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Diagnostic values of soluble triggering receptor expressed on myeloid cells (sTREM-1) and interferon-inducible protein-10 (IP-10) for severe mycoplasma pneumoniae pneumonia in children
Chang Xu, Li-Yan Luo, Bi-Chen Wu, Niu Ding, Shi-Jie Jin, Jian-Bao Huang, Yan-Ping Chen
Corresponding author
hnchengyanping@163.com

Corresponding author.
Department of Respiratory, Hunan Children's Hospital, Changsha, China
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0008" class="elsevierStylePara elsevierViewall">Mycoplasma Pneumoniae &#40;MP&#41; is among the smallest self-replicating bacteria that lack typical bacterial cell walls&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> It is a common pathogenetic organism of respiratory infection in children&#46; Mycoplasma Pneumoniae Pneumonia &#40;MPP&#41; accounts for approximately 8&#37; to 40&#37; of Community-Acquired Pneumonia &#40;CAP&#41; in children aged from 3 to 15 with regional epidemics occurring every 3 to 7 years&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> Although MPP spreads easily among children who are in close contact with each other&#44; it is typically a self-limited disease&#46; However&#44; Severe MPP &#40;SMPP&#41; happens with serious pulmonary and extrapulmonary complications at times&#44; including pulmonary atelectasis&#44; necrotizing pneumonia&#44; myocardial damage and peripheral embolization&#44; which may result in serious impacts on children&#39;s clinical outcome and quality of life&#46; Early diagnosis and prompt treatment are of great significance in reducing the mortality and sequelae of children with SMPP&#46; Therefore&#44; there is an urgent need to identify valid biomarkers that indicate the severity of MPP&#46;</p><p id="para0009" class="elsevierStylePara elsevierViewall">Soluble Triggering Receptors Expressed on Myeloid cell-1 &#40;sTREM-1&#41; is an important inflammatory factor and index of oxidative stress&#46; The increase of its concentration leads to the activation of downstream inflammatory signaling pathways&#44; such as interleukin-6 and interleukin-1&#946;&#46; sTREM-1 cooperates with Toll-Like Receptors &#40;TLRs&#41; and mediates the expansion of inflammatory response&#44; thus promoting the progression of pulmonary infectious disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0004"><span class="elsevierStyleSup">4-6</span></a> sTREM-1 shows diagnostic value in diseases such as Neonatal Sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> IP-10&#44; a chemokine that belongs to the CXC family&#44; was induced by interferon in several cell types such as monocytes&#44; neutrophils&#44; fibroblasts and endothelial cells&#46; IP-10 is also a chemoattractant for activated T-cells&#46; IP-10 was detected in many Th1-type inflammatory diseases&#44; where it is considered to play an important role in recruiting activated T cells into sites of tissue inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> It was reported that IP-10 was involved in infection diseases including pulmonary tuberculosis<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> and lymphoma-associated hemophagocytic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> IP-10 was also implicated in SMPP&#44; however&#44; the diagnostic value of sTREM-1 and IP-10 in MPP remains to be depicted&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">In this prospective study&#44; the authors aimed to explore the relationship between the serum levels of sTREM-1&#47;IP-10 and the severity MPP&#46; The authors also analyzed the diagnosis value of these two cytokines to see if they could act as novel biomarkers for children with SMPP&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Study population</span><p id="para0011" class="elsevierStylePara elsevierViewall">From January to November of 2021&#44; 44 children with MPP from the Hunan Children&#39;s Hospital were recruited for this prospective analysis&#46; Criteria for selecting the subjects were as follows&#58; &#40;i&#41; Clinical presentation &#40;fever&#44; cough&#44; tachypnea&#44; abnormal breath sounds&#41; and radiologic evidence of CAP &#40;interstitial infiltrates&#44; segmental and lobar consolidations&#44; hilar lymph node enlargement&#41;&#59; &#40;ii&#41; Microbiological evidence from serologic testing&#44; positive Polymerase Chain Reaction &#40;PCR&#41; tests of nasopharyngeal secretions or Bronchoalveolar Lavage Fuid &#40;BALF&#41;&#44; indications for bronchoscopy were persistent radiological abnormalities &#40;atelectasis and consolidation of lung felds&#41;&#46; Exclusion criteria were the following&#58; &#40;i&#41; Patients with