Quantification of Enteric Dysfunction in Cystic Fibrosis: Inter- and Intraindividual Variability

Abstract

ObjectivesTo test the utility of various biomarkers as indicators of gut dysfunction in cystic fibrosis (CF) and determine whether intra-individual variations in these measures are repeatable over short intervals and whether inter-individual variations correlate with clinical outcomes. Study DesignWe performed a cross-sectional, limited longitudinal study of children with CF aged 1-21 years who provided blood and stool samples at 2 or 3 visits, 2 weeks and 3 months apart, which were assayed for markers of intestinal inflammation (fecal calprotectin [fCal], lipocalin-2 [fLcn2], neopterin [fNeo]) and permeability (plasma lipopolysaccharide [LPS] antibodies, LPS-binding protein) by enzyme immunoassays. Control specimens were obtained from children without CF who had undergone esophagogastroduodenoscopy and had no evidence of gut inflammation. ResultsTwenty-six of 29 participants with CF completed the study. Sixty-nine stools (57 case/12 control) and 76 plasmas (60 case/16 control) were analyzed. LPS antibody had reliable intra-individual stability. fCal, fLcn2, and fNeo were significantly greater in CF than in control samples. fCal was negatively correlated with 3-month interval change (Δ) in weight-for-age z-score, body mass index/weight-for-length z-score (BMIZ/WLZ), and FEV1. fLcn2 was negatively correlated with FEV1 but not with anthropometrics. No marker correlated with ΔBMIZ/WLZ or ΔFEV1. ConclusionsLcn2 is elevated in people with CF and might predict worse interval pulmonary function. Expanded studies are warranted to test if fLcn2 correlates with changes in additional outcomes.