Kerstin Jost

Changes in breathing pattern upon 100% oxygen in children at early school age

Nitrogen multiple-breath washout (N2MBW) is an increasingly used tidal breathing test in young children to assess ventilation inhomogeneity. However, the test requires 100% oxygen to perform. We aimed to examine the potential influence of pure oxygen on breathing pattern in school-aged children. We performed tidal breathing measurements under room air followed by N2MBW in 16 former preterm children and 24 healthy controls. We compared tidal volume (VT), coefficient of variation of VT (CVVT), respiratory rate (RR), and minute ventilation (VE) between tidal breathing and N2MBW, and between the start and end of tidal breathing. Mean (range) age was 6.8 (5.9, 9.0) years. VT, RR and VE showed no significant change upon oxygen-exposure, while CVVT significantly decreased by 5% (95% CI: 1.2, 9.0; p=0.012). However CVVT was also the only parameter which significantly decreased during tidal breathing. Overall, pure oxygen has no systematic effect on breathing pattern in young school-aged children. N2MBW can reliably be used as tracer gas in this age group.

Leaks during multiple-breath washout: characterisation and influence on outcomes

Nitrogen multiple-breath washout (N2MBW) is increasingly used in patients with cystic fibrosis. The current European Respiratory Society/American Thoracic Society consensus statement for MBW recommends the rejection of measurements with leaks. However, it is unclear whether this is necessary for all types of leaks. Here, our aim was to 1) model and 2) apply air leaks, and 3) to assess their influence on the primary MBW outcomes of lung clearance index and functional residual capacity. We investigated the influence of air leaks at various locations (pre-, intra- and post-capillary), sizes, durations and stages of the washout. Modelled leaks were applied to existing N2MBW data from 10 children by modifying breath tables. In addition, leaks were applied to the equipment during N2MBW measurements performed by one healthy adolescent. All modelled and applied leaks resulted in statistically significant but heterogeneous effects on lung clearance index and functional residual capacity. In all types of continuous inspiratory leaks exceeding a certain size, the end of the washout was not reached. For practical application, we illustrated six different “red flags”, i.e. signs that enable easy identification of leaks during measurements. Air leaks during measurement significantly influence N2MBW outcomes. The influence of leaks on MBW outcomes is dependent on the location, relation to breath cycle, duration, stage of washout and size of the leak. We identified a range of signs to help distinguish leaks from physiological noise. The influence of leaks on nitrogen MBW outcomes is complex, dynamic and dependent on the size, duration, location and position of leaks during the washout and breathing cycle http://ow.ly/PbHV30hB91H

Lung clearance index and moment ratios at different cut-off values in infant multiple-breath washout measurements

Multiple‐breath washout (MBW) is increasingly used for infant lung function testing. Current guidelines recommend calculating lung clearance index (LCI) and functional residual capacity (FRC) at 2.5% of normalized tracer gas concentration, without clear recommendation for moment ratios (MR). Whether the 2.5% cut‐off has the highest discriminative power to detect ventilation inhomogeneity in infants with lung diseases is unknown.

Sigh‐induced changes of breathing pattern in preterm infants

Sighs are thought to play an important role in control of breathing. It is unclear how sighs are triggered, and whether preterm birth and lung disease influence breathing pattern prior to and after a sigh in infants. To assess whether frequency, morphology, size, and short‐term variability in tidal volume (VT) before, during, and after a sigh are influenced by gestational age at birth and lung disease (bronchopulmonary dysplasia, BPD) in former preterm infants and healthy term controls measured at equivalent postconceptional age (PCA). We performed tidal breathing measurements in 143 infants during quiet natural sleep at a mean (SD) PCA of 44.8 (1.3) weeks. A total of 233 sighs were analyzed using multilevel, multivariable regression. Sigh frequency in preterm infants increased with the degree of prematurity and severity of BPD, but was not different from that of term controls when normalized to respiratory rate. After a sigh, VT decreased remarkably in all infants (paired t‐test: P < 0.001). There was no major effect of prematurity or BPD on various indices of sigh morphology and changes in VT prior to or after a sigh. Short‐term variability in VT modestly increased with maturity at birth and infants with BPD showed an earlier return to baseline variability in VT following a sigh. In early infancy, sigh‐induced changes in breathing pattern are moderately influenced by prematurity and BPD in preterm infants. The major determinants of sigh‐related breathing pattern in these infants remain to be investigated, ideally using a longitudinal study design.

Changes in minute ventilation after exposure to 4% sulfur hexafluoride (SF6) in infants

