Table 2 - uploaded by Ian Brent Masters
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Previous studies of the abnormal physical properties of lung surfactant derived from infants experiencing prolonged expiratory apnoea, or who have died of sudden infant death syndrome (SIDS), have led to a search for the agent responsible. Bronchoalveolar lavage (BAL) has been performed upon 12 infants under 12 months at necropsy and the rinsings a...
Citations
... Interestingly, a similar amount of bile acids (5 mmol/L) increases sPLA2 activity and is able to impair surfactant biophysical function in vitro while lower bile acids amount do not reach the same effect; in fact, Donoso et al. (61) showed that bile acids significantly changed the hysteresis area of surface tension-area loop by %25% with a biphasic behavior. The interaction between bile acids and sPLA2 enzymes has been proposed for the first time as a physiopathological mechanism of sudden infant death syndrome by studying BAL fluid samples obtained postmortem, although in these cases the origin of bile acids remained unclear (62). ...
The presence of bile acids in lung tissue is associated with some clinical features observed in various medical specialties, but it took time to understand that these are due to a "bile acid-induced lung injury" since specific translational studies and cross-disciplinary awareness were lacking. We used a reverse translational approach to update and summarize the current knowledge about the mechanisms of bile acid-induced lung injury. This has been done in a cross-disciplinary fashion since these conditions may occur in patients of various age and in different medical fields. We here define these clinical conditions, then we review the physiopathology of these conditions and the animal models used to mimic them and, finally, their pathobiology. Mechanisms of bile acid-induced lung injury have been partially clarified overtime and are represented by: 1) the interaction with secretory phospholipase A2 pathway, 2) the effect on surfactant function and structure, 3) the biological effects on inflammation and local immunity, 4) the direct cellular toxicity. These mechanisms are schematically illustrated and histological comparisons between ARDS induced by bile acids and other triggers are also provided. Based on these mechanisms we propose possible direct therapeutic applications and, finally, we discuss further research steps to improve the understanding of processes that generate pathological clinical conditions.
... As a consequence, bile acids accumulate in the amniotic fluid and can contribute to the onset of premature labor, infant respiratory distress, and stillbirth. Several studies have demonstrated increased levels of bile acids in the serum and bronchoalveolar lavage fluid (BALF) of neonates with ICP-associated respiratory distress (160,514,517,518), while bile acids have also been shown to be elevated in BALF of infants after sudden infant death syndrome (165). ...
Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer. Driven by discovery of specific receptors on intestinal epithelial cells, new insights into mechanisms that control their synthesis and enterohepatic circulation, and a growing appreciation of their roles as bioactive bacterial metabolites, bile acids are currently receiving a great deal of interest as critical regulators of epithelial function in health and disease. This review aims to summarize recent advances in this field and to highlight how bile acids are now emerging as exciting new targets for disease intervention.
... This can be due in part to the earlier gestational age at delivery, but neonatal respiratory distress syndrome has been demonstrated to be associated with ICP based on the analysis of bronchoalveolar lavage fluid of neonates born to mothers with ICP [35] and they hypothesized that bile acids can produce surfactant depletion in the alveoli [34]. Hills et al. suggested a possible interaction between bile acids and surfactants mediated through the phospholipase A2, which synthesizes surfactants in the lung [36]. Corresponding with our results, Glantz et al. found a significantly higher rate of fetal complications such as asphyxial events, spontaneous preterm deliveries and meconium staining of the amniotic fluid, placenta and membranes in patients similar to our group II -women with ICP and bile acid levels of 40 mol/L. ...
The aim of this study was to assess total bile acid (TBA) levels and its impact on systolic and diastolic functions in fetuses of mothers with intrahepatic cholestasis of pregnancy (ICP) using tissue Doppler imaging (TDI), and to explore the correlation between TBA levels and fetal cardiac function.
The study employed 98 pregnant women with ICP who were divided into two groups according to their bile acid levels. Fifty pregnant women without ICP represented the control group.
