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1.
J Lipid Res ; 65(9): 100622, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39154734

RESUMO

This prospective observational study compared the 1H NMR blood lipidomes and metabolomes of 71 patients with community-acquired pneumonia (CAP), 75 patients with COVID-19 pneumonia, and 75 healthy controls (matched by age and sex) to identify potential biomarkers and pathways associated with respiratory infections. Both pneumonia groups had comparable severity indices, including mortality, invasive mechanical ventilation, and intensive care unit admission rates. Patients with COVID-19 pneumonia exhibited more pronounced hypolipidemia, with significantly lower levels of total cholesterol and LDL-c compared to patients with CAP. Atherogenic lipoprotein subclasses (VLDL-cholesterol, IDL-cholesterol, IDL-triglyceride, and LDL-triglyceride/LDL-cholesterol) were significantly increased in severe cases of both pneumonia types, while lower HDL-c and small, dense HDL particles were associated with more severe illness. Both infected groups showed decreased esterified cholesterol and increased triglycerides, along with reduced phosphatidylcholine, lysophosphatidylcholine, PUFA, omega-3 fatty acids, and DHA. Additionally, infected patients had elevated levels of glucose, lactate, 3-hydroxybutyrate, and acetone, which are linked to inflammation, hypoxemia, and sepsis. Increased levels of branched-chain amino acids, alanine, glycine, and creatine, which are involved in energy metabolism and protein catabolism, were also observed. Neurotransmitter synthesis metabolites like histidine and glutamate were higher in infected patients, especially those with COVID-19. Notably, severe infections showed a significant decrease in glutamine, essential for lymphocyte and macrophage energy. The severity of COVID-19 pneumonia was also associated with elevated glycoprotein levels (glycoprotein A, glycoprotein B, and glycoprotein F), indicating an inflammatory state. These findings suggest that metabolomic and lipidomic changes in pneumonia are connected to bioenergetic pathways regulating the immune response.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Lipidômica , Humanos , COVID-19/sangue , COVID-19/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Infecções Comunitárias Adquiridas/sangue , Idoso , Estudos Prospectivos , Metabolômica , SARS-CoV-2/isolamento & purificação , Metaboloma , Biomarcadores/sangue
2.
BMC Infect Dis ; 24(1): 946, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251931

RESUMO

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP. METHODS: We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis. RESULTS: A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality. CONCLUSION: Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP.


Assuntos
Biomarcadores , Infecções Comunitárias Adquiridas , Hospitalização , Pneumonia , Curva ROC , Humanos , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/mortalidade , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Pneumonia/sangue , Pneumonia/mortalidade , Pneumonia/diagnóstico , Biomarcadores/sangue , Idoso de 80 Anos ou mais , Índice de Gravidade de Doença , Adulto
3.
J Immunol ; 208(2): 321-327, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911771

RESUMO

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/sangue , Infecções Comunitárias Adquiridas/patologia , Pneumonia/sangue , Pneumonia/mortalidade , Índice de Gravidade de Doença , Idoso , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/sangue , Cuidados Críticos/estatística & dados numéricos , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Pneumonia/patologia , Prognóstico , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos
4.
BMC Pulm Med ; 24(1): 472, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334006

