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The Study of Routine Laboratory
Factors in Children with Mycoplasma
Pneumonia: Serum Uric Acid may have
Anti-inflammatory Effect
Journal of Clinical Laboratory Analysis
Published By: Wiley Periodicals LLC
MIRABEL, HYGENIA HYACINTH O.
BMLS – 1B
Background
Introduction
Materials and
Method
Results
Content of Presentation
01
02
03
04
05
06
Discussion
Conclusion
High uric acid levels are a risk factor for cardiovascular disorders, and metabolic diseases; however, the role of
serum uric acid (sUA) during the mycoplasma pneumoniae pneumonia (MPP) of children is poorly known. This
study aimed to clarify the effects of sUA during the MPP of children.
01
Introduction
• Uric acid (UA), the product of purine catabolism, is a damage-associated molecular pattern (DAMP) released
from ischemic tissues and dying cells. Primates include humans lost the uricase gene, and the direct
consequence is that they have higher serum uric acid levels than other animals.
• Mycoplasma pneumoniae is an atypical bacterial respiratory pathogen known to cause a range of airway
inflammation and lung and extrapulmonary pathologies. Segoviady et al. reported that M. pneumoniae
infection activates the NLRP3 inflammasome complex, leading to IL-1 secretion, inflammation, and innate
immune cell activation in the lungs of infected C57BL/6 mice and in mouse bone marrow-derived
macrophages (BMDMs).
• The result of the study showed that Serum Uric Acid during MPP of children had a protective effect on the
body, which mechanism is needed to be further studied.
02
Materials and Method
This was a prospective cohort study of children with MPP from multi-center
inpatient departments from September 2019 to August 2020. Routine
laboratory characteristics analyzed including ALT, AST, BUN, CREA, UA, LDH,
CK-MB, WBC, N%, PLT, and CRP. Subjects were divided into 3 groups: non-
MPP, mild MPP (MMPP), and severe MPP (SMPP).
03
• Research data were collected from multi-center inpatient departments, including Shanghai Tenth
People's Hospital, School of Medicine, Tongji University; Hainan Maternal and Children's Medical Center;
Maternity Service Center of Pengzhou Maternal and Child Health Care Hospital; Huai'an First People's
Hospital, Nanjing Medical University.
• The diagnosis of MP infection was based on the positive results for a serologic test (MP IgM positive and
antibody titer 1:160) while having the positive results for MP polymerase chain reaction (PCR) tests of
nasopharyngeal secretions. This study was approved by the Ethics Committee of Shanghai Tenth People's
Hospital.
• All of the procedures performed in studies involving human participants were in accordance with the
ethical standards of the national guidelines.
3.1 Subjects
• Laboratory data were retrospectively collected from all children who were included in the study.
Characteristics analyzed liver function markers, including alanine aminotransferase (ALT), aspartate
aminotransferase (AST) and renal function [blood urea nitrogen (BUN), creatinine (CREA), and uric
acid(UA)], lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), white blood cell (WBC),
neutrophil(%), platelet(PLT), and C-reactive protein (CRP).
• The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital, School of
Medicine, Tongji University, and the data from patients were analyzed anonymously.
3.2 Data Collection
• All data were analyzed using SPSS 20 (IBM), and p < 0.05 was considered statistically significant.
Receiver operating characteristic (ROC) curves were used to analyze the optimal cutoff value of uric acid.
Normally distributed data were reported as mean ± standard deviation. One-way ANOVA was used to
compare these data.
• The comparisons were made by Kruskal-Wallis test. Binary logistic regression was used to analyze
protect or risk effects of laboratory factors between non-MPP and MPP. Protect or risk effects of
laboratory characteristics were made by multiple logistic regression among non-MPP, MMPP, and SMPP.
3.3 Statistical Analysis
Result
04
• Table 1 showed that the main clinical features and laboratory values. The age
was older in the SMMP samples than that in the non-MPP and MMPP, and
the result was consistent with the previous report.
