Ventilated Preterm Infants Research Articles

Endoglin (CD105) Up-regulation in Pulmonary Microvasculature of Ventilated Preterm Infants

Preterm infants exposed to mechanical ventilation and oxygen are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development. Studies have described disruption of microvascular development in BPD, characterized by primitive angioarchitectural patterns reminiscent of the canalicular/saccular stages of lung development. The molecular regulation of this BPD-associated dysangiogenesis remains undetermined. Endoglin (CD105), a hypoxia-inducible transforming growth factor-beta coreceptor, has been implicated as an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions. The aim of this study was to investigate the expression of endoglin and other angiogenesis-related factors in ventilated preterm human lungs. We have studied endoglin protein and mRNA expression in postmortem lungs of short-term and long-term ventilated preterm infants. Control subjects were age-matched infants who had lived for less than 1 hour. Lungs of short-term ventilated preterm infants showed significant upregulation of endoglin mRNA and protein levels, immunolocalized to the microvasculature. Similar but more variable endoglin upregulation was noted in lungs of long-term ventilated infants with BPD. The mRNA levels of vascular endothelial growth factor, angiopoietin-1, and their respective receptors were significantly lower in ventilated lungs than in age-matched nonventilated control lungs. BPD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as endoglin, which may contribute to BPD-associated microvascular dysangiogenesis.

Methods and evidence on volume-targeted ventilation in preterm infants

Several modalities of volume-targeted ventilation have been developed for the premature infant or were adopted from those used in older populations. The article describes these modalities, their clinical application in preterm infants and reviews the evidence for the possible beneficial effects in this population. Evidence from physiologic studies indicates increased stability of tidal volume and gas exchange while requiring less ventilatory support. Randomized trials of volume-targeted ventilation indicate faster weaning and shorter duration of mechanical ventilation, but this has not resulted in better respiratory outcome. The proposed benefits of volume-targeted ventilation on respiratory outcome have not been fully confirmed by the existing data. Some trends suggest possible benefits, but these need to be further explored. The efficacy of volume-targeted ventilation may be method dependent and may also be influenced by the magnitude of the volume targeted.

Caffeine enhances sodium influx and sodium‐linked fluid transport in respiratory epithelium

Caffeine minimizes the time on assisted ventilation in premature infants, possibly as a result of an effect on central respiratory drive. Alternatively, we considered that caffeine improves outcome as a result of improved lung water balance. To test this notion, we studied the effect of caffeine on ion transport in cultured lung cells. We treated an immortal lung epithelial cell line (A549) and distal lung epithelial cells from fetal sheep (FDLE) with caffeine (10−5 M) for 24 h and measured the accumulation of 22Na through pathways that are inhibited by amiloride. Caffeine increased the fraction of amiloride‐sensitive Na uptake by 25% in both cell lines (A549: control 214 ± 51 v caffeine 282 ± 133; FDLE: control 126 ± 29 v caffeine 150 ± 48 nmol/mg protein/5 min, P < 0.05). To study the associated change in fluid movement, we grew the cells on a semi‐permeable surface and measured the change in protein concentration in the supernatant as an index of fluid movement across the monolayer. Caffeine treatment as above increased fluid clearance by 30% (A549: control 106 ± 29 v caffeine 137 ± 26; FDLE: control 79 ± 29 v caffeine 106 ± 30 μL/24h, P < 0.05), an effect that was inhibited in the presence of amiloride (A549: control 61 ± 24 v caffeine 69 ± 25; FDLE: control 103 ± 14 v caffeine 109 ± 16 μL/24h). Our results indicate caffeine increases transepithelial sodium reabsorption and fluid movement through amiloride‐sensitive pathways. We speculate that the beneficial effect of caffeine on respiratory function in the premature lung may be, at least in part, a result of an improvement in lung water balance.

Plasma Biomarkers of Oxidative Stress: Relationship to Lung Disease and Inhaled Nitric Oxide Therapy in Premature Infants

Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress. As part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of <1250 g birth weight who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Plasma was assayed for total protein and for 3-nitrotyrosine and carbonylation by using immunoassays. The demographic characteristics and primary outcome for the infants were representative of the entire group of infants who were in the Nitric Oxide Chronic Lung Disease Trial. For all infants at baseline, before receiving study gas, the concentration of total protein was inversely correlated with the respiratory severity score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1-10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation. Inhaled nitric oxide treatment for premature infants who are at risk for bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy.

Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone

To study the association between angiopoietin 2 (Ang2) concentrations in tracheal aspirates (TAs) and adverse outcome (bronchopulmonary dysplasia (BPD)/death) in ventilated premature infants (VPIs) and modulation of Ang2 concentrations with dexamethasone (Dex) use. Serial TA samples were collected on days 1, 3, 5 and 7, and Ang2 concentrations were measured. Ang2 TA concentrations were compared prior to and after 48 to 72 h of using Dex. A total of 151 TA samples were collected from 60 VPIs. BPD was defined as the oxygen requirement at 36 weeks postmenstrual age (PMA). Twelve infants (mean+/-s.d.) (gestational age (GA) 26.5+/-2.1 weeks, birth weight (BW) 913+/-230 g) had no BPD, 32 infants (GA 25.8+/-1.4 weeks, BW 768+/-157 g) developed BPD and 16 infants (GA 24.5+/-1.1 weeks, BW 710+/-143 g) died before 36 weeks PMA. Ang2 concentrations were significantly lower in infants with no BPD (median, 25th and 75th percentile) (157, 16 and 218 pg mg(-1)) compared with those who developed BPD (234, 138 and 338 pg mg(-1), P=0.03) or BPD and/or death (234, 157 and 347 pg mg(-1), P=0.017), in the first week of life. Twenty-six VPIs (BW 719+/-136 g, GA 25.1+/-1.3 weeks) received 27 courses of Dex. Ang2 concentrations before starting Dex were 202, 137 and 278 pg mg(-1) and significantly decreased to 144, 0 and 224 pg mg(-1) after therapy (P=0.007). Higher Ang2 concentrations in TAs are associated with the development of BPD or death in VPIs. Dex use suppressed Ang2 concentrations.

Optimal Endotracheal Tube Tip Position in Extremely Premature Infants

Although right main bronchus intubation is associated with adverse consequences, the optimal endotracheal tube (ETT) tip position above the carina in neonates is not known. The aim of this study was to determine the association between ETT tip position and adverse pulmonary effects as assessed by chest radiographs (CXRs). Lung aeration was examined after masking ETT positions in the first two CXRs taken after birth in 74 consecutive ventilated premature infants <or= 28 weeks. All the CXRs of the infants during the first week were examined for predefined combined adverse pulmonary outcomes by two examiners (right upper lobe collapse, localized pulmonary interstitial emphysema [PIE], and pneumothorax). Infants who had ETT tips below T4 or in the right main bronchus were excluded. The ETT tip was above T1 in 4 (5.4%), at T1 in 11 (14.8%), at T2 in 19 (25.6%), at T3 in 27 (36.5%), and at T4 in 13 (17.6%) infants. The patients were categorized into group A (ETT tips at T1/2) or group B (ETT above T1 or below T2). The combined adverse pulmonary outcome of pneumothorax, localized PIE, and right upper lobe collapse was significantly higher in group B compared with group A ( P=0.03). On logistic regression analysis, the only independent association for adverse pulmonary outcome and asymmetrical lung aeration was the ETT position. The odds ratio for developing nonuniform lung aeration was 6 (95% confidence interval [CI] 1.8, 20) and for adverse pulmonary outcome was 8 (95% CI 1.1, 73) when the ETT tip was at T3/T4 compared with T1/2. We concluded that the ETT tip should be kept at the level of the first or second thoracic vertebrae in extremely premature babies to reduce the incidence of nonuniform lung aeration and adverse pulmonary outcomes.

Analysis of bacterial colonization in lower respiratory tract and pathogens for ventilator-associated pneumonia in ventilated premature

目的 了解机械通气早产儿下呼吸道定植细菌菌谱,并进一步探讨呼吸机相关性肺炎(VAP)的病原学细菌谱及耐药性.方法 对2004年1月～2005年12月我院早产儿监护病房住院的165例机械通气患儿行支气管肺泡灌洗液定量培养和药敏试验,进行细菌监测.结果 机械通气3 d以上的患儿全部出现下呼吸道的细菌定植,其中有37.5%(62/165)的患儿诊断为VAP.支气管肺泡灌洗液定量培养均以G-杆菌为主,其中肺炎克雷白杆菌、铜绿假单胞菌、鲍曼不动杆菌分别占前3位;VAP的病原菌耐药性分析显示对头孢类抗生素广泛耐药,而对亚胺培南-西司他丁、头胞哌酮/舒巴坦钠、环丙沙星仍保持较高敏感性.结论 G-杆菌是机械通气患儿下呼吸道定植和VAP的优势菌群,对目前临床常用抗生素有多重耐药现象。

Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome

Both prophylactic and early surfactant replacement therapy reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS) compared with later selective surfactant administration. However, continued post-surfactant intubation and ventilation are risk factors for bronchopulmonary dysplasia (BPD). The purpose of this review was to compare outcomes between two strategies of surfactant administration in infants with RDS; prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation. To compare two treatment strategies in preterm infants with or at risk for RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation vs. later selective surfactant administration, continued mechanical ventilation, and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (who receive surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (who receive prophylactic surfactant administration within 15 minutes after birth). Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2006), CINAHL (1982 to December Week 2, 2006), EMBASE (1980 - December 2006), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006), Pediatric Research (1990 - 2006), abstracts, expert informants and hand searching. No language restrictions were applied. Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation vs. selective surfactant administration continued mechanical ventilation, and extubation from low respiratory support. Data were sought regarding effects on the incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, duration of oxygen therapy, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Stratified analysis was performed according to inspired oxygen threshold for early intubation and surfactant administration in the treatment group: inspired oxygen within lower (FiO2< 0.45) or higher (FiO2 > 0.45) range at study entry. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. Six randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs and symptoms of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.67, 95% CI 0.57, 0.79], air leak syndromes [typical RR 0.52, 95% CI 0.28, 0.96] and BPD [typical RR 0.51, 95% CI 0.26, 0.99]. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.62, 95% CI 1.41, 1.86]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.57 doses per patient, 95% CI 0.44, 0.69]. In stratified analysis by FIO2 at study entry, a lower threshold for treatment (FIO2< 0.45) resulted in lower incidence of airleak [typical RR 0.46 and 95% CI 0.23, 0.93] and BPD [typical RR 0.43, 95% CI 0.20, 0.92]. A higher treatment threshold (FIO2 > 0.45) at study entry was associated with a higher incidence of patent ductus arteriosus requiring treatment [typical RR 2.15, 95% CI 1.09, 4.13]. Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2< 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2< 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation.

Azithromycin Suppresses Activation of Nuclear Factor-kappa B and Synthesis of Pro-inflammatory Cytokines in Tracheal Aspirate Cells From Premature Infants

Nuclear factor-kappaB (NF-kappaB) plays a central role in regulating key proinflammatory mediators. The activation of NF-kappaB is increased in tracheal aspirate (TA) cells from premature infants developing bronchopulmonary dysplasia (BPD). We studied the effect of azithromycin (AZM) on the suppression of NF-kappaB activation and the synthesis of pro-inflammatory cytokines IL-6 and IL-8 by TA cells obtained from premature infants. Tracheal aspirate cells were stimulated with tumor necrosis factor-alpha (TNF-alpha) and incubated with AZM. The nuclear NF-kappaB-DNA binding activity, the levels of inhibitory kappaB-alpha (IkappaB-alpha) in the cytoplasmic fraction and IL-6 and IL-8 release in the cell culture media were measured. Stimulation of TA cells by TNF-alpha increased the activation of NF-kappaB, which was suppressed by the addition of AZM. Increased activation of NF-kappaB was also associated with increased levels of pro-inflammatory cytokines (IL-6 and IL-8). AZM significantly reduced the IL-6 and IL-8 production to the levels similar to control. TNF-alpha stimulation also increased the degradation of IkappaB-alpha, which was restored with the addition of AZM. Our data suggest that AZM therapy may be an effective alternative to steroids in reducing lung inflammation and prevention of BPD in ventilated premature infants.

Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant

BackgroundDeleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function.MethodsDMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA.ResultsPulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation.ConclusionOur data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease.

The effect of inhaled nitric oxide on pulmonary function in preterm infants

Bronchopulmonary dysplasia (BPD) in preterm infants is associated with impaired alveolar growth, inflammation and airway hyperreactivity. In animal models of BPD, inhaled nitric oxide (NO) improves alveolar growth and inhibits airway smooth muscle proliferation. This study was designed to assess the effect of inhaled NO on resistance and compliance in ventilated preterm infants with evolving BPD. Expiratory resistance and compliance of the respiratory system were measured in 71 ventilated preterm infants, < or = 32 weeks gestation, randomized to NO (n=34) versus placebo (n=37) for > or = 24 days at 7 to 21 days of life. At baseline expiratory resistance (231+/-71 versus 215+/-76 cm H(2)O l(-1) s(-1)) and compliance (0.49+/-0.14 versus 0.53+/-0.13 ml cm H(2)O(-1) kg(-1)) were comparable between placebo and NO groups, respectively. There was no effect of NO on expiratory resistance or compliance at 1 h, 1 week or 2 weeks of study gas administration. NO had no short- or medium-term effect on expiratory resistance or compliance in ventilated preterm infants.