RESUMO

BACKGROUND: Previous research has discovered that surfactant protein A (SP-A) is involved in the pathophysiology processes of certain lung illnesses. However, no definitive clinical studies have delved into the function of SP-A in individuals afflicted with community-acquired pneumonia (CAP). A prospective cohort study was used to investigate the relationships between blood SP-A levels and the severity and prognosis among CAP patients. MATERIALS AND METHODS: This study included 260 patients with CAP. Clinical traits and demographic data were examined during hospitalization. The concentrations of serum SP-A and serum interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). In addition, to evaluate the severity of CAP, a variety of scores, including the CURB-65, PSI, SMART-COP, and APACHE II, were employed. RESULTS: The serum levels of SP-A at admission exhibited a gradual decline as the severity scores of CAP increased. Through Spearman correlation analysis, we observed an association between serum SP-A and some clinical indicators among CAP patients. Furthermore, results from a multiple linear regression model suggested changes in PSI scores (-17.868 scores, 95% CI: -32.743, -2.993) affect serum SP-A more than CURB-65 (-0.547 scores, 95% CI: -0.964, -0.131), SMART-COP (-1.097 scores, 95% CI: -1.889, -0.304) and APACHE II (-3.475 scores, 95% CI: -5.874, -1.075) with age, hypertension, diabetes mellitus, cerebral infarction, coronary heart disease, and bronchitis adjusted. In addition, the prognosis in CAP patients was monitored. Throughout their hospital stay, higher serum levels of SP-A decreased the risks of mechanical ventilation (RR: 0.315; 95% CI: 0.106, 0.937), vasoactive agents (RR: 0.165; 95% CI: 0.034, 0.790), intensive care unit (ICU) admissions (RR: 0.218; 95% CI: 0.066, 0.717) and longer hospital stays (RR: 0.397; 95% CI: 0.167, 0.945). CONCLUSION: In CAP patients, inverse dose-response correlations exist between serum SP-A levels with severity scores as well as prognosis at admission, suggesting that SP-A may take part in the CAP pathophysiological processes. Moreover, lower serum SP-A on admission is associated with an elevated prognostic risk of mechanical ventilation, the use of vasoactive agents, longer hospital stays, ICU admission, and mortality. Therefore, as a biomarker, SP-A may have the potential to predict the severity and poor prognosis of CAP patients.


Assuntos
Infecções Comunitárias Adquiridas , Interleucina-6 , Pneumonia , Proteína A Associada a Surfactante Pulmonar , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , APACHE , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/sangue , Interleucina-6/sangue , Modelos Lineares , Pneumonia/sangue , Pneumonia/diagnóstico , Prognóstico , Estudos Prospectivos , Proteína A Associada a Surfactante Pulmonar/sangue , Índice de Gravidade de Doença
5.
BMC Pediatr ; 24(1): 496, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095744

RESUMO

BACKGROUND: Necrotizing pneumonia (NP) is a rare serious complication of community-acquired pneumonia (CAP) in children, which is characterized by a protracted course of the disease and a prolonged hospital stay. This study aimed to assess the role of systemic immune-inflammatory index and systemic inflammatory response index in predicting early lung necrotization in children with CAP. METHODS: This study included all children hospitalized in Pediatric Pulmonology Unit, Tanta University, Egypt, with CAP between the ages of two months and 18 years. Systemic inflammatory indices, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI), were calculated on patients' admission. RESULTS: The study involved a total of 228 children, 42 patients had NP, 46 patients had parapneumonic effusion, and 140 patients had non-complicated CAP. Patients with NP were substantially younger (p = 0.002), stayed in the hospital longer (p < 0.001), had a longer duration of symptoms before hospital admission (p < 0.001), and had fever for a longer duration than those in the other groups (p < 0.001). Regarding the inflammatory ratios, patients with NP had significantly higher MLR, PLR, SII, and SIRI than those in the other groups (p = 0.020, p = 0.007, p = 0.001, p = 0.037, respectively). ROC curve analysis showed that the combined SII + SIRI + D-dimer showed the highest AUC with a good specificity in predicting the diagnosis of NP. CONCLUSIONS: SII, SIRI, and D-dimer may be beneficial biomarkers for predicting the occurrence of NP in children when performed on patients' admission. In addition, it was found for the first time that combined SII + SIRI + D-dimer had a good sensitivity and specificity in the diagnosis of NP.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia Necrosante , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Lactente , Pneumonia Necrosante/diagnóstico , Adolescente , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/sangue , Neutrófilos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Contagem de Plaquetas , Curva ROC , Biomarcadores/sangue , Contagem de Linfócitos
6.
Aging Clin Exp Res ; 36(1): 175, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172286

