High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations
ABSTRACT Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated.
This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes.
The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status.
Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.
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ABSTRACT: Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an 'office-based' method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and-SAP, n=27). 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0-59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52-311)ng/mL and GORD, 121(29-252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0-40) ng/mL). A positive test had 77.6% sensitivity and 63.2% specificity for diagnosis of GORD+HO (likelihood ratio: 2.2). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 96% specificity (likelihood ratio: 24.4). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.Gut 05/2014; 64(3). DOI:10.1136/gutjnl-2014-307049 · 13.32 Impact Factor
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ABSTRACT: To investigate the concentrations of pepsin and pepsinogen within the middle ear cavity and determine whether pepsin and pepsinogen affect the prognosis of children with otitis media with effusion (OME). All middle-ear lavage fluid from patients with OME undergoing myringotomy (M subgroup) or tympanostomy tube insertion (T subgroup) was collected and pepsin and pepsinogen were detected using enzyme-linked immunosorbent assay. After close follow-up over 2 years, the effects of pepsin and pepsinogen on the prognosis of the patients with OME in the M and T subgroups were analyzed. The average pepsin and pepsinogen concentrations were significantly lower in the M subgroup (n=54; 24.38±16.10mg/mL and 286.49±91.95mg/mL, respectively) than in the T subgroup (n=55; 45.56±16.60mg/mL and 664.92±107.06mg/mL; t=2.484, P=0.018 and t=2.670, P=0.011, respectively). In the M subgroup, the average time to tympanic membrane healing and tympanic pressure restoration to normal was much longer in pepsin(+) patients (17.0±2.0 days and 26.0±2.5 days, respectively) than in pepsin(-) patients (14.0±1.1 days and 22.0±1.0 days; t=3.871, P=0.001 and t=5.734, P=0.000, respectively), and the hearing level of pepsin(+) patients with OME ascended to 13.08±1.19dB, which was much lower than that of pepsin(-) patients (18.29±1.27dB; t=11.001, P=0.000). In the T subgroup, the complication rate including otorrhea and myringosclerosis was much higher in patients with high pepsin concentrations than in those with low pepsin concentrations (P<0.05). Finally, in both subgroups, the recurrence rates of OME in pepsin(+) or patients with high pepsin concentrations (34.6% [9/26] and 28.6% [10/35]) were significantly higher than those in pepsin(-) or low pepsin concentrations (10.7% [3/28] and 5.0% [1/20]; χ(2)=4.456, P=0.035 and χ(2)=4.420, P=0.036). However, pepsinogen had no significant effect on OME prognosis or recurrence. Pepsin but not pepsinogen could postpone tympanic membrane healing and pressure restoration in children with OME undergoing myringotomy and increase the incidence of recurrence and complications including otorrhea and myringosclerosis for those undergoing tympanostomy tube insertion. Therefore, pepsin could be considered a poor prognostic factor for OME, further emphasizing the important role of pepsin in OME pathogenesis. Copyright © 2014. Published by Elsevier Ireland Ltd.International Journal of Pediatric Otorhinolaryngology 10/2014; 78(12):2250-2254. DOI:10.1016/j.ijporl.2014.10.026 · 1.32 Impact Factor
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ABSTRACT: The role of flexible bronchoscopy and bronchoalveolar lavage (BAL) for the care of children with airway and pulmonary diseases is well established, with collected BAL fluid most often used clinically for microbiologic pathogen identification and cellular analyses. More recently, powerful analytic research methods have been used to investigate BAL samples to better understand the pathophysiological basis of pediatric respiratory disease. Investigations have focused on the cellular components contained in BAL fluid, such as macrophages, lymphocytes, neutrophils, eosinophils, and mast cells, as well as the noncellular components such as serum molecules, inflammatory proteins, and surfactant. Molecular techniques are frequently used to investigate BAL fluid for the presence of infectious pathologies and for cellular gene expression. Recent advances in proteomics allow identification of multiple protein expression patterns linked to specific respiratory diseases, whereas newer analytic techniques allow for investigations on surfactant quantification and function. These translational research studies on BAL fluid have aided our understanding of pulmonary inflammation and the injury/repair responses in children. We review the ethics and practices for the execution of BAL in children for translational research purposes, with an emphasis on the optimal handling and processing of BAL samples.Pediatrics 06/2014; 134(1). DOI:10.1542/peds.2013-1911 · 5.30 Impact Factor