primary or secondary immune deficiency&#47;dysfunction&#44; including congenital heart disease&#44; chronic liver or kidney disease&#44; oncologic disorders&#44; connective tissue disease&#44; chronic lung disease&#59; &#40;ii&#41; Patients in convalescent-phase&#59; &#40;iii&#41; Patients with mixed infection&#59; &#40;iv&#41; Patients diagnosed with severe MPP later during the hospitalization as the disease progressed&#46; The chart of patient selection was displayed&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">Patients were categorized into mild MPP group &#40;<span class="elsevierStyleItalic">n</span> &#61; 22&#41; and SMPP group &#40;<span class="elsevierStyleItalic">n &#61;</span> 22&#41;&#44; according to the clinical parameters and laboratory tests on admission&#46;<a class="elsevierStyleCrossRefs" href="#bib0013"><span class="elsevierStyleSup">13-15</span></a> Severity MPP was defined based on the criteria of community-acquired pneumonia&#46; The mild MPP group was defined as respiratory rate &#60; 70 breaths&#47;min at age &#60; 3 years old or respiratory rate &#60; 50 breaths&#47;min at age &#8805; 3 years old&#44; no dehydration&#44; and normal food intake&#46; Meanwhile&#44; the SMPP group was defined as tachypnea with a respiratory rate &#8805; 70 breaths&#47;min at age &#60; 3 years old or respiratory rate &#8805; 50 breaths&#47;min at age &#8805; 3 years old &#40;without interference from fever and cry&#41;&#44; increased work of breathing &#40;faring of the nares&#44; marked retractions&#44; grunting&#41;&#44; capillary ref time &#8805; 2s&#44; cyanosis&#44; anorexia and dehydration&#44; the appearance of pulmonary and extrapulmonary combinations including pleural effusion&#44; lung necrosis&#47;lung abscess&#44; myocardial damage and peripheral embolization&#46; This study received ethical clearance from the Ethics Committee at Hunan Children&#39;s Hospital &#40;Ethics Committee study protocol number&#58; HCHLL-2022-99&#41; in Changsha City&#46; All methods were carried out in accordance with relevant guidelines and regulations&#46; Parents or legal guardians of all the participants provided written informed consent&#46; Detection of serum cytokines levels venous blood samples of each patient were collected on admission&#46; Measurements of cytokine IL-10 and chemokines CCL2&#44; CCL8 in serum were quantified by Human Inflammatory Cytokine ELISA Kit and Human Chemokine Kit &#40;Becton&#44; Dickinson and Company&#41;&#44; according to the manufacturer&#39;s standard protocol &#40;data not shown&#41;&#46; This study conforms to the STARD guidelines&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Statistical analysis</span><p id="para0013" class="elsevierStylePara elsevierViewall">Statistical analyses were performed with the SPSS software&#44; version 20&#46;0&#46; Continuous variables were summarized as median &#40;interquartile range&#41; while categorical variables were described as proportion&#46; Clinical characteristics that were significant &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;1&#44; univariate analysis&#41; were included in the multivariate forward stepwise logistic regression analysis to identify independent influence factors&#46; Diagnostic accuracy was estimated by the Receiver Operating Characteristic &#40;ROC&#41; curve analysis&#46; Spearman rank correlations were used to assess correlations between variables&#46; A <span class="elsevierStyleItalic">p-value</span> &#60; 0&#46;05 was considered as statistically significant&#46;</p></span></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Results</span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Serum levels of sTREM-1 and IP-10 in children with MPP</span><p id="para0014" class="elsevierStylePara elsevierViewall">The serum levels of sTREM-1 and IP-10 in individuals with MPP were detected with enzyme-linked immunosorbent assay&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#44; both levels of sTREM-1 and IP-10 were significantly increased in subjects of MPP than that in healthy control&#46; Notably&#44; levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP&#44; indicating a role of these cytokines in the pathogenesis of MPP&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Diagnostic value of serum sTREM-1 and IP-10 levels in children with SMPP</span><p id="para0015" class="elsevierStylePara elsevierViewall">Once sTREM-1 and IP-10 have potential in the diagnosis of infectious diseases&#44; the authors therefore analyzed the diagnosis value of sTREM-1 and IP-10 with the Receiver Operating Characteristic &#40;ROC&#41; curve&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>&#44; the Area Under Cure &#40;AUC&#41; for sTREM-1 was 0&#46;8564 with a cut-off-value of 151 pg&#47;mL &#40;<span class="elsevierStyleItalic">p-value</span> &#61; 0&#46;0001&#44; 95&#37; CI 0&#46;7461 to 0&#46;9668&#41; and AUC for IP-10 was 0&#46;8086 with a cut-off-value of 995&#46;5 pg&#47;mL &#40;<span class="elsevierStyleItalic">p-value</span> &#61; 0&#46;0002&#44; 95&#37; CI 0&#46;6918 to 0&#46;9254&#41;&#46; These data suggested that serum levels of sTREM-1 and IP-10 may have significant diagnosis value in children with SMPP&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Diagnostic value of serum sTREM-1 and IP-10 in children with SMPP</span><p id="para0016" class="elsevierStylePara elsevierViewall">To make the diagnostic value of serum sTREM-1 and IP-10 higher&#44; the authors also analyzed the combined diagnostic value&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>&#44; the AUC is 0&#46;911 &#40;<span class="elsevierStyleItalic">p-value</span> &#60; 0&#46;001&#44; 95&#37; CI 0&#46;830 to 0&#46;993&#41;&#44; indicating a promising value in the diagnosis of SMPP<span class="elsevierStyleItalic">&#46;</span></p><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Discussion</span><p id="para0017" class="elsevierStylePara elsevierViewall">MPP is the smallest pathogenic organism capable of living independently on a cell-free culture medium between the size of the bacterium and the virus&#46; It causes respiratory diseases in children&#44; including pharyngitis&#44; bronchitis&#44; and pneumonia&#46; It also causes airway hyperresponsiveness&#44; including asthma&#44; as well as numerous extrapulmonary manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a> Mycoplasma pneumoniae enters into the body through respiratory tract or contact infection and then grows between ciliated epithelia&#44; inhibiting ciliated activity and destroying epithelial cells to cause local tissue damage&#44; thus causing MPP&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> MPP is a common respiratory tract infectious disease in pediatrics&#46; Most of the cases are mild and have a good prognosis&#46; However&#44; in recent years&#44; the reports of SMPP have gradually increased&#46; Its pathogenesis may involve many aspects&#44; such as children of large lactone class antibiotic resistance&#44; excessive immune inflammatory response&#44; diagnostic delays&#44; and mixed infection&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> Clinical symptoms are often characterized by severe symptoms&#44; long course of disease&#44; many internal and external pulmonary complications&#44; and poor therapeutic effect&#44; and sequelae such as atelectasis&#44; bronchiectasis obliterans&#44; bronchiolitis obliterans&#44; and other sequelae can be left&#44; which have a serious impact on the physical and mental health of children&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> In recent years&#44; with the emergence of resistant strains&#44; the originally effective antimicrobial effect has been reduced and even invalid&#46; Coupled with the combination of factors such as bacteria and virus infection&#44; SMPP cases are increasing&#46; SMPP is easy to merge pulmonary complications and the clinical treatment is challenging&#46; Patients with SMPP have a high mortality risk and there are a lot of bad effects on children&#39;s health&#46; Therefore&#44; early diagnosis and timely treatment of mycoplasma pneumonia are of great significance in clinics&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">In the present article&#44; the authors enrolled 44 children with MPP and among them 22 patients are diagnosed with SMPP&#46; The authors detected the serum levels of sTREM-1 and IP-10 and find that serum levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP&#46; In addition&#44; the authors used ROC curve analysis to evaluate the diagnosis values of sTREM-1 and IP-10&#46; As expected&#44; levels of sTREM-1 and IP-10 show a potential value in SMPP with an AUC of 0&#46;8564 and 0&#46;8086 respectively&#46; Notably&#44; the combined diagnosis efficiency was much higher with an AUC of 0&#46;911&#46; These data indicate a potential utility of sTREM-1 and IP-10 in the diagnosis of SMPP&#46;</p><p id="para0019" class="elsevierStylePara elsevierViewall">In summary&#44; the levels of serum sTREM-1 and IP-10 in children with MPP are elevated and are positively correlated with the severity of the disease&#44; suggesting that these two cytokines are involved in the pathogenesis of MPP&#46; Furthermore&#46; The ROC curve shows that sTREM-1 combined with IP-10 has a high diagnosis efficiency for children with SMP&#46; Therefore&#44; sTREM-1 and IP-10 may act as feasible