Lung function in very low birth weight infants after pharmacological and surgical treatment of patent ductus arteriosus - a retrospective analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Validation of computerized wheeze detection in young infants during the first months of life.

BACKGROUND: 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. METHODS: Lung sounds in 120 sleeping infants, of median (interquartile range) postmenstrual age of 51 (44.5-67.5) weeks, were recorded on 144 test occasions by an automatic wheeze detection device (PulmoTrack®). The records were retrospectively evaluated by three trained clinicians blinded to the results. Optimal cut-off values for the automatically determined relative durations of inspiratory and expiratory wheezing were determined by receiver operating curve analysis, and sensitivity and specificity were calculated. RESULTS: The optimal cut-off values for the automatically detected durations of inspiratory and expiratory wheezing were 2% and 3%, respectively. These cutoffs had a sensitivity and specificity of 85.7% and 80.7%, respectively, for inspiratory wheezing and 84.6% and 82.5%, respectively, for expiratory wheezing. Inter-observer reliability among the experts was moderate, with a Fleiss' Kappa (95% confidence interval) of 0.59 (0.57-0.62) for inspiratory and 0.54 (0.52 - 0.57) for expiratory wheezing. CONCLUSION: Computerized wheeze detection is feasible during the first year of life. This method is more objective and can be more readily standardized than subjective auscultation, providing quantitative and noninvasive information about the extent of wheezing.

Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: longitudinal assessment during the first 15 months of corrected age.

BACKGROUND: Very low birth weight (VLBW) infants (< 1,500 g) with bronchopulmonary dysplasia (BPD) develop lung damage caused by mechanical ventilation and maturational arrest. We compared functional lung development after discharge from hospital between VLBW infants with and without BPD. METHODS: Comprehensive lung function assessment was performed at about 50, 70, and 100 weeks of postmenstrual age in 55 sedated VLBW infants (29 with former BPD [O2 supplementation was given at 36 weeks of gestational age] and 26 VLBW infants without BPD [controls]). Mean gestational age (26 vs. 29 weeks), birth weight (815 g vs. 1,125 g), and the proportion of infants requiring mechanical ventilation for ≥7 d (55% vs. 8%), differed significantly between BPD infants and controls. RESULTS: Both body weight and length, determined over time, were persistently lower in former BPD infants compared to controls, but no significant between-group differences were noted in respiratory rate, respiratory or airway resistance, functional residual capacity as determined by body plethysmography (FRC(pleth)), maximal expiratory flow at the FRC (V'max (FRC)), or blood gas (pO2, pCO2) levels. Tidal volume, minute ventilation, respiratory compliance, and FRC determined by SF6 multiple breath washout (representing the lung volume in actual communication with the airways) were significantly lower in former BPD infants compared to controls. However, these differences became non-significant after normalization to body weight. CONCLUSIONS: Although somatic growth and the development of some lung functional parameters lag in former BPD infants, the lung function of such infants appears to develop in line with that of non-BPD infants when a body weight correction is applied. Longitudinal lung function testing of preterm infants after discharge from hospital may help to identify former BPD infants at risk of incomplete recovery of respiratory function; such infants are at risk of later respiratory problems.

Computerized wheeze detection in young infants: comparison of signals from tracheal and chest wall sensors.

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.

Relationship between computerized wheeze detection and lung function parameters in young infants.

OBJECTIVE: Computerized respiratory sound analysis (CORSA) has been validated in the assessment of wheeze in infants, but it is unknown whether automatically detected wheeze is associated with impaired lung function. This study investigated the relationship between wheeze detection and conventional lung function testing (LFT) parameters. METHODS: CORSA was performed using the PulmoTrack® monitor in 110 infants, of median (interquartile range) postmenstrual age 50 (46-56) weeks and median body weight 4,810 (3,980-5,900) g, recovering from neonatal intensive care. In the same session, LFT was performed, including tidal breathing measurements, occlusion tests, body plethysmography, forced expiratory flow by rapid thoracoabdominal compression, sulfur hexafluoride (SF6 ) multiple breath washout (MBW), and capillary blood gas analysis. Infants were classified as wheezers or non-wheezers using predefined cut-off values for the duration of inspiratory and expiratory wheeze. RESULTS: Wheezing was detected in 72 (65%) infants, with 43 (39%) having inspiratory and 53 (48%) having expiratory wheezing. Endotracheal mechanical ventilation in the neonatal period for > 24 hr was associated with inspiratory wheeze (P = 0.009). Airway resistance was increased in both inspiratory (P = 0.02) and expiratory (P = 0.004) wheezers and correlated with the duration of expiratory wheeze (r = 0.394, P < 0.001). Expiratory wheezers showed a significant increase in respiratory resistance (P = 0.001), time constant (0.012), and functional residual capacity using SF6 MBW (P = 0.019). There was no association between wheezing and forced expiratory flow or blood gases. CONCLUSION: CORSA can help identify neonates and young infants with subclinical airway obstruction and may prove useful in the follow-up of high-risk infants.