Neurobehavior of Preterm Infants at 36 Weeks Postconception as a Function of Morphine Analgesia

This study evaluated early neurobehavioral outcomes in ventilated preterm infants randomized to receive morphine analgesia or placebo in the Neurological Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial. Eight hundred and ninety-eight infants between 23 and 32 weeks of gestation were randomized to receive preemptive morphine analgesia (morphine) or placebo. Infants also received additional analgesia (AA) with open-label morphine. The Neurobehavioral Assessment of the Preterm Infant (NAPI) was used to evaluate 572 of 793 survivors (72.1%) at 36 weeks of postconceptual age. The Neonatal Medical Index (NMI) was used to evaluate the severity of medical complications. Regression analyses were used to determine the effect of covariates. Infants were equally distributed in morphine and placebo groups with similar neonatal and demographic characteristics. Infants assessed with the NAPI were more likely to have sepsis ( P = 0.03), bronchopulmonary dysplasia ( P = 0.02), and longer length of stay ( P = 0.008). Infants randomized to the morphine group had higher NMI scores (odds ratio [OR]; 95% confidence interval [CI]: 1.75; 1.23 to 2.50; P = 0.002). Use of AA was associated with higher NMI scores (OR; 95% CI: 4.5; 2.9 to 5.9; P < 0.001). Of the NAPI subscales, the (mean +/- standard deviation [SD]) popliteal angle cluster scores were significantly higher in the morphine group compared with placebo (51.2 +/- 33.2 versus 45.0 +/- 33.5; P = 0.03). AA use was associated with lower (mean +/- SD) MOTOR scores in the morphine group (48.2 +/- 16.1 versus 52.7 +/- 19.1; P = 0.03) and with lower POPLITEAL ANGLE cluster scores in both the morphine group (41.5 +/- 34.0 versus 59.5 +/- 30.1; P < 0.0001) and the placebo group (40.8 +/- 36.8 versus 49.4 +/- 28.0; P = 0.004). No differences were noted in the other NAPI subscales cluster scores in either subgroup. We conclude that morphine analgesia may result in subtle neurobehavioral differences in premature infants.

Role of Abdominal Muscles Activity on Duration and Severity of Hypoxemia Episodes in Mechanically Ventilated Preterm Infants

Background: Episodes of hypoxemia are often observed in ventilated preterm infants. The factors that determine their duration, severity and the failure of the mechanical breaths to maintain ventilation have not been fully defined. Objective: To determine the relation between activity of the abdominal muscles and the duration and severity of hypoxemia episodes in ventilated preterm infants. Methods: Clinically stable ventilated preterm infants weighing between 500 and 1,000 g at birth, who presented with frequent episodes of hypoxemia, were studied. Recordings of arterial oxygen saturation (SpO₂), tidal volume and abdominal surface electromyography were obtained during 4 h to assess the temporal relationship between activation of abdominal musculature with the onset, duration and severity of hypoxemia episodes. Results: In 15 infants, GA (mean ± SD) 25 ± 1.5 weeks, BW 697 ± 141 g, age 37 ± 14 days, synchronized intermittent mandatory ventilation rate 17 ± 6 breaths/min, peak inspiratory pressure 18 ± 1.9 cm H₂O, positive end-expiratory pressure 4.8 ± 0.6 cm H₂O, and fraction of inspired oxygen (FiO₂) 0.4 ± 0.1 were studied. These infants presented with 7.2 ± 4.4 episodes of hypoxemia (SpO₂ <88%) per hour. The number of abdominal muscle contractions per episode correlated with the duration and severity of the episodes of hypoxemia. The episode duration increased by 14 ± 18 s per abdominal muscle contraction. The lowest SpO₂ reached during an episode of hypoxemia decreased by 1.7 ± 1.4% for every abdominal muscle contraction. Conclusions: These data document a relationship between abdominal muscles contraction and the duration and severity of hypoxemia episodes in ventilated preterm infants. These findings can explain the failure of mechanical ventilation to prevent their occurrence or decrease their severity.