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a significant health issue among the elderly, with severe cases (SCAP) having high mortality rates. This study assesses the predictive significance of the stress hyperglycemia ratio (SHR) in elderly SCAP patients and its impact on outcomes in both diabetic and non-diabetic patients. METHODS AND MATERIALS: This retrospective study included 406 SCAP patients aged 65 or older from the Second People's Hospital of Lianyungang (January 2020 to December 2023). Data collected included demographics, medical history, vital signs, and lab results. SHR was calculated from initial blood glucose and estimated average glucose (HbA1c). Statistical analyses, including Cox regression and Kaplan-Meier analysis, evaluated SHR's impact on mortality. Mediation models explored the effects of neutrophil-lymphocyte ratio (NLR) and SHR. RESULTS: The 28-day mortality rate was 21.67%. Deceased patients had higher age, Charlson Comorbidity Index, procalcitonin, NLR, glucose, and SHR levels compared to survivors (P < 0.05). Both SHR and NLR significantly increased mortality risk, particularly in non-diabetic patients. Combining NLR and SHR improved ROC AUC to 0.898, with 89.80% sensitivity and 81.10% specificity. Kaplan-Meier analysis showed higher cumulative survival for SHR < 1.14, regardless of diabetes status (P < 0.05). NLR mediated 13.02% of the SHR-survival relationship, while SHR mediated 14.06% of the NLR-survival relationship. CONCLUSION: Elevated SHR is a significant mortality risk factor in elderly SCAP patients, independent of diabetes status. Stringent glucose control and careful monitoring of SHR may improve outcomes in elderly patients with acute respiratory conditions.


Assuntos
Infecções Comunitárias Adquiridas , Hiperglicemia , Pneumonia , Humanos , Idoso , Estudos Retrospectivos , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/sangue , Masculino , Feminino , Hiperglicemia/mortalidade , Hiperglicemia/sangue , Pneumonia/mortalidade , Pneumonia/sangue , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Neutrófilos
7.
Medicina (Kaunas) ; 60(10)2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39459346

RESUMO

Background and Objectives: The predictive value of changes in C-reactive protein (CRP), procalcitonin, and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. The aim of this study was to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of 230 patients admitted to the intensive care unit (ICU) with the diagnosis of sepsis and pneumonia-related septic shock between 1 April 2022 and 31 December 2023, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Materials and Methods: This single-center, retrospective, cross-sectional observational study included patients who developed sepsis and septic shock due to community-acquired pneumonia and were admitted to the ICU. Demographic data, 1-month and 90-day mortality rates, length of stay in the ICU, discharge to the ward or an outside facility, need for dialysis after sepsis, need for invasive or noninvasive mechanical ventilation during the ICU stay and the duration of this support, whether patients admitted with sepsis or septic shock required inotropic agent support during their stay in the ICU and whether they received monotherapy or combination therapy with antibiotics during their admission to the ICU, the Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score were analyzed. Additionally, CRP, procalcitonin, and leukocyte levels were recorded, and univariate and multivariate logistic regression analyses were performed to evaluate their effects on 1- and 3-month mortality outcomes. In all statistical analyses, a p-value of <0.05 was accepted as a significant level. Results: According to multivariate logistic regression analysis, low BMI, male gender, and high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p < 0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both the 1-month and 3-month mortality cases (p < 0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared with those who survived (p = 0.004). Conclusions: In patients with pneumoseptic or pneumonia-related septic shock, the persistent elevation and concurrent increase in PCT, CRP, and leukocyte values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality.


Assuntos
Biomarcadores , Proteína C-Reativa , Unidades de Terapia Intensiva , Pró-Calcitonina , Choque Séptico , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Pró-Calcitonina/sangue , Choque Séptico/sangue , Choque Séptico/mortalidade , Proteína C-Reativa/análise , Estudos Transversais , Prognóstico , Biomarcadores/sangue , Contagem de Leucócitos , Valor Preditivo dos Testes , Sepse/sangue , Sepse/mortalidade , Sepse/complicações , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/complicações , Pneumonia/sangue , Pneumonia/mortalidade , Pneumonia/complicações , Idoso de 80 Anos ou mais
8.
Crit Care ; 27(1): 79, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859478