• There was no significant difference in sex distribution among the 3 groups
• Pleural effusion, extrapulmonary complications, PLT, CRP, ALT, AST, LDH,
BUN, CREA, and UA had significance; but WBC and CK-MB had no
significance among the 3 groups
Parameter Control MMPP SMPP p
Clinical information
Age (year) 2 (3) 4 (4) 5 (4) ≤0.001
Sex (male/female) 132/99 277/264 93/83 0.317
Thermal spike
a
3 (1) 0 (3) 3 (1) 0.002
Fever>7 days
b
0 (0) 0 (0) 1 (1) ≤0.001
Range of lung
invasion
c
0 (0) 1 (0) 2 (0) ≤0.001
Pleural effusion
(1/3)
d
0 (0) 0 (0) 1 (1) ≤0.001
Extrapulmonary
complications
e
0 (0) 0 (0) 1 (1) ≤0.001
TABLE 1. Comparison of patients with non-MPP, MMPP, and SMPP
Parameter Control MMPP SMPP p
Laboratory values
WBC (*10
9
/L) 8 (4.33) 7.1 (3.3) 7.4 (3.8) 0.085
N (%) 41 (34.25) 53 (22) 57 (21) ≤0.001
PLT (*10
9
/L) 278.5 (146.5) 322 (157.5) 335 (169) ≤0.001
CRP (mg/L) 4.36 (13.46) 12.3 (20.25) 15.935 (28.53) ≤0.001
ALT (IU/L) 14 (13) 14 (7.5) 15.5 (12.0) ≤0.001
AST (IU/L) 36 (20) 32 (13) 34 (18) ≤0.001
LDH (IU/L) 291 (89) 287 (93.5) 325 (131.5) 0.020
CK-MB (IU/L) 26 (15) 25 (13) 22.5 (11) 0.082
BUN (mmol/L) 3.74 (1.58) 3.28 (1.2) 2.775 (1.63) ≤0.001
CREA (μmol/L) 29.6 (6.9) 29.1 (10.25) 28.5 (10.5) ≤0.001
UA (μmol/L) 264.469 ± 92.793 236.1763 ± 65.51
937
221.7881 ± 75.28
576
≤0.001
Discussion
05
• Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase
activity by various mutations of its gene during the Miocene epoch, which led to humans having
higher UA levels than other mammals.
• It has been argued that due to the powerful antioxidant activity of UA, the evolutionary benefit
could be the increased life expectancy of hominids, maintain blood pressure in times of very
low salt ingestion, and have higher intelligence in humans. Some researchers reported that
hyperuricemia is the primary risk factor for developing gout, hypertension, renal disease,
metabolic syndrome, diabetes, and cardiovascular disease.
• When humans suffered from stress and disease such as MPP, the human can respond by
mobilizing multiple systems and organs of the whole body to deal with it, increasing the
concentration of serum uric acid, especially SSMP to protect the body.
• If the sustained elevation of sUA will have harmful effects on the body such as hypertension, kidney
disease, obesity, diabetes, and gout, after the recovery from SMPP, the concentration of uric acid gradually
returns to normal, which whether it maintains a minimal level of anti-inflammation needs to be further
researched.
• The secretion of CRP starts within 4–6 h, and its level doubles every 8 h; it then reaches its maximum level
within 36–50 h. After the stimulation is removed, the CRP level falls relatively quickly, with a half-life of 19 h.
• Therefore, their effects must be analyzed together with other indicators. The present study had several
limitations. First, it was a retrospective observational study, and therefore, there may have been some
selection bias. Secondly, there are some cases in which the patients had a combined MP and other
pathogens infection which cannot be detected. Thirdly, the number of SMPP is not very enough.
Conclusion
06
In conclusion, we found that sUA has a protective effect during the MPP of children, which
suggested it had the anti-inflammatory activity in the present study. The results suggested
that urease loss may be one of the causes during human evolution. Further research needs
to do determine whether NLRP3 and other signaling pathways are responsible for this anti-
inflammation and whether physiological sUA is part of innate immune molecules. Both
multivariate and binary logistic regression demonstrated that sUA displayed a protective
effect during the MPP of children, which meant sUA is anti-inflammatory.
