Atemwegserkrankungen und Allergien

Aufgrund ihrer großen Oberfläche und des dort stattfindenden Gasaustauschs ist die Lunge den zahlreichen Luftschadstoffen unmittelbar ausgesetzt. Besonders empfindlich hierfür ist die noch wachsende Lunge. Atemwegserkrankungen und Allergien können dann die Folge sein. Sowohl in Mitteleuropa wie auch in den sog. Entwicklungsländern sind Atemwegserkrankungen eine bedeutende Ursache der Krankheitslast (Burden of Disease). Betroffen sind vorwiegend Kinder und ältere Menschen. In Entwicklungsländern tragen Lungenentzündung und Tuberkulose signifikant zur Gesamtmortalität bei, in den westlichen Industrienationen sind chronische Atemwegserkrankungen wie COPD und Asthma für einen erheblichen Teil der Gesamtmorbidität verantwortlich. In diesem Abschnitt betrachten wir die Entwicklung der Lungenfunktion im Laufe des Lebens, die unterschiedliche Vulnerabilität der Lunge gegenüber Umwelteinflüssen in den verschiedenen Entwicklungsstadien sowie die globale Krankheitslast als Folge von respiratorischen Erkrankungen. Anschließend beschreiben wir das Asthma und die COPD hinsichtlich ihrer Risikofaktoren und erörtern, mit welchen präventiven Maßnahmen diese Erkrankungen zu verhindern wären. Schweizerische Lernziele: CPH 4

Giant Cardiac Fibroma: An Unusual Cause of Failure to Thrive

Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thriv

Regional and overall ventilation inhomogeneities in preterm and term-born infants

Objectives: We compared ventilation inhomogeneity assessed by electrical impedance tomography (EIT) and multiple breath washout (MBW) in preterm and term-born infants. We hypothesised that EIT measurements in spontaneously breathing infants are repeatable and that differences in regional ventilation distribution measured by EIT can distinguish between preterm and term-born infants. Design: Cross-sectional group comparison study. Setting: Lung function laboratory at a University Children's Hospital. Participants: Seventeen healthy term-born and 15 preterm infants at a matched postmenstrual age of 44weeks. Measurements and results: We concurrently measured ventilation inhomogeneity by EIT, ventilation inhomogeneity (LCI) and functional residual capacity (FRC) by MBW and tidal breathing variables during unsedated quiet sleep. EIT measurements were highly repeatable (coefficient of variation 3.6%). Preterm infants showed significantly more ventilation of the independent parts of the lungs compared to healthy term-born infants assessed by EIT (mean difference 5.0, 95 CI 1.3-8%). Whereas the two groups showed no differences in lung volumes or ventilation inhomogeneities assessed by MBW, EIT discriminated better between term and preterm infants. (FRC/kg: mean difference 1.1mL, 95% CI −1.4-3.8mL; LCI: mean difference 0.03, 95% CI −0.32-0.25). Conclusions: EIT shows distinct differences in ventilation distribution between preterm and term-born infants, which cannot be detected by MBW. Although preterm infants are capable of dynamically maintaining overall functional residual volume and ventilation distribution, they show some spatial differences from fullterm infant

Air pollution modelling for birth cohorts: a time-space regression model

To investigate air pollution effects during pregnancy or in the first weeks of life, models are needed that capture both the spatial and temporal variability of air pollution exposures.; We developed a time-space exposure model for ambient NO2 concentrations in Bern, Switzerland. We used NO2 data from passive monitoring conducted between 1998 and 2009: 101 rural sites (24,499 biweekly measurements) and 45 urban sites (4350 monthly measurements). We evaluated spatial predictors (land use; roads; traffic; population; annual NO2 from a dispersion model) and temporal predictors (meteorological conditions; NO2 from continuous monitoring station). Separate rural and urban models were developed by multivariable regression techniques. We performed ten-fold internal cross-validation, and an external validation using 57 NO2 passive measurements obtained at study participant's homes.; Traffic related explanatory variables and fixed site NO2 measurements were the most relevant predictors in both models. The coefficient of determination (R(2)) for the log transformed models were 0.63 (rural) and 0.54 (urban); cross-validation R(2)s were unchanged indicating robust coefficient estimates. External validation showed R(2)s of 0.54 (rural) and 0.67 (urban).; This approach is suitable for air pollution exposure prediction in epidemiologic research with time-vulnerable health effects such as those occurring during pregnancy or in the first weeks of life

Strain-level resolution and pneumococcal carriage dynamics by single-molecule real-time (SMRT) sequencing of the plyNCR marker: a longitudinal study in Swiss infants

