Pathogenesis Of Community-acquired Pneumonia Research Articles

The role of certain essential and toxic trace elements in the pathogenesis of community-acquired pneumonia.

The role of certain essential and toxic trace elements in the pathogenesis of community-acquired pneumonia.

Bacterial profile and their antimicrobial resistance patterns among patients with community-acquired pneumonia in southwestern Iran.

Community-acquired pneumonia (CAP) is one of the most common life-threatening infections, occurring in the community or within the first 48 hours of a patient's hospitalization. The present study aimed to investigate the frequency of pathogenic bacteria and their antibiotic resistance pattern in the sputum of patients with community-acquired pneumonia in Yasuj from 2018 to 2019. In the present study, 128 patients with CAP were included. Under aseptic conditions clinical samples including sputum collected from each patient were sent to the Microbiology Laboratory. Specific culture media and biochemical tests were used to identify the bacteria. Antimicrobial resistance patterns of the isolates were examined by disc diffusion. DNA was extracted from sputum using the phenol-chloroform method. The PCR method was used for the molecular detection of bacteria. Data were analyzed using SPSS software version 22 and the chi-square test. The most common clinical symptoms in patients were sputum (68.8%), fever (64.1%), shortness of breath (60.2%), cough (50.8%), and chest pain (24.2%). A total of 133 bacteria were identified by culture and 117 bacteria by PCR. In the current study, the most prevalent organisms were Streptococcus pneumoniae (24.1%), Hemophilus influenzae (18%), Staphylococcus aureus (13.5%), and Moraxella catarrhalis (11.4%). Antibiogram test showed that most of the Gram-negative bacteria were resistant to levofloxacin (22.6%), rifampin (20.8%) and ceftriaxone (17%), and the highest resistance rate to clindamycin (43.1%), ciprofloxacin (43.1%) and amoxicillin (41.4%) were detected in the Gram-positive bacteria. Cefepime was the most effective antibiotic against Gram negative bacteria. S. pneumoniae was the most prevalent bacteria identified by culture and PCR methods in patients with CAP, indicating an important role of this bacterium in the pathogenesis of CAP. According to the results, cefepime can be used to treat patients with CAP with Gram-negative bacteria. In the present study, S. pneumoniae, S. aureus, P. aeruginosa, H. influenzae, M. catarrhalis, and K. pneumoniae have been isolated from the CAP patient population with varying frequencies. This is consistent with various studies in different parts of the world.

Prediction of target genes in community-acquired pneumonia based on the bioinformatics method.

To screen the related genes of community-acquired pneumonia (CAP) by bioinformatics technology, and to analyze the clinical value of key genes. Gene chip data sets containing CAP patients and normal controls were screened from the Gene Expression Omnibus (GEO) database. The downregulated differentially expressed genes (DEGs) were screened using a gene expression analysis tool (GEO2R). Simultaneously, gene set enrichment analysis (GSEA) was used to explore the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and core genes related to CAP. The candidate genes were then intersected with the genes reported in Online Mendelian Inheritance in Man (OMIM), and the clinical value of these candidate genes was examined based on a literature search. Finally, the clinical data of the CAP patients were retrospectively analyzed. Detect the type of pathogenic bacteria in bronchial-alveolar lavage fluid (BALF) using metagenomics next-generation sequencing (mNGS) high throughput sequencing technology, and detect the expression of key genes through liquid based cell immunohistochemistry to analyze the correlation between pathogenic bacteria and key genes. Through the intersection of Venn diagrams, 175 co-expressed downregulated DEGs related to CAP were identified. A total of 4 candidate genes, including ICOS, IL7R, ITK, and ZAP70, were obtained by constructing the protein mutual aid network and conducting a module analysis of the common differentially expressed genes. The core genes in the GSEA enrichment pathways were intersected with the CAP-related genes reported in the relevant literature retrieved from the OMIM database. In the Venn diagram, two genes that coexist with OMIM include IL7R and PIK3R1. After considering our findings and the relevant literature, we determined that the key gene related to the occurrence and development of CAP was IL7R. The mNGS detected 13 kinds of bacteria, 4 kinds of fungi, and 2 kinds of viruses. Based on immunohistochemical results, it was found that there were relatively more bacteria detected in the IL7R high expression group. The identification of the key gene IL7R and the related signaling pathways extend understanding of the pathogenesis of CAP and provide a theoretical basis for clinical targeted therapy research.