Significant differences in the myocardial tissue velocities of both mitral and tricuspid valves were found between the fetuses of mothers with ICP and TBA levels of <40 mmol/L and the control group, versus fetuses of mothers with ICP and TBA levels >40 mmol/L. There was a significant increase in neonatal respiratory distress, meconium staining and neonatal TBAs in group II compared to the control group and group I. There was a correlation between maternal TBA levels and preterm delivery, APGAR scores and neonatal TBA levels at birth. There was also a positive correlation between maternal TBA and fetal myocardial tissue velocities of both mitral and tricuspid, and fetal diastolic myocardial tissue Doppler velocities.
ICP is a very serious condition especially when maternal TBA levels are >40 mmol/L. Fetal echocardiography with tissue Doppler is a useful tool for fetal assessment in patients with ICP. It could be an indication of induction of labor in cases of ICP and bile acid levels ≥40 mol/L. Neonatal echocardiography is mandatory for follow-up and management of these neonates.
... This can be due in part to the earlier gestational age at delivery, but neonatal respiratory distress syndrome has been demonstrated to be associated with ICP based on the analysis of bronchoalveolar lavage fluid of neonates born to mothers with ICP [35] and they hypothesized that bile acids can produce surfactant depletion in the alveoli [34]. Hills et al. suggested a possible interaction between bile acids and surfactants mediated through the phospholipase A2, which synthesizes surfactants in the lung [36]. Corresponding with our results, Glantz et al. found a significantly higher rate of fetal complications such as asphyxial events, spontaneous preterm deliveries and meconium staining of the amniotic fluid, placenta and membranes in patients similar to our group II -women with ICP and bile acid levels of 40 mol/L. ...
... Sepulveda found that cholic acid in high concentrations could constrict blood vessels (22) which would lead to a decrease in pulmonary blood flow and even pulmonary hypoxia. Some researchers figured that cholic acid may cause lung damage through hindering the synthesis of pulmonary surfactant and cause an inflammatory reaction (20,23). These above researches explained how cholestasis could injure the development of the lung which may even cause the occurrence of BPD. ...
Bronchopulmonary Dysplasia (BPD) is a rare chronic lung disease and one of the most difficult complications to treat in premature infants. With the progress at the medical treatment level, an increasing number of BPD premature infants are born, meanwhile, they would be at an increasing risk for numerous complications and rehospitalization because BPD affects many vital organ systems. The pathogenesis of BPD is clearly multifactorial. As the prognosis is closely connected with the severity of BPD, early diagnosis and treatment are of great help to control the development of BPD. This article focuses on risk factors that could influence the severity of BPD in order to provide a reliable basis for early diagnosis, treatment, and better patient assessment.
... When treated with surfactant, alveoli responded appropriately, and had increased aeration [15]. In another study, bronchial alveolar lavage was performed during necropsy on 12 infants and it was found that there were lower phospholipid levels, and higher bile acid levels [16]. This suggests a possible interaction between bile acids and surfactant mediated through the phospholipase A2, which synthesizes surfactant in the lung [16]. ...
... In another study, bronchial alveolar lavage was performed during necropsy on 12 infants and it was found that there were lower phospholipid levels, and higher bile acid levels [16]. This suggests a possible interaction between bile acids and surfactant mediated through the phospholipase A2, which synthesizes surfactant in the lung [16]. More details are necessary to determine the effects of bile acids on fetal lung maturity, surfactant production, and respiratory distress. ...
Intrahepatic cholestasis of pregnancy (ICP) has important fetal implications. There is increased risk for poor fetal outcomes, including preterm delivery, meconium staining of amniotic fluid, respiratory distress, fetal distress and demise.
One hundred and one women diagnosed with ICP between January 2005 and March 2009 at San Francisco General Hospital were included in this study. Single predictor logistic regression models were used to assess the associations of maternal clinical and biochemical predictors with fetal complications. Clinical predictors analyzed included age, race/ethnicity, gravidity, parity, history of liver or biliary disease, history of ICP in previous pregnancies, and induction. Biochemical predictors analyzed included serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, albumin, total protein, and total bile acids (TBA).
