Changes in pulmonary mechanics following caffeine administration in infants with bronchopulmonary dysplasia

The effects of caffeine upon pulmonary mechanics were measured in 16 infants with bronchopulmonary dysplasia (BPD). Pulmonary function tests were performed immediately prior to and 1 hour following a dose of 10 mg/kg of caffeine. A 37% increase in minute ventilation (mean +/- SEM; 436.6 +/- 26.3 to 580.8 +/- 30.7 ml/min/kg) was seen with caffeine administration (P less than 0.001), primarily from a 42% increase in tidal volume (6.2 +/- 0.4 to 8.5 +/- 0.4 ml/kg) (P less than 0.001). Total lung resistance decreased by 20% (134.6 + 24.2 to 105.3 +/- 20.1 cmH2O/L/sec) (P = 0.01), and total pulmonary compliance improved by 47% (0.642 +/- 0.104 to 0.908 +/- 0.190 ml/cmH2O/kg) (P less than 0.01). In five matched control infants with BPD, no effects of placebo upon pulmonary mechanics were detected. Since caffeine has a wide therapeutic index with few side effects, it may be an effective adjunct in the treatment of infants with BPD.     

Pulmonary sequelae at six months following extracorporeal membrane oxygenation.

Mechanical assisted ventilation for neonatal respiratory failure is associated with residual lung disease. Because ECMO rests the lungs, it has been suggested that ECMO will prevent chronic lung disease in survivors. To determine whether or not ECMO survivors have evidence of pulmonary sequelae, we studied 19 infants who were treated with ECMO for neonatal respiratory failure. Ten infants still required supplemental oxygen or pulmonary medications or both to treat clinical lung disease during the first six months of life. Thoracic gas volume was normal. Pulmonary mechanics in ECMO survivors were compared with those of 13 preterm infants with BPD at similar age. We conclude that a significant proportion of ECMO survivors have residual abnormalities in pulmonary mechanics at 6 months of age. We speculate that neonatal lung injury due to meconium aspiration and other causes is a more important determinant of abnormal pulmonary sequelae than the method of treatment.     

Pulmonary mechanics during respiratory distress syndrome in the prediction of outcome and differentiation of mild and severe bronchopulmonary dysplasia

Pulmonary mechanics was prospectively and longitudinally studied in a cohort of 58 infants who suffered from respiratory distress syndrome. The aim was to determine if early compliance and resistance measurements had additional value to simple clinical variables in predicting poor outcome ie nonsurvival or severe bronchopulmonary dysplasia (BPD) at 28 days. Second, we wanted to determine whether and when the recently described type 1 (mild) BPD and type 2 (severe) BPD could be differentiated by means of lung function tests. In a logistic model, neither lung Compliance nor pulmonary resistance at days 1 and 4 of life were selected as predictive variables. On the other hand, gestational age and the ventilatory index no. 1 (ventilator frequency × maximal inspiratory pressure) on day 3 were the best early predictors of poor outcome. Type 2 BPD was characterized by a lower lung compliance and a higher pulmonary resistance than type 1 BPD, although the differences were only significant at 28 days. In conclusion, pulmonary function tests were not helpful in the early prediction of poor outcome at 28 days. They might, however, be of value in the follow-up of BPD patients after 28 days. Pediatr Pulmonol. 1994; 17:218–224. © 1994 Wiley-Liss, Inc.     

Compliance measurement in respiratory distress syndrome: the prediction of outcome

Dynamic compliance (Cdyn) measurements within the first three days of life predicted survival in 60 preterm infants suffering from respiratory distress syndrome. Cdyn was measured in 47 survivors at 2.3 +/- 1.4 days of life and in 13 nonsurvivors on 2.7 +/- 1.7 days. All nonsurvivors died from respiratory failure within the first two weeks of life. Mean Cdyn of the survivors was 0.83 +/- 0.33 ml/cm H2O and of the nonsurvivors 0.35 +/- 0.19 ml/cm H2O (p less than 0.001). Cdyn values below 0.45 ml/cm H2O predicted 11 of 13 deaths in infants, and Cdyn measurements above this value predicted 45 of 47 survivals, with a specificity of 81% and a sensitivity of 89%. Eleven of the survivors, who subsequently developed bronchopulmonary dysplasia (BPD), had a mean Cdyn of 0.56 +/- 0.23 ml/cm H2O. When these infants were matched with infants of comparable weight without evidence of BPD, the BPD group had a significantly lower Cdyn (p less than 0.05). Cdyn measurements during the first three days of life are useful in predicting outcome of respiratory failure secondary to respiratory distress syndrome.     

