled cavities filled with gas or fluid; multiple small cavities may also have fused to form larger cavities, [12] which may also have included liquid–gas planes.

There are no clear diagnostic criteria for SMPP, but reference can be made to the ‘Code of Practice for the Treatment of Community-Acquired Pneumonia in Children’ (2019), [13] the ‘Expert Consensus on the Combined Diagnosis and Treatment of Mycoplasma pneumoniae Pneumonia in Children with Chinese and Western Medicine’ (developed in 2017), and the ‘Expert Consensus on the Laboratory Diagnostic Specifications and Clinical Practice of Mycoplasma pneumoniae Infection in Children in China’ (2019). The diagnostic criteria for SMPP include: (1) obvious shortness of breath or tachycardia, with or without dyspnea and cyanosis; (2) hypoxemia with pulse oximetry ≤ 0.92 on inspired air; (3) chest imaging showing multi-lobar segmental involvement or involvement of more than two-thirds of the lung; (4) intra-pulmonary complications, such as pleural effusion, atelectasis, necrosis and abscess; and (5) combination of severe damage to other systems (central nervous system infection, heart failure, myocarditis, gastrointestinal bleeding, significant electrolyte/acid-base balance disorders, etc.). Severe MPP can be diagnosed when any of the above is met together with a diagnosis of MPP.

Abnormal coagulation functioning was established using the following: thrombin time (TT) and prothrombin time (PT) prolongation of > 3 s; activated partial thromboplastin time (aPTT) prolongation of > 10 s; and fibrinogen (FIB), FIB degradation products (FDP) and D-dimer levels outside the normal reference range. Any instance where the above indicators were met was considered to reflect abnormal coagulation functioning. All of the patients with NP induced by MP infection were considered to have SMPP.

The exclusion criteria for the current study were as follows: (1) inadequate clinical information available for the child; (2) the condition was in the recovery stage at the time of admission; (3) evidence of co-infection with other pathogenic microorganisms (e.g. Staphylococcus aureus, Streptococcus pneumoniae, fungi and tuberculosis); (4) presence of other systemic diseases, such as severe congenital heart disease, chronic kidney disease, chronic lung disease, blood disorders and tumours; (5) patients who have received recent anticoagulant treatment or were using anticoagulants for other medical conditions; (6) patients with a recent history of major surgery or serious trauma and blood transfusion; and (7) patients with an immunodeficiency or other diseases that could cause abnormal immune function, as well as those who had recently received immunomodulatory agents.

The study population was divided into the SMPP group and the normal MPP (NMPP) group according to the severity of the disease. Following this, the population was further divided into the NMPP group (Group A, n = 83), NMPP combined with solid lung lesions (Group B, n = 37), MPP combined with solid lung lesions and pleural effusion (Group C, n = 28) and MPP combined with NP (Group D, n = 22), based on different imaging presentations. In addition, children with MPP combined with solid lung changes who underwent a bronchoscopy were divided into a mucus plug group and a non-mucus plug group according to their bronchoscopic presentation. This study was approved by the Ethics Committee of Luoyang Maternal and Child Health Hospital (no. KY2022052004.0).

Based on the diagnosis and treatment standard, in the NMPP group, anti-microbial treatment (macrolide anti-microbial drug anti-infection), nebulised inhaled glucocorticoid, sputum and other comprehensive treatments were administered. In the SMPP group, in addition to anti-infection and nebulised inhaled glucocorticoid and sputum treatments, intravenous glucocorticoid treatment was administered according to the severity of the disease. For the children with combined MPP and solid lung lesions, which were in line with the bronchoscopy indications, bronchoscopy and alveolar lavage treatment were performed after obtaining the consent of family members. Moreover, for those with obvious abnormalities in coagulation function, anticoagulant treatment of heparin sodium was given, and the aPTT was monitored.

Methods

The NMPP group (i.e. the control group) received a combination of treatments based on anti-microbial therapy, according to the treatment norms. The SMPP group (i.e. the observation group) received glucocorticoid therapy in addition to anti-infection and combination therapy, depending on the severity of the disease. [14] Fibreoptic bronchoscopy is generally only performed for patients receiving mechanical ventilation and patients with risk factors for rare microbial infections or complex pneumonia (e.g. immunocompromised or failure of empirical therapy). A bronchoscopy was performed for children who met the indications for the procedure according to the Chinese Guidelines for Paediatric Bendable Bronchoscopy (2018). [15] In addition, those with significant coagulation abnormalities received anticoagulation treatment with sodium heparin and were monitored for aPTT. The incidence of NP induced by MP was 12.35%.

Clinical information that may influence the severity of the disease was collected, including the patient’s general condition, coagulation indicators (TT, PT, aPTT, FIB, FDP), general inflammatory indicators (white blood cell count, neutrophil ratio [NE%], C-reactive protein [CRP], serum ferritin [SF] and serum lactate dehydrogenase), in addition to clinical features/indicators (total length of fever, total length of hospital stay, chest imaging, bronchoscopic manifestations, concurrent tensor and sequelae). All children underwent venous blood sampling within 24 h of admission for routine blood and CRP, coagulation, ferritin, lactate dehydrogenase (LDH) and MP antibody (immunoglobulin [Ig]M). If the first serum MP antibody IgM was negative, blood could be drawn again seven days after the onset of the illness. All patients had acute onset (most within one week of onset; some cases were more than a week old, but the infection was still progressing). All of the children underwent a chest radiograph or CT chest examination on admission according to the ‘Code of Practice for the Management of Community Acquired Pneumonia in Children’ (2019).

The study data were processed for statistical analysis using SPSS Statistics 25.0 (IBM, Chicago, USA) and GraphPad Prism 7.0 statistical analysis software (GraphPad ,California, USA). Relevant information was obtained via a Shapiro–Wilk test, and comparison information across the groups was obtained using the one-way analysis of variance method. Categorical information was expressed as percentages and tested using Chi-square tests. An independent samples t-test was conducted if the measures conformed to a normal or approximately normal distribution, using mean ± standard deviation (\(\bar x\) ± s ). A non-parametric test (Mann–Whitney) was used for non-normally distributed data, expressed in terms of median and interquartile spacing (M [P25, P75]). Analysis of the predictive value of coagulation indicators in the development of NP in MPP was conducted using logistic regression. Receiver operating characteristic (ROC) curves were created using the variables associated with MPP severity to analyse their sensitivity, specificity and optimal threshold values for predicting MPP combined with NP. All of the above statistical results were considered statistically significant at P < 0.05.

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