Association of enteral feeding with microaspiration in critically ill adults.

AIM: This study explored relationships between enteral feeding and tracheal pepsin A. BACKGROUND: Mechanically ventilated (MV) patients receiving enteral feeding are at risk for microaspiration. Tracheal pepsin A, an enzyme specific to gastric cells, was a proxy for microaspiration of gastric secretions. METHODS: Secondary analysis of RCT data from critically ill, MV adults was conducted. Microaspiration prevention included elevated head of bed, endotracheal tube cuff pressure management, and regular oral care. Tracheal secretions for pepsin A were collected every 12 h. Microaspiration was defined as pepsin A ≥ 6.25 ng/mL. Positive pepsin A in >30 % of individual tracheal samples was defined as abundant microaspiration (frequent aspirator). Chi-squared, Fisher's Exact test, and generalized linear model (GLM) were used. RESULTS: Tracheal pepsin A was present in 111/283 (39 %) mechanically ventilated patients and 48 (17 %) had abundant microaspiration. Enteral feeding was associated with tracheal pepsin A, which occurred within 24 h of enteral feeding. Of the patients who aspirated, the majority received some enteral feeding 96/111 (86 %), compared to only 15/111 (14 %) who received no feeding. A greater number of positive pepsin A events occurred with post-pyloric feeding tube location (55.6 %) vs. gastric (48.6 %), although significant only at the event-level. Frequent aspirators (abundant pepsin A) had higher pepsin A levels compared to infrequent aspirators. CONCLUSIONS: Our findings confirmed the stomach as the microaspiration source. Contrary to other studies, distal feeding tube location did not mitigate microaspiration. Timing for first positive pepsin A should be studied for possible association with enteral feeding intolerance.

Metabolomic profiling of extraesophageal reflux disease in children.

Although respiratory symptoms in children are often attributed to gastroesophageal reflux disease, establishing a clear diagnosis of extraesophageal reflux disease (EERD) can be challenging, as there are no sensitive or specific EERD biomarkers. The aim of this study was to evaluate the metabolite profile in bronchoalveolar (BAL) fluid from children with suspected EERD and assess the impact of reflux treatment on these metabolites. In this prospective pilot study, we performed nontargeted global metabolomic profiling on BAL fluid from 43 children undergoing testing with bronchoscopy, upper endoscopy, and multichannel intraluminal impedance with pH (pH-MII) for evaluation of chronic respiratory symptoms. Twenty-three (54%) patients had an abnormal pH-MII study. Seventeen (40%) patients were on proton pump inhibitors (PPIs) for testing. Levels of histamine, malate, adenosine 5'-monophosphate, and ascorbate were significantly lower in subjects with abnormal pH-MII studies compared to those normal studies. Furthermore, in children off PPI therapy, those with abnormal pH-MII studies had robust increases in a number of glycerophospholipids within phospholipid metabolic pathways, including derivatives of glycerophosphorylcholine, glycerophosphoglycerol, and glycerophosphoinositol, compared to those with normal pH-MII studies. These findings offer insight into the impact of reflux and PPIs on the lungs and provide a foundation for future studies using targeted metabolomic analysis to identify potential biomarkers of EERD.

Proximal reflux: biochemical mediators, markers, therapeutic targets, and clinical correlations.

Airway reflux is implicated in the pathophysiology of a wide range of adult and pediatric upper and lower airway diseases. However, the diagnosis of proximal reflux-associated disease remains challenging due to evolving clinical criteria and institutional and regional variances in diagnostic practices. Evidence suggests that nonacidic contents of reflux may serve as both pathologic mediators of and biomarkers for reflux in the upper airway. Furthermore, they offer potential pharmaceutical and surgical intervention targets and are the focus of novel clinical diagnostic tools currently under investigation.

The profibrotic effects of chronic microaspiration of bile acids on lungs of rats at different stages.

This study aimed to explore the profibrotic effects of chronic microaspiration of two major bile acids, including chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), on lungs of rats at different stages, as well as the underlying mechanisms in vivo. A rat model was induced by weekly intratracheal instillation of DCA and CDCA. Our results showed that chronic microaspiration of bile acids resulted in alveolar structure disorder, and inflammatory cells infiltration in the pulmonary interstitium at the early stage. Subsequently, numerous fibroblasts were proliferated, and collagen deposition was profoundly increased over the interstitium of the airways and vessels. Compared with control group, the expression of α-smooth muscle actin, type I collagen, hydroxyproline, transforming growth factor-ß1 (TGF-ß1), and matrix metalloproteinase-9 in the lung tissues were remarkably elevated at the 2nd week, reached the highest level at the 6th week, and maintained high at the 8th week in both DCA- and CDCA-treated groups (P < 0.05). Furthermore, chronic microaspiration of bile acids led to higher levels of glutathione and malondialdehyde, while lower level of superoxide dismutase in lung tissues compared with controls (P < 0.05), thereby resulting in the oxidant/antioxidant enzyme imbalance in the formation of fibrosis. In addition, we also found a consistent growth in the expression of farnesoid X receptor (FXR) in both DCA- and CDCA-treated groups. Our findings suggested that chronic microaspiration of bile acids could initiate the process of pulmonary fibrosis from the early phase and promote its progression in a time-dependent manner, which likely involved the TGF-ß1, oxidative stress, and FXR-related pathways.

