Tracheobronchial aspirate proinflammatory cytokines: early predictors of chronic lung disease in neonates with respiratory distress syndrome

The objectives of the present study were to investigate if early measurements of proinflammatory cytokines in tracheobronchial aspirate fluid from neonates with respiratory distress syndrome [RDS] could be used to early predict chronic lung disease [CLD]. This is in comparison with other risk factors including gestational age, birth weight, prenatal steroid, mode of delivery, duration of exposure to FiO[2] >0.21, peak inspiratory pressure [PIP] and duration of ventilatory support, air leaks, patent ductus arteriosus [PDA], and intraventricular hemorrhage [IVH]. Thirty-six preterm infants less than 34 weeks of gestation with RDS were mechanically ventilated and days 2 and 7 - measurements of concentrations of tumor necrosis factor-alpha [TNF-alpha] and the interleukins IL-1beta, IL-6, and IL-8 were made, using enzyme immunoassay techniques. Echo-Doppler and head ultrasonography studies were done for each patient. Each patient was followed-up for 28 days. Ten patients developed CLD, six patients died before the elapse of 28 days, and 20 patients experienced uncomplicated course of RDS. Infants who developed CLD had significantly increased concentrations of TNF-alpha, IL-1beta, IL-8, and IL-6 on days 2 that persist by day 7. TNF-alpha, IL-6, IL-8, and IL-1beta concentrations correlated significantly with lower gestational age, birth weight, time spent on a ventilator, duration of supplemental oxygen, maximal PIP, symptomatic PDA, and appearance of air leak. IL-6 cut-off point level of 650 pg/ml at day 2 predicts CLD with accuracy of 100%, and IL-1beta cut-off point level of 165 pg/ml at day 2 predicts CLD with accuracy of 100%. In conclusion, increased concentrations of tracheobronchial aspirate fluid proinflammatory cytokines could be the most valuable early predictor of CLD and will assist in selecting infants for early interventions including corticosteroid treatment or more selective blockage of components of inflammation

Adrenergic apoptosis in children with chronic heart failure: preventive role of carvedilol

The objectives of the present study were to investigate adrenergic-apoptotic pathway in children with chronic heart failure and to validate the usefulness of beta-blocker, carvedilol, as a novel therapy in such children, A total of 40 children with Ross classes I [No, 10], II [No, 15], and III [No, 15] chronic heart failure with a mean age of 4.7 +/- 3.5 years were enrolled. They included 18 males and 22 females. Children who belong to Ross class IV were excluded. A total of 20 matched healthy children served as controls. Serum levels of adrenaline, noradrenaline, beta-adrenergic receptors density, soluble Fas, soluble Fas-Ligand were determined in all of the patients before and 3 months after carvedilol therapy. Results of the study showed [1] Children with all classes of chronic heart failure demonstrated significantly elevated levels of serum norepinephrine, significantly reduced levels of beta-Adrenergic receptor density, and significant rise in serum sFas, sFas ligand as well as sFasL/sFas ratios Vs controls [P <0,05 for all]; [2] The elevated serum norepinephrine levels and reduced beta-Adrenergic receptor density levels correlated significantly with the elevated levels of serum sFas, sFas ligand as well as sFasL/sFas ratios [P <0.05 for all]; [3] All these changes correlated significantly with the clinical severity of CHF as well as with echocardiographic systolic and diastolic dysfunctions [P <0.05 for all]; [4] Three months after carvedilol therapy there was significant reduction in serum levels of norepinephrine, significant elevation of beta-Adrenergic receptor density, significant reduction in serum sFas, sFas ligand as well as sFasL/sFas ratios [P <0.05 for all]. There was associated significant improvement of clinical staging as well as echocardiographic systolic and diastolic functions [P <0.05 for all]. [1] Children with chronic heart failure expressed a hyperadrenergic accelerated apoptotic state that might be responsible for progression of heart failure. [2] Carvedilol therapy might improve the clinical course of children with chronic heart failure

Plasminogen activator inhibitor type 1 in pediatric patients after successful cardiopulmonary resuscitation

Elevated serum plasminogen activator inhibitor type 1 [PAI-1] have been suggested to be responsible for the downhill course after initial successful cardiopulmonary resuscitation [CPR] in adults. The objectives of the present study were to investigate serum PAI-1 concentrations in pediatric patients after initial successful CPR, and to analyze its relationship to the outcome including pediatric intensive care unit survival, renal failure 1 week after CPR, and cerebral performance at hospital discharge. Seventy-five patients admitted to pediatric intensive care unit [PICU], after in-hospital cardiac arrest with initial successful CPR together with 75 matched controls were eligible for the study. Patients included 35 boys and 40 girls, their mean age was 4.8 +/- 3.4 years. Patients' variables, CPR variables and outcome variables were recorded. ELISA method was used to quantify plasma total and active PAI-1 antigen in 2 samples, 1st taken immediately after successful CPR, and 2nd taken on the second day. The results of the study showed: [1] 24-hour non-survival was significantly associated with CPR duration >15 min and administration of >/= 3 doses of epinephrine during CPR [P<0.05 for both]. [2] CPR duration >15 minutes was the only variable that showed significant positive association with 7th and 30th day non-survival, renal failure 7 days after CPR, and cerebral unfavorable outcome at discharge [P<0.05 for all]. [3] Serum active and total PAI-1 antigens in patients samples taken immediately after CPR were comparable with controls [P>0.05], whereas 2nd day samples showed significantly increased levels of active and total PAI-1 antigen Vs matched controls [P<0.05 for both]. [4] Total and active PAI-1 antigen correlated significantly in a positive manner with 7th and 30th day non-survival, 7th day renal failure, and unfavorable cerebral outcome at discharge [P<0.05 for all outcome patterns]. [5] Total PAI-1 antigen cut off level <180 ng/ml on the second day, is a reliable predictor of favorable outcome [P<0.05 for all] whereas levels >/= 180 ng/ml, is a reliable predictor of unfavorable outcome particularly when CPR duration is > 15 minutes [P<0.05 for all outcome patterns]. [1] PAI-1 antigen might play a pivotal role in reproducing downhill course after initial successful CPR in pediatric patients. [2] Total PAI-1 antigen cut off level <180 ng/ml on the second day, is a reliable predictor of favorable outcome whereas levels >/= 180 ng/ml, is a reliable predictor of unfavorable outcome if CPR duration is > 15 minutes. [3] Future prolonged life support measures may include inhibitors of PAI-1 as vitamin E or acute phase protein alpha 1-acid glycoprotein, these novel therapies might improve the outcome