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Frank D’Ovidio
Thomas K. Waddell
Andrew Pierre
Gail Darling
Shaf Keshavjee
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Right arrow Lung - transplantation

J Thorac Cardiovasc Surg 2005;129:1144-1152
© 2005 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

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

Toronto Lung Transplant Program, University of Toronto, Toronto, Ontario, Canada

Read at the Eighty-fourth Annual Meeting of The American Association for Thoracic Surgery, Toronto, Ontario, Canada, April 25–28, 2004.

Received for publication April 23, 2004; revisions received October 15, 2004; accepted for publication October 21, 2004.

* Address for reprints: S. Keshavjee, MD, Director, Toronto Lung Transplant Program, Toronto General Hospital, 200 Elizabeth St, EN10-224, Toronto, Ontario, Canada M5G 2C4 (E-mail: S.Keshavjee{at}utoronto.ca).

BACKGROUND: Aspiration of gastroesophageal refluxate may contribute to lung transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in bronchoalveolar lavage fluid (BALF) and studied its role in BOS.

MATERIALS AND METHODS: Surveillance pulmonary function tests and BALF were evaluated in 120 lung recipients. BOS-(0p-3) was diagnosed after 6 months’ survival. BOS was defined as "early" if diagnosed within 12 months after a transplant. BALF was assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile acids were considered elevated if greater than normal serum levels (≥8 µmol/L).

RESULTS: Elevated BALF bile acids were measured in 20 (17%) of 120 patients. BOS was diagnosed in 36 (34%) of 107 patients and judged "early" in 21 (57%) of 36. Median BALF bile acid values were 1.6 µmol/L (range, 0–32 µmol/L) in BOS patients and 0.3 µmol/L (range, 0–16 µmol/L) in non-BOS patients (P = .002); 2.6 µmol/L (range, 0–32 µmol/L) in early BOS patients and 0.8 µmol/L (range, 0–4.6 µmol/L) in late BOS patients, (P = .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P = .0004, and r = 0.3, P = .004, respectively), but not with IL-15. Freedom from BOS was significantly shortened in patients with elevated BALF bile acids (Cox-Mantel test, P = .0001).

CONCLUSIONS: Aspiration of duodenogastroesophageal refluxate is prevalent after lung transplantation and is associated with the development of BOS. Elevated BALF bile acids may promote early BOS development via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.




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