Influence of clinical and ventilatory parameters on morphology of bronchopulmonary dysplasia

Our aim was to assess multiple factors which contribute to bronchopulmonary dysplasia (BPD) in prematurely born neonates. Specific morphologic features might relate to cumulative oxygen dose Barotrauma, prematurity, infection, and persistent ductus arteriosus (PDA). Seventy-two patients dying from BPD as defined by the histopathologic criteria of Stocker were analyzed retrospectively. Median (range) gestational age was 28 (25-35) weeks, and median survival was 16 (5-386) days. The infants were ventilated for 15 (5-149) days with a mean inspired oxygen fraction (FiO₂,) of 0.78. The cumulative oxygen dose and mean airway pressures were determined. The presence of neonatal infection, PDA, and interstitial lung emphysema (ILE) was assessed. Baseline lung disease was estimated as proposed by Palta. At autopsy, the degree of hyaline membranes, epithelial cell necrosis, emphysema, atelectasis, interstitial cell proliferation, and lung fibrosis was scored semiquantitatively (0 to 3+). The influence of neonatal infection, PDA, gestational age, survival, oxygen dose, or barotrauma on morphological findings was examined by multivariate analysis. We found “acute” BPD in 22, “reparative” in 34 and long-standing-healed in 16 cases. ILE within the first week was associated with interstitial cell proliferation and lung fibrosis in infants surviving more than 28 days. Initial barotrauma contributes to lung fibrosis in infants with BPD. © 1995 Wiley-Liss, Inc.     

Effect of posture on respiratory function and drive in preterm infants prior to discharge

Our objective was to determine the effect of posture on respiratory function and drive in prematurely born infants immediately prior to discharge. Twenty infants (6 oxygen-dependent), median gestational age 29 weeks (range, 25-32), were studied at a median postconceptional age (PCA) of 36 weeks (range, 33-39). On 2 successive days, infants were studied both supine and prone; each posture was maintained for 3 hr. The order on each day in which postures were studied was randomized between infants. At the end of each 3-hr period, tidal volume (Vt), inspiratory (Ti) and expiratory (Te) time, respiratory rate, and minute ventilation were measured. In addition, respiratory drive was assessed by measuring the pressure generated in the first 100 msec of an imposed airway occlusion (P(0.1)), and respiratory muscle strength was assessed by recording the maximum inspiratory pressure (Pimax) generated against an occlusion which was maintained for at least five breaths. Overall, tidal volume was higher (P < 0.05), but respiratory rate (P < 0.05), P(0.1) (P < 0.05), and Pimax (P < 0.05) were lower in the prone compared to the supine position. There were no significant differences in Ti or Te between the two postures. In oxygen-dependent infants only, minute volume was higher in the prone position (P < 0.05). In conclusion, posture-related differences in respiratory function are present in prematurely born infants studied prior to neonatal unit discharge.     

Frontiers in pulmonary hypertension in infants and children with bronchopulmonary dysplasia

Pulmonary hypertension (PH) is an increasingly recognized complication of premature birth and bronchopulmonary dysplasia (BPD), and is associated with increased morbidity and mortality. Extreme phenotypic variability exists among preterm infants of similar gestational ages, making it difficult to predict which infants are at increased risk for developing PH. Intrauterine growth retardation or drug exposures, postnatal therapy with prolonged positive pressure ventilation, cardiovascular shunts, poor postnatal lung and somatic growth, and genetic or epigenetic factors may all contribute to the development of PH in preterm infants with BPD. In addition to the variability of severity of PH, there is also qualitative variability seen in PH, such as the variable responses to vasoactive medications. To reduce the morbidity and mortality associated with PH, a multi‐pronged approach is needed. First, improved screening for and increased recognition of PH may allow for earlier treatment and better clinical outcomes. Second, identification of both prenatal and postnatal risk factors for the development of PH may allow targeting of therapy and resources for those at highest risk. Third, understanding the pathophysiology of the preterm pulmonary vascular bed may help improve outcomes through recognizing pathways that are dysregulated in PH, identifying novel biomarkers, and testing novel treatments. Finally, the recognition of conditions and exposures that may exacerbate or lead to recurrent PH is needed to help with developing treatment guidelines and preventative strategies that can be used to reduce the burden of disease. Pediatr Pulmonol. 2012. 47:1042–1053. © 2012 Wiley Periodicals, Inc.     

