Diagnostic and prognostic value of plasma adrenomedullin in COPD exacerbation.

BACKGROUND: Adrenomedullin (ADM) is a regulatory peptide with many biological actions, but little is known about its role in patients with COPD exacerbation. The purpose of this study was to evaluate the diagnostic and prognostic value of plasma ADM levels on hospital admission in patients with COPD exacerbation. METHODS: Consecutive subjects admitted to the hospital for COPD exacerbation were included and were followed up for 1 y; in addition, subjects with stable COPD from an out-patient clinic and healthy volunteers were recruited as controls. RESULTS: Compared with healthy subjects (145 pg/mL [interquartile range {IQR} 103-290 pg/mL]), plasma ADM levels were significantly higher in subjects with COPD exacerbation (270 pg/mL [IQR 170-510 pg/mL], P = .001) and in subjects with stable COPD (400 pg/mL [IQR 210-525 pg/mL], P < .001). In subjects with COPD exacerbation, ADM levels were significantly elevated during exacerbation (560 pg/mL [IQR 495-630 pg/mL]) compared with the recovery phase (470 pg/mL [IQR 393-553 pg/mL], P = .01) and the stable phase (200 pg/mL [IQR 143-308 pg/mL], P < .001). In receiver operating characteristic analysis, in subjects with COPD exacerbation, ADM had high diagnostic accuracy in differentiating between exacerbation and the stable phase (area under the curve 0.97, 95% CI 0.93-1.02, P < .001). In Cox regression analysis, plasma ADM was not independently associated with 1-y survival (P = .97), but it could accurately predicted the need for ICU care (hazard ratio 1.37, 95% CI 1.09-1.72, P = .008). CONCLUSIONS: Plasma ADM is a valuable biomarker to confirm COPD exacerbation; furthermore, plasma ADM independently predicts the need of ICU care, although it is not associated with long-term mortality in patients with COPD exacerbation.

Reactive oxygen species and x-ray disrupted spontaneous [Ca²âº]I oscillation in alveolar macrophages.

Radiation leads to a rapid burst of reactive oxygen species (ROS), which is considered to be one of the major causes of radiation-induced injury. ROS have previously been shown to induce changes in cytosolic Ca²âº ([Ca²âº]i) including [Ca²âº]i oscillation. However, the role of radiation in [Ca²âº]i oscillation is poorly understood. The purpose of this study was to identify the effect of ROS and X ray on [Ca²âº]i oscillation, as well as their role in radiation-induced lung injury. Alveolar macrophages were cultured in the absence and presence of different doses of hydrogen peroxide (H2O2) or exposed to X-ray irradiation with or without pretreatment of diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidases) or tetrandrine (TET, a calcium entry blocker) and cytosolic Ca²âº concentration was detected by fluorescent Ca²âº indicator Fura-2. Rat radiation lung injury was induced in vivo by using 40 Gy X ray and DPI or TET was used to prevent radiation-induced lung injury. The results showed that there was spontaneous [Ca²âº]i oscillation in alveolar macrophages under normal conditions, and treatment of H2O2 (100-500 µM) or 2 Gy X ray inhibited the spontaneous [Ca²âº]i oscillation and induced [Ca²âº]i rise. TET abolished H2O2 or X ray induced [Ca²âº]i rise in alveolar macrophages, and attenuated X ray- induced rat alveolitis in vivo. DPI prevented X-ray-induced inhibition of [Ca²âº]i oscillation in alveolar macrophages and prevented X-ray-induced rat alveolitis. Taken together, the data suggest that the disruption of [Ca²âº]i oscillation and induction of [Ca²âº]i rise through ROS is involved in the mechanism of radiation-induced lung injury.