Reference
So A, Thorens B. Uric acid transport and disease. J Clin
Invest. 2010; 120(6): 1791- 1799.
https://doi.org/10.1002/jcla.24026

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The Study of Routine Laboratory Factors in Children with Mycoplasma Pneumonia: Serum Uric Acid may have Anti-inflammatory Effect

  • 1. The Study of Routine Laboratory Factors in Children with Mycoplasma Pneumonia: Serum Uric Acid may have Anti-inflammatory Effect Journal of Clinical Laboratory Analysis Published By: Wiley Periodicals LLC MIRABEL, HYGENIA HYACINTH O. BMLS – 1B
  • 2. Background Introduction Materials and Method Results Content of Presentation 01 02 03 04 05 06 Discussion Conclusion
  • 3. High uric acid levels are a risk factor for cardiovascular disorders, and metabolic diseases; however, the role of serum uric acid (sUA) during the mycoplasma pneumoniae pneumonia (MPP) of children is poorly known. This study aimed to clarify the effects of sUA during the MPP of children. 01
  • 4. Introduction • Uric acid (UA), the product of purine catabolism, is a damage-associated molecular pattern (DAMP) released from ischemic tissues and dying cells. Primates include humans lost the uricase gene, and the direct consequence is that they have higher serum uric acid levels than other animals. • Mycoplasma pneumoniae is an atypical bacterial respiratory pathogen known to cause a range of airway inflammation and lung and extrapulmonary pathologies. Segoviady et al. reported that M. pneumoniae infection activates the NLRP3 inflammasome complex, leading to IL-1 secretion, inflammation, and innate immune cell activation in the lungs of infected C57BL/6 mice and in mouse bone marrow-derived macrophages (BMDMs). • The result of the study showed that Serum Uric Acid during MPP of children had a protective effect on the body, which mechanism is needed to be further studied. 02
  • 5. Materials and Method This was a prospective cohort study of children with MPP from multi-center inpatient departments from September 2019 to August 2020. Routine laboratory characteristics analyzed including ALT, AST, BUN, CREA, UA, LDH, CK-MB, WBC, N%, PLT, and CRP. Subjects were divided into 3 groups: non- MPP, mild MPP (MMPP), and severe MPP (SMPP). 03
  • 6. • Research data were collected from multi-center inpatient departments, including Shanghai Tenth People's Hospital, School of Medicine, Tongji University; Hainan Maternal and Children's Medical Center; Maternity Service Center of Pengzhou Maternal and Child Health Care Hospital; Huai'an First People's Hospital, Nanjing Medical University. • The diagnosis of MP infection was based on the positive results for a serologic test (MP IgM positive and antibody titer 1:160) while having the positive results for MP polymerase chain reaction (PCR) tests of nasopharyngeal secretions. This study was approved by the Ethics Committee of Shanghai Tenth People's Hospital. • All of the procedures performed in studies involving human participants were in accordance with the ethical standards of the national guidelines. 3.1 Subjects
  • 7. • Laboratory data were retrospectively collected from all children who were included in the study. Characteristics analyzed liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and renal function [blood urea nitrogen (BUN), creatinine (CREA), and uric acid(UA)], lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), white blood cell (WBC), neutrophil(%), platelet(PLT), and C-reactive protein (CRP). • The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital, School of Medicine, Tongji University, and the data from patients were analyzed anonymously. 3.2 Data Collection
  • 8. • All data were analyzed using SPSS 20 (IBM), and p < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were used to analyze the optimal cutoff value of uric acid. Normally distributed data were reported as mean ± standard deviation. One-way ANOVA was used to compare these data. • The comparisons were made by Kruskal-Wallis test. Binary logistic regression was used to analyze protect or risk effects of laboratory factors between non-MPP and MPP. Protect or risk effects of laboratory characteristics were made by multiple logistic regression among non-MPP, MMPP, and SMPP. 3.3 Statistical Analysis