Effect of early ambroxol treatment on lung functions in mechanically ventilated preterm newborns who subsequently developed a bronchopulmonary dysplasia (BPD)

In a randomized trial in 102 preterm newborns with respiratory distress syndrome (RDS) it has been shown that early Ambroxol treatment (30 mg kg(-1) over the first 5 days) significantly reduces the incidence of RDS-associated complications [bronchopulmonary dysplasia (BPD), intraventricular haemorrhage, post-natal acquired pneumonia]. The aim of the present analysis was to investigate the effect of Ambroxol treatment on lung function in newborns who developed BPD. Respiratory function testing (RFT) was performed immediately after extubation and at day 28. Tidal volume (VT) and respiratory frequency (f) were measured during tidal breathing using the deadspace free flow-through technique. The lung mechanic parameter VT/maxPes was determined by measuring the maximal oesophageal pressure changes, maxPes, with a catheter tip pressure transducer. In the placebo group 36/50 infants were extubated within the first 28 days of life and 13/36 (36%) developed BPD. In the Ambroxol group 44/52 were extubated and 9/44 (20%) developed BPD. After extubation, RFT showed (i) no statistically significant difference in the ventilatory parameters of either treatment group, (ii) improved (P<0.05) lung mechanics (VT/maxPes) in Ambroxol group compared to controls (94+/-27 ml kPa(-1) vs. 8.1+/-2.6 ml kPa(-1)) and (iii) no statistically significant difference in lung function between infants with and without BPD. At day 28 we found (i) no effect of early Ambroxol treatment on lung functions, (ii) significantly (P < 0.05) higher f (58.5+/-11.7 min(-1) vs. 49.7+/-10.1 min(-1)) and significantly (P<0.01) lower V(T) (9.6+/-1.9 ml vs. 12.3+/-2.7 ml) and V(T)/maxPes (8.9+/-2.6 ml kPa(-1)] vs. 12.0+/-2.9 ml kPa(-1)) in infants with BPD compared to infants without and (iii) these differences are not influenced by early Ambroxol treatment. If the process of BPD development is induced, early Ambroxol treatment has no influence on impaired lung function at day 28.     

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.     

Serial measurement of pulmonary mechanics assists in weaning from extracorporeal membrane oxygenation in neonates with respiratory failure

Extracorporeal membrane oxygenation (ECMO) is a highly invasive therapy for intractable neonatal respiratory failure, and serious complications may occur with increasing duration of bypass. Weaning from bypass is empirical at present. Thus, there is a need to accurately predict when infants can be successfully decannulated. We hypothesized that pulmonary mechanics would reflect lung recovery and, therefore, predict successful weaning from ECMO. We measured pulmonary mechanics daily in 22 neonates, at gestational age of 37.8 +/- 0.6 weeks (SE) requiring ECMO for severe respiratory failure (oxygen index 66 +/- 6). Pulmonary resistance (Rpul), dynamic compliance (Cdyn), and tidal volume (VT) were measured. Rpul did not predict lung recovery. Cdyn within 24 hours of starting ECMO was 0.3 +/- 0.04 ml/cm H2O. Cdyn within 24 hours of weaning from ECMO was 1.2 +/- 0.09 ml/cm H2O (p less than 0.001). All 22 infants had Cdyn greater than 0.6 ml/cm H2O at the time of decannulation, but four infants (20 percent) with Cdyn less than 0.6 ml/cm H2O could not be weaned from ECMO within 20 hours (p less than 0.01). Thus, a minimum Cdyn of 0.6 ml/cm H2O is associated with successful weaning from ECMO. Cdyn of 0.8 ml/cm H2O provided better overall discrimination between those who could be successfully weaned from ECMO. We conclude that serial measurement of dynamic pulmonary compliance predicts successful weaning from ECMO.     