The role of antioxidant enzymes in the development of respiratory diseases in children

Background. Redox reactions are an important part of metabolism and are necessary both for replenishing energy needs and for delivering and utilizing oxygen. In the progression of bronchopulmonary pathology, an important role belongs to the excess amount of various compounds accumulated as a result of activation of lipid peroxidation, which leads to disruption of the membrane structure, lipid metabolism and toxic effects on cells and tissues of various organs and systems. The article summarizes current knowledge about the role of antioxidant enzymes in the pathogenesis of community-acquired pneumonia and non-obstructive bronchitis in children. They are of key importance in the stabilization of oxidative stress in the respiratory system pathology. A regulatory role in the antioxidant defense system of the enzyme superoxide dismutase (SOD) has been shown.Design and methods. The study involved 68 children (10–16 years old): 37 children with bronchitis, 31 with community-acquired pneumonia and 25 healthy children. Blood samples were taken for the subsequent SOD level determination.Results. A significant decrease in the SOD level and a low rate of normalization of its parameters in children with pneumonia were revealed. In children with bronchitis, the initial change in the SOD level was less significant, with a higher rate of its recovery.Conclusion. A significant SOD decrease in pneumonia indicates decompensation of oxidative stress processes in this group.

Differential metabolic host response to pathogens associated with community-acquired pneumonia

BackgroundMetabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens. MethodTargeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified. ResultsSeveral acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae. ConclusionsIn this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children.

Heparin-binding protein (HBP) is a novel biomarker for inflammatory diseases. This study aimed to investigate the role of serum HBP in community-acquired pneumonia (CAP) in children and the association of HBP with the severity and prognosis. A total of 125 children with CAP admitted to the hospital were enrolled in this retrospective study. We analyzed the differences in clinical characteristics and examination findings between patients with different levels of HBP. The severe or complicated CAP was defined as having severe radiographic findings and/or systemic manifestations. Receiver operator characteristic (ROC) curves detected the performance of biomarkers in identifying patients with severe or complicated pneumonia. The multivariate logistic regression models assessed the association between HBP levels and the severity and prognosis. Finally, we constructed a predictive model based on HBP. The rate of severe or complicated CAP for patients with upper-quartile HBP concentration (≥60 ng/mL) was 54.8%, significantly higher than that of patients with lower HBP concentration (26.6%). The level of HBP is substantially correlated with neutrophil counts, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A protein (r = 0.31, 0.26, 0.36, and 0.26, respectively). HBP achieved the highest level of discrimination for severe or complicated CAP among the biomarkers. Higher HBP concentration (≥60 ng/mL) was associated with a three-fold higher risk of severe or complicated CAP (adjusted odds ratio = 3.11, p < 0.05). A predictive model including four characteristics (HBP, lactate dehydrogenase, age and non-viral infection) for predicting severe or complicated CAP (with area under the ROC curve = 0.75) was built to create a nomogram. Substantially elevated serum HBP is significantly associated with severe or complicated CAP and poor prognosis in children. This finding warrants further investigation of the function of HBP in the pathogenesis of CAP.

