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Original Research: BRONCHIOLITIS OBLITERANS SYNDROME |

Reflux-Induced Collagen Type V Sensitization: Potential Mediator of Bronchiolitis Obliterans Syndrome

Joseph L. Bobadilla, MD; Ewa Jankowska-Gan, MS; Qingyong Xu, PhD; Lynn D. Haynes, MS; Alejandro Munoz del Rio, PhD; Keith Meyer, MD; Daniel S. Greenspan, PhD; Nilto De Oliveira, MD; William J. Burlingham, PhD; James D. Maloney, MD
Author and Funding Information

From the Department of Surgery (Drs Bobadilla, Xu, Munoz del Rio, De Oliveira, Burlingham, and Maloney and Mss Jankowska-Gan and Haynes), Department of Medicine (Dr Meyer), and Department of Pathology and Laboratory Medicine (Dr Greenspan), School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI.

Correspondence to: James D. Maloney, MD, University of Wisconsin–Madison, Department of Surgery, Division of Cardiothoracic Surgery, Box 3236 Clinical Sciences Center–H4/320, 600 Highland Ave, Madison, WI 53792; e-mail: maloney@surgery.wisc.edu


Funding/Support: This study was supported by the National Institutes of Health [Grants R01 AI48624 (Drs Bobadilla and Meyer and Mss Jankowska-Gan and Haynes), R21 A1049900 (Dr Bobadilla and Mss Haynes and Jankowska-Gan), and R01 AR47746 (Dr Greenspan)]. Dr Maloney is supported by a CHEST Foundation award for clinical investigation in lung transplantation.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(2):363-370. doi:10.1378/chest.09-2610
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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 × 10−4 inches vs 18.3 × 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 × 10−4 inches vs 13.1 × 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.

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