Cardiorespiratory effects of changes in end expiratory pressure in ventilated newborns

Background:Positive pressure ventilation in premature infants can improve oxygenation but may diminish cerebral blood flow and cardiac output. Low superior vena cava (SVC) flow increases risk of intraventricular haemorrhage, and...

A review on noninvasive ventilation: The Cochrane Systematic Reviews 2006

The following is an overview of the evidence evaluating the risks and benefits of noninvasive methods of ventilation in premature infants. This evidence is taken from a variety of reviews in the Cochrane Library that address the issue of continuous distending pressure (CDP) or nasal intermittent positive pressure ventilation (NIPPV).

Nasal Intermittent Mandatory Ventilation Versus Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome: A Randomized, Controlled, Prospective Study

To evaluate whether nasal intermittent mandatory ventilation (NIMV) compared with nasal continuous positive airway pressure (NCPAP) would decrease the requirement for endotracheal ventilation in the treatment of respiratory distress syndrome (RDS) in preterm infants <35 weeks. Randomized, controlled, prospective, single-center study. Forty-one infants were randomized to NCPAP and 43 comparable infants to NIMV (birth weight 1533 +/- 603 vs 1616 +/- 494 g, gestational age 30.6 +/- 3.0 vs 31.1 +/- 2.3 weeks, P = .5, respectively). Infants treated with NIMV and with NCPAP had comparable cardio-respiratory status at study entry. In the total cohort, infants treated initially with NIMV needed less endotracheal ventilation than infants treated with NCPAP (25% vs 49%, P < .05) with a similar trend in infants <1500 g; 31% vs 62%, P =. 06). When controlling for weight and gestational age, NIMV was more successful in preventing endotracheal ventilation (P < .05). Infants treated with NIMV had a decreased incidence of bronchopulmonary dysplasia (BPD) compared with those treated with NCPAP (2% vs 17%, P <. 05, in the total cohort and 5% vs 33%, P <. 05, for infants <1500 g). NIMV compared with NCPAP decreased the requirement for endotracheal ventilation in premature infants with RDS. This was associated with a decreased incidence of BPD.

TNF-a and IL-10 levels in tracheobronchial lavage of ventilated preterm infants and subsequent lung function

The role of airway inflammation in ventilated preterm newborns and the risk factors associated with the development of chronic lung disease are not well understood. Our objective was to analyze the association of the airway inflammatory response in ventilated preterm infants by serial measurements of TNF-alpha and IL-10 in tracheobronchial lavage (TBL) with perinatal factors and lung function measured early in life. A series of TBL samples were collected from ventilated preterm infants (less than 32 weeks of gestational age) and concentrations of TNF-alpha and IL-10 were measured by ELISA. Pulmonary function tests were performed after discharge by the raised volume rapid compression technique. Twenty-five subjects were recruited and 70 TBL samples were obtained. There was a significant positive association between TNF-alpha and IL-10 levels and length of time between the rupture of the amniotic membranes and delivery (r = 0.65, P = 0.002, and r = 0.57, P < 0.001, respectively). Lung function was measured between 1 and 22 weeks of corrected age in 10 patients. Multivariable analysis with adjustment for differences in lung volume showed a significant negative association between TNF-alpha levels and forced expiratory flow (FEF(50); r = -0.6; P = 0.04), FEF(75) (r = -0.76; P = 0.02), FEF(85) (r = -0.75; P = 0.03), FEF(25-75) (-0.71; P = 0.02), and FEV(0.5) (r = -0.39; P = 0.03). These data suggest that TNF-alpha levels in the airways during the first days of life were associated with subsequent lung function abnormalities measured weeks or months later.

Nerve growth factor levels in the bronchial aspirates of ventilated preterm infants

Nerve growth factor levels in the bronchial aspirates of ventilated preterm infants

Outcome of Extremely Preterm Infants Randomized at Birth to Different PaCO2 Targets during the First Seven Days of Life

Background: Ventilation with higher PaCO₂ goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO₂ goal than in previous trials. Objective: To determine the clinical benefits and safety of higher PaCO₂ goals for ventilated preterm infants. Study Design: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO₂ target between 55 and 65 mm Hg (7.3– 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7– 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18–22 months corrected age. Results: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). Conclusion: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.

The lung in the balance: arginine, methylated arginines, and nitric oxide

the lung is a major source of nitric oxide (NO), be it from nitric oxide synthase (NOS) III in the endothelium of the vast pulmonary circulation, NOS II in the epithelium of the large surface area of the airways, or NOS I in the nonadrenergic noncholinergic nerves ([6][1]). NO produced in the lung