John Loggins

Monocyte chemoattractant protein-1 and interleukin-8 are increased in bronchopulmonary dysplasia: relation to isolation of Ureaplasma urealyticum.

Background An exaggerated inflammatory response occurs in infants who subsequently develop bronchopulmonary dysplasia (BPD). Ureaplasma urealyticum (Uu) is frequently isolated from cultures of tracheal secretions obtained from very low birth weight infants and is associated with an increased risk of BPD. Methods We examined the relationships between isolation of genital mycoplasmas, tracheal aspirate (TA) interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) concentrations and the development of BPD. Serial TAs were obtained prospectively from 35 very low birth weight infants, and IL-8 and MCP-1 concentrations were determined by enzyme-linked immunoadsorbent assay. Tracheal cultures for bacteria and genital mycoplasmas were performed on aspirates obtained during the first 2 days of life. Results Infants who developed BPD (n=18) were less mature (25.2±0.2 vs 27.8±0.5 weeks; P <0.001), of lower birth weight (746±28 vs 1052±41 g; P <0.001), and more likely to have a positive tracheal culture for Uu (39% vs 6%; P=0.026) than those who did not develop BPD (n=17). Tracheal concentrations of IL-8 and MCP-1 were significantly increased in infants who developed BPD (IL-8: P=0.0001; MCP-1: P <0.001, analysis of variance) and correlated with duration of mechanical ventilation and oxygen treatment. Uu-positive infants had an increased incidence of BPD (88% in infants with Uu vs 42% in infants without Uu; P=0.020) and had TA concentrations of IL-8 and MCP-1 that were significantly increased compared with those of Uu-negative infants. Conclusions Increased TA concentrations of IL-8 and MCP-1 during the first 2 weeks of life are associated with the development of BPD. Recovery of Uu from TAs is associated with a more robust inflammatory reaction and an increased risk of BPD.

Tumor necrosis factor alpha -- 308 polymorphism associated with increased sepsis mortality in ventilated very low birth weight infants.

Background: Sepsis commonly complicates the clinical course of critically ill very low birth weight infants, with as many as 30% developing hospital-acquired bacteremia. The tumor necrosis factor &agr; (TNF-&agr;) −308 G/A single nucleotide polymorphism (SNP) is associated with adverse outcome in septic adult patients. Methods: One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-&agr; −308 G/A SNP. Results: One hundred twenty (69%) infants were homozygous GG, 45 (26%) were heterozygous AG and 8 (5%) were homozygous AA; 2 of 120 (2%) infants developed early bacteremia in the GG group, and 1 of 53 (2%) developed early bacteremia in the AA/AG group (P = 0.919). One or more episodes of late bacteremia/fungemia developed in 59 of 120 (49%) infants with the GG genotype and 23 of 53 (43%) infants with the AG/AA genotype (P = 0.484). Endotracheal tube colonization rates were 65 of 120 (54%) for infants with the GG genotypes and 28 of 53 (53%) for infants with the AG/AA genotypes (P = 0.871). Nosocomial pneumonia developed in a similar number of infants in both genotype groups (9 of 120 infants vs. 3 of 53 infants; P = 0.461). Mortality from sepsis was 3 times greater in infants with the AA/AG genotypes than in those with the GG genotype (10%vs. 3%; P = 0.038). This difference in sepsis mortality was even greater when only bacteremic/fungemic infants are considered (4 of 59 infants vs. 6 of 23 infants; P = 0.026). Conclusions: These data suggest that the TNF-&agr; −308 A allele does not affect the development of sepsis in ventilated premature infants but may increase mortality once sepsis develops.

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Does Not Alter Sepsis Outcome in Ventilated Very Low Birth Weight infants

OBJECTIVE:This study compared the effect of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms on the incidence and outcome of sepsis in ventilated very low birth weight infants.STUDY DESIGN:Infectious complications were retrospectively determined in 295 (234 African-American, 58 Caucasian and three Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 g at birth) and compared ACE I/D genotype.RESULTS:The incidence of the D allele in the study population was 0.60. A total of 113 (38.3%) infants were homozygous DD, 128 (43.4%) were heterozygous ID and 54 (18.3%) were homozygous II. One or more episodes of late BSI developed in 28 (52%) of 54 infants with the II genotype, 66 (52%) of 128 infants with the ID genotype and 52 (46%) of 113 infants with the DD genotype (p=0.618). Neither the rates of non-CONS BSI (II: 24%, ID: 23%, DD: 22%; p=0.937) nor multiple bacteremic/fungemic episodes (II: 13%, ID: 16%, DD: 12%; p=0.641) were different between genotype groups. The ACE I/D polymorphism had no effect on sepsis-related mortality (II: 7%, ID: 5%, DD: 4%; p=0.692). Sepsis mortality for infants with late BSI was 14% in infants with the II genotype, 9% with the ID genotype and 10% with the DD genotype (p=0.764).CONCLUSIONS:The ACE I/D polymorphism does not have a significant effect on the incidence or outcome of sepsis in ventilated VLBW infants.

Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

BackgroundChronic lung disease (CLD) in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB), a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA) concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS), its relationship to the development of CLD, pulmonary hemorrhage (PH) and its relationship to airway colonization with Ureaplasma urealyticum (Uu).MethodsInfants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques.ResultsFifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway.ConclusionsPDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD.

Pulmonary Hemorrhage (PH) Is Associated with Increased Tracheal Concentrations of Pro-Inflammatory Cytokines and Increased Risk of Bronchopulmonary Dysplasia (BPD)

Pulmonary Hemorrhage (PH) Is Associated with Increased Tracheal Concentrations of Pro-Inflammatory Cytokines and Increased Risk of Bronchopulmonary Dysplasia (BPD)

Monocyte chemoattractant protein (MCP-1) is increased in tracheal aspirates of infants that develop bronchopulmonary dysplasia (BPD). 1606

Monocyte chemoattractrant protein-1 (MCP-1), a monocyte chemoattractrant and activating chemokine has been implicated in the pathogenesis of fibrotic lung diseases. We wanted to determine if tracheal aspirate concentrations of MCP-1 correlated with the development of BPD (defined as requirement for supplemental oxygen with compatible Xray changes at 28 days). Tracheal aspirates were obtained from 24 very low birth weight infants during the first 2 weeks of life. Concentrations of MCP-1 and secretory component of IgA concentrations were determined by ELISA. Concentrations of MCP-1 were normalized to secretory component, which does not change with inflammation or steroid use. Tracheal concentrations of MCP-1 increased from day 1 through day 5 in infants with RDS. However, infants with BPD had significantly greater concentrations of MCP-1 than infants that did not develop BPD at all days examined.These results demonstrate a correlation between increased MCP-1 concentrations and the development of BPD. Thus MCP-1 production and subsequent macrophage activation may contribute to the pathogenesis observed in BPD. Concentrations of MCP-1 are expressed as pg MCP-1/ug Secretory Component. Data represent Mean±SE (*p<0.05). Table