Early life surfactant protein-D levels in bronchoalveolar lavage fluids of extremely preterm neonates

International audienceSurfactant protein-D (SP-D) is a hydrophilic protein with multiple crucial anti-inflammatory and immunological functions. It might play a role in the development and course of pulmonary infections, acute respiratory distress syndrome, and other respiratory disorders. Only few small neonatal studies have investigated SP-D: we aimed to investigate the links between this protein, measured in the first hours of life in extremely preterm neonates, and clinical outcomes, as well its relationship with pulmonary secretory phospholipase A2 (sPLA2). Bronchoalveolar lavage fluids were obtained within the first 3 h of life. SP-D and sPLA2 were measured with ELISA and radioactive method, respectively; epithelial lining fluid concentrations were estimated with urea ratio. Clinical data were prospectively collected. One hundred extremely preterm neonates were nonconsecutively studied. SP-D was significantly raised with increasing gestational age (24–26 wk: 68 [0–1,694], 27 or 28 wk: 286 [0–1,328], 29 or 30 wk: 1,401 [405–2,429] ng/mL, overall P = 0.03). SP-D was significantly higher in cases with clinical chorioamnionitis with fetal involvement (1,138 [68–3,336]) than in those without clinical chorioamnionitis with fetal involvement (0 [0–900] ng/mL, P < 0.001). SP-D was lower in infants with bronchopulmonary dysplasia (BPD) (251 [0–1,550 ng/mL]) compared with those without bronchopulmonary dysplasia (BPD) or who died before its diagnosis (977 [124–5,534 ng/mL], P = 0.05) and this was also significant upon multivariate analysis [odds ration (OR): 0.997 (0.994–0.999), P = 0.024], particularly in neonates between 27- and 28-wk gestation. SP-D significantly correlated with the duration of hospital stay (ρ = −0.283, P = 0.002), invasive ventilation (ρ = −0.544, P = 0.001), and total sPLA2 activity (ρ = 0.528, P = 0.008). These findings help understanding the role of SP-D early in life and support further investigation about the role of SP-D in developing BPD

Extrapulmonary surfactant therapy: review of available data and research/development issues

Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized. Here we aim to comprehensively review the data about surfactant biology and pharmacology in organs other than the lung, especially focusing in the more promising surfactant extrapulmonary roles.We also review any preclinical or clinical data available about the therapeutic use of surfactant in these contexts. We offer a summary of knowledge and research/development milestones, as possible useful guidance for researchers of multidisciplinary background.Sección Deptal. de Bioquímica y Biología Molecular (Biológicas)Fac. de Ciencias BiológicasTRUEpu

Respiratory and haemodynamic effects of 6h-pronation in neonates recovering from respiratory distress syndrome, or affected by acute respiratory distress syndrome or evolving bronchopulmonary dysplasia: a prospective, physiological, crossover, controlled cohort study

Background: Pronation ameliorates oxygenation in adults with acute respiratory distress syndrome (ARDS); the effect in neonates with ARDS or other types of respiratory failure is unknown. We aimed to verify if pronation has similar respiratory and haemodynamic effects in three common types of neonatal respiratory failure. Methods: Prospective, physiologic, crossover, quasi-randomised, controlled cohort study performed in a tertiary academic neonatal intensive care unit. We enrolled neonates with: 1) recovering respiratory distress syndrome (RDS, mild restrictive pattern); 2) neonatal ARDS (NARDS, severe restrictive pattern); or 3) evolving bronchopulmonary dysplasia (BPD), that is chronic pulmonary insufficiency of prematurity (mixed restrictive/obstructive pattern). Neonates with other lung disorders, malformations or haemodynamic impairment were excluded. Patients were started prone or supine and then shifted to the alternate position for 6h; measurements were performed after 30' of "wash out" from the positioning and at the end of 6h period. Primary outcomes were respiratory (PtcCO2, modified ventilatory index, PtcO2/FiO2, SpO2/FiO2, oxygenation index, ultrasound-assessed lung aeration) and haemodynamic (perfusion index, heart rate, arterial pressure, cardiac output) parameters. Findings: Between May 1st, 2019, and May 31st, 2021, 161 participants were enrolled in this study, and included in the final analysis. Pronation improved gas exchange and lung aeration (p always <0.01) and these effects were overturned in the alternate position, except for lung aeration in NARDS where the improvement persisted. The effects were greater in patients recovering from RDS than in those with evolving BPD than in those with NARDS, in this order (p always <0.01). Pronation produced a net recruitment as lung ultrasound score decreased in patients shifted from supine (16.9 (standard deviation: 5.8)) to prone (14.1 (standard deviation: 3.3), p < 0.01) and this reduction correlated with oxygenation improvement. Haemodynamic parameters remained within normal ranges. Interpretation: 6h-pronation can be used to improve gas exchange and lung aeration in neonates with recovering RDS, evolving BPD or NARDS without relevant haemodynamic effects. Funding: None

Effect of Different Probes and Expertise on the Interpretation Reliability of Point-of-Care Lung Ultrasound

International audienceBackground: The effect of different probes and operator experience on the reliability of lung ultrasound (LU) interpretation has not been investigated. We studied the effect of probes and operator experience on the interpretation reliability of LU in critically ill neonates.Methods: This was a prospective, blind, cohort study enrolling patients with basic patterns ("B," "severe B," consolidation). Patients were scanned with microlinear (15 MHz; L15), phased-array sectorial (6-12 MHz; S7), and microconvex (8 MHz; C8) probes, in random order. Static images were acquired in high resolution, anonymized, and included in a pictorial database in random sequences. Seventeen clinicians with different LU experience were asked to blindly assess the pictorial database. Interrater agreement and interpretation reliability were analyzed. Subanalyses according to expertise and probe, and multivariate linear regression (including an "expertise × probe" interaction factor), were also performed.Results: The agreement tends to be lower and more heterogeneous for residents (intraclass correlation coefficient [ICC], 0.82 [95% CI, 0.74-0.9], P < .001; I2, 67%, P = .04) and for fellows (ICC, 0.93 [95% CI, 0.9-0.97], P < .001; I2, 69%, P = .04), especially when using nonlinear probes, compared with senior physicians (ICC, 0.95 [95% CI, 0.93-0.96], P < .001; I2, 0%, P = .433). Area under the curve (AUC) values were high for all probes (L15, 0.96 [95% CI, 0.93-0.99]; C8, 0.91 [95% CI, 0.85-0.98]; S7, 0.86 [95% CI, 0.82-0.91]) and physicians (senior physicians, 0.95 [95% CI, 0.83-0.99]; fellows, 0.95 [95% CI, 0.75-0.99]; residents, 0.86 [95% CI, 0.5-0.99]). Worse reliability and higher heterogeneity were found when the evaluation was performed by residents (AUC, 0.9 [95% CI, 0.85-0.94], P < .01; I2, 93.6%, P < .001) than by fellows (AUC, 0.99 [95% CI, 0.9-0.999], P < .001; I2, 34.3%, P = .09) and/or by senior physicians (AUC, 0.99 [95% CI, 0.9-0.999], P < .001; I2, 18%, P = .236). The "expertise × probe" interaction factor was associated with lower ICC (standardized regression coefficient β, -0.69; P < .0001; adjusted R2, 0.99) and AUC (standardized regression coefficient β, -0.76; P < .0001; adjusted R2, 0.98).Conclusions: LU interpretation in neonates shows good interrater agreement and reliability, irrespective of the probe and rater expertise. The use of nonlinear probes by novice operators is associated with the lowest agreement and reliability

Secretory phospholipase A2 expression and activity in preterm clinical chorioamnionitis with fetal involvement

Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma (P < 0.001) and amniotic fluid (P < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid (P = 0.045) or increased, although without statistical significance, in maternal plasma (P = 0.06) and amniotic fluid (P = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-a and IL-1b) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-a (P = 0.028), IL-1b (P < 0.001), and IL-8 (P = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth

A Parallel Tracking of Salivary and Gut Microbiota Profiles Can Reveal Maturation and Interplay of Early Life Microbial Communities in Healthy Infants

In this study, the onset and shaping of the salivary and gut microbiota in healthy newborns during the first period of life has been followed, evaluating the impact of salivary microbiota on the development of early fecal microbial communities. The microbiota of 80 salivary and 82 fecal samples that were collected from healthy newborns in the first six months of life, was investigated by 16S rRNA amplicon profiling. The microbial relationship within and between the saliva and gut ecosystems was determined by correlation heatmaps and co-occurrence networks. Streptococcus and Staphylococcus appeared as early commensals in the salivary microbiota, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella, and Veillonella were late colonizers. Enterobacteriaceae, Staphylococcus and Streptococcus were gut pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella, and Bacteroides. Streptococcus, Staphylococcus, and Veillonella were shared by the gut and saliva ecosystems. The saliva and gut microbiota seem to evolve independently, driven by local adaptation strategies, except for the oral Streptococcus and Veillonella that are involved in gut microbiota development as seeding species. This study offers a piece of knowledge on how the oral microbiota may affect the gut microbiota in healthy newborns, shedding light onto new microbial targets for the development of therapies for early life intestinal dysbiosis

Otogenic lateral sinus thrombosis in children: proposal of an experience-based treatment flowchart

Purpose: To describe the prevalent clinical, laboratory, and radiological features of otogenic lateral sinus thrombosis (OLST) in children; to identify clinical predictors of outcome; to propose a management algorithm derived from experience. Methods: A retrospective review was conducted of the clinical records of patients with OLST, treated in a single tertiary care referral center for pediatric disease from 2006 to 2017. The inclusion criteria were pediatric age (0–16&nbsp;years) and OLST diagnosis confirmed by a pre- and post-contrast CT or venography–MRI scan. Primary outcome measures were early (1–2&nbsp;months) and late (6&nbsp;months) sinus recanalization assessed by means of neuroimaging. Results: Twenty-five patients (8 females and 17 males; mean age = 6 ± 3&nbsp;years) were included. A genetic abnormality associated with thrombophilia was found in 24 (96%) patients. At diagnosis, anticoagulant treatment with low-molecular-weight heparin (LMWH) was started in all subjects, while surgical treatment (mastoidectomy and tympanostomy tube insertion) was performed in 16/25 (64%) patients. Follow-up neuroimaging showed lateral sinus recanalization in 12/25 (48%) patients after 1–2&nbsp;months and in 17/25 (68%) after 6&nbsp;months. At multivariate logistic regression analysis, no significant predictors of the early and late neuroradiological outcome were found. Conclusions: All children with OLST should be screened for thrombophilia to decide on treatment duration and to assess the need for future antithrombotic prophylaxis. Immediately after diagnosis, anticoagulant treatment with LMWH should be started according to the international guidelines. Instead, our experience suggests that surgical treatment should not be indicated in all patients, but decided on a case-to-case basis