SFTA2 - a novel secretory peptide highly expressed in the lung - is modulated by lipopolysaccharide but not hyperoxia

Tissue-specific transcripts are likely to be of importance for the corresponding organ. While attempting to define the specific transcriptome of the human lung, we identified the transcript of a yet uncharacterized protein, SFTA2. In silico analyses, biochemical methods, fluorescence imaging and animal challenge experiments were employed to characterize SFTA2. Human SFTA2 is located on Chr. 6p21.33, a disease-susceptibility locus for diffuse panbronchiolitis. RT-PCR verified the abundance of SFTA2-specific transcripts in human and mouse lung. SFTA2 is synthesized as a hydrophilic precursor releasing a 59 amino acid mature peptide after cleavage of an N-terminal secretory signal. SFTA2 has no recognizable homology to other proteins while orthologues are present in all mammals. SFTA2 is a glycosylated protein and specifically expressed in nonciliated bronchiolar epithelium and type II pneumocytes. In accordance with other hydrophilic surfactant proteins, SFTA2 did not colocalize with lamellar bodies but colocalized with golgin97 and clathrin-labelled vesicles, suggesting a classical secretory pathway for its expression and secretion. In the mouse lung, Sfta2 was significantly downregulated after induction of an inflammatory reaction by intratracheal lipopolysaccharides paralleling surfactant proteins B and C but not D. Hyperoxia, however, did not alter SFTA2 mRNA levels. We have characterized SFTA2 and present it as a novel unique secretory peptide highly expressed in the lung

Clinically stable very low birthweight infants are at risk for recurrent tissue glucose fluctuations even after fully established enteral nutrition

Objective: In previous cases, we have observed occasional hypoglycaemic episodes in preterm infants after initial intensive care. In this prospective study, we determined the frequency and severity of abnormal tissue glucose (TG) in clinically stable preterm infants on full enteral nutrition. Methods: Preterm infants born at <1000 g (n=23; G1) and birth weight 1000–1500 g (n=18; G2) were studied at a postmenstrual age of 32±2 weeks (G1) and 33±2 weeks (G2). Infants were fed two or three hourly, according to a standard bolus-nutrition protocol, and continuous subcutaneous glucose measurements were performed for 72 h. Normal glucose values were assumed at ≥2.5 mmol/L (45 mg/dL) and ≤8.3 mmol/L (150 mg/dL). Frequency, severity and duration of glucose values beyond normal values were determined. Results: We observed asymptomatic low TG values in 39% of infants in G1 and in 44% in G2. High TG values were detected in 83% in G1 and 61% in G2. Infants in G1 experienced prolonged and more severe low TG episodes, and also more frequent and severe high TG episodes. In G1 and G2, 87% and 67% of the infants, respectively, showed glucose fluctuations characterised by rapid glucose increase followed by a rapid glucose drop after feeds. In more mature infants, glucose fluctuations were less pronounced and less dependent on enteral feeds. Conclusions: Clinically stable well-developing preterm infants beyond their initial period of intensive care show interstitial glucose instabilities exceeding values as low as 2.5 mmol/L and as high as 8.3 mmol/L. This novel observation may play an important role for the susceptibility of these high-risk infants for the development of the metabolic syndrome

Intensivtransport Neugeborener mit respiratorischem Versagen

&lt;jats:title&gt;Zusammenfassung&lt;/jats:title&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Hintergrund und Ziel der Studie&lt;/jats:title&gt; &lt;jats:p&gt;Der Transport von Früh und Neugeborenen mit respiratorischem Versagen ist mit einem hohen Transportrisiko assoziiert und stellt höchste Anforderungen an medizinisches Personal und technische Ausrüstung. Eine kontinuierliche Überprüfung der Qualität ist daher unumgänglich. Ziel dieser monozentrischen retrospektiven Analyse ist es, die Mortalität transportierter Neugeborener mit respiratorischem Versagen mithilfe eines Outcomescores, Transport Risk index of Physiologic Stability, Version II, (TRIPS-II-Score) und im Vergleich zu bereits publizierter Literatur zu analysieren.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Methodik&lt;/jats:title&gt; &lt;jats:p&gt;Es wurden 79 Intensivtransporte von Früh- und Neugeborenen mit hochgradigem respiratorischem Versagen retrospektiv analysiert. Zur Einschätzung des Transportrisikos und der Transportqualität wurde der TRIPS-II-Score erhoben und mit der Literatur verglichen.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Ergebnisse&lt;/jats:title&gt; &lt;jats:p&gt;Insgesamt wurden 77 Patienten luft- (&lt;jats:italic&gt;n&lt;/jats:italic&gt; = 56, 73 %) oder bodengebunden (&lt;jats:italic&gt;n&lt;/jats:italic&gt; = 21, 27 %) transportiert. Zwei Patienten verstarben vor dem Transport. Kein Patient verstarb während des Transports. Alle Patienten mussten invasiv beatmet werden, davon 22 (29 %) mit Hochfrequenzoszillation (HFOV) und 55 (71 %) erhielten inhalatives Stickoxid (iNO). Der mittlere Oxygenierungsindex (OI) betrug 33 [4-100, min.-max.] Insgesamt mussten 24 Patienten (31 %) nach Aufnahme einer ECMO-Therapie unterzogen werden. Insgesamt verstarben 20 (26 %) Neugeborene, 7 davon in der ECMO-Therapie-Gruppe.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Schlussfolgerung&lt;/jats:title&gt; &lt;jats:p&gt;Transporte von Neugeborenen mit schwerem Lungenversagen können durch den Einsatz eines spezialisierten Teams mit Sonderequipment meist komplikationslos durchgeführt werden. Die scheinbar sehr hohe Mortalität ist mit Daten der internationalen Literatur vergleichbar.&lt;/jats:p&gt; &lt;/jats:sec&gt

Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach

BACKGROUND: Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles. METHODS: Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP). For analysis, we employed two independent, prospective cohorts, comprising a total of 530 very preterm infants: AIRR ("Attention to Infants at Respiratory Risks") and NEuroSIS ("Neonatal European Study of Inhaled Steroids"). Using a data-driven strategy, we successfully characterized morbidity profiles of preterm infants in a stepwise approach and (1) quantified pairwise morbidity correlations, (2) assessed the discriminatory power of BPD (complemented by imaging-based structural and functional lung phenotyping) in relation to these morbidities, (3) investigated collective co-occurrence patterns, and (4) identified infant subgroups who share similar morbidity profiles using machine learning techniques. RESULTS: First, we showed that, in line with pathophysiologic understanding, BPD and ROP have the highest pairwise correlation, followed by BPD and PH as well as BPD and mild cardiac defects. Second, we revealed that BPD exhibits only limited capacity in discriminating morbidity occurrence, despite its prevalence and clinical indication as a driver of comorbidities. Further, we demonstrated that structural and functional lung phenotyping did not exhibit higher association with morbidity severity than BPD. Lastly, we identified patient clusters that share similar morbidity patterns using machine learning in AIRR (n=6 clusters) and NEuroSIS (n=8 clusters). CONCLUSIONS: By capturing correlations as well as more complex morbidity relations, we provided a comprehensive characterization of morbidity profiles at discharge, linked to shared disease pathophysiology. Future studies could benefit from identifying risk profiles to thereby develop personalized monitoring strategies

Gas exchange mechanisms in preterm infants on HFOV - a computational approach

High-frequency oscillatory ventilation (HFOV) is a commonly used therapy applied to neonates requiring ventilatory support during their first weeks of life. Despite its wide application, the underlying gas exchange mechanisms promoting the success of HVOF in neonatal care are not fully understood until today. In this work, a highly resolved computational lung model, derived from Magnetic Resonance Imaging (MRI) and Infant Lung Function Testing (ILFT), is used to reveal the reason for highly efficient gas exchange during HFOV, in the preterm infant. In total we detected six mechanisms that facilitate gas exchange during HFOV: (i) turbulent vortices in large airways;(ii) asymmetric in-and expiratory flow profiles;(iii) radial mixing in main bronchi;(iv) laminar flow in higher generations of the respiratory tract;(v) pendelluft;(vi) direct ventilation of central alveoli. The illustration of six specific gas transport phenomena during HFOV in preterm infants advances general knowledge on protective ventilation in neonatal care and can support decisions on various modes of ventilatory therapy at high frequencies

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Standardized outcome measures for preterm and hospitalized neonates : an ICHOM standard set

Introduction: Approximately, one in ten infants is born preterm or requires hospitalization at birth. These complications at birth have long-term consequences that can extend into childhood and adulthood. Timely detection of developmental delay through surveillance could enable tailored support for these babies and their families. However, the possibilities for follow-up are limited, especially in middle- and low-income countries, and the tools to do so are either not available or too expensive. A standardized and core set of outcomes for neonates, with feasible tools for evaluation and follow-up, could result in improving quality, enhance shared decision-making, and enable global benchmarking. Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group, which was comprised of 14 health-care professionals (HCP) and 6 patient representatives in the field of neonatal care. An outcome set was developed using a three-round modified Delphi process, and it was endorsed through a patient representative-validation survey and an HCP survey. Results: A literature review revealed 1,076 articles and 26 registries which were screened for meaningful outcomes, patient-reported outcome measures, clinical measures, and case mix variables. This resulted in a neonatal set with 21 core outcomes covering three domains (physical, social, and mental functioning) and 14 tools to assess these outcomes at three timepoints. Discussion: This set can be implemented globally and it will allow comparison of outcomes across different settings and countries. The transparent consensus-driven development process which involved stakeholders and professionals from all over the world ensures global relevance

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified