Antenatal creatine supplementation reduces persistent fetal lung inflammation and oxidative stress in an ovine model of chorioamnionitis.

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties. The objective of the study was to evaluate the efficacy of direct fetal creatine supplementation to reduce inflammation and oxidative stress in fetal lungs arising from an in utero proinflammatory stimulus. Fetal lambs (n = 51) were instrumented at 90 days gestation to receive a continuous infusion of creatine monohydrate (6 mg·kg-1·h-1) or saline for 17 days. Maternal chorioamnionitis was induced with intra-amniotic lipopolysaccharide (LPS; 1 mg, O55:H6) or saline 7 days before delivery at 110 days gestation. Tissue creatine content was assessed with capillary electrophoresis, and inflammatory markers were analyzed with Luminex Magpix and immunohistochemistry. Oxidative stress was measured as the level of protein thiol oxidation. The effects of LPS and creatine were analyzed using a two-way ANOVA. Fetal creatine supplementation increased lung creatine content by 149% (PCr < 0.0001) and had no adverse effects on lung morphology. LPS-exposed groups showed increased levels of interleukin-8 in the bronchoalveolar lavage (PLPS < 0.0001) and increased levels of CD45+ leukocytes (PLPS < 0.0001) and MPO+ (PLPS < 0.0001) cells in the lung parenchyma. Creatine supplementation significantly reduced the levels of CD45+ (PCr = 0.045) and MPO+ cells (PCr = 0.012) in the lungs and reduced thiol oxidation in plasma (PCr < 0.01) and lung tissue (PCr = 0.02). In conclusion, fetal creatine supplementation reduced markers of inflammation and oxidative stress in the fetal lungs arising from chorioamnionitis.NEW & NOTEWORTHY We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine.

Influence of head flexion and rotation on obstructive sleep apnea severity during supine sleep.

Head posture influences the collapsibility of the passive upper airway during anaesthesia. However, little is known about the impact of head posture during sleep. The objective of this study was to develop and validate an instrument to measure head posture during supine sleep and to apply this instrument to investigate the influence of head posture on obstructive sleep apnea (OSA) severity. A customized instrument to quantify head flexion and rotation during supine sleep was developed and validated in a benchtop experiment. Twenty-eight participants with suspected OSA were successfully studied using diagnostic polysomnography with the addition of the customized instrument. Head posture in supine sleep was discretized into four categories by two variables: head flexed or not (flexion >15°); and head rotated or not (rotation >45°). Sleep time in each posture and the posture-specific apnea-hypopnea index (AHI) were quantified. Linear mixed-effect modelling was applied to determine the influence of flexion and rotation on supine OSA severity. Twenty-four participants had ≥15 min of supine sleep in at least one head-posture category. Only one participant had ≥15 min of supine sleep time with the head extended. Head flexion was associated with a 12.9 events/h increase in the AHI (95% CI: 3.7-22.1, p = .007). Head rotation was associated with an 11.0 events/h decrease in the AHI (95% CI: 0.3-21.6, p = .04). Despite substantial interparticipant variability, head flexion worsened OSA severity, and head rotation improved OSA severity. Interventions to promote rotation and restrict flexion may have therapeutic benefit in selected patients.

An emerging technology for the identification and characterization of postural-dependent obstructive sleep apnea.

STUDY OBJECTIVES: Body posture has a significant impact on the presence and severity of obstructive sleep apnea (OSA). The majority of polysomnography (PSG) systems have the capacity to categorize body (torso) posture as supine, left-lateral, right-lateral or prone, each within a 90-degree range. However, such broad categorization may limit the identification of subtle relationships between posture and OSA severity. The aim of this study was to quantify sleeping posture as a continuous variable; and to develop an intuitive tool for visualizing the relationship between body posture and OSA severity. METHODS: A customized triaxial accelerometer-based posture sensor which quantifies torso posture as a continuous variable was developed. 38 participants attending the sleep laboratory for suspected OSA were recruited. Each participant underwent a diagnostic PSG with an additional customized posture sensor securely attached to the sternum. Individual data were presented using a novel circular histogram-based visualization which displays sleeping position and position-specific OSA severity. RESULTS: Acceptable measurements were obtained in 21 participants. The mean ± standard deviation percentage of total sleep time spent within ± 15 degrees of the center of supine, left-lateral, right-lateral and prone was 59.7 ± 26.0%. A further 40.3 ± 26.0% of sleep time was spent in intermediate positions outside these traditional categorizations. The novel visualization revealed a wide variety of positional OSA phenotypes. CONCLUSIONS: Quantification of torso posture as a continuous variable and analysis of these data using a novel visualization enables the identification of subtle relationships between body posture and OSA severity that are not apparent using standard clinical sensors and summary statistics.