Analysis of the Local and Systemic Cytokine Response Profiles in Patients with Community-Acquired Pneumonia. Relationship with Disease Severity and Outcomes.

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, IL-12p40, IL-17A, IFNg, TNFa and CXCL10) in plasma and sputum on hospital admission, a “pro-inflammatory cytokine score (PICS)” was defined. PICS in plasma and sputum were plotted against each other and quadrants used to define profiles based on the four possible high/low combinations. A similar approach was used to contrast sputum PICS vs. anti-inflammatory cytokines (IL-1ra and IL-10). Some of the “profiles” thus defined were found to group patients with common etiologic characteristics and/or associate with similar measures of disease severity and/or clinical outcomes, suggesting the predictive value of the use of cytokine data in CAP patients

Serum and exhaled breath condensate inflammatory cytokines in community-acquired pneumonia: a prospective cohort study

Background The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation. Methods This was an observational, prospective, cohort study of hospitalised patients with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin [IL]-1, IL-1\u3b1, IL-1\u3b2, IL-2, IL-6, IL-8, tumor necrosis factor [TNF]\u3b1 and interferon [IFN]\u3b3) and anti-inflammatory cytokines (IL-4 and IL-10) were measured in both serum and exhaled breath condensate within 24 h after hospital admission. Results A total of 74 patients (median age: 76 years; gender: 61 % male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in patients with severe disease on admission and prolonged time to reach clinical stability. This was due to lower levels of anti-inflammatory cytokines in the exhaled breath condensate and higher levels of pro-inflammatory cytokines in serum. Conclusions Dis-regulation between pro- and anti-inflammatory pathways might be a part of the pathogenic mechanisms that lead to severe infection and worse early clinical outcomes in CAP patients

Neutrophil Function in Elderly Patients Hospitalized with Community- Acquired Pneumonia

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP. Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H2O2) production. The Mann-Whitney U-test was used to compare differences in neutrophil function. Results: A total of 12 HC, 28 NE-CAP, and 12 E-CAP were evaluated. There were no significant differences between NE-CAP and E-CAP patients in regard to CD35 expression (p=0.465), CD66b expression (p=0.601), phagocytosis (p=0.654), or H2O2 production (p=0.541) Conclusions: We failed to demonstrate any significant difference in neutrophil function in nonelderly versus elderly patients hospitalized with CAP in relation to membrane expression of CD35 and CD66b, phagocytosis, and respiratory burst. Abnormal neutrophil function is unlikely to be an important component of the immunosenescence described in elderly patients with CAP

Neutrophil function in elderly patients hospitalized with community-acquired pneumonia.

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP. Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H2O2) production. The Mann-Whitney U-test was used to compare differences in neutrophil function. Results: A total of 12 HC, 28 NE-CAP, and 12 E-CAP were evaluated. There were no significant differences between NE-CAP and E-CAP patients in regard to CD35 expression (p=0.465), CD66b expression (p=0.601), phagocytosis (p=0.654), or H2O2 production (p=0.541) Conclusions: We failed to demonstrate any significant difference in neutrophil function in nonelderly versus elderly patients hospitalized with CAP in relation to membrane expression of CD35 and CD66b, phagocytosis, and respiratory burst. Abnormal neutrophil function is unlikely to be an important component of the immunosenescence described in elderly patients with CAP

Characteristics and Outcomes of Adults Hospitalized with SARS-CoV-2 Community-Acquired Pneumonia in Louisville, Kentucky

Background: Patients infected with the novel coronavirus SARS-CoV-2 are frequently hospitalized with community-acquired pneumonia (CAP). The objective of this study was to define the clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 CAP in the city of Louisville, KY. Methods: This was a retrospective observational study of 700 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients with 1) a positive RT-PCR for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate at chest imaging were defined as having SARS-CoV-2 CAP. Demographic characteristics of the study population were compared with census data from the city of Louisville. For each patient more than 500 variables were abstracted from electronic medical records and recorded using Research Electronic Data Capture software. Data was analyzed by descriptive and inferential statistics using R version 3.4.0. Results: SARS-CoV-2 CAP was identified in 632 (90%) patients hospitalized with COVID-19. The median age of the patients was 63 years, 53% were females, 31% were black and 12% Hispanic. The most frequent comorbidities were hypertension (56%), obesity (50%), and diabetes (33%). Mortality was 17% for the total population and 34% for the 249 patients admitted to ICU. For each category of race, ethnicity and comorbidities, the proportion of hospitalized patients with SARS-CoV-2 CAP was significantly different when compared to the Louisville population (p \u3c 0.001). Conclusion: Patients of black race, Hispanic ethnicity, and patients with history of hypertension, obesity or diabetes are overrepresented among hospitalized patients with SARS-CoV-2 CAP when compared to the Louisville population. Hospitalized patients with SARS-CoV-2 CAP are likely to require ICU care, with death occurring in approximately one of six hospitalizations