RESUMO

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Proteômica , Criança , Pré-Escolar , Humanos , Coagulação Sanguínea , Proteína C-Reativa , Morte Celular , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Metabolômica , Pneumonia/sangue , Pneumonia/diagnóstico
10.
Int J Med Sci ; 19(1): 74-81, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975300

RESUMO

Background: The previous studies have revealed that IL-27 was involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of IL-27 in community-acquired pneumonia (CAP) was unclear. The goal of this research was to explore the associations of serum IL-27 with the severity and prognosis among CAP patients through a prospective cohort study. Methods: The whole of 239 healthy population and 239 CAP patients were enrolled. Fasting blood samples were collected. Inflammatory cytokines were detected using enzyme linked immunosorbent assay (ELISA). Demographic characteristics and clinical information were analyzed. Results: Serum IL-27 on admission was significantly risen in CAP patients compared with control subjects. Besides, serum IL-27 was gradually increased in line with CAP severity scores. Correlative analysis suggested that serum IL-27 was associated with blood routine indices, renal function, liver function, myocardial function and inflammatory cytokines. Linear and logistic regression analyses revealed that serum IL-27 was positively correlated with CAP severity scores. Logistic regression analysis demonstrated that serum higher IL-27 on admission elevated the risks of vasoactive agent usage and longer hospital stay during hospitalization among CAP patients. Conclusions: Serum IL-27 is markedly and positively associated with the severity and poor prognosis among CAP patients, indicating that IL-27 may involve in the pathophysiological process of CAP. Serum IL-27 may be used as a biomarker for diagnosis and prognosis in CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Interleucina-27/sangue , Idoso , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
11.
J Cell Mol Med ; 25(16): 7621-7630, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34272809

RESUMO

Community-acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non-coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP-associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non-infectious control participants. Plasma small RNA-sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over-represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways.


Assuntos
Infecções Comunitárias Adquiridas/patologia , MicroRNAs/genética , Infecções Pneumocócicas/patologia , Pneumonia/patologia , Pequeno RNA não Traduzido/genética , Sepse/patologia , Streptococcus pneumoniae/genética , Idoso , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/genética , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/genética , Infecções Pneumocócicas/microbiologia , Pneumonia/sangue , Pneumonia/genética , Pneumonia/microbiologia , Pequeno RNA não Traduzido/sangue , Sepse/sangue , Sepse/genética , Índice de Gravidade de Doença , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade
12.
Am J Physiol Lung Cell Mol Physiol ; 321(4): L764-L774, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34318685

RESUMO

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of patients with CAP (n = 139) as compared with age-matched donors (n = 58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of women with CAP as compared with sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared with donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Proteína Inibidora do Complemento C1/análise , Fator XII/análise , Cininogênios/sangue , Pneumonia/sangue , Idoso , Infecções Comunitárias Adquiridas/patologia , Estradiol/sangue , Feminino , Humanos , Masculino , Pneumonia/patologia , Albumina Sérica/análise , Fatores Sexuais
13.
Crit Care Med ; 49(11): 1901-1911, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33935163

