Original clinical science
Acute Cellular Rejection Is a Risk Factor for Bronchiolitis Obliterans Syndrome Independent of Post-transplant Baseline FEV1

https://doi.org/10.1016/j.healun.2009.04.022Get rights and content

Background

Post-transplant baseline forced expiratory volume in 1 second (FEV1) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV1.

Methods

A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4).

Results

The first maximum FEV1 occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV1 was a significant confounder in all survival and competing risk analyses of BOS (p < 0.05).

Conclusion

Despite early diagnosis and prompt treatment, acute cellular rejection remains an independent risk factor for the development of BOS after adjusting for the confounding of post-transplant baseline FEV1.

Section snippets

Methods

All patients receiving SLT, BLT or combination heart–lung transplantation (HLT) at the Danish National Centre for Lung Transplantation, Copenhagen University Hospital, Rigshospital, during the period 1992 to 2004, were included in the analysis (n = 389). Patients not surviving at least 3 months after transplantation were not considered to be at risk of developing BOS (n = 39) and were excluded from the study. Patients for whom there were insufficient or missing lung function measurements were

Results

A total of 346 (89%) consecutive patients were evaluated with respect to the development of BOS. Basic demographic information on these patients is shown in Table 1.

The first maximum FEV1 used in the calculation of baseline FEV1 occurred at a median 183 (quartiles 72, 366) days post-transplant.

The freedom from BOS, BOS-free survival and cumulative incidence of BOS according to type of transplant is shown in Figure 1. In this cohort, the overall freedom from BOS Grade 1 was 81%, 53%, 38% and 15%

Discussion

In this study we have evaluated a number of recipient and donor demographic and clinical risk factors for the development of BOS Grade 1. This is the first study to correct for the overall size of the transplanted lung and address the inherent bias of determining BOS grade as a proportion of baseline lung function. The main findings were: (1) baseline lung function remained a strong confounder in all analyses of freedom from and cumulative incidence of BOS; and (2) increased exposure to ACR

Disclosure Statement

Supported by a PhD grant from the University of Copenhagen.

References (24)

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