Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation  Frank D’Ovidio, MD, Marco Mura, MD, Melanie Tsang, MSc, Thomas K. Waddell, MD, Michael A. Hutcheon, MD, Lianne G. Singer, MD, Denis Hadjiliadis, MD, Cecilia Chaparro, MD, Carlos Gutierrez, MD, Andrew Pierre, MD, Gail Darling, MD, Mingyao Liu, PhD, Shaf Keshavjee, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 129, Issue 5, Pages 1144-1152 (May 2005) DOI: 10.1016/j.jtcvs.2004.10.035 Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 The BALF total bile acids quantified in patients grouped for presence or absence of BOS. The median bile acid level was 0.3 μmol/L (range, 0–16 μmol/L) for the BOS-0 group and 1.6 μmol/L (range, 0–32 μmol/L) in the BOS-(0p-3) group (P = .002). In a stratification of the BOS-(0p-3) group with regard to early (≤12 months) versus late (>12 months) BOS development, total bile acids were 2.6 μmol/L (range, 0.06–32 μmol/L) and 0.8 μmol/L (range, 0–4.6 μmol/L), respectively (P = .02). The box plots indicate the 25th, 50th and 75th percentile and the bars, the 10th and 90th percentile. The Journal of Thoracic and Cardiovascular Surgery 2005 129, 1144-1152DOI: (10.1016/j.jtcvs.2004.10.035) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Bile acid within the BALF showed a significant association with IL-8 levels, although no difference was noted for IL-15. The median IL-8 was 118 pg/mL (range, 1.6–358 pg/mL) for patients with high bile acids, 107 pg/mL (range, 0–381 pg/mL) for patients with low BALF bile acids, and 61 pg/mL (range, 0–296 pg/mL) for patients with no bile acids (P = .01, Kruskal-Wallis; Mann-Whitney test between no bile versus low bile groups and versus the high bile group showed a P = .02 and P = .01 respectively). The median IL-15 was 19 pg/mL (range, 1–80 pg/mL) for high bile acids group, 21 pg/mL (range, 0–615 pg/mL) for the low bile acids group, and 15 pg/mL (range, 0–109 pg/mL) for the no bile acid group (P = .4, Kruskal-Wallis test). Bile acid in the BALF showed a significant association with the relative neutrophil cell count but no relationship to the lymphocyte count. When grouped according to bile acid levels, the median neutrophils were 2% (range, 0%–27%) in the patients with no bile acids in the BALF; 2% (range, 0%–34%) in the group with low BALF bile acids; and 5% (range, 2%–27%) in the group with high BALF bile acid (P = .015, Kruskal-Wallis test; Mann-Whitney test for comparison between the high bile acids group versus the low and no bile acids groups showed a P = .007 and P = .008, respectively). The median lymphocyte count was 2% (range, 0%–18%) for the no bile acid group, 1.5% (range, 0%–13%) for the low BALF bile acid group, and 1.1% (range, 0%–3%) in the high bile acid group (P = .7, Kruskal-Wallis). The boxes indicate the 25th, 50th, and 75th percentile and the bars, the 10th and 90th percentile. The Journal of Thoracic and Cardiovascular Surgery 2005 129, 1144-1152DOI: (10.1016/j.jtcvs.2004.10.035) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Interval from transplant to development of BOS-(0p-3). The actuarial curves show a significantly reduced interval of time from transplant to BOS-(0p-3) development in patients with high BALF bile acids levels. Breslow-Gehan-Wilcoxon test and Cox-Mantel log-rank test showed P = .007 and P = .002, respectively, for the comparison between the group with low bile levels and the group with high bile levels; P = .0001 for both tests for the comparison between the group with no detection of bile acids and the group with the high levels of bile acids within the BALF; and P = .1 for the comparison between the group with no BALF bile acids and the group with low BALF bile acid levels. The Journal of Thoracic and Cardiovascular Surgery 2005 129, 1144-1152DOI: (10.1016/j.jtcvs.2004.10.035) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions