A computerized tool for the systematic visual quality assessment of infant multiple-breath washout measurements.

Background: Multiple-breath washout (MBW) is a sensitive method for assessing lung volumes and ventilation inhomogeneity in infants, but remains prone to artefacts (e.g., sighs). There is a lack of tools for systematic retrospective analysis of existing datasets, and unlike N2-MBW in older children, there are few specific quality control (QC) criteria for artefacts in infant SF6-MBW. Aim: We aimed to develop a computer-based tool for systematic evaluation of visual QC criteria of SF6-MBW measurements and to investigate interrater agreement and effects on MBW outcomes among three independent examiners. Methods: We developed a software package for visualization of raw Spiroware (Eco Medics AG, Switzerland) and signal processed WBreath (ndd Medizintechnik AG, Switzerland) SF6-MBW signal traces. Interrater agreement among three independent examiners (two experienced, one novice) who systematically reviewed 400 MBW trials for visual artefacts and the decision to accept/reject the washin and washout were assessed. Results: Our tool visualizes MBW signals and provides the user with (i) display options (e.g., zoom), (ii) options for a systematic QC assessment [e.g., decision to accept or reject, identification of artefacts (leak, sigh, irregular breathing pattern, breath hold), and comments], and (iii) additional information (e.g., automatic identification of sighs). Reviewer agreement was good using pre-defined QC criteria (κ 0.637-0.725). Differences in the decision to accept/reject had no substantial effect on MBW outcomes. Conclusion: Our visual quality control tool supports a systematic retrospective analysis of existing data sets. Based on predefined QC criteria, even inexperienced users can achieve comparable MBW results.

Differences in autophagy marker levels at birth in preterm vs. term infants.

BACKGROUND: Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants. METHODS: In the prospective Basel-Bern Infant Lung Development (BILD) birth cohort we compared cord blood levels of macroautophagy (Beclin-1, LC3B), selective autophagy (p62) and regulation of autophagy (SIRT1) in 64 preterm and 453 term infants. RESULTS: Beclin-1 and LC3B did not differ between preterm and term infants. However, p62 was higher (0.37, 95% confidence interval (CI) 0.05;0.69 in log2-transformed level, p = 0.025, padj = 0.050) and SIRT1 lower in preterm infants (-0.55, 95% CI -0.78;-0.31 in log2-transformed level, padj < 0.001). Furthermore, p62 decreased (padj-value for smoothing function was 0.018) and SIRT1 increased (0.10, 95% CI 0.07;0.13 in log2-transformed level, padj < 0.001) with increasing gestational age. CONCLUSION: Our findings suggest differential levels of key autophagy markers between preterm and term infants. This adds to the knowledge of the sparsely studied field of autophagy mechanisms in preterm infants and might be linked to impaired oxidative stress response, preterm birth, impaired lung development and higher susceptibility to respiratory morbidity in preterm infants. IMPACT: To the best of our knowledge, this is the first study to investigate autophagy marker levels between human preterm and term infants in a large population-based sample in cord blood plasma This study demonstrates differential levels of key autophagy markers in preterm compared to term infants and an association with gestational age This may be linked to impaired oxidative stress response or developmental aspects and provide bases for future studies investigating the association with respiratory morbidity.

Antibiotics in pregnancy influence nasal microbiome and respiratory morbidity in infancy.

Background: The effects of prenatal antibiotic exposure on respiratory morbidity in infancy and the involved mechanisms are still poorly understood. We aimed to examine whether prenatal antibiotic exposure in the third trimester is associated with nasal microbiome and respiratory morbidity in infancy and at school age, and whether this association with respiratory morbidity is mediated by the nasal microbiome. Methods: We performed 16S ribosomal RNA gene sequencing (regions V3-V4) on nasal swabs obtained from 296 healthy term infants from the prospective Basel-Bern birth cohort (BILD) at age 4-6 weeks. Information about antibiotic exposure was derived from birth records and standardised interviews. Respiratory symptoms were assessed by weekly telephone interviews in the first year of life and a clinical visit at age 6 years. Structural equation modelling was used to test direct and indirect associations accounting for known risk factors. Results: α-Diversity indices were lower in infants with antibiotic exposure compared to nonexposed infants (e.g. Shannon index p-value 0.006). Prenatal antibiotic exposure was also associated with a higher risk of any, as well as severe, respiratory symptoms in the first year of life (risk ratio 1.38, 95% CI 1.03-1.84; adjusted p-value (padj)=0.032 and risk ratio 1.75, 95% CI 1.02-2.97; padj=0.041, respectively), but not with wheeze or atopy in childhood. However, we found no indirect mediating effect of nasal microbiome explaining these clinical symptoms. Conclusion: Prenatal antibiotic exposure was associated with lower diversity of nasal microbiome in infancy and, independently of microbiome, with respiratory morbidity in infancy, but not with symptoms later in life.