Metabolomics of bronchoalveolar lavage in children with persistent wheezing.

BACKGROUND: Recent studies have demonstrated the important role of metabolomics in the pathogenesis of asthma. However, the role of lung metabolomics in childhood persistent wheezing (PW) or wheezing recurrence remains poorly understood. METHODS: In this prospective observational study, we performed a liquid chromatography/mass spectrometry-based metabolomic survey on bronchoalveolar lavage samples collected from 30 children with PW and 30 age-matched infants (control group). A 2-year follow-up study on these PW children was conducted. RESULTS: Children with PW showed a distinct characterization of respiratory metabolome compared with control group. Children with PW had higher abundances of choline, oleamide, nepetalactam, butyrylcarnitine, L-palmitoylcarnitine, palmitoylethanolamide, and various phosphatidylcholines. The glycerophospholipid metabolism pathway was the most relevant pathway involving in PW pathophysiologic process. Additionally, different gender, prematurity, and systemic corticoids use demonstrated a greater impact in airway metabolite compositions. Furthermore, for PW children with recurrence during the follow-up period, children who were born prematurely had an increased abundance of butyrylcarnitine relative to those who were carried to term. CONCLUSIONS: This study suggests that the alterations of lung metabolites could be associated with the development of wheezing, and this early alteration could also be correlated with wheezing recurrence later in life.

The effect of high-frequency oscillatory ventilation or airway pressure release ventilation on children with acute respiratory distress syndrome as a rescue therapy.

BACKGROUND: To investigate the effects of high-frequency oscillatory ventilation (HFOV) or airway pressure release ventilation (APRV) as a rescue therapy on children with moderate and severe acute respiratory distress syndrome (ARDS). METHODS: We retrospectively enrolled 47 children with ARDS who were transitioned from synchronized intermittent mandatory ventilation (SIMV) to either HFOV or APRV for 48 h or longer after failure of SIMV. The parameters of demographic data, arterial blood gases, ventilator settings, oxygenation index (OI), and PaO2/FiO2 (PF) ratio during the first 48 h of HFOV and APRV were recorded. RESULTS: There was no significant difference between the HFOV and APRV groups with survival rates of 60% and 72.7%, respectively. Compared to pre-transition, the mean airway pressures at 2 and 48 h after transition were higher in both groups (P<0.01), and the PF ratio at 2 and 48 h in both modes was significantly improved (P<0.001). PF ratio and PaCO2 have significant differences at 48 h between two groups. The OI at 2 h after transition had no improvement in either group and was substantially lower at 48 h relative to the pre-transition level (P<0.001) in both groups. At 48 h after the transition to both HFOV and APRV, the survivors had lower mean airway pressures, higher PF ratios, and a lower OIs than non-survivors (P<0.01). CONCLUSIONS: There was no significant difference on the survival rates of HFOV and APRV application as a rescue therapy for ARDS, but improved oxygenation at 48 h reliably discriminated survivors from non-survivors in both groups.

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

BACKGROUND: Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR. METHODS: An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR. RESULTS: Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma. CONCLUSIONS: These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.