adrenomedullin and Pneumonia--Pneumococcal

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia.. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation.. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut).. MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

Topics: Adrenomedullin; Animals; Bronchodilator Agents; Female; Mice; Mice, Inbred C57BL; Pneumonia, Pneumococcal; Respiration, Artificial; Sepsis; Ventilator-Induced Lung Injury

Adrenomedullin is a vasodilatory polypeptide with pleiotropic effects secreted by various organs. Adrenomedullin is produced first as a prepropeptide, and then cleaved into mature adrenomedullin and mid-regional proadrenomedullin. Whereas levels of the latter have been shown to correlate with severity of sepsis and carry prognostic value, adrenomedullin plays a role in vascular tone homeostasis. In the previous issue of Critical Care, the infusion of exogenous adrenomedullin is suggested to protect against increased lung endothelial permeability and end-organ dysfunction in a model of pneumococcal pneumonia in mechanically ventilated mice, possibly by stabilizing vascular endothelia. Since adrenomedullin is a strong vasodilatory molecule, further studies are needed to evaluate its potential as a future treatment of sepsis.

Topics: Adrenomedullin; Animals; Bronchodilator Agents; Female; Pneumonia, Pneumococcal; Respiration, Artificial; Sepsis; Ventilator-Induced Lung Injury

A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome.. Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci.. There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01).. In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults.

Topics: Adolescent; Adrenomedullin; Adult; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; HIV Infections; Hospitalization; Humans; Nasopharynx; Pneumonia; Pneumonia, Pneumococcal; Protein Precursors; Real-Time Polymerase Chain Reaction; Severity of Illness Index; South Africa; Streptococcus pneumoniae

Topics: Adrenomedullin; Aged; Biomarkers; Cardiovascular Diseases; Child; Community-Acquired Infections; Forecasting; Hospital Mortality; Humans; Middle Aged; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Protein Precursors; Vaccines, Conjugate