RESUMO

OBJECTIVES: Plasma ferritin levels above 4,420 ng/mL have been proposed as a diagnostic marker for macrophage activation-like syndrome in sepsis and used for selection of sepsis patients for anti-inflammatory therapy. We here sought to determine the frequency, presentation, outcome, and host response aberrations of macrophage activation-like syndrome, as defined by admission ferritin levels above 4,420 ng/mL, in critically ill patients with community-acquired pneumonia. DESIGN: A prospective observational cohort study. SETTING: ICUs in two tertiary hospitals in the Netherlands. PATIENTS: One hundred fifty-three patients admitted with community-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: Patients were stratified in community-acquired pneumonia-macrophage activation-like syndrome (n = 15; 9.8%) and community-acquired pneumonia-control groups (n = 138; 90.2%) based on an admission plasma ferritin level above or below 4,420 ng/mL, respectively. Community-acquired pneumonia-macrophage activation-like syndrome patients presented with a higher disease severity and had a higher ICU mortality (46.7% vs 12.3% in community-acquired pneumonia-controls; p = 0.002). Twenty-three plasma biomarkers indicative of dysregulation of key host response pathways implicated in sepsis pathogenesis (systemic inflammation, cytokine responses, endothelial cell activation, and barrier function, coagulation activation) were more disturbed in community-acquired pneumonia-macrophage activation-like syndrome patients. Hematologic malignancies were overrepresented in community-acquired pneumonia-macrophage activation-like syndrome patients (33.3% vs 5.1% in community-acquired pneumonia-controls; p = 0.001). In a subgroup analysis excluding patients with hematologic malignancies (n = 141), differences in mortality were not present anymore, but the exaggerated host response abnormalities in community-acquired pneumonia-macrophage activation-like syndrome patients remained. CONCLUSIONS: Macrophage activation-like syndrome in critically ill patients with community-acquired pneumonia occurs more often in patients with hematologic malignancies and is associated with deregulation of multiple host response pathways.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Estado Terminal/terapia , Ferritinas/sangue , Ativação de Macrófagos , Pneumonia Bacteriana/sangue , Idoso , Biomarcadores/sangue , Estudos de Coortes , Infecções Comunitárias Adquiridas/terapia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Países Baixos , Pneumonia Bacteriana/terapia , Estudos Prospectivos , Índice de Gravidade de Doença
14.
Eur J Clin Invest ; 51(6): e13480, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33350464

RESUMO

INTRODUCTION: Studies have suggested that an inappropriate inflammatory response is a major cause of treatment failure and mortality in patients with community-acquired pneumonia (CAP). We aimed to determine the effect of age and comorbidities on serum inflammatory markers in CAP. METHODS: We performed a prospective cohort study of adults hospitalized with CAP. For the purposes of this study, we compared patients according to comorbidities and age. Inflammatory markers were measured at hospital admission, focusing on acute phase proteins, cytokines and monocyte human leucocyte antigen DR (mHLA-DR) expression. RESULTS: In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mHLA-DR expression, as well as the C-reactive protein (CRP), compared with patients who had no comorbidities. Similarly, patients with chronic heart disease had a significantly reduced CRP levels and mHLA-DR expression, whereas patients with chronic kidney disease had significantly higher serum levels of procalcitonin and TNF-α. Lower procalcitonin, IL-6 and IL-10 levels, as well as mHLA-DR expression, were documented in older patients, but with no significant differences compared to younger patients. Multimorbidity in older patients was associated with significant lower levels of CRP and mHLA-DR expression. CONCLUSIONS: The circulating inflammatory markers to CAP have profiles that differ with age and underlying comorbidities. Multimorbidity in the elderly is also associated with lower serum levels of some inflammatory markers. Our findings suggest that inflammatory markers in CAP should be interpreted after considering age and comorbid conditions.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Citocinas/sangue , Pneumonia/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , Estudos de Coortes , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/imunologia , Comorbidade , Citocinas/imunologia , Feminino , Antígenos HLA-DR/imunologia , Cardiopatias/epidemiologia , Hospitalização , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Pneumonia/epidemiologia , Pneumonia/imunologia , Pró-Calcitonina/sangue , Pró-Calcitonina/imunologia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
15.
Eur J Clin Microbiol Infect Dis ; 40(12): 2497-2504, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34245388