With interest, we read the recent publication by G. Banton et al. Exposure to 4% sulfur hexafluoride (SF6) during multiple breath washout (MBW) in infants was associated with diminished minute ventilation (VE) and increased tidal volume (VT). 1 Infants studied were heterogeneous regarding disease state, age, and use of sedation.Wewondered if changes in breathing pattern are reproducible in a more homogenous cohort of a narrow age range and always measured without sedation. In order to answer this, we took advantage of existing data from our birth cohort and assessed post-hoc breathing pattern encountered during 4% SF6 exposure for MBW. We analyzed tidal breathing and MBWSF6 measurements conducted between 2004 and 2014 in 30 preterm infants with a gestational age at birth between 23.9–35.4 weeks, and in 30 healthy term-born controls. The Ethics Committee of Bern approved the study, written parental informed consent was obtained. Lung functionwasmeasured during natural, quiet sleep as described. Each infant underwent one tidal breathing measurement (dry medical air) lasting 10min, followed by at least two MBWSF6 measurements using an open bypass system (Exhalyzer D, Eco Medics AG, Switzerland). Infants breathed the SF6 gas mixture via face mask until an equilibrium (washin) was established between inand exhaled SF6 fractions. The setup was switched to dry medical air for subsequent washout. Primary outcomes were VT, coefficient of variation of VT (CVVT), respiratory rate, and VE. These were compared (i) between the tidal breathing and MBWSF6 measurements and (ii) within tidal breathing measurements to assess physiological fluctuations. Data distribution was visually assessed and paired t-tests were applied using Stata (Release 11. College Station, TX: StataCorp LP). The mean (range) postmenstrual age was 45 (43–49) weeks at the time of the study. Four percent SF6 induced hypopnea in both preterm and healthy infants. When comparing 100 breaths duringmedical air versus 20 breaths during SF6 washin, VT and VE declined while respiratory rate did not. Mean decrease in VE was 140.0ml/min (95% CI: 70.0–210.1; P< 0.001) in preterm infants and 166.0 ml/min (87.2–244.9; P< 0.001) in healthy controls. The relative mean change of VE was 14% in preterm infants and 10% in healthy controls. Interestingly, VTand VE remained comparably low during SF6 washout (Fig. 1). When comparing the last 20 breaths during medical air versus 20 breaths during SF6 washin, VT and VE also declined. VT decreased by 3.1ml (1.9–4.3; P< 0.001) in preterm infants and 3.1ml (1.5–4.8; P< 0.001) in controls. Accordingly, VE decreased by 196.9ml (137.4–256.4; P< 0.001) in preterm infants and of 117.0ml (46.9–187.0; P1⁄4 0.002) in controls. Comparing the first 20 breaths with the last 20 breaths during medical air to assess physiologic fluctuations, VT andCVVTdid not change systematically. In 90%of infants, reduction of VE upon inhalation of SF6 exceeded their own physiologic variability (mean þ2 standard deviations of changes). This effect was even larger in infants remaining asleep (n1⁄4 41/60) compared to those who woke up between tests irrespective of preterm birth. In contrast to the previous study, in our protocol the setup’s CO2 sensor was only attached for tidal breathing but not for MBW measurements. Therefore, we additionally assessed 10 healthy term born infants with the CO2 sensor insertedalsoduringMBW.All these infants remainedasleep during the testing session. The effect size and direction of change in breathing pattern was akin. Comparing 100 breaths during medical air versus 20 breaths during SF6 washin, VE declined by 198.8ml (97.6–230.0, P1⁄4 0.002) without relevant changes in end-tidal CO2. We reassure that exposure to 4% SF6 during MBW systematically influences breathing pattern in infants. This also supports findings in adults, in whom inhalation of a

Surface electromyography for analysis of heart rate variability in preterm infants

OBJECTIVE Characterizing heart rate variability (HRV) in neonates has gained increased attention and is helpful in quantifying maturation and risk of sepsis in preterm infants. Raw data used to derive HRV in a clinical setting commonly contain noise from motion artifacts. Thoracic surface electromyography (sEMG) potentially allows for pre-emptive removal of motion artifacts and subsequent detection of interbeat interval (IBI) of heart rate to calculate HRV. We tested the feasibility of sEMG in preterm infants to exclude noisy raw data and to derive IBI for HRV analysis. We hypothesized that a stepwise quality control algorithm can identify motion artifacts which influence IBI values, their distribution in the time domain, and outcomes of nonlinear time series analysis. APPROACH This is a prospective observational study in preterm infants  <6 days of age. We used 100 sEMG measurements from 24 infants to develop a semi-automatic quality control algorithm including synchronized video recording, threshold-based sEMG envelope curve, optimized QRS-complex detection, and final targeted visual inspection of raw data. MAIN RESULTS Analysis of HRV from sEMG data in preterm infants is feasible. A stepwise algorithm to exclude motion artifacts and improve QRS detection significantly influenced data quality (34% of raw data excluded), distribution of IBI values in the time domain, and nonlinear time series analysis. The majority of unsuitable data (94%) were excluded by automated steps of the algorithm. SIGNIFICANCE Thoracic sEMG is a promising method to assess motion artifacts and calculate HRV in preterm neonates.

Dynamics and complexity of body temperature in preterm infants nursed in incubators

Background Poor control of body temperature is associated with mortality and major morbidity in preterm infants. We aimed to quantify its dynamics and complexity to evaluate whether indices from fluctuation analyses of temperature time series obtained within the first five days of life are associated with gestational age (GA) and body size at birth, and presence and severity of typical comorbidities of preterm birth. Methods We recorded 3h-time series of body temperature using a skin electrode in incubator-nursed preterm infants. We calculated mean and coefficient of variation of body temperature, scaling exponent alpha (Talpha) derived from detrended fluctuation analysis, and sample entropy (TSampEn) of temperature fluctuations. Data were analysed by multilevel multivariable linear regression. Results Data of satisfactory technical quality were obtained from 285/357 measurements (80%) in 73/90 infants (81%) with a mean (range) GA of 30.1 (24.0–34.0) weeks. We found a positive association of Talpha with increasing levels of respiratory support after adjusting for GA and birth weight z-score (p<0.001; R2 = 0.38). Conclusion Dynamics and complexity of body temperature in incubator-nursed preterm infants show considerable associations with GA and respiratory morbidity. Talpha may be a useful marker of autonomic maturity and severity of disease in preterm infants.