BACKGROUND Pneumococcal carriage has often been studied from a serotype perspective; however, little is known about the strain-specific carriage and inter-strain interactions. Here, we examined the strain-level carriage and co-colonization dynamics of Streptococcus pneumoniae in a Swiss birth cohort by PacBio single-molecule real-time (SMRT) sequencing of the plyNCR marker. METHODS A total of 872 nasal swab (NS) samples were included from 47 healthy infants during the first year of life. Pneumococcal carriage was determined based on the quantitative real-time polymerase chain reaction (qPCR) targeting the lytA gene. The plyNCR marker was amplified from 214 samples having lytA-based carriage for pneumococcal strain resolution. Amplicons were sequenced using SMRT technology, and sequences were analyzed with the DADA2 pipeline. In addition, pneumococcal serotypes were determined using conventional, multiplex PCR (cPCR). RESULTS PCR-based plyNCR amplification demonstrated a 94.2% sensitivity and 100% specificity for Streptococcus pneumoniae if compared to lytA qPCR. The overall carriage prevalence was 63.8%, and pneumococcal co-colonization (≥ 2 plyNCR amplicon sequence variants (ASVs)) was detected in 38/213 (17.8%) sequenced samples with the relative proportion of the least abundant strain(s) ranging from 1.1 to 48.8% (median, 17.2%; IQR, 5.8-33.4%). The median age to first acquisition was 147 days, and having ≥ 2 siblings increased the risk of acquisition. CONCLUSION The plyNCR amplicon sequencing is species-specific and enables pneumococcal strain resolution. We therefore recommend its application for longitudinal strain-level carriage studies of Streptococcus pneumoniae. Video Abstract

Strain-level resolution and pneumococcal carriage dynamics by single-molecule real-time (SMRT) sequencing of the plyNCR marker: a longitudinal study in Swiss infants.

BACKGROUND Pneumococcal carriage has often been studied from a serotype perspective; however, little is known about the strain-specific carriage and inter-strain interactions. Here, we examined the strain-level carriage and co-colonization dynamics of Streptococcus pneumoniae in a Swiss birth cohort by PacBio single-molecule real-time (SMRT) sequencing of the plyNCR marker. METHODS A total of 872 nasal swab (NS) samples were included from 47 healthy infants during the first year of life. Pneumococcal carriage was determined based on the quantitative real-time polymerase chain reaction (qPCR) targeting the lytA gene. The plyNCR marker was amplified from 214 samples having lytA-based carriage for pneumococcal strain resolution. Amplicons were sequenced using SMRT technology, and sequences were analyzed with the DADA2 pipeline. In addition, pneumococcal serotypes were determined using conventional, multiplex PCR (cPCR). RESULTS PCR-based plyNCR amplification demonstrated a 94.2% sensitivity and 100% specificity for Streptococcus pneumoniae if compared to lytA qPCR. The overall carriage prevalence was 63.8%, and pneumococcal co-colonization (≥ 2 plyNCR amplicon sequence variants (ASVs)) was detected in 38/213 (17.8%) sequenced samples with the relative proportion of the least abundant strain(s) ranging from 1.1 to 48.8% (median, 17.2%; IQR, 5.8-33.4%). The median age to first acquisition was 147 days, and having ≥ 2 siblings increased the risk of acquisition. CONCLUSION The plyNCR amplicon sequencing is species-specific and enables pneumococcal strain resolution. We therefore recommend its application for longitudinal strain-level carriage studies of Streptococcus pneumoniae. Video Abstract

Breath detection algorithms affect multiple-breath washout outcomes in pre-school and school age children.

BACKGROUND Accurate breath detection is essential for the computation of outcomes in the multiple-breath washout (MBW) technique. This is particularly important in young children, where irregular breathing is common, and the designation of inspirations and expirations can be challenging. AIM To investigate differences between a commercial and a novel breath-detection algorithm and to characterize effects on MBW outcomes in children. METHODS We replicated the signal processing and algorithms used in Spiroware software (v3.3.1, Eco Medics AG). We developed a novel breath detection algorithm (custom) and compared it to Spiroware using 2,455 nitrogen (N2) and 325 sulfur hexafluoride (SF6) trials collected in infants, children, and adolescents. RESULTS In 83% of N2 and 32% of SF6 trials, the Spiroware breath detection algorithm rejected breaths and did not use them for the calculation of MBW outcomes. Our custom breath detection algorithm determines inspirations and expirations based on flow reversal and corresponding CO2 elevations, and uses all breaths for data analysis. In trials with regular tidal breathing, there were no differences in outcomes between algorithms. However, in 10% of pre-school children tests the number of breaths detected differed by more than 10% and the commercial algorithm underestimated the lung clearance index by up to 21%. CONCLUSION Accurate breath detection is challenging in young children. As the MBW technique relies on the cumulative analysis of all washout breaths, the rejection of breaths should be limited. We provide an improved algorithm that accurately detects breaths based on both flow reversal and CO2 concentration