biomarkers for the targeted therapy and rapid and early diagnosis of SMPP&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Ethics approval and consent to participate</span><p id="para0020" class="elsevierStylePara elsevierViewall">Not applicable&#46;</p></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Consent for publication</span><p id="para0021" class="elsevierStylePara elsevierViewall">The authors declare that all the authors have agreed to publish the article&#46;</p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Availability of data and materials</span><p id="para0022" class="elsevierStylePara elsevierViewall">All the data and materials are available&#46;</p></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Funding</span><p id="para0023" class="elsevierStylePara elsevierViewall">This work was supported by the funding from Scientific Research Project of Hunan Provincial Health Commission &#40;NO&#46;202106010531&#41;&#46;</p></span><span id="sec0013a" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020a">CRediT authorship contribution statement</span><p id="para0023a" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Chang Xu&#58;</span> Conceptualization&#44; Resources&#44; Supervision&#44; Writing &#8211; original draft&#46; <span class="elsevierStyleBold">Li-Yan Luo&#58;</span> Methodology&#46; <span class="elsevierStyleBold">Bi-Chen Wu&#58;</span> Methodology&#46; <span class="elsevierStyleBold">Niu Ding&#58;</span> Investigation&#46; <span class="elsevierStyleBold">Shi-Jie Jin&#58;</span> Investigation&#46; <span class="elsevierStyleBold">Jian-Bao Huang&#58;</span> Conceptualization&#46; <span class="elsevierStyleBold">Yan-Ping Chen&#58;</span> Data curation&#44; Formal analysis&#44; Resources&#44; Supervision&#46;</p></span></span>"
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    "highlights" => array:2 [
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      "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara004" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0001" class="elsevierStylePara elsevierViewall">The serum levels of sTREM-1 and IP-10 were increased in children with mycoplasma&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002" class="elsevierStylePara elsevierViewall">Serum levels of sTREM-1 and IP-10 were positively correlated with the severity of the disease&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">&#8226;</span><p id="para0003" class="elsevierStylePara elsevierViewall">sTREM-1 combined with IP-10 has an important value in the diagnosis of children with MPP&#46;</p></li></ul></p></span>"
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        "resumen" => "<span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Objective</span><p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Early diagnosis of Severity Mycoplasma Pneumoniae Pneumonia &#40;SMPP&#41; has been a worldwide concern in clinical practice&#46; Two cytokines&#44; soluble Triggering Receptor Expressed on Myeloid cells &#40;sTREM-1&#41; and Interferon-Inducible Protein-10 &#40;IP-10&#41;&#44; were proved to be implicated in bacterial infection diseases&#46; However&#44; the diagnostic value of sTREM-1 and IP-10 in MPP was poorly known&#46; This study aimed to investigate the diagnostic value of sTREM-1 and IP-10 for SMPP&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara006" class="elsevierStyleSimplePara elsevierViewall">In this prospective study&#44; the authors enrolled 44 children with MPP&#44; along with their clinical information&#46; Blood samples were collected&#44; and cytokine levels of sTREM-1 and IP-10 were detected with ELISA assay&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">Serum levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP&#46; In addition&#44; sTREM-1 and IP-10 have significant potential in the diagnosis of SMPP with an Area Under Curve &#40;AUC&#41; of 0&#46;8564 &#40;<span class="elsevierStyleItalic">p</span>-value &#61; 0&#46;0001&#44; 95&#37; CI 0&#46;7461 to 0&#46;9668&#41; and 0&#46;8086 &#40;<span class="elsevierStyleItalic">p-value</span> &#61; 0&#46;0002&#44; 95&#37; CI 0&#46;6918 to 0&#46;9254&#41; respectively&#46; Notably&#44; the combined diagnostic value of sTREM-1 and IP-10 is up to 0&#46;911 in children with SMPP &#40;<span class="elsevierStyleItalic">p-value</span> &#60; 0&#46;001&#44; 95&#37; CI 0&#46;830 to 0&#46;993&#41;&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusions</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Serum cytokine levels of sTREM-1 and IP-10 have a great potential diagnostic value in children with SMPP&#46;</p></span>"
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos