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.

Measurement of Oxygen Desaturation Is Not Useful for the Detection of Aspiration in Dysphagic Stroke Patients.

BACKGROUND: Dysphagia is one of the most dangerous symptoms of acute stroke. Various screening tools have been suggested for the early detection of this condition. In spite of conflicting results, measurement of oxygen saturation (SpO2) during clinical swallowing assessment is still recommended by different national guidelines as a screening tool with a decline in SpO2 ≥2% usually being regarded as a marker of aspiration. This paper assesses the sensitivity of SpO2 measurements for the evaluation of aspiration risk in acute stroke patients. METHODS: Fifty acute stroke patients with moderate to severe dysphagia were included in this study. In all patients, fiberoptic endoscopic evaluation of swallowing (FEES) was performed according to a standardised protocol. Blinded to the results of FEES, SpO2 was monitored simultaneously. The degree of desaturation during/after swallows with aspiration was compared to the degree of desaturation during/after swallows without aspiration in a swallow-to-swallow analysis of each patient. To minimise potential confounders, every patient served as their control. RESULTS: In each subject, a swallow with and a swallow without aspiration were analysed. Overall, aspiration seen in FEES was related to a minor decline in SpO2 (mean SpO2 without aspiration 95.54 ± 2.7% vs. mean SpO2 with aspiration 95.28 ± 2.7%). However, a significant desaturation ≥2% occurred only in 5 patients during/after aspiration. There was no correlation between aspiration/dysphagia severity or the amount of aspirated material and SpO2 levels. CONCLUSIONS: According to this study, measurement of oxygen desaturation is not a suitable screening tool for the detection of aspiration in stroke patients.

Exhaled Breath Condensate Pepsin: Potential Noninvasive Test for Gastroesophageal Reflux in COPD and Bronchiectasis.

BACKGROUND: Acid gastroesophageal reflux is a common problem in non-cystic fibrosis bronchiectasis and COPD. Invasive methods are used to diagnose gastroesophageal reflux, but the ability to detect pulmonary microaspiration of gastric contents using this method is unclear. A noninvasive option to detect pulmonary microaspiration is to measure pepsin in exhaled breath condensate (EBC), but this has not been related to esophageal pH monitoring in these lung conditions. This study aimed to measure pepsin concentrations and pH in EBC and to determine the relationship to gastroesophageal reflux in bronchiectasis or COPD. METHODS: Subjects with bronchiectasis (n=10) or COPD (n=10) and control subjects (n=10) completed 24-h esophageal pH monitoring for detection of acid gastroesophageal reflux, measuring the percentage of reflux time in the proximal esophagus and the DeMeester score (DMS). Concurrently, 3 samples of EBC were collected from each subject, and pH was measured and pepsin concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: EBC pepsin was detected in subjects with bronchiectasis (44%) or COPD (56%) and in control subjects (10%). A diagnosis of gastroesophageal reflux was not associated with a higher concentration of EBC pepsin in bronchiectasis (P=.21) or COPD (P=.11). EBC pepsin concentration did not correlate with DMS (rs=0.36) or proximal reflux index (rs=0.25) in subjects with bronchiectasis or with DMS (rs=0.28) or proximal reflux index (rs=0.21) in patients with COPD. EBC and sputum pepsin concentrations were moderately correlated in bronchiectasis (rs=0.56) and in COPD (rs=0.43). CONCLUSIONS: Pepsin is detectable in EBC samples in bronchiectasis and COPD. Although no association was found between pepsin concentrations and a diagnosis of gastroesophageal reflux, a moderate relationship between sputum and EBC pepsin concentrations suggests that EBC pepsin may be a useful noninvasive marker of pulmonary microaspiration.

Hunger and thirst numeric rating scales are not valid estimates for gastric content volumes: a prospective investigation in healthy children.

AIM: A rating scale for thirst and hunger was evaluated as a noninvasive, simple and commonly available tool to estimate preanesthetic gastric volume, a surrogate parameter for the risk of perioperative pulmonary aspiration, in healthy volunteer school age children. METHOD: Numeric scales with scores from 0 to 10 combined with smileys to rate thirst and hunger were analyzed and compared with residual gastric volumes as measured by magnetic resonance imaging and fasting times in three settings: before and for 2 h after drinking clear fluid (group A, 7 ml/kg), before and for 4 vs 6 h after a light breakfast followed by clear fluid (7 ml/kg) after 2 vs 4 h (crossover, group B), and before and for 1 h after drinking clear fluid (crossover, group C, 7 vs 3 ml/kg). RESULTS: In 30 children aged 6.4-12.8 (median 9.8) years, participating on 1-5 (median two) study days, 496 sets of scores and gastric volumes were determined. Large inter- and intra-individual variations were seen at baseline and in response to fluid and food intake. Significant correlations were found between hunger and thirst ratings in all groups, with children generally being more hungry than thirsty. Correlations between scores and duration of fasting or gastric residual volumes were poor to moderate. Receiver operating characteristic (ROC) analysis revealed that thirst and hunger rating scales cannot predict gastric content. CONCLUSION: Hunger and thirst scores vary considerably inter- and intra-individually and cannot predict gastric volume, nor do they correlate with fasting times in school age children.

Prevalence of pediatric aspiration-associated extraesophageal reflux disease.

IMPORTANCE: The role of aspiration-associated extraesophageal reflux disease (AERD) in patients with chronic respiratory symptoms is not well defined. Identifying the frequency of AERD in these patients may provide guidance in their treatment. OBJECTIVE: To determine the prevalence of AERD in patients with chronic respiratory symptoms and to assess the utility of pepsin as a new marker for AERD. DESIGN: Case-control study performed from 2008 through 2012.Western blot analysis for pepsin and oil red O staining for lipid-laden macrophages (LLMs) was performed on bronchoalveolar lavage fluid specimens. SETTING: Tertiary referral center. PARTICIPANTS: Sixty-five patients (aged 4.5 months to 24 years) with chronic pulmonary disease, with or without tracheostomy, were compared with controls undergoing elective surgery who had no history of pulmonary disease. MAIN OUTCOMES AND MEASURES: Presence of pepsin and LLMs and quantity of LLMs in specimens. RESULTS: Seventy-six total patients participated: 34 patients who underwent bronchoscopy, 31 patients with tracheostomy, and 11 controls. Pepsin-positive bronchoalveolar lavage fluid specimens were identified in 25 patients who underwent bronchoscopy (74%) and 22 patients with tracheostomy (71%). All specimens from controls were negative for pepsin. Presence of LLMs was identified in specimens from 31 patients in the bronchoscopy group (91%), 16 patients in the tracheostomy group (52%), and 7 controls (64%), with a similar distribution of the quantity of LLMs in each lavage fluid specimen among the groups. CONCLUSIONS AND RELEVANCE: Patients with chronic pulmonary disease have a high prevalence of AERD, which may have important treatment implications. The presence of pepsin was a better predictor of AERD in patients with respiratory symptoms compared with controls than presence of LLMs. Detection of pepsin in bronchoalveolar lavage fluid specimens can serve as a biomarker for AERD and is potentially superior to the current method of measuring LLMs. Whereas there is a significant association between AERD and the presence of chronic respiratory symptoms, this study does not verify causation. Additional study investigating the mechanism of pepsin on the respiratory epithelium may further our understanding of the pathophysiologic characteristics of this association and provide additional management options for these patients.