TY  - JOUR
AU  - Roman, Jesse
AU  - Nunley, David
AU  - Bauldoff, Gerene
AU  - Elkhawas, Ibrahim
AU  - Ritzenthaler, Jeff
AU  - Gualdoni, Jill
PY  - 2019
DA  - 2019/02/20
TI  - Aspiration of Gastrointestinal Material and Induction of Fibronectin Expression in Lung Transplant Recipients: Implications for Early Airway Remodeling
JO  - OBM Transplantation
SP  - 051
VL  - 03
IS  - 01
AB  - Background: Gastroesophageal reflux disease has been associated with the development of chronic lung allograft dysfunction following lung transplantation. While the mechanisms are unclear, it is postulated that microaspiration of gastrointestinal material (GIM) leads to inflammation and airway remodeling that culminates in obliterative bronchiolitis. As the expression of the matrix glycoprotein fibronectin has been shown to be an early marker of this fibroproliferative process, its induction could suggest a causal mechanism for allograft dysfunction in lung transplant (LTX) recipients experiencing microaspiration. Methods: De-identified bronchoalveolar lavage fluid (BALF) samples sequentially collected during surveillance bronchoscopies throughout the first post-transplant year were analysed. Microaspiration was defined by the detection of bile salts in the BALF via an ELISA assay. An in vitro bioassay then detected fibronectin expression as a marker of activation of airway remodeling via incorporation of murine NIH/3T3 fibroblasts transfected with the human fibronectin promoter connected to the luciferase reporter vector. Fibroblasts were cultured with BALF for 24 hours and the ability of the BALF to stimulate fibronectin induction was measured via luciferase activity units. Results: Sequential bronchoscopies on fifteen LTX recipients yielded 101 BALF samples for analysis. Six recipients had at least one BALF ‘positive’ for bile salts indicating GIM aspiration while the remaining nine recipients had no ‘positive’ analyses. Increased fibronectin induction stimulated by the BALF correlated with the presence of one or more episodes of GIM aspiration occurring during the first post-transplant year (rs =0.22, p=0.03). Furthermore, fibronectin luciferase activity in the BALF from recipients experiencing aspiration was significantly greater than that from those recipients who did not aspirate (1.05 ± 0.19 vs. 0.92 ± 0.28 luciferase activity units/µg protein) [p< 0.02]. Conclusions: Increased fibronectin induction is implicated in LTX recipients who experience microaspiration. This may herald early airway remodeling that can lead to later allograft dysfunction.
SN  - 2577-5820
UR  - https://doi.org/10.21926/obm.transplant.1901051
DO  - 10.21926/obm.transplant.1901051
ID  - Roman2019
ER  -