Matrix metalloproteinase-8 and tissue Inhibitor of metalloprotinases-2 in tracheal aspirates from ventilated preterm neonates with respiratory distress syndrome

Matrix metalloproteinases [MMPs] are a family of endoproteinases that act in remodeling and destruction of extracellular matrix and basement membrane. An imbalance among their inducers, activators and specific inhibitors is believed 10 generate parenchymal destruction in pulmonary inflammatory diseases. In this study the concentrations of MMP-8 and tissue inhibitor of metalloprotinases [TIMP]-2 were assessed in tracheal aspirate fluids [TAFs] obtained from ventilated preterm neonates during the first postnatal week. The aim was to investigate their possible role in acute inflammatory lung injury associating respiratory distress syndrome [RDS], assess their relation to disease severity and their possible contribution to the development of chronic lung disease [CLD].Clinical and radiographic assessments of respiratory distress were attempted for 90 ventilated preterm neonates who were defined in 3 groups. Group A comprised 32 neonates with RDS, group B constituted 28 neonates with bronchopneumonia while group C included 30 ventilated neonates for extrapulmonary disorders. The median values for fraction of inspired oxygen [FiO[2]] and arterial/alveolar O[2] tension ratio [a/A O[2]] during the first 24 hours of ventilation, as measures of initial severity of respiratory distress, were calculated. TAF samples were collected for measurement of MMP-8 and TIMP-2 levels by ELISA with calculation of MMP-8/TIMP-2 ratio. Clinical outcome was determined in terms of evolution to CLD. A significant increase in MMP-8/TIMP-2 ratio was found in group A as compared to groups B and C [p<0.01, respectively]. Meanwhile, no significant change in MMP-8/TIMP-2 ratio was encountered in group B in comparison to group C [p>0.05]. Among neonates with RDS, MMP-8 was positively correlated to FiO[2] [r=0.64, p<0.01] and was inversely related to a/A O[2] [r=-0.72, p<0.01]. Nineteen [59%] of RDS neonates developed CLD and those were found to have significantly higher MMP-8, MMP-8/TIMP-2 ratio and initial FiO[2] and significantly lower initial a/A O[2] ratio as compared to RDS neonates with no CLD [p<0.01, respectively]. MMP-8 at an optimum cut-off value of 188 ng/mL was the best to predict RDS progression to CLD with a positive predictive value [PPV] of 94.1% and an efficacy of 87.5%. An imbalance between tracheal aspirate MMP-8 and TIMP-2 levels during the early postnatal period could play a role in the acute inflammatory lung injury in neonatal RDS. This imbalance is associated with disease severity and probably contributes to subsequent evolution of CLD. It could also be speculated that early assessment of tracheal aspirate MMP-8 in preterm neonates with RDS might help prediction of later CLD development

Urinary 8-isoprostane and S100B protein concentrations as predictors of hypoxic-ischemic brain damage in asphyxiated neonates

Newborn infants with perinatal asphyxia are prone to the development of hypoxic-ischemic encephalopathy [HIE]. To date, there are no reliable methods for proper identification of infants who are at high risk of HIE after asphyxial insult. We sought to evaluate urinary levels of a lipid peroxidation marker, 8-isoprostane, and a brain specific protein, S100B protein, as non-invasive tools that might help early identification of postasphyxial hypoxic-ischemic brain damage and prediction of its outcome. Thirty term neonates with perinatal asphyxia were evaluated in comparison to 15 matched healthy controls. Urinary concentrations of 8-isoprostane [by ELISA] and S100B protein [by immunoluminometric technique] were determined at first urination [time 1] and repeated in a second sample obtained 24-48 hours postnatally [time 2]. Asphyxiated neonates were clinically monitored for their neurological pattern over the first two postnatal weeks and were subsequently classified as mild [grade I, n=8], moderate [grade II, n=12] and severe [grade III, n=10] HIE. Eleven of these neonates [36.7%] died in the NICU. The results obtained were interpreted in relation to the grade of HIE severity and mortality. Urinary concentrations of 8-isoprostane and S100B protein were significantly higher in asphyxiated neonates at both monitored times, as compared to controls. Levels of both markers were related to the grade of HIE severity being significantly higher in neonates who developed grade II as compared to grade I, while highest levels were found in grade III. A significant increase in urinary 8-isoprostane from time 1 to time 2 was only found in grade III [p<0.05] while S100B protein increased over that time period in grades II and III [p<0.01, respectively]. Survivors showed significantly lower mean level of each marker as compared to those with fatal outcome [p<0.001, respectively], at both monitored times. Diagnostic performance tests revealed that S100B protein was superior to 8-isoprostane, at the two monitored times, for prediction of HIE severity and mortality. At first urination, a cut-off value for S100B protein of 0.3 micro g/L could best predict development of grades II and III HIE with a positive predictive value [PPV] of 100% and an efficacy of 95.5%. Meanwhile, an optimum cut-off value of 6.89 microg/mg creatinine for 8-isoprostane, had a PPV of 90.48% and an efficacy of 88.89% for grades II and III prediction. As predictors of mortality at first urination, an optimum cut-off value for S100B protein of 2.12 micro g/L and for 8-isoprostane of 10.4 micro g/mg creatinine had corresponding PPVs of 90.9% and 90%, respectively and efficacies of 93.3% and 90%, respectively. There was no significant difference in the overall diagnostic performance of each of the two markers either for disease severity or mortality prediction between both monitored times [p>0.05, respectively]. 8-isoprostane and S100B protein levels are increased in urine following birth asphyxia. S100B protein is superior to 8-isoprostane for prediction of both HIE severity and mortality. It could be speculated that measurement of urinary concentrations of these markers, soon after birth, could serve as a clinically useful and relatively simple non-invasive tool to predict the risk for developing HIE following birth asphyxia and its short-term outcome

