Respiratory mechanics in very low birth weight infants during continuous versus intermittent gavage feeds.

This study was designed to determine whether respiratory mechanics in stable, very low birth weight infants changed after replacing intermittent feeds with continuous feeding. We measured static respiratory system compliance, respiratory system resistance, functional residual capacity (FRC), and tidal volume immediately before feeds and at 20, 60, and 120 min after feeds, and again the next day on continuous feeds. Patients selected for enrollment into the study needed to fulfill the following criteria: 1) birth weight and postnatal weight < 1,500 g, 2) no need for mechanical ventilation, positive airway pressure, or supplemental oxygen, 3) receiving and tolerating at least 100 mL/kg/day of intermittent gavage feeds, and 4) no change in methylxanthine or diuretic dosage for 3 days before the study. Respiratory mechanics were measured using the SensorMedics 2600 Pediatric Pulmonary Cart (Yorba Linda, CA). We studied 16 infants (gestational age 28.3 +/- 3.7 weeks, mean +/- SD) at a postnatal age of 10-82 days. The average interindividual coefficient of variance was 20 +/- 2% for static compliance, 35 +/- 6% for resistance, 18 +/- 3% for FRC, and 19 +/- 3% for tidal volume. Repeated-measures analysis of variance did not reveal any significant difference in respiratory mechanics with intermittent vs. continuous feeding. The data suggest that static respiratory mechanics in stable, very low birth weight infants are not affected by changing enteral feeds from intermittent gavage to a continuous schedule.     

Neonatal chest wall suspension splint: a novel and noninvasive method for support of lung volume

Surfactant and musculoskeletal immaturity results in lower compliance of the lung relative to the chest wall, with clinical manifestations of low lung volume, marked chest wall retractions (CWR), and thoracoabdominal asynchrony. Inspiratory efforts are dissipated on distorting the chest wall inward rather than recruiting lung volumes. The current study tests the hypothesis that a novel neonatal chest wall suspension splint (SP), designed to provide stability to the compliant chest wall, would reduce inspiratory chest wall retractions and improve lung volumes. Nine preterm infants (29 +/- 1 SE weeks of gestation; 1.59 +/- 0.27 SE kg study weight) were studied at 16 +/- 5 SE days of life at baseline (BL) and following application of the front plate (FP) and the full SP (Hug n Snug Neonatal Chest Splint, Respironics, Inc.). Phase angle of thoracoabdominal motion, CWR, functional residual capacity (FRC), and pulmonary function were evaluated during spontaneous breathing. Compared to BL, there was a significant decrease in anterior CWR (2.21 +/- 0.91 SE vs. 0.25 +/- 0.09 SE mm; P < 0.05), an increase in FRC (16.6 +/- 2.8 SE vs. 27.8 +/- 5.5 SE ml/kg; P < 0.05) and tidal volume (4.8 +/- 1.5 SE vs. 7.3 +/- 1.4 SE ml/kg; P < 0.05), minimal effect on pulmonary compliance (1.98 +/- 0.50 SE vs. 1.72 +/- 0.30 SE ml/cmH2O/kg), and a trend for a decrease in phase angle (128.4 +/- 10.9 SE vs. 111.8 +/- 19.3 SE) with the application of the splint. FRC correlated inversely with severity of CWR across all conditions (P < 0.05, r = -0.68). Phase angle was directly correlated to anterior CWR (r = 0.72; P < 0.05) and correlated inversely with FRC (P < 0.005; r = -0.56). We speculate that by improving CW stability, the use of this splint may reduce the energetic requirements of breathing and, potentially, the need for more invasive ventilatory support in the neonate.     

Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy

We studied the effect of prenatal maternal cigarette smoking on passive expiratory mechanics in 53 healthy infants tested early in infancy (mean ± SD, 5.1 ± 1.5 weeks). Maternal smoking was measured by: 1) questionnaire reports of the number of cigarettes smoked per day; and 2) urine cotinine concentrations (corrected for creatinine) at each visit. Respiratory system mechanics were assessed by the single-breath occlusion-passive-flow-volume maneuver. In ten infants born to smoking mothers the time constant of the respiratory system was 23% reduced [0.34 vs. 0.44 s; 95% confidence interval (CI), ?45% + 1%; P = 0.06]. This was related to an estimated 13% decrease in respiratory system compliance (4.86 vs. 5.62 Ml/cmH₂O; 95%Cl, ?33% + 6%; P = 0.18) and a 10% reduction in respiratory system resistance (0.073 vs. 0.081 cmH H₂O/mL/s; 95%Cl, ?42% + 22%; P = 0.56). Functional residual capacity (FRC), measured by helium-dilution, was also decreased by 13% (78 vs. 90 mL; 95%Cl, ?27% + 0.3%; P = 0.06) in smoke-exposed infants. Forced expiratory flow rates at FRC obtained by thoraco-abdominal compression were reduced by 28% in infants of smoking mothers (VFRc, 99 vs. 138 rnlis; 95%Cl, ?54% + 2%; P = 0.04), as reported previously in a larger sample from this population. This study was limited by small numbers of infants exposed to smoking during pregnancy and by ethnic imbalance among the smoking-exposed and unexposed groups. Nevertheless, it suggests that the diminished forced expiratory flows observed in infants exposed in utero to maternal tobacco smoking (UTS) are not attributable to increases in lung compliance, resistance, or a delay in passive lung emptying. Rather, the data support the hypothesis that UTS exposure may cause a reduction in airway size as well as alterations in the growth and/or maturation of passive mechanical properties of the respiratory system in healthy newborns. © 1995 Wiley-Liss, Inc.     

Rehospitalisations for respiratory disease and respiratory syncytial virus infection in preterm infants of 29-36 weeks gestational age

BACKGROUND: To evaluate rates of rehospitalisation due to respiratory illness in preterm infants of 29-36 weeks gestation without chronic lung disease. PATIENTS AND METHODS: Retrospective single centre cohort study including infants from 1998 to 1999 with follow-up over two respiratory syncytial virus (RSV) seasons. RESULTS: Of 435 infants included 61 infants (14%) experienced 78 rehospitalisations. The overall RSV attack rate was 4.4% over two consecutive RSV seasons for infants below 6 months of age at onset of RSV season (7.7 and 1.1%, respectively, p=0.015), with significant differences between infants of 29-32 and 33-36 weeks gestational age (10.5% vs. 2.3%, p=0.008). None of the infants needed mechanical ventilation or admission to the intensive care unit. Infants with RSV infection were younger of age (mean 4.2 vs. 8.2 months; p=0.015), had longer stays at the hospital (11.5 vs. 7.0 days; p=0.006), and more severe courses of disease (score 3.0 vs. 1.8; p<0.001). Additional risk factors for RSV infection were multiple gestation (OR 5.5; CI 95% 1.439-21.028) and congenital heart disease (OR 4.2; CI 95% 1.005-17.669). CONCLUSION: The total burden of respiratory disease and RSV infection in this population was low. A lower gestational age, multiple gestation, and congenital heart disease were associated with increased risk of RSV infection.     

Predictive value of measurements of respiratory mechanics in preterm infants with HMD

Conventional methods for measuring respiratory mechanics model the respiratory system as a single compartment. The interrupter technique allows the respiratory system to be considered as a two compartment model with “flow resistance” of the conducting airways (Pinit), calculated from the initial pressure drop (Pinit), considered separately from Pdiff, as a measure of the viscoelastic properties of the lung and chest wall and any pendelluft present. The pulmonary mechanics of 50 intubated and mechanically ventilated preterm infants (≤1500 g) were studied during the first week of life using conventional methods and the interrupter technique to determine whether it was possible to predict which infants would develop bronchopulmonary dysplasia (BPD). Pulmonary mechanics of preterm infants intubated and ventilated for apnea of prematurity were also studied. The dynamic compliance of the respiratory system (C_rsdyn) was significantly lower on day 1 (P<0.001) and during the first week of life in the infants with HMD who developed BPD (ANOVA, P<0.0001). There was no significant difference in the respiratory system resistance (R_rs), Rinit, or Pdiff between BPD and no-BPD groups. However, Pdiff was significantly higher in infants with HMD, regardless of the outcome, when compared to the infants ventilated for apnea of prematurity. This suggests that the pathology of HMD is distal to the conducting airways and significantly alters the viscoelastic properties of the lung on day 1. Using stepwise logistic regression, C_rsdum on day 1 and birth weight or gestational age were significant independent predictors of the development of BPD, correctly classifying 92% of infants. Due to the correlation between birth weight and gestational age (r = 0.72, P<0.0001). only one of these variables was necessary in the prediction model. In conclusion, C_rsdyn is a better independent predictor of the development of BPD in preterm infants with HMD than gestational age or birth weight. Pediatr Pulmonol. 1993; 16:116–123. © 1993 Wiley-Liss, Inc.     

