Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS). We report here that alveolar macrophages increase AOAH expression upon exposure to LPS and that Aoah+/+ mice recover more rapidly than do Aoah-/- mice from ALI induced by nasally instilled LPS or Klebsiella pneumoniae. Aoah-/- mouse lungs had more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer-lasting alveolar barrier damage. We also describe evidence that the persistently bioactive LPS in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Distinct from the prolonged tolerance observed in LPS-exposed Aoah-/- peritoneal macrophages, alveolar macrophages that lacked AOAH maintained or increased their responses to bioactive LPS and sustained inflammation. Inactivation of LPS by AOAH is a previously unappreciated mechanism for promoting resolution of pulmonary inflammation/injury induced by Gram-negative bacterial infection.
Background: Echocardiography has poor accuracy in grading the severity of pulmonary hypertension (PH) compared to cardiac catheterization. However, the relationship between degree of PH and prognostic outcomes remains uncertain. Our primary objective was to determine whether echocardiogram-assessed PH severity is associated with mortality and hospital readmission in the first year of life.Methods: A retrospective cohort study of infants born less than 32 weeks of gestational age with bronchopulmonary dysplasia (BPD) underwent echocardiography was performed. Echocardiograms were performed at 36-38 weeks postmenstrual age. Data during hospitalization and post-discharge collected at 1-year age were analyzed with cox regression models and logistic regression models to identify the association of PH severity with mortality and readmission. Area under curve (AUC) was calculated to examine the accuracy of these models to reflect the likelihood of outcomes.Results: Fifty-six of 237 (23.6%) infants were diagnosed as PH. Moderate and severe PH was significantly associated with mortality during the first one year of life (moderate PH vs. none HR =26.58, 95% CI: 4.40-160.78, P<0.001; severe PH vs. none HR =36.49, 95% CI: 5.65-235.84, P<0.001). Male, preeclampsia and inhaled nitric oxide were also associated with mortality. Mild PH was significantly associated with readmission (OR =2.42, 95% CI: 1.12-5.26, P=0.025), but not associated with mortality (HR =2.09, 95% CI: 0.43-10.18, P=0.36). The PH severity model based on echocardiography accurately informed mortality (AUC 0.79).Conclusions: Echocardiogram-assessed PH severity is associated with prognostic outcomes, including mortality and readmission in very preterm infants with BPD. The severity of PH based on echocardiography is a potential predictor of mortality in the first year of life.
Metabolic bone disease (MBD) impacts the prognosis of premature infants. There is an urgent need for a portable, noninvasive, and radiation-free method for assessing neonatal bone status. The objective of this study is to evaluate the feasibility of the ultrasonic backscatter technique for assessing and monitoring cancellous bone status in neonates. Ultrasonic backscatter measurements were performed on 766 infants at birth and followed up weekly during hospitalization, utilizing transducers with central frequencies of 3.5 MHz and 5.0 MHz. Backscatter parameters, including apparent integrated backscatter (AIB), frequency intercept of apparent backscatter (FIAB), and frequency slope of apparent backscatter (FSAB) were calculated. Correlations were analyzed with both anthropometric and biochemical indices. We found that AIB (|r| = 0.40−0.47, p < 0.001), FIAB (|r| = 0.36−0.45, p < 0.001), and FSAB (|r| = 0.10−0.25, p < 0.01) were significantly correlated with gestational age, weight, length, and head circumference at birth at both the 3.5 MHz and 5.0 MHz frequencies. Backscatter parameters showed regular changes at different postnatal age and correlations with anthropometric indices persisted during the first month of life. Significant differences were also found in subgroup analyses based on gestational age, birth weight, gender, multiple births, and intrauterine growth. AIB and FIAB were shown to be more effective than FSAB. This study suggests the ultrasonic backscatter technique is feasible for neonatal cancellous bone status evaluation at birth and for dynamic monitoring. INDEX TERMS Metabolic bone disease, neonate, ultrasonic backscatter technique.
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