Longitudinal measures of lung function in infants with bronchopulmonary dysplasia

We previously demonstrated that infants with a history of bronchopulmonary dysplasia (BPD) exhibit airflow obstruction and air trapping. The purpose of this study was to assess longitudinal changes in pulmonary function in infants with a history of BPD over the first 3 years of life, and the relationship to somatic growth. Spirometry was measured using the raised volume rapid thoracoabdominal compression technique, and lung volumes measured by plethysmography. Eighteen infants (mean gestational age ± SD 27.3 ± 2.2 weeks, birthweight 971 ± 259 g) underwent two lung function studies. Average age at first test was 58.8 weeks. Spirometry demonstrated significant reductions in forced expiratory volume in 0.5 sec (FEV_0.5, 76.0 ± 15.9% predicted, Z‐score ?2.13 ± 1.69), forced expiratory flow at 75% of expired forced vital capacity (FEF₇₅, 54.8 ± 31.1%, ?3.58 ± 2.73), and FEF_25–75 (67.8 ± 33.3%, ?1.79 ± 1.76). Group mean total lung capacity (TLC) was in the low normal range (82.9 ± 13.5% predicted) and residual volume (RV)/TLC was mildly elevated (122.4 ± 38.2% predicted). Repeat testing was performed an average of 32.7 weeks after initial testing. At re‐evaluation, group mean lung volumes and flows tracked at or near their previous values; thus, in general, there was a lack of catch‐up growth. However, compared to infants with below average or average somatic growth (as represented by g/day), infants with above average growth showed significantly greater improvements in percent predicted FVC, FEV_0.5, TLC, and RV/TLC (all P < 0.05, ANOVA). We conclude that longitudinal measures of pulmonary function in infants and young children with BPD demonstrate significant airflow obstruction and modest restriction, which tends to persist with time. On the other hand, infants with above average somatic growth showed greater lung growth than their peers. Additional studies examining the effects of various nutritional regimens on lung function are warranted. Pediatr Pulmonol. 2011; 46:369–375. © 2010 Wiley‐Liss, Inc.     

Precursors of cardiorespiratory events in infants detected by home memory monitor

In 1,079 infants monitored for >700,000 hr at home for apnea or bradycardia, we found an association between infants having multiple events exceeding conventional or a priori defined more extreme thresholds and less favorable developmental outcome at 1 year of age than infants with few or no events. If it is necessary to prevent such events to minimize risk for developmental morbidity, there is reason to determine whether there are disturbances in advance of the apnea or bradycardia that herald their onset. In the 85 infants with at least 1 extreme event and 1 conventional event, we hypothesized that apnea and bradycardia do not occur de novo but rather are preceded by cardiorespiratory and hemoglobin O2 saturation changes. We compared recorded time intervals preceding these events, and we analyzed three preceding time intervals for each conventional and extreme event, and each non-event recording: Time-2 hr: up to 2 hr before; Time-1 hr: up to 1 hr before; and Time-75 sec: the 75 sec immediately preceding each event. O2 saturation progressively decreased preceding both conventional and extreme events, and progressive increases occurred in heart and breathing rate variability. Duration of respiratory pauses and of periodic breathing progressively increased preceding conventional events, respiratory rate variability increased immediately preceding conventional events and at 1 hr preceding extreme events, and O2 saturation decreased immediately preceding both conventional and extreme events. Thus, conventional and extreme events do not occur de novo but rather are preceded by autonomic instability of the cardiorespiratory system.     

Tracheostomy placement in infants with bronchopulmonary dysplasia: Safety and outcomes

Optimizing the timing and safety for the placement of a tracheostomy in infants with bronchopulmonary dysplasia (BPD) has not been determined. The purpose of the present study was to describe the data from a single institution about the efficacy and safety of tracheostomy placement in infants with BPD needing long‐term respiratory support. We established a service line for the comprehensive care of infants with BPD and we collected retrospective clinical data from this service line. We identified patients that had a trachostomy placed using the local Vermont‐Oxford database, and obtained clinical data from chart reviews. We identified infants who had a tracheostomy placed for the indication of severe BPD only. Safety and respiratory efficacy was assessed by overall survival to discharge and the change in respiratory supportive care from just before placement to 1‐month post‐placement. Twenty‐two patients (750 ± 236 g, 25.4 ± 2.1 weeks gestation) had a tracheostomy placed on day of life 177 ± 74 which coincided with a post‐conceptual age of 51 ± 10 weeks. At placement these infants were on high settings to support their lung disease. The mean airway pressure (MAP) was 14.3 ± 3.3 cmH₂O, the peak inspiratory pressure was 43.7 ± 8.0 cmH₂O, and the FiO₂ was 0.51 ± 0.13. The mean respiratory severity score (MAP × FiO₂) 1 month after tracheostomy was significantly (P = 0.03) lower than prior to tracheostomy. Survival to hospital discharge was 77%. All patients with tracheostomies that survived were discharged home on mist collar supplemental oxygen. In conclusion, the high survival rate in these patients with severe BPD and the decreased respiratory support after placement of a tracheostomy suggests that high ventilatory pressures should not be a deterrent for placement of a tracheostomy. Future research should be aimed at determining optimal patient selection and timing for tracheostomy placement in infants with severe BPD. Pediatr Pulmonol. 2013; 48:245–249. © 2012 Wiley Periodicals, Inc.     