The prevalence of ICP was 1.9%. Most were Latina (90%). Labor was induced in the majority (87%) and most were delivered by normal spontaneous vaginal delivery (84%). Fetal complications occurred in 33% of the deliveries, with respiratory distress accounting for the majority of complications. There were no statistically significant clinical or biochemical predictors associated with an increased risk of fetal complications. Elevated TBA had little association with fetal complications until reaching greater than 100 µmoL/L, with 3 out of 5 having reported complications. ICP in previous pregnancies was associated with decreased risk of fetal complications (OR 0.21, p = 0.046). There were no cases of late term fetal demise.
Maternal clinical and laboratory features, including elevated TBA, did not appear to be substantial predictors of fetal complications in ICP.
... 22 Uptake from circulation is more probable, because the impaired maternal clearance caused by ICP can limit the passage of BA from the fetal to the maternal circulation. 1,23,24 We measured serum BA levels at birth, and our data support this hypothesis. In fact, BA levels measured in the RDS and NLD groups were similar to those reported by Feldmann et al 25 in healthy neonates (19.6 Ϯ 10.4 mol/L), whereas ICP infants had serum BA levels significantly higher than control subjects. ...
Neonatal respiratory distress syndrome is associated with intrahepatic cholestasis of pregnancy, and bile acids may play a major role in neonatal bile acid pneumonia. Our aim was to demonstrate the bile acid presence in the bronchoalveolar lavage fluid of neonates affected by respiratory distress syndrome who were born from intrahepatic cholestasis of pregnancy and to investigate bile acid mechanisms of action in acute lung injury.
In this prospective study, we enrolled 10 neonates delivered from intrahepatic cholestasis of pregnancy, affected by respiratory distress syndrome requiring mechanical ventilation (intrahepatic cholestasis of pregnancy group) and 2 control groups. The first group consisted of 20 infants with respiratory distress syndrome delivered from pregnancies without any sign of intrahepatic cholestasis of pregnancy (respiratory-distress-syndrome group), and the second group included 20 neonates with no lung disease who were ventilated for extrapulmonary reasons (no-lung-disease group). We measured bile acid and pH in the bronchoalveolar lavage fluid and serum bile acid levels in the first 24 hours of life.
Bile acids were measurable in the bronchoalveolar lavage fluid of all of the infants in the intrahepatic cholestasis of pregnancy group but were absent in the 2 control groups. Bronchoalveolar lavage fluid pH was not different among the 3 groups. Infants in the intrahepatic-cholestasis-of-pregnancy group had significantly higher serum bile acid levels compared with those in both of the control groups.
Bile acids are detectable in the bronchoalveolar lavage fluid of newborns from intrahepatic cholestasis of pregnancy affected by respiratory distress syndrome. Elevated serum bile acid levels in these infants allow us to hypothesize that bile acid reaches the lung after an uptake from the circulation. These findings strongly support a role for bile acid in causing bile acid pneumonia.
The role of gastroesophageal reflux (GER) as a risk factor in chronic lung allograft dysfunction (CLAD) and/or bronchiolitis obliterans syndrome (BOS) is strongly supported by the cumulative evidence collected to date. Proximal gastrointestinal tract motility studies and pH/impedance testing can be used to diagnose motility abnormalities and GER and to determine whether reflux is acid or nonacid. However, a true gold standard methodology for detecting penetrance of refluxed duodeno-gastric secretions into the lung is lacking, and a definitive marker of GER combined with microaspiration that identifies patients at significant risk for associated allograft injury and dysfunction needs to be determined. Prospective, multicenter, adequately powered clinical trials should be performed to better understand the role of GER in CLAD and to identify appropriate criteria for patient selection for possible surgical correction of GER.