Abnormal lung function in healthy preterm infants.

The aim of this study was to assess the consequences of preterm birth for the functional development of the lungs. We studied 32 healthy preterm infants (gestational age 25 to 33 wk at birth) and 53 healthy full-term infants (37 to 42 wk) at the same mean postmenstrual age of 40 wk with a multibreath nitrogen washout technique to assess functional residual capacity (FRC), gas mixing efficiency, and dead space and with the single-breath occlusion technique to calculate compliance and resistance of the respiratory system. Twenty of the preterm infants were also assessed with the same methods at 34.2 (32 to 37) wk. At the same postmenstrual age the preterm infants had lower FRC/kg body weight, lower specific compliance, impaired gas mixing efficiency, and higher total and dead space ventilation/kg than the full-term infants. Specific compliance and specific conductance decreased but gas mixing efficiency increased from 34 to 40 wk. We conclude that premature exposure to extrauterine conditions changes lung function. Preterm infants showed signs of dysfunction of the terminal respiratory units and higher elastic recoil than infants who spent the corresponding time for development in utero. It is suggested that preterm birth per se affects alveolarization and formation of elastic tissue in the lungs.     

Development of Lung Function in Preterm Infants During the First Two Years of Life

IntroductionIt remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30 + 0 to 35 + 6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF_25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV_0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.     

Relationship of symptoms to lung function abnormalities in preterm infants at follow-up.

Recurrent respiratory symptoms are common in preterm infants in the first 2 years of life. The aim of this study was to determine the lung function abnormalities associated with such symptoms. Forty preterm infants, with a median gestational age of 29 weeks were studied at a median postnatal age of 12 months. Twenty-two suffered from recurrent symptoms, defined as wheezing and/or coughing on at least 4 days per week over the previous month. Lung function was assessed by measurement of functional residual capacity (FRC), using a helium gas dilution technique, and airway resistance (Raw) and thoracic gas volume (TGV) plethysmographically. No significant difference was found in TGV between symptomatic and asymptomatic infants, but the median FRC was lower (P less than 0.01), Raw higher (P less than 0.01), and FRC:TGV ratio lower (P less than 0.001) in the symptomatic infants. These lung function abnormalities in the symptomatic infants are suggestive of gas trapping.     

Early prediction of chronic oxygen dependency by lung function test results

Chronic oxygen dependency (COD) is a common sequela to very premature birth. Steroid therapy may reduce COD if given within the first 2 weeks, but has important side effects. It is, therefore, crucial to identify an accurate predictor of COD and hence only expose high-risk infants to intervention therapy. The aim of this study was to determine if, within 48 hr of birth, abnormal lung function predicted COD and whether such results performed better than readily available clinical data. Results from 100 consecutive, very low birth-weight infants, median gestation age 28 weeks (range, 24-33), who were ventilated within 6 hr of birth and survived beyond 36 weeks postconceptional age (PCA), were analyzed. Lung volume was assessed by measurement of functional residual capacity (FRC) using a helium gas dilution technique, and compliance was measured using either a passive inflation or an occlusion technique. The maximum peak inflating pressure and inspired oxygen concentration within the first 48 hr were recorded. The infants who remained oxygen-dependent beyond 28 days (n = 58) and 36 weeks PCA (n = 24) differed from the rest in being more immature (P < 0.001), more had a patent ductus arteriosus, and they had both a lower median lung volume (P < 0.001) and lower compliance (P < 0.01) on day 2. An FRC <19 mL/kg and a low gestational age were the most accurate predictors of COD at 28 days. An FRC <19 mL/kg on day 2 remained the best predictor of COD beyond 28 days if only the 50 infants whose gestational age was < or = 28 weeks were considered. We conclude that demonstration of a low lung volume in the first 48 hr helps to identify infants who might benefit from therapy aimed at preventing COD.     