Alexithymia and interleukin variations in somatoform disorder

Objective: The aim of the present study was to investigate if somatoform disorders (SFD) are associated with changes in the normal serum levels of important interleukins, and further, to establish if these changes are related to the presence and severity of alexithymia in patients with SFD. Methods: Twenty-four unmedicated patients who met the International Classification of Diseases (ICD-10) diagnostic criteria for SFD completed the psychological questionnaire to assess alexithymia (Toronto Alexithymia Scale), symptom reporting (SCL-90-R) and diagnostic criteria for SFD (Screening for Somatoform Symptoms scale). Serum concentrations of soluble interleukin 2 receptor α (sIL-2 Rα), IL-4, IL-6, IL-10 and IL-12 were determined in patients with SFD and in 9 healthy subjects. Results: In patients with SFD, serum levels of IL-6 (p < 0.001), IL-10 (p = 0.047) and immunoglobulin E (p = 0.045) were significantly increased in comparison with healthy controls. Additionally, a negative correlation was observed between the level of alexithymia ('total' Toronto Alexithymia Scale score) and the serum levels of sIL-2 Rα (r = -0.538) in SFD. Conclusions: Taken together, these results suggest that SFD, with clinically significant alexithymia, are associated with a reduction in Th1-mediated immune function and an increase in the activation of the Th2 immune function, indicated by the augmented serum levels of IL-6 and IL-10 and elevated immunoglobulin E. Copyright © 2007 S. Karger AG

No difference in clinical outcomes for African American and White patients hospitalized with SARS-CoV-2 pneumonia in Louisville, Kentucky

Introduction: Current literature indicates that African American individuals are at increased risk of becoming infected with the SARS-CoV-2 virus and suffer higher SARS-CoV-2-related mortality rates. However, there is a lack of consensus as to how the clinical outcomes of African American patients differ from those of other groups. The objective of this study was to define the clinical outcomes of African American and White hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) in Louisville, Kentucky. Methods: This was a retrospective cohort study of hospitalized patients with SARS-CoV-2 CAP at eight hospitals in Louisville, Kentucky. Severity of CAP at time of hospitalization was evaluated using the pneumonia severity index (PSI), CURB-65 score and SARS-CoV-2 viral load. The following thirteen clinical outcomes were compared: discharge alive to home, time to home discharge, admission to the ICU, length of ICU stay, need for invasive mechanical ventilation (IMV), duration of IMV, development of acute respiratory distress syndrome (ARDS), development of septic shock, need for vasopressors, development of cardiovascular events, time to cardiovascular events, in-hospital mortality, and time to death. Results: A total of 541 patients were eligible for this study, 343 White (63%) and 198 African American (37%). None of the thirteen clinical outcomes were statistically significantly different between the two groups. Conclusions: This study indicates that African American and White patients do not have different clinical outcomes after the point of hospitalization due to SARS-CoV-2 CAP

Development of a Quantitative Bead Capture Assay for Soluble IL-7 Receptor Alpha in Human Plasma

IL-7 is an essential cytokine in T-cell development and homeostasis. It binds to the IL-7R receptor, a complex of the IL-7Rα (CD127) and common γ (CD132) chains. There is significant interest in evaluating the expression of CD127 on human T-cells as it often decreased in medical conditions leading to lymphopenia. Previous reports showed the usefulness of CD127 as a prognostic marker in viral infections such as HIV, CMV, EBV and HCV. A soluble CD127 (sCD127) is released in plasma and may contribute to disease pathogenesis through its control on IL-7 activities. Measuring sCD127 is important to define its role and may complement existing markers used in lymphopenic disease management. We describe a new quantitative assay for the measurement of sCD127 in plasma and report sCD127 concentrations in healthy adults.We developed a quantitative bead-based sCD127 capture assay. Polyclonal CD127-specific antibodies were chosen for capture and a biotinylated monoclonal anti-CD127 antibody was selected for detection. The assay can detect native sCD127 and recombinant sCD127 which served as the calibrator. The analytical performance of the assay was characterized and the concentration and stability of plasma sCD127 in healthy adults was determined. The assay's range was 3.2–1000 ng/mL. The concentration of plasma sCD127 was 164±104 ng/mL with over a log variation between subjects. Individual sCD127 concentrations remained stable when measured serially during a period of up to one year.This is the first report on the quantification of plasma sCD127 in a population of healthy adults. Soluble CD127 plasma concentrations remained stable over time in a given individual and sCD127 immunoreactivity was resistant to repeated freeze-thaw cycles. This quantitative sCD127 assay is a valuable tool for defining the potential role of sCD127 in lymphopenic diseases