Evaluation of tracheal pepsin as a biomarker for aspiration

Aspiration is well recognized in children who have chronic lung disease or who are intubated. There is a known association between gastroesophageal reflux (GER) and aspiration. The distinction between aspiration of swallowed material, such as food and the aspiration of refluxed gastric contents is important. Determining whether an aspiration syndrome in an individual is due to GER may be difficult. The most widely used test to determine whether GER is the cause of aspiration involves staining bronchoalveolar lavage (BAL) fluid for lipid laden macrophages (LLM) based on the hypothesis that refluxed and aspirated fluid is phagocytosed by tracheal macrophages.

Pepsinogen is a protein unique to gastric chief cells and also requires acidic conditions for activation. Therefore the presence of pepsin in BAL fluid should only be found when gastric fluid is aspirated. In previous studies, pepsin has been detected in the tracheal fluid of children with chronic lung disease. Thus far, studies of this material have been small, not all have control groups, and LLM were not looked for in all studies.

Based on previous studies and the need to improve diagnostic methods, the following aims are proposed:

1. to determine the frequency of pepsin contamination of children without chronic respiratory disease undergoing elective surgery with intubation
2. to determine frequency of tracheal pepsin and lipid laden macrophages (LLM) in children with chronic respiratory disease or symptoms and in children with tracheostomies
3. to compare the presence or absence and concentration of pepsin to the presence of LLM
4. to relate the presence or absence and concentration of pepsin to clinical status To achieve these aims, BAL fluid will be obtained from subject patients and controls. These fluids will be transported to the research lab and stored on ice until analysis. Determination of LLM will be done in children undergoing diagnostic bronchoscopy in the clinical lab of CHW per routine. BAL analysis will consist of Western blot staining for the presence of pepsin. Demographic data will also be collected from the medical record.

Inclusion Criteria:

• Meet criteria of study population

Exclusion Criteria:

• Lack of informed consent/assent
• Pulmonary disease in normal controls

Normal children undergoing general endotracheal anesthesia Children with tracheostomies Children undergoing bronchoscopy Intubated children in PICU