Pulmonary function in infancy and in childhood following mechanical ventilation in the neonatal period

Pulmonary function was evaluated in both infancy and childhood in the same 19 prematurely born infants, who required mechanical ventilation (MV) during the neonatal period. Results of our patients were compared with those of control subjects. Upon first evaluation, we found that lung resistance (RL) was significantly elevated (24.85 +/- 6.06 vs. 17.77 +/- 2.39 cmH2O/L/s; P less than 0.01). The mean value of dynamic lung compliance (CLdyn) was low, but the difference compared to controls did not reach significance. From infancy to childhood, elevated RL persisted (9.33 +/- 2.51 vs. 6.52 +/- 1.52 cm H2O/L/s; P less than 0.01), and the decrease of CLdyn became significant (46.86 +/- 12.84 vs. 59.34 +/- 15.68 mL/cmH2O; P less than 0.05). In addition, maximum flow at functional residual capacity was significantly decreased (0.824 +/- 0.284 vs. 1.215 +/- 0.358 L/s; P less than 0.01); whereas pulmonary diffusing capacity for carbon monoxide was similar in the patients (7.62 +/- 2.16 mL/min/mm Hg) and in the controls (8.38 +/- 1.6). Pulmonary dysfunction following premature birth, respiratory distress, and prolonged MV may not resolve from infancy to childhood.     

Pulmonary function in bronchopulmonary dysplasia

The purpose of this study was to examine lung function and bronchodilator responsiveness in infants with a history of prematurity and bronchopulmonary dysplasia (BPD), using the raised volume rapid thoracoabdominal compression technique as well as with whole-body plethysmography. Spirometric measurements were obtained in 28 infants with a history of BPD, defined as preterm birth with O2 requirement at 36 weeks postmenstrual age (gestational age at birth, 26.4 +/- 2.1 weeks, mean +/- SD; birthweight, 898 +/- 353 g; age at study, 68.0 +/- 35.6 weeks). Fractional lung volumes were measured in 27 subjects. Values were expressed as percentage of predicted normal values. Compared to normal infants, those with a history of BPD exhibited decreases in forced expiratory flows including forced expiratory volume in 0.5 sec (76.3 +/- 19.6%), forced expiratory flow at 75% of expired forced vital capacity (FEF75; 59.5 +/- 30.7%), and FEF(25-75) (74.0 +/- 26.8%; P<0.01 for all). Functional residual capacity (107.9 +/- 25.3%), residual volume (RV, 124.5 +/- 42.7%), and RV/total lung capacity (RV/TLC, 128.2 +/- 35.3%) were increased in infants with a history of BPD (P<0.05 for each). There was no difference in TLC between groups. Seventeen infants were studied both pre- and postalbuterol, and 6 (35%) demonstrated significant bronchodilator responsiveness. Infants with recurrent wheezing showed greater expiratory flow limitation, hyperinflation, and airways responsiveness, whereas those without wheezing showed only modest airway dysfunction. We conclude that infants with a history of BPD have pulmonary function abnormalities characterized by mild to moderate airflow obstruction and air trapping.     

Respiratorische Langzeitfolgen nach Frühgeburt

The paper reviews the current literature on the long-term impact of bronchopulmonary dysplasia (BPD) on respiratory health in adolescence and early adulthood. A significant proportion of preterm infants suffering from BPD demonstrate persistent respiratory abnormalities into adulthood. These include an obstructive pattern of lung function with increased trapped air, obstructive symptoms during infections, decreased exercise tolerance and computer tomographic findings with emphysematous changes and increased subpleural and peribronchial thickening. Evidence is accumulating that BPD in infancy confers a risk for later chronic obstructive pulmonary disease (COPD) like disease.     

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.     

