Reflux-induced collagen type v sensitization: potential mediator of bronchiolitis obliterans syndrome.
BACKGROUND
Lung transplantation continues to have poor long-term survival partly because of the high incidence of bronchiolitis obliterans syndrome (BOS). Gastroesophageal reflux disease (GERD) has been implicated in BOS pathogenesis. We investigated the role of collagen type V [col(V)] sensitization in this process.


METHODS
Only primary lung transplant recipients were included. Reflux status was assessed with pH monitoring, impedance plethysmography, and esophagogastroduodenoscopy. Sensitivity to col(V) was determined with trans vivo delayed-type hypersensitivity reaction (DTH). Kaplan-Meier analyses were performed.


RESULTS
Of the 54 recipients, 26 had proven GERD. There were no significant between-group differences in diagnosis; donor and recipient age; sex; ischemic time; single vs bilateral; human leukocyte antigen A, B, and DR matching cytomegalovirus status; acute rejections; or mean follow-up period. The mean DTH response in the GERD group was 25.7 x 10(-4) inches vs 18.3 x 10(-4) inches in the non-GERD group (P = .023). There was a significant reduction in BOS-free survival in the GERD group for both BOS-I (GERD+, 28.3%; GERD-, 86.6%; P = .0001) and BOS-II/III (GERD+, 66.2%; GERD-, 91.7%; P = .0374). A second cohort of 53 patients awaiting lung transplantation also was assayed. The mean DTH response in the GERD group was 24.0 x 10(-4) inches vs 13.1 x 10(-4) inches in the non-GERD group (P = .003). There were no differences in age or sex.


CONCLUSIONS
GERD is strongly associated with the development of BOS after primary lung transplantation. Col(V) sensitization is associated with reflux and BOS and may play an intermediary role in the pathogenesis of BOS. Trials using col(V) reactivity to assess the impact of antireflux procedures in patients with lung transplantation and idiopathic pulmonary fibrosis are warranted.
Bobadilla
Joseph L
JL
Department of Surgery, Division of Cardiothoracic Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA. maloney@surgery.wisc.edu
Jankowska-Gan
Ewa
E
Xu
Qingyong
Q
Haynes
Lynn D
LD
Munoz del Rio
Alejandro
A
Meyer
Keith
K
Greenspan
Daniel S
DS
De Oliveira
Nilto
N
Burlingham
William J
WJ
Maloney
James D
JD
D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000503:physiopathology*; D024062:Collagen Type V / Q000502:physiology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications*; D006801:Humans; D008171:Lung Diseases / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged
D024062:Collagen Type V