Reliability of Single-Use PEEP-Valves Attached to Self-Inflating Bags during Manual Ventilation of Neonates--An In Vitro Study.

INTRODUCTION: International resuscitation guidelines suggest to use positive end-expiratory pressure (PEEP) during manual ventilation of neonates. Aim of our study was to test the reliability of self-inflating bags (SIB) with single-use PEEP valves regarding PEEP delivery and the effect of different peak inflation pressures (PIP) and ventilation rates (VR) on the delivered PEEP. METHODS: Ten new single-use PEEP valves from 5 manufacturers were tested by ventilating an intubated 1 kg neonatal manikin containing a lung model with a SIB that was actuated by an electromechanical plunger device. Standard settings: PIP 20 cmH2O, VR 60/min, flow 8 L/min. PEEP settings of 5 and 10 cmH2O were studied. A second test was conducted with settings of PIP 40 cmH2O and VR 40/min. The delivered PEEP was measured by a respiratory function monitor (CO2SMO+). RESULTS: Valves from one manufacturer delivered no relevant PEEP and were excluded. The remaining valves showed a continuous decay of the delivered pressure during expiration. The median (25th and 75th percentile) delivered PEEP with standard settings was 3.4(2.7-3.8) cmH2O when set to 5 cmH2O and 6.1(4.9-7.1) cmH2O when set to 10 cmH2O. Increasing the PIP from 20 to 40 cmH2O led to a median (25th and 75th percentile) decrease in PEEP to 2.3(1.8-2.7) cmH2O and 4.3(3.2-4.8) cmH2O; changing VR from 60 to 40/min led to a PEEP decrease to 2.8(2.1-3.3) cmH2O and 5.0(3.5-6.2) cmH2O for both PEEP settings. CONCLUSION: Single-use PEEP valves do not reliably deliver the set PEEP. PIP and VR have an effect on the delivered PEEP. Operators should be aware of these limitations when manually ventilating neonates.

The lung clearance index in young infants: impact of tidal volume and dead space.

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.

Postnatal lung function in congenital cystic adenomatoid malformation of the lung.

BACKGROUND: Management of prenatally diagnosed but postnatal asymptomatic pulmonary lesions remains controversial. The aim of this study was to investigate the effect of congenital cystic adenomatoid malformation of the lung (CCAM) on postnatal lung function tests (LFT) and to elucidate whether LFTs help identify infants who would benefit from early surgery. METHODS: The LFTs were performed in 26 CCAM infants at a median (interquartile range) postmenstrual age of 42.4 (39.6 to 44.0) weeks and compared with LFT from 30 healthy controls. The LFT included the measurement of tidal breathing, functional residual capacity by body plethysmography, respiratory mechanics (respiratory compliance), and respiratory resistance by occlusion test and blood gas analysis. RESULTS: The CCAM infants showed a restrictive ventilation disorder with increased respiratory rates (p = 0.006) and marginally decreased tidal volumes (p = 0.043). Furthermore, respiratory compliance was significantly reduced as compared with controls (p < 0.001). No statistically significant differences were seen in the respiratory resistance, functional residual capacity, and capillary blood gases. Particularly in CCAM infants who had surgery in the first 2 years of life, a marked reduction of respiratory compliance (p < 0.001) was seen preoperatively. CONCLUSIONS: Congenital cystic adenomatoid malformation can cause restrictive ventilation disorders, which can be detected and monitored by postnatal LFT. Thus, LFT represents an additional tool to support the decision for or against surgical intervention.

