Gerd Schmalisch

The indications and strategies for treatment of patent ductus arteriosus (PDA) are controversial, and the safety and long-term benefits of surgical PDA closure remain uncertain. The aim of this study was to compare the lung function of very low birth weight (VLBW) infants after successful PDA treatment with a cyclooxygenase inhibitor or secondary surgical ligation. A total of 114 VLBW infants (birth weight < 1500 g), including 94 infants (82%) with a birth weight < 1000 g, who received treatment for hemodynamically significant PDA (hsPDA), were examined at a median postmenstrual age of 48 weeks. All infants were initially given pharmacological treatment, and 40 infants (35%) required PDA ligation. Lung function testing (LFT) included tidal breathing measurements, measurement of respiratory mechanics assessed by the occlusion test, whole-body plethysmography, SF6 multiple breath washout, forced expiratory flow (V’maxFRC) by the rapid thoracoabdominal compression technique, exhaled NO (FeNO), and arterialized capillary blood gas analysis. On the day of the LFT, the 2 groups had similar postconceptional age and body weight. However, the PDA ligation group was more immature at birth (p < 0.001) and had reduced respiratory compliance (p < 0.001), lower V’maxFRC (p = 0.006), increased airway resistance (Raw) (p < 0.001), and impaired blood gases (p < 0.001). Multivariate analysis showed that PDA surgery was an independent risk factor for increased Raw. PDA ligation after failed pharmacological treatment is associated with impaired lung function as compared to successful pharmacological closure in infants at a postmenstrual age of 48 weeks. However, only Raw was independently affected by PDA ligation, while all other differences were merely explained by patient characteristics.

Computerized wheeze detection is an established method for objective assessment of respiratory sounds. In infants, this method has been used to detect subclinical airway obstruction and to monitor treatment effects. The optimal location for the acoustic sensors, however, is unknown. The aim of this study was to evaluate the quality of respiratory sound recordings in young infants, and to determine whether the position of the sensor affected computerized wheeze detection. Respiratory sounds were recorded over the left lateral chest wall and the trachea in 112 sleeping infants (median postmenstrual age: 49 weeks) on 129 test occasions using an automatic wheeze detection device (PulmoTrack®). Each recording lasted 10 min and the recordings were stored. A trained clinician retrospectively evaluated the recordings to determine sound quality and disturbances. The wheeze rates of all undisturbed tracheal and chest wall signals were compared using Bland-Altman plots. Comparison of wheeze rates measured over the trachea and the chest wall indicated strong correlation (r ⩾ 0.93, p < 0.001), with a bias of 1% or less and limits of agreement of within 3% for the inspiratory wheeze rate and within 6% for the expiratory wheeze rate. However, sounds from the chest wall were more often affected by disturbances than sounds from the trachea (23% versus 6%, p < 0.001). The study suggests that in young infants, a better quality of lung sound recordings can be obtained with the tracheal sensor.

Although capnography is a standard tool in mechanically ventilated adult and pediatric patients, it has physiological and technical limitations in neonates. Gas exchange differs between small and adult lungs due to the greater impact of small airways on gas exchange, the higher impact of the apparatus dead space on measurements due to lower tidal volume and the occurrence of air leaks in intubated patients. The high respiratory rate and low tidal volume in newborns, especially those with stiff lungs, require main-stream sensors with fast response times and minimal dead-space or low suction flow when using side-stream measurements. If these technical requirements are not fulfilled, the measured end-tidal CO2 (P et CO 2 ), which should reflect the alveolar CO2 and the calculated airway dead spaces, can be misleading. The aim of this survey is to highlight the current limitations of capnography in very young patients to avoid pitfalls associated with the interpretation of capnographic parameters, and to describe further developments.

In preterm infants, lung function monitoring is important for lung-protective mechanical ventilation. In this study, we used a neonatal lung model to investigate the effect of endotracheal tube (ETT) leakage on the monitoring of tidal volume (V_T) and lung mechanics using different ventilators. A neonatal lung model was ventilated via a 3 mm ETT using three ventilators, Babylog 8000, Leoni, and Stephanie. ETT leakage was simulated by open silicone tubes with different lengths. The volume delivered to the lung model was measured and compared with the displayed expiratory V_T of the three ventilators. The effect of ETT leakage on lung mechanical parameters displayed by the ventilators was investigated for respiratory rates from 20 min⁻¹ to 70 min⁻¹ and a constant inspiratory time: expiratory time ratio of 1:1. The displayed ETT leakage depended on the size of the leak, ventilator settings, and the ventilator used. In the presence of ETT leakages, for all three ventilators, the displayed V_T underestimated the true volume delivered to the lung. With increasing ETT leakage, displayed compliance was overestimated by Babylog 8000 and Stephanie, whereas Leoni underestimated compliance. The displayed resistance increased with increasing ETT leakage for the three ventilators, but quite different. The effect of ETT leakage on displayed V_T and lung mechanical parameters is ventilator-dependent. ETT leakage can lead to incorrect measurements that indicate reduced V_T, improvement of lung compliance, or ETT obstruction.