Lung recruitment using oxygenation during open lung high-frequency ventilation in preterm infants

RATIONALE: Changes in oxygenation are often used to guide the recruitment procedure during open lung high-frequency ventilation in preterm infants. However, data on the feasibility and safety of this approach in daily clinical practice are limited. OBJECTIVE: To prospectively collect data on ventilator settings, gas exchange, and circulatory parameters before and after surfactant therapy during open lung high-frequency ventilation. METHODS: In 103 preterm infants with respiratory distress syndrome, the opening, closing, and optimal pressures were determined during high-frequency ventilation by increasing and decreasing stepwise the continuous distending pressure, defining optimal recruitment as adequate oxygenation using a fraction of inspired oxygen not exceeding 0.25. This procedure was repeated after each surfactant treatment. MEASUREMENTS AND MAIN RESULTS: The mean presurfactant opening and optimal continuous distending pressures were, respectively, 20.5 +/- 4.3 and 14.0 +/- 4.0 cm H2O, with a fraction of inspired oxygen of 0.24 +/- 0.04. Surfactant treatment enabled a reduction in the mean optimal pressure of almost 6 cm H2O without compromising oxygenation. Blood pressure and heart rate remained stable and no air leaks were observed during the recruitment procedures. The mortality rate and the incidence of severe intracranial hemorrhage or periventricular leukomalacia and chronic lung disease at 36 wk were comparable to previously reported data. CONCLUSION: Open lung high-frequency ventilation using oxygenation to guide the recruitment process is feasible and safe in preterm infants and enables a reduction of the fraction of inspired oxygen below 0.25 in the majority of preterm infants with respiratory distress syndrome.     

Pulmonary function and respiratory morbidity in school-age children born prematurely and ventilated for neonatal respiratory insufficiency

We examined 72 children aged 6-9 years to assess the effects of prematurity and ventilator treatment on subsequent lung function and respiratory morbidity. The preterm study group (n = 42) was divided into children with a history of bronchopulmonary dysplasia (BPD) (n = 10), children who had had neonatal respiratory treatment but no BPD (n = 19), and children without severe neonatal respiratory problems (n = 13). The BPD children as a group had markedly lower specific airway conductance and larger residual volume than did the full-term control group, but there were no significant differences in spirometric measurements. The BPD group also had higher respiratory morbidity requiring hospitalizations, particularly during the first 2 years of life, than did the children in the other study groups. Therefore, BPD may improve but does not disappear as age increases. Non-BPD children who had had ventilator treatment as neonates recovered well and suffered no severe respiratory problems after infancy. Pulmonary function parameters in prematurely born children without neonatal ventilator treatment did not differ from those in the full-term control group. Thus, neonatal lung disease seems to be a more important determinant of abnormal pulmonary function at a later age than is prematurity alone.     

A randomized placebo-controlled study to evaluate the effects of oral albuterol on pulmonary mechanics in ventilator-dependent infants at risk of developing BPD.

Albuterol is a specific beta-2 agonist that has been reported to be effective in treating infants and children with bronchospastic pulmonary disease. The use of oral albuterol has not been investigated in patients with bronchopulmonary dysplasia (BPD). Thirty premature infants were randomized to receive oral albuterol (0.15 mg/kg/dose q8h) or a volume- and color-matched placebo (D5/W). Pulmonary functions were evaluated at baseline and at 48 and 96 hours after entry to the study. The study was also designed for crossover from placebo to albuterol or albuterol to caffeine in the event that the infant's total pulmonary resistance did not improve at the time of the 48 hour pulmonary function evaluation. Heart rate and respiratory rate showed a statistically significant but clinically unimportant increase in the albuterol-treated infants. There were no significant differences noted in systolic or diastolic blood pressure. Percent improvement in the pulmonary function indices were calculated from baseline to 48 hours and from baseline to 96 hours for the placebo and albuterol-treated groups. The results indicate that at 48 hours there were statistically significant improvements in total resistance (14.5%), inspiratory resistance (10.8%), and expiratory resistance (12.9%) in the albuterol-treated infants as compared to the spontaneous deterioration of the same values by 25%, 81%, and 11%, respectively, in the placebo-treated infants. In conclusion, oral albuterol therapy of 48 hours duration improved pulmonary resistance without major cardiovascular side effects in ventilator-dependent premature infants.     

