Are the enzymatic methods currently being used to measure bronchoalveolar lavage bile salt levels fit for purpose?

Shruti Parikh*, Iain A. Brownlee, Andrew G. Robertson, Nigel T. Manning, Gail E. Johnson, Malcolm Brodlie, Paul A. Corris, Chris Ward, Jeffrey P. Pearson

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

12 Citations (Scopus)

Abstract

Background: Microaspiration after gastroesophageal reflux has been implicated in the chronic loss of allograft function in lung transplant patients. Bronchoalveolar lavage fluid (BALF) assessment for pepsin and bile salts is a common method to document reflux and aspiration. Clinically used methods for bile salt analysis include tandem mass spectrometry and diagnostic enzymatic kits designed to measure bile salts in serum. In clinical research, the enzymatic kits have been commonly used for BALF assays in lung transplant recipients, with reports of detection limits of 0.2 μmol/liter, and the levels used to inform clinical decisions. This study assessed the sensitivity of detection by 2 enzymatic assay kits compared with tandem mass spectrometry. Methods: These 2 kits were used to measure (1) the absorbance changes for 0 to 50 μmol/liter bile salts, (2) levels in gastric juice (10-10,010 μmol/liter), and (3) bile salt levels of 40 BALF samples that were also measured using tandem mass spectrometry (0.01-1.19 μmol/liter). Measurements of pH/impedance were done in 14 of 15 patients. Results: Neither kit had detection limits as low as claimed in previous BALF studies. The kits could be made more sensitive with a longer incubation time, (5 μmol/liter). All patients had detectable lavage bile acids using mass spectroscopy, 71% had pathologic distal gastroesophageal reflux, and 43% had pathologic proximal reflux. Conclusions: The enzymatic kits are not sensitive enough for use in situations where bile salt levels are much below 5 μmol/liter, which is the case in BALF. In addition, reports in the literature of levels significantly below 5 μmol/liter need reassessing. Tandem mass spectrometry with a lower limit of detection of 0.01 μmol/liter should be the method of choice.

Original languageEnglish
Pages (from-to)418-423
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume32
Issue number4
Early online date4 Feb 2013
DOIs
Publication statusPublished - 1 Apr 2013
Externally publishedYes

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