Bronchiolitis obliterans syndrome–free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis

Abstract

Background: Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis-obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death and BOS) incidence exist. Methods: This retrospective cohort study of primary LTx recipients (1994–2011) reported to the ISHLT Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss-to-follow-up, end-of-study, and retransplantation. While standard Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data. Results: Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599/15,268; 43%) and bilateral LTx (8,699/15,268; 57%) recipients had a median BOS-free survival of 3.16 (95% CI, 2.99–3.30) years and 3.58 (95% CI, 3.53–3.72) years, respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses “overestimated” median BOS-free survival by 0.42 years and “underestimated” the median survival after BOS by about a half-year for both single and bilateral LTx (p<0.05). Conclusions: A majority of LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-transplantation. Less inclusive Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events.

Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation

“…CLAD was defined as a persistent decline in FEV1 ≤ 80% for at least 3 weeks without a specific cause . CLAD‐free survival was defined as the earliest occurrence of either CLAD or death, whichever came first …”

“…29 CLAD-free survival was defined as the earliest occurrence of either CLAD or death, whichever came first. 2 Given that colonization with Pseudomonas aeruginosa (as well as other infections) and the occurrence of acute rejection and lymphocytic bronchiolitis could occur simultaneously with the development of DSAs, we treated these risk factors as time-dependent covariates in a Cox proportional hazards model. Thus, our analyses accounted for the time of occurrence of the explanatory variables when determining the risk conferred by these variables on the development of DSA.…”

“…However, long‐term outcomes remain disappointing, and the median survival after transplantation is 6.5 years . Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after transplantation and is attributed to immune‐mediated injury . The development of DSA to mismatched HLA has been increasingly recognized as an independent risk factor for CLAD and death .…”

“…1 Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after transplantation and is attributed to immune-mediated injury. [1][2][3][4] The development of DSA to mismatched HLA has been increasingly recognized as an independent risk factor for CLAD and death. [5][6][7][8][9][10][11] Furthermore, multiple studies have reported a high incidence of DSA after lung transplantation.…”

Expanding the horizons: Uncontrolled donors after circulatory death for lung transplantation—First comparison with brain death donors

“…1,2 Although the number of procedures performed is steadily increasing, 3 we are still far from attending the growing demand of donor organs. Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are still the main limitations of early and late survival.…”