Comparison of dynamic and passive measurements of respiratory mechanics in ventilated newborn infants

Pulmonary mechanics may differ in intubated and ventilated infants depending on whether they are measured by a dynamic or passive method. The objective of this study was to compare respiratory mechanics measured by a dynamic technique with those obtained by a single-breath occlusion technique in ventilated newborn infants. Thirty-one preterm and 15 term infants (mean ± SD: gestational age, 29.3 ± 2.3 and 39.5 ± 1.4 weeks; birth weight, 1.2 ± 0.5 and 3.4 ± 0.4 kg; postnatal age, 12 ± 13 and 5 ± 4 days, respectively) were studied. Flows were measured through a pneumotachometer placed between the endotracheal tube and the ventilator circuit: tidal volume by integration of flow, and airway pressure directly with a pressure transducer. Airway occlusion was performed with a Neonatal Occlusion Valve (Bicore pulmonary monitor) at the end of inspiration, and the following relaxed exhalation was analyzed to give passive respiratory system compliance (C_rs) and resistance (R_rs). These values were compared with dynamic respiratory system compliance (C_dyn) and dynamic expiratory resistance (R_e) obtained with the PEDS system (P) within 1 hour, without an esophageal balloon and on the same ventilator settings. Dynamic respiratory system compliance and resistance measured with the PEDS and the Bicore systems did not differ significantly and were well correlated. Mean C_dyn(P) values in preterm and term infants were 77% and 77% of C_rs the equation of the regression line was c_dyn = 0.75 c_rs + 0.02 and C_dyn = 0.78 c_dyn ? 0.02; and standard error of the estimate (SEE) was 0.2 and 0.3 mL/cmH₂O with a correlation coefficient (r) of 0.89 and 0.89 (P < 0.0001), respectively. The mean R_e (P) values in preterm and term infants were 68% and 64% of R_rs and the equation of the regression line was R_e = 0.3 R_rs + 63 and R_e = 0.5 R_rs + 20, with SEE of 25 and 20 cmH₂O/Lsec, and r of 0.65 and 0.69 (P < 0.0001, P < 0.005). respectively. The two methods are non-invasive and were well tolerated. We conclude that passive and dynamic respiratory compliance and resistance measured in intubated infants are highly correlated, although the values measured by the passive technique are higher than those obtained by the dynamic technique. Pediatr Pulmonol. 1995; 20:258–264 . © 1995 Wiley-Liss, Inc.     

Lung function in 6-20 month old infants born very preterm but without respiratory troubles.

Lung function results of 21 healthy infants born very prematurely are reported. The median gestational age was 29 weeks, but none had developed respiratory distress or required any form of respiratory support in the neonatal period. Lung function was assessed by measurements of thoracic gas volume (TGV) and airway resistance (Raw) plethysmographically, and of functional residual capacity (FRC) using a helium gas dilution technique. Two separate measurements were made between 6 and 20 months of age; all infants were measured once in the first and once in the second year of life. Regression equations were calculated for TGV, Raw, and FRC related to weight, height, and postnatal age. These data provide a new set of values for very preterm infants, in part small for gestational age, without neonatal respiratory trouble.     

Assessment of passive respiratory compliance in healthy preterm infants: A critical evaluation

The airway occlusion techniques for assessing passive respiratory mechanics have become well established methods in fullterm neonates and older infants. The single breath technique (SBT) is frequently used for assessing lung function in intubated infants on neonatal intensive care units. However, less is known about the reliability of these quick and noninvasive techniques in healthy preterm infants. The aim of this study was to evaluate these methods in healthy unintubated preterm infants to facilitate both establishment of reference values and more meaningful interpretation of lung function assessments in the neonatal unit. Forty-seven studies were attempted in 31 healthy preterm infants (gestational age 29–36 weeks; body weight 1.88 ± 0.28 kg; mean ± SD) during the first 2 weeks of life, using both the multiple occlusion technique (MOT) and the SBT. Whereas technically acceptable respiratory system compliance (Crs) data from either the MOT or the SBT were obtained on 37 occasions in 25 infants, satisfactory results from both techniques were achieved only on 22 occasions. In these infants mean ± SD Crs was 28.1± 5.2 mL kPa^?1 when assessed by MOT and 29.1± 5 6.0 mL kPa^?1 when using the SBT. The mean difference between technically satisfactory paired Crs values obtained with MOT and SBT was less than 5% (range, +28 to ?18%). By contrast, in infants in whom data were invalidated as a result of expiratory airflow braking, failure to relax or instability of the end-expiratory level, gross discrepancies occurred between the techniques. In conclusion, assessment of passive respiratory compliance is feasible in healthy, unintubated preterm infants, but strict criteria for quality control should be applied to avoid gross errors in the results. Ideally, passive respiratory mechanics should be assessed using both MOT and SBT in order to increase confidence in the reported results. © 1993 Wiley-Liss, Inc.     

