Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation.
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.


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 ( or =8 micromol/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 micromol/L (range, 0-32 micromol/L) in BOS patients and 0.3 micromol/L (range, 0-16 micromol/L) in non-BOS patients ( P = .002); 2.6 micromol/L (range, 0-32 micromol/L) in early BOS patients and 0.8 micromol/L (range, 0-4.6 micromol/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.
D'Ovidio
Frank
F
Toronto Lung Transplant Program, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Mura
Marco
M
Tsang
Melanie
M
Waddell
Thomas K
TK
Hutcheon
Michael A
MA
Singer
Lianne G
LG
Hadjiliadis
Denis
D
Chaparro
Cecilia
C
Gutierrez
Carlos
C
Pierre
Andrew
A
Darling
Gail
G
Liu
Mingyao
M
Keshavjee
Shaf
S
D000206:Actuarial Analysis; D001647:Bile Acids and Salts / Q000009:adverse effects* / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001999:Bronchoscopy; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000150:complications*; D006801:Humans; D007249:Inflammation; D019409:Interleukin-15 / Q000032:analysis / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis / Q000276:immunology; D007958:Leukocyte Count; D016040:Lung Transplantation / Q000009:adverse effects*; D009504:Neutrophils / Q000276:immunology; D009864:Ontario / Q000453:epidemiology; D015995:Prevalence; D012129:Respiratory Function Tests; D012307:Risk Factors; D013053:Spectrophotometry; D016019:Survival Analysis; D013997:Time Factors
D001647:Bile Acids and Salts; D015415:Biomarkers; D019409:Interleukin-15; D016209:Interleukin-8