RESUMO

There is limited data on persistent bacteremia (PB) caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Here, we aimed to investigate the clinical and microbiological characteristics of PB caused by the major CA-MRSA strain in Korea (ST72-SCCmecIV). All adult patients with S. aureus bacteremia were prospectively investigated from August 2008 to December 2018. Patients with ST72 MRSA bacteremia were included in the study. Patients were stratified into the PB group (defined as positive blood cultures for ≥ 3 days) and short bacteremia (SB) group. A total of 291 patients were included, comprising 115 (39.5%) with PB and 176 (60.5%) with SB. Although the 30-day mortality did not differ between PB and SB, recurrent bacteremia within 12 weeks was significantly more common in PB (8.7% vs 1.7%; P = 0.01). Multivariate analysis showed risk factors of PB were liver cirrhosis (adjusted odds ratio [aOR], 3.27; 95% confidence interval [CI], 1.50-7.12), infective endocarditis (aOR, 7.13; 95% CI, 1.37-37.12), bone and joint infections (aOR, 3.76; 95% CI, 1.62-8.77), C-reactive protein ≥ 10 mg/dL (aOR, 2.20; 95% CI, 1.22-3.95), metastatic infection (aOR, 7.35; 95% CI, 3.53-15.29), and agr dysfunction (aOR, 2.47; 95% CI, 1.05-5.81). PB occurred in approximately 40% of bacteremia caused by ST72 MRSA with a significantly higher recurrence rate. Patients with risk factors of PB, including liver cirrhosis, high initial CRP, infective endocarditis, or bone and joint infections, might require early aggressive treatment.


Assuntos
Bacteriemia/sangue , Bacteriemia/microbiologia , Proteína C-Reativa/análise , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/microbiologia , Staphylococcus aureus Resistente à Meticilina/fisiologia , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estudos Prospectivos , Infecções Estafilocócicas/tratamento farmacológico
16.
Infection ; 49(5): 877-888, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33694084

RESUMO

PURPOSE: Early diagnosis and prognosis of patients with community-acquired pneumonia (CAP) are still difficult clinical challenges. This study aimed to investigate the role of lysophosphatidylethanolamine acyltransferase (LPEAT) in CAP and to evaluate the effectiveness of this enzyme as an indicator of disease severity and risk of death in CAP. METHODS: This retrospective, multi-center study was conducted in 2017. A total of 267 patients with CAP were included. Of these 267 patients, 175 patients had non-severe CAP (non-SCAP) and 92 patients had severe CAP (SCAP). In addition, we recruited 15 healthy volunteers and 42 hospitalized disease controls in our study. The demographic and clinical characteristics were recorded for all participants. Admission levels of LPEAT were determined by quantitative enzyme-linked immunosorbent assay. RESULTS: Admission levels of LPEAT in patients with SCAP were significantly higher, particularly in non-survivors and were not affected by the causative etiology. Furthermore, when the patients were stratified according to PSI and CURB-65 scores, the patients with high severity scores had higher LPEAT levels upon admission than patients with low severity scores. LPEAT also performed well in predicting SCAP in patients with CAP. Moreover, LPEAT could predict the 30-day mortality rate of patients with CAP, and combining LPEAT with the clinical severity score further improved the accuracy of mortality prediction. CONCLUSION: Elevated LPEAT levels can reliably predict the severity of illness in patients with CAP at the time of admission. Adding LPEAT to clinical scoring methods could improve prognostic accuracy. Trial registration ClinicalTrials.gov, NCT03093220. Registered on March 28th, 2017.


Assuntos
Aciltransferases/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia/mortalidade , Adulto , Idoso , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Pneumonia/diagnóstico , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
BMC Infect Dis ; 21(1): 327, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827454

RESUMO

BACKGROUND: Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. METHODS: A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. RESULTS: Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. CONCLUSION: Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.


Assuntos
Calgranulina B/sangue , Infecções Comunitárias Adquiridas/sangue , Pneumonia/sangue , Idoso , Biomarcadores/sangue , Estudos de Coortes , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Pneumonia/diagnóstico , Prognóstico , Estudos Prospectivos
18.
Scand J Clin Lab Invest ; 81(1): 65-71, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33345630