Chronic lung injury in preterm lambs. Disordered respiratory tract development

The cause of chronic lung disease of early infancy, often called bronchopulmonary dysplasia (BPD), remains unclear, partly because large-animal models that reliably reproduce BPD have not been available. We developed a model of BPD in lambs that are delivered prematurely and ventilated for 3 to 4 wk after birth to determine whether the histopathology of chronic lung injury in premature lambs mimics that which occurs in preterm infants who die with BPD, and to compare two ventilation strategies to test the hypothesis that differences in tidal volume (VT) influence histopathologic outcome. The two ventilation strategies were slow, deep ventilation (20 breaths/min, 15 +/- 2 ml/kg body weight VT; n = 5) or rapid, shallow ventilation (60 breaths/min, 6 +/- 1 ml/kg body weight VT; n = 5). Lambs were delivered at 125 +/- 4 d gestation (term = 147 d), treated with surfactant, and mechanically ventilated with sufficient supplemental oxygen to maintain normal arterial oxygenation (60 to 90 mm Hg). Quantitative histologic analysis revealed lung structural abnormalities for both groups of experimental lambs compared with lungs of control term lambs that were < 1 d old (matched for developmental age; n = 5) or 3 to 4 wk old (matched for postnatal age; n = 5). Compared with control lambs, chronically ventilated preterm lambs had pulmonary histopathology characterized by nonuniform inflation patterns, impaired alveolar formation, abnormal abundance of elastin, increased muscularization of terminal bronchioles, and inflammation and edema. Slow, deep ventilation was associated with less atelectasis, less alveolar formation, and more elastin when compared with rapid, shallow ventilation. We conclude that prolonged mechanical ventilation of preterm lambs disrupts lung development and produces pulmonary histopathologic changes that are very similar to those that are seen in the lungs of preterm infants who die with BPD. This chronic lung disease is not prevented by surfactant replacement at birth, does not appear to require arterial hyperoxia, and is influenced by VT.     

Pulmonary vascular extraction of circulating norepinephrine in infants with bronchopulmonary dysplasia

Although the pulmonary circulation in infants with advanced bronchopulmonary dysplasia (BPD) is characterized by abnormal structure and vasoreactivity, metabolic lung functions have not been studied in these infants. To test the hypothesis that patients with severe BPD may have abnormal metabolic lung function, we assessed the pulmonary vascular extraction of circulating norepinephrine in six children with BPD during cardiac catheterization. Plasma norepinephrine levels were measured from simultaneously drawn mixed venous (main pulmonary artery) and left atrium or femoral artery samples. In comparison with four infants with mild heart disease without pulmonary hypertension, we found that infants with BPD extract proportionately less norepinephrine than non-BPD infants [-7 +/- 50% (BPD) versus +27 +/- 6% (non-BPD); P less than 0.001, t test]. Three infants with BPD had higher arterial than mixed venous concentrations of plasma norepinephrine, suggesting net production across the lung. Plasma catecholamine levels and percent extraction correlated poorly with cardiac index and systemic and pulmonary vascular resistance indices. However, this study group was characterized by a high incidence of pulmonary (6/6) and systemic (4/6) hypertension, left ventricular hypertrophy (4/6), and subsequent death (3/6). We conclude that infants with severe BPD and pulmonary hypertension have decreased pulmonary vascular clearance or net production of circulating norepinephrine, but links between altered pulmonary catecholamine metabolism and pulmonary hypertension, or other cardiovascular abnormalities associated with BPD, remain speculative.     

