Discussion
In our study, there was an apparent increase in the incidence of MPP from August to December 2021, which is consistent with other studies [
14,
15]. The aim of this study was to compare the clinical manifestations of febrile and afebrile children with MP infection. During the 4-month study period, 9.42% (51/542) of the children were afebrile, which is similar to the proportion in a previous study [
8]. However, few studies have compared the effect of fever on clinical features, which is unique to this study.
A total of 542 children were included in the study, of whom 491 were febrile and 51 were afebrile. Comparing the general information between the two groups, we found that the patients in the afebrile group were significantly younger than those in the febrile group (
P < 0.001), suggesting a lower incidence of fever in the younger children with MPP. A study by Sun et al. in 2015 including children under 1 year of age with MP infection showed that 63.89% of older children had fever, while 20% of younger children had fever, with a higher frequency [
16]. Other studies including adolescents and other pathogens have also confirmed that the incidence of fever may be lower in infants and younger children [
8,
17‐
20]. This may be because immunity in children improves with age and the immune response is more strongly stimulated in older children [
21]. Studies have shown that children over 5 years of age have a relatively more mature immune function than younger children [
22], which is consistent with the fact that IgA, IgM and IgG were significantly higher in the febrile group than in the afebrile group in this study (
P all < 0.05). In addition, we found that IgE levels were increased in both groups, but the difference was not statistically significant (
P = 0.357). Previous studies have also confirmed that there is indeed an elevated level of IgE in the acute phase of MP infection. In addition to being associated with allergy, MP-infected children with higher IgE levels may have more severe clinical manifestations and complications. IgE may even be a biomarker for complications following MP infection [
23]. The immune response is a double-edged sword. On the one hand, an appropriate immune response can activate macrophages in vivo to clear MP from the lung tissue [
24]; on the other hand, an excessive immune response can lead to an excessive inflammatory response [
22], resulting in severe pneumonia or refractory
Mycoplasma pneumoniae pneumonia (RMPP).
An interesting finding in our study was that children in the afebrile group had a significantly higher proportion of wheezing than those in the febrile group. However, we do not think that this is due to fever but mainly to age. The febrile group was older, and the afebrile group was younger (5.42 years old to 3.75 years old). It is well known that the mechanism of MP infection can cause airway hyper-responsiveness and increase airway secretions, thereby inducing or exacerbating asthma attacks [
25,
26]. Due to the relatively narrow airways, infants are more likely to have airway hypersecretion and hyper-responsiveness after respiratory infection and are more likely to wheeze [
27‐
29]. Therefore, we believe that the wheeze rate of the afebrile group is significantly higher than that of the febrile group, which is related to the physiological and pathological characteristics of age. There was no significant difference between the two groups in the proportion of mixed infections overall and for each pathogen (except EBV). The rate of fever in children infected with EBV is relatively high. However, there are no reports about that EBV infection is associated with wheezing and impairment of pulmonary function, so co-infection isn’t considered an influencing factor.
In this study, inflammatory indicators, including CRP, PCT, ESR, and FER, were significantly higher in the febrile group than in the afebrile group, indicating that the inflammatory response was significantly stronger in children with fever and older age, which is basically consistent with previous literature [
16,
19,
30]. There was no significant difference in the increase in LDH between the two groups. LDH is an enzyme involved in glycolysis. LDH is released from cells into the blood during the inflammatory response, and its level may reflect the intensity of the inflammatory response and the severity of organ damage [
31]. Several studies have found that elevated LDH is a major risk factor for RMPP and postinfectious obliterans [
31‐
34], suggesting that children who are not febrile are equally likely to develop severe disease and have a poor prognosis. In addition, there was no significant difference in ALT, CK-MB or D-dimer, indicating that fever was not associated with organ dysfunction or coagulation abnormalities.
However, beyond expectations, there were no apparent significant differences between the two groups in all the pulmonary function parameters. Eighty-four children underwent TBFV analysis. IOS was performed in all 141 children, and spirometry was performed in 154. In the TBFV analysis used in the younger age group, VT was normal, while TPTEF/TE and VPEF/VE decreased significantly, suggesting that the children in the younger age group had moderate obstructive ventilatory dysfunction. X
5 in IOS was significantly lower than normal, indicating peripheral small airway dysfunction in all children, while R
5 and R
20 were in the normal range, indicating that the total airway pressure, especially the central airway pressure, was not significantly affected. There was no significant difference in the difference in R
5 and R
20 between the two groups. In addition, in spirometry, FEV
1 and FEV
1/FVC were all within the normal range, but FEF
75 was decreased in both groups, suggesting that the children in this group also had small airway dysfunction. MP infection can cause obstructive airway dysfunction [
35]. A large number of studies have confirmed that the reduction is mainly in small airways [
36], and our research data are also consistent with this finding. It is not difficult to see that there was no significant difference in pulmonary function between the two groups. Regardless of the type of pulmonary function test, small airway function decreased significantly in both the febrile and afebrile groups. This means that patients without fever also need to be taken into account, even more than those without fever.
This is a single-center retrospective study with a small sample size, which may have some bias. In addition, the types of pulmonary functions performed were different due to the age of the children, and the number of each pulmonary function test performed was relatively small, which may affect the statistical results. Data on treatment and follow-up are not included in this study, which is our future development direction. As this is a retrospective observational study, there are some confounding factors such as age, co-infection although they have been discussed. A prospective study is needed to confirm this.
This study retrospectively analyzed demographic data, the presence of wheezing or atelectasis, laboratory results and pulmonary function. An important conclusion is drawn: MP infection is more common in older children and fever is more prominent. The rate of fever is lower in younger children, but the rate of wheezing is higher than that in older children. In afebrile children, although the inflammatory indicators were not as high, the degree of the impairment of organ and lung function was no less than in febrile children. Therefore, attention should also be paid to children who are not febrile.
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