Еритроцити та їх значення в патогенезі негоспітальної пневмонії

The purpose of the study was to study the response of erythrocytes in patients with community-acquired pneumonia and to assess its importance in the pathogenesis of this disease. Materials and methods. Thirty patients with community-acquired pneumonia were examined. The diagnosis was established on the basis of epidemiological, clinical, laboratory, radiological data. Erythrocyte count, hemoglobin concentration, hematocrit number, erythrocyte indexes were determined: mean erythrocyte volume, mean hemoglobin content in erythrocyte, mean hemoglobin concentration in erythrocyte. Results and discussion. It is established that with community-acquired pneumonia in the body there is an increase in the formation of reactive oxygen species at all times of observation. The study of the qualitative and quantitative composition of blood cells in our study found significant shifts in all indicators. Thus, the number of erythrocytes on the 1st day of observation increased by 20.9% relative to the group of healthy individuals, and then decreased and remained by 8 % – 10 % less than in the control on the 5th day. Subsequently, after 10 days there was a sharp (2.2 times) decrease in the number of erythrocytes. However, in general, the concentration of erythrocytes in this observation period remained significantly reduced relative to the group of almost healthy individuals by 20%. Changes in hemoglobin concentration had a similar dynamic. The maximum decrease in erythrocytes count and hemoglobin concentration in the blood over time indicates active hemolysis of erythrocytes during this period. Hematocrit in the examined patients increased sharply on the 1st day of the study, which indicated blood clotting. However, on day 5, hematocrit decreased sharply, amounting to only 57% of the level of the practically healthy individuals’ group and practically did not recover to the ascending level on the 10th day. The mean erythrocyte volume did not change significantly during the study. Conclusion. Changes in the number of erythrocytes, hemoglobin and erythrocyte indices in community-acquired pneumonia are due to membrane-destructive processes in erythrocytes, a decrease in their absolute number – due to hemolysis, hematocrit changes – due to redistribution of blood and hypoxia that develops in non-hospital pneumonia. Changes in erythrocytes are oxygen-dependent mechanisms in the pathogenesis of community-acquired pneumonia

Respiratory MUC5B disproportion is involved in severe community-acquired pneumonia

BackgroundMucus production is a process involved in the pathogenesis of Community-acquired pneumonia (CAP). The study is to determine Mucin 5B (MUC5B) protein concentration and its proportion in the bronchoalveolar lavage fluid (BALF) of CAP patients and evaluate its value to help assess disease severity.MethodsA total of 118 patients were enrolled in this cross-sectional study, including 45 with severe CAP (SCAP) and 73 with non-severe CAP (NSCAP). MUC5B concentration in BALF were determined by immunoblotting analysis. Total protein concentration of BALF was detected by Pierce BCA kit. Cytokines IL6, IL10, IFNγ, IL13, and IL17 in BALF were measured using commercial enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was applied to evaluate the relationships between MUC5B concentration or MUC5B/total protein ratio and the CURB-65 score, as well as cytokines. Logistic regression analysis was used to identify the independent factors associated with severe CAP. Receiver operating characteristic (ROC) curve was used to evaluate the assessment value of MUC5B/total protein ratio and other indexes for CAP severity.ResultsMUC5B concentration in the BALF of NSCAP group was higher than that in SCAP group [NSCAP 13.56 µg/ml (IQR 5.92–25.79) vs. SCAP 8.20 µg/ml (IQR 4.97–14.03), p = 0.011]. The total protein concentration in the BALF of NSCAP group was lower than that in SCAP group [NSCAP 0.38 mg/ml (IQR 0.15–1.10) vs. SCAP 0.68 mg/ml (IQR 0.46–1.69), p = 0.002]. The MUC5B/total protein ratio was remarkably higher in NSCAP group than that in SCAP groups [NSCAP 3.66% (IQR 1.50–5.56%) vs. SCAP 1.38% (IQR 0.73–1.76%), p < 0.001]. MUC5B/total protein ratio was negatively correlated with total protein concentration (rs = − 0.576, p < 0.001), IL6 (rs = − 0.312, p = 0.001), IL10 (rs = − 0.228, p = 0.013), IL13 (rs = − 0.183, p = 0.048), IL17 (rs = − 0.282, p = 0.002) and CURB-65 score (rs = − 0.239, p = 0.009). Logistic regression identified that MUC5B/total protein ratio, IL6 level and CURB-65 score as independent variables related to CAP severity. ROC curve demonstrated best assessment value of MUC5B/total protein ratio for SCAP (AUC 0.803, p < 0.001), with a sensitivity of 88.9% and a specificity of 64.4%.ConclusionsRespiratory MUC5B disproportion is related to CAP severity. MUC5B/total protein ratio may serve as an assessment marker and a potential therapeutic target for severe CAP.