Lung clearance index (LCI), measured by multiple breath washout (MBW), is one of the most frequently used measures of ventilation inhomogeneity. This study was designed to investigate the effect of lung volumes on LCI in young infants. The dependence of LCI on dead space volume (VD), tidal volume (VT) and functional residual capacity (FRC) was investigated by mathematical modeling and by MBW measurements using sulfur hexafluoride (SF6) as a tracer gas. MBW was performed in 150 infants, of median postmenstrual age 46.7 weeks, followed up after neonatal intensive care. Wheezing was assessed in 90 of these infants by computerized respiratory sound analysis during quiet sleep. The strongest correlation was observed between LCI and the volume ratios VT/FRC (Spearman rank order correlation coefficient Rs = 0.688, p < 0.001), VD/VT (Rs = 0.733, p < 0.001) and VD/FRC (Rs = 0.854, p < 0.001). LCI calculated from VD, VT, and FRC was linearly related to measured LCI with a coefficient of determination of 75%. There were no significant differences between wheezers and non-wheezers in postmenstrual age and body weight, but FRC was significantly increased (p < 0.001) and median (interquartile range) LCI significantly decreased (5.83 (5.45–6.51) versus (6.54 (6.03–7.22), p < 0.001) in wheezing compared to non-wheezing infants. Model calculations also showed that LCI was significantly reduced in wheezing infants (5.09 (4.79–5.62) versus 5.43 (5.08–5.82), p < 0.018), indicating that the reduction can be explained by differences in the lung volumes, not by improved ventilation homogeneity. In conclusion, the strong dependence of LCI on lung volumes in young infants can lead to misinterpretations regarding the homogeneity of alveolar ventilation.

Several respiratory diseases are associated with specific respiratory sounds. In contrast to auscultation, computerized lung sound analysis is objective and can be performed continuously over an extended period. Moreover, audio recordings can be stored. Computerized lung sounds have rarely been assessed in neonates during the first year of life. This study was designed to determine and validate optimal cut-off values for computerized wheeze detection, based on the assessment by trained clinicians of stored records of lung sounds, in infants aged <1 year.

Exhaled nitric oxide (eNO) is a marker of established airway inflammation in adults and children, but conflicting results have been reported in preterm infants when postnatal eNO is measured during tidal breathing. This study investigated the extent to which intubation and mechanical ventilation (MV) affect eNO and NO production (V'NO) in preterm infants with and without bronchopulmonary dysplasia (BPD). A total of 176 very low birth weight (VLBW) infants (birth weight <1500 g), including 74 (42%) with and 102 (58%) without BPD, were examined at a median postmenstrual age of 49 weeks. Of the 176 infants, 84 (48%) did not require MV, 47 (27%) required MV for <7 days and 45 (26%) required MV for ≥7 days. Exhaled NO and tidal breathing parameters were measured in sleeping infants during tidal breathing, respiratory mechanics were assessed by occlusion tests, and arterialized capillary blood gas was analyzed. eNO was significantly correlated with tidal breathing parameters, while V'NO was correlated with growth parameters, including age and body length (p < 0.001 each). Infants who were intubated and received MV for <7 days had significantly lower eNO (p < 0.01) and V'NO (p < 0.01) than non-ventilated infants. In contrast, eNO and V'NO did not differ significantly in non-ventilated infants and those receiving MV for ≥7 days. Multivariate analysis showed that independent on the duration of MV eNO (p = 0.003) and V'NO (p = 0.018) were significantly increased in BPD infants comparable with the effects of intubation and MV on eNO (p = 0.002) and V'NO (p = 0.017). Preterm infants with BPD show only weak postnatal increases in eNO and V'NO, but these changes may be obscured by the distinct influences of breathing pattern and invasive respiratory support. This limits the diagnostic value of postnatal eNO measurements in the follow-up of BPD infants.

Alveolar–capillary membrane leaks can increase the amount of surfactant protein B (SP-B) in the bloodstream. The purpose of this study was to measure the concentration of C-proSP-B, a SP-B precursor that includes C-terminal domains, in various body fluids of newborn infants and determine its dependence on gestational age.