Role of positive end-expiratory pressure changes on functional residual capacity in surfactant treated preterm infants

Both surfactant replacement and positive end-expiratory pressure (PEEP) increase lung volume in infants with respiratory distress syndrome (RDS). We measured pulmonary mechanics and functional residual capacity (FRC) in 21 preterm infants with RDS, > 48 hr post-surfactant therapy (BW, 1,168 ± 441 g; GA, 28.3 ± 2.8 weeks; postnatal age, 3–7 days). A non-linear but significant increase in mean FRC was noted as PEEP increased from 2 to 5 cmH₂O: 18.4 ± 4.7mL/kg at 2 cmH₂O; 19.7 ± 4.3 mL at 3 cm H₂O; 22.6 ± 5.5ml/kg at 4 cmH₂O; and 26.2 ± 6.2 mL/kg at 5 cmH₂O (P < 0.01). Because of the synergistic combined effect on lung volume, surfactant treated neonates should be weaned cautiously from PEEP during ventilatory management. Our study also suggests that the occurrence of inadvertent end-distending pressure during FRC measurement in the ventilated neonate lead to erroneous results. Pediatr Pulmonal. 1994;18:89–92. © 1994 Wiley-Liss, Inc.     

Lung function tests in neonates and infants with chronic lung disease: lung and chest-wall mechanics

This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which differentiate the tissue and airway components of respiratory mechanics, are likely to require further development before they can be of clinical significance.     

Measurement of lung volumes and pulmonary mechanics during weaning of newborn infants with intractable respiratory failure from extracorporeal membrane oxygenation

Newborn infants with intractable respiratory failure who require extracorporeal membrane oxygenation (ECMO) experience diffuse pulmonary atelectasis shortly after initiation of ECMO. Atelectasis is likely due to the primary lung injury and the reduction of applied inspiratory ventilator pressure when the respirator settings are changed to the “rest settings.” These pathophysiologic changes result in a decrease in lung compliance and lung volumes. We hypothesized that improving lung functions observed during ECMO and indicated by an increase in lung volumes will predict successful weaning from ECMO. Sixteen infants (mean SEM: gestational age, 40.3 ± 0.3 weeks; birth weight, 3.5 ± 0.1 kg) with meconium aspiration syndrome (n = 13), sepsis (n = 2), and persistent pulmonary hypertension (n = 1) were studied. We measured passive respiratory system mechanics and lung volumes initially during full ECMO support (115 ± 18 h on ECMO, Study I), and then within 24 h prior to weaning from ECMO (Study 11). Respiratory system compliance (C_rs), respiratory system resistance (Rrs), functional residual capacity (FRC), and tidal volume (V_T) were measured. Prior to Study I lung volumes were too small to be detected. C, increased between Study I and Study II (0.41±0.05 to 0.63±0.05 mL/cmH₂O/kg, P < 0.05), and V_T, increased between Study I and Study II (5.6 ± 0.6 to 10.4 ± 0.8mL/kg, P = 0.0005). FRC increased from 3.6 ± 1.0 to 7.9 ± 0.9mL/kg(P = 0.0001). There was no change in R_rs (88±8 to 89 ± 6 cm H₂O/Us, P = 0.9). The combination of C_rs > 0.5 mL/cmH₂O/kg and FRC > 5 mL/kg was a better predictor (P = 0.0002) of readiness to wean from ECMO than either C (>0.5 mL/cmH₂O/kg, P = 0.057) or FRC (>5 mL/kg, P = 0.007) alone. The combination of FRC and C_rs had a sensitivity of 73.3% and specificity of 100% for successful decannulation. We conclude that repeated measurements of FRC and C_rs can assess lung recovery and may assist in establishing criteria for successful weaning from ECMO. Pediatr Pulmonol. 1995; 20:145–151 . © 1995 Wiley-Liss, Inc.     