Community-acquired pneumonia in chronic obstructive pulmonary disease.

The aim of this study was to discuss the literature on community-acquired pneumonia (CAP) in patients with chronic obstructive pulmonary disease (COPD). Well designed studies show that COPD is the strongest risk factor for development of CAP. Lung microbiome, abnormal lung immunity and pathogen virulence are important components of the pathogenesis of CAP in COPD. The cause of CAP in patients with COPD is similar to that of non-COPD patients. However, patients with COPD are at an increased risk of infection by Gram-negative bacilli, including Pseudomonas aeruginosa. Empiric treatment regimens for CAP in COPD should contemplate the most common pathogens, and consideration should be given for the coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus depending on the severity of CAP, severity of COPD or prior isolation of these pathogens. COPD has not been consistently shown to be an independent risk factor for worse short-term outcomes in patients with CAP. In a long-term study, COPD is associated with worse outcomes in these patients. Research focused on lung microbiome and abnormal lug immunity in patients with COPD should be prioritized. Further clinical research should try to consolidate the role of additional treatment approaches such as immunomodulating medications in COPD patients with CAP.

Surfactant proteins A and D: role in the pathogenesis of community-acquired pneumonia and possible predictive perspectives

Community-acquired pneumonia is one of the most common infectious diseases and remains one of the leading causes of death in this group of diseases. Studies of community-acquired pneumonia are extremely relevant for modern clinical practice. One of the important role in the pathogenesis of bacterial, viral, fungal invasion in the system of a human lung system belongs to the pulmonary surfactant, in particular, its proteins SP-A and SP-D. This article reviews the well-known mechanisms of important biological properties of immunomodulatory activity of the proteins SP-A and SP-D in response to microbial infection in the lungs. The mechanisms of participation of surfactant proteins SP-A and SP-D in the cascade of reactions that lead to severe life-threatening complications in community-acquired pneumonia are considered. The use of serum levels of surfactant proteins SP-A and SP-D can help finding new diagnostic and prognostic approaches in patients with community-acquired pneumonia.

Circulating sphingosine-1-phosphate as a prognostic biomarker for community-acquired pneumonia.

Early determination of the severity of Community-Acquired Pneumonia (CAP) is essential for better disease prognosis. Current predictors are suboptimal, and their clinical utility remains to be defined, highlighting the need for developing biomarkers with efficacious prognostic value. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid with a documented regulatory role in immune defense and maintenance of endothelial barrier integrity. For early diagnose of CAP and recognition of severe CAP patients, we conduct this pilot study to access the potential utility of the circulating S1P in an Emergency department setting. In the prospective study, plasma S1P levels were quantified in healthy controls and patients with CAP. Also, their discriminating power was assessed by receiver operating characteristic analysis. The association between S1P levels and disease severity indices was assessed by Spearman correlation and logistic regression tests. Patients with CAP had significantly higher plasma S1P levels than healthy individuals (CAP: 27.54 ng/ml, IQR = 14.37–49.99 ng/ml; Controls: 10.58 ng/ml, IQR = 4.781–18.91 ng/ml; p < 0.0001). S1P levels were inversely correlated with disease severity in patients with CAP. Based on multivariate logistic regression analysis, the plasma S1P concentrations showed significant predicting power for mortality (OR: 0.909; CI: 0.801–0.985; p < 0.05), intensive care unit admission (OR: 0.89; CI: 0.812–0.953; p < 0.005) and long hospital stay (OR: 0.978; CI: 0.961–0.992; p < 0.005). Interestingly, significantly elevated levels of S1P were noted in patients who received methylprednisolone treatment during hospitalization. These results suggest that S1P may be associated with the pathogenesis of CAP and may have prognostic utility in CAP and its therapy, especially in the Emergency Department setting.