Altered urinary excretion of elastin cross-links in premature infants who develop bronchopulmonary dysplasia

In order to determine whether elastin degradation is increased in infants whose respiratory insufficiency requires ventilation with high concentrations of O2, we quantitated, by amino acid analysis, the elastin degradation products (desmosines) excreted in the urine of 14 premature male infants during the first 3 wk of life. Eight of these infants, the "low-O2" infants, did not have severe lung disease and did not require more than 40% O2 beyond the first 8 h of life. The other 6 infants, selected retrospectively because they developed bronchopulmonary dysplasia (BPD), were ventilated with more than 60% O2 for at least the first 72 h of life. The pattern of desmosine excretion observed in infants who developed BPD differed significantly (p less than 0.05) from the excretion pattern seen in "low-O2" infants during the first 3 wk of life. At the end of the first week of life, desmosine excretion was significantly greater (p less than 0.05) in the infants who later developed BPD than in the "low-O2" infants without severe lung disease. From Days 7-9 to 20-22, desmosine excretion increased in the "low-O2" infants from 6.9 +/- 1.7 micrograms/kg to 9.0 +/- 3.5 micrograms/kg. In contrast, desmosine excretion did not remain elevated in the BPD infants, decreasing from 10.6 +/- 2.2 micrograms/kg to 6.1 +/- 2.9 micrograms/kg during the same period. In the BPD infants, elevated desmosine excretion through Day 9 is likely to reflect lung injury, whereas decreased desmosine excretion beyond Day 9 suggests that elastin synthesis and turnover is impaired, possibly as a result of nutritional deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a clinically detectable PDA on pulmonary mechanics measures in VLBW infants with RDS.

We examined the effect of a clinically detectable patent ductus arteriosus (PDA) and its successful treatment with indomethacin on serial measures of pulmonary mechanics in 10 very-low-birthweight (VLBW) intubated infants with respiratory distress syndrome (RDS). Pulmonary mechanics were measured by the passive expiratory flow technique. Total respiratory system compliance (Crs) gradually improved as RDS resolved. However, a significant decrease in mean Crs was associated with the development of a clinically detectable PDA, ranging from 1.51 +/- 0.21 to 0.90 +/- 0.08 mL/cmH2O/m (P less than 0.05). We also noted an increase in mean Crs, from 0.90 +/- 0.08 to 1.49 +/- 0.21 mL/cmH2O/m (P less than 0.05), after successful treatment of a PDA with indomethacin. Total respiratory system resistance (Rrs) did not change. We conclude that a clinically significant PDA is associated with a decreased Crs and that successful treatment of a PDA with indomethacin is associated with an improvement in lung compliance. These findings imply that the development of a clinically detectable PDA and its subsequent treatment complicates the interpretation of pulmonary mechanics data in VLBW infants with RDS.     

Evaluation of neonatal pulmonary mechanics and energetics: a two factor least mean square analysis

Pulmonary mechanics, using a two factor least mean square analysis technique, were determined in 22 preterm neonates with respiratory failure. The respiratory system is modelled as a linear mechanical system. Concurrent signals of airflow and transpulmonary pressure were utilized to calculate values of dynamic lung compliance and pulmonary resistances; these determinations were made over the entire tidal volume range. In addition, values of resistive work of breathing, pulmonary time constants, scalar records of sequential breaths, pressure-volume and flow-volume relationships were available for data review and interpretation. The mean +/- SEM value of tidal volume was 7.4 +/- 0.6 ml/kg; dynamic lung compliance was 0.44 +/- 0.04 ml/cmH2O/kg; and the pulmonary resistance of the whole breath was 106 +/- 9.1 cmH2O/liter/s. The resistive work of breathing (hysteresis) was 41.8 +/- 5.9 gm.cm/kg. In correlating the measured values of pressure and flow to those predicted by the model, the mean value of the correlation coefficient for the least mean square analysis for all 22 studies was 0.995 +/- 0.001; the standard error of estimate of the predicted pressure was less than 4.4% of the range of pressures measured. Thereby, the model was considered to be appropriate for the neonatal respiratory system. In addition to the traditional procedures of evaluating the respiratory status of a sick neonate, bedside analysis of pulmonary mechanics provide graphical information, and quantitative data which should be useful in day-to-day pulmonary management.     

Growth of pulmonary microvasculature in ventilated preterm infants

RATIONALE: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. OBJECTIVE: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. METHODS: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. MEASUREMENTS: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. MAIN RESULTS: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. CONCLUSIONS: The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.