Cardiorespiratory status in long-term survivors of prematurity, with and without hyaline membrane disease

Forty-eight children, born at less than 33 weeks' gestation and without bronchopulmonary dysplasia (BPD) or Wilson-Mikity syndrome (WM) were studied at a mean age of 9.1 years, to identify the incidence and possible factors contributing to the development of long-term abnormalities in pulmonary function. As neonates, 30 children had hyaline membrane disease (HMD) of whom 21 required ventilation. Eighteen did not have HMD, of whom 9 required ventilation for nonrespiratory reasons. All patients had grown normally. Four of the 48 (8.3%) had clinical asthma, 5 had persisting chest x-ray abnormalities (10.6% of 47 chest x-rays performed), each having been ventilated for HMD. There was a close association between duration of ventilation, oxygen administration, and subsequent abnormal chest x-ray. Electrocardiogram and M-mode echocardiograms were normal in all but 2 patients. Only 3 patients had significant restrictive lung disease, 3 had evidence of significant airways obstruction, and 13 (27.7%) had signs of air trapping. Methacholine challenge was positive in 30 of 46 patients (65.2%). The incidence of a positive methacholine challenge did not correlate with history of HMD, duration of ventilation, or high oxygen administration. There is an increased incidence of airway hyperreactivity in survivors of prematurity, not associated with any identified therapeutic maneuver during the neonatal period.     

A comprehensive approach to the prevention of bronchopulmonary dysplasia

The current bronchopulmonary dysplasia (BPD) is seen in infants born extremely premature, with less severe respiratory distress syndrome (RDS) and who received prenatal steroids-"new BPD". The pathophysiology of BPD is based on an impairment of lung maturation with prenatal and postnatal multi-hit insults and genetic susceptibility. This multifactorial pathophysiology of BPD suggests that no single "magic bullet" will prevent it. Thus, to avoid BPD we need to implement a complex and comprehensive strategy. This strategy is based on ventilatory and non-ventilatory measures. The ventilatory route allows an individualized endotracheal intubation approach. Early lung recruitment with nasal respiratory support (nasal continuous positive airway pressure [NCPAP] or nasal intermittent positive pressure ventilation [NIPPV] / synchronized NIPPV [SNIPPV]) and the INSURE (intubation, surfactant and early extubation) approach are discussed. Initial treatment with NCPAP did not reduce the rate of BPD compared to endotracheal ventilation and surfactant administration. While NIPPV/SNIPPV may have short-term advantages over NCPAP, the effect on BPD needs to be further studied. During hospitalization the respiratory goals should aim for adequate oxygenation, permissive hypercapnia, and gentle ventilation. However, these goals were found to have short-term benefits but did not reduce significantly the rate of BPD. Selective use of a short course of low dose corticosteroids can be considered after the first or second week of life in infants who are unable to be weaned from the ventilator and are at high risk for BPD. Non-ventilatory measures include early nutritional support with fluid restriction, caffeine and consideration of vitamin A. Hemodynamic significant patent ductus arteriosus (PDA) may be associated with BPD, but medical or surgical treatment of PDA were not shown to decrease BPD. Each component and the strategy as a whole needs to be further studied in large randomized prospective studies or by meta-analyses, especially in the target population of extremely premature infants who are the most prone to BPD.     

Physiologic effects of terbutaline on pulmonary function of infants with bronchopulmonary dysplasia

This study defines the physiologic changes in pulmonary mechanics induced by subcutaneous terbutaline administration in ventilator-dependent infants with severe bronchopulmonary dysplasia (BPD). Eight such infants (mean +/- SEM weight = 2.56 +/- 0.32 kg, postnatal age = 13.0 +/- 3.2 weeks) were chosen for the study. Pulmonary mechanics and arterial blood gases were measured in the control state and at 30 and 60 minutes following the subcutaneous injection of 5 micrograms/kg terbutaline. There was a significant (p less than 0.001) improvement in lung compliance from baseline values at 30 minutes and at 60 minutes (38%). A significant (p less than 0.05) decrease of 23% in the average pulmonary resistance at 30 minutes and a 26% decrease at 60 minutes from control values were observed. An increase in the I/E ratio occurred in all patients at 60 minutes (p less than 0.01). In addition, clinical improvement was noted in six of eight infants. Administration of terbutaline demonstrated a significant improvement in the pulmonary mechanics of infants with severe BPD.     