  • 9. Result 04 • Table 1 showed that the main clinical features and laboratory values. The age was older in the SMMP samples than that in the non-MPP and MMPP, and the result was consistent with the previous report. • There was no significant difference in sex distribution among the 3 groups • Pleural effusion, extrapulmonary complications, PLT, CRP, ALT, AST, LDH, BUN, CREA, and UA had significance; but WBC and CK-MB had no significance among the 3 groups
  • 10. Parameter Control MMPP SMPP p Clinical information Age (year) 2 (3) 4 (4) 5 (4) ≤0.001 Sex (male/female) 132/99 277/264 93/83 0.317 Thermal spike a 3 (1) 0 (3) 3 (1) 0.002 Fever>7 days b 0 (0) 0 (0) 1 (1) ≤0.001 Range of lung invasion c 0 (0) 1 (0) 2 (0) ≤0.001 Pleural effusion (1/3) d 0 (0) 0 (0) 1 (1) ≤0.001 Extrapulmonary complications e 0 (0) 0 (0) 1 (1) ≤0.001 TABLE 1. Comparison of patients with non-MPP, MMPP, and SMPP
  • 11. Parameter Control MMPP SMPP p Laboratory values WBC (*10 9 /L) 8 (4.33) 7.1 (3.3) 7.4 (3.8) 0.085 N (%) 41 (34.25) 53 (22) 57 (21) ≤0.001 PLT (*10 9 /L) 278.5 (146.5) 322 (157.5) 335 (169) ≤0.001 CRP (mg/L) 4.36 (13.46) 12.3 (20.25) 15.935 (28.53) ≤0.001 ALT (IU/L) 14 (13) 14 (7.5) 15.5 (12.0) ≤0.001 AST (IU/L) 36 (20) 32 (13) 34 (18) ≤0.001 LDH (IU/L) 291 (89) 287 (93.5) 325 (131.5) 0.020 CK-MB (IU/L) 26 (15) 25 (13) 22.5 (11) 0.082 BUN (mmol/L) 3.74 (1.58) 3.28 (1.2) 2.775 (1.63) ≤0.001 CREA (μmol/L) 29.6 (6.9) 29.1 (10.25) 28.5 (10.5) ≤0.001 UA (μmol/L) 264.469 ± 92.793 236.1763 ± 65.51 937 221.7881 ± 75.28 576 ≤0.001
  • 12. Discussion 05 • Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase activity by various mutations of its gene during the Miocene epoch, which led to humans having higher UA levels than other mammals. • It has been argued that due to the powerful antioxidant activity of UA, the evolutionary benefit could be the increased life expectancy of hominids, maintain blood pressure in times of very low salt ingestion, and have higher intelligence in humans. Some researchers reported that hyperuricemia is the primary risk factor for developing gout, hypertension, renal disease, metabolic syndrome, diabetes, and cardiovascular disease. • When humans suffered from stress and disease such as MPP, the human can respond by mobilizing multiple systems and organs of the whole body to deal with it, increasing the concentration of serum uric acid, especially SSMP to protect the body.
  • 13. • If the sustained elevation of sUA will have harmful effects on the body such as hypertension, kidney disease, obesity, diabetes, and gout, after the recovery from SMPP, the concentration of uric acid gradually returns to normal, which whether it maintains a minimal level of anti-inflammation needs to be further researched. • The secretion of CRP starts within 4–6 h, and its level doubles every 8 h; it then reaches its maximum level within 36–50 h. After the stimulation is removed, the CRP level falls relatively quickly, with a half-life of 19 h. • Therefore, their effects must be analyzed together with other indicators. The present study had several limitations. First, it was a retrospective observational study, and therefore, there may have been some selection bias. Secondly, there are some cases in which the patients had a combined MP and other pathogens infection which cannot be detected. Thirdly, the number of SMPP is not very enough.
  • 14. Conclusion 06 In conclusion, we found that sUA has a protective effect during the MPP of children, which suggested it had the anti-inflammatory activity in the present study. The results suggested that urease loss may be one of the causes during human evolution. Further research needs to do determine whether NLRP3 and other signaling pathways are responsible for this anti- inflammation and whether physiological sUA is part of innate immune molecules. Both multivariate and binary logistic regression demonstrated that sUA displayed a protective effect during the MPP of children, which meant sUA is anti-inflammatory.
  • 15. Reference So A, Thorens B. Uric acid transport and disease. J Clin Invest. 2010; 120(6): 1791- 1799. https://doi.org/10.1002/jcla.24026