Early Immune Response to Acute Gastric Fluid Aspiration in a Rat Model of Lung Transplantation.

OBJECTIVES: Chronic aspiration of gastric fluid contents can decrease long-term survival of pulmonary transplants due to development of obliterative bronchiolitis. However, little is known about the early immune response and the cascade of events involved in the development of obliterative bronchiolitis. MATERIALS AND METHODS: We utilized a rat orthotopic pulmonary transplant model and a single aspiration of either gastric fluid or normal saline to investigate the histologic, cellular, and cytokine changes associated with an acute gastric fluid aspiration event compared with normal saline at 2 and 10 days after aspiration. RESULTS: Our observations included a decrease in pulmonary compliance and increased airway inflammation and acute rejection of the transplanted lung, as well as increases in macrophages, granulocytes, and proinflammatory cytokines such as interleukin 1ß, transforming growth factor ß1 and ß2, and tumor necrosis factor α in bronchoalveolar lavage fluid from the transplanted lung of gastric fluid-aspirated rats compared with normal saline-aspirated rats. CONCLUSIONS: The acute inflammatory response observed in the present study is consistent with changes found in chronic models of aspiration-associated injury and suggests a potentially important role for mast cells in the development of obliterative bronchiolitis.

Head-of-bed elevation and early outcomes of gastric reflux, aspiration and pressure ulcers: a feasibility study.

BACKGROUND: Guidelines recommending head of bed (HOB) elevation greater than 30º to prevent ventilator-associated pneumonia conflict with guidelines to prevent pressure ulcers, which recommend HOB elevation less than 30º. OBJECTIVES: To examine the feasibility of 45º HOB elevation and describe and compare the occurrence of reflux, aspiration, and pressure ulcer development at 30º and 45º HOB elevation. METHODS: A randomized 2-day crossover trial was conducted. HOB angle was measured every 30 seconds. Oral and tracheal secretions were analyzed for pepsin presence. Skin was assessed for pressure ulcers. Wilcoxon signed rank tests and Kendall τ correlations were conducted. RESULTS: Fifteen patients were enrolled; 11 completed both days. Patients were maintained at 30º (mean, 30º) for 96% of minutes and at 45º (mean, 39º) for 77% of minutes. No patients showed signs of pressure ulcers. A total of 188 oral secretions were obtained, 82 (44%) were pepsin-positive; 174 tracheal secretions were obtained, 108 (62%) were pepsin-positive. The median percentage of pepsin-positive oral secretions was not significantly higher (P = .11) at 30º elevation (54%) than at 45º elevation (20%). The median percentage of pepsin-positive tracheal secretions was not significantly higher (P = .37) at 30º elevation (71%) than 45º elevation (67%). Deeper sedation correlated with increased reflux (P = .03). CONCLUSIONS: HOB elevation greater than 30º is feasible and preferred to 30º for reducing oral secretion volume, reflux, and aspiration without pressure ulcer development in gastric-fed patients receiving mechanical ventilation. More deeply sedated patients may benefit from higher HOB elevations.

Association between tracheal pepsin, a reliable marker of gastric aspiration, and head of bed elevation among ventilated neonates.

OBJECTIVES: To determine the frequency of tracheal pepsin in ventilated neonates and whether the angle of head elevation was associated with tracheal pepsin. STUDY DESIGN: Serial trachael samples (at 3, 7, 14, 21 and 28 days of ventilation) were obtained from intubated, ventilated very low birth weight infants. Presence of tracheal pepsin was determined by Western blot analysis using a specific anti-human pepsin antibody. RESULTS: Tracheal pepsin was detected in 35/66 (53%) of the ventilated neonates (birthweight: 798 ± 268 grams [mean ± standard deviation]). Neonates whose head elevation was in the upper quartile (≥14 degrees) during the first sampling time (day 3) were less likely (4/16 vs 9/10, P = 0.0013) to have tracheal pepsin when compared to neonates whose head elevation was in the lowest quartile (≤8 degrees). CONCLUSIONS: Pepsin, a marker for gastric secretion aspiration, was detected in 53% of ventilated low birth weight neonates; early elevation of the head of the bed was associated with a lower rate of tracheal pepsin.