Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation

Byline: Timothy J. Kroshus, Vibhu R. Kshettry, Kay Savik, Ranjit John, Marshall I. Hertz, R.Morton Bolman Abstract: Objective: This study identifies specific clinical and immunologic factors in lung transplant recipients that influence the subsequent development of chronic allograft dysfunction. Methods: The study group consisted of 132 consecutive patients who received lung allografts (76 single, 25 bilateral single, and 31 heart-lung) and survived at least 90 days. One hundred twenty-one patients were used in the analysis that modeled time to development of histologic obliterative bronchiolitis or bronchiolitis obliterans syndrome. Results: Variables noted to have an effect on the time to development of bronchiolitis obliterans syndrome included cytomegalovirus pneumonitis (RR = 3.2, p = 0.001), late acute rejection (RR = 1.3, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 1.8, p = 0.02), total human leukocyte antigen mismatches (RR = 1.4, p = 0.04), and absence of donor antigen-specific hyporeactivity (52% vs 100% survival free from bronchiolitis obliterans syndrome at 2 years; p = 0.005). Cytomegalovirus pneumonitis had a significant effect on time to obliterative bronchiolitis (RR = 3.6, p = 0.0005), as did donor antigen-specific hyporeactivity (52% vs 100% survival free from obliterative bronchiolitis at 2 years; p = 0.01). In multivariate analysis, cytomegalovirus pneumonitis (RR = 3.2, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 2.4, p = 0.006), and late acute rejection (RR = 1.3, p = 0.02) were identified as predictors of bronchiolitis obliterans syndrome. Cytomegalovirus pneumonitis was associated with time to development of histologic obliterative bronchiolitis (RR = 2.3, p = 0.02). Conclusions: Several risk factors were associated with the development of chronic allograft dysfunction, which, in turn, had a significant impact on long-term survival. Early identification of lung allograft recipients with risk factors for the development of bronchiolitis obliterans syndrome may allow modification in immunosuppression and antiviral therapy to potentially decrease the prevalence of this disorder. J Thorac Cardiovasc Surg 1997;114:195-202 Article History: Received 5 February 1996; Revised 28 March 1996; Revised 25 February 1997; Accepted 27 March 1997 Article Note: (footnote) [star] Address for reprints: R. Morton Bolman III, MD, Department of Surgery, University of Minnesota, Box 207 UMHC, 420 Delaware St. SE, Minneapolis, MN 55455., [star][star] 0022-5223/97 $5.00 + 0 12/1/82360