Acute effects of PEEP on tidal volume and respiratory center output during synchronized ventilation in preterm infants

BACKGROUND: Positive end expiratory pressure (PEEP) is routinely used in mechanically ventilated preterm infants to maintain lung volume. An acute increase in PEEP can affect lung mechanics and tidal volume, but it is unknown if these effects elicit compensatory changes in respiratory center output. OBJECTIVES: To investigate the acute effects of changes in PEEP on tidal volume (V(T)), lung compliance (C(L)), and respiratory center output (RCO) during synchronized intermittent mandatory ventilation (SIMV) in preterm infants at different levels of basal respiratory drive. METHODS: Preterm infants were studied during SIMV at three levels of PEEP (2, 4, and 6 cm H(2)O for 2-3 min each) and at two levels of inspired CO(2). Peak inspiratory pressure (PIP) was adjusted to maintain the same delta pressure at the airway. RCO was assessed by measuring total diaphragmatic electrical activity. The level of inspired CO(2) was adjusted by modifying the instrumental dead space. RESULTS: Sixteen preterm infants GA: 25 +/- 2 weeks, BW: 786 +/- 242 g, age: 18 +/- 15 days, SIMV: rate 14 +/- 3 b/min, Ti: 0.35 +/- 0.01 s, PIP: 16 +/- 1 cm H(2)O, and FiO(2): 0.31 +/- 0.06 were studied. At both levels of inspired CO(2), C(L), V(T), and V'(E) from spontaneous and mechanical breaths decreased significantly with higher PEEP. RCO did not change, but at lower respiratory drive, there was a trend towards an increase in RCO with higher PEEP. CONCLUSION: Higher PEEP levels can have acute negative effects on lung mechanics and ventilation in preterm infants without a sufficient compensatory increase in RCO.     

Epidermal growth factor in the lungs of infants developing chronic lung disease.

Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control versus CLD, 7.3 versus 0.0 pg x mL(-1), p<0.01; control versus RDS, 7.3 versus 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease.     

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.     

Paralysis of ventilated newborn babies does not influence resistance of the total respiratory system.

Paralysis with pancuronium bromide is used in newborn infants to facilitate ventilatory support during respiratory failure. Changes in lung mechanics have been attributed to paralysis. The aim of this study was to examine whether or not paralysis per se has an influence on the passive respiratory mechanics, resistance (Rrs) and compliance (Crs) of the respiratory system in newborn infants. In 30 infants with acute respiratory failure, Rrs was measured during paralysis with pancuronium bromide and after stopping pancuronium bromide (group A). Rrs was also measured in an additional 10 ventilated infants in a reversed fashion (group B): Rrs was measured first in nonparalysed infants and then they were paralysed, mainly for diagnostic procedures, and the Rrs measurement repeated. As Rrs is highly dependent on lung volume, several parameters, that depend directly on lung volume were recorded: inspiratory oxygen fraction (FI,O2), arterial oxygen tension/alveolar oxygen tension (a/A) ratio and volume above functional residual capacity (FRC). In group A, the Rrs was not different during (0.236+/-0.09 cmH2O x s x mL(-1)) and after (0.237+/-0.07 cmH2O x s x mL(-1)) paralysis. Also, in group B, Rrs did not change (0.207+/-0.046 versus 0.221+/-0.046 cm x s x mL(-1) without versus with pancuronium bromide). FI,O2, a/A ratio and volume above FRC remained constant during paralysis. These data demonstrate that paralysis does not influence the resistance of the total respiratory system in ventilated term and preterm infants when measured at comparable lung volumes.     

Growth and differentiation factor 15 (GDF15) levels predict adverse respiratory outcomes in premature neonates

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved from 57 preterm infants at five time points, from birth until 36-weeks postmenstrual age (PMA). GDF15 levels were measured using ELISA in 114 samples. We performed two-sample t-test, correlation and linear regression, logistic regression, and mixed-effects linear models for statistical analysis, and significance was identified when p < 0.05. Contrary to our hypothesis, for every 1-week increase in gestational age at birth, the predicted GDF15 level decreased by 475.0 pg/ml (p < 0.001). Greater PMA was significantly associated with lower serum GDF15 levels (p < 0.001). Interestingly, higher GDF15 levels were associated with a longer need for mechanical ventilation (p = 0.034), prolonged respiratory support need (p < 0.001), and length of hospital stay (p = 0.006). In conclusion, in preterm infants, GDF15 levels show an inverse correlation with gestational age at birth, with higher levels in more preterm babies, and levels trend down postnatally. Furthermore, longitudinal GDF15 levels through 36 weeks PMA predict adverse respiratory outcomes in preterm infants.