Brugada综合征患者的心电图及临床特点分析

目的分析Brugada综合征患者的心电图及临床特点。方法对我院近5年诊断的8例Brugada综合征住院患者的心电图及临床情况进行长期随访观察。结果8例Brugada综合征患者均为男性，年龄平均（40±13）岁。心电图Ⅰ型Brugada波者3例，Ⅱ型4例，Ⅲ型1例；Brugada波具有多变性，提高肋间描记右胸导联心电图可显现Brugada波或使其更明显。8例中4例有猝死家族史，5例有晕厥史，3例在住院期间发生室速／室颤，随访期间2例猝死。结论心电图Brugada波（尤其Ⅰ型）是诊断Brugada综合征的必要条件，明确诊断Brugada综合征尚需联合其他几项临床指标；Brugada综合征患者猝死的风险高，消除晕厥或室速／室颤的诱因是预防的关键。     

Assessment of tidal volume over time in preterm infants using respiratory inductance plethysmography

Non-invasive techniques for monitoring ventilation in infants are widely used in short-term laboratory studies but have not been evaluated in routine clinical settings. To determine whether respiratory inductance plethysmography (RIP) can provide reproducible measurements of tidal volume (V_T) in premature infants over an extended period of time, we monitored respiration in eight healthy preterm infants over 4.9 ± 1.0 hours (mean ± SD). The algebraic sum (Sum) of rib cage (RC) and abdominal (AB) motion signals (obtained by RIP) was calculated and presented over the entire recording period as percent of an initial 5 minute calibration period. V_T was simultaneously measured with a nasal mask pneumotachometer with infants in prone and supine positions during active and quiet sleep. Infants were studied in the morning (am ) and again in the afternoon (pm ). Between these studies they were returned to the nursery wearing the RIP in a continuous record mode. For all patients there was a significant linear relationship between V_T (in mL measured by pneumotachometer) and Sum (in % of calibration value, RIP). Neither the slope of the relationship (0.074 ± 0.03 in am vs. 0.071 ± 0.02 in pm ), nor its variability as measured by standard error of the estimate (SEE) (2.3 ± 0.5 in am vs. 2.5 ± 0.8 in pm ) changed significantly from am to pm . The relationship between V_T and Sum, as well as the variability of that relationship, was not altered by position, asynchrony of RC and AB, respiratory rate, or percent RC contribution to Sum. We conclude that RIP produces consistent measurements of respiratory effort over 5 hours in healthy preterm infants without need for recalibration and is not affected by routine care. Pediatr. Pulmonol. 1997; 23:429–433. © 1997 Wiley-Liss, Inc.     

Surfactant replacement therapy improves ventilation inhomogeneity in infants with respiratory distress syndrome

Surfactant deficiency in newborn infants with hyaline membrane disease (HMD) reduces peripheral airway stability, leading to lung atelectasis, inhomogeneity of distribution of ventilation, ventilation/perfusion mismatch, and hypoxemia. The aim of this study was to evaluate the immediate effect of exogenous surfactant treatment on ventilation inhomogeneity (VIH) in infants with HMD. Homogeneity of ventilation was measured repeatedly in ten infants (median gestational age 30 weeks and birthweight 1.50 kg) after Exosurf®, and in six infants (median gestational age 30 weeks and birthweight 1.42 kg) after Survanta® treatment. Lung function was measured before and 0.5, 2, and 6 hours after administration of a single dose of surfactant. The multiple breath nitrogen washout method was used to measure the time pattern of nitrogen elimination from the lungs. VIH was evaluated by using both a compartmental lung model and a model-independent moment analysis. The two-compartment lung model was found to dominate before surfactant treatment, while a single-compartment model (implying homogeneous ventilation) fitted the washout data best 6 hours after Exosurf® treatment (P < 0.01). The same pattern occurred 2 hours after Survanta® administration. Moment analysis confirmed the reduction in VIH by both surfactants. This study supports the hypothesis that the improved oxygenation after surfactant treatment in infants with HMD results from a reduction in VIH and an increase in functional residual capacity (FRC). Pediatr. Pulmonol. 1997; 24:337–343. © 1997 Wiley-Liss, Inc.