СОВРЕМЕННЫЕ АСПЕКТЫ ВНЕБОЛЬНИЧНОЙ ПНЕВМОНИИ

Thanks to a large number of studies on community-acquired pneumonia (CAP) by scientists around the world, new data are emerging on various aspects of the problem. Therefore, it is necessary to regularly update knowledge on this issue. Despite the tendency to decrease in recent years, the incidence of CAP is 5-10 cases per 1 thousand of the population. In the structure of the general morbidity of respiratory diseases, CAP ranks 2nd in the adult population and 1st in children. Mortality from CAP ranges from 5% to 25-50% depending on the severity, mechanisms of development and personality of the patient (age, nutritional status, concomitant diseases, immune system, etc.), increasing with the growth of diseases of the upper respiratory tract caused by pneumotropic viruses. The clinical lecture presents current data on the features of etiology, previously little known mechanisms of the pathogenesis of CAP, the clinic of typical bacterial, viral, fungal, mycoplasmic and parasitic CAP, as well as the features of the disease in patients with severe immune disorders (AIDS, other diseases/pathological conditions) and aspiration pneumonia. In short form there are discussed the main recommendations for the treatment of CAP in various clinical groups: outpatients, persons with mild CAP, patients with severe CAP with suspected infection with Pseudomonas aeruginosa and aspiration.

Evaluation of dynamic thiol/disulfide homeostasis in adult patients with community-acquired pneumonia

Background: Community-acquired pneumonia is an important cause of mortality and morbidity in all age groups. Oxidant and antioxidant mechanisms play an important role in the pathogenesis and mortality of community-acquired pneumonia. Objectives: In this study, the role of thiol/disulfide homeostasis in the diagnosis and prognosis of community-acquired pneumonia was investigated. Methods: This was a prospective, controlled, observational study involving 73 community-acquired pneumonia patients and 68 healthy volunteers. Results: The native thiol and total thiol, which are thiol/disulfide homeostasis components, were significantly lower in the community-acquired pneumonia group. It was also found that the native thiol was lower in the high-risk community-acquired pneumonia group and that the native thiol and total thiol were associated with the Pneumonia Severity Index, CRB65 (confusion, respiratory rate, blood pressure, ⩾65 years old), and CURB65 (confusion, uremia, respiratory rate, blood pressure, ⩾65 years old) scores. The thiol compound levels were also associated with the C-reactive protein and procalcitonin levels. However, there was no significant difference between the survivors and non-survivors in terms of the thiol/disulfide homeostasis parameters. Conclusion: This study demonstrated the important role that oxidative stress plays in the pathogenesis of community-acquired pneumonia. The thiol/disulfide homeostasis biomarkers especially the native thiol and index-1 levels were significantly lower in patients with community-acquired pneumonia. Further studies are needed to investigate the diagnostic and prognostic value of thiol/disulfide homeostasis parameters in community-acquired pneumonia.

Genetic variants of interferon regulatory factor 5 associated with the risk of community-acquired pneumonia

Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of pro-inflammatory cytokines and immune responses to infection, and multiple polymorphisms of the IFR5 gene have been shown to be associated with autoimmune and infectious diseases. Several studies have investigated single nucleotide polymorphisms (SNPs) in a number of genes associated with the susceptibility to or severity and outcome of community-acquired pneumonia (CAP), but no research has yet been conducted on the role of IRF5 gene polymorphisms in CAP. In this study, we investigated the effects of four IFR5 variants, rs77571059, rs2004640, rs10954213, and rs3807306 on the susceptibility to CAP by genotyping 228 CAP patients and 177 healthy donors. Our results indicated that IFR5 variants rs77571059 and rs2004640 and haplotype GTAA were associated with the susceptibility to CAP and rs77571059 was related to the severity of the disease, suggesting that IFR5 variants may contribute to the pathogenesis of CAP and may serve as prognostic markers of CAP susceptibility and outcome.

