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REFLUX-INDUCED COLLAGEN TYPE V SENSITIZATION: POTENTIAL MEDIATOR OF BRONCHIOLITIS OBLITERANS SYNDROME AND IDIOPATHIC PULMONARY FIBROSIS

University of WI - School of Medicine and Public Health, Department of Surgery, Madison, WI

PURPOSE: Lung transplantation has the poorest long-term survival of all organ transplantations. This is related to the high incidence of Bronchiolitis Obliterans Syndrome (BOS). Gastroesophageal reflux disease (GERD) has been implicated in BOS. We investigated the role of GERD and collagen type V (col(V)) sensitization in BOS pathogenesis.

METHODS: Fifty-four primary lung transplant patients were followed prospectively for allograft function, for a mean follow-up of 4.2 years. Sensitivity to col(V) was determined via the trans-vivo delayed type hypersensitivity reaction (TV-DTH). Medical record review was used to determine reflux status. Kaplan-Meier analysis was performed.

RESULTS: Of the 54 recipients, 26 had documented GERD, and 28 had no reflux. Between groups, there were no significant differences in: diagnosis, donor/recipient age, gender, ischemic time, single/bilateral, HLA-A/B/DR matching, CMV, acute rejections, or mean follow-up. The mean DTH response in the GERD group was 25.7x10-4 inches versus 18.3x10-4 in the non-GERD group, p=0.023. There was a significant reduction in BOS-free survival in the reflux group for both BOS-I and BOS-II/III (p=0.0001, p=0.0374 respectively). For BOS-I, the 5-year BOS free survival was 28.3% (GERD) and 86.6% (no GERD), and for BOS-II/III, 66.2% and 91.7% respectively. A second cohort of 53 patients awaiting lung transplantation was also assayed. The mean DTH response in the GERD group was 24x10-4 inches versus 13x10-4 in the non-GERD group, p=0.003. There were no differences in age or gender. There was a strong correlation between reflux and the diagnosis of Idiopathic Pulmonary Fibrosis (IPF), p=0.002.

CONCLUSION: GERD is strongly associated with the development of BOS after primary lung transplantation. col(V) sensitization is associated with reflux and BOS, and may serve an intermediary role in the pathogenesis of BOS. GERD and subsequent col(V) sensitization are strongly associated with IPF pre-transplant, and may be involved in pathogenesis and disease progression. Trials utilizing col(V) reactivity to asses impact of anti-reflux procedures in lung transplant and IPF patients are warranted.

CLINICAL IMPLICATIONS: Control of reflux may reduce col(V) sensitization, a potential intermediary in BOS and IPF pathogenesis.

DISCLOSURE: Joseph Bobadilla, No Financial Disclosure Information; No Product/Research Disclosure Information