RESUMO

There is limited data on serum biomarkers in distinguishing Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral pneumoniae (VP) etiologies of community-acquired pneumonia (CAP). A retrospective study of inpatients diagnosed with CAP at the First Affiliated Hospital of Dali University (Dali, Yunnan, China) between January 2018 and June 2020 was conducted. The demographic, clinical and laboratory data of the patients with CAP were analyzed. Univariate analyses identified predictors for MP infections. The discriminative power of C-reactive protein (CRP), procalcitonin (PCT), CRP/PCT and CRP/PCT >350 µg/ng was assessed by area under the curve (AUC) of the receiver operating characteristic (ROC) curves. A total of 552 CAP patients, including 247 (44.7%) with MP, 152 (27.6%) with SP and 153 (27.7%) with influenza A and B viruses, were enrolled. When comparing MP with SP, cough and CRP/PCT >350 µg/ng (odds ratio [OR]) 2.88, p < .001) were predictors for MP. CRP/PCT >350 µg/ng had 76% sensitivity and 100% specificity (AUC = 0.89, p < .001, 95% confidence interval [CI]:0.81-0.94) to predict MP infections. Furthermore, similar results were again obtained when comparing MP with VP. CRP/PCT >350 µg/ng present better information (OR: 4.70; AUC = 0.92, p < .001, 87% sensitivity and 100% specificity). In addition, comparing MP and non-MP (SP and VP combined), CRP/PCT >350 µg/ng exhibited excellent performance (AUC = 0.90, 95%CI 0.83-0.95, p < .001, 76% sensitivity and 100% specificity). CRP/PCT ratio may be a potential index to distinguish MP-CAP from non-MP-CAP.


Assuntos
Proteína C-Reativa/metabolismo , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/microbiologia , Hospitalização , Mycoplasma pneumoniae/fisiologia , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/microbiologia , Pró-Calcitonina/sangue , Adulto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
19.
BMC Pulm Med ; 21(1): 393, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856971

RESUMO

BACKGROUND: Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. METHODS: All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. RESULTS: Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. CONCLUSIONS: Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Interleucina-17/sangue , Pneumonia/sangue , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
20.
J Med Internet Res ; 23(2): e23390, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33534722

RESUMO

BACKGROUND: The initial symptoms of patients with COVID-19 are very much like those of patients with community-acquired pneumonia (CAP); it is difficult to distinguish COVID-19 from CAP with clinical symptoms and imaging examination. OBJECTIVE: The objective of our study was to construct an effective model for the early identification of COVID-19 that would also distinguish it from CAP. METHODS: The clinical laboratory indicators (CLIs) of 61 COVID-19 patients and 60 CAP patients were analyzed retrospectively. Random combinations of various CLIs (ie, CLI combinations) were utilized to establish COVID-19 versus CAP classifiers with machine learning algorithms, including random forest classifier (RFC), logistic regression classifier, and gradient boosting classifier (GBC). The performance of the classifiers was assessed by calculating the area under the receiver operating characteristic curve (AUROC) and recall rate in COVID-19 prediction using the test data set. RESULTS: The classifiers that were constructed with three algorithms from 43 CLI combinations showed high performance (recall rate >0.9 and AUROC >0.85) in COVID-19 prediction for the test data set. Among the high-performance classifiers, several CLIs showed a high usage rate; these included procalcitonin (PCT), mean corpuscular hemoglobin concentration (MCHC), uric acid, albumin, albumin to globulin ratio (AGR), neutrophil count, red blood cell (RBC) count, monocyte count, basophil count, and white blood cell (WBC) count. They also had high feature importance except for basophil count. The feature combination (FC) of PCT, AGR, uric acid, WBC count, neutrophil count, basophil count, RBC count, and MCHC was the representative one among the nine FCs used to construct the classifiers with an AUROC equal to 1.0 when using the RFC or GBC algorithms. Replacing any CLI in these FCs would lead to a significant reduction in the performance of the classifiers that were built with them. CONCLUSIONS: The classifiers constructed with only a few specific CLIs could efficiently distinguish COVID-19 from CAP, which could help clinicians perform early isolation and centralized management of COVID-19 patients.


Assuntos
COVID-19/diagnóstico , Infecções Comunitárias Adquiridas/diagnóstico , Aprendizado de Máquina , Pneumonia/diagnóstico , SARS-CoV-2/patogenicidade , Área Sob a Curva , COVID-19/sangue , COVID-19/virologia , Infecções Comunitárias Adquiridas/sangue , Feminino , Humanos , Laboratórios , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumonia/sangue , Pró-Calcitonina/sangue , Curva ROC , Estudos Retrospectivos
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