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia.

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.

The Use of Statins and Risk of Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is still associated with a large burden and causes significant morbidity and mortality. Besides universal vaccination and antibiotic treatment, statins as adjunctive therapy may also have a beneficial role in the prevention and treatment of CAP. Our goal from this review is to discuss the epidemiology of CAP, and role of statins as adjunctive therapy in the development of CAP. Statins are lipid-lowering medications characterized by their ability to control hypercholesterolemia in addition to other pleiotropic effects that could explain their role in the pathogenesis of CAP. While most observational studies have shown that statins reduce risk of pneumonia in the general population, patients with diabetes, and recently in patients with myocardial infarction, no randomized controlled trial (RCT) to date has been conducted to assess the efficacy of statins to prevent development of CAP. Given the paucity of robust randomized evidence to assess statin use and the development of CAP, and considering conflicting results of the observational studies, we are not in favor of initiation of statins for either the prevention or treatment of CAP.

Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP: A case-control study.

Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP.In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism.This was a case–control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method.Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5–5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27–3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3–11.2; P < 0.01).We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP.

Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia.

BackgroundWe hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration. This study evaluated the association between OSA and CAP.MethodsWe performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group). The controls were matched according to age, sex and body mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests.FindingsNo significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) ≥10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29–6·44, p = 0·01). Patients with severe OSA (AHI≥30) also had a higher risk of CAP (OR = 3·18, 95%CI 1·11–11·56, p = 0·047). In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007). Furthermore, OSA was significantly associated with CAP severity (p = 0·0002), and OSA severity was also associated with CAP severity (p = 0·0006).ConclusionsOSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the relationships among gastroesophageal reflux, silent aspiration, laryngeal sensory dysfunction and CAP.Trial RegistrationClinicalTrials.gov NCT01071421

Plasma kallistatin levels in patients with severe community-acquired pneumonia

IntroductionCommunity-acquired pneumonia (CAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory failure with high mortality. Kallistatin, an endogenous tissue kallikrein inhibitor, has been reported to be protective in various human diseases. The aim of this study was to assess the correlations of kallistatin with other biomarkers and to determine whether kallistatin levels have a prognostic value in severe CAP.MethodsPlasma samples and clinical data were prospectively collected from 54 patients with severe CAP requiring ICU admission. Seventeen healthy control subjects were included for comparison. Plasma kallistatin, kallikrein, and other biomarkers of inflammation (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, C-reactive protein (CRP)), and anti-coagulation (protein C, anti-thrombin III) were measured on days 1 and 4 of ICU admission. Comparison between survivors (n = 41) and nonsurvivors (n = 13) was performed.ResultsPlasma kallistatin was significantly consumed in severe CAP patients compared with healthy individuals. Lower day 1 kallistatin levels showed a strong trend toward increased mortality (P = 0.018) and higher day 1 CURB-65 scores (P = 0.004). Plasma kallistatin levels on day 1 of ICU admission were significantly decreased in patients who developed septic shock (P = 0.017) and who had acute respiratory distress syndrome (P = 0.044). In addition, kallistatin levels were positively correlated with anti-thrombin III and protein C and inversely correlated with IL-1β, IL-6, and CRP levels. In a multivariate logistic regression analysis, higher day 1 CURB-65 scores were independent predictors of mortality (odds ratio = 29.9; P = 0.009). Also, higher day 1 kallistatin levels were independently associated with a decreased risk of death (odds ratio, 0.1) with a nearly significant statistical difference (P = 0.056). Furthermore, we found that a cutoff level of 6.5 μg/ml of day 1 kallistatin determined by receiver operating characteristic curves could be used to distinguish between patients who survived in 60 days and those who did not.ConclusionsThese results suggest that kallistatin may serve as a novel marker for severe CAP prognosis and may be involved in the pathogenesis of CAP through antiinflammatory and anticoagulation effects.See related letter by Katz et al., http://ccforum.com/content/17/2/429

HIGH INCIDENCE OF FALSE‐POSITIVE ASPERGILLUS GALACTOMANNAN TEST RESULTS IN PATIENTS WITH ASPIRATION PNEUMONIA

Letter to the Editor: The Platelia Aspergillus assay for detecting circulating galactomannan (GM) has been widely used for diagnosing invasive aspergillosis, but a major difficulty with this enzyme-linked immunosorbent assay (ELISA) is the transient false-positive results that occur with the administration of some beta-lactam antibiotics or with intestinal translocation of lipoteichoic acid of Bifidobacterial species origin in neonates and infants.1, 2 In the present study, an unexpectedly high rate of false-positive Aspergillus GM test results was found in patients with definite aspiration pneumonia. It has been reported that GM is contained in various beverages and foods, such as tea, milk, pasta, rice, and pepper,3 and several reports have suggested that silent aspiration is an important factor in the pathogenesis of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in elderly people.4, 5 In this context, it was hypothesized that GM of food origin reaches the blood circulation through the inflamed respiratory tract mucosa in patients with aspiration pneumonia and causes ELISA reactivity. The study population consisted of 40 patients with pulmonary infection who were admitted to Kumamoto Saishunso National Hospital from April 2007 to March 2008, including 29 patients with definite aspiration pneumonia according to the guidelines of the Japanese Respiratory Society6 and 11 patients with CAP or lower respiratory tract infection without aspiration as controls (7 patients with pneumonia and 4 patients with acute bronchitis). All control patients were younger than 65 and had neither dysphagia nor central nervous system diseases. A serum sample was examined for the presence of GM in each patient with the use of the Platelia Aspergillus kit (Bio-Rad, Marnes-La-Coquette, France).2, 7 The records of these patients were retrospectively reviewed for the diagnosis of invasive aspergillosis, and no patient fulfilled the criteria of the European Organization for Research and Treatment of Cancer-Mycoses Study Group.7 Plateria Aspergillus test results were considered false positives when the GM index was 0.5 or greater and 5.0 or less in the serum without a diagnosis of proven, probable, or possible invasive aspergillosis.2, 7 None of the patients were given the antibiotics that are known to cause false-positive Platelia Aspergillus test results, such as piperacillin-tazobactam, amoxicillin-clavulanic acid, and amoxicillin, before the test was performed.1-3 As shown in Figure 1, 27 of 29 patients with definite aspiration pneumonia showed false-positive results (n=29; mean age±standard deviation=80.8±15.7; 16 men, 13 women). Alternatively, all control patients except one had a negative Platelia Aspergillus test result (n=11; mean age=52.1±14.6; 5 men, 6 women) (Fisher exact probability test, P<.001). The serum GM index was significantly higher in patients with aspiration pneumonia (median 0.8, range 0.1–5.0) than in patients with pneumonia or acute bronchitis without aspiration (median 0.3, range 0.1–0.5) (Mann-Whitney U-test, P<.001). Galactomannan (GM) index values in patients with aspiration pneumonia and patients with pneumonia or acute bronchitis without aspiration. A GM index of ≥0.5 and ≤5.0 was considered a false-positive result. Its retrospective nature and small sample size limit this report, although the preliminary data suggest that the circulating GM in patients with aspiration pneumonia originates from beverages and foods aspirated into the lower respiratory tract. In conclusion, the use of serum GM antigen measurement may be helpful for diagnosing aspiration pneumonia due to silent aspiration in elderly patients with CAP or HAP. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: Yusuke Tomita, Mineharu Sugimoto, Osamu Kawano: study concept and design, acquisition of subjects and data, analysis. Yusuke Tomita, Mineharu Sugimoto, Hirotugu Kohrogi: interpretation of data and preparation of manuscript. Sponsor's Role: None.