Effect of intubation and mechanical ventilation on exhaled nitric oxide in preterm infants with and without bronchopulmonary dysplasia measured at a median postmenstrual age of 49 weeks.

BACKGROUND: 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). PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Differential effects of immaturity and neonatal lung disease on the lung function of very low birth weight infants at 48-52 postconceptional weeks.

BACKGROUND: The pathogenesis of chronic lung disease of prematurity involves maturational arrest and neonatal lung disease (NLD) followed by mechanical ventilation (MV). However, the effect of these factors on postnatal lung function is not well established. Therefore, the aim of this study was to examine the differential effects of immaturity and NLD requiring MV on lung function test (LFT) parameters within 4 months after discharge. PATIENTS AND METHODS: A total of 386 very low birth weight (VLBW) infants (birth weight <1,500 g) were examined at a median postmenstrual age of 49 weeks. Two hundred twenty-six infants (59%) were born before the 28th week of gestation, and 247 infants (64%) had NLD requiring invasive MV. LFTs included tidal breathing measurements, measurement of respiratory mechanics assessed by occlusion test, body plethysmography, SF6 multiple breath washout, forced expiratory flow (VmaxFRC') by rapid thoraco-abdominal compression technique, end-expiratory CO2 (Pet CO2 ), exhaled NO (FeNO), and arterialized capillary blood gas analysis. MAIN RESULTS: Multivariate analysis indicated that severe immaturity was mainly associated with changes in the breathing pattern (reduced tidal volume (P = 0.003) and increased respiratory rate (P = 0.03)), a reduced VmaxFRC' (P = 0.004) and lower respiratory compliance (P < 0.001). NLD requiring MV, but not immaturity, was significantly and independently associated with increased respiratory and airway resistances (both P = 0.003), reduced FRCSF6 (P = 0.03), increased Pet CO2 (P = 0.019) and lower FeNO (P < 0.001). Both immaturity and NLD requiring MV caused a lower paO2 (P < 0.001) and higher a paCO2 . CONCLUSIONS: Lung function after discharge of VLBW infants is differentially affected by both immaturity and NLD requiring MV. With increasing prematurity, intubated and mechanically ventilated infants are at increased risk of developing impaired lung function which can be detected by LFT.

Early lung function testing in infants with aortic arch anomalies identifies patients at risk for airway obstruction.

BACKGROUND: Aortic arch anomalies (AAA) are rare cardio-vascular anomalies. Right-sided and double-sided aortic arch anomalies (RAAA, DAAA) are distinguished, both may cause airway obstructions. We studied the degree of airway obstruction in infants with AAA by neonatal lung function testing (LFT). PATIENTS AND METHODS: 17 patients (10 RAAA and 7 DAAA) with prenatal diagnosis of AAA were investigated. The median (range) post conception age at LFT was 40.3 (36.6-44.1) weeks, median body weight 3400 (2320-4665) g. Measurements included tidal breathing flow-volume loops (TBFVL), airway resistance (R(aw)) by bodyplethysmography and the maximal expiratory flow at functional residual capacity (V'(max)FRC) by rapid thoracic-abdominal compression (RTC) technique. V'(max)FRC was also expressed in Z-scores, based on published gender-, age and height-specific reference values. RESULTS: Abnormal lung function tests were seen in both RAAA and DAAA infants. Compared to RAAA infants, infants with DAAA had significantly more expiratory flow limitations in the TBFVL, (86% vs. 30%, p<0.05) and a significantly increased R(aw) (p = 0.015). Despite a significant correlation between R(aw) and the Z-score of V'(max)FRC (r = 0.740, p<0.001), there were no statistically significant differences in V'(max)FRC and it's Z-scores between RAAA and DAAA infants. 4 (24%) infants (2 RAAA, 2 DAAA) were near or below the 10(th) percentile of V'(max)FRC, indicating a high risk for airway obstruction. CONCLUSION: Both, infants with RAAA and DAAA, are at risk for airway obstruction and early LFT helps to identify and to monitor these infants. This may support the decision for therapeutic interventions before clinical symptoms arise.