To test the hypothesis that the concentration of angiopoietin-2 relative to angiopoietin-1 may be a useful biological marker of mortality in acute lung injury patients. We also tested the association ...of concentration of angiopoietin-2 relative to angiopoietin-1 with physiologic and biological markers of activated endothelium.
Prospective, observational cohort study.
Intensive care units in a tertiary care university hospital and a university-affiliated city hospital.
Fifty-six mechanically ventilated patients with acute lung injury.
Baseline plasma samples and pulmonary dead-space fraction measurements were collected within 48 hrs of acute lung injury diagnosis.
Plasma levels of angiopoietin-1 and angiopoietin-2 and of biomarkers of endothelial activation were measured by enzyme-linked immunosorbent assay. Baseline concentration of angiopoietin-2 relative to angiopoietin-1 was significantly higher in patients who died (median, 58 interquartile range, 17-117 vs. 14 interquartile range, 6-35; p = .01). In a multivariable analysis stratified by dead-space fraction, concentration of angiopoietin-2 relative to angiopoietin-1 was an independent predictor of death, with an adjusted odds ratio of 4.3 (95% confidence interval, 1.3-13.5; p = .01) in those with an elevated pulmonary dead-space fraction (p = .03 for interaction between pulmonary dead-space fraction and concentration of angiopoietin-2 relative to angiopoietin-1). Moderate to weak correlation was found with biological markers of endothelial activation.
The ratio of concentration of angiopoietin-2 relative to angiopoietin-1 may be a prognostic biomarker of endothelial activation in acute lung injury patients and, along with pulmonary dead-space fraction, may be useful for risk stratification of acute lung injury patients, particularly in identifying subgroups for future research and therapeutic trials.
Abstract In patients with dyspnea, prehospital and emergency providers make therapeutic decisions before a diagnosis is established. Inhaled beta-2 agonists are frontline treatment for patients with ...dyspnea due to asthma or chronic obstructive pulmonary disease (COPD) exacerbations. However, these agents have been associated with increased adverse events when administered chronically to heart failure patients. Our goal was to determine the safety and efficacy of acute administration of inhaled beta-2 agonists to patients with heart failure. MEDLINE and EMBASE searches were performed using the terms “beta agonists,” “albuterol,” “congestive heart failure,” and “pulmonary edema.” Bibliographies of relevant articles were searched. Only studies addressing acute effects of beta-2 agonists were included for analysis. Twenty-four studies comprising 434 patients were identified that addressed the acute delivery of beta-2 agonists in subjects with heart failure—five studies with inhaled administration and 19 with systemic administration. No study directly evaluated the effects of inhaled beta-2 agonists to patients with acutely decompensated heart failure. Treatment of heart failure patients with beta-2 agonists resulted in transient improvements in pulmonary function and cardiovascular hemodynamics. Only one investigation reported an association between beta-2 agonist use and an increase in malignant dysrhythmias. Investigations in animal models of heart failure and acute lung injury demonstrated resolution of pulmonary edema with beta agonist administration. There is insufficient evidence to suggest that acute treatment with inhaled beta-2 agonists should be avoided in patients with dyspnea who may have heart failure. Based on small studies and indirect evidence, administration of beta-2 agonists to patients with heart failure seems to improve pulmonary function, cardiovascular hemodynamics, and resorption of pulmonary edema. Although an increase in adverse effects with the use of beta-2 agonists cannot be ruled out based on these data, there was no evidence of an increase in clinically significant dysrhythmias, especially when administered by inhalation. Based on these findings, further study should focus on the clinical outcomes of patients with acutely decompensated heart failure who are treated with inhaled beta-2 agonist therapy.
We present the case of a trauma patient whose persistently abnormal chest radiography led to exploratory bronchoscopy. After the discovery of a foreign body in the right lower lobe bronchus, an ...attempted retrieval resulted in accidental perforation of a cocaine bag and release of the drug, which may have been the cause of the patient's subsequent pneumonitis.
Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI).
We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be ...associated with worse clinical outcomes, and (2) ventilation with lower VT would reduce urine NO as a result of less stretch injury.
Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr).
Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04).
Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.
Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher ...mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P=0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P=0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury.
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