Endothelin-1 in plasma and airways of preterms with respiratory distress syndrome

The objective of the study was to characterize the relationship between endothelin 1 [ET-1] concentration in plasma and airway of the preterm and the severity of respiratory distress syndrome [RDS] in early postnatal period. 44 preterm neonates were enrolled in two groups. Group I comprised 29 preterm with RDS requiring mechanical ventilation. They were further discriminated into 3 subgroups according to severity of RDS [mild, moderate and severe RDS]. Group II comprised 15 preterms on mechanical ventilation for repeated attacks of apnea of prematurity, matched for gestational and postnatal age with group I and served a reference group. Laboratory investigations included plain chest radiographs, sepsis work -up to rule out infection, arterial blood gas analysis with calculation of arterial alveolar oxygen ratio [a/A O2]. ET-1 concentration was measured in plasma and tracheal aspirates within the first 48 hours of life. Mean plasma ET-1 concentrations were significantly elevated in preterms with moderate and severe RDS as compared to reference preterms [P <0.01 and P <0.001, respectively]. Significant negative correlation existed between plasma ET-1 and each of gestational age and 1 and 5 minutes Apgar scores, whereas significant positive correlation-existed between plasma ET-1 and each of fraction of inspired oxygen [Fi02], mean airway pressure [MAP] and radiographic grading of severity of RDS. On the contrary, mean concentration of ET-1 in tracheal aspirate was significantly lower in preterms with severe RDS as compared to reference preterms [P <0.01]. A significant positive correlation was found between tracheal aspirate ET- 1 levels and 5 minutes Apgar score, while a significant negative correlation existed between tracheal aspirate ET-1 and MAP. Finally, a significant negative correlation was found between plasma and tracheal aspirate levels of ET-1 [P <0.001] in preterms with RDS, as well as in reference preterms. High plasma ET-1 level is associated with more severe RDS and could be a specific marker for pulmonary endothelial injury that may contribute to the development of elevated pulmonary vascular resistance in this setting. Meanwhile, the association of low ET-1 level in the airway with severe RDS may be attributable to limitation of its stimulant effect on surfaetant secretion and /or the development of airway epithelium; hence, rise in airway ET-1 is indicative of improved pulmonary status in the early course of the disease

relevance of chlamydia pneumoniae infection to bronchial asthma in children

This study was designed to investigate the relevance of Chlamydia pneumoniae [C. pn.] infection to bronchial asthma in children. Serological analysis of C. pn. specific IgG and IgM antibodies using indirect immunofluorescence technique was attempted in 126 children: 60 with acute asthma exacerbation, 24 stable asthmatics in-between the clinical attacks and 42 age and sex matched healthy children as controls. The results demonstrated significantly higher IgG and IgM titers in acute asthmatics compared to stable asthmatics and to controls. The findings suggested that acute C. pn. infection in children might be a significant cause of acute exacerbation of bronchial asthma. This infection should be suspected in children with acute asthma exacerbation not responding to usual treatment

Procalcitonin: a promising diagnostic and differential diagnostic marker for acute lower respiratory tract infection

The objective of the present study was to evaluate the role of plasma procalcitonin [PCT] as a useful marker for the early diagnosis of acute lower respiratory tract infection [LRTI] and its use as a tool to differentiate between its different etiologies. Moreover, its prognostic role was also evaluated. The study included 40 patients with acute LRTI who were divided into two groups; Group 1: included 20 patients [3-48 months old] with pneumonia and Group 2: included 20 patients [2-24 months old] with bronchiolitis. Twenty healthy age and sex matched infants and children were included as the control group. Serum calcium [Ca], phosphorus [P] and C-reactive protein as well as plasma procalcitonin [PCT] and complete blood counts [CBC] were estimated. Our results showed a significant decrease of serum Ca and P in patients with pneumonia. Patients with acute LRTI had significantly higher total leukocyte count, neutrophil count and lymphocyte count when compared to healthy controls. The level of these parameters in pneumonia patients were higher than those recorded in bronchiolitis patients. Healthy control subjects had a median plasma PCT of 6 pg/mL and an interquartile range of 4-8 pg/mL. Pneumonia patients had the highest PCT levels on admission [median of 370 pg/mL and interquartile range of 250-630 pg/mL]. Bronchiolitis patients had a median PCT of 92 pglmL and an interquartile range of 75.8-152.3 pg/mL. PCT at a cut-off level of 160 pg/mL differentiated between the two clinical conditions with a diagnostic sensitivity of 91% and specificity of 75%. The combined use of PCT at a cut-off level of 160 pg/mL and total leukocyte count at a cut- off level of 14x10 3/mL had a diagnostic sensitivity of 100% and% specificity of 75%. With control of infection plasma PCT levels1 dropped rapidly and significantly [p<0.01, respectively]. Procalcitonin is a useful diagnostic and differential diagnostic marker for the detection of acute LRTI showing higher levels with bacterial etiologies. Moreover, its rapid decline with successful control of the infection promotes its application as a marker for successful treatment and for the prognosis of the clinical outcome of the patients